gebhart/patrepeval huggingface dataset:
Non-muscle myosin heavy chain as a possible target for protein encoded by metastasis-related mts-1 gene. (1994)

The mts-1 gene is associated with the expression of the metastatic phenotype of tumor cells. The protein product of the mts-1 gene belongs to the S100 family of Ca(2+)-binding proteins with unknown biochemical function. In the present work, monoclonal anti-Mts-1 antibodies were used to isolate and characterize Mts-1 protein possible targets. Mts-1 protein can be immunoprecipitated by both anti-Mts-1 and anti-myosin antibodies as a complex with myosin from lysates of different mouse and human cell lines. Precipitation of myosin by anti-Mts-1 antibodies is specific and depends on the presence of Mts-1 protein. Ca(2+)-dependent association between Mts-1 protein and the heavy chain of non-muscle myosin was demonstrated by blot overlay technique. Furthermore, association between myosin and Mts-1 was confirmed by sucrose gradient analysis. Finally, immunofluorescent staining of the mouse mammary adenocarcinoma cell line showed that Mts-1 protein is co-localized with the myosin complex. The data suggest that the target for Mts-1 protein is a heavy chain of non-muscle myosin.
Dual Inhibition of EGFR with Afatinib and Cetuximab in Kinase Inhibitor–Resistant EGFR -Mutant Lung Cancer with and without T790M Mutations (2014)

This article reports the results of a trial combining afatinib and cetuximab in patients with acquired resistance and details the first clinical proof-of-concept for the preclinical hypothesis that a significant proportion of tumors in patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR signaling for survival.
C5 inhibitor rEV576 protects against neural injury in an in vitro mouse model of Miller Fisher syndrome (2008)

Guillain-Barré syndrome and its clinical variants, including the anti-GQ1b ganglioside-mediated Miller Fisher syndrome (MFS), comprise the world's leading cause of acute neuromuscular paralysis. Presently, no specific drug therapies exist. The complement cascade, which is activated in these patients, forms an attractive drug target. In this study, we tested whether the complement C5-inhibiting recombinant protein, rEV576, was able to prevent neural injury in a previously developed in vitro mouse model for MFS. Mouse hemidiaphragm preparations were treated with anti-GQ1b antibody and normal human serum as a source of complement with added rEV576 or control protein. Immunohistology in control tissue showed deposition of C3c and membrane attack complex at neuromuscular junctions (NMJs), along with terminal motor axonal neurofilament degradation as well as ethidium homodimer-2 staining showing perisynaptic Schwann cell (pSC) injury. Electrophysiological and functional analyses showed block of synaptic transmission at the NMJ after an initial period of a dramatically high level of asynchronous acetylcholine release. In tissue treated with rEV576, all these indicators of motor neuronal damage were absent, except for the presence of C3c, indicating effective inhibition of C5. These results demonstrate that rEV576 effectively prevents development of neuronal and pSC damage in experimental murine neuropathy.
A Neural Transducer (2015)

Sequence-to-sequence models have achieved impressive results on various tasks. However, they are unsuitable for tasks that require incremental predictions to be made as more data arrives or tasks that have long input sequences and output sequences. This is because they generate an output sequence conditioned on an entire input sequence. In this paper, we present a Neural Transducer that can make incremental predictions as more input arrives, without redoing the entire computation. Unlike sequence-to-sequence models, the Neural Transducer computes the next-step distribution conditioned on the partially observed input sequence and the partially generated sequence. At each time step, the transducer can decide to emit zero to many output symbols. The data can be processed using an encoder and presented as input to the transducer. The discrete decision to emit a symbol at every time step makes it difficult to learn with conventional backpropagation. It is however possible to train the transducer by using a dynamic programming algorithm to generate target discrete decisions. Our experiments show that the Neural Transducer works well in settings where it is required to produce output predictions as data come in. We also find that the Neural Transducer performs well for long sequences even when attention mechanisms are not used.
Galectin-9/TIM-3 Interaction Regulates Virus-Specific Primary and Memory CD8+ T Cell Response (2010)

In this communication, we demonstrate that galectin (Gal)-9 acts to constrain CD8(+) T cell immunity to Herpes Simplex Virus (HSV) infection. In support of this, we show that animals unable to produce Gal-9, because of gene knockout, develop acute and memory responses to HSV that are of greater magnitude and better quality than those that occur in normal infected animals. Interestingly, infusion of normal infected mice with alpha-lactose, the sugar that binds to the carbohydrate-binding domain of Gal-9 limiting its engagement of T cell immunoglobulin and mucin (TIM-3) receptors, also caused a more elevated and higher quality CD8(+) T cell response to HSV particularly in the acute phase. Such sugar treated infected mice also had expanded populations of effector as well as memory CD8(+) T cells. The increased effector T cell responses led to significantly more efficient virus control. The mechanisms responsible for the outcome of the Gal-9/TIM-3 interaction in normal infected mice involved direct inhibitory effects on TIM-3(+) CD8(+) T effector cells as well as the promotion of Foxp3(+) regulatory T cell activity. Our results indicate that manipulating galectin signals, as can be achieved using appropriate sugars, may represent a convenient and inexpensive approach to enhance acute and memory responses to a virus infection.
Two-dimensional Proton Echo-Planar Spectroscopic Imaging of Brain Metabolic Changes During Lactate-Induced Panic (1999)

Greater overall rises in brain lactate among subjects with panic disorder compared with controls occurred in response to lactate infusion. We were unable to detect a distinct regional pattern for magnitude differences in brain lactate rise by which to identify a specific neuroanatomical substrate underlying a lactate-induced panic response. The wide anatomical distribution of these brain lactate increases suggest metabolic and/or neurovascular mechanisms for the abnormal rise in subjects with panic disorder.
A Feasibility Study of High-Dose Cisplatin and 5-Fluorouracil with Glutathione Protection in the Treatment of Advanced Colorectal Cancer (1990)

On the basis of previous studies supporting that glutathione (GSH) reduced cisplatin nephrotoxicity we have designed a new regimen in the treatment of advanced colorectal cancer, which included GSH as a modulator of cisplatin-induced toxicity. Eleven untreated patients with measurable metastatic colorectal cancer received 5-fluorouracil (750 mg/m2, daily continuous infusion for days 1-5) and cisplatin (40 mg/m2 1 hour-infusion for days 6-8) given every 4 weeks. Reduced glutathione (2.5 g) was delivered i.v. prior to each cisplatin infusion. Toxicity was minimal and reversible and included nausea/vomiting (11 cases), mild neurotoxicity (4 cases) and leukopenia (2 cases); only 2 patients showed moderate and transient increases of serum creatinine (less than 2 mg/dl) and BUN. Renal function impairment was also monitored by magnesemia levels and urinary marker enzymes indicating minimal cumulative nephrotoxicity. Out of 10 evaluable patients, only 2 partial responses were observed. The median survival was 9 months (range 5-26). The study was closed, since the preliminary results do not suggest any therapeutic advantage in adding cisplatin to 5-fluorouracil in the present schedule, even using an intensive regimen. Indirect evidence suggests that these disappointing results are not the consequence of interference of GSH on the cytotoxic efficacy of cisplatin. The lack of incidence of severe toxicity of this regimen supports the role of reduced glutathione as a potential protective against cisplatin nephrotoxicity. Although these preliminary results suggest that further studies with the present regimen in this disease are not warranted, in view of its safety this program deserves evaluation in the treatment of neoplastic diseases responsive to 5-fluorouracil/cisplatin.
Intense ultraviolet emission from Tb3+ and Yb3+ codoped glass ceramic containing CaF2 nanocrystals (2007)

A transparent Tb3+ and Yb3+ codoped oxyfluoride glass ceramic containing CaF2 nanocrystals was developed. This glass ceramic showed an intense ultraviolet emission at 381nm due to the G65, D35→F67 transitions of Tb3+ ion when excited with a 974nm laser at room temperature. The observed intense ultraviolet emission could be attributed to the change of ligand field of Tb3+ and Yb3+ ions due to the incorporation of some Tb3+ and Yb3+ ions into CaF2 nanocrystals, and the resulting increased branching ratio of the transitions and longer lifetime of D45 level of Tb3+ in the glass ceramic.
The Reduction of Acid Amides with Lithium Aluminum Hydride (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Reduction of Acid Amides with Lithium Aluminum HydrideVukic Micovic and Mihailo MihailovicCite this: J. Org. Chem. 1953, 18, 9, 1190–1200Publication Date (Print):September 1, 1953Publication History Published online1 May 2002Published inissue 1 September 1953https://pubs.acs.org/doi/10.1021/jo50015a017https://doi.org/10.1021/jo50015a017research-articleACS PublicationsRequest reuse permissionsArticle Views4541Altmetric-Citations272LEARN 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
A detailed analysis of a time-domain formant-corrected pitch-shifting algorithm (1995)

A novel algorithm to perform real-time pitch shifting of quasiperiodic musical tones in such a way as to preserve the apparent spectral envelope has been proposed by Lent in 1989. A functional and analytical comparison is made of this method and most commercial methods of pitch shifting that shift the spectral envelope along with the fundamental frequency. Analytical results show that this method indeed attempts to preserve the spectral envelope similarly to frequency-domain methods that interpolate between discrete spectral lines and resample the interpolated spectrum at the output fundamental and its harmonics
Association of some cell surface antigens of lymphoid cells and cell surface differentiation antigens with early rat pregnancy. (1984)

Monoclonal antibodies and the immunoperoxidase technique were used to localize some cell surface antigens of rat lymphoid cells and cell surface differentiation antigens on cryostat sections of early rat pregnancies. The W3/13 leucocyte sialoglycoprotein was detected almost constantly on trophoblast. The immunoglobulins were more associated with mother's rather than with embryo-derived tissues. We were unable to detect considerable amounts of class I and class II major histocompatibility complex-derived antigens on trophoblast and adjacent decidual cells. The Ia+ cells of the lymphocyte type were occasionally detected in the sites exhibiting presence of immunoglobulins. The Thy-1 cell surface differentiation antigen was detected on the cells producing Thy-1+ material among decidual cells. Depletion of Thy-1 was followed by the regression of decidualized tissue. The OX-2 antigen, known as minor glycoprotein of rat thymocytes, was detected on trophoblast cells and endothelia of decidual vessels, the latter exhibiting also class I major histocompatibility complex-derived antigens. The non-pregnant uterine tissues, as well as the oviduct epithelium were also investigated. The possible role of some of these antigens in the maintenance of the 'immunologically privileged' stage of trophoblast, and in the control of the rearrangement of maternal tissues surrounding the embryo, is discussed.
Effect of B cell differentiation factor (BCDF) on biosynthesis and secretion of immunoglobulin molecules in human B cell lines. (1985)

Stimulation of human B lymphoblastoid cell lines, CESS and SKW6-CL4 with BCDF induced an increase in IgG- and IgM-secreting cells, as well as a slight increase in IgG and IgM expression on their respective surfaces. Biosynthetic labeling demonstrated that BCDF stimulation induced an increase in synthesis of secretory gamma- and mu-chains, as well as their precursors. A slight but significant increase in synthesis of membrane-bound gamma- and mu-chains and their precursors was also observed by BCDF stimulation. However, an increase in synthesis of secretory heavy chains was much higher than that in membrane-bound heavy chains in both cell lines. Pulse-chase experiments showed that increased synthesis of secretory heavy chains was not due to a decrease in degradation. BCDF stimulation induced a preferential increase in mRNA specific for secretory gamma- and mu-chains in CESS and SKW6-CL4 cells, respectively. These results suggest that BCDF induces an increase in the level of mRNA specific for secretory heavy chains, and then induces final maturation of B cells into immunoglobulin-secreting cells.
Covalently Bridging Gaps in Single-Walled Carbon Nanotubes with Conducting Molecules (2006)

Molecular electronics is often limited by the poorly defined nature of the contact between the molecules and the metal surface. We describe a method to wire molecules into gaps in single-walled carbon nanotubes (SWNTs). Precise oxidative cutting of a SWNT produces carboxylic acid-terminated electrodes separated by gaps of </=10 nanometers. These point contacts react with molecules derivatized with amines to form molecular bridges held in place by amide linkages. These chemical contacts are robust and allow a wide variety of molecules to be tested electrically. In addition to testing molecular wires, we show how to install functionality in the molecular backbone that allows the conductance of the single-molecule bridges to switch with pH.
Fluorescence-based RT PCR analysis: determination of the ratio of soluble to membrane-bound forms of Fc gamma RIIA transcripts in hematopoietic cell lines. (1993)

We have developed a fluorescence-based RT PCR assay for determination of the ratio of two alternatively spliced transcripts in different cell types. Fluorescence detection, by an automated DNA sequencer, allows enhanced sensitivity and ease of data processing. PCR products are fluorescently tagged using a dye-labeled oligonucleotide primer during the PCR reaction. Assay conditions were first defined so that fluorescence intensity of the PCR products was linear with respect to input RNA and exponential relative to PCR cycle number. Sensitivity and reproducibility of detection were evaluated with serial dilutions of RT PCR reactions. We have applied this assay to an analysis of the lineage-specific expression of two human Fc gamma RIIA transcripts, Fc gamma RIIa1 and Fc gamma RIIa2, in different hematopoietic cell lines. Previously, we noted that when standard RT PCR conditions are used with primers that bracket the TM exon, the pattern of expression of these transcripts as assessed by ethidium bromide staining of agarose gels varied in different hematopoietic cell lineages. Using the fluorescence-based RT PCR method, we now confirm our previous findings and quantitate transcript ratios (Fc gamma RIIa2/Fc gamma RIIa1) in several hematopoietic cell lines. The ratio varies from 0.70 (41% Fc gamma RIIa2) in the erythroleukemic cell line HEL, to 0.14 (12% Fc gamma RIIa2) in the monocytic cell line U937, to 0.07 (6% Fc gamma RIIa2) in the multipotential cell line K562. This fluorescent RT PCR method provides a general approach to quantitating mRNA levels and ratios of PCR products in other gene systems.
Intracellular Assembly and Trafficking of MHC Class I Molecules (2009)

The presentation of antigenic peptides by class I molecules of the major histocompatibility complex begins in the endoplasmic reticulum (ER) where the co-ordinated action of molecular chaperones, folding enzymes and class I-specific factors ensures that class I molecules are loaded with high-affinity peptide ligands that will survive prolonged display at the cell surface. Once assembled, class I molecules are released from the quality-control machinery of the ER for export to the plasma membrane where they undergo dynamic endocytic cycling and turnover. We review recent progress in our understanding of class I assembly, anterograde transport and endocytosis and highlight some of the events targeted by viruses as a means to evade detection by cytotoxic T cells and natural killer cells.
Patients' criteria for meaningful relief to determine onset of action (2005)

Background Many investigators1,2 assign onset of action only to drug-treated patients who detect “meaningful” pain relief. Is there a quantifiable level of relief that corresponds to this qualitative description? Methods To make this determination, we asked patients with sore throat who had completed a randomized, double-blind, placebo-controlled trial on a novel formulation3 of acetaminophen (APAP) 1000 mg to indicate which level on a categorical relief scale represented meaningful relief to them. If the patient had detected this level using the same scale in the trial, we examined the patient's responses for evidence of onset. Results Efficacy was demonstrated for all APAP-treated patients compared with placebo beginning at 15 minutes (P<0.05). Of the 73 APAP-treated patients who experienced their own levels of meaningful relief (which was, in general, “moderate relief”), the median (and modal) time to first perceived relief was 15 minutes; 89% reported onset within 30 minutes. Conclusions Because these results accord with how patients assess drug performance in clinical practice, it makes sense, in clinical trials, to analyze the onset of drug action similarly, namely, in patients for whom the drug “works.” One method is to use the patients' own criteria for meaningful relief. Clinical Pharmacology & Therapeutics (2005) 77, P51–P51; doi: 10.1016/j.clpt.2004.12.088
Daily prognostic estimates for critically ill adults in intensive care units (1994)

Equations using initial and repeated physiologic measurements provide a high degree of explanatory power for subsequent hospital mortality rate. These daily prognostic estimates deserve evaluation for their potential role in improving the process and outcome from clinical decision-making.
Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity (2016)

The cAMP response element binding protein (CREB) is induced during fasting in the liver, where it stimulates transcription of rate-limiting gluconeogenic genes to maintain metabolic homeostasis. Adenoviral and transgenic CREB reporters have been used to monitor hepatic CREB activity non-invasively using bioluminescence reporter imaging. However, adenoviral vectors and randomly inserted transgenes have several limitations. To overcome disadvantages of the currently used strategies, we created a ROSA26 knock-in CREB reporter mouse line (ROSA26-CRE-luc). cAMP-inducing ligands stimulate the reporter in primary hepatocytes and myocytes from ROSA26-CRE-luc animals. In vivo, these animals exhibit little hepatic CREB activity in the ad libitum fed state but robust induction after fasting. Strikingly, CREB was markedly stimulated in liver, but not in skeletal muscle, after overnight voluntary wheel-running exercise, uncovering differential regulation of CREB in these tissues under catabolic states. The ROSA26-CRE-luc mouse line is a useful resource to study dynamics of CREB activity longitudinally in vivo and can be used as a source of primary cells for analysis of CREB regulatory pathways ex vivo.
Short‐Term Effects of Biocorrodible Iron Stents in Porcine Coronary Arteries (2007)

The current study demonstrates that stents made of biocorrodible iron are safe. In some of the measured parameters, such as intimal thickness, intimal area, and percentage occlusion, there was a trend in favor of the iron stents.
Antigen-specific identification and cloning of hybridomas with a fluorescence-activated cell sorter. (1979)

Myeloma-spleen cell hybrids (hybridomas) producing antibody to mouse immunoglobulin allotypes have been labeled with fluorescent microspheres coupled with myeloma protein antigens. The ratio of specific to nonspecific microsphere binding by viable hybridoma cells was about 100:1. By using a modified fluorescence-activated cell sorter (FACS), selected hybridoma cells in a mixture have been sorted individually into media in microculture wells, where, with thymocyte feeder cells, they developed into clones producing a desired monoclonal antibody. Viable cells were selected by measurement of their light scattering and autofluorescence properties. Rare antibody-producing clones were obtained without laborious screening and repeated subculturing. This technique should expand the range of monoclonal antibodies readily obtained from hybridomas and greatly facilitate the process of obtaining desired hybridomas.
Molecular sequelae of proteasome inhibition in human multiple myeloma cells (2002)

The proteasome inhibitor PS-341 inhibits IkappaB degradation, prevents NF-kappaB activation, and induces apoptosis in several types of cancer cells, including chemoresistant multiple myeloma (MM) cells. PS-341 has marked clinical activity even in the setting of relapsed refractory MM. However, PS-341-induced apoptotic cascade(s) are not yet fully defined. By using gene expression profiling, we characterized the molecular sequelae of PS-341 treatment in MM cells and further focused on molecular pathways responsible for the anticancer actions of this promising agent. The transcriptional profile of PS-341-treated cells involved down-regulation of growth/survival signaling pathways, and up-regulation of molecules implicated in proapoptotic cascades (which are both consistent with the proapoptotic effect of proteasome inhibition), as well as up-regulation of heat-shock proteins and ubiquitin/proteasome pathway members (which can correspond to stress responses against proteasome inhibition). Further studies on these pathways showed that PS-341 decreases the levels of several antiapoptotic proteins and triggers a dual apoptotic pathway of mitochondrial cytochrome c release and caspase-9 activation, as well as activation of Jun kinase and a Fas/caspase-8-dependent apoptotic pathway [which is inhibited by a dominant negative (decoy) Fas construct]. Stimulation with IGF-1, as well as overexpression of Bcl-2 or constitutively active Akt in MM cells also modestly attenuates PS-341-induced cell death, whereas inhibitors of the BH3 domain of Bcl-2 family members or the heat-shock protein 90 enhance tumor cell sensitivity to proteasome inhibition. These data provide both insight into the molecular mechanisms of antitumor activity of PS-341 and the rationale for future clinical trials of PS-341, in combination with conventional and novel therapies, to improve patient outcome in MM.