gebhart/patrepeval huggingface dataset:
Engineering and characterization of a murine MHC class II- immunoglobulin chimera expressing an immunodominant CD4 T viral epitope (1997)

T cells recognize peptides derived from the processing of proteins by antigen presenting cells (APCs) in association with the major histocompatibility complex (MHC) molecules. We have engineered a murine MHC class II antigen presenting molecule consisting of the extracellular domains of I-E(d)alpha and I-E(d)beta chains to which the CD4 T cell immunodominant epitope HA110-120 of the hemagglutinin (HA) of the A/PR/8/34 influenza virus was covalently linked at the N-terminus of the I-E(d)beta chain. The HA110-120-I-E(d)alphabeta complex was dimerized by the Fc portion of an IgG2a linked at the C-terminus of the I-E(d)beta chain. SF9 insect cells infected with baculovirus carrying both I-E(d)alpha and HA110-120-I-E(d)beta-Fcgamma2a genes, secreted a disulfide-stabilized dimer of the HA110-120-I-E(d)alphabeta-Fcgamma2a molecule, designated as DEF. The chimeric molecule preserved the structural integrity of both MHC-peptide complex and Fc portion of IgG2a, and was able to: (i) bind specifically to the cognate T cell receptors (TCRs) and to the immunoglobulin FcgammaRII receptor (FcR), (ii) induce complement-mediated cell cytotoxicity, and (iii) trigger early production of IL-2 in cognate T cells. Chimeric antigen presenting molecules with these characteristics may represent a novel platform for the development of immunomodulatory agents of therapeutic use.
AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease (2015)

The most common form of the childhood neurodegenerative disease late infantile neuronal ceroid lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene. We tested whether TPP1 gene transfer to the ependyma, the epithelial lining of the brain ventricular system, in TPP1-deficient dogs would be therapeutically beneficial. A one-time administration of recombinant adeno-associated virus (rAAV) expressing canine TPP1 (rAAV.caTPP1) resulted in high expression of TPP1 predominantly in ependymal cells and secretion of the enzyme into the cerebrospinal fluid leading to clinical benefit. Diseased dogs treated with rAAV.caTPP1 showed delays in onset of clinical signs and disease progression, protection from cognitive decline, and extension of life span. By immunostaining and enzyme assay, recombinant protein was evident throughout the brain and spinal cord, with correction of the neuropathology characteristic of the disease. This study in a naturally occurring canine model of TPP1 deficiency highlights the utility of AAV transduction of ventricular lining cells to accomplish stable secretion of recombinant protein for broad distribution in the central nervous system and therapeutic benefit.
The druggable genome and support for target identification and validation in drug development (2017)

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease.
Design and analysis of multiple-bus arbiters with different priority schemes (2002)

The authors present four multiple-user and multiple-server arbiter designs of multiple-bus multiprocessors. All designs are based on decentralized control, which has the advantage of good reliability and potentially high throughput. The priority protocols considered are fixed priority, rotating priority, round-robin priority, and equal priority. For the first two priority protocols, lookahead techniques are used to speed up the arbitration process. The round-robin protocol is based on the decentralized daisy-chain idea and is operated in an asynchronous fashion. Analytical models are developed for the four different priority protocols to evaluate the performance of the different designs. The analyses are based on a probabilistic model for the synchronous case and simple queuing analysis for the asynchronous system. Numerical results obtained from the proposed model show that the equal priority protocol performs better than the others in the system with a few buses. The performance difference is not significant when the number of buses is relatively large.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Isotropic inverse-problem approach for two-dimensional phase unwrapping (2015)

We propose a new technique for two-dimensional phase unwrapping. The unwrapped phase is found as the solution of an inverse problem that consists in the minimization of an energy functional. The latter includes a weighted data fidelity term that favors sparsity in the error between the true and wrapped phase differences, as well as a regularizer based on higher-order total variation. One desirable feature of our method is its rotation invariance, which allows it to unwrap a much larger class of images compared to the state of the art. We demonstrate the effectiveness of our method through several experiments on simulated and real data obtained through the tomographic phase microscope. The proposed method can enhance the applicability and outreach of techniques that rely on quantitative phase evaluation.
Autophosphorylation at Thr 286 of the α Calcium-Calmodulin Kinase II in LTP and Learning (1998)

The calcium-calmodulin-dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the alphaCaMKII gene that blocked the autophosphorylation of threonine at position 286 (Thr286) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N-methyl-D-aspartate receptor-dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of alphaCaMKII at Thr286 appears to be required for LTP and learning.
The insulin-like growth factor I receptor: a key to tumor growth? (1995)

The insulin-like growth factor I receptor (IGF-IR) belongs to the family of transmembrane tyrosine kinase receptors, like the receptors for platelet-derived growth factor, the epidermal growth factor, insulin, and others. Genetic evidence has shown that the IGF-IR is required for optimal growth in vitro and in vivo. Even more important, however, have been recent findings from several laboratories clearly showing that the IGF-IR is an absolute requirement for the establishment and maintenance of the transformed phenotype, both in vivo and in vitro and in several cell types. These findings indicate that the IGF-IR plays a central role in the mechanism of transformation and, as such, could be a preferred target for therapeutic interventions.
Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet -granule biogenesis (2005)

Bleeding problems are associated with defects in platelet alpha-granules, yet little is known about how these granules are formed and released. Mutations affecting VPS33B, a novel Sec1/Munc18 protein, have recently been linked to arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome. We have characterized platelets from patients with ARC syndrome and observed reduced aggregation with arachidonate and adenosine diphosphate (ADP). Structural abnormalities seen in ARC platelets included increased platelet size, a pale appearance in blood films, elevated numbers of delta-granules, and completely absent alpha-granules. Soluble and membrane-bound alpha-granule proteins were significantly decreased or undetectable in ARC platelets, suggesting that both the releasable protein pools and membrane components of alpha-granules were absent. The role of VPS33B in platelet granule biogenesis was evaluated by immunofluorescence microscopy in normal human megakaryocytes. VPS33B colocalized appreciably with markers of alpha-granules, moderately with late endosomes/lysosomes, minimally with delta-granules/lysosomes, and not with cis-Golgi complexes. VPS33B protein expression determined by immunoblotting confirmed the presence of VPS33B in control fibroblasts but not in ARC fibroblasts, and in normal megakaryocytes but not in platelets. We conclude that like other Sec1/Munc18 proteins, VPS33B is involved in intracellular vesicle trafficking, being essential for the development of platelet alpha-granules but not for granule secretion.
Solubilization, purification, and characterization of an inositol trisphosphate receptor. (1988)

Inositol 1,4,5-trisphosphate is a second messenger of the phosphoinositide system which can mobilize calcium from intracellular stores. Rat cerebellum is an abundant source of a receptor for inositol 1,4,5-trisphosphate (Worley, P. F., Baraban, J. M., Supattapone, S., Wilson, V. S., and Snyder, S. H. (1987) J. Biol. Chem. 262, 12132-12136). In this study we have solubilized and purified this receptor to apparent homogeneity from rat cerebellum. Crude membrane, detergent-solubilized, and purified receptor preparations display similar selectivity for inositol 1,4,5-trisphosphate over other inositol phosphates. The purified receptor is globular with a Stokes' radius of approximately 10 nm. Electrophoretic analysis reveals one protein band with an Mr of 260,000. While binding is reversibly inhibited by 300 nM calcium in particulate fractions and detergent-solubilized membranes, the purified protein is not inhibited by calcium concentrations up to 1.5 mM. Inhibition by calcium is reconstituted by addition of detergent-solubilized cerebellar membranes, but not by the cytosolic fraction of cerebellum.
Postictal headache in epileptic patients (2014)

Postictal headache (PIH) is defined by the International Classification of Headache Disorders, third edition beta (ICHD-3 beta), as “headache caused by and occurring within 3 hours after an epileptic seizure, and remitting spontaneously within 72 hours after seizure termination”. People at highest risk of suffering PIH are who have generalized tonic-seizures (GTCSs) and a history of interictal headaches. An occipital epileptogenic focus may be an additional risk factor. Also PIH frequently have characteristics of migraine, the diagnostic criteria of “headache with features of tension-type headache or, in a patient with migraine, of migraine headache” in ICHD-2 has been ruled out from the ICDH-3. The high percentage of PIH in patients with epilepsy which really burden patient’s daily life. For purposes of comparison, trials should adhere to a unified definition of PIH, and ICHD-3 beta revised the ICHD-2 definition which widens the inclusion criteria to any headache attributed to a seizure and following it. In order to improve the diagnosis and management of this symptom, clinicians should pay more attention to epileptic patients with PIH.
Conjugated Polymer-Based Chemical Sensors (2000)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConjugated Polymer-Based Chemical SensorsD. Tyler McQuade, Anthony E. Pullen, and Timothy M. SwagerView Author Information Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 Cite this: Chem. Rev. 2000, 100, 7, 2537–2574Publication Date (Web):June 9, 2000Publication History Received10 September 1999Published online9 June 2000Published inissue 1 July 2000https://pubs.acs.org/doi/10.1021/cr9801014https://doi.org/10.1021/cr9801014research-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views24827Altmetric-Citations3432LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Electrodes,Ions,Organic polymers,Peptides and proteins,Polymers Get e-Alerts
Aluminum Does Not Accumulate in Teenagers and Adults on Prolonged Parenteral Nutrition Containing Free Amino Acids (1986)

Prolonged total parenteral nutrition (TPN) with solutions containing hydrolyzed casein has been associated with aluminum accumulation in patients with bone disease. We investigated the effects of free amino acids in TPN solution on plasma, urine, and bone aluminum in six patients, five of whom had symptoms of bone disease or documented demineralization. No evidence of aluminum accumulation was found. TPN with free amino acids, containing 42 micrograms aluminum per liter or less, does not lead to aluminum loading in adolescents or adults.
Disinfection of eggshells using ultraviolet light and hydrogen peroxide independently and in combination (2010)

Poor hatchability can occur due to eggshell bacterial contamination, which can be decreased by UV light or H(2)O(2) alone. However, antimicrobial effects of these 2 treatments combined, as well as optimum length of UV exposure, are not known. Therefore, the objectives of this study were to determine the optimum length of UV exposure for maximum bacterial reduction and to determine if a greater bacterial reduction would occur using a combination of UV and H(2)O(2) compared with either treatment alone. The first experiment was conducted to determine the optimum length of UV exposure by exposing eggs to 4, 8, 16, and 32 min of UV. Three experiments were also conducted to determine what concentration of H(2)O(2) in combination with UV exposure would yield maximum bacterial reduction. For experiment 2, treatments consisted of a control and UV alone as well as 0, 1, 2, and 3% H(2)O(2) alone and in combination with UV for 8 min. In experiment 3, treatments consisted of a control, UV alone, 3% H(2)O(2) alone, as well as 0, 0.5, 1, 1.5, 2, 2.5, and 3% H(2)O(2) in combination with UV for 8 min. Experiment 4 used 10 treatments including a control and 1.5, 2, and 2.5% H(2)O(2) at UV exposure times of 2, 4, and 8 min for each H(2)O(2) concentration. Results indicated that every control eggshell contained bacteria, resulting in an average bacterial count of 4 log cfu/egg. Exposure to UV alone for 8 min yielded significant bacterial reductions without excessive egg heating. When administered independently, H(2)O(2) and UV each reduced eggshell bacterial counts by 2 log cfu/egg. The combination of 1.5% H(2)O(2) and UV for 8 min reduced bacterial counts by a maximum of 3 log cfu/egg, with only 35% of the eggs positive for bacteria. Because bacterial contamination was further reduced by using a combination of UV and H(2)O(2), it is possible that hatchability and chick quality of breeder eggs might be improved by such treatments.
Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. (1991)

Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, we determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts from 4 +/- 1% to 31 +/- 6% of total purine released (EC50, 1 nM) and by endothelial cells from 24 +/- 4% to 42 +/- 7%. Methotrexate-enhanced adenosine release from fibroblasts was further increased to 51 +/- 4% (EC50, 6 nM) and from endothelial cells was increased to 58 +/- 5% of total purine released by exposure to stimulated (fMet-Leu-Phe at 0.1 microM) neutrophils. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up [14C]adenine and released 14C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils (IC50, 9 nM) and stimulated neutrophils (IC50, 13 nM). Methotrexate treatment inhibited neutrophil adherence by enhancing adenosine release from fibroblasts since digestion of extracellular adenosine by added adenosine deaminase completely abrogated the effect of methotrexate on neutrophil adherence without, itself, affecting adherence. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which (5-aminoimidazole-4-carboxamide ribonucleoside referred to hereafter as acadesine) has previously been shown to cause adenosine release from ischemic cardiac tissue. We found that acadesine also promotes adenosine release from and inhibits neutrophil adherence to connective tissue cells. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs.
Human immunodeficiency virus type 1 cellular host range, replication, and cytopathicity are linked to the envelope region of the viral genome (1990)

Human immunodeficiency virus type 1 (HIV-1) isolates vary in their in vitro biologic characteristics such as cellular host range, replication kinetics, and cytopathicity. In this study, we molecularly exchanged equivalent regions between two cloned HIV-1 isolates with differing replicative and cytopathic properties. To facilitate generation of recombinant viruses, we used a method involving cotransfection of human monolayer cells with plasmid constructs containing half of the biologically active viral genome. The two halves of the genome were subsequently ligated by intracellular processes to form the complete proviral genome. This method simplifies plasmid construction, since new infectious virus particles can be produced easily from the individual constructs that are correctly ligated in vivo. Results obtained by using recombinant viruses generated in this manner indicate that the ability of HIV to replicate in specific cell types and cytopathicity segregate with the env region of the viral genome.
Uveal melanomas in black patients: a case series and comparative review. (1995)

Uveal melanomas are rare in black patients. Of a total of 2586 patients with the diagnosis of posterior uveal melanoma who were managed in the Oncology Service at Wills Eye Hospital from 1974 to 1987, 10 patients (0.39%) were black. Data on patient age (mean: 53.9 years), sex (male-to-female ratio: 7:3), and relative frequency of disease between black (0.39% of total cases) and white patients were similar to that of previous reports. The distinguishing characteristics (incidence, risk factors, complications, and prognostic indicators) of uveal melanoma in black versus white patients also were reviewed.
Compensation for a Transfer Function of a Regenerative Amplifier to Generate Accurately Shaped Ultrashort Pulses in Both the Amplitude and Phase (2004)

We demonstrated accurate pulse shaping of amplified femtosecond optical pulses by modulating the amplitude and phase prior to regenerative chirped-pulse amplification. We measured the amplitude and phase of amplified pulses using a spectral interferometer with a well-defined reference pulse. Based on these measurements, the pulse shaper was adjusted only a few times to compensate for a transfer function of the amplifier consisting of the gain narrowing and self-phase modulation.
Transport state handoff in mobile cellular networks (2002)

We consider the problem of transport state handoff in mobile networks. The problem is motivated by the observation that an efficient way to implement transport connections, where one end is mobile, is to split these connections in two at a node close to the mobile. In such an environment we need to ensure that transport state can be handed off to a new intermediate node if the mobile roams to a location far away from the location where the connection(s) were opened. Our handoff protocols are efficient and we show that they work correctly despite any sequence of moves made by the mobile.
Superconductor digital RF development for software radio (2001)

We review a new "direct digitization" approach for "digital RF" architectures for software radio. Although direct digitization usually implies the simultaneous digitization of all channels in a particular band at a downconverted IF, we use this term to refer exclusively to the direct digitization of all bands, from near DC to RF. Furthermore, we present results on band selection and digitization of RF signals directly at the carrier frequency with high resolution. These novel approaches are enabled by a superconductor analog-to-digital converter technology using an ultra-fast IC logic known as Rapid Single Flux Quantum (RSFQ) logic, with performance capable of enabling envisioned software radios.
Fluorescence Polarization for Monitoring Ribozyme Reactions in Real Time (2000)

Fluorescence polarization has been used recently to monitor diverse macromolecular interactions. In this report, the application of fluorescence polarization has been extended to monitor ribozyme reactions in real time. With fluorescently labeled substrate RNAs, group I ribozyme ligation and hammerhead ribozyme cleavage reactions were studied by fluorescence polarization in substrate excess (multiple turnover) conditions. These results also show that fluorescently labeled RNAs remain active substrates for ribozymes. Furthermore, a direct comparison of fluorescence polarization with fluorescence resonance energy transfer showed that both techniques were comparable for monitoring ribozyme reactions.
Structure and Biological Activity of Human Homologs of the raf/mil Oncogene (1985)

Two human genes homologous to the raf/mil oncogene have been cloned and sequenced. One, c-raf-2, is a processed pseudogene; the other, c-raf-1, contains nine exons homologous to both raf and mil and two additional exons homologous to mil. A 3' portion of c-raf-1 containing six of the seven amino acid differences relative to murine v-raf can substitute for the 3' portion of v-raf in a transformation assay. Sequence homologies between c-raf-1 and Moloney leukemia virus at both ends of v-raf indicate that the viral gene was acquired by homologous recombination. Although the data are consistent with the traditional model of retroviral transduction, they also raise the possibility that the transduction occurred in a double crossover event between proviral DNA and the murine gene.