gebhart/patrepeval huggingface dataset:
Epitope specificity, cytokine production profile and diabetogenic activity of insulin‐specific T cell clones isolated from NOD mice (1995)

T cells are known to play an important role in beta cell destruction in the nonobese diabetic (NOD) mouse model of Type I diabetes and islet-specific T cell clones have been demonstrated to be capable of adoptive transfer of diabetes. One important issue involves the identity of beta cell antigens that are recognized by nominally islet cell-specific T cell clones. We have previously reported that insulin-specific T cells are a predominant component of islet-specific T cells isolated from islet infiltrates of pre-diabetic NOD mice. In this report we examine six independently derived insulin-specific T cell clones established from islet infiltrates of pre-diabetic NOD mice in detail. All six clones were found to be specific to a region of the insulin molecule defined by a synthetic peptide encompassing residues 9-23 of the B chain. Despite this restricted specificity, each member of this panel exhibited a distinct receptor specificity defined either by V beta usage or antigen fine specificity. Five clones produced interferon (IFN)-gamma but not interleukin (IL)-4, placing them in the T helper type 1 (TH1)-like category whereas one clone produced both IL-4 and IFN-gamma, a characteristic of TH0 cells. All six clones were capable of either acceleration of diabetes in young NOD mice or adoptive transfer to NODscid mice. Taken together, these results suggest that spontaneously arising insulin-specific T cells participate in beta cell destruction during development of diabetes in NOD mice.
Thyroliberin receptor binding and adenylyl cyclase activation in cultured prolactin-producing rat pituitary tumor cells (GH cells). (1983)

A thyroliberin (TRH)-responsive particulate bound adenylyl cyclase is present in two rat anterior pituitary tumor cell strains (GH4C1 and GH3) which synthesize and secrete prolactin. At a given Mg2+ concentration, ATP and the guanyl nucleotides GTP and guanyl 5'-yl-imidodiphosphate (GMP-P(NH)P) caused a dose-dependent increase in adenylyl cyclase activity. The maximum response to thyroliberin occurred with ATP and GTP at concentrations above 0.30 mM and 2 microM, respectively. The maximal stimulatory effect of thyroliberin on adenylyl cyclase activity was 2-fold in the presence of GTP. GMP-P(NH)P increased the basal enzyme activity 4- to 10-fold over and above that of equimolar concentrations of GTP but supported poorly the TRH-induced response. Mg2+ caused a dose-dependent increase in the basal enzyme activity and reduced TRH and fluoride-induced responses. Also, Mn2+ and Co2+ stimulated the basal adenylyl cyclase activity while Zn2+, Ca2+, and Cu2+ inhibited the enzyme, and neither cations supported the TRH response. Half-maximal stimulation of the adenylyl cyclase by TRH and half-maximum binding of [3H]TRH to membranes at 35 degrees C were 102 and 56 nM, respectively. Pretreatment with TRH decreased the apparent Vmax of the enzyme and the maximal binding of [3H]TRH. Of 6 TRH analogs tested, only one was able to displace [3H]TRH from its receptor and to increase the adenylyl cyclase activity. We suggest that adenylyl cyclase activation is an early event in the stimulus secretion coupling between TRH and prolactin-producing GH cells.
Advanced glycation end products and the kidney (2005)

Advanced glycation end products (AGEs) are a heterogeneous group of protein and lipids to which sugar residues are covalently bound. AGE formation is increased in situations with hyperglycemia (e.g., diabetes mellitus) and is also stimulated by oxidative stress, for example in uremia. It appears that activation of the renin-angiotensin system may contribute to AGE formation through various mechanisms. Although AGEs could nonspecifically bind to basement membranes and modify their properties, they also induce specific cellular responses including the release of profibrogenic and proinflammatory cytokines by interacting with the receptor for AGE (RAGE). However, additional receptors could bind AGEs, adding to the complexity of this system. The kidney is both: culprit and target of AGEs. A decrease in renal function increases circulating AGE concentrations by reduced clearance as well as increased formation. On the other hand, AGEs are involved in the structural changes of progressive nephropathies such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy. These effects are most prominent in diabetic nephropathy, but they also contribute to renal pathophysiology in other nondiabetic renal diseases. Interference with AGE formation has therapeutic potential for preventing the progression of chronic renal diseases, as shown from data of animal experiments and, more recently, the first clinical trials.
Fluorescence protection immunoassay: a new homogeneous assay technique. (1979)

We describe a "fluorescence protection immunoassay," in which formation of an immune complex of a fluorescer-labeled antigen sterically protects the fluorescer from binding by antibodies to it. Competitive binding of unlabeled antigen by its antibody prevents formation of the fluorescer-labeled antigen immune complex, and allows anti-fluorescein to quench the fluorescence by binding to the fluorescer. This phenomenon is the basis of a new homogeneous assay technique that requires no separation step. The steric exclusion of anti-fluorescein from fluorescein-labeled human IgG immune complexes was altered by changing the molecular dimensions ob both antifluorescein and the immune complex. The assay did not require highly purified fluorescein-labeled human IgG. An assay is demonstrated in which was used a fluorescein-labeled human IgG conjugate containing IgG that was only 10% pure. Measurement of IgG in human serum samples correlated well with results by radial immunodiffusion. The method is applicable to the assay of both proteins and analytes of low molecular mass.
Spectral Gamma-Ray Logging in the Texas Austin Chalk Trend (1980)

This paper reviews properties of Austin chalk and Buda limestone formations of the Cretaceous carbonate trend in Texas and highlights interpretive well logging concepts. Emphasis is on initial field experience with Spectralog, a spectral gamma-ray logging device that has found continuous and widespread application in old and new wells in the Austin chalk formation since Nov. 1977. Introduction Early oil production in the 1920's was developed in the Austin chalk, dolomitic limestone streaks in the Eagle Ford shale, and the Buda limestone of the Luling, Darst Creek, Branyon, and Salt Flat fields in Caldwell and Guadalupe counties of south Texas. Subsequent exploration drilling for the Edwards limestone established incidental production in the Austin chalk in Bexar, Frio, and Wilson counties, with occasional completions being made in the Austin chalk and/or Buda limestone in Atascosa County. Interest in the deeper trend of the Austin/Eagle Ford/Buda has been rekindled, reaching, in fact, into a dozen south Texas counties as well as into east Texas due to indicated successes based on high initial productivity indices (PI's) of new wells in this trend. Long-term performance of some of these wells, however, has been disappointing. Most participants exploring in this Upper Cretaceous trend state that an oilwell completion can be made anywhere in the trend. Hence, the key problem is to distinguish the economical wells, prior to the expensive completion operation. Characteristics of solution-drive oil production in the Austin chalk and Buda limestone are initial PI's indicative of high flow rates followed by rapid pressure decline and eventual stabilized low-level production. The conjecture is that some of these completions are in pay zones that have insufficient porosity, low permeability, and only limited development of macro- and microfracture systems. Thus, after stimulation by acidizing and/or fracturing, the artificially created fracture system delivers high initial production rates that will decline rapidly to low production rates upon stabilization. Where the macro- and microfracture system is extensive and supported by some matrix porosity, the wells behave similarly but stabilize at a higher, more economically attractive production rate. Exceptions to the general patterns of oil accumulation in natural fracture systems are the shallow, older fields of Caldwell and Guadalupe counties. In these counties, formation porosity and permeability, along with natural fracture planes, have been adequate to allow migration of oil into fault-controlled anticlinal traps. Hence, the problem is to define and evaluate the better-developed of more numerous fracture systems by geophysical methods before setting the production string. Several formation evaluation approaches have been attempted in the past.1,2 Application of gamma-ray spectral logging data to locate uranium salts precipitated over geologic time on the fracture planes, along with other geophysical fracture detection methods, appears to offer a reliable evaluation system.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro (2020)

Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
Focusing and steering through absorbing and aberrating layers: Application to ultrasonic propagation through the skull (1998)

The time-reversal process is applied to focus pulsed ultrasonic waves through the human skull bone. The aim here is to treat brain tumors, which are difficult to reach with classical surgery means. Such a surgical application requires precise control of the size and location of the therapeutic focal beam. The severe ultrasonic attenuation in the skull reduces the efficiency of the time reversal process. Nevertheless, an improvement of the time reversal process in absorbing media has been investigated and applied to the focusing through the skull [J.-L. Thomas and M. Fink, IEEE Trans. Ultrason. Ferroelectr. Freq. Control 43, 1122-1129 (1996)]. Here an extension of this technique is presented in order to focus on a set of points surrounding an initial artificial source implanted in the tissue volume to treat. From the knowledge of the Green's function matched to this initial source location a new Green's function matched to various points of interest is deduced in order to treat the whole volume. In a homogeneous medium, conventional steering consists of tilting the wave front focused on the acoustical source. In a heterogeneous medium, this process is only valid for small angles or when aberrations are located in a layer close to the array. It is shown here how to extend this method to aberrating and absorbing layers, like the skull bone, located at any distance from the array of transducers.
Membrane vesiculation function and exocytosis of wild-type and mutant matrix proteins of vesicular stomatitis virus (1995)

Transfection of mammalian CV1 cells with a recombinant M-gene pTM1 plasmid, driven by vaccinia virus-expressed phage T7 polymerase, resulted in the expression of matrix (M) protein, which is progressively released from the exterior surface of the transfected-cell plasma membrane. Exocytosis of M protein begins 2 to 4 h posttransfection and reaches a peak by 10 to 16 h posttransfection; dye uptake studies reveal that > 97% of cells are alive and have intact membranes at 16 h posttransfection. Density gradient centrifugation and labeling with radioactive palmitic acid revealed that the M protein is released from cells in association with lipid vesicles. Expression of M-gene deletion mutants suggests that exocytosis of M protein requires the presence of a membrane-binding site at N-terminal amino acids 1 to 50. Cells transfected with the pTM1 plasmid containing the M gene of the temperature-sensitive mutant tsO23 expressed ample quantities of the mutant M protein at permissive (31 degrees C) and restrictive (39 degrees C) temperatures, but the exocytosis of the mutant M protein occurred only at the permissive temperature. The tsO23 M gene has three site-specific mutations resulting in amino acid substitutions at residues 21, 111, and 227. Expression of wild-type and mutant M genes with mutations or revertants at each of these sites resulted in exocytosis of M protein at the nonpermissive temperature only when wild-type leucine was present at residue 111, but M-protein exocytosis was restricted (to some extent even at the permissive temperature) when mutant phenylalanine was present at residue 111. Past and present data indicate that a specific structural conformation of the M protein is responsible for the formation and budding of vesicles, a property of the M protein which probably also promotes vesicular stomatitis virus assembly and budding of virions from host cells.
A Predictive Framework for Location-Aware Resource Management in Smart Homes (2007)

Rapid advances in a wide range of wireless access and networking technologies, along with ubiquitous computing and communications, have set the stage for the development of smart environments (for example, smart homes or offices). "Context awareness" is perhaps the most salient feature in such intelligent (indoor) environments. Examples of contexts include the "location" and "activities" of the inhabitants among others. In this paper, we develop a predictive framework for location-aware resource optimization in smart homes based on the hypothesis that the mobility of an inhabitant creates an uncertainty of his location. With the help of information theory, the proposed framework is shown to minimize this uncertainty through optimal learning and prediction of the inhabitant's movement (location) profiles captured in the symbolic domain. The concept of the asymptotic equipartition property (AEP) is also used to predict the inhabitant's most likely routes (or path-segments) with a high degree of accuracy. Successful predictions help in several ways, such as automated device control and proactive reservation of resources (for example, electrical energy and other utilities or scarce wireless bandwidth for mobile multimedia applications) along the inhabitant's most probable locations and routes. The goal here is to minimize the maintenance and operations cost of the smart home, as well as to provide better comfort to the inhabitants. Experimental results from a typical smart home floor plan corroborate the prediction success and significant reduction in daily energy consumption and manual operations of devices.
Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies (2013)

Glioblastoma multiforme is one of the most aggressive brain tumors in adults. Despite the use of the best available multimodal therapeutic approaches, the prognosis remains dismal. The identification of glioma stem cells (GSCs) has offered new hope to affected patients, since it could explain, in part, the highly heterogeneous nature of this tumor and its chemo- and radio-resistance. Although still in its infancy, GSC research has unveiled many of its complexities and the theory itself remains controversial. GSC phenotype can significantly vary between patients and a single tumor may present several distinct GSCs. New therapeutic solutions that effectively target this population are of utmost importance, since they may be able to decrease neoplastic recurrence and improve patient survival. Here, we discuss the mechanisms by which GSCs lead to glioma relapse, the main controversies in this field and the most recent treatments that could successfully target this population.
Mucin-Type Glycoproteins (1992)

Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized mainly by a high level of O-linked oligosaccharides. Initially, the glycoproteins were solely known as the major constituents of mucus. Recent studies have shown that mucins from the gastrointestinal tract, lungs, salivary glands, sweat glands, breast, and tumor cells are structurally related to high-molecular-weight glycoproteins, which are produced by epithelial cells as membrane proteins. During mucin synthesis, an orchestrated sequence of events results in giant molecules of Mr 4 to 6 x 10(6), which are stored in mucous granules until secretion. Once secreted, mucin forms a barrier, not only to protect the delicate epithelial cells against the extracellular environment, but also to select substances for binding and uptake by these epithelia. This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.
Self-Assembly of Symmetric Brush Diblock Copolymers (2013)

Self-assembled structures of brush block copolymers (BrBCPs) with polylactide (PLA) and polystyrene (PS) side chains were studied. The polynorbornene-backbone-based BrBCPs containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing ranging from 20 to 240 nm by varying molecular weight of the backbone in the bulk state, as revealed by small-angle X-ray scattering (SAXS). The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state. In situ SAXS measurements suggested that the BrBCPs self-assemble with an extremely fast manner which could be attributed to a reduced number of entanglements between chains. The strong segregation theory and Monte Carlo simulation also confirmed this near-linear dependence of the domain spacing on backbone length, rationalizing experimental results.
Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system. (1994)

Anti-FRP mAbs induced polykaryocyte formation of U2ME-7 cells (CD4+U937 cells transfected with the HIV gp160 gene). Anti-FRP-1 mAb immunoprecipitated gp80-85, gp120 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the alpha 3 subunit of integrin. Both anti-FRP-1 and anti-FRP-2 mAb-induced cell fusion was blocked by anti-beta 1 integrin antibody, fibronectin or inhibiting anti-FRP-1 antibody. Therefore, anti-FRP mAbs were thought to induce the fusion via an integrin system(s). FRP-mediated fusion was temperature, cytoskeleton, energy and Ca2+ dependent. These experiments showed a possible regulatory function of cell fusion by an integrin system(s).
A general method for facilitating heterodimeric pairing between two proteins: application to expression of alpha and beta T-cell receptor extracellular segments. (1994)

Generation of soluble T-cell receptor (TCR) molecules by a variety of genetic engineering methods has been hampered by inefficient pairing of alpha and beta subunits in the absence of their respective transmembrane regions and associated CD3 components. To overcome this obstacle, we have added 30-amino acid-long segments to the carboxyl termini of alpha and beta extracellular domains via a cleavable flexible linker. These peptide segments (BASE-p1 for alpha and ACID-p1 for beta) have been previously shown to selectively associate to form a stable heterodimeric coiled coil termed a leucine zipper. Homodimeric structures are not permitted due to electrostatic repulsion among amino acid side chains. Expression of a representative TCR-leucine zipper fusion protein in a baculovirus expression system results in production of alpha beta TCR heterodimer at 0.6-1.4 mg/liter. This yield is 5- to 10-fold greater than that of the TCR expressed in the absence of the synthetic leucine zipper sequence. The structure of the TCR component of the fusion heterodimer was judged to be native when probed with a panel of 17 mAbs specific for alpha and beta constant and variable domains. A mAb specific for the isolated BASE-p1/ACID-p1 coiled coil was also generated and shown to react with the TCR fusion protein. The above technology should be broadly useful in the efficient production and purification of TCRs as well as other heterodimeric proteins.
Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. (1988)

Proteases that are encoded by animal picornaviruses and plant como- and potyviruses form a related group of cysteine-active-center enzymes that are essential for virus maturation. We show that these proteins are homologous to the family of trypsin-like serine proteases. In our model, the active-site nucleophile of the trypsin catalytic triad, Ser-195, is changed to a Cys residue in these viral proteases. The other two residues of the triad, His-57 and Asp-102, are otherwise absolutely conserved in all the viral protease sequences. Secondary structure analysis of aligned sequences suggests the location of the component strands of the twin beta-barrel trypsin fold in the viral proteases. Unexpectedly, the 2a and 3c subclasses of viral cysteine proteases are, respectively, homologous to the small and large structural subclasses of trypsin-like serine proteases. This classification allows the molecular mapping of residues from viral sequences onto related tertiary structures; we precisely identify amino acids that are strong determinants of specificity for both small and large viral cysteine proteases.
Membrane-bound α-Synuclein Has a High Aggregation Propensity and the Ability to Seed the Aggregation of the Cytosolic Form (2002)

Alpha-synuclein exists as at least two structural isoforms: a helix-rich, membrane-bound form and a disordered, cytosolic form. Here, we investigated the role of membrane-bound alpha-synuclein in the aggregation process. In a cell-free system consisting of isolated brain fractions, spontaneous and progressive aggregation of alpha-synuclein was observed in membranes starting at day 1, whereas no aggregation was observed in the cytosolic fraction in a 3-day period. The addition of antioxidants reduced the aggregation in the membrane fraction, implicating the role of oxidative modifications. When excess cytosolic alpha-synuclein was added to brain membranes, the rate of aggregation was increased, while the lag time was unaffected. Incorporation of cytosolic alpha-synuclein into membrane-associated aggregates was demonstrated by fractionation and co-immunoprecipitation experiments. In our recent study, we showed that mitochondrial inhibitors such as rotenone, induced alpha-synuclein aggregation in cells. In the present study using rotenone-treated cells, the earliest appearance of alpha-synuclein oligomeric species was observed in membranous compartments. Furthermore, alpha-synuclein-positive inclusions were co-stained with DiI, a membrane-partitioning fluorescent dye, confirming the presence of lipid components in alpha-synuclein aggregates. These results suggest that membrane-bound alpha-synuclein can generate nuclei that seed the aggregation of the more abundant cytosolic form.
Efficacy and ototoxicity of different cyclodextrins in Niemann–Pick C disease (2016)

CDs other than HPβCD identified here may provide disease amelioration without ototoxicity and merit long-term treatment studies. While direct interactions of CD-UC are thought central to the mechanism of correction, the data show that this does not strictly correlate with complexation ability and suggest interactions with other NPC disease-relevant substrates should be considered.