gebhart/patrepeval huggingface dataset:
Functional assembly of chimeric T-cell receptor chains. (1992)

We have generated cytotoxic T-cell hybridomas expressing chimeric T-cell receptors (cTCR) with an antibody-type specificity for the TNP hapten. Transfectants expressing the cTCR genes could mediate specific lysis of haptenated tumor cell lines of various types and secrete IL-2 upon stimulation with TNP modified cells. In a previous report, we showed that double-gene transfectants expressing either VHC alpha and VLC beta or VHC beta and VLC alpha could be activated by TNP-modified stimulator cells or TNP proteins immobilized on plastic. Single-chain transfectants (expressing VHC alpha or VHC beta alone) could be mainly activated by TNP-cells. We now report that transfection of chimeric VHC alpha gene into an alpha-chain-defective mutant restores the surface expression of the TCR/CD3 complex. In parallel, such transfectants regained the ability to respond to mitogen and anti-CD3 antibodies and responded weakly to TNP cells. Double gene transfectants, bearing 2 complementary chimeric chains, expressed high amounts of cTCR on their surface, sufficient to acquire sound anti-TNP reactivity. Cells expressing the VHC beta gene only were not functional and had no detectable surface TCR chains. Taken together, our results suggest that chimeric VHC alpha chains can pair with endogenous V beta C beta chains, but that there is preferential association between complementary chimeric chains, resulting in higher functional expression of the chimeric TCR.
Identification of a novel mitochondrial protein (“mitoNEET”) cross-linked specifically by a thiazolidinedione photoprobe (2004)

Thiazolidinediones address underlying causes of type 2 diabetes, although their mechanism of action is not clearly understood. The compounds are thought to function as direct activators of the nuclear receptor PPARgamma (peroxisome proliferator-activated receptor-gamma), although pioglitazone, the weaker agonist of the two thiazolidinediones now in clinical use, seems to have more useful effects on circulating lipids. We have used tritiated pioglitazone and a photoaffinity cross-linker to identify a novel binding site in mitochondria. A saturable binding site for [3H]pioglitazone was solubilized from the membranes with CHAPS and migrated as a large complex by size exclusion chromatography. The binding correlated with a <17-kDa protein (m17), marked by a photoaffinity cross-linker, in both subcellular location and selectivity of competition by analogs. The protein was isolated and identified by mass spectrometry analysis and NH2-terminal sequencing. Three synthetic peptides with potential antigenic properties were synthesized from the predicted nontransmembrane sequence to generate antibodies in rabbits. Western blots show that this protein, which we have termed "mitoNEET," is located in the mitochondrial fraction of rodent brain, liver, and skeletal muscle, showing the identical subcellular location and migration on SDS-PAGE as the protein cross-linked specifically by the thiazolidinedione photoprobe. The protein exists in low levels in preadipocytes, and expression increases exponentially in differentiated adipocytes. The synthetic protein bound to solid phase associated with a complex of solubilized mitochondrial proteins, including the trifunctional beta-oxidation protein. It is possible that thiazolidinedione modification of the function of the mitochondrial target may contribute to lipid lowering and/or antidiabetic actions.
PCSK9 inhibition and LDL cholesterol lowering: the biology of an attractive therapeutic target and critical review of the latest clinical trials (2012)

PCSK9 is a serine protease expressed in the liver and the intestine. Gain-of-function mutations in PCSK9 are associated with autosomal dominant hypercholesterolemia, independently of mutations in apoB-100 or the LDL receptor (LDLR). Wild-type PCSK9 binds to the extracellular domain of the LDLR at the surface of hepatocytes, is internalized with the receptor and redirects it to lysosomes where the complex is degraded. Conversely, loss-of-function mutations in PCSK9 are associated with lower levels of LDL cholesterol (LDL-C) and reduced cardiovascular risk. Inhibition of PCSK9 binding to the LDLR with human monoclonal antibodies or reduction of PCSK9 expression with siRNA are the two main strategies to reduce LDL-C, which are actively pursued in the clinical development phases. In this article, the current evidence for PCSK9 as a target for reducing LDL-C and results of Phase I and II clinical trials with anti-PCSK9 therapeutic strategies are reviewed.
Helper activity is required for the in vivo generation of cytotoxic T lymphocytes (1982)

B6.T1a(a) (Qa-1(a)) mice that are primed in vivo and restimulated in vitro with Qa-1 congenic spleen cells from B6 (Qa-1(b)) animals are unable to generate anti-Qa-1(b) cytotoxic T lymphocytes (CTL). This nonresponsive pattern was observed regardless of the route of immunization or the time of testing in vitro. Although B6.T1a(a) mice are nonresponders to Qa-1(b) when presented on B6 cells, these mice can generate anti-Qa-1(b) CTL when primed in vivo with Qa-1 and H-Y alloantigens (females primed with B6 male cells) or Qa-1 and minor-H- alloantigens (primed with sex-matched A.BY cells). Therefore, the inability to generate anti-Qa-1(b) CTL is due to a lack of helper or accessory antigens on B6 immunizing cells obligatory during in vivo priming, rather than an absence of anti-Qa-1(b) CTL precursors (CTL-P). Demonstration that the additional determinants required during in vivo priming actually function as carrier or helper determinants was shown by the requirement for linked recognition of Qa-1 and the helper determinants (H-Y) in vivo, and the fact that H-Y was not present on susceptible target ceils. Animals primed in vivo with H-Y only could not generate anti-Qa-1 CTL activity when challenged in vitro with both Qa-1 and H-Y, indicating that recognition of the helper determinant causes in vivo priming of CTL-P rather than generating helper activity that might activate unprimed CTL-P in vitro. Whereas unprimed peripheral CTL-P require the presence of both Qa-1 (CTL) and H-Y (helper) determinants for successful in vivo priming, helper determinants were not required in vitro because primed CTL-P from B6.T1a(a) mice could be driven to CTL in vitro using sex-matched B6 stimulator cells. The generation of anti-Qa-1(b) CTL is under immune response (Ir) gene control because F(1) mice, obtained by crossing responder A/J with nonresponder B6.T1a(a) animals, generated CTL to the Qa-1(b) alloantigen when presented on B6 spleen cells. Progeny testing of backcross mice further demonstrated that the Ir gene(s) is linked to the H-2 complex. These data indicate that an H-2-linked Ir gene controls the recognition of helper determinants required for CTL priming in vivo. These helper determinants can be distinguished from CTL determinants and both must be recognized together for successful priming of CTL-P.
Bronchoalveolar Lavage Findings in Cystic Fibrosis Patients with Stable, Clinically Mild Lung Disease Suggest Ongoing Infection and Inflammation (1994)

To determine the extent of airway infection and inflammation in adolescents and adults with cystic fibrosis (CF) who have mild lung disease and are without symptoms of active infection, we performed bronchoalveolar lavage (BAL) on 18 CF patients > or = 12 yr of age who were stable, appeared clinically well, and had mean (+/- SEM) FEV1 of 79 +/- 4% of predicted. We quantitated the bacteria, inflammatory cells, immunoglobulins, and mediators of inflammatory tissue damage in the epithelial lining fluid (ELF) of these patients and in 23 healthy control subjects. All CF patients were found to be infected with Pseudomonas aeruginosa, Staphylococcus aureus, and/or Haemophilus influenzae; no organisms were isolated from the control subjects. The mean number of cells in the ELF was 14 times greater in the CF patients than in the control subjects. Neutrophils constituted 57% of the recovered cells in the CF patients versus 3% in the control subjects, and their concentration was 380 times greater in the CF patients versus the control subjects. IgG, IgA, and IgM were 2.5 to 6 times greater in CF ELF versus that of control subjects. Abundant active elastase was present in the ELF of the CF patients (2.3 +/- 0.9 microM) despite threefold elevated levels of alpha 1-protease inhibitor (alpha 1-PI). No active elastase was detectable in the control subjects. alpha 1-PI was functional in CF as demonstrated by elevated elastase:alpha 1-PI complex (0.045 microM in CF versus 0.002 microM in control subjects). This active elastase caused proteolytic destruction of surface complement receptors on airway neutrophils in situ.(ABSTRACT TRUNCATED AT 250 WORDS)
Lyophilized Hyperimmune Equine Serum as a Source of Antibodies for Neonatal Foals (1981)

In a study with 15 neonatal foals (5 per treatment group), foals were fed within 4 hours of birth as follows: 250 ml of colostrum, 250 ml of lyophilized serum reconstituted at 5 times the original concentration, or 250 ml of a mixture (1:1) of colostrum and lyophilized serum. Foal serum samples were tested for immunoglobulin (Ig)G concentration and titrated for anti-equine rhinovirus 1 and anti-equine influenza A1 and A2 antibodies at 0 and 24 hours after foals were born. Except in a foal which had suckled the dam before treatment, there was no evidence of IgG or specific viral antibodies in the samples taken at birth. There were no significant differences found in the serum IgG concentrations and antibody titers among the 3 treatment groups. Seemingly, IgG was absorbed efficiently from both serum and colostrum, so that the use of reconstituted lyophilized serum as a prophylactic measure of conferring passive immunity to a newborn foal deserves serious consideration.
DNA vaccines: designing strategies against parasitic infections (2004)

The complexity of parasitic infections requires novel approaches to vaccine design. The versatility of DNA vaccination provides new perspectives. This review discusses the use of prime-boost immunizations, genetic adjuvants, multivalent vaccines and codon optimization for optimal DNA vaccine design against parasites.
Lanthanide Recognition: Development of an Asymetric Gadolinium Microsensor Based on N-(2-pyridyl)-N′-(4-nitrophenyl)thiourea (2008)

Abstract The first asymmetric potentiometric Gd(III) microsensor is reported here. N-(2-Pyridyl)-N′-(4-nitrophenyl)thiourea (PyTu4NO2) was found to have a very selective and sensitive behavior toward Gd(III) ions, in comparison to other lanthanide ions as well as inner transition and representative metal ions and hence was used as a sensing material in the construction of a Gd(III) microelectrode. The Gd(III) sensor exhibits a Nernstian slope of 17.46 ± 0.3 mV per decade over the concentration range of 1.0 × 10−8 to 1.0 × 10−3 M and a detection limit of 3.0 × 10−9 M of Gd(III) ions. The potentiometric response of the sensor is independent of the solution pH in the range of 4.0–9.0. It manifests advantages of low detection limit and fast response time (10–15 s). Keywords: Gd(III)microsensorN-(2-pyridyl)-N′-(4-nitrophenyl)thioureapotentiometric membrane The authors express their appreciation to the University of Tehran Research Council for financial support of this work.
A diagnostic trap for the dermatopathologist: granulomatous reactions from cutaneous microimplants for cosmetic purposes (2006)

We present a case of late granulomatous reactions from silicone that first appeared in a site different from that of the injection causing an incorrect diagnosis of liposarcoma in the beginning. The histological picture was a cystic-macrophagic granuloma in both the injection site (upper lip) and the migrating site (paranasal regions). We think that the foreign body has undergone an antigravity migration from the upper lip to the right paranasal region. To our knowledge, such a phenomenon has not been yet reported in literature.
Optical cross-connect system in broad-band networks: system concept and demonstrators description (1993)

A network robust to future evolution in network topologies or transmission formats and bit rates, which would be achieved by introducing an all-optical transparent layer in the transport network hierarchy is considered. The transparency would permit use of physically common fiber lines and nodes for different transmission hierarchies and/or formats. A transparent network could be achieved by combining photonic switching with electronic switching technology in the network nodes. A combination of wavelength routing and space-division switching in the optical layer would increase the capacity, as well as the flexibility in a network, allowing routing with higher granularity within the optical layer. Two optical cross-connect demonstrators have been set up. One demonstrates protection switching and restoration of traffic in a future transport network, and the other demonstrates routing of subscriber signals to different service switches in a local exchange. Space switches, tunable lasers and filters are the key technologies used to obtain enhanced flexibility.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DNA Strand Scissions by Hydroxamic Acids-Copper(II) Ion under Aerobic Conditions (1992)

Abstract Carbazolyloxyacetohydroxamic acid (1), 9,9′-decamethylene-bis-carbazolyloxyacetohydroxamic acid (2), benzohydroxamic acid (3) and acetohydroxamic acid (4) without reducing agent under aerobic conditions induced Col E1 DNA strand scissions with increasing of the activities in the order of 4 &amp;gt; 3 &amp;gt; 2 &amp;gt; 1. Inhibition experiments indicated that hydrogen peroxide and superoxide participated in the reactions, but hydroxyl radical or singlet oxygen did not.
Papilledema revisited: is its pathophysiology really understood? (2009)

The term 'papilledema' is used to describe swelling of the optic disc that is thought or known to be associated with increased intracranial pressure (ICP) transmitted to the subarachnoid space (SAS) surrounding the optic nerve (ON). In most cases, the diagnosis of increased ICP is confirmed by lumbar puncture, the results of which are believed to represent the pressure in all of the cerebrospinal fluid (CSF) spaces. Until recently, all CSF spaces were thought to communicate freely and that CSF pressure and composition in one location were the same throughout the central nervous system (CNS) unless there was an acquired structural disturbance. However, the concept of continuous CSF flow and pressure throughout the CNS does not explain why some patients with elevated ICP do not develop papilledema, why some patients have highly asymmetrical papilledema, or why some patients with papilledema have normal ICP during 24-hour monitoring. In addition, CSF sampling during lumbar puncture and during ON sheath fenestration demonstrates an increased concentration of lipocalin-like prostaglandin D synthase, a substance toxic to astrocytes, in the SAS of the ON compared with that in the lumbar CSF space, and also a difference in CSF dynamics between the lumbar and ON SAS in some patients with papilledema. We therefore suggest that papilledema does not result from raised ICP alone but in some cases by compartmentation of the SAS of the ON, leading to a toxic milieu around the nerve.
Pore-Forming Proteins and their Application in Biotechnology (2002)

Proteins and peptides that form membrane-spanning pores and channels comprise a diverse class of molecules ranging from short peptides that are unregulated and create non-selective pathways to large ion channel proteins that are highly regulated and exhibit exquisite selectivity for particular ions. The diversity of regulation and selectivity, together with recent advances in protein "re-engineering" technology, provide a strong framework on which to build custom molecules with wide-ranging biotechnological application. Here we review a selection of pore-forming peptides and proteins from a number of different species to highlight their structural and functional diversity. The current and potential uses of native and re-engineered molecules are discussed together with a novel strategy to re-engineer alpha-hemolysin to create targeted and regulable cell-killing agents termed proimmunolysins. Numerous pore-forming peptides are currently in development as antimicrobial agents with potential application as anti-tumorigenic agents. In addition to their roles as biotherapeutic agents, pore-forming proteins are also being developed as biosensors for a range of different analytes. Recent examples of this technology include the use of alpha-hemolysin with an adapter molecule to create sensors for organic molecules and gramicidin as a general-purpose sensor for a range of analytes. These approaches promise to deliver a configurable binding site for analytes encoded in a readily measured electrical signal. The number of applications for pore-forming molecules is sure to grow in both quantity and diversity with increased knowledge of the fundamental structure and function of pores.
Magnetic pulse compressor for prepulse discharge in spiker-sustainer excitation technique for XeCl lasers (1994)

A high-voltage pulse output modulator using a step-up transformer with two stages of magnetic pulse compression circuits has been developed as a spiker for the purpose of obtaining the breakdown of the gas mixture when using the spiker-sustainer excitation technique for pumping XeCl discharge lasers. When the transformer input is fed by a current pulse with a peak value and a full width of 1.16 kA and 1.6 μs, respectively, formed by a discharge of an initially charged 19-kV, 57-nF capacitance in series in the transformer primary loop, the 2.7-nF output capacitor bank (Cp) of the spiker can be charged up to 67 kV with a (10%–90%) rise time of 59 ns. The modulator has been tested at a repetition rate of up to 600 Hz in burst mode using a resistor in parallel with Cp as the load.
Alterations in T4 (CD4) Protein and mRNA Synthesis in Cells Infected with HIV (1986)

Cells infected with the human immunodeficiency virus (HIV) show decreased expression of the 58-kilodalton T4 (CD4) antigen on their surface. In this study, the effect of HIV infection on the synthesis of T4 messenger RNA (mRNA) and protein products was evaluated in T-cell lines. Metabolically labeled lysates from the T4+ cell line Sup-T1 were immunoprecipitated with monoclonal antibodies to T4. Compared with uninfected cells, HIV-infected Sup-T1 cells showed decreased amounts of T4 that coprecipitated with both the 120-kilodalton viral envelope and the 150-kilodalton envelope precursor molecules. In four of five HIV-producing T-cell lines studied, the steady-state levels of T4 mRNA were also reduced. Thus, the decreased T4 antigen on HIV-infected cells is due to at least three factors: reduced steady-state levels of T4-specific mRNA, reduced amounts of immunoprecipitable T4 antigen, and the complexing of available T4 antigen with viral envelope gene products. The data suggested that the T4 protein produced after infection may be complexed with viral envelope gene products within infected cells. Retroviral envelope-receptor complexes may thus participate in a general mechanism by which receptors for retroviruses are down-modulated and alterations in cellular function develop after infection.
MPEG systems committee draft-ISO/IEC JTC1/SC2/WG11 (2002)

The MPEG systems committee draft (CD) specifies the syntax and semantics of the information that is necessary in order to reproduce one or more MPEG audio or video compressed data streams in a system. The issues addressed by the systems CD are in four categories: synchronization, absolute time identification, multiplexing and playback start-up.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DNA Helicases (1990)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Memory T‐cell trafficking: new directions for busy commuters (2010)

The immune system is unique in representing a network of interacting cells of enormous complexity and yet being based on single cells travelling around the body. The development of effective and regulated immunity relies upon co-ordinated migration of each cellular component, which is regulated by diverse signals provided by the tissue. Co-ordinated migration is particularly relevant to the recirculation of primed T cells, which, while performing continuous immune surveillance, need to promptly localize to antigenic sites, reside for a time sufficient to carry out their effector function and then efficiently leave the tissue to avoid bystander damage. Recent advances that have helped to clarify a number of key molecular mechanisms underlying the complexity and efficiency of memory T-cell trafficking, including antigen-dependent T-cell trafficking, the regulation of T-cell motility by costimulatory molecules, T-cell migration out of target tissue and fugetaxis, are reviewed in this article.
Analysis of recurrent codes (1963)

A definition of a recurrent code is given in a framework which renders it amenable to mathematical analysis. Recurrent codes for both independent and burst errors are considered, and a necessary and sufficient condition for either type of error correction is established. For burst-error-correcting codes, the problem treated is (for a fixed burst length and redundancy) the minimization of the error-free distance ("guard space") required between bursts. A lower bound is obtained on the guard space, and in certain cases, codes which realize this bound are given. A general code which is close to the lower bound in many cases is also given. For independent errors, a code which will correct any error, provided that no consecutive " <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> " positions have more than " <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">e</tex> " digits in error, is discussed. For <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">e = 1</tex> , a necessary and sufficient condition on <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> is derived; for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">e &gt; 1</tex> , a lower bound on <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> is obtained, and for the case of redundancy <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1/2</tex> , an upper bound on <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">n</tex> is also derived.
Electrocatalytic and homogeneous approaches to conversion of CO2to liquid fuels (2008)

Research in the field of catalytic reduction of carbon dioxide to liquid fuels has grown rapidly in the past few decades. This is due to the increasing amount of carbon dioxide in the atmosphere and a steady climb in global fuel demand. This tutorial review will present much of the significant work that has been done in the field of electrocatalytic and homogeneous reduction of carbon dioxide over the past three decades. It will then extend the discussion to the important conclusions from previous work and recommendations for future directions to develop a catalytic system that will convert carbon dioxide to liquid fuels with high efficiencies.
Bacterial vaginosis and disturbances of vaginal flora (1998)

This prospective study suggests that progressively greater disturbances of vaginal flora, increase HIV acquisition during pregnancy and postnatally. The screening and treating of women with BV could restore normal flora and reduce their susceptibility to HIV.