gebhart/patrepeval huggingface dataset:
Hypoxia-Inducible Factor 1α Regulates the Expression of the Mitochondrial ATPase Inhibitor Protein (IF1) in Rat Liver (2011)

A growing number of reports indicate that bioenergetic failure plays a crucial role in the development of multiple organ failure during sepsis. Our previous results showed that the suppression of IF1 (mitochondrial ATPase inhibitor protein) expression and subsequent elevated mitochondrial F(o)F₁-ATPase activity might contribute to the bioenergetic failure in the liver during sepsis, and the influence of the decreased transcriptional level of IF1 might be an important factor. In this study, we investigated the interaction of IF1 protein expression and hypoxia-inducible factor 1 (HIF-1), a transcription factor that is correlated with the inflammatory status in sepsis. The results showed that nuclear HIF-1α protein, a subunit of HIF-1, and IF1 mRNA expression were coincidently reduced in late septic liver of rats. Furthermore, in vitro, overexpression of HIF-1α by hypoxia or CoCl₂ (HIF-1α activator) treatment augmented IF1 protein levels. On the contrary, HIF-1α antisense oligonucleotide and siRNA were used to specifically downregulate HIF-1α expression, and then IF1 protein levels were significantly decreased in clone 9 cells. Meanwhile, downregulation of HIF-1α expression led to elevate the mitochondrial F(o)F₁-ATPase activity in the presence of Bis-Tris buffer (pH 6.5). In conclusion, these results suggested for the first time that the HIF-1 might play a crucial role in regulating IF1 protein expression in late septic liver.
Vaccine development against infection with Helicobacter pylori (1998)

Infection with Helicobacter pylori, is one of the most prevalent infections world-wide, where approximately 50% of adults in the developed world and over 90% of inhabitants in the developing world are infected. Chronic infection with H. pylori is the cause of gastritis, peptic ulcer disease and is a risk factor for gastric adenocarcinoma. Recent studies have demonstrated the suitability of an immunization strategy in the prevention and treatment of H. pylori infection, and the potential for management of disease. Mucosal administration of purified recombinant sub-unit proteins of H. pylori, together with a mucosal adjuvant, has identified urease to be highly efficacious in prophylactic and therapeutic animal model studies, and show partial therapeutic activity in humans. Several other antigens are also effective, and the recent sequencing of the H. pylori genome has led to an intensive effort in antigen discovery. Other research has centered on the identification of novel approaches for delivery, and the immunological mechanisms underlying protective immunity. In this review, preclinical data and the results of early-stage clinical trials and directions for future research on Helicobacter vaccines are described.
Mining for Implications in Medical Data (2006)

Accruing patients for clinical trials has been a tedious and time consuming task for clinicians. It requires extensive knowledge of the specific criteria for all available clinical trials. Through interviews with clinicians, implications were discovered which reduced the number of required questions/answers to determine eligibility. After gathering and recording data on past breast cancer patients, the answers to the questions asked by an expert system were extracted. An association rule learner, was used to generate implication rules such as: male => not pregnant. It was determined that all current implication rules could be recovered with 100% confidence. Further searching for additional rules resulted in the discovery of several which provided an improvement in the clinical ease of use of the Web-based clinical trial assignment expert system
Can the environment wait : priorities for East Asia (1997)

This report answers the question, Does paying too much attention to environmental problems slow economic growth and industrialization? Although the Asia/Pacific region may say yes and the experience of most industrial countries seems to support this view, in fact 1) today's rich countries did address some of the environmental problems associated with urbanization and growth; 2) advances in knowledge and technology have made the cost of reducing pollution low or negligible; and 3) the costs of environmental damage to health rise as countries invest more in the education and skills of workers. To continue current policies for the next 25 years would 1) leave many households without access to clean water and decent sanitation; 2) worsen urban air quality; and 3) increase the risks posed by heavy metals and persistent organic chemicals in rivers and water supplies. In the immediate future the main environmental priority in Southeast Asia is to expand access to water and urban sanitation and to control motor vehicle pollution. In China the main task is to phase out coal use (with some exceptions) and to develop the infrastructure to supply alternative fuels. Medium term concerns include pretreating industrial wastewater before discharging it into river basins; and similarly treating sewage while charging discharge fees. Longer term issues, such as acid rain and ground-level ozone, should be met with economic incentives like encouraging the use of low-sulfur coal.
Matrix Protein and Another Viral Component Contribute to Induction of Apoptosis in Cells Infected with Vesicular Stomatitis Virus (2001)

The induction of apoptosis in host cells is a prominent cytopathic effect of vesicular stomatitis virus (VSV) infection. The viral matrix (M) protein is responsible for several important cytopathic effects, including the inhibition of host gene expression and the induction of cell rounding in VSV-infected cells. This raises the question of whether M protein is also involved in the induction of apoptosis. HeLa or BHK cells were transfected with M mRNA to determine whether M protein induces apoptosis when expressed in the absence of other viral components. Expression of M protein induced apoptotic morphological changes and activated caspase-3 in both cell types, indicating that M protein induces apoptosis in the absence of other viral components. An M protein containing a point mutation that renders it defective in the inhibition of host gene expression (M51R mutation) activated little, if any, caspase-3, while a deletion mutant lacking amino acids 4 to 21 that is defective in the virus assembly function but fully functional in the inhibition of host gene expression was as effective as wild-type (wt) M protein in activating caspase-3. To determine whether M protein influences the induction of apoptosis in the context of a virus infection, the M51R M protein mutation was incorporated onto a wt background by using a recombinant infectious cDNA clone (rM51R-M virus). The timing of the induction of apoptosis by rM51R-M virus was compared to that by the corresponding recombinant wt (rwt) virus and to that by tsO82 virus, the mutant virus in which the M51R mutation was originally identified. In HeLa cells, rwt virus induced apoptosis faster than did rM51R-M virus, demonstrating a role for M protein in the induction of apoptosis. In contrast to the results obtained with HeLa cells, rwt virus induced apoptosis more slowly than did rM51R-M virus in BHK cells. This indicates that a viral component other than M protein contributes to induction of apoptosis in BHK cells and that wt M protein acts to delay induction of apoptosis by the other viral component. tsO82 virus induced apoptosis more rapidly than did rM51R-M virus in both HeLa and BHK cells. These two viruses contain the same point mutation in their M proteins, suggesting that sequence differences in genes other than that for M protein affect their rates of induction of apoptosis.
Synthesis of the Enzymes of the Mandelate Pathway by Pseudomonas putida I. Synthesis of Enzymes by the Wild Type (1966)

Hegeman, G. D. (University of California, Berkeley). Synthesis of the enzymes of the mandelate pathway by Pseudomonas putida. I. Synthesis of enzymes by the wild type. J. Bacteriol. 91:1140-1154. 1966.-The control of synthesis of the five enzymes responsible for the conversion of d(-)-mandelate to benzoate by Pseudomonas putida was investigated. The first three compounds occurring in the pathway, d(-)-mandelate, l(+)-mandelate, and benzoylformate, are equipotent inducers of all five enzymes. A nonmetabolizable inducer, phenoxyacetate, also induces synthesis of these enzymes; but, unlike the metabolizable inducer-substrates, it does not elicit synthesis of enzymes that mediate steps in the pathway beyond benzoate. Under conditions of semigratuity, dl-mandelate elicits immediate synthesis at a steady rate of the first two enzymes of the pathway, but two enzymes which act below the level of benzoate are synthesized only after a considerable lag. Succinate and asparagine do not significantly repress the synthesis of the enzymes responsible for mandelate oxidation.
Multiple forms of long‐term potentiation and multiple regulatory sites of N‐methyl‐D‐aspartate receptors: Role of the redox site (1995)

Long-term potentiation (LTP) is a form of synaptic plasticity thought to be involved in learning and memory. Although extensively studied, mainly in the CA1 region of the hippocampus, the mechanisms underlying the induction and expression of LTP are poorly elucidated. This is probably due to the fact that LTP is not a unique process and indeed recent studies have shown that several forms of LTP could be generated depending on the experimental conditions. Furthermore, LTP is generally associated with a long-lasting increase of the synaptic efficacy of AMPA receptors but an increasing number of data also suggested that NMDA receptors could be potentiated as well. NMDA receptor responses are modulated by a large number of extracellular and intracellular events, providing additional possibilities for the generation of LTP. The role of these different modulatory sites of the NMDA receptor and their relation with LTP are reviewed with a particular attention to the redox site which seems to be a selective target to distinguish between AMPA and NMDA-LTP.
Molecular Biology and Immunology of Allergens (1993)

HLA Genes Determining Susceptibility to Allergy (D.G. Marsh and L.R. Freidhoff). Structure-Immunogenicity Relationship of a Peptide Allergen, Melittin (T.P. King, M.R. Coscia, and L. Kochoumian). Recombinant Arthropod Allergens (W.R. Thomas and K.-Y. Chua). Pollen Allergens: Botanical Aspects (R.B. Knox, P. Taylor, P. Smith, T. Hough, E.K. Ong, C. Suphioglu, M. Lavithis, S. Davies, A. Avjiouglu, and M. Singh). Biological Functions, Isoforms, and Environmental Control in the Bet V I Gene Family (A. Jilek, I. Swoboda, H. Breiteneder, I. Fogy, F. Ferreira, E. Schmid, E. Heberle-Bors, O. Scheiner, H. Rumpold, H.T. Koller, and M. Breitenbach). Profilin-A Novel Plant Panallergen (R. Valenta, M. Duchene, W. Sperr, P. Valent, S. Vrtala, R. Hirschwehr, F. Ferreira, D. Kraft, and O. Scheiner). Structural Considerations of Antigen Recognition: Three-Dimensional Structure Determination of the Ragweed Allergens Amb t V and Amb a V by Nuclear Magnetic Resonance (W.J. Metzler and l. Mueller). T Cell Epitopes, MHC Antigens and Their Application (R.E. O'Hehir, J.A. Higgins, E.R. Jarman, and J.R. Lamb). Cross-reactivity among Pollen Allergens: Structural Motifs of Allergenic Proteins (S.S. Mohapatra). New Therapeutic Modalities for IgE-Mediated Allergies (J.R. Lamb, J.A. Higgins, E.R. Jarman, R.E. O'Hehir). Allergen, Immunoglobulin E, and the Quest for a Rational Inhibitor of the Allergic Responce (B.A. Helm and E.A. Padlan). Good or Bad IgE and Anti-IgE Antibodies: New Molecular Concepts (A.L. De Weck and B. Stadler). Therapeutic Potential of Recombinant Allergens (A.H. Sehon and S.S. Mohapatra). Index.
Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure (2011)

These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression.
Mechanisms of Quenching of Alexa Fluorophores by Natural Amino Acids (2010)

Quenching of fluorophores by the same proteins that they covalently label is a phenomenon that is neither well-known nor well-characterized. It is often assumed that fluorophores are unperturbed by their target proteins. However, it has been observed that attached fluorophores can be quenched by contact with amino acids within the same protein, and this property has been exploited to report on changing conformational states or intramolecular dynamics of proteins. We show in this communication that fluorescence of Alexa dyes is, in fact, quenched by interactions with Trp, Tyr, Met, and His residues through a combination of static and dynamic quenching mechanisms. In light of this finding, the potential effect of intramolecular quenching should be considered in the interpretation of data that involves quantitative measurements of fluorescence intensity in proteins.
The PDZ Protein TIP-1 Interacts with the Rho Effector Rhotekin and Is Involved in Rho Signaling to the Serum Response Element (2000)

The human T-cell lymphotrophic virus, type 1 Tax protein can interact via its C terminus with various proteins including a PDZ domain. In this work, one of them, TIP-1, is characterized as a cytoplasmic 14-kDa protein mainly corresponding to one PDZ domain. A two-hybrid screen performed with TIP-1 as bait showed that it interacts with the human homologue of rhotekin that was previously identified in mice as a Rho effector. Both human and mouse rhotekins exhibit at their C termini the sequence QSPV-COOH that matches the X(S/T)XV-COOH consensus known for proteins recognizing PDZ domains. Mutation of the serine and valine residues to alanine impairs interaction of rhotekin with TIP-1. Transient expression experiments with a reporter construct including the c-Fos serum response element (SRE) showed that coexpression of TIP-1 with the constitutively active RhoA.V14 mutant and human rhotekin caused a strong activation of the SRE. A negative mutant of Rho, RhoA.N19, was unable to cooperate with TIP-1 and rhotekin. The positive effect of TIP-1 was also lost when the C terminus of rhotekin was mutated. These data show that the complex of active Rho with its effector rhotekin bound to TIP-1 produces in the cytoplasm a signal that triggers strong activation of the SRE.
Next Generation Mobile Fronthaul Architectures (2015)

The evolution to ever higher radio bandwidths and the massive introduction of new services and technologies in 5G networks, along with their challenging requirements in the time and frequency domain will warrant revisiting the present CPRI fronthaul approach.
Accessing and selecting menu items by in-air touch (2019)

Is it possible to realize a non-visual, purely tactile version of an icon-based menu? Driven by such question, a hierarchical tactile dock was designed for an array of ultrasound emitters. The icons were conceived as spatio-temporal variable-speed sequences of tactile stimulation points, that are passively perceived as trajectories drawn on the palm of the hand. The recognition rate on four icons largely improved prior performance results obtained by active haptic exploration. As a result, a four-icons set can be used as the first level of a hierarchy of symbols that can be navigated by touch and gesture. The design process, based on controlled recognition experiments and exploration of dissimilarity data, can be iterated to converge to a set of icons that are suitable for a functional tactile dock.
Truly single-mode polarization maintaining hollow core PCF (2012)

Fabrication of a truly single mode, low loss and polarization maintaining HC-PCF is reported. This fiber has a 50 nm wide strictly single mode region with good polarization holding (h-parameter below 10<sup>-4</sup> m<sup>-1</sup>) and low loss (&lt;20 dB/km).
Synovial Fibroblasts from Patients with Rheumatoid Arthritis, Like Fibroblasts from Graves’ Disease, Express High Levels of IL-16 When Treated with Igs against Insulin-Like Growth Factor-1 Receptor (2004)

We have reported recently that IgG from patients with Graves' disease (GD) can induce the expression of the CD4-specific T lymphocyte chemoattractant, IL-16, and RANTES, a C-C chemokine, in their fibroblasts. This induction is mediated through the insulin-like growth factor-1 receptor (IGF-1R) pathway. We now report that Abs from individuals with active rheumatoid arthritis (RA-IgG) stimulate in their synovial fibroblasts the expression of these same cytokines. IgG from individuals without known autoimmune disease fails to elicit this chemoattractant production. Furthermore, RA-IgG fails to induce IL-16 or RANTES expression in synovial fibroblasts from donors with osteoarthritis. RA-IgG-provoked IL-16 and RANTES production also appears to involve the IGF-1R because receptor-blocking Abs prevent the response. RA fibroblasts transfected with a dominant-negative mutant IGF-1R fail to respond to RA-IgG. IGF-1 and the IGF-1R-specific analog Des(1-3) also induce cytokine production in RA fibroblasts. RA-IgG-provoked IL-16 expression is inhibited by rapamycin, a specific macrolide inhibitor of the Akt/FRAP/mammalian target of rapamycin/p70(s6k) pathway, and by dexamethasone. GD-IgG can also induce IL-16 in RA fibroblasts, and RA-IgG shows similar activity in GD fibroblasts. Thus, IgGs from patients with RA, like those associated with GD, activate IGF-1R, and in so doing provoke T cell chemoattraction expression in fibroblasts, suggesting a potential common pathway in the two diseases. Immune-competent cell trafficking to synovial tissue is integral to the pathogenesis of RA. Recognition of this novel RA-IgG/fibroblast interaction and its functional consequences may help identify therapeutic targets.
Structural Determinants of the Substrate and Stereochemical Specificity of Phosphotriesterase (2001)

Bacterial phosphotriesterase (PTE) catalyzes the hydrolysis of a wide variety of organophosphate nerve agents and insecticides. Previous kinetic studies with a series of enantiomeric organophosphate triesters have shown that the wild type PTE generally prefers the S(P)-enantiomer over the corresponding R(P)-enantiomers by factors ranging from 1 to 90. The three-dimensional crystal structure of PTE with a bound substrate analogue has led to the identification of three hydrophobic binding pockets. To delineate the factors that govern the reactivity and stereoselectivity of PTE, the dimensions of these three subsites have been systematically altered by site-directed mutagenesis of Cys-59, Gly-60, Ser-61, Ile-106, Trp-131, Phe-132, His-254, His-257, Leu-271, Leu-303, Phe-306, Ser-308, Tyr-309, and Met-317. These studies have shown that substitution of Gly-60 with an alanine within the small subsite dramatically decreased k(cat) and k(cat)/K(a) for the R(P)-enantiomers, but had little influence on the kinetic constants for the S(P)-enantiomers of the chiral substrates. As a result, the chiral preference for the S(P)-enantiomers was greatly enhanced. For example, the value of k(cat)/K(a) with the mutant G60A for the S(P)-enantiomer of methyl phenyl p-nitrophenyl phosphate was 13000-fold greater than that for the corresponding R(P)-enantiomer. The mutation of I106, F132, or S308 to an alanine residue, which enlarges the small or leaving group subsites, caused a significant reduction in the enantiomeric preference for the S(P)-enantiomers, due to selective increases in the reaction rates for the R(P)-enantiomers. Enlargement of the large subsite by the construction of an H254A, H257A, L271A, or M317A mutant had a relatively small effect on k(cat)/K(a) for either the R(P)- or S(P)-enantiomers and thus had little effect on the overall stereoselectivity. These studies demonstrate that by modifying specific residues located within the active site of PTE, it is possible to dramatically alter the stereoselectivity and overall reactivity of the native enzyme toward chiral substrates.
Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway (2002)

Efferent activity in the vagus nerve can prevent endotoxin-induced shock by attenuating tumor necrosis factor (TNF) synthesis. Termed the "cholinergic antiinflammatory pathway," inhibition of TNF synthesis is dependent on nicotinic alpha-bungarotoxin-sensitive acetylcholine receptors on macrophages. Vagus nerve firing is also stimulated by CNI-1493, a tetravalent guanylhydrazone molecule that inhibits systemic inflammation. Here, we studied the effects of pharmacological and electrical stimulation of the intact vagus nerve in adult male Lewis rats subjected to endotoxin-induced shock to determine whether intact vagus nerve signaling is required for the antiinflammatory action of CNI-1493. CNI-1493 administered via the intracerebroventricular route was 100,000-fold more effective in suppressing endotoxin-induced TNF release and shock as compared with intravenous dosing. Surgical or chemical vagotomy rendered animals sensitive to TNF release and shock, despite treatment with CNI-1493, indicating that an intact cholinergic antiinflammatory pathway is required for antiinflammatory efficacy in vivo. Electrical stimulation of either the right or left intact vagus nerve conferred significant protection against endotoxin-induced shock, and specifically attenuated serum and myocardial TNF, but not pulmonary TNF synthesis, as compared with sham-operated animals. Together, these results indicate that stimulation of the cholinergic antiinflammatory pathway by either pharmacological or electrical methods can attenuate the systemic inflammatory response to endotoxin-induced shock.
Directed evolution of a protein: selection of potent neutrophil elastase inhibitors displayed on M13 fusion phage. (1992)

Inhibitors of human neutrophil elastase were engineered by designing and producing a library of phage-displayed protease inhibitory domains derived from wild-type bovine pancreatic trypsin inhibitor and fractionating the library for binding to the target protease. The affinity of one of the engineered variants for human neutrophil elastase (Kd = 1.0 pM) is 3.6 x 10(6)-fold higher than that of the parental protein and exceeds the highest affinity reported for any reversible human neutrophil elastase inhibitor by 50-fold. Thus the display phage method has allowed us to obtain protein derivatives that exhibit greatly increased affinity for a predetermined target. The technology can be applied to design high-affinity proteins for a wide variety of target molecules.
Epidermal growth factor receptor mutation type iii transfected into a small cell lung cancer cell line is predominantly localized at the cell surface and enhances the malignant phenotype (2001)

In the present study we transfected the epidermal growth factor receptor (EGFR)-negative small cell lung cancer cell line, GLC3, with the type III EGFR mutation (EGFRvIII). The EGFRvIII protein could be detected by Western blot analysis as a 145-kDa protein, which by immunohistochemistry appeared to be localized at the cell surface. Ultrastructurally EGFRvIII was expressed mainly at the cell surface with clusters at cell-cell contacts. In the in vitro invasion assay, GLC3-EGFRvIII cells had a approximately 5-fold increased invasion compared with uninduced GLC3-EGFRvIII, GLC3-Tet-On and the parental cell line. GLC3-Tet-On appeared uniform in size with adherence junctions at cell-cell contacts. In uninduced GLC3-EGFRvIII cells adherence junctions were also present but less distinct. In doxycycline-pretreated GLC3-EGFRvIII cells, adherence junctions were absent. We conclude that the expression of EGFRvIII results in a more malignant phenotype. This effect appears to involve the disruption of adherence junctions.