gebhart/patrepeval huggingface dataset:
Proteolytically Stable Foldamer Mimics of Host-Defense Peptides with Protective Activities in a Murine Model of Bacterial Infection (2016)

The synthesis of bioinspired unnatural backbones leading to foldamers can provide effective peptide mimics with improved properties in a physiological environment. This approach has been applied to the design of structural mimics of membrane active antimicrobial peptides (AMPs) for which activities in vitro have been reported. Yet activities and pharmacokinetic properties in vivo in animal models have remained largely unexplored. Here, we report helical oligourea AMP mimics that are active in vitro against bacterial forms of Bacillus anthracis encountered in vivo, as well as in vivo in inhalational and cutaneous mouse models of B. anthracis infection. The pharmacokinetic profile and the tissue distribution were investigated by β-radio imager whole-body mapping in mice. Low excretion and recovery of the native oligourea in the kidney following intravenous injection is consistent with high stability in vivo. Overall these results provide useful information that support future biomedical development of urea-based foldamer peptide mimics.
Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS (2017)

AZD4785 is a therapeutic antisense oligonucleotide targeting KRAS mRNA with promising preclinical antitumor activity and a favorable safety profile.
Supracondylar Fractures of the Femur Adjacent to Resurfacing and MacIntosh Arthroplasties of the Knee in Patients with Rheumatoid Arthritis (1988)

Twelve cases of supracondylar fracture of the femur in rheumatoid arthritis patients with previously implanted resurfacing or MacIntosh arthroplasty of the knee had long standing severe polyarticular rheumatoid arthritis (duration, ten to 41 years; mean 24.8 years). The fractures occurred following a long interval after implantation of the prosthesis (five to 204 months; mean, 92.3 months). Two fractures were treated by stable and two by unstable fixation; eight were treated nonoperatively. The fractures healed in a normal time with one exception, but the femur was shortened in ten cases (mean, 2.8 cm), and axially malaligned in nine. The ability to walk long distances decreased in eight cases and pain increased in seven; two prostheses were loosened and displaced. Because of the poor results of nonoperative management, internal fixation of these fractures is recommended in selected cases.
Fuel properties of tallow and soybean oil esters (1995)

Abstract Fuel properties of beef tallow, soybean oil, their esters, and blends with No. 2 diesel fuel and ethanol were determined. Fuel properties tested were viscosity, specific gravity, API gravity, distillation ranges, calculated cetane index, energy content, flash point, water content, sulfur content, carbon residue, particulate matter, acid value, copper‐strip corrosion test, ash content, melting point, cloud point, and pour point. Gas‐chromatographic analyses of tallow, soybean oil, and their esters were performed to determine their major constituents. Viscosities of soybean oil and tallow were significantly reduced by esterification. Other fuel properties of the esters and their blends with No. 2 diesel fuel and ethanol were similar to the properties of No. 2 diesel fuel.
Two patterns of ion channelopathy in the myocardium: perspectives for development of anti-arrhythmic agents. (2005)

Cardiac arrhythmia remains a significant problem, due to the high morbidity and mortality associated with cardiovascular diseases with prominent cardiac remodeling. There is still a lack of effective drugs with which to combat this life-threatening disorder. The abnormal electrophysiological properties of the heart can be explained in terms of ion channels and channelopathy and, in recent years, advances have been made in understanding these properties. There are two patterns of ion channelopathies in the diseased heart: Single insufficiency disorder, which is attributed to mutations in genes, and a multiple derangement of channels. Malignant arrhythmias in a diseased heart usually occur when ventricular hypertrophy is evident, and when they are associated with abnormal repolarization. Abnormalities in the ryanodine receptor-calcium release channel complex (RyR)2, FK-506 binding protein (FKBP 12.6), cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) and phospholamban (PLB) are involved in the initiation of cardiac arrhythmias, and can be identified as targets for therapeutic interventions.
Motor neuron disease in a patient with a mitochondrial tRNAIle mutation (2005)

This case adds to the phenotypic variation seen in mitochondrial DNA disease but also highlights the potential role of mitochondrial dysfunction in the cause of MND.
Human tribbles homologue 2 is expressed in unstable regions of carotid plaques and regulates macrophage IL-10 in vitro (2008)

Mammalian orthologues of the Drosophila tribbles protein (Trb1, Trb2 and Trb3) are a recently described family of signalling molecules that regulate gene expression by modulation of protein kinase signalling pathways. In the present study, a screen for mRNA species specifically regulated in vulnerable regions of human atherosclerotic plaque demonstrated the up-regulation of both Trb1 and Trb2, the latter by more than 8-fold. In vitro experiments in primary human monocyte-derived macrophages showed that Trb2 expression was up-regulated by treatment with oxidized LDL (low-density lipoprotein), and that expression of recombinant Trb2 specifically reduced macrophage levels of IL-10 (interleukin-10) mRNA. Our results thus identify Trb2 as a highly regulated gene in vulnerable atherosclerotic lesions, and demonstrate inhibition of macrophage IL-10 biosynthesis as a potential pro-inflammatory consequence of high Trb2 expression, which may contribute to plaque instability.
Nitric Oxide Synthase Inhibitors That Interact with Both Heme Propionate and Tetrahydrobiopterin Show High Isoform Selectivity (2014)

Overproduction of NO by nNOS is implicated in the pathogenesis of diverse neuronal disorders. Since NO signaling is involved in diverse physiological functions, selective inhibition of nNOS over other isoforms is essential to minimize side effects. A series of α-amino functionalized aminopyridine derivatives (3-8) were designed to probe the structure-activity relationship between ligand, heme propionate, and H4B. Compound 8R was identified as the most potent and selective molecule of this study, exhibiting a Ki of 24 nM for nNOS, with 273-fold and 2822-fold selectivity against iNOS and eNOS, respectively. Although crystal structures of 8R complexed with nNOS and eNOS revealed a similar binding mode, the selectivity stems from the distinct electrostatic environments in two isoforms that result in much lower inhibitor binding free energy in nNOS than in eNOS. These findings provide a basis for further development of simple, but even more selective and potent, nNOS inhibitors.
Impact of Quaternary Organization on the Antigenic Structure of the Tick-Borne Encephalitis Virus Envelope Glycoprotein E (2009)

The envelope protein E of flaviviruses mediates both receptor-binding and membrane fusion. At the virion surface, 180 copies of E are tightly packed and organized in a herringbone-like icosahedral structure, whereas in noninfectious subviral particles, 60 copies are arranged in a T=1 icosahedral symmetry. In both cases, the basic building block is an E dimer which exposes the binding sites for neutralizing antibodies at its surface. It was the objective of our study to assess the dependence of the antigenic structure of E on its quaternary arrangement, i.e., as part of virions, recombinant subviral particles, or soluble dimers. For this purpose, we used a panel of 11 E protein-specific neutralizing monoclonal antibodies, mapped to distinct epitopes in each of the three E protein domains, and studied their reactivity with the different soluble and particulate forms of tick-borne encephalitis virus E protein under nondenaturing immunoassay conditions. Significant differences in the reactivities with these forms were observed that could be related to (i) limited access of certain epitopes at the virion surface; (ii) limited occupancy of epitopes in virions due to steric hindrance between antibodies; (iii) differences in the avidity to soluble forms compared to the virion, presumably related to the flexibility of E at its domain junctions; and (iv) modulations of the external E protein surface through interactions with its stem-anchor structure. We have thus identified several important factors that influence the antigenicity of the flavivirus E protein and have an impact on the interaction with neutralizing antibodies.
Nucleosides. XXI. Synthesis of Some 3'-Substituted 2',3'-Dideoxyribonucleosides of Thymine and 5-Methylcytosine1 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. XXI. Synthesis of Some 3'-Substituted 2',3'-Dideoxyribonucleosides of Thymine and 5-Methylcytosine1Naishun Miller and Jack J. FoxCite this: J. Org. Chem. 1964, 29, 7, 1772–1776Publication Date (Print):July 1, 1964Publication History Published online1 May 2002Published inissue 1 July 1964https://pubs.acs.org/doi/10.1021/jo01030a026https://doi.org/10.1021/jo01030a026research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-Citations40LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Protein and solvent engineering of subtilisin BPN' in nearly anhydrous organic media (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein and solvent engineering of subtilisin BPN' in nearly anhydrous organic mediaPramod P. Wangikar, Thomas P. Graycar, David A. Estell, Douglas S. Clark, and Jonathan S. DordickCite this: J. Am. Chem. Soc. 1993, 115, 26, 12231–12237Publication Date (Print):December 1, 1993Publication History Published online1 May 2002Published inissue 1 December 1993https://pubs.acs.org/doi/10.1021/ja00079a001https://doi.org/10.1021/ja00079a001research-articleACS PublicationsRequest reuse permissionsArticle Views188Altmetric-Citations54LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Weighted Multi-Hypothesis Inter Prediction for Video Coding (2019)

A key component of state-of-the art video coding is motion-compensated prediction, also called inter prediction. Current standards allow uni- and bi-prediction, i.e. linear superposition of up to two motion-compensated prediction signals. It is well-known that by a superposition of more than two prediction signals (or hypotheses), the energy of the prediction error can be further reduced. In this paper, it is shown that allowing the encoder to choose among different weights for the individual hypotheses is beneficial from a rate-distortion perspective. A practical multi-hypothesis inter prediction scheme based on the Versatile Video Coding Test Model (VTM) is presented. For VTM-1, in the Random Access configuration according to the JVET Common Test Conditions, the average luma BD bit rate is in the range of -1.6 % to -1.9 % for different settings using up to four prediction hypotheses. For VTM-2, the corresponding BD bit rate is -0.95 %. For higher bit rates (i.e., QP values 12, 17, 22, 27) the BD bit rates are -2.2 % for VTM-1 and -1.4 % for VTM-2.
Hydrogen sulfide protects from intestinal ischaemia-reperfusion injury in rats (2009)

Hydrogen sulfide (H2S) is an endogenously gaseous mediator, regulating many pathophysiological functions in mammalian cells. H2S has been shown to inhibit myocardial ischaemia–reperfusion (I/R) injury. However, little is known about whether H2S could modulate intestinal I/R injury. This study aimed to investigate the effect of H2S on intestinal I/R injury and potential mechanism(s) underlying the action of H2S in regulating the development of intestinal I/R injury in rats. Following surgical induction of intestinal I/R injury for 1 h, groups of Sprague-Dawley rats were treated with, or without, tetramethylpyrazine (8 mg/kg), or sodium hydrosulfide (NaHS, an H2S donor at 7 or 14 μmol/kg) 30 min after occlusion. All rats were sacrificed immediately after the reperfusion. Their intestinal injury, together with that of sham-control rats, was histologically examined and their sera and intestinal malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (GSH-Px) activities were characterized by biochemical analysis. The results showed that NaHS significantly reduced intestinal I/R injury and the levels of sera and intestinal MDA activity, and dramatically increased the levels of serum and intestinal SOD and GSH-Px activity. The results suggest that H2S protects from intestinal I/R injury in rats, which is associated with increase in the activity of antioxidant enzymes.
Pulse shape optimization for defect prevention in pulsed laser welding of stainless steels (1993)

A variety of stainless steels were exposed to pulsed Nd:YAG laser with the rectangular shape power to first investigate practical problems related to pulsed laser welding. Porosities, cracks and undercuts were found as weld defects. A large porosity was formed in a key-hole mode of deep penetration weld metal of any stainless steel. Solidification cracks were present in Type 310S with above 0.017%P and undercuts were formed in Type 303 with about 0.3%S. The conditions for the formation of porosity were determined in further detail in Type 316. With the objectives of obtaining a fundamental knowledge of formation and prevention of weld defects, the fusion and solidification behavior of a molten puddle was observed during laser spot welding of Type 310S through high speed video photographing technique and the behavior was estimated by using a heat-conduction and solidification theory model. It was deduced that cellular dendrite tips grew rapidly from the bottom to the surface, and consequently residual liquid remained at the grain boundaries in wide regions and enhanced the solidification cracking susceptibility. Several laser pulse shapes were investigated and optimum pulse shapes were proposed for the reduction and prevention of porosity and solidification cracking.
Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery (2001)

Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood.Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation.While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N G -monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress.L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation.With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise.S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation.Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood.S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients.These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function.This effect may have application for the treatment of diseases characterized by endothelial dysfunction.
Large-Scale Production of Porcine Mature Interleukin-18 (IL-18) in Silkworms Using a Hybrid Baculovirus Expression System. (2003)

In this report, a hybrid baculovirus expression system, which means a hybrid virus of the Autographa californica nuclear polyhedrosis virus and the Bombyx mori nuclear polyhedrosis virus, was used for the large-scale production of porcine mature interleukin-18 (IL-18) in silkworms. Two recombinant hybrid baculoviruses containing cDNA of the porcine precursor IL-18 and the porcine caspase-1 were constructed and were used to infect silkworm larvae. After the co-infection of the two viruses, porcine mature IL-18 was efficiently produced in the haemolymph. The concentration of IL-18 in the haemolymph was 80-100 μg/ml, as determined by porcine IL-18 specific ELISA. This yield was twenty-times more than that of the insect cell expression system described previously. The porcine mature IL-18 produced by the silkworms strongly induced interferon-γ (IFN-γ) production from porcine PBMC. An insect factory system for the large-scale production of useful cytokines for livestock animals will be available in the near future.
Therapeutic Inhibition of the Epidermal Growth Factor Receptor in High-Grade Gliomas: Where Do We Stand? (2009)

High-grade gliomas account for the majority of intra-axial brain tumors. Despite abundant therapeutic efforts, clinical outcome is still poor. Thus, new therapeutic approaches are intensely being investigated. Overexpression of the epidermal growth factor receptor (HER1/EGFR) is found in various epithelial tumors and represents one of the most common molecular abnormalities seen in high-grade gliomas. Dysregulated HER1/EGFR is found in 40% to 50% of glioblastoma, the most malignant subtype of glioma. Several agents such as tyrosine kinase (TK) inhibitors, antibodies, radio-immuno conjugates, ligand-toxin conjugates, or RNA-based agents have been developed to target HER1/EGFR or its mutant form, EGFRvIII. To date, most agents are in various stages of clinical development. Clinical data are sparse but most advanced for TK inhibitors. Although data from experimental studies seem promising, proof of a significant clinical benefit is still missing. Among the problems that have to be further addressed is the prediction of the individual patient's response to HER1/EGFR-targeted therapeutics based on molecular determinants. It is quite possible that blocking HER1/EGFR alone will not sufficiently translate into a clinical benefit. Therefore, a multiple target approach concomitantly aimed at different molecular sites might be a favorable concept. This review focuses on current HER1/EGFR-targeted therapeutics and their development for high-grade gliomas.
Viscous scattering of a pressure wave: Calculation of the fluid tractions on a biomimetic acoustic velocity sensor (2006)

In the paper we give a method for calculating the tractions (local forces) of the fluid motion determined by an incoming plane pressure wave on an artificial hair cell transducer structure. The sensing element of the transducer is a standing high aspect ratio cilium in the shape of a narrow thin curved beam (tape-like), which can be easily fabricated in micro-/nanotechnology. The method is based on considering the system of partial differential equations describing the motion of the compressible viscous fluid in an acoustic linearized approximation, and representation of the velocity field as a viscous acoustic single-layer potential. The boundary conditions, stating the cancellation of the velocity components on the solid beam, yield a two-dimensional (2-D) system of three integral equations over the beam's surface for the traction components. In the case of a narrow cilium, the system of integral equations furnishes a system of two 1-D integral equations over the symmetry curve of the structure for obtaining the tangential and normal components of the traction. This system is solved numerically by a finite (boundary) element method. The numerical code written for solving the problem was applied to some particular structures. The last structure is similar to the trichobothrium of a spider Cupiennius salei. The results obtained show that the curvature of the hair is enhancing sensitivity to flows directed normal to the main shaft of the hair confirming the assertion of Barth et al. [Philos. Trans. R. Soc. London, Ser. B 340, 445-461 (1993)].
Large UV-induced negative index changes in germanium-freenitrogen-doped planar SiO 2 waveguides (1998)

Negative refractive index changes of up to 1.7 × 10–3 have been induced by 248 nm excimer laser light in planar germanium-free SiON waveguides. Highly temperature-stable 40 dB Bragg gratings with a length of 8 mm have been written. A novel mechanism of photosensitisation was used to create the high-index changes.
ASSESSMENT OF TRAFFIC FLOW BENEFITS OF FLYOVERS: A CASE STUDY (2013)

This paper describes the results of a pilot study of the benefits of a flyover bridge which wasconstructed over an existing at-grade intersection to increase capacity of traffic flow in two directionson one of the main highway. Under the flyover, the existing traffic signalization for the intersectionstill uses the same fixed time control plans. This is a main reason why traffic flows underneath theflyover still experience long delays and queue length similar to the situation ‘before’. The purpose ofthis research is to evaluate the benefits of the flyover. The paper presents the performance of theflyover upgraded intersection and points out the remaining problems including long delays under theflyover. It was found that about 35-40% of the total traffic volume diverted to the flyover, and despitean increase in traffic volume of +29.46%, at the intersection, the vehicle delays were reduced by30.41% over the same period; the saving in travel time and vehicle operating costs amounted to421.65 Million Baht.