gebhart/patrepeval huggingface dataset:
Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations (2010)

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), are present in most gliomas and secondary glioblastomas, but are rare in other neoplasms. IDH1/2 mutations are heterozygous, and affect a single arginine residue. Recently, IDH1 mutations were identified in 8% of acute myelogenous leukemia (AML) patients. A glioma study revealed that IDH1 mutations cause a gain-of-function, resulting in the production and accumulation of 2-hydroxyglutarate (2-HG). Genotyping of 145 AML biopsies identified 11 IDH1 R132 mutant samples. Liquid chromatography-mass spectrometry metabolite screening revealed increased 2-HG levels in IDH1 R132 mutant cells and sera, and uncovered two IDH2 R172K mutations. IDH1/2 mutations were associated with normal karyotypes. Recombinant IDH1 R132C and IDH2 R172K proteins catalyze the novel nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of alpha-ketoglutarate (alpha-KG) to 2-HG. The IDH1 R132C mutation commonly found in AML reduces the affinity for isocitrate, and increases the affinity for NADPH and alpha-KG. This prevents the oxidative decarboxylation of isocitrate to alpha-KG, and facilitates the conversion of alpha-KG to 2-HG. IDH1/2 mutations confer an enzymatic gain of function that dramatically increases 2-HG in AML. This provides an explanation for the heterozygous acquisition of these mutations during tumorigenesis. 2-HG is a tractable metabolic biomarker of mutant IDH1/2 enzyme activity.
Krupaseep?The Next Generation Seepage Meter (1998)

jffffff KRUPA, S.L.; BELANGER, T.V.; HECK, H.H.; BROCK, J.T., and JONES, B.J., 1998. Krupaseep-The Next Gener ation Seepage Meter. Journal of Coastal Research, SI(26), 210-213. Royal Palm Beach (Florida), ISSN 0749-0208. ^M_^%* We designed, built and tested a new kind of seepage metering device to study the exchange of ground water and river ^2^5^S^5^ water at the bottom of streams and lakes. The dome-shaped seepage meter is fabricated from translucent polycar ^S^SS^^S^ bonate plastic. A flow meter, installed in a port at the apex of the dome, utilizes heat-pulse technology to measure ^^^^^^ real-time fluxes. Electronic data loggers record the flow, as well as water quality data, obtained by sensors located both inside and outside of the dome. Additionally, water quality samples are remotely extracted from inside and outside the dome for laboratory analysis. All real-time data is captured by on-shore computers. The new design eliminates problems such as induced anaerobic conditions and methane accumulation, which are inherent to the traditional, low-tech devices commonly used today. The data are quite promising and will allow, for the first time, a clear understanding of interactions between ground water and surface water, with an emphasis on water quality.
Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood. (1995)

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.
Identification of a Lipid A Binding Site in the Acute Phase Reactant Lipopolysaccharide Binding Protein (1989)

Lipopolysaccharide (LPS) binding protein (LBP), a recently discovered 60-kDa acute phase protein, is present in the acute phase serum of many species including human, rabbits, mice, and rats. Using either highly purified LBP from acute phase rabbit serum or unfractionated acute phase rabbit serum as a source of LBP, we examined the binding of LBP to LPS immobilized on plastic microtiter plates and to LPS electrotransferred to nitrocellulose after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of LBP bound to LPS was detected with goat anti-rabbit LBP and peroxidase-conjugated rabbit anti-goat IgG. LBP was found to bind to a variety of LPS types from both rough and smooth strains of Gram-negative bacteria, to lipid A, and to the tetraacyl glucosamine disaccharide diphosphate precursor IVA, but bound very poorly to the diacyl glucosamine phosphate, lipid X. No binding to 3-deoxyoctulosonic acid was observed. Binding affinities for LPS are near 10(9) M-1. The data presented here support the concept that LBP contains a binding site for lipid A.
Isolation of tumor cell‐specific single‐chain Fv from immunized mice using phage‐antibody libraries and the re‐construction of whole antibodies from these antibody fragments (1994)

Enhanced expression of epidermal growth factor receptor (EGFR) occurs on a variety of malignant tissues thus making anti-EGFR antibodies possible agents for the diagnosis and therapy of human tumors. Standard hybridoma technology has been used successfully to isolate anti-EGFR antibodies from immunized mice and rats. This report demonstrates that phage-antibody libraries are an alternative, and more versatile, method for isolating antibodies from immunized mice. Anti-EGFR antibodies were isolated from phage-antibody libraries constructed not only from the spleen of an immunized mouse but also from the draining lymph node of an immunized mouse and from in vitro immunized mouse cells. Two of the single-chain Fv isolated from the phage-antibody libraries were engineered to create partially humanized whole antibody molecules.
Induction of transformation progression in type 5 adenovirus-transformed rat embryo cells by a cloned protein kinase C beta 1 gene and reversal of progression by 5-azacytidine. (1994)

Protein kinase C (PKC) is a key component in signal transduction in eucaryotic cells and when specific PKC isoforms are over-expressed in immortal mammalian cells they can induce transformation-associated properties. In the present study we demonstrate that a cloned PKC beta 1 gene can induce an enhanced expression of the transformed phenotype in type 5 adenovirus (Ad5)-transformed rat embryo (RE) cells (clone E11), a process termed transformation progression. E11 cells expressing the PKC beta 1 gene, clone B1/PKC, produce PKC beta 1 mRNA and display enhanced PKC enzymatic activity and binding of [3H]-phorbol-12,13-dibutyrate (PDBu) to cell surface phorbol ester receptors. B1/PKC cells grow with increased efficiency in agar in comparison with parental E11 cells and anchorage-independence is further enhanced in both cell types by addition of the tumor promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A single-exposure of B1/PKC cells to 5-azacytidine (AZA), followed by growth in the absence of this demethylating agent, results in B1/PKC-AZA clones which display a stable reversion of the progression phenotype to that of the unprogressed parental E11 clone. Loss of the progression phenotype corresponds with a reduction in PKC beta 1-induced biochemical and cellular changes. In contrast, progression-suppression does not involve an alteration in expression of the Ad5 transforming genes, E1A and E1B, or the endogenous PKC epsilon gene. TPA cannot induce the progression phenotype in B1/PKC-AZA cells, but it can reversibly induce an increase in the transcriptional rate and steady-state mRNA levels of PKC beta 1 and c-jun and it increases AP-1 DNA-binding. These results indicate that the PKC beta 1 gene can serve as a transformation progression-inducing gene in rat embryo cells previously transformed by Ad5 and progression may be mediated by the inactivation by methylation of an AZA-sensitive 'progression suppressor gene(s)'. The suppression process in B1/PKC cells is independent of expression of the Ad5-transforming genes but correlates directly with the reduced expression of the transfected PKC beta 1 gene in AZA-treated B1/PKC cells.
Monoclonal Idiotope Vaccine Against Streptococcus pneumoniae Infection (1984)

A monoclonal anti-idiotope antibody coupled to a carrier protein was used to immunize BALB/c mice against a lethal Streptococcus pneumoniae infection. Vaccinated mice developed a high titer of antibody to phosphorylcholine, which is known to protect against infection with Streptococcus pneumoniae. Measurement of the median lethal dose of the bacteria indicated that anti-idiotope immunization significantly increased the resistance of BALB/c mice to the bacterial challenge. Antibody to an idiotope can thus be used as an antigen substitute for the induction of protective immunity.
C-reactive protein immunohistochemical localization in normal and atherosclerotic human aortas. (1987)

We examined immunohistochemically 104 formaldehyde-fixed, paraffin-embedded, human autopsy aortic specimens for C-reactive protein (CRP) presence and localization. In addition, we correlated immunoreactivity with a spectrum of the following histologic categories: normal aorta, fatty streak, atheromatous plaque, and fibrous plaque. Using appropriate controls, we confirmed CRP immunoreactivity in 3.3% of normal specimens, 75% of fatty streaks, 90.2% of atheromatous plaques, and 64.6% of fibrous plaques. Immunoreactivity in fatty streaks was located around collections of foam cells. Immunoreactivity in atheromatous plaques was in a bandlike distribution corresponding to the pale-staining insudative zone frequently seen in such lesions. The correlation and localization of CRP immunoreactivity in atherosclerotic lesions presented here suggests a functional role for CRP in the pathogenesis of atherosclerosis. Our results encourage efforts to determine more precisely the physiologic contributions of CRP to the development and exacerbation of atherosclerosis.
Comparison of UWB Doppler radar and camera based photoplethysmography in non-contact multiple heartbeats detection (2016)

RF and optical based photoplethysmography (PPG) have been recently developed for non-contact vital sign detection, due to their numerous advantages. In this paper, UWB radar, and camera-based monitoring are applied in vital sign detection and compared. In this paper, a mathematical signal model for the UWB Doppler radar, and another one for the camera-based photoplethysmography PPG are introduced. Vital signals have been recorded using both methods and compared. Capabilities and limitations of multiple subjects tracking have been demonstrated for multiple heartbeat detection. For validation, experimental results were compared to commercial contact sensors as well. Furthermore, the pros and cons of the Doppler radar and remote PPG in vital signs detection is discussed and summarized.
Induction of a stable hapten-specific immunosuppression by a hapten conjugated to poly(N-vinylpyrrolidone) (PVP). (1978)

The ability of a hapten coupled to a clinically permissive synthetic polymer (NIP-PVP) to induce suppression was investigated. NIP coupled to the low molecular weight non-immunogenic form of poly(N-vinylpyrrolidone) (PVP) was found to be capable of inducing a hapten-specific longlasting suppression of both primary and secondary responses. The previous use of PVP as a plasma expander in humans makes this polymer a potentially suitable tool for the induction of specific immunosuppression to a variety of clinically important drug and tissue specific epitopes. The possible use of low molecular weight PVP for that purpose will be investigated further, specifically with larger antigenic components.
Epitope Targeting of Tertiary Protein Structure Enables Target‐Guided Synthesis of a Potent In‐Cell Inhibitor of Botulinum Neurotoxin (2015)

Botulinum neurotoxin (BoNT) serotype A is the most lethal known toxin and has an occluded structure, which prevents direct inhibition of its active site before it enters the cytosol. Target-guided synthesis by in situ click chemistry is combined with synthetic epitope targeting to exploit the tertiary structure of the BoNT protein as a landscape for assembling a competitive inhibitor. A substrate-mimicking peptide macrocycle is used as a direct inhibitor of BoNT. An epitope-targeting in situ click screen is utilized to identify a second peptide macrocycle ligand that binds to an epitope that, in the folded BoNT structure, is active-site-adjacent. A second in situ click screen identifies a molecular bridge between the two macrocycles. The resulting divalent inhibitor exhibits an in vitro inhibition constant of 165 pM against the BoNT/A catalytic chain. The inhibitor is carried into cells by the intact holotoxin, and demonstrates protection and rescue of BoNT intoxication in a human neuron model.
Biomarkers in cervical cancer. (2007)

Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus (HPV) is the single most important etiological agent in cervical cancer, contributing to neoplastic progression through the action of viral oncoproteins, mainly E6 and E7. Cervical screening programs using Pap smear testing have dramatically improved cervical cancer incidence and reduced deaths, but cervical cancer still remains a global health burden. The biomarker discovery for accurate detection and diagnosis of cervical carcinoma and its malignant precursors (collectively referred to as high-grade cervical disease) represents one of the current challenges in clinical medicine and cytopathology.
Cardiac safety of noncardiac drugs : practical guidelines for clinical research and drug development (2005)

Part I. Introduction Cardiac Safety of Noncardiac Drugs: Historical Recollections Raymond John Lipicky Part II. Preclinical and Pharmacogenomic Cardiac Safety Evaluations Molecular Physiology of Ion Channels That Control Cardiac Repolarization Jeanne M. Nerbonne and Robert S. Kass Cellular, Molecular, and Pharmacologic Mechanisms Underlying Drug-Induced Cardiac Arrhythmogenesis Charles Antzelevitch hERG Assay, QT Liability, and Sudden Cardiac Death Arthur M. Brown Pharmacogenomics in Drug Development: When and How to Apply Richard Judson and Arthur J. Moss Part III. Clinical Methodologies and Technical Aspects of Assessing Cardiac Safety of Investigational Drugs: Focus on Cardiac Repolarization Assessment of Ventricular Repolarization From Body-Surface ECGs in Humans Jean-Philippe Couderc and Wojciech Zareba ECG Acquisition and Signal Processing: 12-Lead ECG Acquisition Justin L. Mortara Digital 12-Lead Holter vs Standard Resting Supine Electrocardiogram for the Assessment of Drug-Induced QTc Prolongation: Assessment by Different Recording and Measurement Methods Nenad Sarapa Holter Monitoring for QT: The RR Bin Method in Depth Fabio Badilini and Pierre Maison-Blanche Part IV. Application of Electrocardiology in Clinical Research Fundamentals of ECG Interpretation in Clinical Research and Cardiac Safety Assessment Ihor Gussak, Robert Kleiman, and Jeffrey S. Litwin Design and Conduct of the Thorough Phase I ECG Trial for New Bioactive Drugs Joel Morganroth Use of ECGs in Support of Cardiac Safety in Phase II and III Clinical Trials Martin P. Bedigian Cardiac Arrhythmia Assessment in Phase IV Clinical Studies Gerald A. Faich and Annette Stemhagen Statistical Analysis Plans for ECG Data: Controlling the Intrinsic and Extrinsic Variability in QT Data Alan S. Hollister and Timothy H Montague Interpretation of Clinical ECG Data: Understanding the Risk From Non-Antiarrhythmic Drugs Rashmi R. Shah Part V. Regulatory Considerations The FDA's Digital ECG Initiative and Its Impact on Clinical Trials Barry D. Brown Quality Control and Quality Assurance for Core ECG Laboratories Amy M. Annand-Furlong ECG Digital Communities and Electronic Reporting of Cardiac Safety Data: New Technologies for Reporting Digital ECG Data in Clinical Research Settings Scott Grisanti and Robert Brown Index
From brain passage to cell adaptation: the road of human rabies vaccine development (2011)

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.
Unified speech and audio coding scheme for high quality at low bitrates (2009)

Traditionally, speech coding and audio coding were separate worlds. Based on different technical approaches and different assumptions about the source signal, neither of the two coding schemes could efficiently represent both speech and music at low bitrates. This paper presents a unified speech and audio codec, which efficiently combines techniques from both worlds. This results in a codec that exhibits consistently high quality for speech, music and mixed audio content. The paper gives an overview of the codec architecture and presents results of formal listening tests comparing this new codec with HE-AAC(v2) and AMR-WB+. This new codec forms the basis of the reference model in the ongoing MPEG standardization activity for Unified Speech and Audio Coding.
Synthesis of Peptides for Use as Immunogens (1992)

An increasing problem in cell and molecular biology is the preparation of antibodies specific to proteins that are present in minute quantities within cells or tissues. With the advent of recombinant DNA technology, it is now often possible to deduce the primary amino acid sequence of a polypeptide without its purification. Two strategies then exist to raise appropriate antibodies. Either the gene can be expressed in a heterologous species, usually bacteria, and the resultant protein used as an immunogen, or alternatively, small synthetic peptides can be made that contain amino acid sequences inferred from that of the gene. Such antipeptide antibodies crossreact with the intact native protein with surprisingly high frequency and have the additional advantage that the epitope recognized by the antibody is already well defined (1). In this way, antibodies can be raised against novel gene products that are specifically directed against sites of interest, for example, unique regions, highly conserved regions, active sites, extracellular or intracellular domains. Moreover, the ready availability of the pure peptide immunogen against which the antibody was raised means that sera can be rapidly and easily screened, e.g., using an enzyme-linked immunosorbent assay (ELISA) for antipeptide activity. Free peptide can also be used to block antibody binding and so demonstrate immunological specificity, and it may be coupled to a solid support (e.g., agarose) to generate an affinity matrix for antibody purification.
Functions Required for Extracellular Quinolone Signaling by Pseudomonas aeruginosa (2002)

A set of 30 mutants exhibiting reduced production of the phenazine poison pyocyanin were isolated following transposon mutagenesis of Pseudomonas aeruginosa PAO1. The mutants could be subdivided into those with defects in the primary phenazine biosynthetic pathway and those with more pleiotropic defects. The largest set of pleiotropic mutations blocked the production of the extracellular Pseudomonas quinolone signal (PQS), a molecule required for the synthesis of secondary metabolites and extracellular enzymes. Most of these pqs mutations affected genes which appear to encode PQS biosynthetic functions, although a transcriptional regulator and an apparent response effector were also represented. Two of the genes required for PQS synthesis (phnA and phnB) had previously been assumed to encode phenazine biosynthetic functions. The transcription of one of the genes required for PQS synthesis (PA2587/pqsH) was regulated by the LasI/R quorum-sensing system, thereby linking quorum sensing and PQS regulation. Others of the pleiotropic phenazine-minus mutations appear to inactivate novel components of the quorum-sensing regulatory network, including one regulator (np20) previously shown to be required for virulence in neutropenic mice.
Poxvirus Orthologous Clusters: toward Defining the Minimum Essential Poxvirus Genome (2003)

Increasingly complex bioinformatic analysis is necessitated by the plethora of sequence information currently available. A total of 21 poxvirus genomes have now been completely sequenced and annotated, and many more genomes will be available in the next few years. First, we describe the creation of a database of continuously corrected and updated genome sequences and an easy-to-use and extremely powerful suite of software tools for the analysis of genomes, genes, and proteins. These tools are available free to all researchers and, in most cases, alleviate the need for using multiple Internet sites for analysis. Further, we describe the use of these programs to identify conserved families of genes (poxvirus orthologous clusters) and have named the software suite POCs, which is available at www.poxvirus.org. Using POCs, we have identified a set of 49 absolutely conserved gene families-those which are conserved between the highly diverged families of insect-infecting entomopoxviruses and vertebrate-infecting chordopoxviruses. An additional set of 41 gene families conserved in chordopoxviruses was also identified. Thus, 90 genes are completely conserved in chordopoxviruses and comprise the minimum essential genome, and these will make excellent drug, antibody, vaccine, and detection targets. Finally, we describe the use of these tools to identify necessary annotation and sequencing updates in poxvirus genomes. For example, using POCs, we identified 19 genes that were widely conserved in poxviruses but missing from the vaccinia virus strain Tian Tan 1998 GenBank file. We have reannotated and resequenced fragments of this genome and verified that these genes are conserved in Tian Tan. The results for poxvirus genes and genomes are discussed in light of evolutionary processes.
Sphingolipid Mediators in Cardiovascular Cell Biology and Pathology (2001)

Sphingolipids have emerged as a new class of lipid mediators. In response to various extracellular stimuli, sphingolipid turnover can be stimulated in vascular cells and cardiac myocytes. Subsequent generation of sphingolipid molecules such as ceramide, sphingosine, and sphingosine-1-phosphate, is followed by regulation of ion fluxes and activation of various signaling pathways leading to smooth muscle cell proliferation, endothelial cell differentiation or apoptotic cell death, cell contraction, retraction, or migration. The importance of sphingolipids in cardiovascular signaling is illustrated by recent observations implicating them in physiological processes such as vasculogenesis as well as in frequent pathological conditions, including atherosclerosis and its complications.