gebhart/patrepeval huggingface dataset:
A sequence‐specific function for the N‐terminal signal‐like sequence of the TonB protein (1993)

TonB is a proline-rich protein which provides a functional link between the inner and outer membranes of Gram-negative bacteria. TonB is anchored to the inner membrane via an N-terminal signal-like sequence and spans the periplasm, interacting with transport receptors in the outer membrane. We have investigated the role of the N-terminal signal-like peptide in TonB function. Replacement of the N-terminal sequence with heterologous sequences indicates that it has at least three distinct roles in TonB function: (i) to facilitate translocation of TonB across the cytoplasmic membrane; (ii) to anchor TonB to the cytoplasmic membrane; (iii) a sequence-specific functional interaction with the ExbBD proteins.
[Expression and clinical significance of GRHL2 in colorectal cancer]. (2015)

Taking together, our findings demonstrate that GRHL2 is overexpressed in CRC, and plays an important role in the progression of CRC.
T CELL ANTIGEN RECEPTOR SIGNAL TRANSDUCTION PATHWAYS (1996)

The T cell antigen receptor (TCR) regulates the activation and growth of T lymphocytes. The initial membrane proximal event triggered by the TCR is activation of protein tyrosine kinases with the resultant phosphorylation of cellular proteins. This biochemical response couples the TCR to a divergent array of signal transduction molecules including enzymes that regulate lipid metabolism, GTP binding proteins, serine/threonine kinases, and adapter molecules. The ultimate aim of studies of intracellular signaling mechanisms is to understand the functional consequences of a particular biochemical event for receptor function. The control of cytokine gene expression is one of the mechanism that allows the TCR to control immune responses. Accordingly, one object of the present review is to discuss the role of the different TCR signal transduction pathways in linking the TCR to nuclear targets: the transcription factors that control the expression of cytokine genes.
Rapid evaluation of the durability of cortical neural implants using accelerated aging with reactive oxygen species (2015)

ROS, which are known to be present in vivo, can create structural damage and change electrical properties of MEAs. Broad-spectrum electrical impedance spectroscopy demonstrates increased sensitivity to electrode damage compared with single-frequency measurements. RAA can be a useful tool to simulate worst-case in vivo damage resulting from chronic electrode implantation, simplifying the device development lifecycle.
Effect of Theophylline on Sleep-Disordered Breathing in Heart Failure (1996)

In patients with stable heart failure, oral theophylline therapy reduced the number of episodes of apnea and hypopnea and the duration of arterial oxyhemoglobin desaturation during sleep.
Studies on the mechanism of polyclonal B cell stimulation by TH2 cells (1989)

Recently, it has been shown that cloned L1/1 T helper cells of type 2 (TH2-cells), when stimulated with antigen, are able to induce polyclonal B cell proliferation. Here we present evidence that this process is dependent on direct cell-cell interaction between T and B cells, which in the effector phase, i.e., during stimulation of the B cells by activated T cells, can be mediated by a mechanism other than cognate interaction. This conclusion is derived from experiments in which highly purified, small B cells of high density were polyclonally stimulated by L1/1 T cells triggered by an anti-T3 monoclonal antibody in the absence of antigen. The triggering process was independent of the presence of the Fc part of the antibody and occurred in cultures devoid of macrophages. Thus, the well-established cognate recognition does not appear to be the only mechanism of B cell induction by T helper cells.
Genetics of Parkinson's disease and essential tremor (2011)

GWA studies and positional cloning approaches have led to the identification of a number of risk genes for Parkinson's disease, which give novel insights into pathogenic pathways of the disease. In contrast, our knowledge of the genetics of essential tremor is scarce. Except for LINGO1, no other risk gene has so far been identified. New technologies such as next generation high throughput sequencing might help to identify more risk genes.
Relationship of Axonal Voltage-gated Sodium Channel 1.8 (NaV1.8) mRNA Accumulation to Sciatic Nerve Injury-induced Painful Neuropathy in Rats (2011)

Painful peripheral neuropathy is a significant clinical problem; however, its pathological mechanism and effective treatments remain elusive. Increased peripheral expression of tetrodotoxin-resistant voltage-gated sodium channel 1.8 (NaV1.8) has been shown to associate with chronic pain symptoms in humans and experimental animals. Sciatic nerve entrapment (SNE) injury was used to develop neuropathic pain symptoms in rats, resulting in increased NaV1.8 mRNA in the injured nerve but not in dorsal root ganglia (DRG). To study the role of NaV1.8 mRNA in the pathogenesis of SNE-induced painful neuropathy, NaV1.8 shRNA vector was delivered by subcutaneous injection of cationized gelatin/plasmid DNA polyplex into the rat hindpaw and its subsequent retrograde transport via sciatic nerve to DRG. This in vivo NaV1.8 shRNA treatment reversibly and repeatedly attenuated the SNE-induced pain symptoms, an effect that became apparent following a distinct lag period of 3-4 days and lasted for 4-6 days before returning to pretreatment levels. Surprisingly, apparent knockdown of NaV1.8 mRNA occurred only in the injured nerve, not in the DRG, during the pain alleviation period. Levels of heteronuclear NaV1.8 RNA were unaffected by SNE or shRNA treatments, suggesting that transcription of the Scn10a gene encoding NaV1.8 was unchanged. Based on these data, we postulate that increased axonal mRNA transport results in accumulation of functional NaV1.8 protein in the injured nerve and the development of painful neuropathy symptoms. Thus, targeted delivery of agents that interfere with axonal NaV1.8 mRNA may represent effective neuropathic pain treatments.
Synthesis and Polymerization of Atom-bridged Bicyclic Lactams (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and Polymerization of Atom-bridged Bicyclic LactamsH. K. Hall Jr.Cite this: J. Am. Chem. Soc. 1960, 82, 5, 1209–1215Publication Date (Print):March 1, 1960Publication History Published online1 May 2002Published inissue 1 March 1960https://pubs.acs.org/doi/10.1021/ja01490a044https://doi.org/10.1021/ja01490a044research-articleACS PublicationsRequest reuse permissionsArticle Views416Altmetric-Citations55LEARN 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
L-685,458, an Aspartyl Protease Transition State Mimic, Is a Potent Inhibitor of Amyloid β-Protein Precursor γ-Secretase Activity (2000)

Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels of A beta(42) peptide formation have been linked to early-onset familial AD-causing gene mutations in the amyloid beta-protein precursor (A beta PP) and the presenilins. Sequential cleavage of A beta PP by the beta- and gamma-secretases generates the N- and C-termini of the A beta peptide, making both the beta- and gamma-secretase enzymes potential therapeutic targets for AD. The identity of the A beta PP gamma-secretase and the mechanism by which the C-termini of A beta are formed remain uncertain, although it has been suggested that the presenilins themselves are novel intramembrane-cleaving gamma-secretases of the aspartyl protease class [Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999) Nature 398, 513-517]. In this study we report the identification of L-685,458 as a structurally novel inhibitor of A beta PP gamma-secretase activity, with a similar potency for inhibition of A beta(42) and A beta(40) peptides. This compound contains an hydroxyethylene dipeptide isostere which suggests that it could function as a transition state analogue mimic of an aspartyl protease. The preferred stereochemistry of the hydroxyethylene dipeptide isostere was found to be the opposite to that required for inhibition of the HIV-1 aspartyl protease, a factor which may contribute to the observed specificity of this compound. Specific and potent inhibitors of A beta PP gamma-secretase activity such as L-685,458 will enable important advances toward the identification and elucidation of the mechanism of action of this enigmatic protease.
Serum tumor markers. (2003)

Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.
Characterization of Recombinant Human Aromatic l‐Amino Acid Decarboxylase Expressed in COS Cells (1990)

The expression vector containing the full-length cDNA of human aromatic L-amino acid decarboxylase (EC 4.1.1.28) was transfected in COS cells by a modified calcium phosphate coprecipitation method. The cells transfected with plasmids that had a true direction of the cDNA gave a major immunoreactive band at 50 kDa. This expressed enzyme catalyzed the decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA), L-5-hydroxytryptophan (L-5-HTP) and L-threo-3,4-dihydroxyphenylserine. The optimal pH of the enzyme activity with L-DOPA as a substrate was 6.5, whereas the enzyme had a broad pH optimum when L-5-HTP was used as a substrate. Addition of pyridoxal phosphate to the incubation mixture greatly enhanced the activity for both L-DOPA and L-5-HTP.
Antisense Oligodeoxynucleotide Inhibition of Tumor Necrosis Factor-α Expression Is Neuroprotective After Intracerebral Hemorrhage (2001)

These results indicate a pathogenic role for TNF-alpha during ICH and demonstrate that reducing TNF-alpha expression using antisense oligodeoxynucleotides is neuroprotective.
CascadePSP: Toward Class-Agnostic and Very High-Resolution Segmentation via Global and Local Refinement (2020)

State-of-the-art semantic segmentation methods were almost exclusively trained on images within a fixed resolution range. These segmentations are inaccurate for very high-resolution images since using bicubic upsampling of low-resolution segmentation does not adequately capture high-resolution details along object boundaries. In this paper, we propose a novel approach to address the high-resolution segmentation problem without using any high-resolution training data. The key insight is our CascadePSP network which refines and corrects local boundaries whenever possible. Although our network is trained with low-resolution segmentation data, our method is applicable to any resolution even for very high-resolution images larger than 4K. We present quantitative and qualitative studies on different datasets to show that CascadePSP can reveal pixel-accurate segmentation boundaries using our novel refinement module without any finetuning. Thus, our method can be regarded as class-agnostic. Finally, we demonstrate the application of our model to scene parsing in multi-class segmentation.
Acute respiratory distress syndrome and acute lung injury (2011)

Acute respiratory distress syndrome (ARDS) is a life threatening respiratory failure due to lung injury from a variety of precipitants. Pathologically ARDS is characterised by diffuse alveolar damage, alveolar capillary leakage, and protein rich pulmonary oedema leading to the clinical manifestation of poor lung compliance, severe hypoxaemia, and bilateral infiltrates on chest radiograph. Several aetiological factors associated with the development of ARDS are identified with sepsis, pneumonia, and trauma with multiple transfusions accounting for most cases. Despite the absence of a robust diagnostic definition, extensive epidemiological investigations suggest ARDS remains a significant health burden with substantial morbidity and mortality. Improvements in outcome following ARDS over the past decade are in part due to improved strategies of mechanical ventilation and advanced support of other failing organs. Optimal treatment involves judicious fluid management, protective lung ventilation with low tidal volumes and moderate positive end expiratory pressure, multi-organ support, and treatment where possible of the underlying cause. Moreover, advances in general supportive measures such as appropriate antimicrobial therapy, early enteral nutrition, prophylaxis against venous thromboembolism and gastrointestinal ulceration are likely contributory reasons for the improved outcomes. Although therapies such as corticosteroids, nitric oxide, prostacyclins, exogenous surfactants, ketoconazole and antioxidants have shown promising clinical effects in animal models, these have failed to translate positively in human studies. Most recently, clinical trials with β2 agonists aiding alveolar fluid clearance and immunonutrition with omega-3 fatty acids have also provided disappointing results. Despite these negative studies, mortality seems to be in decline due to advances in overall patient care. Future directions of research are likely to concentrate on identifying potential biomarkers or genetic markers to facilitate diagnosis, with phenotyping of patients to predict outcome and treatment response. Pharmacotherapies remain experimental and recent advances in the modulation of inflammation and novel cellular based therapies, such as mesenchymal stem cells, may reduce lung injury and facilitate repair.
Risk prediction models for dementia constructed by supervised principal component analysis using miRNA expression data (2019)

Alzheimer's disease (AD) is the most common subtype of dementia, followed by Vascular Dementia (VaD), and Dementia with Lewy Bodies (DLB). Recently, microRNAs (miRNAs) have received a lot of attention as the novel biomarkers for dementia. Here, using serum miRNA expression of 1,601 Japanese individuals, we investigated potential miRNA biomarkers and constructed risk prediction models, based on a supervised principal component analysis (PCA) logistic regression method, according to the subtype of dementia. The final risk prediction model achieved a high accuracy of 0.873 on a validation cohort in AD, when using 78 miRNAs: Accuracy = 0.836 with 86 miRNAs in VaD; Accuracy = 0.825 with 110 miRNAs in DLB. To our knowledge, this is the first report applying miRNA-based risk prediction models to a dementia prospective cohort. Our study demonstrates our models to be effective in prospective disease risk prediction, and with further improvement may contribute to practical clinical use in dementia.
Progressive Failure Analysis of Laminated Composite Structures Based on Puck's Failure Criteria (2012)

We first review Puck and Schurmann’s progressive failure criteria for three-dimensional deformations of unidirectional fiber-reinforced composites, and then simplify these for plane stress deformations. These criteria have been implemented as an USDFLD subroutine in the commercial software, ABAQUS/Standard. Several example problems have been analyzed with the developed software, and for some problems computed results have been compared with those obtained by using the CLPT for stress analysis and Puck and Schurmann’s criteria for failure analysis. A close agreement between the two set of results verifies the implementation of the failure criteria in the software, ABAQUS. These examples illustrate that the ultimate failure load is significantly higher than that when the failure initiates first which is usually called the first ply failure load.
Gelling of urea‐linked gelatin with fresh frozen plasma (1989)

Urea-linked gelatin and succinylated gelatin were mixed with fresh frozen plasma and human albumin solutions in vitro, in varying concentrations and at different temperatures. Gelling was only seen in those mixtures that contained fresh frozen plasma and urea-linked gelatin. It occurred at both room temperature and 37 degrees C when the mixture contained more than 40% by volume of urea-linked gelatin. Further tests confirmed that this was the result of calcium ions in the urea-linked gelatin allowing coagulation to occur in the fresh frozen plasma.
Dynamic viscosity of azeotropic and quasi-azeotropic mixtures of organic compounds (2002)

Azeotropic and quasi-azeotropic mixtures of organic compounds are becoming the most effective candidates as replacement fluids. Heat and mass transfer phenomena in organic compound mixtures have been theoretically studiedfrom several different points of view. Despite these efforts, theoretical models are frequently inaccurate while empirical methods are usually more accurate but they are often specialised and tuned to cover a small number of compounds and/or a limited temperature range. Based on the development of effective prediction formulas for several families of pure organic compounds, the problem of the evaluation of mixture dynamic viscosity is approached from a rather different point of view. Azeotropic mixtures are treated as pure compounds rather than a combination of several pure substances, and a single, specialised formula for the evaluation of saturated liquid dynamic viscosity is developed. The prediction method requires the knowledge of few equilibrium properties of the mixture to be analysed thus becoming a simple and powerful tool for exhaustive analysis of alternatives. It has been tested against experimental data leading to deviations far below those required for engineering purposes.
p53 gene mutations in non-small cell lung cancer detected by polymerase chain reaction single-strand conformation polymorphism analysis. (1999)

Mutations of the p53 tumor suppressor gene are the most frequent genetic alterations detected in human lung cancer. To assess the pathogenic significance of p53 gene alterations in Chinese non-small cell lung cancer (NSCLC), 74 paired samples of primary lung cancer and normal lung tissue far away from the cancer were analyzed for mutations of the p53 gene (exons 5-8) using exon-specific PCR, single-strand conformation polymorphism (PCR-SSCP). p53 mutations were observed in 55.4% (41/74) of the samples. No linkages were detected between the incidence of p53 mutations and histological type, lymph node metastasis, age or sex. Significant association between p53 mutations and degree of differentiation in adenocarcinomas, not in squamous cell carcinomas, was observed. The frequency of p53 mutations in smokers (65.3%) was higher than in nonsmokers (33.3%) and reached statistical significance. We also found p53 mutations in 6/7 samples which had tissue invasion and distant metastasis. These results suggest that smoking could be an important factor in lung carcinogenesis, p53 mutation is a worse prognosis indicator in adenocarcinomas and related to high aggressive behavior of human lung cancer.
Three-Dimensional Structure of the LDL Receptor-Binding Domain of Human Apolipoprotein E (1991)

Human apolipoprotein E, a blood plasma protein, mediates the transport and uptake of cholesterol and lipid by way of its high affinity interaction with different cellular receptors, including the low-density lipoprotein (LDL) receptor. The three-dimensional structure of the LDL receptor-binding domain of apoE has been determined at 2.5 angstrom resolution by x-ray crystallography. The protein forms an unusually elongated (65 angstroms) four-helix bundle, with the helices apparently stabilized by a tightly packed hydrophobic core that includes leucine zipper-type interactions and by numerous salt bridges on the mostly charged surface. Basic amino acids important for LDL receptor binding are clustered into a surface patch on one long helix. This structure provides the basis for understanding the behavior of naturally occurring mutants that can lead to atherosclerosis.
Breast cancer statistics, 2013 (2013)

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 232,340 new cases of invasive breast cancer and 39,620 breast cancer deaths are expected to occur among US women in 2013. One in 8 women in the United States will develop breast cancer in her lifetime. Breast cancer incidence rates increased slightly among African American women; decreased among Hispanic women; and were stable among whites, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives from 2006 to 2010. Historically, white women have had the highest breast cancer incidence rates among women aged 40 years and older; however, incidence rates are converging among white and African American women, particularly among women aged 50 years to 59 years. Incidence rates increased for estrogen receptor-positive breast cancers in the youngest white women, Hispanic women aged 60 years to 69 years, and all but the oldest African American women. In contrast, estrogen receptor-negative breast cancers declined among most age and racial/ethnic groups. These divergent trends may reflect etiologic heterogeneity and the differing effects of some factors, such as obesity and parity, on risk by tumor subtype. Since 1990, breast cancer death rates have dropped by 34% and this decrease was evident in all racial/ethnic groups except American Indians/Alaska Natives. Nevertheless, survival disparities persist by race/ethnicity, with African American women having the poorest breast cancer survival of any racial/ethnic group. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.