gebhart/patrepeval huggingface dataset:
Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose (2019)

Based on its high affinity for μ opiate receptors and reported half-life after oral administration, the pharmacokinetic properties of intranasal naltrexone were examined to evaluate its potential to treat opioid overdose. This study was prompted by the marked rise in overdose deaths linked to synthetic opioids like fentanyl, which may require more potent, longer-lived opiate antagonists than naloxone. Both the maximum plasma concentration (C<sub>max</sub> ) and the time (T<sub>max</sub> ) to reach C<sub>max</sub> for intranasal naltrexone (4 mg) were comparable to values reported for a Food and Drug Administration-approved 4-mg dose of intranasal naloxone. The addition of the absorption enhancer dodecyl maltoside (Intravail) increased C<sub>max</sub> by ∼3-fold and reduced the T<sub>max</sub> from 0.5 to 0.17 hours. Despite these very rapid increases in plasma concentrations of naltrexone, its short half-life following intranasal administration (∼2.2 hours) could limit its usefulness as a rescue medication, particularly against longer-lived synthetic opioids. Nonetheless, the ability to rapidly attain high plasma concentrations of naltrexone may be useful in other indications, including an as-needed dosing strategy to treat alcohol use disorder.
Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers (2016)

The emerging concept of psychobiotics-live microorganisms with a potential mental health benefit-represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.
Instability of the Amyloidogenic Cystatin C Variant of Hereditary Cerebral Hemorrhage with Amyloidosis, Icelandic Type (1998)

A cystatin C variant with L68Q substitution and a truncation of 10 NH2-terminal residues is the major constituent of the amyloid deposited in the cerebral vasculature of patients with the Icelandic form of hereditary cerebral hemorrhage with amyloidosis (HCHWA-I). Variant and wild type cystatin C production, processing, secretion, and clearance were studied in human cell lines stably overexpressing the cystatin C genes. Immunoblot and mass spectrometry analyses demonstrated monomeric cystatin C in cell homogenates and culture media. While cystatin C formed concentration-dependent dimers, the HCHWA-I variant dimerized at lower concentrations than the wild type protein. Amino-terminal sequence analysis revealed that the variant and normal proteins produced and secreted are the full-length cystatin C. Pulse-chase experiments demonstrated similar levels of normal and variant cystatin C production and secretion. However, the secreted variant cystatin C exhibited an increased susceptibility to a serine protease in conditioned media and in human cerebrospinal fluid, explaining its depletion from the cerebrospinal fluid of HCHWA-I patients. Thus, the amino acid substitution may induce unstable cystatin C with intact inhibitory activity and predisposition to self-aggregation and amyloid fibril formation.
Evaluation of Quantitative PCR and Branched-Chain DNA Assay for Detection of Hepatitis B Virus DNA in Sera from Hepatocellular Carcinoma and Liver Transplant Patients (2000)

This study evaluated the applicability of quantitative PCR (Q-PCR) and branched-chain DNA assays for detection of hepatitis B virus (HBV) DNA in sera. For 42 samples, the detection rates were 81 and 41%, respectively, with a correlation coefficient of 0.633. The Q-PCR is useful for early monitoring of HBV load in high-risk patients.
Changes in β2-Glycoprotein I Antigenicity Induced by Phospholipid Binding (1993)

beta 2-glycoprotein I (beta 2GPI) or apolipoprotein H has been described as a necessary cofactor for antiphospholipid antibody (aPA) binding in ELISA. Some investigators disagree with the beta 2-GPI requirement whereas data from other laboratories indicate that beta 2GPI, not phospholipid (PL), is the antigen for aPA. To investigate the cofactor we have produced three IgG1 monoclonal antibodies (mAb) to human beta 2GPI; 3G9, 1B4 and 3D11. Western blot analyses showed the mAb to bind human beta 2GPI (40 kDa), but no reactivity was observed with adult or fetal bovine sera. In contrast, rabbit anti-beta 2GPI reacted with both human and bovine sera. None of the mAb reacted with phosphatidylserine (PS) or cardiolipin (CL) by ELISA. There were no significant differences in ELISA binding to purified beta 2GPI when the mAb were adjusted to the same concentration. mAb 3G9 and 1B4 gave stronger signals in ELISA after beta 2GPI bound to PS; the increase for 3G9 was significantly greater than for 1B4 (p < 0.002). mAb 3D11 was unique inasmuch as it failed to recognize beta 2PGI bound to PS. In comparison, the rabbit anti-beta 2GPI was unaffected by PS-beta 2GPI binding. These observations indicate that the mAb recognize three distinct epitopes on beta 2GPI. The data suggest that beta 2GPI undergoes conformational changes subsequent to binding PL. Our findings are consistent with the hypothesis that aPA recognize a beta 2GPI neotope formed subsequent to binding PL.
Stabilizing LiCoO<sub>2</sub>/Graphite at High Voltages with an Electrolyte Additive (2019)

The energy density of commercial Li-ion batteries (LIBs) using LiCoO<sub>2</sub> is adversely affected by the limited access to the Li stored in the CoO<sub>2</sub> lattice, which is imposed partially by the instability of carbonate-based electrolytes at potentials higher than 4.5 V. In this work, we report a novel approach to fully utilize these extra Li via simultaneously stabilizing anode and cathode interfaces with a designed additive, 4-propyl-[1,3,2]dioxathiolane-2,2-dioxide (PDTD), which strongly coordinates with Co ions dissolved in electrolytes while decomposing to form protective interphases on both cathode and anode surfaces. The Co ions present in the electrolyte deposit on the anode in the form of a coordination complex with PDTD, avoiding the formation of Co metal that will catalyze the reduction decomposition of the additive-free electrolyte. The presence of PDTD in the electrolyte enables a higher charging potential of 4.45 V for LiCoO<sub>2</sub>/graphite cells, which significantly improves the energy density and cycling stability of this cathode chemistry that has already been used extensively in commercial LIBs.
Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils (2014)

The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified - predominantly Streptomyces - that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen.
A Study on Correlations for Void Ratio, Coefficient of Uniformity and Coefficient of Curvature for Determination of Relative Density for Sands (2013)

Determination of geotechnical characteristics of soil is either to use the field samples to measure the characteristics of soil through laboratory test or measuring the characteristics directly in the field. Field test can be derived similar value by considering characteristics of site and laboratory test can be confirmed the characteristic of soil by testing with field samples. This article describes relative density as the measure of compaction for cohesionless soils and presents several simple and mathematical relationships to help engineers estimate needed parameters for relative density calculations. The main purpose of this research is to investigate possible correlations between coefficient of uniformity, coefficient of curvature, maximum and minimum void ratio, mean grain size. Results show a linear relationship between the minimum and maximum void ratios and a power function relationship between coefficient of uniformity and the limiting void ratios. Void ratio range, which is the difference between the maximum and minimum void ratios, appeared to be log normally distributed but showed no simple mathematical fit to the data. these results were shown to help engineers estimate needed parameters for relative density calculations.
Phospholipase A<sub>2</sub> engineering: Design, synthesis, and expression of a gene for bovine (pro)phospholipase A<sub>2</sub> (1989)

A gene coding for the (pro)phospholipase A2 (PLA2) from bovine pancreas has been designed, synthesized, and expressed in Escherichia coli. The gene was designed with a variety of restriction sites that will facilitate future mutagenesis studies. Codons occurring frequently in prokaryotic systems were chosen whenever possible. The total gene spans 404 base pairs and was divided into 33 oligonucleotides. The gene was constructed in two halves of 224 and 180 base pairs from the oligonucleotides by the shotgun ligation technique using pBSM13- as the cloning vehicle. The two fragments were then ligated and cloned into pBSM13- to complete the gene. The (pro)PLA2 gene was then verified by restriction site mapping and dideoxy sequencing. The gene was expressed to high levels from a high copy number vector, designated as pJPN, derived from the E. coli secretion vector pIN-III-ompA3. Although the protein failed to be excreted and was in the form of insoluble inclusion body, active PLA2 could be obtained by renaturation of the inclusion body pellet followed by tryptic activation, which removes the signal sequence and the pro-peptide of proPLA2. The PLA2 thus obtained reacted with the antisera raised against the natural PLA2 purified from bovine pancreas, and the specific activity of the expressed PLA2 was identical to that of the natural PLA2. The shotgun ligation and synthetic gene approaches are simple and inexpensive and can be adapted to express most of the enzymes in the phospholipase A2 family.
Fast mixed-mode PLL simulation using behavioral baseband models of voltage-controlled oscillators and frequency dividers (2010)

This article presents a new approach to fast mixed-mode simulation of phase-locked loops (PLLs) in time domain using Spice-like simulators and behavioral Verilog-A baseband (BB) models of voltage-controlled oscillators (VCO) and frequency dividers (FD). Other PLL blocks like phase-frequency detectors (PFD), charge pumps (CP), and loop filters (LP) can be transistor level and/or behavioral models. The use of both VCO and FD BB models in mixed-mode test bench allows fast PLL simulation and optimization of modern sophisticated PFD and CP blocks on transistor level with speedups of about 2-3 orders of magnitude.
Coupling of fluoroform with aldehydes using an electrogenerated base (1998)

Trifluoromethylated alcohols are easily obtained in a one pot electroreaction in which cathodic reduction of iodobenzene generates a strong base which deprotonates fluoroform, inducing its coupling with aldehydes.
Healthy human gut phageome (2016)

The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.
Is outcome from ARDS related to the severity of respiratory failure? (1997)

The characteristics and outcome of acute respiratory distress syndrome (ARDS) may have changed with time. Some studies have reported that mortality is more commonly related to the development of sepsis/multiple organ failure (MOF), and others that it is related to the severity of acute respiratory failure (ARF). The present study evaluates the relative importance of the two phenomena in a large series of patients. The clinical and biological data of all patients who developed ARDS during a 26 month period (January 1993 until February 1995) in our intensive care unit (ICU) were reviewed retrospectively. A total of 129 patients developed ARDS during the study period, representing an incidence of 2.4% of all ICU admissions. The mortality rate was 52%. The primary cause of death was sepsis/MOF (49%), followed by respiratory failure (16%), cardiac failure or arrhythmias (15%), neurological failure (10%), and other causes (8%). The mortality rate was related to age and degree of organ failure. MOF was not always a cause of late death, since half the deaths occurred within 5 days after admission. In addition, mortality was higher in septic than in nonseptic patients, and lower in trauma and surgical than in medical patients. We conclude that sepsis/multiple organ failure is still the most common cause of death in acute respiratory distress syndrome. Improvements in outcome of acute respiratory distress syndrome may depend more on treatment of sepsis and multiple organ failure than on oxygenation measures.
IN VITRO CYTOKINE PROFILES AND THEIR RELEVANCE TO REJECTION FOLLOWING RENAL TRANSPLANTATION (1995)

Graft rejection remains an important cause of renal allograft failure, despite improvements in immunosuppression and HLA typing. Although HLA matching is beneficial, ensuring an exact match it is often impractical. Thus, a reliable in vitro method for quantitating and qualitating alloreactivity is an important goal. In this study, we measured in vitro the cytokine secretion profiles of mononuclear cells from patients prior to renal transplantation by stimulating with anti-CD3 monoclonal antibody and suppressing with cyclosporine. Mononuclear cells from patients who subsequently developed acute cellular rejection secreted higher mean levels of interleukin (IL)-2 and gamma-interferon (IFN-gamma) than those from patients who had no rejection episodes. IFN-gamma secretion was significantly associated with rejection (P = 0.002), whereas IL-2 secretion did not quite reach statistical significance. There was no significant correlation between IL-4 levels and rejection. Although cyclosporine suppressed the secretion of both IL-2 and IFN-gamma, there was no difference in sensitivity to suppression between rejectors and nonrejectors. These results further emphasize the importance of the TH1 lymphocyte subset in renal allograft rejection. The IFN-gamma secretory capacity of alloreactive T cells may influence the outcome of a renal allograft by (1) activating graft infiltrating macrophages and/or (2) up-regulating HLA molecules on the graft.
Radiation Fields of a Tapered Film and a Novel Film-to-Fiber Coupler (1975)

Light in a tapered thin-film optical waveguide radiates into the substrate because the waveguide mode in the taper becomes cut off. Our measurement of the radiation pattern shows that the light emerges from the taper as a narrow beam with an angular width of only 2/spl deg/-4/spl deg/. We have studied the problem based on ray optics and based on a wave theory of radiation modes. We also have demonstrated a film-to-fiber coupler in which an optical fiber collects all the light emerging from the taper.
Candidacidal activity of myeloperoxidase: therapeutic influence of the enzyme in vivo (1985)

Mice were injected intravenously with Candida albicans blastospores to establish chronic renal infection. Seventy-five percent of the animals inoculated with 10(6) blastospores died as a consequence of infection during the subsequent 60 days of observation. Intraperitoneal administration of 10 mU of partially purified human myeloperoxidase 1 day after injection of the pathogen increased survival of the mice from 25 to 80% over this time period. Administration of myeloperoxidase complexed with soluble C. albicans cell wall mannan abrogated the protective influence of the enzyme. These results demonstrate that exogenous myeloperoxidase has a therapeutic influence on murine renal candidiasis and suggest that exogenous myeloperoxidase may also be effective in the treatment of certain forms of candidiasis in humans. These results also demonstrate the important role of the mannan-binding function of myeloperoxidase for effective treatment of candidiasis and suggest a mechanism of inhibition of the candidacidal effect of free enzyme in vivo by mannan accumulating in tissue fluids.
What's in a Note? Unpacking Predictive Value in Clinical Note Representations. (2018)

Electronic Health Records (EHRs) have seen a rapid increase in adoption during the last decade. The narrative prose contained in clinical notes is unstructured and unlocking its full potential has proved challenging. Many studies incorporating clinical notes have applied simple information extraction models to build representations that enhance a downstream clinical prediction task, such as mortality or readmission. Improved predictive performance suggests a "good" representation. However, these extrinsic evaluations are blind to most of the insight contained in the notes. In order to better understand the power of expressive clinical prose, we investigate both intrinsic and extrinsic methods for understanding several common note representations. To ensure replicability and to support the clinical modeling community, we run all experiments on publicly-available data and provide our code.
Lateral inhibition and cell fate during neurogenesis in <i>Drosophila:</i> the interactions between <i>scute, Notch</i> and <i>Delta</i> (1990)

Abstract A comparison of the patterns of expression of AS-C (T3) RNA and protein suggests that an important level of regulation occurs post-transcriptionally. First, when the RNA is abundant in the early embryo the protein is barely detectable. Later, the protein starts to accumulate in only a subset of the nuclei of those cells expressing the RNA. Only the cells in the subsets become the neuroblasts. This post-transcriptional regulation is suppressed in embryos mutant for the genes Notch and Delta; where all cells expressing RNA accumulate protein. These findings suggest that deployment of T3 protein expression is one of the causal factors that assigns specific fates to the neuroblasts and, in consequence, a basis for the mechanism of lateral inhibition is proposed.
Partial-Differential Distributed Cyclic Delay Diversity for Nonregenerative Two-Way Relaying System (2009)

In wireless <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ad-hoc</i> networks, network coding can take advantage of the bi-directional traffic flows to increase the achievable throughput. In this letter, on the one hand, cooperative diversity based on distributed cyclic delay diversity is integrated into the physical network coding scheme to combat fading in wireless channel. On the other hand, to reduce the system overhead for the coherent detection at each destination terminal, differential modulation based on linear constellation precoding is proposed. Theoretical analysis and numerical results both confirm that our two-way relaying scheme can achieve full spatial diversity. Furthermore, the proposed scheme can significantly improve the performance over traditional one-way wireless relay scheme and the existing two-way wireless relay schemes due to its enhanced spectral efficiency and lower implementation complexity.
Learning One-hidden-layer ReLU Networks via Gradient Descent (2018)

We study the problem of learning one-hidden-layer neural networks with Rectified Linear Unit (ReLU) activation function, where the inputs are sampled from standard Gaussian distribution and the outputs are generated from a noisy teacher network. We analyze the performance of gradient descent for training such kind of neural networks based on empirical risk minimization, and provide algorithm-dependent guarantees. In particular, we prove that tensor initialization followed by gradient descent can converge to the ground-truth parameters at a linear rate up to some statistical error. To the best of our knowledge, this is the first work characterizing the recovery guarantee for practical learning of one-hidden-layer ReLU networks with multiple neurons. Numerical experiments verify our theoretical findings.