gebhart/patrepeval huggingface dataset:
GCN2 phosphorylation of eIF2α activates NF-κB in response to UV irradiation (2005)

In response to UV irradiation, mammalian cells elicit a gene expression programme designed to repair damage and control cell proliferation and apoptosis. Important members of this stress response include the NF-kappaB (nuclear factor-kappaB) family. However, the mechanisms by which UV irradiation activates NF-kappaB are not well understood. In eukaryotes, a variety of environmental stresses are recognized and remediated by a family of protein kinases that phosphorylate the alpha subunit of eIF2 (eukaryotic initiation factor-2). In the present study we show that NF-kappaB in MEF (murine embryo fibroblast) cells is activated by UV-C and UV-B irradiation through a mechanism requiring eIF2alpha phosphorylation. The primary eIF2alpha kinase in response to UV is GCN2 (general control non-derepressible-2), with PEK/PERK (pancreatic eIF2alpha kinase/RNA-dependent-protein-kinase-like endoplasmic-reticulum kinase) carrying out a secondary function. Our studies indicate that lowered protein synthesis accompanying eIF2alpha phosphorylation, combined with eIF2alpha kinase-independent turnover of IkappaBalpha (inhibitor of kappaBalpha), reduces the levels of IkappaBalpha in response to UV irradiation. Release of NF-kappaB from the inhibitory IkappaBalpha would facilitate NF-kappaB entry into the nucleus and targeted transcriptional control. We also find that loss of GCN2 in MEF cells significantly enhances apoptosis in response to UV exposure similar to that measured in cells deleted for the RelA/p65 subunit of NF-kappaB. These results demonstrate that GCN2 is central to recognition of UV stress, and that eIF2alpha phosphorylation provides resistance to apoptosis in response to this environmental insult.
Lune/eye gone, a Pax-like protein, uses a partial paired domain and a homeodomain for DNA recognition (1998)

Pax proteins, characterized by the presence of a paired domain, play key regulatory roles during development. The paired domain is a bipartite DNA-binding domain that contains two helix-turn-helix domains joined by a linker region. Each of the subdomains, the PAI and RED domains, has been shown to be a distinct DNA-binding domain. The PAI domain is the most critical, but in specific circumstances, the RED domain is involved in DNA recognition. We describe a Pax protein, originally called Lune, that is the product of the Drosophila eye gone gene (eyg). It is unique among Pax proteins, because it contains only the RED domain. eyg seems to play a role both in the organogenesis of the salivary gland during embryogenesis and in the development of the eye. A high-affinity binding site for the Eyg RED domain was identified by using systematic evolution of ligands by exponential enrichment techniques. This binding site is related to a binding site previously identified for the RED domain of the Pax-6 5a isoform. Eyg also contains another DNA-binding domain, a Prd-class homeodomain (HD), whose palindromic binding site is similar to other Prd-class HDs. The ability of Pax proteins to use the PAI, RED, and HD, or combinations thereof, may be one mechanism that allows them to be used at different stages of development to regulate various developmental processes through the activation of specific target genes.
Chemosensitizing effects of sphingosine kinase-1 inhibition in prostate cancer cell and animal models (2008)

We have previously reported that, in prostate cancer, inhibition of the oncogenic sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway is a key element in chemotherapy-induced apoptosis. Here, we show that selective pharmacologic inhibition of SphK1 triggers apoptosis in LNCaP and PC-3 prostate cancer cells, an effect that is reversed by SphK1 enforced expression. More importantly, we show for the first time that the up-regulation of the SphK1/S1P pathway plays a crucial role in the resistance of prostate cancer cells to chemotherapy. Importantly, pharmacologic SphK1 inhibition with the B-5354c compound sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to S1P sphingolipid ratio. To conclude, our study highlights the notion that drugs specifically designed to inhibit SphK1 could provide a means of enhancing the effects of conventional treatment through the prosurvival antiapoptotic SphK1/S1P pathway.
Monitoring Earth Surface Dynamics With Optical Imagery (2008)

The increasing availability of high‐quality optical satellite images should allow, in principle, continuous monitoring of Earth's surface changes due to geologic processes, climate change, or anthropic activity. For instance, sequential optical images have been used to measure displacements at Earth's surface due to coseismic ground deformation [e.g., Van Puymbroeck et al. , 2000], ice flow [ Scambos et al. , 1992; Berthier et al. , 2005], sand dune migration [ Crippen , 1992], and landslides [ Kääb , 2002; Delacourt et al. , 2004]. Surface changes related to agriculture, deforestation, urbanization, and erosion—which do not involve ground displacement—might also be monitored, provided that the images can be registered with sufficient accuracy. Although the approach is simple in principle, its use is still limited, mainly because of geometric distortion of the images induced by the imaging system, biased correlation techniques, and implementation difficulties.
Choosing a concomitant chemotherapy and radiotherapy regimen for squamous cell head and neck cancer: A systematic review of the published literature with subgroup analysis (2001)

Platinum-based concomitant CT and RT is superior to conventional RT alone in improving survival in locally advanced SCHNC. Subgroup analyses can be used to help in choosing the most appropriate concomitant regimen.
Effects of Antenna Size and Configurations in Large-Area RF Plasma Production with Internal Low-Inductance Antenna Units (2006)

Recent trends of liquid crystal display (LCD) fabrication toward a significant enlargement of glass substrates require large-area plasma sources with a scale length exceeding 1 m. To meet this requirement, large-area plasma sources with internal low-inductance antenna (LIA) units have been developed for uniform processes, in which design principles for selecting antenna size and configurations in the multiple installation of the LIA units are established. In this study, the effects of antenna size were examined in terms of plasma production characteristics indicating small increase in plasma density with a decrease in antenna size (or antenna impedance). Furthermore, plasma density distributions with the LIA units were investigated to understand the nature of plasma diffusion, which can be utilized for designing plasma profiles with multiple LIA units. First, it was shown that the plasma density distributions followed exponential decay as a function of distance from the antenna. Secondly, the measured plasma density profiles with multiple LIA units were shown to agree well with those obtained by superposing those described by exponential functions, which can be utilized for prediction.
Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. (1983)

We describe the production of the monoclonal antibody B73.1, reacting with a subset of human lymphocytes and, in about one-half of the donors, with neutrophilic polymorphonuclear leukocytes. In the peripheral blood from normal adult donors, 14.6 +/- 8.5% of the lymphocytes react with B73.1 antibody. The B73.1(+) lymphocyte subset does not bear markers of typical T or B cells and corresponds to the lymphocyte subset containing antibody-dependent killer (K) and natural killer (NK) cells. We demonstrate that: a) virtually all lymphocytes with K/NK cytotoxic activity are found in the lymphocyte subpopulation bearing the B73.1-defined antigen; b) the B73.1(+) lymphocyte subset bears the combination of antigens known to be present on K/NK cells; and c) there is a positive correlation between the level of cytotoxicity and the actual number of B73.1(+) lymphocytes in individual donors. We also report the distribution of B73.1(+) lymphocytes according to donor age and tissue types. The use of the B73.1 antibody in quantitating the actual number of K/NK cells and in performing functional studies on spontaneous cytotoxicity is discussed.
Heat Production and Body Temperature During Cooling and Rewarming in Overweight and Lean Men (2006)

Overweight subjects showed a blunted mild cold-induced thermogenesis. The insulative cold response was not different among the groups. The energy-efficient response of the overweight subjects can have consequences for energy balance in the long term. The results support the concept of a dynamic heat regulation model instead of temperature regulation around a fixed set point.
Oligodeoxynucleotides containing 2'-O-modified adenosine: Synthesis and effects on stability of DNA:RNA duplexes (1993)

Hybridization thermodynamics were compared for oligonucleotide sequences containing 2'-fluoro dA, 2'-O-methyl A, 2'-O-ethyl A, 2'-O-propyl A, 2'-O-butyl A, 2'-O-pentyl A, 2'-O-nonyl A, 2'-O-allyl A, and 2'-O-benzyl A in place of deoxyadenosine. Although the effect of 2'-modified adenosine on duplex stability is sequence dependent, a clear trend is apparent. For six sequences containing a few 2'-modified adenosines in a background of unmodified deoxynucleotides, the average delta TM per substitution ranged from +1.3 degrees C for 2'-fluoro dA to -2.0 degrees C for 2'-O-nonyl A. For the 2'-O-alkyl series, the average delta TM per substitution correlates well with size of the substituent; the order of stability is 2'-O-methyl A > 2'-O-ethyl A > 2'-O-propyl A > 2'-O-butyl A > 2'-O-pentyl A > 2'-O-nonyl A. This correlation also extends to 2'-fluoro dA, 2'-O-allyl A, and 2'-O-benzyl A if chain length is measured by number of carbon atoms. When examined in the background of 2'-O-methyl ribonucleotides, all 2'-modified adenosines with a substituent no larger than 2'-O-pentyl stabilized the duplex nearly 2 degrees C per substitution compared to unmodified dA. These thermodynamic results and CD spectra of modified and unmodified hybrids support a model of DNA:RNA hybrids in which the geometry is between that of B-form and A-form.
Linking Mind and Brain in the Study of Mental Illnesses: A Project for a Scientific Psychopathology (1997)

Brain research on mental illnesses has made substantial advances in recent years, supported by conceptual and technological developments in cognitive neuroscience. Brain-based cognitive models of illnesses such as schizophrenia and depression have been tested with a variety of techniques, including the lesion method, tract tracing, neuroimaging, animal modeling, single-cell recording, electrophysiology, neuropsychology, and experimental cognitive psychology. A relatively sophisticated picture is emerging that conceptualizes mental illnesses as disorders of mind arising in the brain. Convergent data using multiple neuroscience techniques indicate that the neural mechanisms of mental illnesses can be understood as dysfunctions in specific neural circuits and that their functions and dysfunctions can be influenced or altered by a variety of cognitive and pharmacological factors.
A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat. (1990)

Regulation of human immunodeficiency virus (HIV) gene expression is dependent on specific regulatory regions in the long terminal repeat. These regions include the enhancer, SP1, "TATA," and trans-activating (TAR) regions. In addition, viral regulatory proteins such as tat and rev are important in regulating HIV gene expression. The mechanism of tat activation remains the subject of investigation, but effects at both transcriptional and posttranscriptional levels seem likely. Previous mutagenesis of the tat protein revealed that the amino terminus, the cysteine-rich domain, and the basic domain were all required for complete tat activation. Mutants of other viral trans-acting regulatory proteins, including E1A, tax, and VM65, have been identified that were capable of antagonizing the activity of their corresponding wild-type proteins. We wished to determine whether mutants of the tat protein could be identified that exhibited a similar phenotype. One mutant (delta tat) that truncated the basic domain of tat resulted in a transdominant phenotype inhibiting tat-induced gene expression of the HIV long terminal repeat but not other viral promoters. This mutant exhibited its maximal phenotype in cotransfection experiments when present in an 8- to 30-fold molar excess over the wild-type tat gene. Trans-activation of the HIV long terminal repeat by delta tat was very defective at the DNA concentrations used in these experiments. RNase protection analysis indicated that this mutant decreased tat-induced steady-state mRNA levels of the HIV long terminal repeat. Second-site mutations of the delta tat gene in either the amino terminus or cysteine region eliminated the transdominant phenotype. In contrast to tat, which was localized predominantly to the nucleolus, delta tat was present in both the nucleus and cytoplasm, suggesting that it may inhibit tat function by preventing nucleolar localization. Transdominant mutants of tat may have a role in potentially inhibiting HIV gene expression.
Plasminogen activator inhibitor in the blood of patients with coronary artery disease. (1985)

many years (more than 10 years in some cases). Given the varia- tion in sesquiterpene lactone content between varieties of fever- few and plants harvested in different seasons (P J Hylands, unpublished findings), it would seem desirable for commercial preparations of feverfew to be standardised chemically.
Gene therapy in diabetes (2010)

Type 1 diabetes (T1D) is a chronic autoimmune disease, whereby auto-reactive cytotoxic T cells target and destroy insulin-secreting β-cells in pancreatic islets leading to insulin deficiency and subsequent hyperglycemia. These individuals require multiple daily insulin injections every day of their life without which they will develop life-threatening diabetic ketoacidosis (DKA) and die. Gene therapy by viral vector and non-viral transduction may be useful techniques to treat T1D as it can be applied from many different angles; such as the suppression of autoreactive T cells to prevent islet destruction (prophylactic) or the replacement of the insulin gene (post-disease). The need for a better method for providing euglycemia arose from insufficient numbers of cadaver islets for transplantation and the immunosuppression required post-transplant. Ectopic expression of insulin or islet modification have been examined, but not perfected. This review examines the various gene transfer methods, gene therapy techniques used to date and promising novel techniques for the maintenance of euglycemia in the treatment of T1D.
Planar light-emitting devices fabricated with luminescent electrochemical polyblends (1997)

Light emitting devices were fabricated in planar (surface cell) configurations with low operating voltage. Polymer blends composed of a red or green color luminescent polymer and solid state electrolyte were used as the active materials. Under external bias, electrochemical doping occurs in the vicinity of the contact, and a dynamic p-n junction forms between the electrodes. Light emission is observed in the junction area at bias voltages greater than 2 V, reaching 102cd/m2 at voltage well below 5 V. The planar configuration allows display devices to be hybridized with integrated circuits on a silicon wafer. On transparent substrates, such as glass or plastic films, light emission can be viewed from both sides of the device. Emissive displays in the planar surface cell configuration can be fabricated using roll-to-roll processing at room temperature without need for vacuum equipment.
Enhanced elimination of implantation damage upon exceeding the solid solubility (1987)

Implantation of silicon wafers with Ga and P, under specific conditions, results in enhanced category-II (end of range) dislocation loop elimination after short thermal cycling. Comparison of these results with transmission electron microscopy studies of Si-, Ge-, As-, Al-, and Sb-implanted samples indicate that the enhanced elimination process occurs only when the peak of the impurity concentration exceeds the solid solubility of the impurity in silicon at the annealing temperature and the resulting precipitates are dissolving. The activation energy for enhanced elimination of these extrinsic catetory-II dislocation loops is shown to be 5±0.5 eV. It is proposed that vacancy emission by the dissolving precipitates is responsible for the enhanced elimination.
Local temperature in quantum thermal states (2009)

We consider blocks of quantum spins in a chain at thermal equilibrium, focusing on their properties from a thermodynamical perspective. In a classical system the temperature behaves as an intensive magnitude, above a certain block size, regardless of the actual value of the temperature itself. However, a deviation from this behavior is expected in quantum systems. In particular, we see that under some conditions the description of the blocks as thermal states with the same global temperature as the whole chain fails. We analyze this issue by employing the quantum fidelity as a figure of merit, singling out in detail the departure from the classical behavior. As it may be expected, we see that quantum features are more prominent at low temperatures and are affected by the presence of zero-temperature quantum phase transitions. Interestingly, we show that the blocks can be considered indeed as thermal states with a high fidelity, provided an effective local temperature is properly identified. Such a result may originate from typical properties of reduced subsystems of energy-constrained Hilbert spaces. Finally, the relation between local and global temperatures is analyzed as a function of the size of the blocks and the system parameters.
Frog: a FRee Online druG 3D conformation generator (2007)

In silico screening methods based on the 3D structures of the ligands or of the proteins have become an essential tool to facilitate the drug discovery process. To achieve such process, the 3D structures of the small chemical compounds have to be generated. In addition, for ligand-based screening computations or hierarchical structure-based screening projects involving a rigid-body docking step, it is necessary to generate multi-conformer 3D models for each input ligand to increase the efficiency of the search. However, most academic or commercial compound collections are delivered in 1D SMILES (simplified molecular input line entry system) format or in 2D SDF (structure data file), highlighting the need for free 1D/2D to 3D structure generators. Frog is an on-line service aimed at generating 3D conformations for drug-like compounds starting from their 1D or 2D descriptions. Given the atomic constitution of the molecules and connectivity information, Frog can identify the different unambiguous isomers corresponding to each compound, and generate single or multiple low-to-medium energy 3D conformations, using an assembly process that does not presently consider ring flexibility. Tests show that Frog is able to generate bioactive conformations close to those observed in crystallographic complexes. Frog can be accessed at http://bioserv.rpbs.jussieu.fr/Frog.html.
Multirate-aware Multicast Routing in MANETs (2006)

We propose a rate-adaptive multicast (RAM) routing protocol for mobile ad-hoc networks (MANETs) that is multirate-aware. During the process of path discovery, the quality of wireless links is estimated to suggest optimal transmission rates, which are then used to calculate the total transmission time incurred by the mobile nodes on a path. Among several considered paths from a source to a destination, RAM selects the path with the lowest total transmission time. Simulation results have shown that RAM outperforms single-rate multicast in terms of packet delivery ratio, packet end-to-end delay, and throughput of the multicast group. In this paper, we apply RAM to effectively support video multicast in MANETs
A 6 bp Z‐DNA hairpin binds two Zα domains from the human RNA editing enzyme ADAR1 (1999)

The Z alpha domain of the human RNA editing enzyme double-stranded RNA deaminase I (ADAR1) binds to left-handed Z-DNA with high affinity. We found by analytical ultracentrifugation and CD spectroscopy that two Z alpha domains bind to one d(CG)3T4(CG)3 hairpin which contains a stem of six base pairs in the Z-DNA conformation. Both wild-type Z alpha and a C125S mutant show a mean dissociation constant of 30 nM as measured by surface plasmon resonance and analytical ultracentrifugation. Our data suggest that short (> or = 6 bp) segments of Z-DNA within a gene are able to recruit two ADAR1 enzymes to that particular site.
Enzymatic Gene Amplification: Qualitative and Quantitative Methods for Detecting Proviral DNA Amplified in Vitro (1988)

We evaluated various detection methods to identify amplified human retroviral sequences after Thermus aquaticus-directed polymerase chain reaction (PCR). A combination of hybridization formats and direct incorporation assays provided the most information. This multiphasic approach enabled us to detect specific human T cell leukemia virus type I (HTLV-I)-homologous regions in several HTLV-I-seronegative patients with T cell lymphoma, as well as variants of HTLV-I and human immunodeficiency virus type 1 in patients with prototype disease. In all diagnostic assays designed to detect a particular retrovirus, it was necessary to include a hybridization step, because sequences (endogenous or exogenous) homologous to certain primers were present in most human DNA preparations and yielded discrete products, sometimes of the predicted molecular weight, after amplification. These products could be discriminated by hybridization from amplified prototype proviral sequences. The intensity of the signal generated after hybridization was proportional to input target DNA, an observation making it feasible to quantitatively measure the proviral load in a DNA sample.
The product of the protooncogene c-src is modified during the cellular response to platelet-derived growth factor. (1985)

We have observed a modification of the cellular protein kinase pp60c-src, elicited in murine 3T3 fibroblasts by platelet-derived growth factor (PDGF). The modification occurred rapidly after addition of PDGF to the culture medium and was first detected as a reduction in the electrophoretic mobility of a portion of the pp60c-src molecules. A similarly modified form of the viral homologue pp60v-src occurs in vivo in the absence of stimulation by PDGF. The occurrence of modified forms of both pp60c-src and pp60v-src was associated with a novel phosphorylation at tyrosine in the amino-terminal domains of the proteins. The time-course and dose-response for this modification of pp60c-src paralleled PDGF-induced increases in phosphorylation of pp36, a major cellular substrate for several tyrosine-specific protein kinases. In parallel experiments, treatment of cells with PDGF increased the kinase activity of pp60c-src in an immunocomplex assay. These results suggest pp60c-src may play a role in the mitogenic response to PDGF.