gebhart/patrepeval huggingface dataset:
Immune responses to human tumors: development of tumor vaccines. (2003)

Strong evidence has been accumulated demonstrating that tumor cells in humans and animal are recognized in general as non-self by the immune system and they are able to induce an immune response which often leads to their elimination. In humans, this evidence includes: (a) The development of T-cell lines and clones with antitumor activity (cytotoxic or helper) which is restricted to autologous tumor cells or to cells expressing the same tumor peptide/HLA epitope; (b) the presence of oligoclonal T cells infiltrating many tumors; (c) the identification and molecular cloning of tumor antigens and of peptides derived from these antigens, which elicit HLA-restricted immune responses. Their discovery provided the ultimate proof for the presence of specific immune responses in human tumors. The availability for the first time of molecularly cloned tumor antigens permitted the development of peptide or recombinant tumor vaccines. Although significant progress has been made and tumor peptide vaccines capable of eliciting biological responses in more than 50% of the patients and objective clinical responses in 10 to 42% of the patients have been reported, certain major problems remain and need to be resolved in order to develop effective tumor vaccines. These problems emanate from the following mechanisms that the tumor cells are employing to avoid detection and destruction by the immune system: (i) Down-regulation of HLA class I expression on the surface of tumor cells; (ii) Down-regulation of tumor antigen expression or selection of negative tumor variants; (iii) Expression of naturally occurring altered peptide ligands by tumor cells; (iv) Lack of costimulatory molecules on tumors cells; (v) Production of immunosuppressive cytokines, such as TGF-beta and IL-10; (vi) Induction of lymphocyte apoptosis by tumor cells using the Fas/Fas L pathway; (vii) Down-regulation or absence of CD3 zeta (zeta) transcripts or protein in tumor-infiltrating lymphocytes (TIL), and others. The selection of optimal tumor antigens for vaccine development is another issue that requires attention. Lineage specific or differentiation antigens appear to be better candidates for the development of tumor vaccines because they are expressed in all tumor cells. Methods for antigen presentation, such as those using dendritic cells, also play a critical role in the development of tumor vaccines. In addition to the progress towards the development of tumor vaccines, substantial progress has been made in developing advanced methods of adoptive immunotherapy based on TIL. This approach can be effective when an immune response can not be elicited in vivo. The progress made towards the development of tumor vaccines and approaches for adoptive immunotherapy has been substantial. Additional studies need to be carried out to develop new and effective tumor vaccines and adoptive immunotherapy methods.
Biotinylated recombinant human erythropoietins: bioactivity and utility as receptor ligand [see comments] (1989)

Recombinant human erythropoietin labeled covalently with biotin at sialic acid moieties has been prepared, and has been shown to possess high biological activity plus utility as a receptor ligand. Initially, the effects on biological activity of covalently attaching biotin to erythropoietin alternatively at carboxylate, amino, or sialic acid groups were compared. Biotinylation of erythropoietin at carboxylate groups using biotin-amidocaproyl hydrazide plus 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide led to substantial biological inactivation, although biotinylated molecules retained detectable activity when prepared at low stoichiometries. Biotinylation at amino groups using sulfosuccinimidyl 6-(biotinamido) hexanoate resulted in a high level of biological inactivation with little, if any, retention of biological activity, regardless of labeling stoichiometries. Biotinylation at sialic acid moieties using periodate and biotinamidocaproyl hydrazide proceeded efficiently (greater than 95% and 80% labeling efficiencies for human urinary and recombinant erythropoietin, respectively) and yielded stably biotinylated erythropoietin molecules possessing comparably high biological activity (ie, 45% of the activity of unmodified hormone). Utility of recombinant biotin-(sialyl)-erythropoietin (in combination with 125I-streptavidin) in the assay of cell surface receptors was demonstrated using two distinct murine erythroleukemia cell lines, Friend 745 and Rauscher Red 1. The densities and affinities of specific hormone binding sites were 116 +/- 4 sites, 3.3 +/- 0.4 nmol/L kd and 164 +/- 5 sites, 2.7 +/- 0.4 nmol/L kd, respectively. It is predicted that the present development of biotin-(sialyl)-erythropoietin as a chemically and biologically stable, bioactive ligand will assist in advancing an understanding of the regulated expression and physicochemistry of the human and murine erythropoietin receptors.
THE GENETICS OF PSORIASIS AND AUTOIMMUNITY (2005)

Psoriasis is an inflammatory/autoimmune disease and, as with many autoimmune diseases, is associated with alleles from the major histocompatibility complex (MHC). With psoriasis and autoimmune disease, the penetrance of the MHC-associated alleles is never 100%, even for monozygotic twins. This may be because development requires additional environmental and/or genetic modifiers or requires specific T-cell receptor arrangements. Families segregating single or multilocus susceptibility alleles other than the MHC have also been reported. Overlapping genetic locations of loci for different autoimmune diseases have been known for several years and are starting to reveal common genes or genetic variants. These include genes normally involved in preventing spontaneous T-cell activation or proliferation, immune synapse formation, or cytokine production via pathways such as those mediated by NFkappaB and those involved in thymic selection. Autoimmunity may also involve dysregulation of genes or pathways regulated by the RUNX family of transcription factors. RUNX is involved in hematopoietic cell development, development of T cells in the thymus, chromatin remodeling, and gene silencing. Hence, its effect on cells of the immune system may be due to variable changes in gene expression and could account for variable body surface involvement and waxing and waning of disease.
Sepsis-associated encephalopathy and its differential diagnosis (2009)

Sepsis is often complicated by an acute and reversible deterioration of mental status, which is associated with increased mortality and is consistent with delirium but can also be revealed by a focal neurologic sign. Sepsis-associated encephalopathy is accompanied by abnormalities of electroencephalogram and somatosensory-evoked potentials, increased in biomarkers of brain injury (i.e., neuron-specific enolase, S-100 beta-protein) and, frequently, by neuroradiological abnormalities, notably leukoencephalopathy. Its mechanism is highly complex, resulting from both inflammatory and noninflammatory processes that affect all brain cells and induce blood-brain barrier breakdown, dysfunction of intracellular metabolism, brain cell death, and brain injuries. Its diagnosis relies essentially on neurologic examination that can lead one to perform specific neurologic tests. Electroencephalography is required in the presence of seizure; neuroimaging in the presence of seizure, focal neurologic signs or suspicion of cerebral infection; and both when encephalopathy remains unexplained. In practice, cerebrospinal fluid analysis should be performed if there is any doubt of meningitis. Hepatic, uremic, or respiratory encephalopathy, metabolic disturbances, drug overdose, withdrawal of sedatives or opioids, alcohol withdrawal delirium, and Wernicke's encephalopathy are the main differential diagnoses of sepsis-associated encephalopathy. Patient management is based mainly on controlling infection, organ system failure, and metabolic homeostasis, at the same time avoiding neurotoxic drugs.
Variable structure control of nonlinear multivariable systems: a tutorial (1988)

The design of variable-structure control (VSC) systems for a class of multivariable, nonlinear, time-varying systems is presented. Using the Utkin-Drazenovic method of equivalent control and generalized Lyapunov stability concepts, the VSC design is described in a unified manner. Complications that arise due to multiple inputs are examined, and several approaches useful in overcoming them are developed. Recent developments are investigated, as is the kinship of VSC and the deterministic approach to the control of uncertain systems. All points are illustrated by numerical examples. The recent literature on VSC applications is surveyed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Identification of Indacaterol as an Ultralong-Acting Inhaled β2-Adrenoceptor Agonist (2010)

Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.
Overnight pulse oximetry in normal children and in children undergoing adenotonsillectomy (1996)

This study investigates the hypoxia that has been described during sleep in children admitted for adenotonsillectomy. Two hundred and twenty-two randomly selected children and 33 children awaiting adenotonsillectomy had overnight pulse oximetry performed at home. Children undergoing surgery had a second study in hospital on the eve of surgery and a third at home 3 months post-operation. Analysis of pulse oximetry data failed to detect a clinically significant difference in oxygen saturation levels between these populations. Snoring is reported in 76% of children undergoing adenotonsillectomy and 11% of the normal population. Sleep apnoeic episodes occur in 52% of children prior to surgery compared with 8% of the normal population. Overnight pulse oximetry has failed to differentiate children with symptoms suggestive of obstructive sleep apnoea from the normal population. Its use as a screening procedure should be used with caution until more is known about its ability to predict significant disease.
Making Drugs Out of Oligonucleotides: A Brief Review and Perspective (1999)

I provide a brief review and perspective thoughts concerning the antisense oligonucleotide, drug discovery paradigm.
Characterization of a Cofactor That Regulates Dimerization of a Mammalian Homeodomain Protein (1991)

Dimerization among transcription factors has become a recurrent theme in the regulation of eukaryotic gene expression. Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) is a homeodomain-containing protein that functions as a dimer. A dimerization cofactor of HNF-1 alpha (DCoH) was identified that displayed a restricted tissue distribution and did not bind to DNA, but, rather, selectively stabilized HNF-1 alpha dimers. The formation of a stable tetrameric DCoH-HNF-1 alpha complex, which required the dimerization domain of HNF-1 alpha, did not change the DNA binding characteristics of HNF-1 alpha, but enhanced its transcriptional activity. However, DCoH did not confer transcriptional activation to the GAL4 DNA binding domain. These results indicate that DCoH regulates formation of transcriptionally active tetrameric complexes and may contribute to the developmental specificity of the complex.
N-(2,3-Butadienyl)-1,4-butanediamine derivatives: potent irreversible inactivators of mammalian polyamine oxidase (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTN-(2,3-Butadienyl)-1,4-butanediamine derivatives: potent irreversible inactivators of mammalian polyamine oxidasePhilippe Bey, Frank N. Bolkenius, Nikolaus Seiler, and Patrick CasaraCite this: J. Med. Chem. 1985, 28, 1, 1–2Publication Date (Print):January 1, 1985Publication History Published online1 May 2002Published inissue 1 January 1985https://pubs.acs.org/doi/10.1021/jm00379a001https://doi.org/10.1021/jm00379a001research-articleACS PublicationsRequest reuse permissionsArticle Views321Altmetric-Citations99LEARN 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
How to Make a Multiprocessor Computer That Correctly Executes Multiprocess Programs (1979)

Many large sequential computers execute operations in a different order than is specified by the program. A correct execution is achieved if the results produced are the same as would be produced by executing the program steps in order. For a multiprocessor computer, such a correct execution by each processor does not guarantee the correct execution of the entire program. Additional conditions are given which do guarantee that a computer correctly executes multiprocess programs.
The structural basis of protein folding and its links with human disease (2001)

The ability of proteins to fold to their functional states following synthesis in the intracellular environment is one of the most remarkable features of biology. Substantial progress has recently been made towards understanding the fundamental nature of the mechanism of the folding process. This understanding has been achieved through the development and concerted application of a variety of novel experimental and theoretical approaches to this complex problem. The emerging view of folding is that it is a stochastic process, but one biased by the fact that native-like interactions between residues are on average more stable than non-native ones. The sequences of natural proteins have emerged through evolutionary processes such that their unique native states can be found very efficiently even in the complex environment inside a living cell. But under some conditions proteins fail to fold correctly, or to remain correctly folded, in living systems, and this failure can result in a wide range of diseases. One group of diseases, known as amyloidoses, which includes Alzheimer's and the transmissible spongiform encephalopathies, involves deposition of aggregated proteins in a variety of tissues. These diseases are particularly intriguing because evidence is accumulating that the formation of the highly organized amyloid aggregates is a generic property of polypeptides, and not simply a feature of the few proteins associated with recognized pathological conditions. That such aggregates are not normally found in properly functional biological systems is again a testament to evolution, in this case of a variety of mechanisms inhibiting their formation. Understanding the nature of such protective mechanisms is a crucial step in the development of strategies to prevent and treat these debilitating diseases.
Physically Inspired Neural Network Model for RF Power Amplifier Behavioral Modeling and Digital Predistortion (2011)

In this paper, a novel two hidden layers artificial neural network (2HLANN) model is proposed to predict the dynamic nonlinear behavior of wideband RF power amplifiers (PAs). Starting with a generic low-pass equivalent circuit of the PA, several circuit transformations are applied in order to build an appropriate artificial neural network structure and improve the modeling accuracy. This approach culminates in the development of a real-valued and feed-forward 2HLANN-based model. The parameters (number of neurons, memory depth, etc.) of the proposed model and the back propagation learning algorithm (learning rate, momentum term, etc.) used for its training were carefully studied and thoughtfully chosen to ensure the generality of the constructed model. The validation of the proposed models in mimicking the behavior of a 250-W Doherty amplifier driven with a 20-MHz bandwidth signal is carried out in terms of its accuracy in predicting its output spectrum, dynamic AM/AM and AM/PM characteristics, and in minimizing the normalized mean square error. In addition, the linearization of the Doherty PA using the 2HLANN enabled attaining an output power of up to 46.5 dBm and an average efficiency of up to 40% coupled with an adjacent channel power ratio higher than 50 dBc.
On the Inheritance of Handedness (1968)

Journal Article On the Inheritance of Handedness: I. Laterality in Inbred Mice Get access ROBERT L. COLLINS ROBERT L. COLLINS The author is associated staff ScientistThe Jackson LaboratoryBar Harbour, Maine 04609 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Heredity, Volume 59, Issue 1, January 1968, Pages 9–12, https://doi.org/10.1093/oxfordjournals.jhered.a107656 Published: 01 January 1968
Syntheses of Nucleosides Designed for Combinatorial DNA Sequencing (1999)

Fluorescent and photolabile nucleotide analogues 1 and 2 were prepared to test an unconventional approach to DNA sequencing that, ideally, would not involve gel electrophoresis. These particular compounds were not incorporated, but modeling studies indicate how further refinements to their structures could facilitate the proposed sequencing scheme. B = adenine, thymine; TP = triphosphate,
Sequence-selective DNA binding to the regulatory subunit of cAMP-dependent protein kinase (1989)

The fluorescence of Trp-226 in the regulatory subunit of bovine type II cAMP-dependent protein kinase is unaffected by the binding of cAMP, but is quenched by the binding of 2'-dansyl-cAMP (DNS-cAMP). Up to 67% of the fluorescence of Trp-226 can be quenched by resonant energy transfer to the DNS-cAMP bound to the first site, and 96% of the fluorescence can be quenched by saturating both sites with DNS-cAMP. The observed efficiencies of energy transfer gave a distance of 16 A between Trp-226 and the DNS-cAMP bound at the first site and a distance of 12.7 A between Trp-226 and the DNS-cAMP bound at second site. The fluorescence of Trp-226 was suppressed by incubation of RII with the self-complementary octanucleotide TGACGTCA (CRE) due to binding of the oligonucleotide to RII. A detailed study of the binding equilibrium showed that each RII(cAMP)2 molecule binds 1 molecule of CRE with Kd = 80 nM. The corresponding Kd value for cAMP-depleted RII was found to be 25-fold higher. RII was also found to bind randomly selected DNA fragments with an average Kd value much higher than that of CRE. These observations show for the first time that the binding of oligonucleotide to RII is cAMP-enhanced and sequence-selective.
Characterization of a cis-acting regulatory mutation that maps at the distal end of the Escherichia coli glyA gene (1985)

We have isolated a phage Mu cts-generated glyA mutant with only 30% of the normal level of serine hydroxymethyltransferase activity. Genetic and physical mapping studies show that Mu cts has inserted between the end of the glyA structural gene and its proposed transcription termination site. The mutation is cis acting and shows that sequences distal to the glyA structural gene play an important role in the expression of this gene.
Handbook of bioseparations (2000)

Preface. S. Ahuja, Bioseparations: An Overview. D.O. O'Keefe, Analysis of Protein Impurities in Pharmaceuticals Derived from Recombinant DNA. M.T.W. Hearn, Physicochemical Factors in Polypeptide and Protein Purification and Analysis by High Performance Liquid Chromatographic Techniques. S.Ahuja, Capillary Electrophoresis of Compounds of Biological Interest. D.E. Garfin, Isoelectric Focusing. D. Gibson, C.E. Costello, Mass Spectrometry of Biomolecules. T. Gu, Liquid-Liquid Partitioning Methods for Bioseparations. R. Harve, R. Bajpai, Separation of Nucleic Acids and Proteins. A.A. Shukla, S.M. Cramer, Bioseparations by Displacement Chromatography. B. Mattiasson, M.P.Nandakumar, Physicochemical Basis for Expanded-Bed Adsorption for Protein Purification. J. Shiloach, R.M. Kennedy, Expanded-Bed Adsorption Process for Protein Capture. R.R. Deshmukh, T.N. Warner, Adsorptive Membranes for Bioseparations. R.M.Nicoud, Simulated Moving Bed Chromatography for Biomolecules. R.R. Deshmukh, W.E. Leitch II, Y.S. Sanghvi, D.L. Cole, Large-Scale Chromatographic Purification of Oligonucleotides. E. Boschetti, A. Jungbauer, Separation of Antibodies by Liquid Chromatograpy. P. Bowles, Processing Plants and Equipment. R.M. Price, A. Sadana, Engineering Process Control of Biosepartion Processes. A. Ramakrishnan, A. Sadana, Economics of Bioseparation Processes. S. Ahuja, Future Developments. Index.
Space-variant holographic optical elements for switching networks and general interconnects (1991)

Optical interconnects enable the transmission of signals with ultra high frequencies with small crosstalk and rather low waste energy per transmission line. Two fields of application for optical wiring concepts can be discerned, i.e. fixed pattern chip to chip (or board to board) interconnects and reconfigurable switching networks or bus systems where the interconnect path is selected out of a number of fixed interconnects by means of e.g. so-called exchange bypass modules (EBM) 1,2 .
Micromechanical mass sensors for biomolecular detection in a physiological environment (2005)

Micromechanical cantilever arrays are used to measure time-resolved adsorption of tiny masses based on protein-ligand interactions. Here, streptavidin-biotin interactions are investigated in a physiological environment. A measurement method is introduced using higher flexural modes of a silicon cantilever in order to enhance the sensitivity of mass detection. Modeling the cantilever vibration in liquid allows the measurement of absolute mass changes. We show time-resolved mass adsorption of final 7+/-0.7 ng biotinylated latex beads. The sensitivity obtained is about 2.5 pg/Hz measuring at a center frequency of 750 kHz.