gebhart/patrepeval huggingface dataset:
Antibodies of predetermined specificity against chemically synthesized peptides of human interleukin 2. (1984)

This communication describes the preparation of antibodies to human interleukin 2 (IL-2), using as immunogens synthetic peptides derived from the predicted amino acid sequence of IL-2. Rabbits and mice were immunized with protein carrier conjugates of eight chemically synthesized IL-2-derived peptides, each consisting of 13-15 amino acids. The immune antisera were screened in a solid-phase ELISA for reactivity to a native human IL-2. Antibodies to four of the eight peptides were found by a variety of biological and immuno-chemical criteria to react against human IL-2. Furthermore, an affinity-purified antibody to one of the IL-2 peptides (peptide 84) specifically stained the cytoplasm of phytohemagglutinin-stimulated human peripheral blood lymphocytes or T-leukemic cells (Jurkat). Antibodies to synthetic IL-2 peptides should serve as useful probes for studying this lymphokine and for developing quantitative assays for measuring its levels in biological fluids and its association with disease.
Large-Scale Proteomic Analysis of the Human Spliceosome (2002)

In a previous proteomic study of the human spliceosome, we identified 42 spliceosome-associated factors, including 19 novel ones. Using enhanced mass spectrometric tools and improved databases, we now report identification of 311 proteins that copurify with splicing complexes assembled on two separate pre-mRNAs. All known essential human splicing factors were found, and 96 novel proteins were identified, of which 55 contain domains directly linking them to functions in splicing/RNA processing. We also detected 20 proteins related to transcription, which indicates a direct connection between this process and splicing. This investigation provides the most detailed inventory of human spliceosome-associated factors to date, and the data indicate a number of interesting links coordinating splicing with other steps in the gene expression pathway.
Pumpless Respiratory Assistance Using a Membrane Oxygenator as an Artificial Placenta: A Preliminary Study in Newborn and Preterm Lambs (1995)

Newborns suffering from severe respiratory difficulties and not responding to conventional methods have been successfully treated by extracorporeal circulation with a membrane oxygenator (ECMO). However, the technique needs a highly specialized staff, excellent laboratory support, and continuous surveillance of the procedure to prevent complications. In a series of experiments on newborn and preterm lambs, we have investigated a relatively simpler technique of respiratory support that involves a pumpless arteriovenous bypass by cannulating both umbilical arteries and the umbilical vein. A highly efficient microporous membrane oxygenator (MO) with very low resistance was selected. This type of perfusion that mimics the placental circulation, besides providing an additional amount of oxygen to the blood, has proven to be very effective for CO2 extraction. Before its application in humans, however, improvements in the catheters to be inserted in the umbilical vessels, some modifications in the design of the MO, and improvements in the blood compatibility of all foreign surfaces in contact with blood are needed.
Mechanisms of angiogenic incompetence in Hutchinson–Gilford progeria via downregulation of endothelial NOS (2021)

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder with features of accelerated aging. The majority of HGPS cases are caused by a de novo point mutation in the LMNA gene (c.1824C>T; p.G608G) resulting in progerin, a toxic lamin A protein variant. Children with HGPS typically die from coronary artery diseases or strokes at an average age of 14.6 years. Endothelial dysfunction is a known driver of cardiovascular pathogenesis; however, it is currently unknown how progerin antagonizes normal angiogenic function in HGPS. Here, we use human iPSC-derived endothelial cell (iPSC-EC) models to study angiogenesis in HGPS. We cultured normal and HGPS iPSC-ECs under both static and fluidic culture conditions. HGPS iPSC-ECs show reduced endothelial nitric oxide synthase (eNOS) expression and activity compared with normal controls and concomitant decreases in intracellular nitric oxide (NO) level, which result in deficits in capillary-like microvascular network formation. Furthermore, the expression of matrix metalloproteinase 9 (MMP-9) was reduced in HGPS iPSC-ECs, while the expression of tissue inhibitor metalloproteinases 1 and 2 (TIMP1 and TIMP2) was upregulated relative to healthy controls. Finally, we used an adenine base editor (ABE7.10max-VRQR) to correct the pathogenic c.1824C>T allele in HGPS iPSC-ECs. Remarkably, ABE7.10max-VRQR correction of the HGPS mutation significantly reduced progerin expression to a basal level, rescued nuclear blebbing, increased intracellular NO level, normalized the misregulated TIMPs, and restored angiogenic competence in HGPS iPSC-ECs. Together, these results provide molecular insights of endothelial dysfunction in HGPS and suggest that ABE could be a promising therapeutic approach for correcting HGPS-related cardiovascular phenotypes.
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum* (2009)

Although some common patterns of gene expression exist across the pediatric SIRS, sepsis, and septic shock spectrum, septic shock is particularly characterized by repression of genes corresponding to adaptive immunity and zinc-related biology.
Quantitative Detection of EGFR Mutations in Circulating Tumor DNA Derived from Lung Adenocarcinomas (2011)

The major advantage of BEAMing is its ability to calculate the fraction of T790M-positive alleles from the alleles with activating mutations. This feature enables the detection of increases and decreases in the number of T790M mutations in cancer cells, regardless of normal cell DNA contamination, which may be useful for monitoring disease progression. Circulating tumor DNA could potentially be used as an alternative method for EGFR mutation detection.
Novel Small Molecule Entry Inhibitors of Ebola Virus (2015)

We have identified 2 novel EBOV inhibitors, MBX2254 and MBX2270, that can serve as starting points for the development of an anti-EBOV therapeutic agent. Our findings also highlight the importance of NPC1-GP interaction in EBOV entry and the attractiveness of NPC1 as an antifiloviral therapeutic target.
Genome-Wide Identification of Alternative Splice Forms Down-Regulated by Nonsense-Mediated mRNA Decay in Drosophila (2009)

Alternative mRNA splicing adds a layer of regulation to the expression of thousands of genes in Drosophila melanogaster. Not all alternative splicing results in functional protein; it can also yield mRNA isoforms with premature stop codons that are degraded by the nonsense-mediated mRNA decay (NMD) pathway. This coupling of alternative splicing and NMD provides a mechanism for gene regulation that is highly conserved in mammals. NMD is also active in Drosophila, but its effect on the repertoire of alternative splice forms has been unknown, as has the mechanism by which it recognizes targets. Here, we have employed a custom splicing-sensitive microarray to globally measure the effect of alternative mRNA processing and NMD on Drosophila gene expression. We have developed a new algorithm to infer the expression change of each mRNA isoform of a gene based on the microarray measurements. This method is of general utility for interpreting splicing-sensitive microarrays and high-throughput sequence data. Using this approach, we have identified a high-confidence set of 45 genes where NMD has a differential effect on distinct alternative isoforms, including numerous RNA-binding and ribosomal proteins. Coupled alternative splicing and NMD decrease expression of these genes, which may in turn have a downstream effect on expression of other genes. The NMD-affected genes are enriched for roles in translation and mitosis, perhaps underlying the previously observed role of NMD factors in cell cycle progression. Our results have general implications for understanding the NMD mechanism in fly. Most notably, we found that the NMD-target mRNAs had significantly longer 3' untranslated regions (UTRs) than the nontarget isoforms of the same genes, supporting a role for 3' UTR length in the recognition of NMD targets in fly.
Rapid detection and identification of mycobacteria in sputum samples by nested polymerase chain reaction and restriction fragment length polymorphisms of dnaJ heat shock protein gene. (1993)

In the diagnosis of mycobacterial infection, more than 4-8 weeks is required to identify the species of mycobacterium responsible for an infection. Therefore, the development of a method for the rapid detection and identification of mycobacteria is necessary for selecting an optimal therapeutic plan early in the patient's course. For this purpose, we developed a method combining a nested polymerase chain reaction (nested PCR) procedure and a restriction fragment length polymorphisms (RFLP) analysis of the dnaJ gene of mycobacteria, which codes for a heat shock protein. The PCR procedure allowed the sensitive detection of mycobacterial DNA in clinical samples. Using only 10 femtograms of mycobacterial DNA as a reaction mixture, a detectable band of target DNA segments could be yielded on an agarose gel. This indicates that even with a single genome amount, the PCR is able to detect mycobacteria. The RFLP analysis of the PCR products allowed us rapidly to distinguish the strains belonging to the M.tuberculosis complex from 11 different strains of nontuberculous mycobacteria. Within 2 days, the method is able to identify the mycobacterial species present in the sputum. Moreover, it has the advantage of not requiring the use of radioisotopes, which strongly enhances its clinical usefulness.
Cost-effectiveness of Extending Cervical Cancer Screening Intervals Among Women With Prior Normal Pap Tests (2006)

II-2.
Drosophila homologs of two mammalian intracellular Ca2+-release channels: identification and expression patterns of the inositol 1,4,5- triphosphate and the ryanodine receptor genes (1992)

We have identified and cloned portions of two Drosophila genes homologous to two classes of mammalian intracellular Ca(2+)-release channels, the ryanodine receptor and the inositol 1,4,5-triphosphate (IP3) receptor. The Drosophila ryanodine receptor gene (dry) encodes an approx. 15 kb mRNA. It is expressed in the mesoderm of early stage-9 embryos and subsequently in somatic muscles and their precursor cells. In adults, dry mRNA was detected in tubular muscles and at a lower level in neuronal tissues. Embryonic expression of the Drosophila IP3 receptor gene (dip) appears more dynamic and is associated with developing anterior sense organs. In adults, dip expression occurs in several tissues, and relatively high levels of dip mRNA in adult antennae suggest a role for this gene product during olfactory transduction.
Loop-mediated isothermal amplification of DNA (2000)

We have developed a novel method, termed loop-mediated isothermal amplification (LAMP), that amplifies DNA with high specificity, efficiency and rapidity under isothermal conditions. This method employs a DNA polymerase and a set of four specially designed primers that recognize a total of six distinct sequences on the target DNA. An inner primer containing sequences of the sense and antisense strands of the target DNA initiates LAMP. The following strand displacement DNA synthesis primed by an outer primer releases a single-stranded DNA. This serves as template for DNA synthesis primed by the second inner and outer primers that hybridize to the other end of the target, which produces a stem-loop DNA structure. In subsequent LAMP cycling one inner primer hybridizes to the loop on the product and initiates displacement DNA synthesis, yielding the original stem-loop DNA and a new stem-loop DNA with a stem twice as long. The cycling reaction continues with accumulation of 10(9) copies of target in less than an hour. The final products are stem-loop DNAs with several inverted repeats of the target and cauliflower-like structures with multiple loops formed by annealing between alternately inverted repeats of the target in the same strand. Because LAMP recognizes the target by six distinct sequences initially and by four distinct sequences afterwards, it is expected to amplify the target sequence with high selectivity.
THERMAL INACTIVATION KINETICS of TRYPSIN AT ASEPTIC PROCESSING TEMPERATURES (1993)

Kinetics of thermal inactivation of trypsin (bovine pancreas) were evaluated in the temperature range, 90–130C, common to aseptic processing of high/low acid foods. Aliquots of trypsin in buffer, at three pH values, 3.8, 5.1 and 6.0, were subjected to selected heat treatments at various temperatures. Kinetic parameters were evaluated from the residual enzyme activity. Reference k and D values (at 121.1C) ranged from 0.0719 to 0.349 min −1 and 32.0 to 6.6 min, and E a and z values ranged from 84.9 to 69.9 kJ/mole and 33.1 to 39.9C, respectively, in the pH range 3.8–6.0. the thermal inactivation resistance of trypsin in the acid and low acid pH range makes it a potential bioindicator for high temperature thermal processes.
Real world drug discovery: a chemist's guide to biotech and pharmaceutical research (2009)

Drug discovery increasingly requires a common understanding by researchers of the many and diverse factors that go into the making of new medicines. The scientist entering the field will immediately face important issues for which his education may not have prepared him: project teams, patent law, consultants, target product profiles, industry trends, Gantt charts, target validation, pharmacokinetics, proteomics, phenotype assays, biomarkers, and many other unfamiliar topics for which a basic understanding must somehow be obtained. Even the more experienced scientist can find it frustratingly difficult to get an overview of the many factors involved in modern drug discovery and often only after years of exploring does a whole and integrated picture emerge in the mind of the researcher. Real World Drug Discovery: A Chemist's Guide to Biotech and Pharmaceutical Research presents this kind of map of the landscape of drug discovery. In a single, readable volume it outlines processes and explains essential concepts and terms for the recent science graduate wondering what to expect in pharma or biotech, the medicinal chemist seeking a broader and more timely understanding of the industry, or the contractor or collaborator whose understanding of the commercial drug discovery process could increase the value of his contribution to it. This book includes interviews with well-known experts in many of the fields involved, giving insightful comments from authorities on many of the sub-disciplines important to cutting-edge drug discovery. It provides helpful suggestions gleaned from years of experience in biotech and pharma, which represents a repository drug discovery 'lore' not previously available in any book. It includes a 'Periodic Table of Drugs' listing current top-selling drugs arranged by target and laid out so that structural similarities and differences are plain and clear, with regular updates available at the book's website. It extensively uses diagrams to illustrate concepts like biotech startup models, preteomic profiling for target identification, Gantt charts for project planning, etc.
Activation of Mitogen-Activated Protein Kinase Kinase by v-Raf in NIH 3T3 Cells and in Vitro (1992)

Mitogen-activated protein (MAP) kinases are 42- and 44-kD serine-threonine protein kinases that are activated by tyrosine and threonine phosphorylation in cells stimulated with mitogens and growth factors. MAP kinase and the protein kinase that activates it (MAP kinase kinase) were constitutively activated in NIH 3T3 cells infected with viruses containing either of two oncogenic forms (p35EC12, p3722W) of the c-Raf-1 protein kinase. The v-Raf proteins purified from cells infected with EC12 or 22W viruses activated MAP kinase kinase from skeletal muscle in vitro. Furthermore, a bacterially expressed v-Raf fusion protein (glutathione S-transferase-p3722W) also activated MAP kinase kinase in vitro. These findings suggest that one function of c-Raf-1 in mitogenic signaling is to phosphorylate and activate MAP kinase kinase.
Biodistribution of a Bispecific Single-chain Diabody and Its Half-life Extended Derivatives (2009)

Small recombinant antibody molecules such as bispecific single-chain diabodies (scDb) possessing a molecular mass of approximately 55 kDa are rapidly cleared from circulation. We have recently extended the plasma half-life of scDb applying various strategies including PEGylation, N-glycosylation and fusion to an albumin-binding domain (ABD) from streptococcal protein G. Here, we further analyzed the influence of these modifications on the biodistribution of a scDb directed against carcinoembryonic antigen (CEA) and CD3 capable of retargeting T cells to CEA-expressing tumor cells. We show that a prolonged circulation time results in an increased accumulation in CEA+ tumors, which was most pronounced for scDb-ABD and PEGylated scDb. Interestingly, tumor accumulation of the scDb-ABD fusion protein was approximately 2-fold higher compared with PEGylated scDb, although both molecules exhibit similar plasma half-lives and similar affinities for CEA. Comparing half-lives in neonatal Fc receptor (FcRn) wild-type and FcRn heavy chain knock-out mice the contribution of the FcRn to the long plasma half-life of scDb-ABD was confirmed. The half-life of scDb-ABD was approximately 2-fold lower in the knock-out mice, while no differences were observed for PEGylated scDb. Binding of the scDb derivatives to target and effector cells was not or only marginally affected by the modifications, although, compared with scDb, a reduced cytotoxic activity was observed for scDb-ABD, which was further reduced in the presence of albumin. In summary, these findings demonstrate that the extended half-life of a bispecific scDb translates into improved accumulation in antigen-positive tumors but that modifications might also affect scDb-mediated cytotoxicity.
Are Antipsychotics Effective for the Treatment of Anorexia Nervosa? (2012)

Although limited by small samples, this meta-analysis failed to demonstrate antipsychotic efficacy for body weight and related outcomes in females with anorexia nervosa.
Robust Mouse Tracking in Complex Environments using Neural Networks (2018)

Abstract The ability to track animals accurately is critical for behavioral experiments. For video-based assays, this is often accomplished by manipulating environmental conditions to increase contrast between the animal and the background, in order to achieve proper foreground/background detection (segmentation). However, as behavioral paradigms become more sophisticated with ethologically relevant environments, the approach of modifying environmental conditions offers diminishing returns, particularly for scalable experiments. Currently, there is a need for methods to monitor behaviors over long periods of time, under dynamic environmental conditions, and in animals that are genetically and behaviorally heterogeneous. To address this need, we developed a state-of-the-art neural network-based tracker for mice, using modern machine vision techniques. We test three different neural network architectures to determine their performance on genetically diverse mice under varying environmental conditions. We find that an encoder-decoder segmentation neural network achieves high accuracy and speed with minimal training data. Furthermore, we provide a labeling interface, labeled training data, tuned hyperparameters, and a pre-trained network for the mouse behavior and neuroscience communities. This general-purpose neural network tracker can be easily extended to other experimental paradigms and even to other animals, through transfer learning, thus providing a robust, generalizable solution for biobehavioral research.
Electric vehicle charging and grid constraints: Comparing distributed and centralized approaches (2013)

The expected rise of electric vehicles will lead to significant additional demand on low voltage (LV) distribution systems. Uncontrolled charging could lead to problems such as thermal overload of transformers and lines, voltage deviation, harmonics, and phase unbalance. We propose two electric vehicle charging algorithms, one centralized and one distributed, and compare their performance in simulations that use real vehicle data, on a model based on a real LV network in northern Melbourne, Australia. Our experiments confirm that the locations of the vehicles in the network are an important factor in predicting adverse effects. Furthermore, our coordinated charging solutions allow penetrations of electric vehicles approximately 3-6 times higher than is possible using uncoordinated charging, in our network.
Specific Reading Disability: Differences in Contrast Sensitivity as a Function of Spatial Frequency (1980)

Contrast thresholds for sine-wave gratings of spatial frequencies of 2, 4, 12, and 16 cycles per degree were determined for normal and disabled readers at a range of stimulus durations. Normal readers demonstrated monotonically decreasing sensitivity with increasing spatial frequency at exposure durations between 40 and 100 milliseconds. At exposure durations of 150 to 1000 milliseconds, they showed peak sensitivity at 4 cycles per degree. In comparison, disabled readers showed monotonically decreasing sensitivity with increasing spatial frequency at all stimulus durations. The difference in sensitivity pattern across spatial frequencies was greatest at stimulus durations approximately equal to fixation durations during reading.
Distinct autophosphorylation sites sequentially produce autonomy and inhibition of the multifunctional Ca2+/calmodulin-dependent protein kinase (1989)

The multifunctional Ca2+/calmodulin-dependent protein kinase (multifunctional CaM kinase) may be an important mediator for neurotransmitters and hormones that utilize Ca2+ as a "second messenger." We examined the ability of autophosphorylation to convert the multifunctional CaM kinase to a Ca2+/calmodulin-independent (autonomous) form to determine whether autophosphorylation is a mechanism for short- or long-term enhancement of Ca2+ action. As the kinase incorporates phosphate during continuous stimulation by Ca2+/calmodulin, its ability to phosphorylate exogenous substrates becomes increasingly autonomous. Withdrawal of Ca2+ after a critical level of phosphate incorporation is reached leads to a "burst" or rapid increase in Ca2+-independent autophosphorylation. The "burst" of autophosphorylation is distinct from the initial Ca2+-dependent autophosphorylation, however, since it inhibits substrate phosphorylation. Both Ca2+-dependent and Ca2+-independent substrate phosphorylation are inhibited by this autonomous autophosphorylation. Thus, autophosphorylation has a dual role in modulating the activity of multifunctional CaM kinase. It initially enables the kinase to continue phosphorylating substrates after Ca2+ levels decline, but it eventually suppresses this autonomous activity. Tryptic phosphopeptide mapping demonstrates that appearance of phosphothreonine-containing peptides is common to several conditions used to generate an autonomous enzyme. Sequencing reveals the critical "autonomy" site to be threonine286. The inhibitory mode of autophosphorylation involves 3 additional phosphopeptides containing a serine and a threonine residue.