gebhart/patrepeval huggingface dataset:
COVID-19 susceptibility and severity risks in a survey of over 500,000 individuals (2020)

ABSTRACT Background The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analyzing population-scale datasets in real time to monitor and better understand the evolving pandemic. Methods The AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors, and exposures for over 563,000 adult individuals in the U.S. in just under four months, including over 4,700 COVID-19 cases as measured by a self-reported positive test. Results We replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for males even after adjusting for known exposures and age (adjusted odds ratio [aOR]=1.36, 95% confidence interval [CI] = (1.19, 1.55)). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualized COVID-19 susceptibility (area under the curve [AUC]=0.84) and severity outcomes including hospitalization and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex, and genetic ancestry groups within the study. Conclusion The results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic. THUMBNAIL What is already known on this subject The COVID-19 pandemic has exacted a historic toll on human lives, healthcare systems and global economies, with over 83 million cases and over 1.8 million deaths worldwide as of January 2021. COVID-19 risk factors for susceptibility and severity have been extensively investigated by clinical and public health researchers. Several groups have developed risk models to predict COVID-19 illness outcomes based on known risk factors. What this study adds We performed association analyses for COVID-19 susceptibility and severity in a large, at-home survey and replicated much of the previous clinical literature. Associations were further adjusted for known COVID-19 exposures, and we observed elevated positive test odds for males even after adjustment for these known exposures. We developed risk models and evaluated them across different age, sex, and genetic ancestry cohorts, and showed robust performance across all cohorts in a holdout dataset. Our results establish large-scale, self-reported surveys as a potential framework for investigating and monitoring rapidly evolving pandemics.
Cold plasma selectivity and the possibility of a paradigm shift in cancer therapy (2011)

The development of cold plasma tumour ablation has the potential of shifting the current paradigm of cancer treatment and enabling the transformation of cancer treatment technologies by utilisation of another state of matter.
Uma nova síntese de alfa-bromo-acetofenonas e sua aplicação na obtenção de 2-benzoil-benzofuranas (2006)

SYNTHESIS OF -BROMOACETOPHENONES AND ITS APPLICATION IN OBTAINING 2-BENZOYLBENZOFURANES. -Bromoacetophenones are important in organic synthesis. They have been widely used as precursors of several natural products. Several methods of bromination aiming at their synthesis have been described, however they furnish a mixture of starting material 10, mono 8 and dibromide 11 products. We developed a novel, simple and efficient synthesis of these compounds with applications in the synthesis of benzoylbenzofurans 9, compounds with important pharmacological properties, such as the ability of dilating the coronary artery and analgesic action. Such compounds have also been used as key intermediates to obtain quinone systems.
Design and Synthesis of (Z)-5-(Substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one Analogues as Anti-Tyrosinase and Antioxidant Compounds: In Vitro and In Silico Insights (2022)

Many compounds containing the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, including cinnamamide derivatives, have been shown to inhibit tyrosinase potently in vitro and in vivo. Structural changes to cinnamamide derivatives were produced by adding a dithionate functional group to provide eight (<i>Z</i>)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs with high log <i>p</i> values for skin. These analogs were synthesized using a two-step reaction, and their stereochemistry was confirmed using the <sup>3</sup><i>J</i><sub>C4-Hβ</sub> values of C4 measured in proton-coupled <sup>13</sup>C mode. Analogs <b>2</b> (IC<sub>50</sub> = 5.21 ± 0.86 µM) and <b>3</b> (IC<sub>50</sub> = 1.03 ± 0.14 µM) more potently inhibited mushroom tyrosinase than kojic acid (IC<sub>50</sub> = 25.26 ± 1.10 µM). Docking results showed <b>2</b> binds strongly to the active site of tyrosinase, while <b>3</b> binds strongly to an allosteric site. Kinetic studies using l-tyrosine as substrate indicated <b>2</b> and <b>3</b> competitively and non-competitively inhibit tyrosinase, respectively, which was supported by our docking results. In B16F10 cells, <b>3</b> significantly and concentration-dependently reduced α-MSH plus IBMX induced increases in cellular tyrosinase activity and melanin production and the similarity between these inhibitory patterns implied that the anti-melanogenic effect of <b>3</b> might be due to its tyrosinase-inhibitory ability. In addition, <b>2</b> and <b>3</b> exhibited strong antioxidant effects; for example, they reduced ROS and ONOO<sup>-</sup> levels and exhibited radical scavenging activities, suggesting that these effects might underlie their anti-melanogenic effects. Furthermore, <b>3</b> suppressed the expressions of melanogenesis-associated proteins and genes in B16F10 cells. These results suggest (<i>Z</i>)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs offer a means of producing novel anti-melanogenesis agents.
Pharmacologic Treatment of Acute Traumatic Brain Injury (1996)

During the past several years, results of clinical trials have generated considerable optimism about the prospects for effective treatment of acute central nervous system (CNS) injuries. A multicenter trial demonstrated the effectiveness of methylprednisolone, as well as naloxone hydrochloride, in improving neurologic recovery after spinal cord injury.<sup>1</sup>In ischemic stroke, early treatment with tissue plasminogen activator<sup>2</sup>or treatment with low-molecular-weight heparin<sup>3</sup>led to improved outcome for some patients. To date, however, no effective pharmacotherapy has been developed for head injury. One of the more promising experimental strategies for treatment of acute CNS injury has been the use of antioxidants or free-radical scavengers. This approach is based on the concept that oxygen free radicals are generated in response to the insult, thereby overwhelming endogenous antioxidant or free radical-scavenging systems such as superoxide dismutase (SOD), catalase, glutathione, ascorbic acid, and α-tocopherol.<sup>4,5</sup>Free radicals are believed to contribute to
The Optical Properties of 'Moth Eye' Antireflection Surfaces (1982)

Abstract A 'moth eye' antireflection surface is a very fine array of protuberances which behaves as a gradation of refractive index, and which substantially reduces the reflectance. The reflection and transmission properties of such surfaces are described, and are shown to be equal to those of the best multilayer antireflection coatings.
Survival of Early Stripped Eggs of the Noble Crayfish, <i>Astacus astacu</i>, and Effects of Saline Solution During Artificial Incubation (2014)

There is growing interest in using recirculating aquaculture systems (RAS) to produce juvenile noble crayfish, Astacus astacus (Linnaeus), a valuable and once plentiful food species in Europe, now a highly endangered species. The survival rates of early stripped eggs of A. astacus were compared across anti-fungal treatments in an artificial RAS incubation system based on a saline bath of approx. 20 – 22 mS cm-1 or 15 – 16 PSU over two different durations. Time from fertilisation to hatching was 54 days or 1220 degree-days. Low survival rates (live successfully hatched juveniles at end of experimental period) between 13.9 ± 2.5% and 25.4 ± 1.5% were obtained. Survival was significantly affected by the duration of egg bath within the saline solution with twice as high survival rates when eggs were saline-bathed once every two days for five minutes in comparison to eggs without treatment. Fungal rates were significantly affected by treating the eggs with a saline solution with infection rates decreasing from 3.7 ± 1.0% to 0.8 ± 0.5% in the ten minute saline bath treatment. Appropriately applied saline bathing can markedly improve survival of early-stripped noble crayfish eggs. However, further research is required to determine whether viable levels of hatching success can be obtained using early stripping and saline treatment.
Deficiency of Prdx6 in lens epithelial cells induces ER stress response-mediated impaired homeostasis and apoptosis (2011)

The multifunctional cytoprotective protein peroxiredoxin 6 (Prdx6) maintains cellular homeostasis and membrane integrity by regulating expression of intracellular reactive oxygen species (ROS) and phospholipid turnover. Using cells derived from targeted inactivation of Prdx6 gene or its depletion by RNA interference or aging, we showed that Prdx6 deficiency in cells evoked unfolded protein response (UPR), evidenced by increased expression or activation of proapoptotic factors, CHOP, ATF4, PERK, IRE-α and eIF2-α and by increased caspases 3 and 12 processing. Those cells displayed enhanced and sustained expression of endoplasmic reticulum (ER) stress-related chaperon proteins, Bip/glucose-regulated protein 78, calnexin, and calreticulin. Under cellular stress induced by hypoxia (1% O(2) or CoCl(2) treatment) or tunicamycin, Prdx6-deficient cells exhibited aberrant activation of ER stress-responsive genes/protein with higher expression of ROS, and died with apoptosis. Wild-type cells exposed to tunicamycin or hypoxia remained relatively insensitive with lower expression of ROS and ER-responsive genes than did Prdx6-deficient cells, but upregulation of ER stress responsive proteins or chaperones mimicked the UPR response of Prdx6-deficient or aging cells. Expression of Prdx6 blocked ER stress-induced deleterious signaling by optimizing physiologically aberrant expression of ER stress responsive genes/proteins in Prdx6-deficient cells or cells facing stressors, and rescued the cells from apoptosis. These findings demonstrate that impaired homeostasis and progression of pathogenesis in Prdx6-deficient lens epithelial cells or in aging cells should be blocked by a supply of Prdx6. The results provide a new molecular basis for understanding the etiology of several age-associated degenerative disorders, and potentially for developing antioxidant Prdx6-based therapeutics.
Neuroanatomy of morphine-modulating peptides. (1987)

Antisera against two mammalian peptides related to the molluscan cardioexcitatory peptide Phe-Met-Arg-Phe-NH2 were used to locate immunoreactive neurons in the rat brain, nerve fibres and terminals in the spinal cord, sympathetic ganglion cells and adrenal chromaffin cells. Immunoreactivity for the newly characterised octa- and octadecapeptide was detected in nerve cell bodies in the hypothalamic area, including parts of the dorsomedial, periventricular and paraventricular nuclei, and in the nucleus tractus solitarii. Nerve terminals in the superficial laminae of the spinal cord were also immunoreactive for these peptides, while the sensory ganglia were nonreactive. Some principal ganglion cells in the superior cervical ganglia exhibited bright immunofluorescence for the peptides, and a few adrenal medullary cells were immunoreactive. The presence of these peptides in the substantia gelatinosa of the spinal cord suggests that they may be involved in sensory neurotransmission, especially in the mechanisms mediating pain. In the hypothalamo-hypophysial system these peptides may be involved in the regulation of hormonal systems. They may also act as co-transmitters in the sympathetic nervous system.
Neuroengineering challenges of fusing robotics and neuroscience (2020)

Advances in neuroscience are inspiring developments in robotics and vice versa.
High reliability CoFeB/MgO/CoFeB magnetic tunnel junction fabrication using low-damage ion beam etching (2020)

Abstract In this work, the impact of pattern edge of MgO films due to electrode separation process on its electrical reliability was investigated by measuring and analyzing I – V and time-dependent dielectric breakdown (TDDB) characteristics of MgO films with different pattern edge length. The measured TDDB lifetime at 63% drastically decreased from 1440 to 2 s when the pattern edge length increased from 32 to 320 μ m, thus the electric reliability of MgO films can be significantly degraded due to the pattern edge. It was found that this issue can be solved by improving the process condition of ion bean etching (IBE), by turning the IBE angle and the IBE angle divergence. These findings can lead to high reliability magnetic tunnel junction fabrication in spin-transfer torque magnetic random access memory.
Obesity genes (1996)

This review highlights the considerable advances in the understanding of the inheritance of fatness and the possible genetic mechanisms. The investigation of animal models confirms the fundamental importance of genes in determining fatness and demonstrates a genetic link between adipocyte function, derangements of steroid metabolism, insulin secretion and hypothalamic regulation. The heterogeneous nature of human obesity makes it unwise to extrapolate directly from the findings in animals but these findings do provide important clues to the situation in man. It is crucial that advances in the knowledge of genes involved in human obesity are paralleled by an understanding of gene-gene interactions and the influence of environmental factors. The rapidly increasing prevalence of obesity in society underlines the paramount influence of the environment.
Why b-values for hydraulic fracture stimulations are so high (2015)

Summary The estimation of b-value from the Gutenberg-Richter relationship is widely used to aid the interpretation of hydraulic fracture treatments. However, it is difficult to calculate b-values for microseismic datasets because of the low range of magnitudes present and the low number of events (Bender, 1983; Felzer, 2006). The maximum likelihood method (MLE) (Aki, 1965) is a common approach for b-value estimation, although it can lead to higher values than when using binned magnitudes. Also, b-value dependence on the event count is discussed.
3,5-Dioxopyrazolidines, Novel Inhibitors of UDP- N - Acetylenolpyruvylglucosamine Reductase (MurB) with Activity against Gram-Positive Bacteria (2006)

A series of 3,5-dioxopyrazolidines was identified as novel inhibitors of UDP-N-acetylenolpyruvylglucosamine reductase (MurB). Compounds 1 to 3, which are 1,2-bis(4-chlorophenyl)-3,5-dioxopyrazolidine-4-carboxamides, inhibited Escherichia coli MurB, Staphyloccocus aureus MurB, and E. coli MurA with 50% inhibitory concentrations (IC50s) in the range of 4.1 to 6.8 microM, 4.3 to 10.3 microM, and 6.8 to 29.4 microM, respectively. Compound 4, a C-4-unsubstituted 1,2-bis(3,4-dichlorophenyl)-3,5-dioxopyrazolidine, showed moderate inhibitory activity against E. coli MurB, S. aureus MurB, and E. coli MurC (IC50s, 24.5 to 35 microM). A fluorescence-binding assay indicated tight binding of compound 3 with E. coli MurB, giving a dissociation constant of 260 nM. Structural characterization of E. coli MurB was undertaken, and the crystal structure of a complex with compound 4 was obtained at 2.4 A resolution. The crystal structure indicated the binding of a compound at the active site of MurB and specific interactions with active-site residues and the bound flavin adenine dinucleotide cofactor. Peptidoglycan biosynthesis studies using a strain of Staphylococcus epidermidis revealed reduced peptidoglycan biosynthesis upon incubation with 3,5-dioxopyrazolidines, with IC50s of 0.39 to 11.1 microM. Antibacterial activity was observed for compounds 1 to 3 (MICs, 0.25 to 16 microg/ml) and 4 (MICs, 4 to 8 microg/ml) against gram-positive bacteria including methicillin-resistant S. aureus, vancomycin-resistant Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae.
The impact of in vivo reflectance confocal microscopy for the diagnosis of melanoma. (2007)

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Special projects. Automation of a mass spectrometer for the National Center for Toxicological Research (NCTR) (1975)

Progress is reported in the following studies: automation of a mass spectrometer for the national center for toxicological research (NCTR); automation of the Davies-Gray/New Brunswick Laboratory method for the determination of U; real-time materials control in a nuclear fuel plant; simulation modeling of mixed-oxide fuel-rod fabrication plants; pilot, laboratory- automation project with the National Environmental Research Center, Cincinnati, Ohio; thallium in human erythrocyte membranes; an x-ray photoelectron spectroscopy study; ESCA study of sulfur-bearing particulates; and chemical and statistical analysis of an inventory of precious metal at the LLL metal finishing shop. (JGB)
1171 CAN1012: a selective and potent TLR7 agonist with strong antitumoral properties mediated by localized innate immune activation (2022)

<h3>Background</h3> Toll-like receptors (TLRs) are commonly expressed on innate immune cells such as macrophages and dendritic cells (DC), and they play crucial roles in 1) mediating the first-line innate immune response against a wide variety of pathogens and 2) promoting adaptive immunity involving T and B cells. The TLR family consists of 10 subtypes (TLR1-TLR10) in humans and 12 (TLR1-TLR9, TLR11-TLR13) in mice. CAN1012 was developed as a selective TLR7 agonist uniquely designed for intratumoral (IT) administration. <h3>Methods</h3> CAN1012 was evaluted by<i> in vitro</i> cell-based assays and <i>in vivo</i> animal models. Its DMPK, safety and toxicitology properties were also studied. <h3>Results</h3> Based on the receptor screening study, CAN1012 has been proved to have a significant stimulatory effect (NF-κB activation) via human and mouse TLR7. In addition, CAN1012 stimulated significant IFN-α release from human PBMC at low concentrations (nM), whereas TNF-α secretion required a relatively high concentration. Most importantly, CAN1012 induced a robust production of IFN-α exclusively by plasmacytoid DCs in human PBMC. When given intratumorally, CAN1012 exposure in tumor tissues was over 1,000-fold higher than in blood, resulting in much less systemic toxicity. The antitumoral effects of IT-administered CAN1012 monotherapy or combined with other therapeutical agents were investigated in mouse SCC7, CT26, and MC38 syngeneic tumor models. The results showed that CAN1012 possessed significant anti-tumor growth effects in a dose-dependent and schedule-dependent manner, and antitumoral effects could be augmented when combined with other agents. Pharmacodynamic studies revealed that IT administration of CAN1012 increased CD4+ and CD8+ T cell infiltration but decreased the number of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME). CAN1012 has a favorable ADME/PK profile when administered subcutaneously in mice, rats and monkeys, and its pharmaceutical properties have also been optimized for IT administration. <h3>Conclusions</h3> In conclusion, CAN1012 is a potent, safe, and selective TLR7 agonist and could be a best-in-class agent for cancer immunotherapy. A first-in-human Phase I clinical study in advanced cancer patients is ongoing in the US (NCT04987112). <h3>Trial Registration</h3> NCT04987112 <h3>Ethics Approval</h3> Aniaml studies had been approved by the ethics review committee at the institution at which the studies were conducted
Generation of human monoclonal a cellular antigens (hybridoma/cell-surface antigens/intracellular antigens/cancer imnm (2016)

Human lymphocytes from lymph node, periph- eral blood, spleen, and tumor specimens have been fused with the LICR-LON-HMy2 (LICR-2) or SKO-007 human cell lines or the NS-1 mouse myeloma line. Over 75 fusions with the three my- eloma-lymphoblastoid lines have been performed. Several factors appeared to improve the fusion outcome, including maintenance of the myeloma-lymphoblastoid lines in logarithmic phase growth at >95% viability, a delay of 24 hr in the introduction of amino- pterin to the fused cells, and preselection of the fetal calf serum used in the medium. For a given number of lymphocytes, fusions with NS-1 produced 5-20 times more clones than fusions with LICR- 2 or SKO-007, and LICR-2 produced 4,times as many clones as SKO-007. The percentage of clones secreting human immuno- globulin, the range of immunoglobulin production, and the pro- portion of IgM, IgA, and IgG secretors were comparable for clones derived from the three myeloma-lymphoblastoid lines. Stable Ig- secreting clones were isolated with approximately equal frequency from LICR-2 and NS-1 fusions. A number of stable clones pro- ducing human monoclonal antibodies reacting with cell-surface, cytoplasmic, or nuclear antigens have been isolated from tumor- bearing patients and normal individuals. A surface antigenic sys- tem present on normal and malignant cells has been defined with a human monoclonal antibody derived from-a patient with breast cancer. Techniques for producing human monoclonal antibody now appear to be sufficiently advanced to initiate a serological dissection of the humoral immune response to cancer.
Trauma, Mental Health, Distrust, and Stigma Among HIV-Positive Persons: Implications for Effective Care (2008)

Individuals living with HIV often have complicated histories, including negative experiences such as traumatic events, mental illness, and stigma. As the medical community in the United States adapts to managing HIV as a chronic disease, understanding factors such as these negative experiences that may be associated with poorer adherence to treatment regimens, greater HIV risk behavior, and lower patient quality of life becomes critical to HIV care and prevention. In less wealthy nations, these issues are also critical for addressing quality of life as well as medication adherence in the areas where antiretroviral therapies are being made available. This article presents a review of the literature regarding the following psychosocial factors as they relate to HIV/AIDS in the US and globally: traumatic events; mental illness, including depression, anxiety, and posttraumatic stress disorder; lack of trust in the healthcare system and government; and experiences of stigma among individuals with HIV disease. These factors have been found to be prevalent among individuals with HIV/AIDS, regardless of gender or race/ethnicity. Traumatic events, mental illness, distrust, and stigma have also been linked with poorer adherence to medication regimens and HIV risk behavior.
High Average Power Optical Systems for the Jefferson Lab FEL (2006)

High average power free-electron lasers based on energy-recovering accelerators challenges the laser designer to deliver stable output over a long period of time. This talk discusses our experiences at the FEL User Facility. Article not available.