gebhart/patrepeval huggingface dataset:
Apoptosis: Programmed cell death in health and disease (1994)

Apoptosis is a normal physiological cell death process of eliminating unwanted cells from living organisms during embryonic and adult development. Apoptotic cells are characterised by fragmentation of nuclear DNA and formation of apoptotic bodies. Genetic analysis revealed the involvement of many death and survival genes in apoptosis which are regulated by extracellular factors. There are multiple inducers and inhibitors of apoptosis which interact with target cell specific surface receptors and transduce the signal by second messengers to programme cell death. The regulation of apoptosis is elusive, but defective regulation leads to aetiology of various ailments. Understanding the molecular mechanism of apoptosis including death genes, death signals, surface receptors and signal pathways will provide new insights in developing strategies to regulate the cell survival/death. The current knowledge on the molecular events of apoptotic cell death and their significance in health and disease is reviewed.
Preclinical validation of anti-TMEFF2-auristatin E–conjugated antibodies in the treatment of prostate cancer (2004)

Current treatments for advanced stage, hormone-resistant prostate cancer are largely ineffective, leading to high patient mortality and morbidity. To fulfill this unmet medical need, we used global gene expression profiling to identify new potential antibody-drug conjugate (ADC) targets that showed maximal prostate cancer-specific expression. TMEFF2, a gene encoding a plasma membrane protein with two follistatin-like domains and one epidermal growth factor-like domain, had limited normal tissue distribution and was highly overexpressed in prostate cancer. Immunohistochemistry analysis using a specific monoclonal antibody (mAb) to human TMEFF2 showed significant protein expression in 74% of primary prostate cancers and 42% of metastatic lesions from lymph nodes and bone that represented both hormone-naïve and hormone-resistant disease. To evaluate anti-TMEFF2 mAbs as potential ADCs, one mAb was conjugated to the cytotoxic agent auristatin E via a cathepsin B-sensitive valine-citrulline linker. This ADC, Pr1-vcMMAE, was used to treat male severe combined immunodeficient mice bearing xenografted LNCaP and CWR22 prostate cancers expressing TMEFF2. Doses of 3 to 10 mg/kg of this specific ADC resulted in significant and sustained tumor growth inhibition, whereas an isotype control ADC had no significant effect. Similar efficacy and specificity was shown with huPr1-vcMMAE, a humanized anti-TMEFF2 ADC. No overt in vivo toxicity was observed with either murine or human ADC, despite significant cross-reactivity of anti-TMEFF2 mAb with the murine TMEFF2 protein, implying minimal toxicity to other body tissues. These data support the further evaluation and clinical testing of huPr1-vcMMAE as a novel therapeutic for the treatment of metastatic and hormone-resistant prostate cancer.
Alternative binding proteins: Anticalins – harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities (2008)

Antibodies are the paradigm for binding proteins, with their hypervariable loop region supported by a structurally rigid framework, thus providing the vast repertoire of antigen-binding sites in the immune system. Lipocalins are another family of proteins that exhibit a binding site with high structural plasticity, which is composed of four peptide loops mounted on a stable beta-barrel scaffold. Using site-directed random mutagenesis and selection via phage display against prescribed molecular targets, it is possible to generate artificial lipocalins with novel ligand specificities, so-called anticalins. Anticalins have been successfully selected both against small hapten-like compounds and against large protein antigens and they usually possess high target affinity and specificity. Their structural analysis has yielded interesting insights into the phenomenon of molecular recognition. Compared with antibodies, they are much smaller, have a simpler molecular architecture (comprising just one polypeptide chain) and they do not require post-translational modification. In addition, anticalins exhibit robust biophysical properties and can easily be produced in microbial expression systems. As their structure-function relationships are well understood, rational engineering of additional features such as site-directed pegylation or fusion with functional effector domains, dimerization modules or even with another anticalin, can be readily achieved. Thus, anticalins offer many applications, not only as reagents for biochemical research but also as a new class of potential drugs for medical therapy.
Kinetics of glucose transport in rat muscle: effects of insulin and contractions (1987)

The effects of insulin and prior muscle contractions, respectively, on 3-O-methylglucose (3-O-MG) transport in skeletal muscle were studied in the perfused rat hindquarter. Initial rates of entry of 3-O-MG in red gastrocnemius, soleus, and white gastrocnemius muscles as a function of perfusate 3-O-MG concentration exhibited Michaelis-Menten kinetics. Uptake by simple diffusion could not be detected. The maximum 3-O-MG transport velocity (Vmax) was increased more by maximum isometric contractions (10- to 40-fold, depending on fiber type) than by insulin (20,000 microU/ml; 3- to 20-fold) in both red and white muscles. The effects of both contractions and insulin were greater in red than in white muscles. In red but not in white muscles, maximum increases in Vmax elicited by contractions and by insulin were additive. Both insulin and contractions decreased the half-saturating substrate concentration for glucose transport (apparent Km) in all three muscles, in fast-twitch fibers from 70 to approximately 7 mM and in slow-twitch fibers from 12 to 7 mM. After contractions, reversal of contraction-induced glucose transport was monoexponential in red fibers, with a half-time of 7 and 15 min in slow- and fast-twitch fibers, respectively. In white muscle, Vmax continued to increase after contractions, reached a plateau after 10 min, and had only decreased 45% after 70 min. In contrast to the prevailing opinion, in all fiber types, reversal of contraction-induced glucose transport took place in the absence of muscle glycogen repletion.
Glomerular basement membrane-derived perlecan inhibits mesangial cell adhesion to fibronectin. (1996)

To explore whether the heparan sulfate proteoglycan, periecan, may act as a regulator of glomerular cell behavior, we examined the effects of perlecan on adhesive properties of rat and human mesangial cells in culture. We observed that mesangial cells did not adhere to purified perlecan. Mesangial cell adhesion to fibronectin, but not to laminin, was inhibited when perlecan was present in the substratum, reaching complete inhibition at 20 micrograms/ml perlecan. Similarly, perlecan reduced mesangial cell adhesion to the 120 kDa fragment of fibronectin and to bovine serum albumin-coupled RGD peptides both lacking the fibronectin heparin-binding domains, indicating that the inhibitory effect of perlecan does not require interaction of its heparan sulfate chains with fibronectin. The core protein of perlecan seems to be relevant, since perlecan retained most of its anti-adhesive potency after total deglycosylation. It is unlikely that perlecan causes steric inhibition of the cell binding sites of fibronectin by direct binding, since the 120 kDa fragment of fibronectin which includes the cell binding site, did not bind to intact perlecan. In the presence of submaximal inhibitory concentrations of perlecan, soluble RGD peptides (100 micrograms/ml), by themselves without effect, completely inhibited cell adhesion to fibronectin. Using immunocytochemistry, we examined the effects of perlecan on the organization of fibronectin-specific, RGD-dependent beta 1 integrins in focal contacts. When perlecan was added to the substratum, human mesangial cells adhered to fibronectin only in the presence of collagen I. Under these conditions, perlecan did not significantly alter the organization of alpha 5 beta 1 integrin into focal contacts of mesangial cells which adhered to a substratum composed of collagen I plus fibronectin. These data suggest that perlecan exerts its anti-adhesive effects on mesangial cells via a core protein-dependent mechanism which reduces the avidity of the fibronectin receptor. The resulting avidity level is too low for mediating cell binding but sufficient to induce integrin organization into focal contacts.
Synthesis of 4‘-Methyl and 4‘-Cyano Carbocyclic 2‘,3‘-Didehydro Nucleoside Analogues via 1,4-Addition to Substituted Cyclopentenones (2004)

Carbocyclic 4'-methyl and 4'-cyano nucleoside analogues were synthesized using the Michael reaction to introduce the 4'-substituent and Pd-catalyzed allylic substitution to introduce the nucleoside base. Use of both the desired beta- and undesired alpha-1'-carbonate diastereomers in the Pd-catalyzed substitution was demonstrated in principle by epimerization of the alpha-diastereomer and kinetic diastereodifferentiation of a 1:1 alpha/beta mixture of 1'-carbonates.
Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. (1994)

The B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites.
Complete nucleotide sequence of a 16S ribosomal RNA gene from Escherichia coli. (1978)

The complete nucleotide sequence of the 16S RNA gene from the rrnB cistron of Escherichia coli has been determined by using three rapid DNA sequencing methods. Nearly all of the structure has been confirmed by two to six independent sequence determinations on both DNA strands. The length of the 16S rRNA chain inferred from the DNA sequence is 1541 nucleotides, in close agreement with previous estimates. We note discrepancies between this sequence and the most recent version of it reported from direct RNA sequencing [Ehresmann, C., Stiegler, P., Carbon, P. & Ebel, J.P. (1977) FEBS Lett. 84, 337-341]. A few of these may be explained by heterogeneity among 16S rRNA sequences from different cistrons. No nucleotide sequences were found in the 16S rRNA gene that cannot be reconciled with RNase digestion products of mature 16S rRNA.
Immunosenescence and Cancer (2013)

The immune system, interacting intimately with the cancer cells in a tumor, may combat or favor cancer development and progression, or both. One of the most important risk factors for solid cancers is age. With increasing age, numerous alterations at multiple levels including molecular, cellular, organ, and systemic are occurring. With age many physiological systems are changing, including the immune system. Several alterations occur in both arms of the immune system with aging. Although the innate immune system shows changes with aging, the most important alterations occur in the adaptive immune system, especially involving T cells. Many changes in the immune system may decrease its capacity to combat the emerging or progressing tumor. Further, the age-related immune changes may favor the cancer development. The most important changes which may decrease the immune response efficiency are the changes in T cell functions and phenotypes, concomitant with the presence of a low-grade inflammation. A consensus is now emerging in oncology that not only the cancer cells themselves should be studied but also their macro- and microenvironments. In this context, the study of the interrelation of the immune response and the tumor at various stages is essential to enhance our capacity for intervention in elderly cancer patients.
Localization in wireless sensor networks: Classification and evaluation of techniques (2012)

Localization in wireless sensor networks: Classification and evaluation of techniques Recent advances in technology have enabled the development of low cost, low power and multi functional wireless sensing devices. These devices are networked through setting up a Wireless Sensor Network (WSN). Sensors that form a WSN are expected to be remotely deployed in large numbers and to self-organize to perform distributed sensing and acting tasks. WSNs are growing rapidly in both size and complexity, and it is becoming increasingly difficult to develop and investigate such large and complex systems. In this paper we provide a brief introduction to WSN applications, i.e., properties, limitations and basic issues related to WSN design and development. We focus on an important aspect of the design: accurate localization of devices that form the network. The paper presents an overview of localization strategies and attempts to classify different techniques. A set of properties by which localization systems are evaluated are examined. We then describe a number of existing localization systems, and discuss the results of performance evaluation of some of them through simulation and experiments using a testbed implementation.
Dynamic mixture models for multiple time series (2007)

Traditional probabilistic mixture models such as Latent Dirichlet Allocation imply that data records (such as documents) are fully exchangeable. However, data are naturally collected along time, thus obey some order in time. In this paper, we present Dynamic Mixture Models (DMMs) for online pattern discovery in multiple time series. DMMs do not have the noticeable drawback of the SVD-based methods for data streams: negative values in hidden variables are often produced even with all nonnegative inputs. We apply DMM models to two real-world datasets, and achieve significantly better results with intuitive interpretation. 1
Does fish oil lower blood pressure? A meta-analysis of controlled trials. (1993)

There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease or hypercholesterolemia.
Low-Density, Mutually Interpenetrating Organic-Inorganic Composite Materials via Supercritical Drying Techniques (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLow-Density, Mutually Interpenetrating Organic-Inorganic Composite Materials via Supercritical Drying TechniquesBruce M. Novak, David Auerbach, and Celine VerrierCite this: Chem. Mater. 1994, 6, 3, 282–286Publication Date (Print):March 1, 1994Publication History Published online1 May 2002Published inissue 1 March 1994https://pubs.acs.org/doi/10.1021/cm00039a006https://doi.org/10.1021/cm00039a006research-articleACS PublicationsRequest reuse permissionsArticle Views800Altmetric-Citations115LEARN 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
Tetrazolium Violet Induced Apoptosis and Cell Cycle Arrest in Human Lung Cancer A549 Cells (2012)

Tetrazolium violet is a tetrazolium salt and has been proposed as an antitumor agent. In this study, we reported for the first time that tetrazolium violet not only inhibited human lung cancer A549 cell proliferation but also induced apoptosis and blocked cell cycle progression in the G1 phase. The results showed that tetrazolium violet significantly decreased the viability of A549 cells at 5-15 μM. Tetrazolium violet -induced apoptosis in A549 cells was confirmed by H33258 staining assay. In A549, tetrazolium violet blocked the progression of the cell cycle at G1 phase by inducing p53 expression and further up-regulating p21/WAF1 expression. In addition, an enhancement in Fas/APO-1 and its two forms of ligands, membrane-bound Fas ligand (mFasL) and soluble Fas ligand (sFasL), as well as caspase, were responsible for the apoptotic effect induced by tetrazolium violet. The conclusion of this study is that tetrazolium violet induced p53 expression which caused cell cycle arrest and apoptosis. These findings suggest that tetrazolium violet has strong potential for development as an agent for treatment lung cancer.
SB202190, a selective inhibitor of p38 mitogen-activated protein kinase, is a powerful regulator of LPS-induced mRNAs in monocytes (1998)

Inhibitors of p38 mitogen-activated protein kinase (p38) have been reported to block tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production in monocytes at the level of mRNA translation. Yet, several studies document that p38 can phosphorylate and activate specific transcription factors. Thus, to understand better the role of p38 during monocyte activation, we sought to determine the extent to which p38 is required for lipopolysaccharide (LPS)-induced gene expression. For this, differential mRNA display was used to identify LPS-induced genes whose expression was blocked by SB202190, a specific inhibitor of p38. A partial screen identified 10 genes in monoyctes induced 4- to 74-fold by LPS. Of these, genes encoding interferon-induced gene 15, neuroleukin, radiation-inducible immediate-early gene-1, A20, IL-1beta, and superoxide dismutase were suppressed >50% by SB202190. LPS-induced gene activation was not blocked by cycloheximide, indicating that synthesis of intermediate proteins was not required. SB202190 blocked gene induction by 50% when present between 41 and 123 nM, consistent with the potency of this compound as a p38 inhibitor. Furthermore, the ability of SB202190 to block gene activation was stimulus-dependent. LPS and interferon-alpha (IFN-alpha) both up-regulated neuroleukin mRNA, but only LPS-induced neuroleukin mRNA was suppressed by SB202190. In contrast, TNF-alpha and LPS both induced IL-8 mRNA, and induction by either TNF-alpha or LPS was blocked by SB202190. These data were consistent with the ability of LPS and TNF-alpha, but not IFN-alpha, to activate p38 in monocytes. The results provide pharmacological evidence that p38 may be a key mediator of inducible gene expression in monocytes, but its role is stimulus and gene specific.
Mapping adenines, guanines, and pyrimidines in RNA (1977)

The positions of adenines, guanines, and pyrimidines can be determined by partial nuclease digestion of a terminally labeles RNA molecule. In urea, at elevated temperatures, RNase T1 generates a pattern reflecting cleavage at guanines while RNase U2 cleaves only at adenine. A limited alkaline hydrolysis provides a continuum of fragments derived from breaks at every phosphodiester bond. The reaction products are electrophoretically fractionated by size in adjacent lanes of a polyacrylamide gel. An autoradiograph of the gel displays the sequence up to 100 nucleotides from the end of the molecule, although uracil cannot as yet be distinguished from cytosine. These techniques form the basis of an RNA sequencing method and are demonstrated on yeast 5.8S ribosomal RNA.
Measuring bloat, overfitting and functional complexity in genetic programming (2010)

Recent contributions clearly show that eliminating bloat in a genetic programming system does not necessarily eliminate overfitting and vice-versa. This fact seems to contradict a common agreement of many researchers known as the minimum description length principle, which states that the best model is the one that minimizes the amount of information needed to encode it. Another common agreement is that overfitting should be, in some sense, related to the functional complexity of the model. The goal of this paper is to define three measures to respectively quantify bloat, overfitting and functional complexity of solutions and show their suitability on a set of test problems including a simple bidimensional symbolic regression test function and two real-life multidimensional regression problems. The experimental results are encouraging and should pave the way to further investigation. Advantages and drawbacks of the proposed measures are discussed, and ways to improve them are suggested. In the future, these measures should be useful to study and better understand the relationship between bloat, overfitting and functional complexity of solutions.
A new pleurotomariid gastropod assemblage from the Jurassic sequence of Kutch, western India (2005)

Mesozoic gastropod assemblages currently emerged from Kutch, western India constitute one of the most diverse communities known during the Bathonian–Oxfordian worldwide. The present paper describes part of the Jurassic gastropod faunas of the family Pleurotomariidae from Kutch, comprising ten species belonging to three genera, of which eight species are new. They are: Bathrotomaria reticulata (Sowerby), B. waageni sp. nov., B. calloviana sp. nov., B. buddhai sp. nov., B. prasantai sp. nov., B. dhosaensis sp. nov., B. tewarii (Maithani); Leptomaria daityai sp. nov.; L. asurai sp. nov. and Obornella wuerttembergensis (Sieberer). The assemblage shows a strong Tethyan affinity at generic level, but has a distinctly endemic species content, and thus merits a distinct subprovince within the Indo-Madagascan Faunal Province. The genus Pleurotomaria is discussed in historical perspective and shown to be Mesozoic genus. The six species of Bathrotomaria described herein are considered to have evolved from the early immigrant species, B. reticulata of Europe.
Molecular Genetics of Parathyroid Disease (2009)

Molecular genetic studies of parathyroid tumors are well designed basic experimental studies providing strong level III evidence, with data frequently confirmed by subsequent studies.
The Structural and Synthetic Implications of the Biosynthesis of the Calycanthaceous Alkaloids, the Communesins, and Nomofungin. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.