Journal articles: 'QU 475' – Grafiati (2024)

Abstract:

With the use of the additive, the clay's shear strength and bearing capacity increased. Usage waste material, Wooden Hush Ash (WHA), is tiny. The silicate content of WHA is almost the same as RHA. This study aims to utilize ASK for a stabilization material of high plasticity clay to increase shear strength. Unconfined Compression Strength (UCS) tests were performed to compare the UCS value of clay; clay with 5% cement; clay with lime; clay-cement with WHA; clay-cement with lime and WHA; and clay with lime and WHA. Before the UCS test, the sample was separated into two groups: with and without curing for 28 days, and with and without soaking for 4 days. While in conditions unsoaked, the qu value is uniform. Results show, without curing and soaked, qu values of all variations have the same value in the range of 350 kPa to 380 kPa. In conditions with curing 28 days with and without soaked, qu values range from 365 kPa to 485 kPa for mixtures with WHA and a combination of lime with ASK. While adding of 10% lime additive increases the qu value to 1100 kPa UCS testing results prove, with and without curing and soaked, lime is more optimal to increase the value of UCS than WHA. Replacement lime with WHA by 4% to 6% increases the qu value from 160 kPa to 465 kPa and 485 kPa and 110 kPa to 440 kPa to 475 kPa of soaked and unsoaked condition respectively. WHA can be used to reduce lime in soil stabilization.

Abstract:

Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg−1) and QU (50 mg kg−1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.

Abstract:

In some cases, structures are built on or near aslope. The ultimate bearing capacity of the foundations for these structures issignificantly affected by the presence of the slope. In this paper, the ultimate bearing capacity of footings near slopes is investigated by the finiteelement method. Consideration is given to the effect of slope angle, height ofslope, the distance from the edge of the slope to the footing, soil propertiesand the interaction between the soil and footing. Conclusions are drawn: Ingeneral, the dimensionless bearing capacity qu/γB increases with theincrease of the ratio cu/γB, the increase of L/B, and decrease ofthe slope angle β. Thecurves describing the relationship between cu/γB and qu/γBcan be characterized using three main properties, namely a linear section, anon-linear section, and zero bearing capacity point. Within the linear section,local bearing capacity failure contained to within the face of the slope; theheight of the slope does not influence the bearing capacity. In the non-linearsection, the curves of the relation (cu/γB, qu/γB) isgoverned by overall slope failure.

Abstract:

Nilai uji kuat tekan bebas tanah lempung ekspansif menggunakan campuran abu kayu dan pasir zeolit. Penelitian ini berguna untuk mengetahui kuat tekan bebas tanah lempung ekspansif setelah dilakukan stabilisasi tanah menggunakan bahan tambahan abu kayu dan pasir zeolit dengan persentase campuran abu kayu dan pasir zeloit 0%, 2%, 5%, 8% lolos saringan no. 4 (4,75 mm), untuk lama pemeraman selama 24 jam. Metode yang dilakukan dalam penelitian ini adalah metode desain empiris secara eksperimen yaitu metode yang dilakukan dengan mengadakan kegiatan percobaan untuk mendapatkan data. Pada penelitian yang telah dilakukan dilaboratorium untuk dapat mengetahui hasil dari Analisis Kepadatan Tanah Lempung Ekspansif Menggunakan Campuran Abu Kayu Dan Pasir Zeloit Dengan Pengujian Kuat Tekan Bebas, serta menggunakan campuran abu kayu dan pasir zeloit yang berbeda, yaitu : 0%, 2%, 5%, 8%. dari sampel yang telah diujikan dengan abu kayu dan pasir zeolit yakni dengan campuran 0%, 2%, 5%, 8% pada 10x tubukan, 25x tumbukan, 56x tumbukan yang berbeda menghasilkan perubahan nilai qu dan cu. Nilai qu terbesar dihasilkan pada saat berada dikondisi tanah dengan (abukayu & pasir zeolit),5% dan jumlah tumbukan 56 kali yang mehasilkan nilai qu sebesar 2,2495 kg/cm² sedangkan untuk nilai qu terkecil berada pada kondisi tanah dengan (abukayu & pasir zeolit) 0% dan jumlah tumbukan 10 kali yang mehasilkan nilai qu sebesar 0,6440 kg/cm² . Nilai cu terbesar dihasilkan pada saat berada di kondisi tanah dengan (abu kayu & pasir zeolit) 5%, jumlah tumbukan 56 kali yang mehasilkan nilai cu sebesar 1,1247kg/cm² sedangkan untuk nilai cu terkecil berada pada kondisi tanah dengan (abu kayu & pasir zeolit) 0% dan jumlah tumbukan 10 kali yang mehasilkan nilai cu sebesar 0,3220 kg/cm².

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Penelitian ini bertujuan menganalisis sifat fisik-mekanik tanah yang digunakan sebagai pondasi jalan dan menganalisis pengaruh perubahan kadar air terhadap nilai CBR dan daya dukung tanah. Pengujian yang dilakukan di laboratorium meliputi uji sifat fisik tanah asli, pengujian sifat mekanik tanah asli dan kemudian menghitung daya dukung tanah. Dari pengujian didapatkan berat isi tanah (γ) = 1,76 g/cm3; berat jenis (Gs) = 2,67; kadar air (w) =29,33%; persentase lolos saringan no 200 = 53,99%; batas cair (LL) = 53,64%, indeks plastisitas (PI) = 16,16%, hasil klasifikasi tanah sistem USCS adalah tanah masuk kedalam kelompok OH dan hasil klasifikasi tanah sistem AASHTO adalah tanah termasuk dalam klasifikasi kelompok A-7-6(8). Dari pengujian pemadatan tanah asli, didapat nilai kadar air optimum (OMC) = 20% dan berat isi kering maksimum (γd max) = 1,29 g/cm3. Hasil pengujian CBR tanah asli didapat nilai CBR sebesar 4,6. Nilai CBR Setelah penambahan air 10% dari kadar air optimum pada tanah asli didapat nilai CBR 4,4 dan DDT = 4,4. Setelah penambahan air 15% dari kadar air optimum pada tanah asli didapat nilai CBR = 3,7 dan DDT = 4,1. Untuk kadar air berkurang 10% dari kadar air optimum didapat CBR = 5 dan DDT = 4,7, dan kadar air berkurang 15% dari kadar air optimum didapat CBR = 5,3 dan DDT = 4,5. Dari hasil Pengujian kuat geser langsung didapat nilai daya dukung tanah asli (qu) = 1,048 kg/cm2. Setelah penambahan air 10% dari kadar air tanah asli (qu) = 0,853 kg/cm2. Setelah penambahan air 15% (qu)= 0,539 kg/cm2 maka daya dukung sebesar 48,53%. Pada penelitian ini kadar air tanah memiliki pengaruh terhadap nilai daya dukung tanah dasar.

Abstract:

Abstract The effective thermal conductivity of soils is a crucial parameter for many applications such as geothermal engineering, environmental science, and agriculture and engineering. However, it is pretty challenging to accurately determine it due to soils’ complex structure and components. In the present study, the influences of different parameters, including silt content (m si), sand content (m sa), clay content (m cl), quartz content (m qu), porosity, and water content on the effective thermal conductivity of soils, were firstly analyzed by the Pearson correlation coefficient. Then different artificial neural network (ANN) models were developed based on the 465 groups of thermal conductivity of unfrozen soils collected from the literature to predict the effective thermal conductivity of soils. Results reveal that the parameters of m si, m sa, m cl, and m qu have a relatively slight influence on the effective thermal conductivity of soils compared to the water content and porosity. Although the ANN model with six parameters has the highest accuracy, the ANN model with two input parameters (porosity and water content) could predict the effective thermal conductivity well with acceptable accuracy and R 2 = 0.940. Finally, a correlation of the effective thermal conductivity for different soils was proposed based on the large number of results predicted by the two input parameters ANN-based model. This correlation has proved to have a higher accuracy without assumptions and uncertain parameters when compared to several commonly used existing models.

Abstract:

445 Background: Optimizing outcomes in RCC or GIST patients (pts) receiving TKI (e.g. sunitinib ([U]) involves therapy management as a key component. Reduction/elimination of adverse events (AEs) by prevention/early intervention may improve quality of life and enable adequate duration of therapy. Published recommendations (RECs) for AE management are heterogeneous and often rely on hypothetical considerations or limited evidence. A collaborative effort of physicians, patients, and Pfizer addresses these issues. An initial analysis of a patient survey on real-life validity of RECs in 27 TKI-treated pts was shown at ASCO 2012 (abstr. 99588). We report an updated combined analysis with an expert survey in 23 physicians experienced in SU use for RCC and GIST. Methods: RECs for AE management in pts receiving SU or other VEGFR-TKIs were retrieved from the literature since 2006 and listed in a questionnaire (QU). For the patient survey, RECs were converted into patient-friendly language, RECs requiring physician intervention/decision were excluded. Pts rated RECs in 5 categories (positive/negative experience [self/others]; no information). Experts rated the RECs according to strength of their consent and own experiences. Results: 27 pts had evaluable QUs. Pts were on SU for 16 months (median). On average, 49% of RECs were rated positive; 44% based on individual experience. 20 RECs were rated positively by >80% of pts. Pts had most positive experiences with RECs concerning pt/physician communication on AEs, care/protection of feet and skin, food preference, hydration, and fatigue. Pts had a preference for RECs with low interference in daily life. RECs rated positive by >80% of pts were supported by most experts. Several RECs supported by most experts were unknown to many pts, including dermatological interventions, dietary counselling, and self-perception. Conclusions: To our knowledge, this is the first patient and expert survey on validity and practicability of published AE management RECs. The data identify useful consensual RECs from real-life perspective. TKI therapy management may be improved by enhanced pt education.

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AbstractThe present study describes the total phenolic content, concentrations of flavonoids and in vitro antioxidant and antimicrobial activity of methanol extracts from Seseli pallasii Besser, S. libanotis (L.) Koch ssp. libanotis and S. libanotis (L.) Koch ssp. intermedium (Rupr.) P. W. Ball, growing wild in Serbia. The total phenolic content in the extracts was determined using Folin-Ciocalteu reagent and their amounts ranged between 84.04 to 87.52 mg GA (gallic acid)/g. The concentrations of flavonoids in the extracts varied from 4.75 to 19.37 mg Qu (quercetin)/g. Antioxidant activity was analyzed using DPPH reagent. Antioxidant activity ranged from 0.46 to 4.63 IC50 (mg/ml) and from 1.98 to 2.19 mg VitC (vitamin C)/g when tested with the DPPH and ABTS reagents, respectively, using BHA and VitC as controls. The antimicrobial activity of the extracts was investigated using a micro-well dilution assay for the most common human gastrointestinal pathogenic bacterial strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, Salmonella enteritidis ATCC 13076, Bacillus cereus ATCC 10876, Listeria monocytogenes ATCC15313, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 10231. This finding suggests that Seseli species may be considered as a natural source of antioxidants and antimicrobial agents.

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This paper presents the experimental study of Soil-Cement Pile (SCpile) by wet mixing method in sandy soils, with the typical project at An Trung Complex apartment, Da Nang city, Vietnam. With the characteristic of soil layers is sandy soil, the strength of laboratory stabilized soils with the amount of cement from 150¸300 kg/m3 was determined. Simultaneously, the authors also performed the experiments of 20 test piles collected from the site which has cement content about 280 kg/m3 and the unconfined compressive strength qu= (4.5-6.0) MPa. After that, a full-scale model static axial compressive load tests of two single piles and a group of four piles with diameter 800 mm and 12 m length were also conducted. The experiment results show that the bearing capacity of every single pile is 1.200 kN with settlement 6.93 mm and the group of four CSpiles is 3.200 kN with settlement 5.03 mm. The results presented in the paper illustrate that SCpile is the suitable solution for foundation construction process with low cost and saving time for high rise buildings. The result shows a capable application of soil cement piles for support of high-rise buildings.

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Abstract Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor 5-year overall survival rate at all stages of disease (7-10%). The immunohistochemistry of pancreatic cancer tissue has shown a significantly higher level of positive LDLR (low-density lipoprotein receptor) staining in primary tumors compared to the normal adjacent pancreas. LDLR is overexpressed in the epithelial pancreatic adenocarcinoma, irrespectively of tumor size, stage, and aggressiveness. The objective of this study was to determine the LDLR-targeting properties of 68Ga-labeled peptide conjugate, 68Ga-RMX-VH, in pancreatic adenocarcinoma cell lines. Methods: RMX-VH peptide conjugate (25-50μg) was labeled with 68Ga (50-100mCi, ITM Germany) in mild conditions in the presence of scavenger, sodium ascorbate (8mg/ml). The cellular uptake and competition studies of the radiotracer (15μCi/well) were completed in multiple pancreatic adenocarcinoma cell lines and in vivo in PDAC xenografts generated in athymic nude mice. The PET/CT images were acquired using a G4 PET/X-ray camera (Sofie Biosciences; 10min/scan) at 1h, 2h post-injection. This study determined in vivo and in vitro time-dependent accumulation of this agent in LDLR-overexpressing pancreatic adenocarcinoma cells. Results: 68Ga-RMX-VH was synthesized with higher than 95% radiochemical purity. The radiotracer was incubated in pancreatic adenocarcinoma cell lines for 1h and has shown the highest uptake in HPAF-II (6.7%ID/mg) and BxPC-3 (5.3 %ID/mg) and MiaPaCa2 (4.75 %ID/mg), respectively. Western blot showed a variable level of LDLR overexpression in human pancreatic cancer cells. The microPET imaging studies confirmed rapid accumulation and retention of radiotracer in the tumor (1.18 %ID/g) and elimination through kidneys (4.5 %ID/g) and bladder (SUV ratio of tumor to kidneys: 0.21). These results correlate with previously reported retention of the agent in Pk4a pancreatic adenocarcinoma. Conclusions: RMX-VH has the potential to evaluate the role of LDL receptors in pancreatic adenocarcinoma. We have initiated the exploratory clinical study of this agent in LDLR-overexpressing solid tumors, including pancreatic adenocarcinoma. Citation Format: Leo Flores, Xuewei Qu, Cedric Malicet, Pascaline Lecorche, Ebrahim Delpassand, Jamal Temsamani, Izabela Tworowska. Targeting low density lipoprotein receptors in the pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB066.

Abstract:

Soft soils have a high compressibility, and low shear strength, and constructions on such soils often require the use of ground-improvement techniques. This paper compares the use of an electrokinetic (EK) treatment of soft soils using the ionic solutions calcium chloride and sodium carbonate. The effects of the ionic-solution type, the EK-treatment duration, the cation exchange capacity (CEC), the specific surface area (Sa), the pH, the electrical conductivity (σ), and the ionic strength (Is) were considered in this study. Examining the parameters and evaluating their effects on soil behavior are difficult and complex. The design of experiments (DOE) software program was used to evaluate the effects of the parameters and determine the significant input factors for the EK treatment on soft soils. The analysis and optimization of the data produced the threshold values using the design-expert® software. In this study, the EK-treated soil with CEC = 4.9 meq 100/g, Sa = 4.5 m2/g , pH = 9.5, σ = 6.0 S/m, Is = 1.55·10-4 mol/L, and electrolyte-type setup of CaCl2-Na2CO3 gave better soil strengthening. The gain in strength is attributed to the flocculation and aggregation of the EK-treated soil particles. The analysis of the data by DOE indicated that it could be used to assess the significant effects of the input factors on the unconfined compressive strength, qu of the EK-treated soft soils.

Abstract:

The cytosolic SHP-2 (Src hom*ology protein tyrosine phosphatase 2) has previously been implicated in IL-3 (interleukin-3) signalling [Bone, Dechert, Jirik, Schrader and Welham (1997) J. Biol. Chem. 272, 14470 –14476; Craddock and Welham (1997) J. Biol. Chem. 272, 29281–29289; Welham, Dechert, Leslie, Jirik and Schrader (1994) J. Biol. Chem. 269, 23764–23768; Qu, Nguyen, Chen and Feng (2001) Blood 97, 911–914]. To investigate the role of SHP-2 in IL-3 signalling in greater detail, we have inducibly expressed WT (wild-type) or two potentially substrate-trapping mutant forms of SHP-2, generated by mutation of Asp-425 to Ala (D425A) or Cyst-459 to Ser (C459S), in IL-3-dependent BaF/3 cells. Effects on IL-3-induced tyrosine phosphorylation, signal transduction and functional responses were examined. Expression of C459S SHP-2 protected the β-chain of the murine IL-3R (IL-3 receptor), the adaptor protein Gab2 (Grb2-associated binder 2), and a cytosolic protein of 48 kDa from tyrosine dephosphorylation, consistent with them being bona fide substrates of SHP-2 in IL-3 signalling. The tyrosine phosphorylation of a 135 kDa transmembrane protein was also protected upon expression of C459S SHP-2. We have identified the inhibitory immunoreceptor PECAM-1 (platelet endothelial cell adhesion molecule-1)/CD31 (cluster determinant 31) as a component of this 135 kDa substrate and also show that IL-3 can induce tyrosine phosphorylation of PECAM-1. Expression of WT, C459S and D425A forms of SHP-2 had little effect on IL-3-driven proliferation or STAT5 (signal transduction and activators of transcription) phosphorylation or activation of protein kinase B. However, expression of WT SHP-2 increased ERK (extracellular-signal-regulated kinase) activation. Interestingly, expression of C459S SHP-2 decreased ERK activation at later times after IL-3 stimulation, but potentiated IL-3-induced activation of Jun N-terminal kinases. In addition, expression of C459S SHP-2 decreased cell survival in suboptimal IL-3 and upon IL-3 withdrawal. These findings indicate that SHP-2 plays an important role in mediating the anti-apoptotic effect of IL-3 and raises the possibility that PECAM-1 participates in the modulation of cytokine-induced signals.

Abstract:

The white-backed planthopper (WBPH) is a major pest of rice crops and causes severe loss of yield. We previously developed the WBPH-resistant rice cultivar “OxF3H” by overexpressing the OsF3H gene. Although there was a higher accumulation of the flavonoids kaempferol (Kr) and quercetin (Qu) as well as salicylic acid (SA) in OxF3H transgenic (OsF3H or Trans) plants compared to the wild type (WT), it is still unclear how OsF3H overexpression affects these WBPH resistant-related changes in gene expression in OxF3H plants. In this study, we analyze RNA-seq data from OxF3H and WT at several points (0 h, 3 h, 12 h, and 24 h) after WBPH infection to explain how overall changes in gene expression happen in these two cultivars. RT-qPCR further validated a number of the genes. Results revealed that the highest number of DEGs (4735) between the two genotypes was detected after 24 h of infection. Interestingly, it was found that several of the DEGs between the WT and OsF3H under control conditions were also differentially expressed in OsF3H in response to WBPH infestation. These results indicate that significant differences in gene expression between the “OxF3H” and “WT” exist as the infection time increases. Many of these DEGs were related to oxidoreductase activity, response to stress, salicylic acid biosynthesis, metabolic process, defense response to pathogen, cellular response to toxic substance, and regulation of hormone levels. Moreover, genes involved in salicylic acid (SA) and ethylene (Et) biosynthesis were upregulated in OxF3H plants, while jasmonic acid (JA), brassinosteroid (Br), and abscisic acid (ABA) signaling pathways were found downregulated in OxF3H plants during WBPH infestation. Interestingly, many DEGs related to pathogenesis, such as OsPR1, OsPR1b, OsNPR1, OsNPR3, and OsNPR5, were found to be significantly upregulated in OxF3H plants. Additionally, genes related to the MAPKs pathway and about 30 WRKY genes involved in different pathways were upregulated in OxF3H plants after WBPH infestation. This suggests that overexpression of the OxF3H gene leads to multiple transcriptomic changes and impacts plant hormones and pathogenic-related and secondary-metabolites-related genes, enhancing the plant’s resistance to WBPH infestation.

Abstract:

Background:Primary Sjögren’s syndrome(pSS) is a classical systemic autoimmune disease. Thrombocytopenia is one of the hematological manifestations of pSS with great challenges in clinic.Objectives:To identify the candidate genes and functionally enriched pathways in the immune genesis and progression of primary Sjögren’s syndrome (pSS) associated thrombocytopenia.Methods:High-throughput sequencing was performed on 3 patients with pSS, 3 patients with pSS associated thrombocytopenia and 3 healthy individuals. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were processed. The protein-protein interaction network (PPI) was constructed, followed by calculation of topological characteristics and sub-module analysis in order to obtain hub DEGs. The expression of some hub genes was verified by Real-Time PCR in 24 pSS patients.Results:A total of 19 DEGs were identified. The enriched functions and pathway of the DEGs include Toll-like receptor signaling pathway, Salmonella infection, Viral protein interaction with cytokine and cytokine receptor, NF-kappa B signaling pathway and Human cytomegalovirus infection. Seven hub genes (TNF, IL1B, CXCL8, CCL3, CCL4, CCL3L1, CCL4L1) were identified and pathway enrichment analysis revealed that these genes were mainly enriched in toll-like receptor pathway. The relative expression of the CXCL8 mRNA in B-lymphocytes in patients with pSS associated thrombocytopenia was higher than that in the pSS without thrombocytopenia group. No differences were observed in the IL-1β or TNFα expression between these two groups.Conclusion:PSS associated thrombocytopenia might be a subset characterized by a systemic inflammatory state. The identification of upregulated genes involved in thrombocytopenia of pSS provides insight in disease pathogenesis and opens avenues for the design of novel therapeutic strategies.References:[1] Fox RI: Sjögren’s syndrome. Lancet, 2005; 366: 321–31.[2]Baldini C, Ferro F, Elefante E, Bombardieri S. Biomarkers for Sjögren’s syndrome. Biomark Med. 2018;12(3):275-286.[3]Hua F, Li Y, Zhao X, et al. The expression profile of toll-like receptor signaling molecules in CD19(+) B cells from patients with primary immune thrombocytopenia. Immunol Lett. 2016, 176:28-35.Table 1.Differentially expressed genes among patients with pSS associated thrombocytopenia, pSS without thrombocytopenia, and healthy controlsGeneLogFCin group2FDRin group 2LogFCin group1FDRin group 1TNF4.961.29E-034.554.98E-05CXCL88.881.29E-039.743.23E-05CCL35.654.54E-035.611.70E-05G0S27.384.54E-0312.331.09E-05LILRA38.427.23E-0310.264.31E-05IER35.449.53E-037.712.98E-06DUSP23.509.53E-033.918.12E-05TNFAIP32.639.53E-032.241.36E-03CCL44.531.19E-025.423.35E-06CCL4L26.721.40E-028.925.19E-05CCL4L14.721.40E-025.943.94E-06IL1B5.541.66E-0210.233.27E-06METRNL3.551.80E-024.022.08E-04ID22.932.43E-023.786.57E-03PER12.332.99E-022.427.68E-04EGR12.983.09E-022.931.80E-04CCL3L15.863.20E-026.665.94E-03FFAR24.944.09E-028.401.34E-05FOSB3.234.86E-023.491.39E-03Figure 1.DEGs in pSS associated thrombocytopenia. 183 DEGs (31 up- and 151 down- regulated) between pSS patients with and without thrombocytopenia(a, c). 459 DEGs between pSS associated thrombocytopenia patients and healthy individuals were identified (2up- and 457 down- regulated) (b, d). The overlap among the 2 groups contained 19 genes represents the DEGs specified in pSS associated thrombocytopenia (e).Figure 2.KEGG pathway analysis.Acknowledgments:The authors apologize to all colleagues whose work has not been separately cited or discussed here due to limitations in space or knowledge.Disclosure of Interests:SHUO ZHANG: None declared, Jingge Qu: None declared, Li Wang: None declared, Mengtao Li: None declared, Xiaofeng Zeng Consultant of: MSD Pharmaceuticals

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Abstract Background and purpose: Colorectal cancer (CRC) is the third leading cause of cancer deaths in the U.S. Establishing new genetic variants associated with CRC risk may lead to early CRC detection and novel treatment options. Recently, mouse genetic studies identified the cystic fibrosis transmembrane conductance regulator (CFTR) gene as a tumor suppressor in CRC. In line with this, a human study using MarketScan claims data showed that cystic fibrosis (CF) carriers – individuals with one copy of mutant CFTR – are at increased CRC risk. Although there are more than 10 million CF carriers in the U.S., to our knowledge, no studies comprehensively examined CFTR mutations in relation to CRC risk. Our hypothesis is that CFTR mutations are associated with an increased risk of CRC. Methods: We used whole exome sequencing (WES) data in 454,333 individuals (age 44-82 years), including 4,975 cases of CRC, in the UK Biobank study. We utilized risk set sampling to select up to four controls per CRC case based on age of diagnosis, gender, race, and year of joining the study. To examine associations between CFTR mutations and CRC risk, logistic regression (odds ratio and p-value) was used after adjusting for age, gender and 10 principal components capturing global ancestry. An aggregate burden score was constructed that included all variants listed as CF-causing in the CFTR2 online database. Results: Of the 465 CFTR variants in the CFTR2 database, 378 are classified as CF-causing, and of those 153 were observed in the UK Biobank WES data set. Individuals with two CF-causing alleles were excluded from further analysis (8 cases and 35 controls), since the association between CF and CRC is already well established. The frequency of the F508del variant, the most common CF-causing mutation, was 3.77% in cases versus 3.11% in controls, while the frequency of any other CF-causing mutation was 1.07% in cases versus 0.80% in controls. Having any CF-causing mutation was associated with a significant 24% increased CRC risk (one-sided p=0.002). Having one copy of the F508del mutation, was associated with a significant 21% increased risk of CRC (one-sided p=0.012), while having one copy of any other CF-causing mutation was associated with a slightly larger 34% increased risk of CRC (one-sided p=0.036). Conclusions: CF-causing mutations in the heterozygous state lead to a significantly increased risk of CRC. Individuals with multiple genetic risk factors, such as in CFTR, may require earlier screening for CRC. Citation Format: Anna E. Prizment, Abigail Standafer, Shuo Wang, Conghui Qu, Ulrike Peters, Patricia Scott, Timothy Starr, Nathan Pankratz. Heterozygote carriers of cystic fibrosis mutations have increased risk of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A031.

Abstract:

Abstract Acute Myeloid Leukemia (AML) is the third hematological malignancies with the worst relative overall 5-year survival rate (11.7%) in hematological malignancies. AML is a heterogeneous disease with a broad spectrum of genomic changes and molecular mutations that lead to a poor prognosis and clinical outcome. Leukemic stem cells progress to myoblasts that continue to proliferate without differentiating, namely, immature blasts in AML. The hedgehog (HH)/glioma-associated oncogene hom*olog (GLI) signaling pathway is essential for embryonic and stem cell developments. This pathway has been one of the most promising targets for drug discovery and developments for AML. Although HH inhibitor Glasdegib in combo with low-dose cytarabine achieved FDA approval for AML, Venetoclax (BCL-2 inhibitor/ABT-199) plus a hypomethylating agent (HMA) have been dominating the regimens in AML recently. Here we reported GT1708, a HH inhibitor, improves ABT-199 (venetoclax)-induced apoptosis by down-regulating MCL-1 proteins in AML cells. GT1708 is a potent HH inhibitor (IC50=0.11 nM in HH pathway-driven cellular assay) and inhibited GLI expression with doses of 1, 3 and 10 mpk in a HH-dependent medulloblastoma animal models. In Molm-13 (AML) cells, GT1708 was shown to down-regulate the expression of MCL-1 proteins (anti-apoptotic proteins). In contrast, ABT-199 increased the expression of MCL-1. Furthermore, ABT+Aza (Azacidine/HMA drug) induced more MCL-1 expression than ABT-199. Importantly, GT1708 was shown to induce the expression of cleaved-PARP (c-PARP/apoptotic marker) and to increase c-PARP expression when combined with ABT-199. Due to ABT+Aza induced MCL-1 overexpression, the combination of both agents failed to induce c-PARP, suggesting MCL-1 overexpression conferring resistance to ABT+Aza therapy in Molm-13 cells. GT1708 was further evaluated in flow cytometry-based apoptotic assays. GT1708, ABT-199 and Aza were demonstrated to induce an early apoptosis by 9.98%, 47.5%, and 8.64%, respectively. In comparation, ABT+GT1708 were revealed to induce a 61% of apoptosis superior to 47% or 48.5% of apoptosis induced by either ABT or ABT+Aza in Molm-13 cells. These results confirm the role of MCL-1 overexpression in conferring resistance to ABT+Aza therapy, which can be overcome by ABT+GT1708 combo. GT1708/ABT combo were also shown a marginable superior antitumor activity than ABT along in Molm-13 animal models. GT1708 has been testing in a phase I study in AML patients with previous multiple lines of regimens. GT1708 has been shown to reduce blast counts in three of 13 AML patients treated with higher doses and demonstrated favorite PK and safety profiles. In brief, these results support the clinical development of GT1708 in combination with ABT-199 in AML patients. Citation Format: Liandong Ma, Qianxiang Zhou, Honghua Yan, Min Dong, Xiahe Han, Jiangwie Li, Jie Qu, Weidong Qian, Youzhi Tong. Combination of a clinical stage-hedgehog inhibitor, GT1708, improves Venetoclax-induced apoptosis by down-regulating MCL-1 proteins in AML cells. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4978.

Abstract:

Background:Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease, usually involving multiple systems of the whole body (1). A variety of factors can affect SLE, such as genetic, environmental, immunoregulatory, hormonal and epigenetic (2). Long non-coding RNA is a type of RNA greater than 200 nucleotides that does not encode proteins. With the development of research, lncRNA gradually becomes the key regulator of gene expression in the immune system (3). Studies have shown that several lncRNAs, such as NEAT1 and GAS5 are dysregulated in SLE and are involved in the pathogenesis of SLE (4,5). These results suggest that lncRNA can be used as a potential biomarker for disease diagnosis and treatment. However, our current understanding of SLE related lncRNAS is still limited.Objectives:The purpose of this study was to find new lncRNAs in peripheral blood monouclear cells of SLE patients by transcriptome sequencing and explore their potential as biomarkers and their correlation with clinical features.Methods:Transcriptome sequencing was used to screen differentially expressed lncRNAs (DELs) and mRNAs (DEMs). DAVID and WebGestalt were used to perform enrichment analysis. Cytoscape was used to constructed protein-protein network, co-expression network and competitive endogenous RNA network to reveal the regulatory mechanism of lncRNAs in transcriptome level. The expression of these selected lncRNAs in SLE patients and healthy controls were verified by qPCR.Results:A toal of 1737 DELs and 4078 DEMs were identified between 5 SLE patients and 5 healthy controls. Most of upregulated genes were enriched in defense and immune response, while downregulated genes were mainly enriched in SLE related pathways. Topology network analysis reveal the regulatory mechanism of lncRNAs in transcriptome level including directly acting on mRNA or indirectly affecting gene expression after acting on miRNA. Ten lncRNAs and eight genes was verified by qPCR in bigger samples including 77 SLE patients and 25 healthy controls. LncRNA NONHSAT101022.2 was significantly downregulated in SLE patients (p=0.001) and the expression of NONHSAT101022.2 showed a significant negative correlation with SLE disease activity index (SLEDAI, r=-0.3592, p=0.0013).Conclusion:In this work, we identified a large number of mRNAs and novel lncRNAs by transcriptome sequence. The function and regulatory mechanism of these lncRNAs were analyzed by bioinformatics methods. LncRNA NONHSAT101022.2 is significantly downregulated in SLE patients and significantly related to the activity and severity of disease. Additionally, we put forward that NONHSAT101022.2 may enhance the signal transduction of β2-AR by cis-regulating its target gene, LMBRD2, which induces NK cells to produce high levels of IFN-γ, thereby exacerbating SLE.References:[1]Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 2016;12(10):605-20.[2]Han EC. Systemic lupus erythematosus. N Engl J Med. 2012;366(6):573-4; author reply.[3]Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol. 2017;18(9):962-72.[4]Zhang F, Wu L, Qian J, Qu B, Xia S, La T, et al. Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus. Journal of autoimmunity. 2016;75:96-104.[5]Liu Q, Deng Y, Li C, Xie H, Liu Q, Ming S, et al. LncRNA GAS5 suppresses CD4(+) T cell activation by upregulating E4BP4 via inhibiting miR-92a-3p in systemic lupus erythematosus. Immunol Lett. 2020;227:41-7.Disclosure of Interests:None declared

Abstract:

The amino acid transporter ASCT2, encoded by the gene SLC1A5, is the main glutamine importer in proliferating human and mouse cells. We recently showed that glutamine is the main fuel of the tricarboxylic acid (TCA) cycle in cells from chronic lymphocytic leukemia (CLL) patients, and that blocking its import attenuated CD40/BCR-induced venetoclax (VEN) resistance 1. In the current study, we have investigated the role of ASCT2 and the consequences of its inhibition in human and mouse CLL cells and in healthy lymphocytes by flow cytometry, gene expression analysis, extracellular flux analysis, metabolomics, CRISPR/Cas9 gene editing and adoptive-cell transfer experiments. To enable in vivo assessment of ASCT2 in the future with Positron Emission Tomography (PET), we have explored the potential use of 18F-labelelled ( 2S,2R)-4-fluoroglutamine (4- 18F]FGln) 2 as PET tracer. Increased expression of ASCT2 upon PMA/ionomycin stimulation was observed in healthy B and T cells. In BCR/CD40-stimulated CLL cells, the increased expression was irrespective of IGHV status. We dissected the main routes of glutamine usage in CD40- and BCR-stimulated CLL cells and found that in addition to its role in the TCA cycle, glutamine import is linked to mTOR signaling. The ASCT2 inhibitor V9302 impaired mTOR signaling and decreased translation of new proteins, including the anti-apoptotic proteins Bcl-XL and Mcl-1. Of relevance for therapeutic approaches, the effector and proliferative capacity of human T cells was preserved upon V9302 treatment. This suggests that blocking ASCT2 will not affect immune responses. The SLC1A5 gene was deleted by CRISPR/Cas9 technique in murine TCL1 cells 3. Adoptive cell transfer experiments of SLC1A5-KO and WT TCL1 cells injected at 50-50% ratio in recipient mice showed selective outgrowth of SLC1A5-WT cells, with no detection of the SLC1A5-KO in the spleen of overt leukemic mice. This indicates that TCL1 leukemic cells rely on SLC1A5/ASCT2 for growth. Finally, we explored the high expression of ASCT2 and glutamine addiction in CLL from the diagnostic perspective. With the aim of improving the currently suboptimal [ 18F]FDG PET for imaging of CLL LN sites 4, we successfully synthesized 4-[ 18F]FGln. We observed uptake in CD40-stimulated CLL cells, which was decreased in the presence of V9302. Experiments to perform PET with 4-[ 18F]FGln in TCL1 mice to demonstrate an in vivo proof of concept are ongoing. Overall, these data support a crucial role for ASCT2 and glutamine in leukemia development and VEN resistance in CLL. This provides a basis for targeting the transporter for therapeutic options and/or taking advantage of its function for diagnostic approaches using 4-[ 18F]FGln as PET tracer. 1. Chen, Z. et al. Characterization of metabolic alterations of chronic lymphocytic leukemia in the lymph node microenvironment. Blood 140, 630-643, doi:10.1182/blood.2021013990 (2022). 2. Qu, W. et al. Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. J Am Chem Soc 133, 1122-1133, doi:10.1021/ja109203d (2011). 3. Nardi, F. et al. Assessing gene function in human B cells: CRISPR/Cas9-based gene editing and mRNA-based gene expression in healthy and tumor cells. Eur J Immunol 52, 1362-1365, doi:10.1002/eji.202149784 (2022). 4. Rhodes, J. M. & Mato, A. R. PET/Computed Tomography in Chronic Lymphocytic Leukemia and Richter Transformation. PET Clin 14, 405-410, doi:10.1016/j.cpet.2019.03.007 (2019).

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Abstract Introduction: PDZ and LIM domain protein 2 (PDLIM2) acts as tumor suppressor by downregulating NF-κB and STAT3 signaling, modulating inflammation, immune response, and cell survival. Mouse model studies have demonstrated that downregulation of PDLIM2 leads to PD-1 immune blockade and chemotherapy resistance. We present a large clinical and molecular characterization of PDLIM2 expression in non-small cell lung cancer (NSCLC). Methods: NextGen sequencing of DNA (whole exome)/RNA (whole transcriptome) was performed for NSCLC (Total N = 29126; Adenocarcinoma [-A, N = 15765], Squamous [-S, N = 6416]) patient tumors submitted to Caris Life Sciences (Phoenix, AZ). Mutations were defined as pathogenic SNVs/indels. Samples were stratified by PDLIM2 expression quartiles (in transcripts per million [TPM]) for all NSCLC tumors (Q4: H, Q1: L). PD-L1 expression [22C3; Positive (+): tumor proportion score (TPS) ≥1%]was assessed by IHC. High tumor mutational burden (TMB-high) set as ≥10 mutations per Mb. Cell infiltration in the tumor microenvironment was estimated by QuantiSEQ. Gene expression profiles were analyzed for transcriptional signatures predictive of response to immunotherapy (T cell-inflamed). Real-world overall survival was assessed from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined subpopulations. Mann-Whitney U and X2/Fisher-Exact tests were applied where appropriate, with P-values adjusted for multiple comparisons (p < 0.05). Results: Median PDLIM2 expression was higher in NSCLC-A compared to NSCLC-S (15.3 vs 13.6 TPM, p < 0.001). PDLIM2-AL had a lower prevalence of EGFR mutations than PDLIM2-AH (15.5% vs 19.4%, p < 0.01), but the opposite pattern was observed for STK11 (21.5% vs 11.2%), RB1 (7.5% vs 3.8%), TP53 (62.9% vs 52.8%), KEAP1 (18.4% vs 10.9%), and SMARCA4 (9.15 vs 4.5%) alterations (all p < 0.001). PDLIM2-AL tumors had decreased PD-L1+ (L: 52.4% vs H: 58.4% p < 0.001) but increased TMB-High status (L: 40.9% vs H: 28.5%, p < 0.001). PD-L1+ and TMB-H frequency did not vary with PDLIM2 expression in NSCLC-S. In both NSCLC-A and -S tumors, PDLIM2H had increased infiltration of NK cells, macrophages, dendritic cells, T cells, neutrophils, monocytes, and B cells compared to PDLIM2L (all p < 0.05), in addition to increased T cell-inflammed scores (p < 0.001). PDLIM2-AH was associated with improved overall survival (OS) (median 21.7 vs L: 15.6 months; p < 0.001; Hazard ratio [HR] = 0.825, 95% Confidence Interval [CI] 0.765 - 0.889) and time on pembrolizumab treatment (median 6.2 vs L: 5.6 months; p = 0.009; HR = 0.825 95% CI 0.714 - 0.953). No difference in OS was observed between PDLIM2-SH vs L tumors (H: 14.8 vs L: 14.0 months; p = 0.37; HR = 0.95, CI 0.85-1.06). Conclusions: NSCLC-A with high PDLIM2 expression have a unique mutational profile, increased immune cell infiltration and favorable OS. Therapeutic strategies for targeting PDLIM2 to modulate NF-κB and STAT3 signaling should be further explored. Citation Format: Karam Ashouri, Harris Krause, Andrew Elliott, Stephen V. Liu, Patrick C. Ma, Balazs Halmos, Zhaoxia Qu, Gutian Xiao, Ari Vanderwalde, Jorge J. Nieva. Characterization of PDLIM2 in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5201.

Abstract:

Abstract Downsizing metal nanoparticle catalysts to form single-atom catalysts (SACs) has proven to be one of the best ways to enhance the catalysts’ activity and selectivity1-2 due to their unique characteristics such as nearly 100% atom utilization and well-defined active sites.3 However, the broad application of SACs in catalytic reactions is limited by their poor stability as they possess high surface energy and thus tend to aggregate and form nanoclusters or nanoparticles.4 To address this challenge, various supports such as metal oxides, carbon materials, and porous materials are widely used to stabilize the SACs.5 Metal organic frameworks (MOFs), a class of porous crystalline materials, have proven to be an ideal candidate to support SACs owing to their high surface area, high porosity, and abundant potential anchoring sites.6 It has been shown that immobilizing SACs on MOFs, which forms MOF supported SACs, can integrate the unique properties of SACs and MOFs and led to remarkable catalytic activity, selectivity, and stability toward various catalytic reactions.6-8 Application of MOF supported SACs in photocatalysis, organic linkers of metal-organic frameworks act as photosensitive units,9 However most pristine metal-organic frameworks possesses poor light absorption properties due to wide band gap.9To enhance the light harvesting properties of the metal organic framework its organic linker is functionalized.10-11 In my poster presentation, I will present my work where post-synthetic modification of UiO-66-NH2 MOF linker with 3,4,9,10 perylene tetracarboxylic dianhydride (PDA) an organic molecule with broad absorption edge,12and immobilization of Ni single atom catalyst on the zirconium cluster of the MOF was done. This resulted in enhanced optical properties and charge separation efficiency which was proved by a combination of UV-visible spectroscopy (UV-Vis), photoelectrochemical techniques, and X-ray absorption spectroscopy (XAS). Observed photophysical effects posed by the modifications of the UiO-66-NH2 were evaluated by photocatalytic hydrogen generation. References Yan, J.; Kong, L.; Ji, Y.; White, J.; Li, Y.; Zhang, J.; An, P.; Liu, S.; Lee, S.-T.; Ma, T., Single atom tungsten doped ultrathin α-Ni (OH) 2 for enhanced electrocatalytic water oxidation. Nature communications 2019, 10 (1), 1-10. Jiao, L.; Jiang, H.-L., Metal-organic-framework-based single-atom catalysts for energy applications. Chem 2019, 5 (4), 786-804. Qiao, B.; Wang, A.; Yang, X.; Allard, L. F.; Jiang, Z.; Cui, Y.; Liu, J.; Li, J.; Zhang, T., Single-atom catalysis of CO oxidation using Pt1/FeO x. Nature chemistry 2011, 3 (8), 634-641. Xia, C.; Qiu, Y.; Xia, Y.; Zhu, P.; King, G.; Zhang, X.; Wu, Z.; Kim, J. Y.; Cullen, D. A.; Zheng, D., General synthesis of single-atom catalysts with high metal loading using graphene quantum dots. Nature chemistry 2021, 13 (9), 887-894. Wu, J.; Xiong, L.; Zhao, B.; Liu, M.; Huang, L., Densely populated single atom catalysts. Small Methods 2020, 4 (2), 1900540. Huang, H.; Shen, K.; Chen, F.; Li, Y., Metal–organic frameworks as a good platform for the fabrication of single-atom catalysts. ACS Catalysis 2020, 10 (12), 6579-6586. Qu, W.; Chen, C.; Tang, Z.; Wen, H.; Hu, L.; Xia, D.; Tian, S.; Zhao, H.; He, C.; Shu, D., Progress in metal-organic-framework-based single-atom catalysts for environmental remediation. Coordination Chemistry Reviews 2023, 474, 214855. Szilágyi, P.; Rogers, D.; Zaiser, I.; Callini, E.; Turner, S.; Borgschulte, A.; Züttel, A.; Geerlings, H.; Hirscher, M.; Dam, B., Functionalised metal–organic frameworks: a novel approach to stabilising single metal atoms. Journal of Materials Chemistry A 2017, 5 (30), 15559-15566. He, J.; Wang, J.; Chen, Y.; Zhang, J.; Duan, D.; Wang, Y.; Yan, Z., A dye-sensitized Pt@ UiO-66 (Zr) metal–organic framework for visible-light photocatalytic hydrogen production. Chemical communications 2014, 50 (53), 7063-7066. Elcheikh Mahmoud, M.; Audi, H.; Assoud, A.; Ghaddar, T. H.; Hmadeh, M., Metal–Organic Framework Photocatalyst Incorporating Bis(4′-(4-carboxyphenyl)-terpyridine)ruthenium(II) for Visible-Light-Driven Carbon Dioxide Reduction. Journal of the American Chemical Society 2019, 141 (17), 7115-7121. Hendrickx, K.; Joos, J. J.; De Vos, A.; Poelman, D.; Smet, P. F.; Van Speybroeck, V.; Van Der Voort, P.; Lejaeghere, K., Exploring lanthanide doping in UiO-66: a combined experimental and computational study of the electronic structure. Inorganic Chemistry 2018, 57 (9), 5463-5474. Yu, H.; Joo, P.; Lee, D.; Kim, B. S.; Oh, J. H., Photoinduced Charge‐Carrier Dynamics of Phototransistors Based on Perylene Diimide/Reduced Graphene Oxide Core/Shell p–n Junction Nanowires. Advanced Optical Materials 2015, 3 (2), 241-247.

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Journal of Marriage and Family, 72(5), 1377-1390.

Abstract:

BackgroundThe experience of art offers an emerging field in healthcare staff development, much of which is appropriate to the practice of palliative care. The workings of aesthetic learning interventions such as interactive theatre in relation to palliative and end of-life care staff development programmes are widely uncharted.AimTo investigate the use of aesthetic learning interventions used in palliative and end-of-life care staff development programmes.DesignScoping review.Data sourcesPublished literature from 1997 to 2015, MEDLINE, CINAHL and Applied Social Sciences Index and Abstracts, key journals and citation tracking.ResultsThe review included 138 studies containing 60 types of art. Studies explored palliative care scenarios from a safe distance. Learning from art as experience involved the amalgamation of action, emotion and meaning. Art forms were used to transport healthcare professionals into an aesthetic learning experience that could be reflected in the lived experience of healthcare practice. The proposed learning included the development of practical and technical skills; empathy and compassion; awareness of self; awareness of others and the wider narrative of illness; and personal development.ConclusionAesthetic learning interventions might be helpful in the delivery of palliative care staff development programmes by offering another dimension to the learning experience. As researchers continue to find solutions to understanding the efficacy of such interventions, we argue that evaluating the contextual factors, including the interplay between the experience of the programme and its impact on the healthcare professional, will help identify how the programmes work and thus how they can contribute to improvements in palliative care.References. 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Abstract:

The pandemic of COVID-19 has afflicted every individual and has initiated a cascade of directly or indirectly involved events in precipitating mental health issues. The human species is a wanderer and hunter-gatherer by nature, and physical social distancing and nationwide lockdown have confined an individual to physical isolation. The present review article was conceived to address psychosocial and other issues and their aetiology related to the current pandemic of COVID-19. The elderly age group has most suffered the wrath of SARS-CoV-2, and social isolation as a preventive measure may further induce mental health issues. Animal model studies have demonstrated an inappropriate interacting endogenous neurotransmitter milieu of dopamine, serotonin, glutamate, and opioids, induced by social isolation that could probably lead to observable phenomena of deviant psychosocial behavior. Conflicting and manipulated information related to COVID-19 on social media has also been recognized as a global threat. Psychological stress during the current pandemic in frontline health care workers, migrant workers, children, and adolescents is also a serious concern. Mental health issues in the current situation could also be induced by being quarantined, uncertainty in business, jobs, economy, hampered academic activities, increased screen time on social media, and domestic violence incidences. The gravity of mental health issues associated with the pandemic of COVID-19 should be identified at the earliest. Mental health organization dedicated to current and future pandemics should be established along with Government policies addressing psychological issues to prevent and treat mental health issues need to be developed. References World Health Organization (WHO) Coronavirus Disease (COVID-19) Dashboard. 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Abstract:

BackgroundThe World Health Organization (WHO) declared COVID-19 as a pandemic on 11 March 2020. Many efforts were performed to contain the virus worldwide. People's knowledge and attitude should be directed toward strict preventive practices to halt the spread of the virus. We aimed to assess the knowledge, attitude, practices, and sources of information (KAPS) used by Qatar University (QU) attendees.MethodsA cross-sectional web-based questionnaire was answered by 500 employees and students in the QU community. It included questions on KAPS toward COVID-19. Information on sociodemographics was collected and analyzed. This study was conducted during the second wave of COVID-18 in the state of Qatar (April–May 2021).ResultsA total of 475 participants aged between 18 and 68 years old consented to complete the survey questionnaire. The study involved 279 (58.7%) non-Qatari nationals and 196 (41.3%) natives, with 254 (53.5%) participants pursuing postgraduate studies and 221 (46.5%) undergraduates. Approximately two-thirds of the sample were employed (64.8%), while one-third were unemployed (35.2%). Knowledge scores on average were 66.4% (M = 5.31, SD = 1.45, and range: 0–8), with only significant differences were noted between nationalities (natives and non-natives) Participants' average score in practices was 69.72% (M = 4.18, SD = 1.7, and range 0–6) with a significant difference in safe COVID-19 practice scores based on the educational level. Adherence with COVID-19 policies and rules were 82% (M = 2.46, SD = 0.7, and range: 0–3) with no differences noted between groups. In addition, the population reported relying on governmental press conferences (76.0%) as their primary source of gaining details concerning COVID-19, followed by social media (64.4%). The least popular resources were information gained from family, relatives, friends, and coworkers (47.4%) and the news channels on TV (46.7%).ConclusionOverall, this study provides insights into Qatar's KAPS toward COVID-19 during the quarantine of the second wave of this pandemic. This study, being the first of its kind to be conducted in the state of Qatar, is expected to help the ministry of public health and the government communication office to establish a suitable measurement of response to the spread of COVID-19 and develop the best practices for any future epidemics that might occur.

Abstract:

Abstract Background Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Deep learning (DL) algorithms could automate interpretation of echocardiographic strain imaging. Methods We developed and trained an automated DL-based algorithm for left ventricular (LV) strain measurements in an internal dataset. Global longitudinal strain (GLS) was validated externally in (1) a real-world Taiwanese cohort of participants with and without heart failure (HF), (2) a core-lab measured dataset from the multinational PROMIS-HFpEF study, and regional strain in (3) the HMC-QU-MI study of patients with suspected myocardial infarction. Outcomes included measures of agreement (bias, mean absolute difference [MAD], root-mean-squared-error [RMSE] and Pearson’s correlation [R]) and area under the curve (AUC) to identify HF and regional wall-motion abnormalities. Results The DL workflow successfully analysed 3741 (89%) studies in the Taiwanese cohort, 176 (96%) in PROMIS-HFpEF and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements (mean ± SD): -18.9 ± 4.5% vs -18.2 ± 4.4%, respectively, bias 0.68 ± 2.52%, MAD 2.0 ± 1.67, RMSE = 2.61, R = 0.84 in the Taiwanese cohort; and -15.4 ± 4.1% vs -15.9 ± 3.6%, respectively, bias -0.65 ± 2.71%, MAD 2.19 ± 1.71, RMSE = 2.78, R = 0.76 in PROMIS-HFpEF. In the Taiwanese cohort, automated GLS accurately identified patients with HF (AUC = 0.89 for total HF and AUC = 0.98 for HF with reduced ejection fraction). In HMC-QU-MI, automated regional strain identified regional wall-motion abnormalities with an average AUC = 0.80. Conclusion DL algorithms can interpret echocardiographic strain images with similar accuracy as conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements and reduce time-spent and costs for echo labs globally.

Abstract:

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Us2ai. Background Echocardiographic strain imaging reflects myocardial deformation and is a sensitive measure of cardiac function and wall-motion abnormalities. Manual strain analysis is time-consuming, prone to error and requires considerable expertise. Deep learning (DL) algorithms could automate interpretation of echocardiographic strain imaging. Purpose To develop and externally validate automated DL-based measurement of the left ventricle (LV) global longitudinal strain (GLS) and regional strain. Methods We developed and validated an automated DL workflow using convolutional neural networks to automatically annotate and assess individual 2D videos of apical 4-chamber, 2-chamber and 3-chamber views. We trained the algorithm in an internal dataset and validated GLS externally in (1) a real-world general population dataset from Taiwan, (2) a core-lab measured dataset from the multinational PROMIS-HFpEF study, and regional strain in (3) the HMC-QU-MI study of patients with suspected myocardial infarction (MI). Results In the external datasets, the DL workflow successfully analysed 3741 (89%) studies in the real-world cohort, 176 (96%) in PROMIS-HFpEF and 158 (98%) in HMC-QU-MI. Automated GLS showed good agreement with manual measurements in the real-world dataset (mean ± SD −18.9±4.5% vs −.18.2±4.4%, respectively; bias 0.7±2.5%, root-mean-squared error [RMSE] 2.6, Pearson’s correlation 0.84; Figure 1A) and in PROMIS-HFpEF (−15.4±4.1% vs −15.9±3.6%, respectively; bias −0.6±2.7%, RMSE 2.8, Pearson’s correlation 0.76; Figure 1B). In the general population cohort, automated GLS measurements accurately identified patients with vs without heart failure (ROC-AUC 0.89 for total HF and 0.98 for HF with reduced ejection fraction). In patients with suspected MI, automated regional strain identified regional wall-motion abnormalities with average ROC-AUC 0.80 (range 0.74–0.86 for apical 4-chamber view [Figure 2A] and 0.69–0.90 for apical 2-chamber view [Figure 2B]). Conclusions DL algorithms can interpret cardiac strain images with similar accuracy compared with conventional measurements. These results highlight the potential of DL algorithms to democratize the use of cardiac strain measurements.

Abstract:

We extend the adaptive moving mesh (AMM) central-upwind schemes recently proposed in [A. Kurganov, Z. Qu, O. Rozanova and T. Wu, Commun. Appl. Math. Comput., 3 (2021), pp. 445–479] in the context of one- (1-D) and two-dimensional (2-D) Euler equations of gas dynamics and granular hydrodynamics, to the 1-D and 2-D Saint-Venant system of shallow water equations. When the bottom topography is nonflat, these equations form hyperbolic systems of balance laws, for which a good numerical method should be capable of preserving a delicate balance between the flux and source terms as well as preserving the nonnegativity of water depth even in the presence of dry or almost dry regions. Therefore, in order to extend the AMM central-upwind schemes to the Saint-Venant systems, we develop special positivity preserving reconstruction and evolution steps of the AMM algorithms as well as special corrections of the solution projection step in (almost) dry areas. At the same time, we enforce the moving mesh to be structured even in the case of complicated 2-D computational domains. We test the designed method on a number of 1-D and 2-D examples that demonstrate robustness and high resolution of the proposed numerical approach.

Abstract:

We extend the adaptive moving mesh (AMM) central-upwind schemes recently proposed in [A. Kurganov, Z. Qu, O. Rozanova and T. Wu, Commun. Appl. Math. Comput., 3 (2021), pp. 445–479] in the context of one- (1-D) and two-dimensional (2-D) Euler equations of gas dynamics and granular hydrodynamics, to the 1-D and 2-D Saint-Venant system of shallow water equations. When the bottom topography is nonflat, these equations form hyperbolic systems of balance laws, for which a good numerical method should be capable of preserving a delicate balance between the flux and source terms as well as preserving the nonnegativity of water depth even in the presence of dry or almost dry regions. Therefore, in order to extend the AMM central-upwind schemes to the Saint-Venant systems, we develop special positivity preserving reconstruction and evolution steps of the AMM algorithms as well as special corrections of the solution projection step in (almost) dry areas. At the same time, we enforce the moving mesh to be structured even in the case of complicated 2-D computational domains. We test the designed method on a number of 1-D and 2-D examples that demonstrate robustness and high resolution of the proposed numerical approach.

Abstract:

We extend the adaptive moving mesh (AMM) central-upwind schemes recently proposed in [A. Kurganov, Z. Qu, O. Rozanova and T. Wu, Commun. Appl. Math. Comput., 3 (2021), pp. 445–479] in the context of one- (1-D) and two-dimensional (2-D) Euler equations of gas dynamics and granular hydrodynamics, to the 1-D and 2-D Saint-Venant system of shallow water equations. When the bottom topography is nonflat, these equations form hyperbolic systems of balance laws, for which a good numerical method should be capable of preserving a delicate balance between the flux and source terms as well as preserving the nonnegativity of water depth even in the presence of dry or almost dry regions. Therefore, in order to extend the AMM central-upwind schemes to the Saint-Venant systems, we develop special positivity preserving reconstruction and evolution steps of the AMM algorithms as well as special corrections of the solution projection step in (almost) dry areas. At the same time, we enforce the moving mesh to be structured even in the case of complicated 2-D computational domains. We test the designed method on a number of 1-D and 2-D examples that demonstrate robustness and high resolution of the proposed numerical approach.

Abstract:

Résumé Partant de l’hypothèse de Coveney (1995) que la structure informationnelle influence la sélection de l’interrogative in situ ‘Tu fais quoi ?’ (SVQ), ce travail s’appuie sur les données du Corpus suisse de SMS (2009-2015) pour évaluer l’incidence des principes dits ‘End-Weight’ et ‘End-Focus’. En suivant l’étude de Coveney (1995), nous analyserons l’incidence des paramètres suivants : (i) longueur de la proforme Q et (ii) celle de la partie SVC; paramètres du (iii) Sujet, (iv) Verbe, (v) Complément; et (vi) identité du mot Q. Suite à l’analyse de 217 occurrences de SVQ (sur 425 QU), nos résultats corroborent, fût-ce avec quelques nuances, plusieurs tendances observées par Coveney (1995). En même temps, notre étude révèle que les tendances en cause, telles qu’elles s’observent dans le Corpus de SMS, prennent la forme plus extrême et tendent à fonctionner comme des environnements morphosyntaxiques à variabilité faible : en débouchant régulièrement sur l’emploi de SVQ, elles réduisent drastiquement les chances d’apparition d’autres variantes ex situ. Ces tendances s’expliqueraient par le fait qu’en français informel l’usage de SVQ est en train d’évincer d’autres variantes, principalement dans ces contextes linguistiques qui se sont avérés initialement propices à sa rapide propagation au 20e siècle (Farmer 2015).

Abstract:

The geometries, stabilities of VGen0/- (n = 9 - 13) clusters were systematically studied by the density functional theory (DFT) using the BP86 functional and LANL2DZ basis set. Several possible multiplicities of each cluster were tested to determine the most stable structure among the isomers. The average binding energy per atom, fragmentation energy, second order energy difference and hom*o-LUMO gaps were evaluated. The results indicated that the neutral and anionic clusters possess higher stability when n = 10 and 12. The vertical detachment energy (VDE) and adiabatic detachment energy (ADE) were also calculated for anionic cluster to investigate their stabilities. Among neutral clusters, VGe10 had both the highest vertical ionization potential (VIP) and chemical hardness. Keywords BP86/LANL2DZ, binding energy, VGen0/- clusters, structure of clusters References [1] Shunping Shi, Yiliang Liu, Chuanyu Zhang, Banglin Deng, Gang Jiang (2015). A Computational Investigation of Aluminum-doped Germanium Clusters by Density Functional Theory Study. Computational and Theoretical Chemistry, 1054, pp. 8-15[2] Wen-Jie Zhao, Yuan-Xu Wang (2009). Geometries, stabilities, and Magnetic Properties of MnGen (n = 2 – 16) Clusters: Density-functional Theory Investigations. Journal of Molecular Structure: THEOCHEM, 901 (1–3), pp. 18-23.[3] Shi Shun-Ping, Liu Yi-Liang, Deng Bang-Lin, Zhang Chuan-Yu, and Jiang Gang (2016). Density Functional Theory Study of The Geometrical and Electronic Structures of (n = 1 - 9) clusters. World Scientific Publishing Company, 30, pp. 1750022-1750039.[4] J.Stato, H.Kobayashi, K. Ikarashi, N.Saito, H.Nishiyama, and Y. Inoue (2004). Photocatalitic Activity for Water Decomposition of RuO2-Dispersed Zn2GeO4 with d10 Configuration. The Journal of Physical Chemistry B, 108 (14), pp. 4369-4375.[5] Daoxin Dai, Molly Piels, and John E. Bowers (2014). Monolithic Germanium/Silicon Photodetectors With Decoupled Structures: Resonant APDs and UTC Photodiodes. IEEE Journal of Selected Topics in Quantum Electronics, 20 (6), pp. 3802214-3802227.[6] Chia-Yun Chou, Gyeong S. Hwang (2014). On The Origin of The Significant Difference in Lithiation Behavior Between Silicon and Germanium. Journal of Power Sources, 263, pp. 252-258.[7] Siwen Zhang, Bosi Yin, Yang Jiao, Yang Liu, Xu Zhang, Fengyu Qu, Ahmad Umar, Xiang Wu (2014). Ultra-long Germanium Oxide Nanowires: Structures and Optical Properties. Journal of Alloys and Compounds, 606, pp. 149-153.[8] T. Herrmannsdörfer, V. Heera, O. Ignatchik, M. Uhlarz, A. Mücklich, M. Posselt, H. Reuther, B. Schmidt, K.-H. Heinig, W. Skorupa, M. Voelskow, C. Wündisch, R. Skrotzki, M. Helm, and J. Wosnitza (2009).Superconducting State in a Gallium-Doped Germanium Layer at Low Temperatures. Physical Review Letters, 102, pp. 217003-217006.[9] Vijay Kumar, and Yoshiyuki Kawazoe (2002). Metal-Encapsulated Caged Clusters of Germanium with Large Gaps and Different Growth Behavior than Silicon. Physical Review Letters, 88, pp. 235504-235507.[10] Xiao-Jiao Deng, Xiang-Yu Kong, Hong-Guang Xu, Xi-Ling Xu, Gang Feng, and Wei-Jun Zheng (2015). Photoelectron Spectroscopy and Density Functional Calculations of VGen- (n = 3 − 12) Clusters. The Journal of Physical Chemistry C, 119 (20), pp. 11048-11055.[11] John P. Perdew, Kieron Burke, and Matthias Ernzerhof (1996).Generalized Gradient Approximation Made Simple. Physical Review Letters, 77, pp. 3865-3868.[12] Chaouki Siouani, Sofiane Mahtout, Sofiane Safer, and Franck Rabilloud (2017).Structure, Stability and Electronic and Magnetic Properties of VGen (n = 1 - 19) Clusters. The Journal of Physical Chemistry A, 121 (18), pp. 3540-3554.[13] Jin Wang, and Ju-Guang Han (2006).A Theoretical Study on Growth Patterns of Ni-Doped Germanium Clusters.The Journal of Physical Chemistry B, 110 (15), pp. 7820-7827.[14] Debashis Bandyopadhyay and Prasenjit Sen (2010). Density Functional Investigation of Structure and Stability of Gen and GenNi (n = 1 − 20) Clusters: Validity of the Electron Counting Rule. The Journal of Physical Chemistry A, 114 (4), pp. 1835-1842[15] Soumaia Djaadi, Kamal Eddine Aiadi, and Sofiane Mahtout (2018). Frist Principles Study of Structural, electronic and magnetic properties of (n = 1 - 17) clusters. Journal of Semiconductors, 39 (4), pp. 42001-420013.[16] İskender Muz,Mustafa Kurban,Kazım Şanlıc (2018). Analysis of the Geometrical Properties and Electronic Structure of Arsenide Doped Boron Cluster: Ab-initio approach. Inorganica Chimica Acta, 474, pp. 66-72.[17] Axel D. Becke (1988). Density-functional exchange - energy approximation with correct asymptotic behavior.Physical Review A, 38, pp. 3098-3100.[18] Willard R. Wadt, P. Jeffrey Hay (1985). Ab initio effective core potentials for molecular calculations.Potentials for main group elements Na to Bi.The Journal of Chemical Physics, 82 (1), pp. 284-298.[19] Willard R. Wadt, P. Jeffrey Hay (1985). Ab initio effective core potentials for molecular calculations.Potentials for K to Au including the outermost core orbitals.The Journal of Chemical Physics, 82 (1), pp. 299-310.[20] Willard R. Wadt, P. Jeffrey Hay (1985). Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to Hg. The Journal of Chemical Physics, 82 (1), pp. 270-283.[21] Gabriele Manca, Samia Kahla, Jean-Yves Saillard, Rémi Marchal, Jean-François Halet (2017). Small Ligated Organometallic Pdn Clusters (n = 4 - 12): A DFT Investigation. Journal of Cluster Science, 28 (2), pp. 853-868.[22] Tran Dieu Hang, Huynh Minh Hung, Lam Ngoc Thiem. Hue M. T. Nguyen (2015). Electronic structure and thermochemical properties of neutral and anionic rhodium clusters Rhn, n = 2 – 13. Evolution of structures and stabilities of binary clusters RhmM (M = Fe, Co, Ni; m = 1 – 6). Computational and Theoretical Chemistry, 1068, pp. 30–41.[23] Michael J. Frisch, et al. (2010). Gaussian 09, Revision C.01.Gaussian, Inc., Wallingford CT.

Abstract:

Sweet corn (Zea mays L.) is widely consumed as fresh or frozen vegetable worldwide, and Zhengtian68 is a popular commercial variety cultivated extensively in southeast China. In May 2021, 40% of the inbred line YK063 (the female parent of Zhengtian68) showed early yellowing of the leaves at flowering time in a commercial seed production field with a total area of 0.5 ha in Guangzhou, Guangdong Province after a heavy rain. Black and rotten roots were observed in the diseased plants after digging the whole plant out of the soil. Grain filling was also severely affected, adversely impacting seed production. Diseased plants were more easily found in the lower section of the field, where water accumulated after rainfall. Three plants with rotten roots were collected randomly from the field to identify the causal pathogen. The diseased roots were cut into 2-3 mm sections, washed in 75% ethanol for 2 minutes and rinsed three times in sterile distilled water. Four to five sections per plant were placed on potato dextrose agar (PDA) and incubated at 28℃ in the dark for three days. Three isolates GF1, GF2, and GF3 from different plants were purified by hyphal tip isolation and transferred to new PDA and 10% V8 juice agar (16 g agar, 3 g CaCO3, 100 ml V8 juice, and 900 ml distilled water) and incubated at 28℃ for 10 days in darkness for further investigation. Translucent, glassy mycelial growth was observed on the PDA media. Morphological characteristics of the 3 isolates were observed under a microscope from the 10%V8 media. The hyphae were aseptate and 2.7 to 4.5 μm wide (mean±SD,3.3±0.44μm, n=44). Sporangia were inflated, or lobulate, terminal, or intercalary. Oogonia were globose, smooth-walled, terminal, or occasionally intercalary, with a diameter of 17.2-24.1 μm (mean±SD, 21.3±2.14μm, n=29). Oospores were globose, plerotic, smooth, and 14.5-21.2 μm (mean±SD, 18.7±2.07μm, n=35) in diameter. The antheridia were diclinous or monoclinous, not intercalary, and one to six antheridia were attached to each oogonium. Based on these morphological characteristics, 3 isolates were identified as Pythium spp. including Pythium graminicola (Van der Plaats-Niterink 1981). Genomic DNA was extracted from the mycelia grown on PDA using a Fungal Genomic DNA kit (Scintol, Beijing, China) according to the manufacturer’s instructions. The cytochrome oxidase II (Cox II) gene and internal transcribed spacer (ITS) region of the rDNA were amplified using the primers FM58/FM66 (Martin 2000) and ITS4/ITS5 (White et al. 1990) respectively. Amplification was performed in a 50μl reaction volume using 25 μl PCR Mix (Trans Gene, Beijing, China), 3 μl genomic DNA (50 ng/μl), 1 μl each forward and reverse primer (10 μM), and 20 μl ddH2O. The PCR program was as follows: initial denaturation at 95°C for 30 s, 35 cycles of denaturation at 95°C for 30 s, annealing at 60°C for 60 s, extension at 72°C for 60 s, and a final extension at 72°C for 10 min. PCR products were sequenced and submitted to GenBank (accession no. OQ504322, OQ933130, and OQ933212 for ITS; OQ512002, OQ942203, and OQ942204 for Cox II). BLASTn analysis revealed that the ITS and Cox II sequences showed more than 98.62% similarity (721/724bp, 722/724bp,723/724bp for ITS; 514/514bp, 506/507bp, 500/507bp for Cox II) to P. graminicola ATCC96234 (accession no. AB095045 for ITS, and AB160849 for Cox II), respectively, supporting the morphological analysis. A neighbor-joining phylogenetic analysis of the ITS and Cox II concatenated sequence further confirmed that the isolates were P. graminicola. To test the pathogenicity of GF1, GF2, and GF3 a wheat seed inoculum was prepared as previously described (Qu et al. 2016). Sweet corn YK063 plants were planted in sterilized nutrient soil in plastic pots (one plant per pot) and grown in a greenhouse at 28℃ with 60% humidity and a 12-h/12-h light-dark cycle. For each isolate,10 plants were inoculated with 20 infected wheat seeds around the roots at the V5 stage, while 10 other YK063 plants were inoculated with the non-infected wheat seeds as a control. The experiment was repeated once. Three weeks later, the non-inoculated plants were asymptomatic. In contrast, inoculated plants showed stunning, yellowing of the leaves, root rot, and decreased production of lateral roots, exhibiting symptoms similar to those originally described for the disease. P. graminicola was successfully reisolated from the diseased roots and identified by morphological characteristics and sequencing of the ITS and Cox II as the causal agent for this root rot disease, fulfilling Koch’s postulate for defining a causal agent. P. graminicola was reported as a causal agent of damping-off on dent corn in Georgia (Li et al. 2018). To our knowledge, this is the first report of P. graminicola causing root rot in sweet corn in southeast China. Identification of this pathogen will facilitate further research on this disease and the development of effective strategies to control the disease.

Abstract:

Medicinal plants are a potential source of enzyme acetylcholinesrerase (AChE) inhibitors, a key target in the treatment of Alzheimer’s disease. This paper studies the AChE inhibitory activity and the antioxidant effect of Persea Americana Mill extract. The sample leave, seed, exocarp and mesocarp of avocado were extracted with 50% ethanol and subsequently fractionated with n-hexane, ethyl acetate (EtOA) and n-butanol (n-BuOH) solvents. The AChE inhibitory activity was evaluated by Ellman’s colorimetric method and the antioxidant activity by screening DPPH free radicals. The results show that the seed of Persea Americana extract had the strongest AChE inhibitory activity and antioxidant effect, followed by the leave extract, and the exocarp extract and mesocarp extract were the weakest. The Persea Americana seed extract inhibited AChE activity in a dose-dependent manner with an IC50 value of 47.43 ± 0.5 μg/mL and the antioxidant effect with an IC50 value of 68.7 ± 0.35 µg/mL. The results also show that n–BuOH fraction of Persea Americana seed extract had strong AChE inhibitory and antioxidant activities with an IC50 value of 15.24 ± 0.52 µg/ml and 15.73 ± 0.42 μg/mL, respectively. The study results suggest that the Persea Americana Mill is a promising ingredient in Alzheimer’s disease prevention and treatment. Keywords Persea Americana Mill, Acetylcholinesrerase inhibitors (AChE), Alzheimer, DPPH. References [1] M.M. Essa et al., Neuroprotective effect of natural products against Alzheimer's disease, Neurochem Res. 37(9) (2012) 1829.[2] B. McGleenon, K. Dynan, A. Passmore,. Acetylcholinesterase inhibitors in Alzheimer's disease, British journal of clinical pharmacology. 48 (1999) 471.[3] P. B. Watkins et al, Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease, In: Jama. pp. 992 (1994).[4] O. Adeyemi, S. Okpo, O. Ogunti,. Analgesic and anti-inflammatory effects of the aqueous extract of leaves of Persea americana Mill (Lauraceae). In: Fitoterapia. pp. 375 (2002).[5] P.D.D. Dzeufiet, et al, Antihypertensive potential of the aqueous extract which combine leaf of Persea americana Mill. (Lauraceae), stems and leaf of Cymbopogon citratus (DC) Stapf.(Poaceae), fruits of Citrus medical L.(Rutaceae) as well as honey in ethanol and sucrose experimental model. In: BMC complementary and alternative medicine. p. 507 (2014).[6] B.I. Brai, A. Odetola, P. Agomo,. Hypoglycemic and hypocholesterolemic potential of Persea americana leaf extracts, Journal of medicinal food. 10(2) (2007) 356.[7] Phạm Khuê. Bệnh Alzheimer. Nhà xuất bản Y học (2002).[8] Đàm Trung Bảo. Các gốc tự do, Tạp chí Dược học. 6 (2001) 29 [9] F.R. Mowsumi, A. Rahaman, N.C. Sarker, B.K. Choudhury, S. Hossain, In vitro relative free radical scavenging effects of Calocybe indica (milky oyster) and Pleurotus djamor (pink oyster), World J Pharm Pharm Sci. 4(07) (2015) 186.[10] Y. Bao, Y. Qu, J. Li, Y. Li, X. Ren, K. Maffuci, et al. In vitro and in vivo antioxidant activities of the flowers and leaves from Paeonia rockii and identification of their antioxidant constituents by UHPLC-ESI-HRMSn via pre-column DPPH reaction, Molecules. 23(2) (2018) 392.[11] Phan Kế Sơn. Đánh giá tác dụng ức chế enzym Acetylcholinsterase in vitro của các phân đoạn dịch chiết Hoàng Liên Ô rô (Mahonia Nepalensis DC., họ Berberidaceae). Khóa luận tốt nghiệp Đại học ngành Dược học. Khoa Y Dược - Đại học Quốc Gia Hà Nội (2017).[12] D. Mohammad, P. Chan, J. Bradley, K. Lanctôt, N. Herrmann, Acetylcholinesterase inhibitors for treating dementia symptoms-a safety evaluation, Expert opinion on drug safety. 16(9) (2017) 1009.[13] A. Mohammadi-Farani, S.S. Darbandi, A. Aliabadi, Synthesis and acetylcholinesterase inhibitory evaluation of 4-(1, 3-dioxoisoindolin-2-yl)-N-phenyl benzamide derivatives as potential anti-alzheimer agents, Iranian journal of pharmaceutical research. IJPR 15(3) (2016) 313.[14] T.B. Fernandes, M.R. Cunha, R.P. Sakata, T.M. Candido, A.R. Baby, M.T. Tavares, et al. Synthesis, Molecular Modeling, and Evaluation of Novel Sulfonylhydrazones as Acetylcholinesterase Inhibitors for Alzheimer's Disease, Archiv der Pharmazie. 350(11) (2017) 1700163.[15] M.I. Alkhalf, W.S. Alansari, E.A. Ibrahim, M.E. Elhalwagy, Anti-oxidant, anti-inflammatory and anti-cancer activities of avocado (Persea americana) fruit and seed extract. Journal of King Saud University-Science (2018).[16] F. Gómez, S. Sánchez, M. Iradi, N. Azman, M. Almajano, Avocado seeds: extraction optimization and possible use as antioxidant in food, Antioxidants. 3(2) (2014) 439.[17] O.A. Folasade, R.A. Olaide, T.A. Olufemi, Antioxidant properties of Persea americana M. seed as affected by different extraction solvent, Journal of Advances in Food Science & Technology. 3(2) (2016) 101.[18] C.A. Alagbaoso, I.I. Tokunbo, O.S. Osakwe, Comparative study of antioxidant activity and mineral composition of methanol extract of seeds of ripe and unripe avocado pear (Persea americana, Mill.). NISEB Journal. 15(4) (2017).[19] G. Oboh, V.O. Odubanjo, F. Bello, A.O. Ademosun, S.I. Oyeleye, E.E. Nwanna et al. Aqueous extracts of avocado pear (Persea americana Mill.) leaves and seeds exhibit anti-cholinesterases and antioxidant activities in vitro, Journal of basic and clinical physiology and pharmacology. 27(2) (2016) 131.[20] H. Cavdar, M. Senturk, M. Guney , S. Durdagi, G. Kayik, C.T. Supuran, et al. Inhibition of acetylcholinesterase and butyrylcholinesterase with uracil derivatives: kinetic and computational studies, Journal of enzyme inhibition and medicinal chemistry. 34(1) (2019) 429.

Abstract:

This study uses an in silico screening docking model to evaluate the ACE2 inhibitory activity of natural compounds and drugs. The study collected 49 compounds and evaluated the ACE2 inhibitory effect in silico. The study results show that 11 out of the 49 compounds had stronger inhibitory activity on ACE2 than MLN-4760. Lipinski’s rule of five criteria and predictive pharmaco*kinetic-toxicity analysis show that eight compounds including quercetin, galangin, quisinostat, fluprofylline, spirofylline, RS 504393, TNP and GNF-5 had drug-likeness. These compounds could be potential drug for the Covid-19 treatment. Keywords SARS-CoV-2S, Covid-19, ACE2, molecular docking, in silico. References [[1] C. Wang, P.W. Horby, F.G. Hayden, G.F. Gao. A novel coronavirus outbreak of global health concern. The Lancet 395(10223) (2020) 470.[2] WHO. WHO Coronavirus Disease (COVID-19) Dashboard. WHO, 2020.[3] N. Chen, M. Zhou, X. Dong, J. Qu, F. Gong, Y. Han, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 395(10223) (2020) 507.[4] J. Yang, Y. Zheng, X. Gou, K. Pu, Z. Chen, Q. Guo, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. International Journal of Infectious Diseases 94 (2020) 91.[5] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet 395(10224) (2020) 565.[6] R. Hilgenfeld. From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design. The FEBS journal 281(18) (2014) 4085.[7] D. Wrapp, N. Wang, K.S. Corbett, J.A. Goldsmith, C.L. Hsieh, O. Abiona, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science (New York, NY) 367(6483) (2020) 1260.[8] P.A. Rota, M.S. Oberste, S.S. Monroe, W.A. Nix, R. Campagnoli, J.P. Icenogle, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science (New York, NY) 300(5624) (2003) 1394.[9] M. Donoghue, F. Hsieh, E. Baronas, K. Godbout, M. Gosselin, N. Stagliano, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research 87(5) (2000) E1.[10] H. Zhang, Z. Kang, H. Gong, D. Xu, J. Wang, Z. Li, et al. The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes. bioRxiv (2020) 2020.01.30.927806.[11] Y. Zhao, Z. Zhao, Y. Wang, Y. Zhou, Y. Ma, W. Zuo. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. bioRxiv (2020) 2020.01.26.919985.[12] E.I. Bahbah, A. Negida, M.S. Nabet. Purposing Saikosaponins for the treatment of COVID-19. Med Hypotheses 140 (2020) 109782.[13] I.W. Cheung, S. Nakayama, M.N. Hsu, A.G. Samaranayaka, E.C. Li-Chan. Angiotensin-I converting enzyme inhibitory activity of hydrolysates from oat (Avena sativa) proteins by in silico and in vitro analyses. Journal of agricultural and food chemistry 57(19) (2009) 9234.[14] T. Joshi, T. Joshi, P. Sharma, S. Mathpal, H. Pundir, V. Bhatt, et al. In silico screening of natural compounds against COVID-19 by targeting Mpro and ACE2 using molecular docking. European review for medical and pharmacological sciences 24(8) (2020) 4529.[15] S. Shahid, A. Kausar, M. Khalid, S. Tewari, T. Alghassab, T. Acar, et al. analysis of binding properties of angiotensin-converting enzyme 2 through in silico molecular docking, 2018.[16] K. Teralı, B. Baddal, H.O. Gülcan. Prioritizing potential ACE2 inhibitors in the COVID-19 pandemic: Insights from a molecular mechanics-assisted structure-based virtual screening experiment. J Mol Graph Model 100 (2020) 107697.[17] M. Muchtaridi, M. Fauzi, N.K. Khairul Ikram, A. Mohd Gazzali, H.A. Wahab. Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2. Molecules 25(17) (2020) 3980.[18] M.J. Huentelman, J. Zubcevic, J.A. Hernández Prada, X. Xiao, D.S. Dimitrov, M.K. Raizada, et al. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension (Dallas, Tex : 1979) 44(6) (2004) 903.[19] S. Choudhary, Y.S. Malik, S. Tomar. Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach. Front Immunol 11((2020) 1664.[20] C.A. Lipinski. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies 1(4) (2004) 337.[21] B. Jayaram, T. Singh, G. Mukherjee, A. Mathur, S. Shekhar, V. Shekhar, Eds. Sanjeevini: a freely accessible web-server for target directed lead molecule discovery. Proceedings of the BMC bioinformatics; 2012. Springer (Year).[22] D.E. Pires, T.L. Blundell, D.B. Ascher. pkCSM: predicting small-molecule pharmaco*kinetic and toxicity properties using graph-based signatures. Journal of medicinal chemistry 58(9) (2015) 4066.[23] P. Towler, B. Staker, S.G. Prasad, S. Menon, J. Tang, T. Parsons, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. The Journal of biological chemistry 279(17) (2004) 17996.[24] N.A. Dales, A.E. Gould, J.A. Brown, E.F. Calderwood, B. Guan, C.A. Minor, et al. Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. Journal of the American Chemical Society 124(40) (2002) 11852.[25] P. Pandey, J.S. Rane, A. Chatterjee, A. Kumar, R. Khan, A. Prakash, et al. Targeting SARS-CoV-2 spike protein of COVID-19 with naturally occurring phytochemicals: an in silico study for drug development. Journal of Biomolecular Structure and Dynamics (2020) 1.[26] C.A. Lipinski. Lead- and drug-like compounds: the rule-of-five revolution. Drug discovery today Technologies 1(4) (2004) 337.[27] R.O. Barros, F.L. Junior, W.S. Pereira, N.M. Oliveira, R.M. Ramos. Interaction of drug candidates with various SARS-CoV-2 receptors: An in silico study to combat COVID-19. Journal of Proteome Research (2020).

Abstract:

Alloys used in engines are subjected to challenging environments characterized by thermal and mechanical cyclic loadings during start-up and shut-down processes. These conditions can significantly increase the occurrence of fatigue failure mechanisms. Therefore, this study focuses on investigating the low cycle fatigue (LCF) behavior of directionally-solidified alloy at two distinct temperatures, namely 600 °C and 800 °C. Strain-controlled LCF tests were conducted at the specified temperatures, utilizing constant total strain amplitudes of 0.4%, 0.6%, 0.8%, and 1% under a totally reversed loading ratio (R = -1). The Coffin-Manson model, based on plastic deformation, along with a hysteresis energy-based criterion model, were employed to predict and evaluate fatigue life and LCF behavior. Notably, the hysteresis energy and Coffin-Manson models exhibited superior capability in predicting LCF life at 800 °C compared to 600 °C. REFERENCES Salehnasab, J. Marzbanrad, E. 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Abstract:

Babies and toddlers are amassing huge followings on social media, achieving microcelebrity status, and raking in five figure sums. In East Asia, many of these lucrative “micro­-microcelebrities” rise to fame by inheriting exposure and proximate microcelebrification from their social media Influencer mothers. Through self-branding techniques, Influencer mothers’ portrayals of their young’ children’s lives “as lived” are the canvas on which (baby) products and services are marketed to readers as “advertorials”. In turning to investigate this budding phenomenon, I draw on ethnographic case studies in Singapore to outline the career trajectory of these young children (under 4yo) including their social media presence, branding strategies, and engagement with their followers. The chapter closes with a brief discussion on some ethical considerations of such young children’s labour in the social media age.Influencer MothersTheresa Senft first coined the term “microcelebrity” in her work Camgirls as a burgeoning online trend, wherein people attempt to gain popularity by employing digital media technologies, such as videos, blogs, and social media. She describes microcelebrities as “non-actors as performers” whose narratives take place “without overt manipulation”, and who are “more ‘real’ than television personalities with ‘perfect hair, perfect friends and perfect lives’” (Senft 16), foregrounding their active response to their communities in the ways that maintain open channels of feedback on social media to engage with their following.Influencers – a vernacular industry term albeit inspired by Katz & Lazarsfeld’s notion of “personal influence” that predates Internet culture – are one type of microcelebrity; they are everyday, ordinary Internet users who accumulate a relatively large following on blogs and social media through the textual and visual narration of their personal lives and lifestyles, engage with their following in “digital” and “physical” spaces, and monetize their following by integrating “advertorials” into their blog or social media posts and making physical appearances at events. A pastiche of “advertisem*nt” and “editorial”, advertorials in the Influencer industry are highly personalized, opinion-laden promotions of products/services that Influencers personally experience and endorse for a fee. Influencers in Singapore often brand themselves as having “relatability”, or the ability to persuade their followers to identify with them (Abidin). They do so by make consciously visible the backstage (Goffman) of the usually “inaccessible”, “personal”, and “private” aspects of mundane, everyday life to curate personae that feel “authentic” to fans (Marwick 114), and more accessible than traditional celebrity (Senft 16).Historically, the Influencer industry in Singapore can be traced back to the early beginnings of the “blogshop” industry from the mid-2000s and the “commercial blogging” industry. Influencers are predominantly young women, and market products and services from diverse industries, although the most popular have been fashion, beauty, F&B, travel, and electronics. Most prominent Influencers are contracted to management agencies who broker deals in exchange for commission and assist in the production of their vlogs. Since then, the industry has grown, matured, and expanded so rapidly that Influencers developed emergent models of advertorials, with the earliest cohorts moving into different life stages and monetizing several other aspects of their personal lives such as the “micro-microcelebrity” of their young children. What this paper provides is an important analysis of the genesis and normative practices of micro-microcelebrity commerce in Singapore from its earliest years, and future research trajectories in this field.Micro-Microcelebrity and Proximate MicrocelebrificationI define micro-microcelebrities as the children of Influencers who have themselves become proximate microcelebrities, having derived exposure and fame from their prominent Influencer mothers, usually through a more prolific, deliberate, and commercial form of what Blum-Ross defines as “sharenting”: the act of parents sharing images and stores about their children in digital spaces such as social networking sites and blogs. Marwick (116-117), drawing from Rojek’s work on types of celebrity – distinguishes between two types of microcelebrity: “ascribed microcelebrity” where the online personality is made recognizable through the “production of celebrity media” such as paparazzi shots and user-produced online memes, or “achieved microcelebrity” where users engage in “self-presentation strateg[ies]”, such as fostering the illusion of intimacy with fans, maintaining a persona, and selective disclosure about oneself.Micro-microcelebrities lie somewhere between the two: In a process I term “proximate microcelebrification”, micro-microcelebrities themselves inherit celebrity through the preemptive and continuous exposure from their Influencer mothers, many beginning even during the pre-birth pregnancy stages in the form of ultrasound scans, as a form of “achieved microcelebrity”. Influencer mothers whose “presentational strategies” (cf. Marshall, “Promotion” 45) are successful enough (as will be addressed later) gain traction among followers, who in turn further popularize the micro-microcelebrity by setting up fan accounts, tribute sites, and gossip forums through which fame is heightened in a feedback loop as a model of “ascribed microcelebrity”.Here, however, I refrain from conceptualizing these young stars as “micro-Influencers” for unlike Influencers, these children do not yet curate their self-presentation to command the attention of followers, but instead are used, framed, and appropriated by their mothers for advertorials. In other words, Influencer mothers “curate [micro-microcelebrities’] identities into being” (Leaver, “Birth”). Following this, many aspects of their micro-microcelebrities become rapidly commodified and commercialized, with advertisers clamoring to endorse anything from maternity hospital stays to nappy cream.Although children of mommybloggers have the prospect to become micro-microcelebrities, both groups are conceptually distinct. Friedman (200-201) argues that among mommybloggers arose a tension between those who adopt “the raw authenticity of nonmonetized blogging”, documenting the “unglamorous minutiae” of their daily lives and a “more authentic view of motherhood” and those who use mommyblogs “primarily as a source of extra income rather than as a site for memoir”, focusing on “parent-centered products” (cf. Mom Bloggers Club).In contrast, micro-microcelebrities and their digital presence are deliberately commercial, framed and staged by Influencer mothers in order to maximize their advertorial potential, and are often postured to market even non-baby/parenting products such as fast food and vehicles (see later). Because of the overt commerce, it is unclear if micro-microcelebrity displays constitute “intimate surveillance”, an “almost always well-intentioned surveillance of young people by parents” (Leaver, “Born” 4). Furthermore, children are generally peripheral to mommybloggers whose own parenting narratives take precedence as a way to connect with fellow mothers, while micro-microcelebrities are the primary feature whose everyday lives and digital presence enrapture followers.MethodologyThe analysis presented is informed by my original fieldwork with 125 Influencers and related actors among whom I conducted a mixture of physical and digital personal interviews, participant observation, web archaeology, and archival research between December 2011 and October 2014. However, the material presented here is based on my digital participant observation of publicly accessible and intentionally-public digital presence of the first four highly successful micro-microcelebrities in Singapore: “Baby Dash” (b.2013) is the son of Influencer xiaxue, “#HeYurou” (b.2011) is the niece of Influencer bongqiuqiu, “#BabyElroyE” (b.2014) is the son of Influencer ohsofickle, and “@MereGoRound” (b.2015) is the daughter of Influencer bongqiuqiu.The microcelebrity/social media handles of these children take different forms, following the platform on which their parent/aunt has exposed them on the most. Baby Dash appears in all of xiaxue’s digital platforms under a variety of over 30 indexical, ironic, or humourous hashtags (Leaver, “Birth”) including “#pointylipped”, #pineappledash”, and “#面包脸” (trans. “bread face”); “#HeYurou” appears on bongqiuqiu’s Instagram and Twitter; “#BabyElroyE” appears on ohsofickle’s Instagram and blog, and is the central figure of his mother’s new YouTube channel; and “@MereGoRound” appears on all of bongqiuqiu’s digital platforms but also has her own Instagram account and dedicated YouTube channel. The images reproduced here are screenshot from Influencer mothers’ highly public social media: xiaxue, bongqiuqiu, and ohsofickle boast 593k, 277k, and 124k followers on Instagram and 263k, 41k, and 17k followers on Twitter respectively at the time of writing.Anticipation and Digital EstatesIn an exclusive front-pager (Figure 1) on the day of his induced birth, it was announced that Baby Dash had already received up to SGD25,000 worth of endorsem*nt deals brokered by his Influencer mother, xiaxue. As the first micro-microcelebrity in his cohort (his mother was among the pioneer Influencers), Baby Dash’s Caesarean section was even filmed and posted on xiaxue’s YouTube channel in three parts (Figure 2). xiaxue had announced her pregnancy on her blog while in her second trimester, following which she consistently posted mirror selfies of her baby bump.Figure 1 & 2, screenshot April 2013 from ‹instagram.com/xiaxue›In her successful attempt at generating anticipation, the “bump” itself seemed to garner its own following on Twitter and Instagram, with many followers discussing how the Influencer dressed “it”, and how “it” was evolving over the weeks. One follower even compiled a collage of xiaxue’s “bump” chronologically and gifted it to the Influencer as an art image via Twitter on the day she delivered Baby Dash (Figure 3 & 4). Followers also frequently speculated and bantered about how her baby would look, and mused about how much they were going to adore him. Figure 3 & 4, screenshot March 2013 from ‹twitter.com/xiaxue› While Lupton (42) has conceptualized the sharing of images that precede birth as a “rite of passage”, Influencer mothers who publish sonograms deliberately do so in order to claim digital estates for their to-be micro-microcelebrities in the form of “reserved” social media handles, blog URLs, and unique hashtags for self-branding. For instance, at the 3-month mark of her pregnancy, Influencer bongqiuqiu debuted her baby’s dedicated hashtag, “#MereGoRound” in a birth announcement on her on Instagram account. Shortly after, she started an Instagram account, “@MereGoRound”, for her baby, who amassed over 5.5k followers prior to her birth. Figure 5 & 6, screenshot March 2015 from instagram.com/meregoround and instagram.com/bongqiuqiuThe debut picture features a heavily pregnant belly shot of bongqiuqiu (Figure 5), creating much anticipation for the arrival of a new micro-microcelebrity: in the six months leading up to her birth, various family, friends, and fans shared Instagram images of their gifts and welcome party for @MereGoRound, and followers shared congratulations and fan art on the dedicated Instagram hashtag. During this time, bongqiuqiu also frequently updated followers on her pregnancy progress, not without advertising her (presumably sponsored) gynecologist and hospital stay in her pregnancy diaries (Figure 6) – like Baby Dash, even as a foetus @MereGoRound was accumulating advertorials. Presently at six months old, @MereGoRound boasts almost 40k followers on Instagram on which embedded in the narrative of her growth are sponsored products and services from various advertisers.Non-Baby-Related AdvertorialsPrior to her pregnancy, Influencer bongqiuqiu hopped onto the micro-microcelebrity bandwagon in the wake of Baby Dash’s birth, by using her niece “#HeYurou” in her advertorials. Many Influencers attempt to naturalize their advertorials by composing their post as if recounting a family event. With reference to a child, parent, or partner, they may muse or quip about a product being used or an experience being shared in a bid to mask the distinction between their personal and commercial material. bongqiuqiu frequently posted personal, non-sponsored images engaging in daily mundane activities under the dedicated hashtag “#HeYurou”.However, this was occasionally interspersed with pictures of her niece holding on to various products including storybooks (Figure 8) and shopping bags (Figure 9). At first glance, this might have seemed like any mundane daily update the Influencer often posts. However, a close inspection reveals the caption bearing sponsor hashtags, tags, and campaign information. For instance, one Instagram post shows #HeYurou casually holding on to and staring at a burger in KFC wrapping (Figure 7), but when read in tandem with bongqiuqiu’s other KFC-related posts published over a span of a few months, it becomes clear that #HeYurou was in fact advertising for KFC. Figure 7, 8, 9, screenshot December 2014 from ‹instagram.com/bongqiuqiu›Elsewhere, Baby Dash was incorporated into xiaxue’s car sponsorship with over 20 large decals of one of his viral photos – dubbed “pineapple Dash” among followers – plastered all over her vehicle (Figure 10). Followers who spot the car in public are encouraged to photograph and upload the image using its dedicated hashtag, “#xiaxuecar” as part of the Influencer’s car sponsorship – an engagement scarcely related to her young child. Since then, xiaxue has speculated producing offshoots of “pineapple Dash” products including smartphone casings. Figure 10, screenshot December 2014 from ‹instagram.com/xiaxue›Follower EngagementSponsors regularly organize fan meet-and-greets headlined by micro-microcelebrities in order to attract potential customers. Photo opportunities and the chance to see Baby Dash “in the flesh” frequently front press and promotional material of marketing campaigns. Elsewhere on social media, several Baby Dash fan and tribute accounts have also emerged on Instagram, reposting images and related media of the micro-microcelebrity with overt adoration, no doubt encouraged by xiaxue, who began crowdsourcing captions for Baby Dash’s photos.Influencer ohsofickle postures #BabyElroyE’s follower engagement in a more subtle way. In her YouTube channel that debut in the month of her baby’s birth, ohsofickle produces video diaries of being a young, single, mother who is raising a child (Figure 11). In each episode, #BabyElroyE is the main feature whose daily activities are documented, and while there is some advertising embedded, ohsofickle’s approach on YouTube is much less overt than others as it features much more non-monetized personal content (Figure 12). Her blog serves as a backchannel to her vlogs, in which she recounts her struggles with motherhood and explicitly solicits the advice of mothers. However, owing to her young age (she became an Influencer at 17 and gave birth at 24), many of her followers are teenagers and young women who respond to her solicitations by gushing over #BabyElroyE’s images on Instagram. Figure 11 & 12, screenshot September 2015 from ‹instagram.com/ohsofickle›PrivacyAs noted by Holloway et al. (23), children like micro-microcelebrities will be among the first cohorts to inherit “digital profiles” of their “whole lifetime” as a “work in progress”, from parents who habitually underestimate or discount the privacy and long term effects of publicizing information about their children at the time of posting. This matters in a climate where social media platforms can amend privacy policies without user consent (23), and is even more pressing for micro-microcelebrities whose followers store, republish, and recirculate information in fan networks, resulting in digital footprints with persistence, replicability, scalability, searchability (boyd), and extended longevity in public circulation which can be attributed back to the children indefinitely (Leaver, “Ends”).Despite minimum age restrictions and recent concerns with “digital kidnapping” where users steal images of other young children to be re-posted as their own (Whigham), some social media platforms rarely police the proliferation of accounts set up by parents on behalf of their underage children prominently displaying their legal names and life histories, citing differing jurisdictions in various countries (Facebook; Instagram), while others claim to disable accounts if users report an “incorrect birth date” (cf. Google for YouTube). In Singapore, the Media Development Authority (MDA) which governs all print and digital media has no firm regulations for this but suggests that the age of consent is 16 judging by their recommendation to parents with children aged below 16 to subscribe to Internet filtering services (Media Development Authority, “Regulatory” 1). Moreover, current initiatives have been focused on how parents can impart digital literacy to their children (Media Development Authority, “Empowered”; Media Literacy Council) as opposed to educating parents about the digital footprints they may be unwittingly leaving about their children.The digital lives of micro-microcelebrities pose new layers of concern given their publicness and deliberate publicity, specifically hinged on making visible the usually inaccessible, private aspects of everyday life (Marshall, “Persona” 5).Scholars note that celebrities are individuals for whom speculation of their private lives takes precedence over their actual public role or career (Geraghty 100-101; Turner 8). However, the personae of Influencers and their young children are shaped by ambiguously blurring the boundaries of privacy and publicness in order to bait followers’ attention, such that privacy and publicness are defined by being broadcast, circulated, and publicized (Warner 414). In other words, the publicness of micro-microcelebrities is premised on the extent of the intentional publicity rather than simply being in the public domain (Marwick 223-231, emphasis mine).Among Influencers privacy concerns have aroused awareness but not action – Baby Dash’s Influencer mother admitted in a national radio interview that he has received a death threat via Instagram but feels that her child is unlikely to be actually attacked (Channel News Asia) – because privacy is a commodity that is manipulated and performed to advance their micro-microcelebrities’ careers. As pioneer micro-microcelebrities are all under 2-years-old at present, future research warrants investigating “child-centred definitions” (Third et al.) of the transition in which they come of age, grow an awareness of their digital presence, respond to their Influencer mothers’ actions, and potentially take over their accounts.Young LabourThe Ministry of Manpower (MOM) in Singapore, which regulates the employment of children and young persons, states that children under the age of 13 may not legally work in non-industrial or industrial settings (Ministry of Manpower). However, the same document later ambiguously states underaged children who do work can only do so under strict work limits (Ministry of Manpower). Elsewhere (Chan), it is noted that national labour statistics have thus far only focused on those above the age of 15, thus neglecting a true reflection of underaged labour in Singapore. This is despite the prominence of micro-microcelebrities who are put in front of (video) cameras to build social media content. Additionally, the work of micro-microcelebrities on digital platforms has not yet been formally recognized as labour, and is not regulated by any authority including Influencer management firms, clients, the MDA, and the MOM. Brief snippets from my ethnographic fieldwork with Influencer management agencies in Singapore similarly reveal that micro-microcelebrities’ labour engagements and control of their earnings are entirely at their parents’ discretion.As models and actors, micro-microcelebrities are one form of entertainment workers who if between the ages of 15 days and 18 years in the state of California are required to obtain an Entertainment Work Permit to be gainfully employed, adhering to strict work, schooling, and rest hour quotas (Department of Industrial Relations). Furthermore, the Californian Coogan Law affirms that earnings by these minors are their own property and not their parents’, although they are not old enough to legally control their finances and rely on the state to govern their earnings with a legal guardian (Screen Actors Guild). However, this similarly excludes underaged children and micro-microcelebrities engaged in creative digital ecologies. Future research should look into safeguards and instruments among young child entertainers, especially for micro-micrcocelebrities’ among whom commercial work and personal documentation is not always distinct, and are in fact deliberately intertwined in order to better engage with followers for relatabilityGrowing Up BrandedIn the wake of moral panics over excessive surveillance technologies, children’s safety on the Internet, and data retention concerns, micro-microcelebrities and their Influencer mothers stand out for their deliberately personal and overtly commercial approach towards self-documenting, self-presenting, and self-publicizing from the moment of conception. As these debut micro-microcelebrities grow older and inherit digital publics, personae, and careers, future research should focus on the transition of their ownership, engagement, and reactions to a branded childhood in which babies were postured for an initimate public.ReferencesAbidin, Crystal. “Communicative Intimacies: Influencers and Perceived Interconnectedness.” Ada: A Journal of Gender, New Media, & Technology. Forthcoming, Nov 2015.Aiello, Marianne. “Mommy Blog Banner Ads Get Results.” Healthcare Marketing Advisor 17 Nov. 2010. HealthLeaders Media. 16 Aug. 2015 ‹http://healthleadersmedia.com/content/MAR-259215/Mommy-Blog-Banner-Ads-Get-Results›.Azzarone, Stephanie. “When Consumers Report: Mommy Blogging Your Way to Success.” Playthings 18 Feb. 2009. 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