gebhart/patrepeval huggingface dataset:
G-protein-coupled receptor genes as protooncogenes: constitutively activating mutation of the alpha 1B-adrenergic receptor enhances mitogenesis and tumorigenicity. (1991)

The alpha 1B-adrenergic receptor (alpha 1B-ADR) is a member of the G-protein-coupled family of transmembrane receptors. When transfected into Rat-1 and NIH 3T3 fibroblasts, this receptor induces focus formation in an agonist-dependent manner. Focus-derived, transformed fibroblasts exhibit high levels of functional alpha 1B-ADR expression, demonstrate a catecholamine-induced enhancement in the rate of cellular proliferation, and are tumorigenic when injected into nude mice. Induction of neoplastic transformation by the alpha 1B-ADR, therefore, identifies this normal cellular gene as a protooncogene. Mutational alteration of this receptor can lead to activation of this protooncogene, resulting in an enhanced ability of agonist to induce focus formation with a decreased latency and quantitative increase in transformed foci. In contrast to cells expressing the wild-type alpha 1B-ADR, focus formation in "oncomutant"-expressing cell lines appears constitutively activated with the generation of foci in unstimulated cells. Further, these cell lines exhibit near-maximal rates of proliferation even in the absence of catecholamine supplementation. They also demonstrate an enhanced ability for tumor generation in nude mice with a decreased period of latency compared with cells expressing the wild-type receptor. Thus, the alpha 1B-ADR gene can, when overexpressed and activated, function as an oncogene inducing neoplastic transformation. Mutational alteration of this receptor gene can result in the activation of this protooncogene, enhancing its oncogenic potential. These findings suggest that analogous spontaneously occurring mutations in this class of receptor proteins could play a key role in the induction or progression of neoplastic transformation and atherosclerosis.
I/O-complexity of graph algorithms (1999)

We show lower bounds of \\Omega\\Gamma E V Sort(V )) for the I/Ocomplexity of graph theoretic problems like connected components, biconnected components, and minimum spanning trees, where E and V are the number of edges and vertices in the input graph, respectively. We also present a deterministic O( E V Sort(V ) \\Delta max(1; log log V BD E )) algorithm for the problem of graph connectivity, where B and D denote respectively the block size and number of disks. Our algorithm includes a breadth first search; this maybe of independent interest. 1 Introduction Data sets of many modern applications are too large to fit into main memory, and must reside on disk. To run such applications efficiently, it is often necessary to explicitly manage disk accesses as a part of the algorithm. In other words, the algorithm must be designed for a model that includes disk, rather than the customary RAM model. Recently, this area has received a lot of attention, and algorithms have been developed for...
Depressed protein synthesis is the dominant characteristic of muscle wasting and cachexia (1983)

Wasting of skeletal muscle is a characteristic of many conditions besides those involving primary muscle disease, for example, cancer, cachexia and postoperative catabolism. There is now strong evidence from studies in animals, normal men and in patients with a variety of diseases to suggest that the muscle mass is regulated primarily by alterations in the protein synthetic rate and that changes in muscle protein degradation are largely secondary and adaptive. If this is so, attention should be focused on possible means of therapeutic intervention to increase protein synthesis rather than on ways of decreasing protein degradation.
Décret du comité de Salut public envoyant les représentants Treilhard et Rougemont en qualité de commissaires à l’établissement de Meudon, lors de la séance du 19 vendémiaire an III (10 octobre 1794) (1995)

Richard Joseph-Etienne. Décret du comité de Salut public envoyant les représentants Treilhard et Rougemont en qualité de commissaires à l’établissement de Meudon, lors de la séance du 19 vendémiaire an III (10 octobre 1794). In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XCIX - Du 18 vendémiaire au 2 brumaire an III (9 au 23 octobre 1794) Paris : CNRS éditions, 1995. p. 52.
Comparison of Adenoviral and Adeno-Associated Viral Vectors for Pancreatic Gene Delivery In Vivo (2004)

Although effective gene therapy vectors have been developed for organ systems such as the liver, an effective delivery vector to the pancreas in vivo has remained elusive. Of the currently available viral vectors, adenovirus and adeno-associated virus (AAV) are two of the most efficient at transducing nondividing cells. We have constructed recombinant adenovirus (AdVLacZ), adeno-associated virus serotype 2 (AAV2LacZ), and pseudotyped adeno-associated virus serotype 5 and 8 (AAV5LacZ, AAV8LacZ) carrying the LacZ reporter, and compared the transduction efficiency of these four vectors in the pancreas of mice in vivo. We showed that adenovirus, AAV2, and AAV8 are capable of transducing the pancreas in vivo, but with different expression kinetics, efficiencies of transduction, and persistence. AdVLacZ-transduced pancreas exhibited maximum LacZ expression at 1 week postdelivery, with greater than 90% of expression lost at 4 weeks. AAV2LacZ-transduced pancreas displayed peak LacZ levels at 4 weeks postdelivery, with no significant decrease in expression for up to 8 weeks. AAV8LacZ was at least 10-fold more efficient than AAV2LacZ in transducing the pancreas in vivo, with significant levels of expression detectable at 1 week, whereas AAV5LacZ did not result in any detectable transgene expression at all tested time points. All three vectors primarily transduced pancreatic acinar cell types, with limited transduction of pancreatic endocrine cells. AdVLacZ elicited a significant leukocyte infiltration early after delivery into the pancreas, whereas none of the AAV vectors elicited a significant leukocyte response. None of the tested vectors caused significant changes in serum amylase or blood glucose levels, suggesting that they do not significantly alter pancreatic function. These vectors will be useful for studying novel gene delivery based treatments in animal models for diabetes and other pancreatic disorders.
Extreme Beam Broadening using Phase Only Pattern Synthesis (2006)

This paper describes methods for broadening the beam of a phased array antenna using phase-only element weights. This type of broadening can be valuable for improving the search occupancy and/or reducing the search frame time for large phased arrays, when transmit beam broadening is combined with multiple simultaneous receive beams. Phase-only broadening is required for typical solid-state (active phased) arrays because control of the transmit amplitude at each element is not practical. A notable result is that there is a relationship between the amount of beam broadening and the efficiency (directivity) of the resulting beam. In particular it is shown that broadening less than ~2.5:1 results in reduced beam efficiency for both linear and circular arrays, while a broadening of greater than ~2.5:1 results in improved beam efficiency, and that, therefore, certain broadening configurations will be preferable to the radar designer (e.g. 4:1 in one plane rather than 2:1 in two planes, due to a large difference in efficiency). The algorithms used to achieve the broadening patterns presented here are based on a combination of homotopy from known optimality with a stochastic gradient descent approach using a carefully constructed one parameter family of penalty functions
IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance (2015)

Polymorphisms near the interferon lambda 3 (IFNL3) gene strongly predict clearance of hepatitis C virus (HCV) infection. We analyzed a variant (rs4803217 G/T) located within the IFNL3 mRNA 3' untranslated region (UTR); the G allele (protective allele) is associated with elevated therapeutic HCV clearance. We show that the IFNL3 3' UTR represses mRNA translation and the rs4803217 allele modulates the extent of translational regulation. We analyzed the structures of IFNL3 variant mRNAs at nucleotide resolution by SHAPE-MaP. The rs4803217 G allele mRNA forms well-defined 3' UTR structure while the T allele mRNA is more dynamic. The observed differences between alleles are among the largest possible RNA structural alterations that can be induced by a single nucleotide change and transform the UTR from a single well-defined conformation to one with multiple dynamic interconverting structures. These data illustrate that non-coding genetic variants can have significant functional effects by impacting RNA structure.
Building Predictive Models for Protein Tyrosine Phosphatase 1B Inhibitors Based on Discriminating Structural Features by Reassembling Medicinal Chemistry Building Blocks (2004)

A new approach to predicting the biological activity of small molecule pharmaceutics is demonstrated. Structural features of medicinal chemistry building blocks are used as 2-D molecular descriptors. These descriptors include predefined structural features and macrostructures obtained from a supervised process in which features in the core library are reassembled to provide larger features that strongly differentiate the desired biological response variable. Chemical features derived in this manner can serve as predictor variables for diverse modeling algorithms, and application using partial least squares techniques is demonstrated here. Models are presented for inhibition by benzofuran and benzothiophene biphenyl analogues of protein tyrosine phosphatase 1B (PTP1B), a target for insulin-resistant disease states. Results are compared to models for PTP1B inhibitors available in the literature based on CoMFA-related techniques and 3-D molecular descriptors.
Condor-G: a computation management agent for multi-institutional grids (2002)

In recent years, there has been a dramatic increase in the amount of available computing and storage resources, yet few have been able to exploit these resources in an aggregated form. We present the Condor-G system, which leverages software from Globus and Condor to allow users to harness multi-domain resources as if they all belong to one personal domain. We describe the structure of Condor-G and how it handles job management, resource selection, security and fault tolerance.
Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles (2004)

We find that single- and double-stranded oligonucleotides have different propensities to adsorb on gold nanoparticles in colloidal solution. We use this observation to design a hybridization assay based on color changes associated with gold aggregation. Because the underlying adsorption mechanism is electrostatic, no covalent functionalization of the gold, the probe, or the target DNA is required. Hybridization conditions can be optimized because it is completely separated from the detection step. The assay is complete within 5 min, and <100 femtomoles of target produces color changes observable without instrumentation. Single-base-pair mismatches are easily detected.
THETA-Rhythm Makes the World Go Round: Dissociative Effects of TMS Theta Versus Alpha Entrainment of Right pTPJ on Embodied Perspective Transformations (2017)

Being able to imagine another person's experience and perspective of the world is a crucial human ability and recent reports suggest that humans "embody" another's viewpoint by mentally rotating their own body representation into the other's orientation. Our recent Magnetoencephalography (MEG) data further confirmed this notion of embodied perspective transformations and pinpointed the right posterior temporo-parietal junction (pTPJ) as the crucial hub in a distributed network oscillating at theta frequency (3-7 Hz). In a subsequent transcranial magnetic stimulation (TMS) experiment we interfered with right pTPJ processing and observed a modulation of the embodied aspects of perspective transformations. While these results corroborated the role of right pTPJ, the notion of theta oscillations being the crucial neural code remained a correlational observation based on our MEG data. In the current study we therefore set out to confirm the importance of theta oscillations directly by means of TMS entrainment. We compared entrainment of right pTPJ at 6 Hz vs. 10 Hz and confirmed that only 6 Hz entrainment facilitated embodied perspective transformations (at 160° angular disparity) while 10 Hz slowed it down. The reverse was true at low angular disparity (60° between egocentric and target perspective) where a perspective transformation was not strictly necessary. Our results further corroborate right pTPJ involvement in embodied perspective transformations and highlight theta oscillations as a crucial neural code.
Comparative Absorption of a Standardized Curcuminoid Mixture and Its Lecithin Formulation (2011)

The relative absorption of a standardized curcuminoid mixture and its corresponding lecithin formulation (Meriva) was investigated in a randomized, double-blind, crossover human study. Clinically validated dosages were used for both products, and plasma levels of all three major curcuminoids [curcumin (1a), demethoxycurcumin (1b), and bisdemethoxycurcumin (1c)] were evaluated. Total curcuminoid absorption was about 29-fold higher for Meriva than for its corresponding unformulated curcuminoid mixture, but only phase-2 metabolites could be detected, and plasma concentrations were still significantly lower than those required for the inhibition of most anti-inflammatory targets of curcumin. Remarkably, phospholipid formulation increased the absorption of demethoxylated curcuminoids much more than that of curcumin (1a), with significant differences in plasma curcuminoid profile between Meriva and its corresponding unformulated curcuminoid mixture. Thus, the major plasma curcuminoid after administration of Meriva was not curcumin (1a), but demethoxycurcumin (1b), a more potent analogue in many in vitro anti-inflammatory assays. The improved absorption, and possibly also a better plasma curcuminoid profile, might underlie the clinical efficacy of Meriva at doses significantly lower than unformulated curcuminoid mixtures.
Multiple-Point Equalization in a Room Using Adaptive Digital Filters (1989)

&lt;p&gt;A method is present for designing an equalization filter for a sound-reproduction system by adjusting the filter coefficients to minimize the sum of the squares of the errors between the equalized responses at multiple points in the room and delayed versions of the original electrical signal. Such an equalization filter can give a more uniform frequency response over a greater volume of the enclosure than a filter designed to equalize at one point only. The results of computer simulations are presented for equalization in a 'room' with dimensions and acoustic damping typical of a car interior, using various algorithms to adapt automatically the coefficients of a digital equalization filter.&lt;/p&gt;
Cellular Localization and Regulation of Expression of Testicular Estrogen Sulfotransferase (1997)

Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the specific sulfonation of estrogens at the 3-hydroxyl position using 3'-phosphoadenosine-5'-phosphosulfate as an activated sulfate donor. Sulfated estrogens no longer bind to the estrogen receptor and are, therefore, hormonally inactive. Although liver has been considered a primary site for steroid sulfotransferase activities, we previously have cloned the mouse EST complementary DNA and found the enzyme to be expressed abundantly in the testis of normal mice. In this study we show by reverse transcription-PCR that EST is also expressed in the testes of rat and man, suggesting that testicular expression of EST may be a common phenomenon among different species. Using a purified polyclonal antibody raised against the bacterially expressed mouse EST protein, we demonstrate by immunohistochemistry that EST is localized selectively to the androgen-producing Leydig cells within the mouse testis. Additionally, we show that Leydig cell expression of EST is under the control of the pituitary hormone LH and is regulated differentially during development. In contrast to the high level of expression in mature intact animals, EST is not present in Leydig cells of hypophysectomized mice or in Leydig cells of fetal and prepubertal (day 5 or 17) mouse testes. Administration of hCG to hypophysectomized mice restored the testicular expression of EST. Together, these results suggest that testicular expression of EST may play an important role in male reproduction, conceivably by modulating the activity of locally synthesized estrogen in the testis of a sexually mature animal.
Nickel Complexes of Cysteine- and Cystine-Containing Peptides:  Spontaneous Formation of Disulfide-Bridged Dimers at Neutral pH (1998)

A series of nine tripeptide ligands of the type XCH (X = glycine or lysine, C = cysteine, H = histidine) was prepared, and the coordination chemistry of these peptides with Ni(II) was investigated. The cysteine residues were incorporated as free thiols, as protected (tert-butyl) thiols, or as disulfide-bridged cystine dimers, and the histidine residues had either carboxylate (CO2H) or carboxamide (CONH2) C-termini. The Ni(II) complexes of the protected thiols exhibited no interaction of the side chain with the metal, giving UV and electrochemical data which were consistent with related tripeptide species. The Ni(II) complexes of the free thiol-containing ligands GCH−CONH2, KCH−CONH2, and GCH−CO2H were found to dimerize rapidly via disulfide bond formation in the presence of air at pH 7. These processes were confirmed by independent synthesis of the dimeric (cystine) ligands and preparation of their Ni(II) complexes. The disulfide-bridged complex with a carboxylate terminus Ni2(GCH−CO2H)2 showed no further reactivity with oxygen, which was unusual, since Ni(II) complexes of XXH−CO2H peptides are known to spontaneously decarboxylate in air.
Fast detection of a protozoan pathogen, Perkinsus marinus, using AlGaN/GaN high electron mobility transistors (2009)

Antibody-functionalized, Au-gated AlGaN/GaN high electron mobility transistors (HEMTs) were used to detect Perkinsus marinus. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN/GaN HEMT drain-source current showed a rapid response of less than 5 s when the infected solution was added to the antibody-immobilized surface. The sensor can be recycled with a phosphate buffered saline wash. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN/GaN HEMTs for Perkinsus marinus detection.
Anti-idiotype-induced, lipopolysaccharide-specific antibody response to Pseudomonas aeruginosa . (1990)

Antibody directed to the O-specific polysaccharide (Ps) side chain of Pseudomonas aeruginosa LPS provides immunotype-specific protection against infection by virtue of enhancing opsonophagocytosis. We have developed a syngeneic anti-idiotypic antibody (mAb2) directed to a functionally active monoclonal immunotype 1 Ps-antibody (mAb1). The mAb2 performed as a molecular mimic of Ps as evidenced by 1) blocking of mAb1/mAb2 interaction by Ps, 2) blocking of mAb1/Ps binding by mAb2, 3) cross-species binding of mAb2 to human Ps antibodies from individuals immunized with the same immunotype 1 Ps, and 4) induction of anti-LPS antibody by immunization with mAb2 in syngeneic mice. Our studies thus show that an anti-idiotypic antibody may functionally mimic the O-polysaccharide of P. aeruginosa LPS, and bind to cross-reactive Id present in human Ps antibodies. We have further shown that this anti-idiotypic antibody induces anti-LPS antibody when used as an Ag in syngeneic mice, suggesting that this approach may eventually be used to successfully immunize humans.
Mutational Study of Heparan Sulfate 2-O-Sulfotransferase and Chondroitin Sulfate 2-O-Sulfotransferase (2007)

Heparan sulfate (HS) and chondroitin sulfate (CS) are highly sulfated polysaccharides with a wide range of biological functions. Heparan sulfate 2-O-sulfotransferase (HS-2OST) transfers the sulfo group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the 2-OH position of the hexauronic acid that is adjacent to N-sulfated glucosamine, whereas chondroitin sulfate 2-O-sulfotransferase (CS-2OST) transfers the sulfo group to the hexauronic acid that is adjacent to N-acetylated galactosamine. Here we report a systematic mutagenesis study of HS-2OST and CS-2OST based on their structural homology to estrogen sulfotransferase and HS 3-O-sulfotransferase isoform 3 (3-OST3), for which crystal structures exist. We have identified six residues possibly involved in binding to PAPS. HS-2OST carrying mutations of these residues lacks sulfotransferase activity and the ability to bind 3'-phosphoadenosine 5'-phosphate, a PAPS analogue, as determined by isothermal titration calorimetry. Similar residues involved in binding to PAPS were also identified in CS-2OST. Additional residues that participate in carbohydrate substrate binding were also identified in both enzymes. Mutations at these residues led to the loss of sulfotransferase activity but maintained the ability to bind to phosphoadenosine 5'-phosphate. The catalytic function of HS-2OST appears to involve two histidine residues (His140 and His142), whereas only one histidine (His168) of CS 2-OST is likely to be critical. This unique feature of HS 2-OST catalytic residues directed us to characterize the Drosophila heparan sulfate 2-O-sulfotransferase. The results from this study provide insight into the differences and similarities various residues play in the biological roles of the HS-2OST and CS-2OST enzymes.
CD4 Dimers Constitute the Functional Component Required for T Cell Activation (2002)

The CD4 molecule plays a key role in the development and activation of helper T cells. Dimerization and oligomerization is often a necessary step in the function of several cell surface receptors. Herein, we provide direct biochemical evidence confirming the presence of CD4 as dimers in transfected cells from hemopoetic and fibroblastic origin as well as in primary T cells. Such dimers are also observed with murine CD4 confirming selective pressure during evolution to maintain such a structure. Using a series of point mutations, we have precisely mapped the dimerization site at residues K318 and Q344 within the fourth extracellular domain of CD4. These residues are highly conserved and their mutation results in interference with dimer formation. More importantly, we demonstrate that dimer formation is essential for the coligand and coreceptor functions of CD4 in T cell activation. These data strongly suggest that CD4 dimerization is necessary for helper T cell function.