Miracle-dz/UniFAR-FTUs huggingface dataset:
Embryo Aggregation Promotes Derivation Efficiency of Outgrowths from Porcine Blastocysts

Porcine embryonic stem cells (pESCs) have become an advantageous experimental tool for developing therapeutic applications and producing transgenic animals. However, despite numerous reports of putative pESC lines, deriving validated pESC lines from embryos produced in vitro remains difficult. Here, we report that embryo aggregation was useful for deriving pESCs from in vitro-produced embryos. Blastocysts derived from embryo aggregation formed a larger number of colonies and maintained cell culture stability. Our derived cell lines demonstrated expression of pluripotent markers (alkaline phosphatase, Oct4, Sox2, and Nanog), an ability to form embryoid bodies, and the capacity to differentiate into the three germ layers. A cytogenetic analysis of these cells revealed that all lines derived from aggregated blastocysts had normal female and male karyotypes. These results demonstrate that embryo aggregation could be a useful technique to improve the efficiency of deriving ESCs from in vitro-fertilized pig embryos, studying early development, and deriving pluripotent ESCs in vitro in other mammals.
A Universal Approximation Theorem for Mixture-of-Experts Models

The mixture-of-experts (MoE) model is a popular neural network architecture for nonlinear regression and classification. The class of MoE mean functions is known to be uniformly convergent to any unknown target function, assuming that the target function is from a Sobolev space that is sufficiently differentiable and that the domain of estimation is a compact unit hypercube. We provide an alternative result, which shows that the class of MoE mean functions is dense in the class of all continuous functions over arbitrary compact domains of estimation. Our result can be viewed as a universal approximation theorem for MoE models. The theorem we present allows MoE users to be confident in applying such models for estimation when data arise from nonlinear and nondifferentiable generative processes.
Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode network in early stage Alzheimer's disease

In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a pivotal role in neurocognition, and its gene contains a functional polymorphism (Val66Met) that may explain individual differences in brain volume and memory-related activity. In this study, we enrolled 186 Alzheimer's disease (AD) patients who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM) structural covariance networks (SCN). The patients were divided into three groups according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n = 55). Seed-based analysis was performed focusing on four SCN networks. Neurobehavioral scores served as the major outcome factor. Only peak cluster volumes of default mode medial temporal lobe network showed significant genotype interactions, of which the interconnected peak clusters showed dose-dependent genotype effects. There were also significant correlations between the cognitive test scores and interconnected-cluster volumes, especially in the orbitofrontal cortex. These findings support the hypothesis that BDNF rs6265 polymorphisms modulate entorhinal cortex-interconnected clusters and the valine allele was associated with stronger structural covariance patterns that determined the cognitive outcomes.
Classification of Arctic, midlatitude and tropical clouds in the mixed-phase temperature regime

Abstract. The degree of glaciation of mixed-phase clouds constitutes one of the largest uncertainties in climate prediction. In order to better understand cloud glaciation, cloud spectrometer observations are presented in this paper, which were made in the mixed-phase temperature regime between 0 and −38 °C (273 to 235 K), where cloud particles can either be frozen or liquid. The extensive data set covers four airborne field campaigns providing a total of 139 000 1 Hz data points (38.6 h within clouds) over Arctic, midlatitude and tropical regions. We develop algorithms, combining the information on number concentration, size and asphericity of the observed cloud particles to classify four cloud types: liquid clouds, clouds in which liquid droplets and ice crystals coexist, fully glaciated clouds after the Wegener–Bergeron–Findeisen process and clouds where secondary ice formation occurred. We quantify the occurrence of these cloud groups depending on the geographical region and temperature and find that liquid clouds dominate our measurements during the Arctic spring, while clouds dominated by the Wegener–Bergeron–Findeisen process are most common in midlatitude spring. The coexistence of liquid water and ice crystals is found over the whole mixed-phase temperature range in tropical convective towers in the dry season. Secondary ice is found at midlatitudes at −5 to −10 °C (268 to 263 K) and at higher altitudes, i.e. lower temperatures in the tropics. The distribution of the cloud types with decreasing temperature is shown to be consistent with the theory of evolution of mixed-phase clouds. With this study, we aim to contribute to a large statistical database on cloud types in the mixed-phase temperature regime.
Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer

Background Approximately 15%–23% of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), which leads to the activation of signaling pathways that stimulate cell proliferation and survival. HER2-targeted therapy has substantially improved outcomes in patients with HER2-positive breast cancer. However, both de novo and acquired resistance are observed. Design A literature search was performed to identify proposed mechanisms of resistance to HER2-targeted therapy and identified novel targets in clinical development for treating HER2-resistant disease. Results Proposed HER2-resistance mechanisms include impediments to HER2-inhibitor binding, signaling through alternative pathways, upregulation of signaling pathways downstream of HER2, and failure to elicit an appropriate immune response. Although continuing HER2 inhibition beyond progression may provide an additional clinical benefit, the availability of novel therapies targeting different mechanisms of action could improve outcomes. The developmental strategy with the most available data is targeting the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway. The oral mTOR inhibitor everolimus has shown promising activity in combination with chemotherapy and trastuzumab in trastuzumab-refractory, advanced breast cancer. Conclusions Non-HER2-targeted therapy is a promising means of overcoming resistance to HER2-targeted treatment. Ongoing clinical studies will provide additional information on the efficacy and safety of novel targeted therapies in HER2-resistant advanced breast cancer.
Linkage Disequilibrium Estimation of Effective Population Size with Immigrants from Divergent Populations: A Case Study on Spanish Mackerel (Scomberomorus commerson)

Estimates of genetic effective population size (Ne) using molecular markers are a potentially useful tool for the management of endangered through to commercial species. However, pitfalls are predicted when the effective size is large because estimates require large numbers of samples from wild populations for statistical validity. Our simulations showed that linkage disequilibrium estimates of Ne up to 10,000 with finite confidence limits can be achieved with sample sizes of approximately 5000. This number was deduced from empirical allele frequencies of seven polymorphic microsatellite loci in a commercially harvested fisheries species, the narrow-barred Spanish mackerel (Scomberomorus commerson). As expected, the smallest SD of Ne estimates occurred when low-frequency alleles were excluded. Additional simulations indicated that the linkage disequilibrium method was sensitive to small numbers of genotypes from cryptic species or conspecific immigrants. A correspondence analysis algorithm was developed to detect and remove outlier genotypes that could possibly be inadvertently sampled from cryptic species or nonbreeding immigrants from genetically separate populations. Simulations demonstrated the value of this approach in Spanish mackerel data. When putative immigrants were removed from the empirical data, 95% of the Ne estimates from jacknife resampling were greater than 24,000.
Cannabis use among middle and high school students in Ontario: a school-based cross-sectional study.

BACKGROUND Cannabis use can have serious detrimental effects in children and adolescents. It is therefore important to continually assess the use of cannabis among young people in order to inform prevention efforts. We assessed the prevalence of cannabis use among middle and high school students in Ontario and examined its association with demographic and behavioural factors. METHODS Data were obtained from the 2015 Ontario Student Drug Use and Health Survey, a province-wide school-based survey of students in grades 7 through 12. Analyses included a representative sample of 9920 middle and high school students. Bivariate cross-tabulations and logistic regression analyses were used to investigate the factors associated with cannabis use. RESULTS Overall, 21.5% and 13.9% of students reported using cannabis in the previous year and previous month, respectively. The conditional probability that an adolescent who reported cannabis use in the previous year would report daily use was 12.5%. There was a significant dose-response gradient with age, with older students being more likely to use cannabis than younger students. In multivariable analyses, being in grades 10 through 12 (odds ratios [ORs] ranged from 3.71 to 3.85), being black (OR 2.67 [95% confidence interval (CI) 1.76-4.05]), using tobacco cigarettes (OR 10.10 [95% CI 8.68-13.92]) and being an occasional (OR 5.35 [95% CI 4.01-7.13]) or regular (OR 14.6 [95% CI 10.8-19.89]) alcohol user were associated with greater odds of cannabis use. Being an immigrant was associated with lower odds of cannabis use (OR 0.55 [95% CI 0.39-0.78]). INTERPRETATION The findings suggest that cannabis use is prevalent among middle and high school students in Ontario and is strongly associated with tobacco cigarette smoking and alcohol consumption. Future research should document trends in cannabis use over time, including its risks, especially when the legalization of recreational cannabis comes into effect.
Simultaneous analysis of T helper subsets (Th1, Th2, Th9, Th17, Th22, Tfh, Tr1 and Tregs) markers expression in periapical lesions reveals multiple cytokine clusters accountable for lesions activity and inactivity status

Previous studies demonstrate that the balance between pro- and anti-inflammatory mediators determines the stable or progressive nature of periapical granulomas by modulating the balance of the osteoclastogenic factor RANKL and its antagonist OPG. However, the cytokine networks operating in the development of periapical lesions are quite more complex than what the simple pro- versus anti-inflammatory mediators' paradigm suggests. Here we simultaneously investigated the patterns of Th1, Th2, Th9, Th17, Th22, Thf, Tr1 and Tregs cytokines/markers expression in human periapical granulomas. Methods The expression of TNF-α, IFN-γ, IL-17A, IL23, IL21, IL-33, IL-10, IL-4, IL-9, IL-22, FOXp3 markers (via RealTimePCR array) was accessed in active/progressive (N=40) versus inactive/stable (N=70) periapical granulomas (as determined by RANKL/OPG expression ratio), and also to compare these samples with a panel of control specimens (N=26). A cluster analysis of 13 cytokine levels was performed to examine possible clustering between the cytokines in a total of 110 granulomas. Results The expression of all target cytokines was higher in the granulomas than in control samples. TNF-α, IFN-γ, IL-17A and IL-21 mRNA levels were significantly higher in active granulomas, while in inactive lesions the expression levels of IL-4, IL-9, IL-10, IL-22 and FOXp3 were higher than in active granulomas. Five clusters were identified in inactive lesion groups, being the variance in the expression levels of IL-17, IL-10, FOXp3, IFN-γ, IL-9, IL-33 and IL-4 statistically significant (KW p<0.05). Three clusters were identified in active lesions, being the variance in the expression levels of IL-22, IL-10, IFN-γ, IL-17, IL-33, FOXp3, IL-21 and RANKL statistically significant (KW p<0.05). Conclusion There is a clear dichotomy in the profile of cytokine expression in inactive and active periapical lesions. While the widespread cytokine expression seems to be a feature of chronic lesions, hierarchical cluster analysis demonstrates the association of TNF-α, IL-21, IL-17 and IFN-γ with lesions activity, and the association of FOXP3, IL-10, IL-9, IL-4 and IL-22 with lesions inactivity.
Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss

Significance Bone deficits are frequent complications observed in HIV-1–infected patients. Our study demonstrates that HIV-1 infects osteoclasts, the cells specialized in bone degradation, using different models including HIV-1–infected humanized mice. We decipher the cellular mechanisms by which HIV-1 contributes to enhanced bone degradation in human osteoclasts, showing that the virus modifies the structure and function of the sealing zone, the bone resorption machinery of osteoclasts. We identify the viral protein Nef as the key factor responsible for such effects. As a proof-of-concept, we correlate bone deficit in transgenic Nef-expressing mice with enhanced osteoclast activity. Therefore, our findings provide formal evidence that osteoclasts constitute HIV-1 host target cells, contributing to bone deficits in vivo. Bone deficits are frequent in HIV-1–infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery. Indeed, the sealing zone is broader due to F-actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef is involved in all HIV-1–induced effects partly through the activation of Src, a regulator of podosomes and of their assembly as a sealing zone. Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived from these animals display high osteolytic activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and their pathological contribution to bone disorders induced by this virus, in part via Nef.
Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California

Background: Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. Objectives: We evaluated the potential effects of low environmental exposures to perchlorate on thyroid function. Methods: Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County, California, during 2000–2003, a period when much of the area’s water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 μg/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. Results: The median urinary perchlorate concentration was 6.5 μg/L, about two times higher than in the general U.S. population. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) [regression coefficient (β) = –0.70; 95% CI: –1.06, –0.34], decreasing free thyroxine (fT4) (β = –0.053; 95% CI: –0.092, –0.013), and increasing log10 thyroid-stimulating hormone (β = 0.071; 95% CI: 0.008, 0.133). Conclusions: These results suggest that environmental perchlorate exposures may affect thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment. Citation: Steinmaus C, Pearl M, Kharrazi M, Blount BC, Miller MD, Pearce EN, Valentin-Blasini L, DeLorenze G, Hoofnagle AN, Liaw J. 2016. Thyroid hormones and moderate exposure to perchlorate during pregnancy in women in Southern California. Environ Health Perspect 124:861–867; http://dx.doi. org/10.1289/ehp.1409614
Biosorption of chromium (VI) from aqueous solutions by the husk of Bengal gram (Cicer arientinum)

The potential to remove Cr (VI) from aqueous solutions through biosorption using the husk of Bengal gram (Cicer arientinum), was investigated in batch experiments. The results showed removal of 99.9% of chromium in the 10 $mgl^{-1}$ chromium solution, the biomass required at saturation was 1 g $mg^{-1}$. Kinetic experiments revealed that the dilute chromium solutions reached equilibrium within 180 min. The biosorptive capacity of the (bgh) was dependent on the pH of the chromium solution, with pH 2 being optimal. The adsorption data fit well with the Langmuir and Freundlich isotherm models. The adsorption capacity calculated from the Langmuir isotherm was 91.64 mg Cr (VI)/g at pH 2. The adsorption capacity increased with increase in agitation speed and an optimum was achieved at 120 rpm. The biosorption of Cr (VI) was studied by Fourier transform infrared spectroscopy (FTIR), which suggested that the presence of Cr (VI)ions in the biomass affects the bands corresponding to hydroxyl and carboxyl groups. Comprehensive characterisation of parameters indicates bgh to be an excellent material for biosorption of Cr (VI) to treat wastewaters containing low concentration of the metal.
Comparison of culture, single and multiplex real‐time PCR for detection of Sabin poliovirus shedding in recently vaccinated Indian children

Although, culture is considered the gold standard for poliovirus detection from stool samples, real‐time PCR has emerged as a faster and more sensitive alternative. Detection of poliovirus from the stool of recently vaccinated children by culture, single and multiplex real‐time PCR was compared. Of the 80 samples tested, 55 (68.75%) were positive by culture compared to 61 (76.25%) and 60 (75%) samples by the single and one step multiplex real‐time PCR assays respectively. Real‐time PCR (singleplex and multiplex) is more sensitive than culture for poliovirus detection in stool, although the difference was not statistically significant.
Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human Antimicrobial β-Defensin 1

ABSTRACT The antimicrobial peptide human β-defensin 1 (hBD1) is continuously produced by epithelial cells in many tissues. Compared to other defensins, hBD1 has only minor antibiotic activity in its native state. After reduction of its disulfide bridges, however, it becomes a potent antimicrobial agent against bacteria, while the oxidized native form (hBD1ox) shows specific activity against Gram-negative bacteria. We show that the killing mechanism of hBD1ox depends on aerobic growth conditions and bacterial enzymes. We analyzed the different activities of hBD1 using mutants of Escherichia coli lacking one or more specific proteins of their outer membrane, cytosol, or redox systems. We discovered that DsbA and DsbB are essential for the antimicrobial activity of hBD1ox but not for that of reduced hBD1 (hBD1red). Furthermore, our results strongly suggest that hBD1ox uses outer membrane protein FepA to penetrate the bacterial periplasm space. In contrast, other bacterial proteins in the outer membrane and cytosol did not modify the antimicrobial activity. Using immunogold labeling, we identified the localization of hBD1ox in the periplasmic space and partly in the outer membrane of E. coli. However, in resistant mutants lacking DsbA and DsbB, hBD1ox was detected mainly in the bacterial cytosol. In summary, we discovered that hBD1ox could use FepA to enter the periplasmic space, where its activity depends on presence of DsbA and DsbB. HBD1ox concentrates in the periplasm in Gram-negative bacteria, which finally leads to bleb formation and death of the bacteria. Thus, the bacterial redox system plays an essential role in mechanisms of resistance against host-derived peptides such as hBD1.
Thickness Effect on Fatigue Strength of Welded Joint Improved by HFMI

It is known that the fatigue strength of a welded joint decreases with the increase in the thickness of load carrying member as “Thickness Effect”. It is required in the Common Structural Rule (CSR 1) ) that the fatigue strength reduction factor set to 0.25 uniformly for welded structures. However, the coefficient was decided empirically because of insufficient knowledge about the mechanism of the effect, therefore, the research 2) was carried out to investigate the factors which affect thickness effect by Class NK with the Shipbuilders’ Association of Japan. Moreover, economical and rational design production is required to reduce the dimensions and the thickness of welded structures. Post weld treatments are one of useful methods to achieve this requirement; therefore, studies to clarify the fatigue strength improvement effect by post weld treatments for weld toe have been increased for reflecting the effect in design rules. However, there is insufficient experimental data for quantitative evaluation about the thickness effect and the fatigue strength improvement effect of post weld treatments for extremely-thick welded joint. In shipbuilding industry, the following members are given as examples; Penetration of longitudinal members, weldment between Upper Deck plating and trans. Web, Lower Stool and so on. Especially, Hatch side coaming is 80mm thick over.