gebhart/patrepeval huggingface dataset:
EGFR Targeted Therapy: View from Biological Standpoint (2006)

Activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancers (NSCLCs) correlate with responsiveness to EGFR kinase inhibitors. In vitro cell culture studies have demonstrated that EGFR kinase domain mutants but not wild type (wt) EGFR are transforming and essential for cancer cell survival. We and others have recently demonstrated that the induction of EGFR kinase domain mutants specifically in murine lung epithelium in vivo led to development of adenocarcinoma with bronchioloalveolar carcinoma (BAC) features. These tumors depend completely on the sustained expression of EGFR kinase domain mutants for tumor maintenance. The murine tumors with EGFR kinase domain mutations are sensitive to EGFR targeted therapy similarly to NSCLC patients whose tumors harbor EGFR mutations. In contrast, initial results suggest that overexpression of wt EGFR in murine lungs does not seem to be transforming. We therefore divide EGFR targeted therapy in NSCLC patients into two parts: "EGFR mutant targeted therapy" and "wt EGFR targeted therapy". The "EGFR mutant targeted therapy" targets the oncogene essential for tumor initiation and maintenance and is frequently correlated with effective clinical outcome. In contrast, "wt EGFR targeted therapy" likely targets the proto-oncogene product wt EGFR, which is not directly involved in tumor initiation and maintenance, and in these cases, the response has been considerably less dramatic.
Frequency domain data transmission using reduced computational complexity algorithms (2005)

In this paper we describe a frequency domain data transmission method to be used for digital data transmission over analog telephone lines which exploits recently derived reduced computational complexity algorithms, such as the Winograd Fourier Transform, to achieve a significantly lower computational rate than comparable time domain QAM modems implemented digitally using signal processing techniques. In addition to the lower computational rate, the proposed method also allows for better channel bandwidth utilization by allowing optimal signal power allocation based on the channel's signal to noise versus frequency characteristics. Experimental results on this method are presented, indicating that it may be possible to send over 10,000 BPS over an unconditioned telephone line while maintaining a 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> BER.
Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease. (1987)

Lethally irradiated mice were injected with semiallogeneic, T-depleted bone marrow cells and an amount of peripheral T lymphocytes sufficient to induce graft-vs.-host disease (GVHD) becoming apparent on the second week after the graft and leading to an increasing mortality rate within the following weeks (greater than 90% mortality within 80 d). Mice receiving bone marrow cells alone had no GVHD and were used as controls. Beginning on day 8, mice with GVHD were injected weekly with 2 mg of either rabbit anti-mouse recombinant tumor necrosis factor/cachectin (TNF-alpha) IgG, or normal rabbit IgG. On the 16-18th d, mice were killed to examine the skin and intestinal lesions of the acute phase of GVHD. The anti-TNF treatment resulted in an almost complete prevention of the severe lesions seen in the mice treated with normal rabbit IgG, i.e., the skin epidermal cell necrosis, foci of lichenoid hyperplastic reactions, and loss of the hypodermic fat; in the gut dilatation with marked flattening of the villi and elevation of the crypts, with increased numbers of mitoses and isolated crypt cell necrosis. In addition to preventing these acute lesions, anti-TNF treatment resulted in a significantly decreased mortality (approximately 70% survival at 80 d). These results suggest that during acute GVHD, the activation of grafted lymphocytes leads to a local release of TNF in the cutaneous and intestinal mucosae, which induces epithelial cell alterations and increases the inflammatory reaction.
A New Paradigm for DNA Polymerase Specificity (2006)

We show that T7 DNA polymerase exists in three distinct structural states, as reported by a conformationally sensitive fluorophore attached to the recognition (fingers) domain. The conformational change induced by a correct nucleotide commits the substrate to the forward reaction, and the slow reversal of the conformational change eliminates the rate of the chemistry step from any contribution toward enzyme specificity. Discrimination against mismatches is enhanced by the rapid release of mismatched nucleotides from the ternary E.DNA.deoxynucleoside triphosphate complex and by the use of substrate-binding energy to actively misalign catalytic residues to reduce the rate of misincorporation. Our refined model for enzyme selectivity extends traditional thermodynamic formalism by including substrate-induced structural alignment or misalignment of catalytic residues as a third dimension on the free-energy profile and by including the rate of substrate dissociation as a key kinetic parameter.
CondenseNet: An Efficient DenseNet using Learned Group Convolutions (2017)

Deep neural networks are increasingly used on mobile devices, where computational resources are limited. In this paper we develop CondenseNet, a novel network architecture with unprecedented efficiency. It combines dense connectivity with a novel module called learned group convolution. The dense connectivity facilitates feature re-use in the network, whereas learned group convolutions remove connections between layers for which this feature re-use is superfluous. At test time, our model can be implemented using standard group convolutions, allowing for efficient computation in practice. Our experiments show that CondenseNets are far more efficient than state-of-the-art compact convolutional networks such as MobileNets and ShuffleNets.
Expression and activation of 15‐lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition (2002)

The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.
L‐type amino acid transporter 1 expression is a prognostic marker in patients with surgically resected stage I non‐small cell lung cancer (2009)

LAT1 expression is a promising pathological factor for predicting the prognosis in patients with resectable stage I NSCLC.
Structure–Activity Studies of Bis‐O‐Arylglycolamides: Inhibitors of the Integrated Stress Response (2016)

The integrated stress response comprises multiple signaling pathways for detecting and responding to cellular stress that converge at a single event-the phosphorylation of Ser51 on the α-subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α-P) results in attenuation of global protein synthesis via the inhibitory effects of eIF2α-P on eIF2B, the guanine exchange factor (GEF) for eIF2. Herein we describe structure-activity relationship (SAR) studies of bis-O-arylglycolamides, first-in-class integrated stress response inhibitors (ISRIB). ISRIB analogues make cells insensitive to the effects of eIF2α-P by activating the GEF activity of eIF2B and allowing global protein synthesis to proceed with residual unphosphorylated eIF2α. The SAR studies described herein support the proposed pharmacology of ISRIB analogues as binding across a symmetrical protein-protein interface formed between protein subunits of the dimeric eIF2B heteropentamer.
Loss of the B-lineage–specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma (2003)

Hodgkin and Reed-Sternberg (HRS) cells represent the malignant cells in classical Hodgkin lymphoma (HL). Because their immunophenotype cannot be attributed to any normal cell of the hematopoietic lineage, the origin of HRS cells has been controversially discussed, but molecular studies established their derivation from germinal center B cells. In this study, gene expression profiles generated by serial analysis of gene expression (SAGE) and DNA chip microarrays from HL cell lines were compared with those of normal B-cell subsets, focusing here on the expression of B-lineage markers. This analysis revealed decreased mRNA levels for nearly all established B-lineage-specific genes. For 9 of these genes, lack of protein expression was histochemically confirmed. Down-regulation of genes affected multiple components of signaling pathways active in B cells, including B-cell receptor (BCR) signaling. Because several genes down-regulated in HRS cells are positively regulated by the transcriptional activator Pax-5, which is expressed in most HRS cells, we studied HL cell lines for mutations in the Pax-5 gene. However, no mutations were found. We propose that the lost B-lineage identity in HRS cells may explain their survival without BCR expression and reflect a fundamental defect in maintaining the B-cell differentiation state in HRS cells, which is likely caused by a novel, yet unknown, pathogenic mechanism.
Solid-state microelectrochemistry: electrical characteristics of a solid-state microelectrochemical transistor based on poly(3-methylthiophene) (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid-state microelectrochemistry: electrical characteristics of a solid-state microelectrochemical transistor based on poly(3-methylthiophene)Shuchi Chao and Mark S. WrightonCite this: J. Am. Chem. Soc. 1987, 109, 7, 2197–2199Publication Date (Print):April 1, 1987Publication History Published online1 May 2002Published inissue 1 April 1987https://pubs.acs.org/doi/10.1021/ja00241a057https://doi.org/10.1021/ja00241a057research-articleACS PublicationsRequest reuse permissionsArticle Views486Altmetric-Citations147LEARN 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
Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women (2006)

The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction.
Antibody-free quantification of seven tau peptides in human CSF using targeted mass spectrometry (2015)

Tau protein concentration in cerebrospinal fluid (CSF) is currently used as a sensitive and specific biomarker for Alzheimer's disease. Its detection currently relies on ELISA but the perspective of using mass spectrometry (MS) to detect its different proteoforms represents an interesting alternative. This is however an analytical challenge because of its low concentration in the CSF, a biological fluid collected in small volume by lumbar puncture, and with a high structural heterogeneity. To overcome these issues, instead of using immunocapture as previously done, we rather relied on an original two steps pre-fractionation technique of CSF: perchloric acid (PCA) followed by micro solid phase extraction (μSPE). We could then measure seven tau trypsic peptides by Multiple Reaction Monitoring (MRM) on a triple quadrupole mass spectrometer. Quantification was performed using isotopically labeled (15)N- recombinant tau protein as internal standard and validated using CSF pools with low, medium, or high tau concentrations (HTCs). Repeatability, intermediate precision, linearity, limit of quantification (LOQ), and recovery were calculated for the different peptides. This new MRM assay, which allowed for the first time CSF tau protein quantification without immunocapture, has important potential application to follow tau metabolism in both diagnostic and therapeutic research.
Modulation of Neutrophil Chemokine Receptors byStaphylococcus aureusSupernate (2000)

In a previous study, we showed that Staphylococcus aureus supernate (SaS) is a potent agonist for both neutrophils and mononuclear cells. To further investigate the immunomodulating effects of SaS, the effect on different neutrophil receptors was studied. Expression of various neutrophil receptors, before and after treatment with SaS, was quantified by flow cytometry. We found that SaS treatment of neutrophils resulted in a specific and total downregulation of the C5a and the fMLP receptor, both serpentine receptors, while other receptors were totally unaffected. Since these two receptors are both involved in chemotaxis, we tested the effect of SaS in calcium flux and chemotaxis assays. We showed that preincubation with SaS abrogated the rise in intracellular calcium concentration upon triggering with fMLP and C5a. We also showed that SaS is a potent inhibitor of neutrophil chemotaxis towards fMLP and C5a, but does not interfere with chemotaxis towards interleukin-8. These findings indicate that S. aureus produces a virulence factor extracellularly, which impairs chemotaxis towards the infected site.
Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor (2003)

Nerve growth factor (NGF) causes a rapid sensitisation of nociceptive sensory neurones to painful thermal stimuli owing to an action on the heat and capsaicin receptor TRPV1 (formerly known as VR1). We have developed a new technique to study this rapid sensitisation of TRPV1 by monitoring the effects of NGF on the increase in intracellular calcium concentration ([Ca2+]i) following exposure to capsaicin. Brief applications of capsaicin caused a rise in [Ca2+]i, and NGF was found to enhance this rise in 37 % of capsaicin-responsive neurones within 2 min. Pathways responsible for transducing the sensitisation of TRPV1 by TrkA, the NGF receptor, were characterised by observing the effects of inhibitors of key members of NGF-activated second messenger signalling cascades. Specific inhibitors of the ras/MEK (mitogen-activated protein and extracellular signal-regulated kinases) pathway and of phospholipase C did not abolish the NGF-induced sensitisation, but wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), totally abolished the effect of NGF. Pharmacological blockade of protein kinase C (PKC) or calcium-calmodulin-dependent protein kinase II (CaMK II) activation also prevented NGF-induced sensitisation, while blockade of protein kinase A (PKA) was without effect. These data indicate that the crucial early pathway activated by NGF involves PI3K, while PKC and CaMK II are also involved, probably at subsequent stages of the NGF-activated signalling pathway.
The molecular structure of the TLR3 extracellular domain (2006)

Toll-like receptors (TLRs), type I integral membrane receptors, recognize pathogen associated molecular patterns (PAMPs). PAMP recognition occurs via the N-terminal ectodomain (ECD) which initiates an inflammatory response that is mediated by the C-terminal cytosolic signaling domain. To understand the molecular basis of PAMP recognition, we have begun to define TLR—ECD structurally. We have solved the structure of TLR3-ECD, which recognizes dsRNA, a PAMP associated with viral pathogens. TLR3-ECD is a horseshoe-shaped solenoid composed of 23 leucine-rich repeats (LRRs). The regular LRR surface is disrupted by two insertions at LRR12 and LRR20 and 11 N-linked carbohydrates. Of note, one side of the ECD is carbohydrate-free and could form an interaction interface. We have shown that TLR3-ECD binds directly to pI:pC, a synthetic dsRNA ligand, but not to p(dI):p(dC). Without a TLR3—dsRNA complex structure, we can only speculate how ligand binds. Analysis of the unliganded structure reveals two patches of basic residues and two binding sites for phosphate backbone mimics, sulfate ions, that may be capable of recognizing ligand. Mutational and co-crystallization studies are currently underway to determine how TLR3 binds its ligand at the molecular level.
The human keratins: biology and pathology (2008)

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins--including numerous keratins characterized only recently--are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family.
A Novel Method for Imaging Apoptosis Using a Caspase-1 Near-Infrared Fluorescent Probe (2004)

Here we describe a novel method for imaging apoptosis in cells using a near-infrared fluorescent (NIRF) probe selective for caspase-1 (interleukin 1beta-converting enzyme, ICE). This biocompatible, optically quenched ICE-NIRF probe incorporates a peptide substrate, which can be selectively cleaved by caspase-1, resulting in the release of fluorescence signal. The specificity of this probe for caspase-1 is supported by various lines of evidence: 1) activation by purified caspase-1, but not another caspase in vitro; 2) activation of the probe by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-lacZ) expressing a catalytically active caspase-1-lacZ fusion protein; 3) inhibition of HGC-ICE-lacZ vector-induced activation of the probe by coincubation with the caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4) activation of the probe following standard methods of inducing apoptosis with staurosporine, ganciclovir, or ionizing radiation in culture. These results indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and vector-expressed caspase-1 activity in cells. Furthermore, tumor implant experiments indicate that this ICE-NIRF probe can be used to detect caspase-1 activity in living animals. This novel ICE-NIRF probe should prove useful in monitoring endogenous and vector-expressed caspase-1 activity, and potentially apoptosis in cell culture and in vivo.
Inference of high resolution HLA types using genome-wide RNA or DNA sequencing reads (2014)

PHLAT significantly leverages the accuracy and flexibility of high resolution HLA typing based on genome-wide sequencing data. It may benefit both basic and applied research in immunology and related fields as well as numerous clinical applications.
Broadband and Low-Loss 1 : 9 Transmission-Line Transformer in 0.18- $\mu\hbox{m}$ CMOS Process (2010)

This letter proposes a transmission-line transformer (TLT) with high impedance-transformation ratio of 1 : 9 for wideband power amplifier design. The 1 : 9 TLT is realized with broadside-coupled and multiple-metal stacked transmission lines and achieves a broadband impedance transformation from 5.0 ±0.1Ω optimal load impedance of the power cell to 50-Ω load with a bandwidth of 4.4 to 6.6 GHz, which covers the required bandwidth of the IEEE 802.11a WLAN application. The measured minimum insertion loss is 1.07 dB at 5.8 GHz with a 3-dB bandwidth of 164%. This 1 : 9 TLT is fabricated in standard 0.18-μm CMOS process with a chip area of 426 μm × 589 μm including the test pad.
Enzymatic Aspects of Isoprenoid Chain Elongation (1998)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTEnzymatic Aspects of Isoprenoid Chain ElongationKyozo Ogura and Tanetoshi KoyamaView Author Information Institute for Chemical Reaction Science, Tohoku University, Katahira 2-1-1, Sendai 980-8577 Japan Cite this: Chem. Rev. 1998, 98, 4, 1263–1276Publication Date (Web):May 30, 1998Publication History Received31 July 1997Revised3 March 1998Published online30 May 1998Published inissue 1 June 1998https://pubs.acs.org/doi/10.1021/cr9600464https://doi.org/10.1021/cr9600464research-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1462Altmetric-Citations276LEARN 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 SUBJECTS:Anions,Bacteria,Genetics,Monomers,Peptides and proteins Get e-Alerts
Cell surface markers of regulatory T cells are not associated with increased forkhead box p3 expression in blood CD4+ T cells from HIV‐infected patients responding to antiretroviral therapy (2006)

Regulatory T (Treg) cells may attenuate host immune responses to pathogens, including HIV and opportunistic pathogens in HIV-infected patients. Treated and untreated progressive HIV disease represent a range of immunological scenarios with potentially different roles for Treg cells. A cell surface marker to determine Treg cell numbers would assist in identifying situations where Treg cells are important. Here we show that levels of Foxp3 mRNA are increased in CD4+ T cells from HIV-infected patients responding to antiretroviral therapy. However, the proportion of peripheral blood CD4+ and CD8+ T cells expressing CD25, neuropilin-1, glucocorticoid-induced TNF receptor and lymphocyte activation gene-3 did not differ as a result of treated or untreated HIV infection when compared with HIV-seronegative controls. Hence, none of the putative Treg cell surface markers identified T-cell populations in peripheral blood that mirrored the effects of HIV infection and antiretroviral therapy on Foxp3 expression.