gebhart/patrepeval huggingface dataset:
Diazepam dependence prevented by glutamate antagonists. (1993)

Long-term treatment leads to tolerance to and dependence on benzodiazepines. Abrupt termination of benzodiazepine administration triggers the expression of signs of dependence. Mice withdrawn from chronic treatment with diazepam showed a time-related evolution of anxiety, muscle rigidity, and seizures between days 4 and 21 after treatment discontinuation. A period between withdrawal days 1 and 3 was symptom-free. Surprisingly, during this "silent phase" the susceptibility of mice to alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate (ATPA) and kainate seizures and the magnitude of monosynaptic reflexes mediated by non-N-methyl-D-aspartate (NMDA) mechanisms were enhanced. In apparent contrast, the "active phase", between withdrawal days 4 and 21, was characterized by increased susceptibility to NMDA seizures and enhanced magnitude of polysynaptic reflexes, which are NMDA dependent. Treatment of mice with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) or 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline but not with the NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) during the silent phase prevented signs of dependence. In contrast, treatment with CPP but not with GYKI 52466 during the active phase prevented the symptoms. The development of tolerance to and dependence on diazepam was prevented by concurrent treatment of mice with CPP but was not prevented by GYKI 52466. These data indicate that NMDA-dependent mechanisms contribute to the development of tolerance to diazepam and to the expression of signs of dependence in mice after termination of long-term treatment with diazepam. Nevertheless, the non-NMDA-mediated silent phase is essential for triggering the symptoms. Therefore, AMPA antagonists may offer a therapeutic approach for preventing dependence on benzodiazepines that is an alternative to NMDA antagonism.
Expression of Sensory Neuropeptides in Tendon is Associated with Failed Healing and Activity-Related Tendon Pain in Collagenase-Induced Tendon Injury (2010)

There was increased expression of SP and CGRP after collagenase-induced tendon injury, and their expression was positively associated with double-stance duration. Clinical Relevance Substance P and CGRP might be involved in the pathogenesis and origin of pain of tendinopathy and could be the targets for future intervention.
Cystic fibrosis and endobronchial pseudomonas infection (1993)

The discovery of the cystic fibrosis gene has provided new approaches to gene therapy and drug therapy. At the present time, however, we are still faced with the morbidity and mortality due to lung infections caused by Pseudomonas aeruginosa and Pseudomonas cepacia. The present survey of some of the recently published articles shows that applied science related to the clinical care of cystic fibrosis (CF) patients is also progressing. Cross-infection in CF centers and during social contacts between CF patients out of the hospital environment has been described in some countries. Prophylactically, cohort isolation procedures are effective. The individual clinical course of the chronic pulmonary infection is adversely influenced during prediabetic mellitus periods and by development of high titers of specific IgG2 and IgG3 antibodies against P. aeruginosa. A vaccine against P. aeruginosa is currently being tested in CF patients. The induced antibodies have much higher affinity and opsonophagocytic activity than infection-induced antibodies. Ciprofloxacin, which is widely used in CF, easily gives rise to resistance in P. aeruginosa and Staphylococcus aureus. Restricting the use of this drug in CF is therefore necessary. Aerosolized recombinant DNase is a promising and efficient new drug for management of airflow limitation due to purulent airway secretion in CF. For end-stage CF, double-lung and heart-lung transplantation show encouraging intermediate-term results, the two main obstacles being donor organ shortage and obliterative bronchiolitis.
Menthol Stereoisomers Exhibit Different Effects on α4β2 nAChR Upregulation and Dopamine Neuron Spontaneous Firing (2018)

Menthol contributes to poor cessation rates among smokers, in part because menthol enhances nicotine reward and reinforcement. Mentholated tobacco products contain (-)-menthol and (+)-menthol, in varying proportions. We examined these two menthol stereoisomers for their ability to upregulate α4β2 nAChRs and to alter dopamine neuron firing frequency using long-term, low-dose (≤500 nm) exposure that is pharmacologically relevant to smoking. We found that (-)-menthol upregulates α4β2 nAChRs while (+)-menthol does not. We also found that (-)-menthol decreases dopamine neuron baseline firing and dopamine neuron excitability, while (+)-menthol exhibits no effect. We then examined both stereoisomers for their ability to inhibit α4β2 nAChR function at higher concentrations (>10 µm) using the <i>Xenopus</i> oocyte expression system. To probe for the potential binding site of menthol, we conducted flooding simulations and site-directed mutagenesis. We found that menthol likely binds to the 9´ position on the TM2 (transmembrane M2) helix. We found that menthol inhibition is dependent on the end-to-end distance of the side chain at the 9´ residue. Additionally, we have found that (-)-menthol is only modestly (∼25%) more potent than (+)-menthol at inhibiting wild-type α4β2 nAChRs and a series of L9´ mutant nAChRs. These data reveal that menthol exhibits a stereoselective effect on nAChRs and that the stereochemical effect is much greater for long-term, submicromolar exposure in mice than for acute, higher-level exposure. We hypothesize that of the two menthol stereoisomers, only (-)-menthol plays a role in enhancing nicotine reward through nAChRs on dopamine neurons.
Photochemical Studies. L. The Ketene-Oxygen System at Higher Temperatures1 (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemical Studies. L. The Ketene-Oxygen System at Higher Temperatures1Richard A. Holroyd and W. Albert Noyes Jr.Cite this: J. Am. Chem. Soc. 1956, 78, 19, 4831–4836Publication Date (Print):October 1, 1956Publication History Published online1 May 2002Published inissue 1 October 1956https://pubs.acs.org/doi/10.1021/ja01600a003https://doi.org/10.1021/ja01600a003research-articleACS PublicationsRequest reuse permissionsArticle Views39Altmetric-Citations14LEARN 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
Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically “Silent” Non‐B, Non‐C Chronic Hepatitis (1996)

Abstract Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically “silent” non‐B, non‐C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8‐nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the C‐terminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically “silent” NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.
High Degree Accuracy Modelling and Calibration of Serial Robots with Large Errors (2006)

The paper deals with the improvement of accuracy modelling and calibration process, in the case of serial robots with large errors. Beginning from the first degree kinematic modelling, a general third-degree modelling of errors in serial robot chains is generated and applied for a RRR Puma type serial robot-structure. The model is based on the use of error Jacobian matrices, namely first, second and third-degree error Jacobian, respectively. Through the high-degree error model, the end-effector positioning can be more accurately estimated. Furthermore, a general calibration algorithm based on the third degree error model is presented, with application for the same RRR serial manipulator. Finally, a numerical example of the proposed algorithms is presented and conclusions.
Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines (2015)

Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc.
YaConv: Convolution with Low Cache Footprint (2022)

This article introduces YaConv , a new algorithm to compute convolution using GEMM microkernels from a Basic Linear Algebra Subprograms library that is efficient for multiple CPU architectures. Previous approaches either create a copy of each image element for each filter element or reload these elements into cache for each GEMM call, leading to redundant instances of the image elements in cache. Instead, YaConv loads each image element once into the cache and maximizes the reuse of these elements. The output image is computed by scattering results of the GEMM microkernel calls to the correct locations in the output image. The main advantage of this new algorithm—which leads to better performance in comparison to the existing im2col approach on several architectures—is a more efficient use of the memory hierarchy. The experimental evaluation on convolutional layers from PyTorch, along with a parameterized study, indicates an average 24% speedup over im2col convolution. Increased performance comes as a result of 3× reduction in L3 cache accesses and 2× fewer branch instructions.
Factors Shaping Young and Mature Bacterial Biofilm Communities in Two Drinking Water Distribution Networks (2021)

Abstract The presence of biofilms in drinking water distribution systems (DWDS) can affect both water quality and system integrity; yet these systems remain poorly studied due to lack of accessibility. We established two independent full-scale DWDS Testbeds (A and B) on two different campuses situated in a tropical urban environment and equipped them with online sensors. Testbed B experienced higher levels of monochloramine and lower water age than Testbed A within the campus. Based on long amplicon-sequencing of bacterial 16S rRNA genes extracted from the mature biofilms (MPB) growing on pipes and young biofilms (YSB) growing on the sensors, a core community was identified in the two testbeds. The relative abundances of operational taxonomic units at the family level, including Mycobacteriaceae, Methylobacteriaceae, Rhodospirillaceae, Nitrosomonadaceae, and Moraxellaceae, were consistent for MPB and YSB on each campus. The MPB community was found to be influenced by conductivity, sample age, and pipe diameter as determined by both canonical correlation analysis and fuzzy set ordination. MPB displayed higher α-diversity based on Hill numbers than YSB; in general, second order Hill numbers correlated positively with conductivity and sample age, but negatively with ORP and nitrite. Pseudomonas spp. together with Bacillus spp. likely initiated biofilm formation of YSB on Testbed A under conditions of reduced monochloramine and high water age. Significant levels of orthophosphate were detected in YSB samples at two stations and associated with higher levels of stagnation based on long-term differential turbidity measurement (DTM). Orthophosphate and DTM may act as indicators of the biofilm growth potential within DWDS. Highlights - Established two testbeds to study biofilms in full-scale distribution system - Biofilms on pipes and sensors had core community - Temporal effect and higher α-diversity for biofilms on pipes - Water chemistry was related to biofilm community differences Graphical Abstract
Synthesis and Biological Evaluation of 1-Arylsulfonyl-5-(N-hydroxyacrylamide)indoles as Potent Histone Deacetylase Inhibitors with Antitumor Activity in Vivo (2012)

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indoles has been identified as a new class of histone deacetylase inhibitors. Compounds 8, 11, 12, 13, and 14 demonstrated stronger antiproliferative activities than 1 (SAHA) with GI(50) values ranging from 0.36 to 1.21 μM against Hep3B, MDA-MB-231, PC-3, and A549 human cancer cell lines. Lead compound 8 showed remarkable HDAC 1, 2, and 6 isoenzymes inhibitory activities with IC(50) values of 12.3, 4.0, 1.0 nM, respectively, which are comparable to 1. In in vivo efficacy evaluation against lung A549 xenograft model, 8 displayed better antitumor activity than compound 1.
ChemInform Abstract: Synthetic Models Related to DNA Intercalating Molecules: Preparation of 9‐Aminoacridines Linked to the Nucleotide Bases Adenine, Guanine and Thymine. (1986)

Abstract Das Q‐Phenoxy‐acridin (I) wird mit Aminoalkoholen kondensiert und mit HBr in Bromalkylamino‐acridine (II) übergeführt, clie mit den Nucleotid‐Basen (III) bzw. (V) zu den Kondensationsprodukten (IV) bzw. (VI) führen.
Nanog-Independent Reprogramming to iPSCs with Canonical Factors (2014)

It has been suggested that the transcription factor Nanog is essential for the establishment of pluripotency during the derivation of embryonic stem cells and induced pluripotent stem cells (iPSCs). However, successful reprogramming to pluripotency with a growing list of divergent transcription factors, at ever-increasing efficiencies, suggests that there may be many distinct routes to a pluripotent state. Here, we have investigated whether Nanog is necessary for reprogramming murine fibroblasts under highly efficient conditions using the canonical-reprogramming factors Oct4, Sox2, Klf4, and cMyc. In agreement with prior results, the efficiency of reprogramming Nanog (-/-) fibroblasts was significantly lower than that of control fibroblasts. However, in contrast to previous findings, we were able to reproducibly generate iPSCs from Nanog (-/-) fibroblasts that effectively contributed to the germline of chimeric mice. Thus, whereas Nanog may be an important mediator of reprogramming, it is not required for establishing pluripotency in the mouse, even under standard conditions.
Peroxynitrite modulates tyrosine‐dependent signal transduction pathway of human erythrocyte band 3 (1997)

Peroxynitrite, the product of the reaction between nitric oxide and superoxide anion, is able to nitrate protein tyrosines. If this modification occurs on phosphotyrosine kinase substrates, it can down-regulate cell signaling. We investigated the effects of peroxynitrite on band 3-mediated signal transduction of human erythrocytes. Peroxynitrite treatment induced two different responses. At low concentrations (10-100 microM) it stimulated a metabolic response, leading to 1) a reversible inhibition of phosphotyrosine phosphatase activity, 2) a rise of tyrosine phosphorylation in the 22K cytoplasmic domain of band 3, 3) the release of glyceraldehyde 3-phosphate dehydrogenase from the membrane, and 4) the enhancement of lactate production. At high concentrations (200-1000 microM), peroxynitrite induced 1) cross-linking of membrane proteins, 2) inhibition of band 3 tyrosine phosphorylation, 3) nitration of tyrosines in the 22K cytoplasmic domain of band 3, 4) binding of hemoglobin to the membrane, 5) irreversible inhibition of phosphotyrosine kinase activity, 6) massive methemoglobin production, and 7) irreversible inhibition of lactate production. Our results demonstrate that at concentrations that could conceivably be achieved in vivo (10-100 microM), peroxynitrite behaves like other oxidants, i.e., it stimulates band 3 tyrosine phosphorylation and increases glucose metabolism. Thus, one plausible physiologic effect of peroxynitrite is the up-regulation of signaling through the reversible inhibition of phosphotyrosine phosphatase activity. At high concentrations of peroxynitrite, the tyrosine phosphorylation ceases in parallel with the nitration of band 3 tyrosines, but at these concentrations phosphotyrosine kinase activity and glycolysis are also irreversibly inhibited. Thus, at least in red blood cells, the postulated down-regulation of signaling by peroxynitrite cannot merely be ascribed to the nitration of tyrosine kinase targets.
[Insights into auto-transplantation--the unexpected discovery of transdifferentiation systems in bone marrow stromal cells and its application]. (2007)

Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered candidates for cell transplantation therapy for muscle-degenerative diseases. Bone marrow stromal cells (MSCs) also have great potential as therapeutic agents since they are easily isolated and can be expanded from patients without serious ethical or technical problems. Recently, new methods for the highly efficient and specific induction of functional skeletal muscle cells have been found in MSCs. Induced cells differentiate into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. Furthermore, the induced population contained Pax7-positive cells that contribute to subsequent regeneration of muscle upon repetitive damage without additional transplantation of cells. Here I describe the discovery of these induction systems and focus on the potential use of MSC-derived cells for "auto-cell transplantation therapy" in muscle-degenerative diseases.
Activation-induced peripheral blood T cell apoptosis is Fas independent in HIV-infected individuals (1996)

T cell apoptosis has been proposed as an important contributor to the functional defects and depletion of T cells in HIV-infected individuals. However, the mechanisms involved in this apoptosis have not been elucidated. We recently showed that peripheral blood T cells from HIV-infected individuals are especially susceptible to Fas antigen-induced apoptosis. In this study we examine the role of Fas, CTLA-4, tumor necrosis factor (TNF) receptors (TNFR) and CD30, receptors known to be involved in T cell activation-induced cell death (AICD), in the spontaneous and activation (anti-CD3)-induced apoptosis of peripheral blood T cells from asymptomatic HIV-infected individuals. We report here that spontaneous and activation-induced T cell apoptosis cannot be inhibited by reagents that block interactions of Fas, CTLA-4, p55 and p75 TNFR and CD30 with their respective ligands. We also show that IL-12, IFN-gamma, IL-4 and IL-10 cannot modify spontaneous, activation- and anti-Fas-induced apoptosis. Anti-Fas preferentially induced CD4+ T cell apoptosis whereas AICD induced apoptosis equally in CD4+ and CD8+ T cells. We conclude that T cell AICD in HIV infection is not mediated by Fas, thus indicating that Fas-induced and activation-induced T cell apoptosis are independent mechanisms of apoptosis which may play different roles in the pathogenesis of HIV infection.
An Adaptive Model Predictive Approach to Power Oscillation Damping Utilizing Variable Series Reactance Facts Devices (2006)

This paper describes an adaptive method of controlling FACTS devices for power oscillation damping. The method is based on step-wise series reactance modulation. Here, a reduced model of the power system with only two rotating masses is used as a basis for the control design. The model parameters are updated using local measurements of the active power on the controlled line. An adaptive closed loop controller is developed based on the principle that it is possible to stabilize an oscillation in a power system which is characterized by one major mode of oscillation by switching a reactance in series with one transmission line in a small number of steps. The reduced model parameters are recomputed when new information of the system response is known making the control scheme an adaptive one. The paper also includes the derivation of a damping controller with a power flow control feature and a verification of the controllers using digital simulations of power system models of different complexities
Supplementary Figure 2B from BRaf and MEK Inhibitors Differentially Regulate Cell Fate and Microenvironment in Human Hepatocellular Carcinoma (2023)

&lt;p&gt;(B) The phosphorylation of the given proteins in lysates of HepG2 (left), Hep3B (middle) and Huh-7 (right) cells after treatment with 0.2, 1, and 5µM GW5074 or sunitinib at different time points. The values represent MFI of 30-60 beads for each kinase and time point. One of two or three representative experiments is shown.&lt;/p&gt;
Synthesis of M-UiO-66 (M = Zr, Ce or Hf) employing 2,5-pyridinedicarboxylic acid as a linker: defect chemistry, framework hydrophilisation and sorption properties (2017)

Metal-organic frameworks of general composition [M<sub>6</sub>(OH)<sub>4</sub>(O)<sub>4</sub>(PDC)<sub>6-x</sub>(Cl)<sub>2x</sub>(H<sub>2</sub>O)<sub>2x</sub>] with M = Zr, Ce, Hf; PDC<sup>2-</sup> = 2,5-pyridinedicarboxylate and 0 ≤ x ≤ 2 were obtained under reflux using formic, nitric or acetic acid as an additive. Rietveld refinements carried out using a fixed occupancy of the linker molecules according to the results of thermogravimetric measurements confirmed that the MOFs crystallize in the UiO-66 type structure and demonstrate that the structural models describe the data well. Further characterization was carried out by NMR spectroscopy, thermogravimetric analysis, Zr K-edge EXAFS- and Ce L<sub>3</sub>-edge XANES measurements. To highlight the influence of the additional nitrogen atom of the pyridine ring, luminescence and vapour sorption measurements were carried out. The hydrophilisation of the MOFs was shown by the adsorption of water at lower p/p<sub>0</sub> (<0.2) values compared to the corresponding BDC-MOFs (0.3). For water and methanol stability cycling adsorption experiments were carried out to evaluate the MOFs as potential adsorbents in heat transformation applications.