gebhart/patrepeval huggingface dataset:
INHIBITION OF HUMAN CARDIAC FIBROBLAST MITOGENESIS BY BLOCKADE OF MITOGEN‐ACTIVATED PROTEIN KINASE AND PHOSPHATIDYLINOSITOL 3‐KINASE (1999)

1. Interstitial fibroblast proliferation is an elemental feature in the development of cardiac fibrosis. The effects of inhibitors of the intracellular signalling proteins, MEK, a kinase involved in the mitogen-activated protein kinase (MAPK) pathway and phosphatidylinositol 3-kinase (PI3-K), were tested on growth of cultured human cardiac fibroblasts. 2. Cardiac fibroblasts were isolated from transplant recipient myocardium and made quiescent by serum deprivation for 48 h. Cells were incubated for 24 h with the inhibitors PD 098059 (0.3-30 mumol/L) and LY294002 (1-25 mumol/L) in the presence and absence of platelet-derived growth factor-AB (PDGF-AB, 10 ng/mL). DNA synthesis was measured by [3H]-thymidine incorporation assay (20-24 h). 3. Both compounds markedly inhibited both basal and PDGF-stimulated increases in DNA synthesis in a concentration-dependent manner. Cardiac fibroblast DNA synthesis was reduced to near control levels by PD 098059, while it was inhibited completely by LY294002. 4. These results implicate the importance of MAPK and PI3-K activation in the signal transduction pathways necessary for cardiac fibroblast replication.
Spontaneous Cross Linking of Small-Diameter Single-Walled Carbon Nanotubes (2003)

We report surprising findings of spontaneous cross-linking of small-diameter zigzag single-walled carbon nanotubes, with no applied external pressure, using ab initio density functional theory. Sunstantial differences in the cross-linking reactivity of zigzag and armchair single-walled carbon nanotubes are revealed by the calculations. The cross linking creates 2D sheetlike network structures of highly deformed nanotubes linked with covalent C−C bonds. The cross-linking process can be directed by H2 chemisorption.
IS LOW SERUM FREE TESTOSTERONE A MARKER FOR HIGH GRADE PROSTATE CANCER? (2000)

In our study patients with prostate cancer and low free testosterone had more extensive disease. In addition, all men with a biopsy Gleason score of 8 or greater had low serum free testosterone. This finding suggests that low serum free testosterone may be a marker for more aggressive disease.
Evolutionary Mode and Functional Divergence of Vertebrate NMDA Receptor Subunit 2 Genes (2010)

These findings provide intriguing subjects for testing the 2R and 3R hypothesis and we expect it could provide new insights into the underlying evolution mechanisms of cognition in vertebrate.
Thinking Small and Dreaming Big: Medicinal Chemistry Strategies for Designing Optimal Antibody-Drug Conjugates (ADCs) (2017)

Medicinal Chemistry Reviewsis an outstanding 600 page volume providing timely and critical reviews of important topics in medicinal chemistry. It is provided free of charge to MEDI members in electronic format. Members can also order a print copy, for the cost of printing, shipping and handling
Evaluation of High Molecular Weight Poly(Oxyethylene) (Polyox) Polymer: Studies of Flow Properties and Release Rates of Furosemide and Captopril from Controlled-Release Hard Gelatin Capsules (2000)

The powder characteristics and the effect of the molecular weight of polymers as diluents on the release rate of furosemide and captopril from hard gelatin capsules were evaluated. The high molecular weight polymers studied were poly(oxyethylene) homopolymers (Polyox), with molecular weight ranging from 4,000,000 to 7,000,000. Powder characteristics suggested good flowability for these materials and predicted capsule fill weight uniformity. Swelling experiments showed a very high degree of swelling for these materials in both gastric and buffer solution. These polymers can sustain the release rate of both water-soluble and insoluble drugs from drug delivery systems. The low molecular weight polymers have a less pronounced sustained-release effect compared to the high molecular weight polymer material (i.e., those with 7,000,000 molecular weight). An increase in the content of polymer results in a decrease in the release rate of the drug. The solubility of the drugs clearly influenced the release rate. Release kinetics were evaluated and appeared to be influenced by the molecular weight of the polymer, the solubility of drug, and the ratio of the drug to polymer in the capsule. Bimodal release kinetics were exhibited by a number of furosemide formulations (i.e., F5 and F8).
Drug Conjugation Affects Pharmacokinetics and Specificity of Kidney-Targeted Peptide Carriers (2016)

Peptides play a crucial role as biological vectors for targeted drug delivery. In particular, in cases of specific receptor expression, peptides are highly potent carriers for drug targeting approaches. Kidney-targeted peptides require specific attention because of the necessity of fine-tuning their behavior with respect to extraction and retention in the complex architecture of the kidneys. To enable optimal carrier capacity and targeting specificity, this study focuses on pharmacokinetic profiles of different kidney-specific peptides and examines the impact of drug conjugation. γ-Scintigraphy was used to compare the pharmacokinetics and specificity prior to and after drug conjugation of the model drug α-lipoic acid. The results revealed that drug conjugation dramatically affects the targeting specificity, in the worst case leading to a total loss of kidney specificity. Nevertheless, efficient drug transport was achieved with the novel kidney carrier (KKEEE)<sub>3</sub>K, even with a multiple-drug loading of α-lipoic acid after intraveous and intraperitoneal administration. In contrast to other peptidic molecules, (KKEEE)<sub>3</sub>K demonstrated its significant potential as a promising carrier candidate for kidney-targeted drug delivery to proximal tubule cells, especially for the treatment of severe kidney diseases.
Design of multiprocessor systems for concurrent error detection and fault diagnosis (1991)

Results on the design of systems using algorithm-based fault tolerance (ABFT), a low-overhead fault tolerance scheme for high-speed parallel processing systems, are presented. Bounds on the diagnosability of the system and the number of checks needed to design a unit system of given capability are derived. A procedure for forming the target fault-tolerant system from the unit system is introduced. The procedure is applicable to a wide range of systems in which processors may share data elements. The applications of the design scheme are illustrated through examples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
At the Crossroads of Necrosis and Apoptosis: Signaling to Multiple Cellular Targets by HMGB1 (2002)

Cells can die through two mechanisms: necrosis and apoptosis. Necrosis occurs in response to stimuli that cause cellular damage and result in the release of intracellular proteins, which stimulate the inflammatory response. Necrosis is associated with tissue damage and organ deterioration. Apoptosis is a programmed cell death during which the cellular membrane remains intact, but activated enzymes destroy the cell from within. Bustin discusses how the mobility of the nuclear protein high mobility group B1 (HMGB1) may be a key signal for determining whether certain cells undergo necrotic or apoptotic death. Necrosis may result when HMGB1 is released from the cells and stimulates the inflammatory response. HMGB1 appears to have extracellular signaling functions, such as stimulation of cell motility and tumor metastasis and activation of the cytokine signaling pathways. Through its action on the cytokine signaling targets, HMGB1 may be an important therapeutic target for diseases of cytokine excess, including septic shock.
Liposomal Drug Formulations in the Treatment of Rheumatoid Arthritis (2011)

Liposomes have been extensively investigated as drug delivery systems in the treatment of rheumatoid arthritis (RA). Low bioavailability, high clearance rates and limited selectivity of several important drugs used for RA treatment require high and frequent dosing to achieve sufficient therapeutic efficacy. However, high doses also increase the risk for systemic side effects. The use of liposomes as drug carriers may increase the therapeutic index of these antirheumatic drugs. Liposomal physicochemical properties can be changed to optimize penetration through biological barriers and retention at the site of administration, and to prevent premature degradation and toxicity to nontarget tissues. Optimal liposomal properties depend on the administration route: large-sized liposomes show good retention upon local injection, small-sized liposomes are better suited to achieve passive targeting. PEGylation reduces the uptake of the liposomes by liver and spleen, and increases the circulation time, resulting in increased localization at the inflamed site due to the enhanced permeability and retention (EPR) effect. Additionally liposomal surfaces can be modified to achieve selective delivery of the encapsulated drug to specific target cells in RA. This review gives an overview of liposomal drug formulations studied in a preclinical setting as well as in clinical practice. It covers the use of liposomes for existing antirheumatic drugs as well as for new possible treatment strategies for RA. Both local administration of liposomal depot formulations and intravenous administration of passively and actively targeted liposomes are reviewed.
Development and Applications of VSV Vectors Based on Cell Tropism (2012)

Viral vectors have been available in various fields such as medical and biological research or gene therapy applications. Targeting vectors pseudotyped with distinct viral envelope proteins that influence cell tropism and transfection efficiency are useful tools not only for examining entry mechanisms or cell tropisms but also for vaccine vector development. Vesicular stomatitis virus (VSV) is an excellent candidate for development as a pseudotype vector. A recombinant VSV lacking its own envelope (G) gene has been used to produce a pseudotype or recombinant VSV possessing the envelope proteins of heterologous viruses. These viruses possess a reporter gene instead of a VSV G gene in their genome, and therefore it is easy to evaluate their infectivity in the study of viral entry, including identification of viral receptors. Furthermore, advantage can be taken of a property of the pseudotype VSV, which is competence for single-round infection, in handling many different viruses that are either difficult to amplify in cultured cells or animals or that require specialized containment facilities. Here we describe procedures for producing pseudotype or recombinant VSVs and a few of the more prominent examples from envelope viruses, such as hepatitis C virus, Japanese encephalitis virus, baculovirus, and hemorrhagic fever viruses.
Down‐regulation of acetate pathway through antisense strategy in Escherichia coli: Improved foreign protein production (2003)

A problem with the use of Escherichia coli to produce foreign proteins is that although endogenously produced acetate is physiologically indispensable, it inhibits protein expression. Here we firstly employed an antisense RNA strategy as an elaborate metabolic engineering tool to partially block biosynthesis of two major acetate pathway enzymes, phosphotransacetylase (PTA) and acetate kinase (ACK). Three recombinant plasmids containing antisense genes targeting either or both of pta and ackA were constructed, and their effects on the acetate pathway and foreign protein productivity compared to control plasmid without any antisense genes were determined in E. coli BL21. Green fluorescent protein (GFP) was employed as a model foreign protein, and timing of antisense expression was controlled by using the intrinsic ackA promoter. We found that the antisense method partially reduced mRNA levels of target enzyme genes and, over time, lowered the concentration of acetate in culture media in all antisense-regulated strains. Notably, total production of GFP was enhanced 1.6- to 2.1-fold in antisense-regulated strains, even though the degree of acetate reduction was not significantly large. It was revealed that the acetate pathway has more critical roles in cellular physiology than expected in the previous reports. When the scale of culture was increased, enhancement of protein production became larger, demonstrating that this antisense strategy can be successfully applied to practical large-scale protein production processes.
Nucleosides. XVIII. Synthesis of 2'-Fluorothymidine, 2'-Fluorodeoxyuridine, and Other 2'-Halogeno-2'-Deoxy Nucleosides1,2 (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. XVIII. Synthesis of 2'-Fluorothymidine, 2'-Fluorodeoxyuridine, and Other 2'-Halogeno-2'-Deoxy Nucleosides1,2John F. Codington, Iris L. Doerr, and Jack J. FoxCite this: J. Org. Chem. 1964, 29, 3, 558–564Publication Date (Print):March 1, 1964Publication History Published online1 May 2002Published inissue 1 March 1964https://pubs.acs.org/doi/10.1021/jo01026a009https://doi.org/10.1021/jo01026a009research-articleACS PublicationsRequest reuse permissionsArticle Views889Altmetric-Citations129LEARN 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
Server Side Detection of Content Sniffing Attacks (2011)

Content sniffing attacks occur if browsers render non-HTML files embedded with malicious HTML contents or JavaScript code as HTML files. The rendering of these embedded contents might cause unwanted effects such as the stealing of sensitive information through the execution of malicious JavaScript code. The primary source of these attacks can be stopped if the uploading of malicious files can be prevented from the server side. However, existing server side content sniffing attack detection approaches suffer from a number of limitations. First, file contents are checked only to a fixed amount of initial bytes whereas attack payloads might reside anywhere in the file. Second, these approaches do not provide any mechanism to assess the malicious impact of the embedded contents on browsers. This paper addresses these issues by developing a server side content sniffing attack detection mechanism based on content analysis using HTML and JavaScript parsers and simulation of browser behavior via mock download testing. We have implemented our approach in a tool that can be integrated in web applications written in various languages. In addition, we have developed a benchmark suite for the evaluation purpose that contains both benign and malicious files. We have evaluated our approach on three real world PHP programs suffering from content sniffing vulnerabilities. The evaluation results indicate that our approach can secure programs against content sniffing attacks by successfully preventing the uploading of malicious files.
New external neurocontroller for series capacitive reactance compensator in a power network (2004)

Summary form only given. The controllable capacitive reactance can be used as the input variable for the external controller of a series capacitive reactance compensator (SCRC) to improve the damping of low-frequency oscillations of the rotor angle and active power in a power system. Conventional linear PI controllers are tuned for best performance at one specific operating point of the nonlinear power system. At other operating point its performance degrades. Nonlinear optimal neurocontrollers are able to overcome this degradation. In this work, the dual heuristic dynamic programming (DHP) optimization algorithm is applied to design an external nonlinear optimal neurocontroller for the SCRC. Simulation studies using PSCAD/EMTDCO software are presented.
Identification of a Mutated Fibronectin As a Tumor Antigen Recognized by CD4+T Cells (2002)

CD4+ T cells play an important role in orchestrating host immune responses against cancer, particularly by providing critical help for priming and extending the survival of CD8+ T cells. However, relatively little is known about major histocompatibility complex class II-restricted human tumor antigens capable of activating CD4+ T cells. Here, we describe the identification of a mutated fibronectin (FN) as a tumor antigen recognized by human histocompatibility leukocyte antigen-DR2-restricted CD4+ T cells. Deoxyribonucleic acid (DNA) sequencing analysis indicated that this gene contains a mutation that results in the substitution of lysine for glutamic acid and gives rise to a new T cell epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted in the loss of FN matrix formation and the gain of metastatic potential based on the migration pattern compared with that of tumor cells that express wild-type FN. Additional experiments using cell lines stably expressing the mutated FN cDNA demonstrated that the point mutation in FN was responsible for the loss of FN staining in extracellular matrices and the enhancement of tumor cell migration. These findings represent the first demonstration that a mutated gene product recognized by CD4+ T cells is directly involved in tumor metastasis, which indicates the importance of CD4+ T cells in controlling the spread of tumor cells to distant anatomic sites.
Epidemiology of anaphylaxis (2008)

The exact incidence of anaphylaxis is unknown, but appears to be increasing. Foods and drugs are the most common causes. The incidence is affected by geographical location, sex, atopy, and socioeconomic factors.
Purification and Characterization of glpX -Encoded Fructose 1,6-Bisphosphatase, a New Enzyme of the Glycerol 3-Phosphate Regulon of Escherichia coli (2000)

In Escherichia coli, gene products of the glp regulon mediate utilization of glycerol and sn-glycerol 3-phosphate. The glpFKX operon encodes glycerol diffusion facilitator, glycerol kinase, and as shown here, a fructose 1,6-bisphosphatase that is distinct from the previously described fbp-encoded enzyme. The purified enzyme was dimeric, dependent on Mn(2+) for activity, and exhibited an apparent K(m) of 35 microM for fructose 1,6-bisphosphate. The enzyme was inhibited by ADP and phosphate and activated by phosphoenolpyruvate.
The effects of exogenous testosterone on sexuality and mood of normal men. (1992)

The effects of supraphysiological levels of testosterone, used for male contraception, on sexual behavior and mood were studied in a single-blind, placebo-controlled manner in a group of 31 normal men. After 4 weeks of baseline observations, the men were randomized into two groups: one group received 200 mg testosterone enanthate (TE) weekly by im injection for 8 weeks (Testosterone Only group), the other received placebo injections once weekly for the first 4 weeks followed by TE 200 mg weekly for the following 4 weeks (Placebo/Testosterone group). The testosterone administration increased trough plasma testosterone levels by 80%, compatible with peak testosterone levels 400-500% above baseline. Various aspects of sexuality were assessed using sexuality experience scales (SES) questionnaires at the end of each 4-week period while sexual activity and mood states were recorded by daily dairies and self-rating scales. In both groups there was a significant increase in scores in the Psychosexual Stimulation Scale of the SES (i.e. SES 2) following testosterone administration, but not with placebo. There were no changes in SES 3, which measures aspects of sexual interaction with the partner. In both groups there were no changes in frequency of sexual intercourse, masturbation, or penile erection on waking nor in any of the moods reported. The Placebo/Testosterone group showed an increase in self-reported interest in sex during testosterone treatment but not with placebo. The SES 2 results suggest that sexual awareness and arousability can be increased by supraphysiological levels of testosterone. However, these changes are not reflected in modifications of overt sexual behavior, which in eugonadal men may be more determined by sexual relationship factors. This contrasts with hypogonadal men, in whom testosterone replacement clearly stimulates sexual behavior. There was no evidence to suggest an alteration in any of the mood states studied, in particular those associated with increased aggression. We conclude that supraphysiological levels of testosterone maintained for up to 2 months can promote some aspects of sexual arousability without stimulating sexual activity in eugonadal men within stable heterosexual relationships. Raising testosterone does not increase self-reported ratings of aggressive feelings.
Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint (2011)

Our findings indicate that CXCL13 is a novel serologic marker predictive of RA severity.This marker was identified with the help of an in silicomodel of the RA joint.
Automatic Road Detection and Centerline Extraction via Cascaded End-to-End Convolutional Neural Network (2017)

Accurate road detection and centerline extraction from very high resolution (VHR) remote sensing imagery are of central importance in a wide range of applications. Due to the complex backgrounds and occlusions of trees and cars, most road detection methods bring in the heterogeneous segments; besides for the centerline extraction task, most current approaches fail to extract a wonderful centerline network that appears smooth, complete, as well as single-pixel width. To address the above-mentioned complex issues, we propose a novel deep model, i.e., a cascaded end-to-end convolutional neural network (CasNet), to simultaneously cope with the road detection and centerline extraction tasks. Specifically, CasNet consists of two networks. One aims at the road detection task, whose strong representation ability is well able to tackle the complex backgrounds and occlusions of trees and cars. The other is cascaded to the former one, making full use of the feature maps produced formerly, to obtain the good centerline extraction. Finally, a thinning algorithm is proposed to obtain smooth, complete, and single-pixel width road centerline network. Extensive experiments demonstrate that CasNet outperforms the state-of-the-art methods greatly in learning quality and learning speed. That is, CasNet exceeds the comparing methods by a large margin in quantitative performance, and it is nearly 25 times faster than the comparing methods. Moreover, as another contribution, a large and challenging road centerline data set for the VHR remote sensing image will be publicly available for further studies.