gebhart/patrepeval huggingface dataset:
Biologically Active Trifluoromethyl‐Substituted Metallocene Triazoles: Characterization, Electrochemistry, Lipophilicity, and Cytotoxicity (2012)

Abstract We report the facile synthesis of four different trifluoromethylated metallocene triazoles and their biological evaluation (M = Fe and Ru). The cytotoxicity of all compounds was evaluated using MCF‐7, HT‐29, PT‐45 and GM5657 cells and IC 50 values as low as 33 μ M were found. It was shown that the metallocene moiety is crucial for the cytotoxic effect. The electrochemical behavior of triazoles 3 – 6 was investigated by cyclic voltammetry. These electrochemical measurements revealed that all triazoles are less prone to oxidation than ferrocene. Moreover, Log P determination by RP‐HPLC showed increased lipophilicity for the fluorinated derivatives with Log P values up to 3.8. Furthermore, successful bioconjugation could be achieved by coupling triazole 7 to the amino acid L ‐leucine.
Sensory Characteristics and Related Volatile Flavor Compound Profiles of Different Types of Whey (2005)

To characterize the flavor of liquid whey, 11 samples of whey representing a wide range of types were sourced from cheese and casein-making procedures, either industrial or from pilot-plant facilities. Whey samples were assessed for flavor by descriptive sensory evaluation and analyzed for headspace volatile composition by proton transfer reaction-mass spectrometry (PTR-MS). The sensory data clearly distinguished between the samples in relation to the processes of manufacture; that is, significant differences were apparent between cheese, rennet, and acid wheys. For Mozzarella and Quarg wheys, in which fermentation progressed to low pH values, the starter cultures used for cheese making had a significant influence on flavor. In comparison, Cheddar and Gouda wheys were described by milk-like flavors, and rennet casein wheys were described by "sweet" (oat-like and "sweet") and thermally induced flavors. The volatile compound data obtained by PTR-MS differentiated the samples as distinctive and reproducible "chemical fingerprints". On applying partial least squares regression to determine relationships between sensory and volatile composition data, sensory characteristics such as "rancid" and cheese-like odors and "caramelized milk," yogurt-like, "sweet," and oat-like flavors were found to be related to the presence and absence of specific volatile compounds.
The Caspase-8 Modulator c-FLIP (2005)

Death receptors belong to the tumor necrosis factor receptor superfamily and can induce apoptosis through activation of procaspase-8. The cellular FLICE-inhibitory protein (c-FLIP) is able to modulate activation of procaspase-8 and thereby prevents induction of apoptosis mediated by death receptors. As an important modulator of caspase-8, c-FLIP regulates life and death in various types of normal cells and tissues, such as lymphoid cells, and renders resistance to death receptor-mediated apoptosis in many types of cancer cells. In addition to an apoptosis modulator, c-FLIP has been shown to exert other physiological functions related to cell proliferation and tumorigenesis. Dysregulation of c-FLIP expression has been shown to be associated with various diseases, such as cancer and autoimmune diseases, and c-FLIP might be a critical target for therapeutic intervention. This review focuses on recent findings about the physiological function and intracellular regulation of c-FLIP.
Rate-dependent morphology of Li2O2 growth in Li-O2 batteries (2013)

Compact solid discharge products enable energy storage devices with high gravimetric and volumetric energy densities, but solid deposits on active surfaces can disturb charge transport and induce mechanical stress. In this Letter we develop a nanoscale continuum model for the growth of Li2O2 crystals in lithium-oxygen batteries with organic electrolytes, based on a theory of electrochemical non-equilibrium thermodynamics originally applied to Li-ion batteries. As in the case of lithium insertion in phase-separating LiFePO4 nanoparticles, the theory predicts a transition from complex to uniform morphologies of Li2O2 with increasing current. Discrete particle growth at low discharge rates becomes suppressed at high rates, resulting in a film of electronically insulating Li2O2 that limits cell performance. We predict that the transition between these surface growth modes occurs at current densities close to the exchange current density of the cathode reaction, consistent with experimental observations.
The Effect of Angiotensin II Receptor Blockade on an End-Stage Renal Failure Model of Type 2 Diabetes (2006)

The effect of olmesartan medoxomil (OLM), an angiotensin II receptor blocker (ARB), on advanced nephropathy and mortality was evaluated in Zucker Diabetic Fatty (ZDF) rats, a type 2 diabetes model. OLM was administered from 36 weeks of age, when the animals developed advanced proteinuria. OLM effectively suppressed the progression of proteinuria. The ZDF rats started to die at 50 weeks of age, which was accompanied by abrupt increase in blood urea nitrogen, suggesting that the cause of death was renal insufficiency. OLM suppressed increases in blood urea nitrogen and increased the survival rate of the ZDF rats. The histological examination revealed that the renal damage was ameliorated by OLM. The macrophage infiltration and monocyte chemoattractant protein-1 (MCP-1) expression was increased in the glomeruli and tubulointerstitium of the ZDF rat kidneys, and the increase was lessened by OLM. In a separate study, albumin increased MCP-1 release from cultured tubular epithelial cells. These results suggest that protein leakage from the glomeruli stimulates MCP-1 production in tubular cells and that MCP-1 released into the interstitial space induces macrophage infiltration and inflammation. It is conceivable that the beneficial actions of ARB on diabetic nephropathy are, at least in part, due to decrease of proteinuria and the subsequent reduction of inflammatory changes in tubular cells.
Enhancement of Electrochemical Stability about Silicon/Carbon Composite Anode Materials for Lithium Ion Batteries (2015)

Silicon/carbon (Si/C) composite anode materials are successfully synthesized by mechanical ball milling followed by pyrolysis method. The structure and morphology of the composite are characterized by X‐ray diffraction and scanning electron microscopy and transmission electron microscope, respectively. The results show that the composite is composed of Si, flake graphite, and phenolic resin‐pyrolyzed carbon, and Si and flake graphite are enwrapped by phenolic resin‐pyrolyzed carbon, which can provide not only a good buffering matrix but also a conductive network. The Si/C composite also shows good electrochemical stability, in which the composite anode material exhibits a high initial charge capacity of 805.3 mAh g −1 at 100 mA g −1 and it can still deliver a high charge capacity of 791.7 mAh g −1 when the current density increases to 500 mA g −1 . The results indicate that it could be used as a promising anode material for lithium ion batteries.
Chimeric Antigen Receptor beyond CAR-T Cells (2021)

Chimeric antigen receptors (CAR) are genetically engineered receptors that can recognise specific antigens and subsequently activate downstream signalling. Human T cells engineered to express a CAR, also known as CAR-T cells, can target a specific tumour antigen on the cell surface to mediate a cytotoxic response against the tumour. CAR-T cell therapy has achieved remarkable success in treating hematologic malignancies, but not in solid tumours. Currently, extensive research is being carried out to make CAR-T cells a therapy for solid tumours. To date, most of the research interest in the field has focused on cytotoxic T lymphocytes as the carrier of CAR products. However, in addition to T cells, the CAR design can be introduced in other immune cells, such as natural killer (NK)/NKT cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, dendritic cells (DC), macrophages, regulatory T cells (Treg), B cells, etc. Some of the CAR-engineered immune cells, such as CAR- γδ T and CAR-NK/NK-T cells, are directly involved in the anti-tumour response, demonstrated in preclinical studies and/or clinical trials. CAR-Tregs showed promising therapeutic potential in treating autoimmune diseases. In particular, B cells engineered with chimeric receptors can be used as a platform for long-term delivery of therapeutic proteins, such as recombinant antibodies or protein replacement, in an antigen-specific manner. CAR technology is one of the most powerful engineering platforms in immunotherapy, especially for the treatment of cancers. In this review, we will discuss the recent application of the CAR design in non-CAR-T cells and future opportunities in immunotherapy.
Comparison between the Performance of Fluidized Bed and Barrel Rectors for the Plasma Activation of Polymer Particles (2015)

This study reports on a comparison between two types of atmospheric plasma systems, a pulsed fluidized bed and a barrel reactor, for the plasma activation of silicone particles. Both helium and helium /oxygen gas mixtures were used to generate the plasmas in the two reactors. Both reactors are cylindrical in shape with internal dimensions of 100 mm in length and diameters of 30 mm. The two reactors were used to treat 0.5 g of silicone polymer particles. The effects of plasma treatment time, operating voltage and gas flow rate, on changes in the water contact angle of the treated polymer were investigated. Optical Emission Spectroscopy (OES) facilitated the monitoring of reactive plasma species during treatment. Subsequent to their treatment, the polymer particles were analysed using X-ray Photoelectron Spectroscopy (XPS). As expected this analysis demonstrated an increase in oxygen content on the polymer surface after plasma activation. For a helium only plasma treatment, the water contact angle of the silicone slowly decreased from 145° to approx. 75° after a treatment time of 2 hours. In contrast, the addition of a relatively small concentration of oxygen into the helium plasma formed in the barrel reactor, resulted in contact angle of <5° after only 2 minutes treatment. The pulsed fluidized bed reactor however was observed to be less effective using this gas mixture, achieving an average contact angle of only 26° after 2 minutes of treatment. The difference in the level of particle activation achieved using the two reactor types is attributed to the intensity and homogeneity of the plasma generated within the reactor designs.
Agile manufacturing: General challenges and an IoT@Work perspective (2012)

This paper describes the potential impact of the Internet of Things (IoT) technologies and architecture on factory automation. Whereas, IoT use cases range from intelligent infrastructure and smart cities to health care and shopping assistants, it is important to note that factory automation could benefit as well from an IoT approach. In this paper, we argue that there will not be one IoT but many IoTs that could differ in the type of infrastructure they are running or applications they support. In IoT@Work we focus on the potential of making manufacturing environments more agile and flexible. We explain how the IoT-centric architecture for manufacturing also needs a deep understanding of the manufacturing system and its state today. We, therefore, do a reverse engineering based on the requirements and the description of the agility expected in the automation system itself.
Human Safety, Tolerability, and Pharmacokinetics of a Novel Broad-Spectrum Oral Antiviral Compound, Molnupiravir, with Activity Against SARS-CoV-2 (2020)

Abstract Molnupiravir, EIDD-2801/MK-4482, the prodrug of the ribonucleoside analog ß-d-N4-hydroxycytidine (NHC), has activity against a number of RNA viruses including severe acute respiratory syndrome coronavirus 2, severe acute respiratory syndrome coronavirus, Middle East respiratory syndrome coronavirus, seasonal and pandemic influenza viruses, and respiratory syncytial virus. Single and multiple doses of molnupiravir were evaluated in this first-in-human, phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, which included evaluation of the effect of food on pharmacokinetics. EIDD-1931 appeared rapidly in plasma, with a median time of maximum observed concentration of 1.00 to 1.75 hours, and declined with a geometric half-life of approximately 1 hour, with a slower elimination phase apparent following multiple doses or higher single doses (7.1 hours at the highest dose tested). Mean maximum observed concentration and area under the concentration versus time curve increased in a dose-proportional manner, and there was no accumulation following multiple doses. When administered in a fed state, there was a decrease in the rate of absorption, but no decrease in overall exposure. Molnupiravir was well tolerated. Fewer than half of subjects reported an adverse event, the incidence of adverse events was higher following administration of placebo, and 93.3% of adverse events were mild. One discontinued early due to rash. There were no serious adverse events and there were no clinically significant findings in clinical laboratory, vital signs, or electrocardiography. Plasma exposures exceeded expected efficacious doses based on scaling from animal models; therefore, dose escalations were discontinued before a maximum tolerated dose was reached. Clinical trial identifier This study was registered at ClinicalTrials.gov with the identifier NCT04392219 .
Electron heating in silicon nitride and silicon oxynitride films (1986)

The vacuum emission technique has been used to study electron transport and heating in silicon nitride and silicon oxynitride. The experimental results are compared to data for silicon dioxide in which all the conduction-band electrons can gain several eV of energy at electric fields greater than 2 MV/cm. Although average electron energy as a function of electric field curves are very similar to silicon dioxide, the total number of electrons which can be heated to energies greater than 2 eV is greatly reduced because of the increased trapping in these films. Reduction in hot electrons due to increased trapping is correlated to increasing nitrogen content through the oxynitride phases to silicon nitride. Trapping/detrapping on energetically shallow sites in the forbidden gap controls the bulk limited conduction in these films, and very few electrons are allowed to move freely in the conduction band.
Cystic Artery Pseudoaneurysm: Current Review of Aetiology, Presentation, and Management (2021)

Cystic artery pseudoaneurysms are rare complications of a common operation. The most common clinical presentation is haemobilia, which can be difficult to diagnose clinically. A high index of suspicion and prompt investigation with targeted imaging and intervention is required. This is especially pertinent in gastrointestinal bleeding postlaparoscopic cholecystectomy as a missed diagnosis could cause significant morbidity.
Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF‐κB (2011)

Abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed in the skeletal muscle during muscle wasting including sarcopenia. However, the mechanisms that signal ROS production and prolonged maintenance of ROS levels during muscle wasting are not fully understood. Here, we show that myostatin (Mstn) is a pro-oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor-β (TGF-β) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that Mstn induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor-α (TNF-α) signaling via NF-κB and NADPH oxidase. Aged Mstn null (Mstn(-/-) ) muscles, which display reduced sarcopenia, also show an increased basal antioxidant enzyme (AOE) levels and lower NF-κB levels indicating efficient scavenging of excess ROS. Additionally, our results indicate that both TNF-α and hydrogen peroxide (H(2) O(2) ) are potent inducers of Mstn and require NF-κB signaling for Mstn induction. These results demonstrate that Mstn and TNF-α are components of a feed forward loop in which Mstn triggers the generation of second messenger ROS, mediated by TNF-α and NADPH oxidase, and the elevated TNF-α in turn stimulates Mstn expression. Higher levels of Mstn in turn induce muscle wasting by activating proteasomal-mediated catabolism of intracellular proteins. Thus, we propose that inhibition of ROS induced by Mstn could lead to reduced muscle wasting during sarcopenia.
Practical Large-Scale Synthesis of Doripenem:  A Novel 1β-Methylcarbapenem Antibiotic (2003)

A practical large-scale process for the synthesis of doripenem hydrate (1), a novel parenteral 1β-methylcarbapenem antibiotic, from p-nitrobenzyl-protected enolphosphate 2b and N-(p-nitrobenzyloxycarbonyl)-protected aminomethylpyrrolidine 3c is described. We found effective extraction conditions to remove p-toluidine and most other organic impurities using a THF/water system containing an inorganic salt. Significant improvements have been made to the previous synthesis using a medicinal chemical procedure. The new process requires no chromatographic purification and affords the target compound 1 as a sterile crystalline powder. Several kilograms of compound 1 were successfully prepared by this process.
A shape based post processor for Gurmukhi OCR (2002)

A shape based post processing system for an OCR of Gurmukhi script has been developed. Based on the size and shape of a word, the Punjabi corpora has been split into different partitions. The statistical information of Punjabi language syllable combination, corpora look up and holistic recognition of most commonly occurring words have been combined to design the post processor. An improvement of 3% in recognition rate from 94.35% to 97.34% has been reported on machine printed images using the post processing techniques.
Prothrombin complex concentrates in emergency bleeding disorders (2012)

The use of prothrombin complex concentrates (PCCs), a heterogeneous combination of coagulation factors and counterbalancing inhibitor components, has broadened in recent years beyond single-factor replacement in conditions such as hemophilia B, to encompass emergency reversal of anticoagulation secondary to oral vitamin K antagonists, ie, warfarin therapy. PCCs also have been studied in other bleeding disorders, such as surgery-related and trauma-related bleeding. This review provides an updated examination of the differences among PCC formulations, their potential role in the management of bleeding disorders, and the primary safety issues affecting their use. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
A study of high density multilayer LSI (2002)

Describes a new type of high density multilayer LSI chip which is made up of several piled chips. Prescribed interconnections on the conventional wafer, are fabricated first. Thin chips with through-holes (about the size of pad) are fixed to the available parts of the under-layer chip. Each chip is interconnected through the holes. As a result, the chips will be equivalent to a hybrid IC which has several chips. This model is equal to the large scale high density LSI, the multichip substrate system, and hybrid WSI (Wafer Scale Integration).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Nanoparticle aerosol generation methods from bulk powders for inhalation exposure studies (2009)

Inhalation toxicity studies of nanoparticles require production of test aerosols with a number of acceptable characteristics. Five different generation methods for producing a nanoparticle aerosol from the bulk powder were evaluated with the goal of producing an acceptable aerosol that is homogenous, has a consistent concentration over time in which the magnitude may be intentionally varied, and has a size distribution that is both unimodal and has a small geometric mean diameter relative to the primary particle size of the nanoparticle bulk powder. Four types of bulk powders were evaluated including titanium dioxide, silicon dioxide, polymer-coated silver, and single walled carbon nanotubes. A nebulizer was the only tested method able to produce a consistent aerosol of sufficient magnitude. However, the resulting aerosol contains particles derived from the carrier water. Prior sonication of the nanoparticle suspension alone was found to be not useful for deagglomerating nanoparticles.
Multicontrast microscopy technique to dynamically fingerprint live-cell focal contacts during exposure and replacement of a cytotoxic medium (2008)

Multicontrast microscopy techniques were used to comprehensively and dynamically map the cellular contact area adhering to a substrate. The natural fringe patterns observed with interference reflection contrast microscopy were used to map the dynamic fingerprint of a porcine pulmonary artery endothelial cell's ventral surface and to examine the focal and/or close contacts to the substrate when exposed to a toxic agent Cytochalasin D. In addition, differential interference contrast microscopy sequentially imaged the overall cellular morphological responses to the agent. It was observed that focal contacts, which are tightly attached to the substrate, are strongly resistant to even high doses of the cytotoxic agent and that they also form the basis of cellular recovery after replacement of the cytotoxic medium with fresh medium.
Data‐assisted protein structure modeling by global optimization in CASP12 (2018)

Abstract In CASP12, 2 types of data‐assisted protein structure modeling were experimented. Either SAXS experimental data or cross‐linking experimental data was provided for a selected number of CASP12 targets that the CASP12 predictor could utilize for better protein structure modeling. We devised 2 separate energy terms for SAXS data and cross‐linking data to drive the model structures into more native‐like structures that satisfied the given experimental data as much as possible. In CASP11, we successfully performed protein structure modeling using simulated sparse and ambiguously assigned NOE data and/or correct residue‐residue contact information, where the only energy term that folded the protein into its native structure was the term which was originated from the given experimental data. However, the 2 types of experimental data provided in CASP12 were far from being sufficient enough to fold the target protein into its native structure because SAXS data provides only the overall shape of the molecule and the cross‐linking contact information provides only very low‐resolution distance information. For this reason, we combined the SAXS or cross‐linking energy term with our regular modeling energy function that includes both the template energy term and the de novo energy terms. By optimizing the newly formulated energy function, we obtained protein models that fit better with provided SAXS data than the X‐ray structure of the target. However, the improvement of the model relative to the 1 modeled without the SAXS data, was not significant. Consistent structural improvement was achieved by incorporating cross‐linking data into the protein structure modeling.
Testing Relationship between Treatment and Survival Time with an Intermediate Event (2008)

Consider a clinical trial in which the main end-point is survival. Suppose after the start of the study an intermediate event occurs which may be influenced by a covariate(or treatment). In many clinical studies the occurrence of an intermediate event may change the survival distribution. This investigation develops two-stage model which, in the first stage, models the effect of covariate on the intermediate event and models the relationship between survival time and covariate as well as the intermediate event. In this paper, the two-stage model is presented in order to model intermediate event and a test based on this model is also provided. A numerical simulations are carried out to evaluate its overall significance level.