gebhart/patrepeval huggingface dataset:
Aminoacyl tRNA synthetases and their connections to disease (2008)

Aminoacylation of transfer RNAs establishes the rules of the genetic code. The reactions are catalyzed by an ancient group of 20 enzymes (one for each amino acid) known as aminoacyl tRNA synthetases (AARSs). Surprisingly, the etiology of specific diseases-including cancer, neuronal pathologies, autoimmune disorders, and disrupted metabolic conditions-is connected to specific aminoacyl tRNA synthetases. These connections include heritable mutations in the genes for tRNA synthetases that are causally linked to disease, with both dominant and recessive disease-causing mutations being annotated. Because some disease-causing mutations do not affect aminoacylation activity or apparent enzyme stability, the mutations are believed to affect functions that are distinct from aminoacylation. Examples include enzymes that are secreted as procytokines that, after activation, operate in pathways connected to the immune system or angiogenesis. In addition, within cells, synthetases form multiprotein complexes with each other or with other regulatory factors and in that way control diverse signaling pathways. Although much has been uncovered in recent years, many novel functions, disease connections, and interpathway connections of tRNA synthetases have yet to be worked out.
Sudden death risk in overt coronary heart disease: The Framingham Study (1987)

Over 30 years of surveillance of 5127 subjects free of CHD, 760 men and 574 women developed overt CHD, and there were 160 sudden deaths in men and 73 in women. Among those who sustained clinically manifest CHD, the sudden death risk was increased 6.7 times that of those without an interim event. Although the relative risk was comparable in the two sexes, CHD did not eliminate the female advantage over men. Myocardial infarction imposed a greater sudden death risk than angina pectoris, and silent infarctions were as dangerous as symptomatic infarctions. Onset of CHD put young and old at equal risk of sudden death. Some 40% of sudden deaths occurred in the 4% of the general population with overt CHD. The proportion of coronary attacks presenting as sudden death increased from 13% at ages 35 to 64 years to 20% at ages 65 to 94 years. The fraction of CHD deaths classified as sudden deaths was lower in those with than without interim CHD. In those with established CHD, factors reflecting ischemic myocardial damage and cardiac failure were the chief predictors of sudden death. The proportion of CHD deaths presenting as sudden deaths has not declined in subjects with prior CHD over three decades, despite a national decline in the overall CHD mortality rate.
Caveolin-1 in oncogenic transformation, cancer, and metastasis (2005)

Caveolae are 50- to 100-nm omega-shaped invaginations of the plasma membrane that function as regulators of signal transduction. Caveolins are a class of oligomeric structural proteins that are both necessary and sufficient for caveolae formation. Interestingly, caveolin-1 has been implicated in the pathogenesis of oncogenic cell transformation, tumorigenesis, and metastasis. Here, we review the available experimental evidence (gleaned from cultured cells, animal models, and human tumor samples) that caveolin-1 (Cav-1) functions as a "tumor and/or metastasis modifier gene." Genetic evidence from the study of Cav-1(-/-) null mice and human breast cancer mutations [CAV-1 (P132L)] supports the idea that caveolin-1 normally functions as a negative regulator of cell transformation and mammary tumorigenesis. In contrast, caveolin-1 may function as a tumor promoter in prostate cancers. We discuss possible molecular mechanisms to explain these intriguing, seemingly opposing, findings. More specifically, caveolin-1 phosphorylation (at Tyr14 and Ser80) and mutations (P132L) may override or inactivate the growth inhibitory activity of the caveolin-scaffolding domain (residues 82-101).
Ca, P‐rich layer formed on high‐strength bioactive glass‐ceramic A‐W (1990)

Glass-ceramic A-W, containing crystalline apatite and wollastonite in a MgO-CaO-SiO2 glassy matrix shows high bioactivity as well as high mechanical strength, but other ceramics containing the same kinds of crystalline phases in different glassy matrices do not show the same bioactivity. In order to investigate the bone-bonding mechanism of this type of glass-ceramic, surface structural changes of the glass-ceramics after exposure to simulated body fluid were analyzed with various techniques. A solution with ion concentrations which are almost equal to those of the human blood plasma was used as the simulated body fluid, instead of Tris-buffer solution hitherto used. For analyzing the surface structural changes, thin-film x-ray diffraction was used in addition to conventional techniques. It was found that a bioactive glass-ceramic forms a Ca, P-rich layer on its surface in the fluid but nonbioactive ones do not, and that the Ca, P-rich layer consists of carbonate-containing hydroxyapatite of small crystallites and/or defective structure. These findings were common to those of Bioglass-type glasses. So, we conclude that the essential condition for glass and glass-ceramic to bond to bone is the formation of the surface apatite layer in the body environment but it is not essential to contain apatite within the material. Bioactivity of glass and glass-ceramic can be evaluated in vitro by examining the formation of the surface apatite layer in the simulated body fluid described above.
Molecular basis of DNA sequence recognition by the catabolite gene activator protein: detailed inferences from three mutations that alter DNA sequence specificity. (1984)

Previously, we reported that substitution of Glu-181 of the catabolite gene activator protein (CAP) by lysine, leucine, or valine results in a protein that has specificity for A X T base pairs at positions 7 and 16 of the DNA recognition site, rather than G X C base pairs as is the case with the wild-type CAP. In this paper, we deduce from these genetic data both (i) the specific chemical interactions by which amino acid side chains at position 181 interact with base pairs 7 and 16 and (ii) the precise alignment between the structures of the CAP and DNA in the intermolecular CAP-DNA complex. Our analysis supports the idea that the two symmetry-related F alpha-helices of the CAP dimer interact with successive major grooves of right-handed B-type DNA [Pabo, C. & Lewis, M. (1982) Nature (London) 298, 443-447; and Steitz, T., Weber, I. & Matthew, J. (1983) Cold Spring Harbor Symp. Quant. Biol. 47, 419-426].
Aggregation between teratocarcinoma cells and preimplantation mouse embryos (1980)

The ability of two embryonal carcinoma (EC) cell lines, F9 and PC13, to aggregate with preimplantation 8-cell mouse embryos is described. Both adhere to the embryonic cells and subsequently compact with the embryos. The aggregates form blastocysts in culture. The blastocysts sometimes contain the EC cells, located almost always in their inner cell mass. Differentiated derivatives of EC cells, namely PYS-1 and PYS-2, as well as STO fibroblasts do not aggregate with embryos.
ChemInform Abstract: A New Approach to 4‐(2‐Aminoethyl)indoles via Claisen ortho‐Amide Rearrangement of 3‐Hydroxy‐2‐methoxyindolines. (1990)

Abstract The hydroxyindolines (I) react with the amide acetal (II) in o‐dichlorobenzene to produce a mixture of the aromatic N,N‐dimethylacetamides (III) and (IV).
Novel Four‐Drug Salvage Treatment Regimens after Failure of a Human Immunodeficiency Virus Type 1 Protease Inhibitor–Containing Regimen: Antiviral Activity and Correlation of Baseline Phenotypic Drug Susceptibility with Virologic Outcome (1999)

Twenty human immunodeficiency virus-infected patients experiencing virologic failure of an indinavir- or ritonavir-containing treatment regimen were evaluated in a prospective, open-label study. Subjects received nelfinavir, saquinavir, abacavir, and either another nucleoside analog (n=10) or nevirapine (n=10). Patients treated with the nevirapine-containing regimen experienced significantly greater virologic suppression at week 24 than those not treated with nevirapine (P=.04). Baseline phenotypic drug susceptibility was strongly correlated with outcome in both treatment arms. Subjects with baseline virus phenotypically sensitive to 2 or 3 drugs in the salvage regimen experienced significantly greater virus load suppression than those with baseline virus sensitive to 0 or 1 drug (median week-24 change=-2.24 log and -0.35 log, respectively; P=.01). In conclusion, non-nucleoside reverse transcriptase inhibitors may represent a potent drug in salvage therapy regimens after failure of an indinavir or ritonavir regimen. Phenotypic resistance testing may provide a useful tool for selecting more effective salvage regimens.
TGFβ restores hematopoietic homeostasis after myelosuppressive chemotherapy (2013)

Myelosuppression is a life-threatening complication of antineoplastic therapy, but treatment is restricted to a few cytokines with unilineage hematopoietic activity. Although hematopoietic stem cells (HSCs) are predominantly quiescent during homeostasis, they are rapidly recruited into cell cycle by stresses, including myelosuppressive chemotherapy. Factors that induce HSCs to proliferate during stress have been characterized, but it is not known how HSC quiescence is then reestablished. In this study, we show that TGFβ signaling is transiently activated in hematopoietic stem and progenitor cells (HSPCs) during hematopoietic regeneration. Blockade of TGFβ signaling after chemotherapy accelerates hematopoietic reconstitution and delays the return of cycling HSCs to quiescence. In contrast, TGFβ blockade during homeostasis fails to induce cycling of HSPCs. We identified the cyclin-dependent kinase inhibitor Cdkn1c (p57) as a key downstream mediator of TGFβ during regeneration because the recovery of chimeric mice, incapable of expressing p57 in HSPCs, phenocopies blockade of TGFβ signaling after chemotherapy. This study demonstrates that context-dependent activation of TGFβ signaling is central to an unrecognized counterregulatory mechanism that promotes homeostasis once hematopoiesis has sufficiently recovered from myelosuppressive chemotherapy. These results open the door to new, potentially superior, approaches to promote multilineage hematopoietic recovery by blocking the TGFβ signaling that dampens regeneration.
Electronic Markets and Electronic Hierarchies (1994)

Abstract The innovations in information technologies of the past two decades have radically reduced the time and cost of processing and communicating information. These reductions have in turn brought many changes in the ways that tasks are accomplished in firms. Data-processing systems have transformed the ways in which accounting data are gathered and processed, for example, and CAD/CAM (computer-aided design and manufacture) has transformed the ways in which complex machinery is designed. Underlying (and often obscured by) these changes in how business tasks are performed may be more fundamental changes in how firms and markets organize the flow of goods and services through their value-added chains (e.g., see Porter &amp; Millar, 1985). This chapter addresses this more basic issue of how advances in information technology are affecting firm and market structures and discusses the options that these changes present for corporate strategies.
Academic and Social Integration of Chinese International Students in Italy (2013)

The increasing mobility of students has supported the internationalization of higher education. Studying abroad brings to the forefront language and cultural issues. In this paper, through interviews and survey data I investigate the academic and social integration of Chinese students in Italian universities. While these students look forward to academic excellence, social integration is also significant in how well students perform academically and how they feel about their studies. I focus on factors that affect students' abilities and behaviors in blending academically and socially in Italy and attempt to bring out the idea that successful academic and social integration translates into better academic achievements. The results should help Chinese overseas students ascertain whether academic and social integration are effective for their studying abroad, what obstacles they may face and how they may be overcome. This research on social blending finds that there is a significant correlation between academic and social factors. This paper also indicates that a lack of Italian language skills, communication skills, and preparation for studying abroad directly influences social integration, academic achievements, and the expansion of social networks.
Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias (2006)

Persistent activation of Stat5 is frequently found in hematologic neoplasms. Studies conducted with constitutively active Stat5 mutants (Stat51*6 and cS5F) have shown that deregulated Stat5 activity promotes leukemogenesis. To investigate the oncogenic properties of these mutants, we used cS5F-expressing bone marrow cells which induce a multilineage leukemia when transplanted into recipient mice. Here, we show by immunocytochemistry that cS5F is localized mainly in the cytoplasmic compartment of leukemic cells, suggesting that the transforming nature of cS5F may be associated with a cytoplasmic function. In support of this hypothesis, we found that cS5F forms a complex with the p85 subunit of the phosphatidylinositol 3-kinase (PI3-K) and the scaffolding adapter Gab2 in leukemic bone marrow cells, resulting in the activation of Akt/PKB, a crucial downstream target of PI3-K. By using transducible TAT-Gab2 or TAT-Akt recombinant proteins, we were able to demonstrate that activation of the PI3-kinase/Akt pathway by cS5F molecules through Gab2 is essential for induction of cell growth. We also found that persistently phosphorylated Stat5 in primary cells from patients with myeloid leukemias has a cytoplasmic localization. These data suggest that oncogenic Stat5 proteins exert dual transforming capabilities not only as transcriptional activators but also as cytoplasmic signaling effectors.
Acquired immunity to an intracellular pathogen:immunologic recognition of L. monocytogenes‐infected cells (1997)

Listeria monocytogenes (L. monocytogenes) is a pathogenic bacterium, and subclinical infection in mice is utilized as a prototypic model to investigate the development and expression of acquired resistance to facultative intracellular organisms. A key virulence factor of L. monocytogenes is the hemolysin listeriolysin O (LLO), and BALB/c mice immunized with hemolysin-secreting strains of L. monocytogenes develop specific acquired resistance, while mice immunized with hemolysin-negative strains or non-viable preparations of L. monocytogenes do not develop a protective immune response. Adoptive transfer studies show that L. monocytogenes-immune CD8+ T cells mediate acquired resistance. The L. monocytogenes-immune CD8+ population is cytotoxic, and target cells infected with hemolysin-secreting strains of L. monocytogenes are lysed, while target cells infected with hemolysin-negative strains or non-viable preparations of L. monocytogenes are not lysed. MHC class Ia and Ib molecules present L. monocytogenes-derived peptides, and we have identified Qa-Ib, a T-region-encoded MHC class Ib molecule, as a restriction element for L. monocytogenes-specific CD8+ CTL. MHC class Ib-restricted CTL are stimulated following infection with L. monocytogenes and are a significant component of the total MHC class I-restricted CTL population. These findings support the observation that cytoplasmic L. monocytogenes-derived antigens are endogenously processed and presented in association with MHC class Ia and Ib molecules to CD8+ effector cells, and that both populations of effector cells contribute to the immune response to this intracellular pathogen.
C5a Mediates Peripheral Blood Neutrophil Dysfunction in Critically Ill Patients (2009)

Critically ill patients have significant dysfunction of PBNs, which is mediated predominantly by activated complement. Further, profound complement-independent neutrophil dysfunction occurs in the inflamed lung.
Solvent Effect on Thermally Activated Delayed Fluorescence by 1,2,3,5-Tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (2013)

Thermally activated delayed fluorescence (TADF) is fluorescence arising from a reverse intersystem crossing (RISC) from the lowest triplet (T1) to the singlet excited state (S1), where these states are separated by a small energy gap (ΔEst), followed by a radiative transition to the ground state (S0). Rate constants relating TADF processes in 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) were determined at four different solvent polarities (toluene, dichloromethane, ethanol, and acetonitrile). We revealed that the rate constant of RISC, kRISC, which is the most important factor for TADF, was significantly enhanced by a reduced ΔEst in more polar solvents. The smaller ΔEst was mainly attributable to a stabilization of the S1 state. This stabilization also induced a Stokes shift in fluorescence through a relatively large change of the dipole moment between S1 and S0 states (17 D). Despite of this factor, we observed a negative correlation between ΔEst and efficiency of the delayed fluorescence (φd). This was ascribed to a lower intersystem crossing rate, kISC, and increased nonradiative decay from S1, k(s)nrs, in polar solvents.
Phase I Clinical Trial of the Chimeric Anti-Mesothelin Monoclonal Antibody MORAb-009 in Patients with Mesothelin-Expressing Cancers (2010)

MORAb-009 is well tolerated and the MTD when administered weekly is conservatively set at 200 mg/m(2). In this group of previously treated patients, 11 subjects had stable disease. Phase II studies of MORAb-009 in different mesothelin-expressing cancers are ongoing.
EM interaction of handset antennas and a human in personal communications (1995)

In personal communications, the electromagnetic interaction between handset-mounted antennas and the nearby biological tissue is a key consideration. This paper presents a thorough investigation of this antenna-tissue interaction using the finite-difference time-domain (FDTD) electromagnetic simulation approach with detailed models of real-life antennas on a transceiver handset. The monopole, side-mounted planar inverted F, top-mounted bent inverted F, and back-mounted planar inverted F antennas are selected as representative examples of external and internal configurations. Detailed models of the human head and hand are implemented to investigate the effects of the tissue location and physical model on the antenna performance. Experimental results are provided which support the computationally obtained conclusions. The specific absorption rate (SAR) in the tissue is examined for several different antenna/handset configurations. It is found that for a head-handset separation of 2 cm, the SAR in the head has a peak value between 0.9 and 3.8 mW/g and an average value between 0.06 and 0.10 mW/g for 1 W of power delivered to the antenna. Additionally, the head and hand absorb between 48 and 68% of the power delivered to the antenna.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An Investigation of Pulse Transit Time as a Non-Invasive Blood Pressure Measurement Method (2011)

The objective of this paper is to examine the Pulse Transit Method (PTT) as a non-invasive means to track Blood Pressure over a short period of time. PTT was measured as the time it takes for an ECG R-wave to propagate to the finger, where it is detected by a photoplethysmograph sensor. The PTT method is ideal for continuous 24-hour Blood Pressure Measurement (BPM) since it is both cuff-less and non-invasive and therefore comfortable and unobtrusive for the patient. Other techniques, such as the oscillometric method, have shown to be accurate and reliable but require a cuff for operation, making them unsuitable for long term monitoring. Although a relatively new technique, the PTT method has shown to be able to accurately track blood pressure changes over short periods of time, after which re-calibration is necessary. The purpose of this study is to determine the accuracy of the method.
A general approach for cloning and characterizing dNDP-glucose dehydratase genes from actinomycetes (1996)

Oligonucleotide primers were designed and successfully applied to amplify DNA fragments of dNDP-glucose dehydratase genes from actinomycete species producing natural compounds which contain deoxysugar moieties. The deduced amino acid sequence of the isolated fragments revealed similarity to known dNDP-glucose dehydratases. A phylogeny for the deduced proteins of the obtained fragments and for dNDP-glucose dehydratases described in the data bases was constructed. dNDP-glucose dehydratases from actinomycetes were more related to each other than to dehydratases from species of other orders. The phylogenetic analysis also revealed a close relation between dehydratases from strains producing natural compounds with similar deoxysugar moieties.
Complexity-effective superscalar processors (1997)

The performance tradeoff between hardware complexity and clock speed is studied. First, a generic superscalar pipeline is defined. Then the specific areas of register renaming, instruction window wakeup and selection logic, and operand bypassing are analyzed. Each is modeled and Spice simulated for feature sizes of 0.8&amp;micro;m, 0.35&amp;micro;m, and 0.18&amp;micro;m. Performance results and trends are expressed in terms of issue width and window size. Our analysis indicates that window wakeup and selection logic as well as operand bypass logic are likely to be the most critical in the future.A microarchitecture that simplifies wakeup and selection logic is proposed and discussed. This implementation puts chains of dependent instructions into queues, and issues instructions from multiple queues in parallel. Simulation shows little slowdown as compared with a completely flexible issue window when performance is measured in clock cycles. Furthermore, because only instructions at queue heads need to be awakened and selected, issue logic is simplified and the clock cycle is faster --- consequently overall performance is improved. By grouping dependent instructions together, the proposed microarchitecture will help minimize performance degradation due to slow bypasses in future wide-issue machines.
Design and synthesis of polyacrylamide-based oligonucleotide supports for use in nucleic acid diagnostics (1993)

Polyacrylamide supports, in a range of pore sizes, were investigated as nucleic acid affinity matrices for the detection of target DNA or RNA sequences using a sandwich hybridization format. Bromoacetyl and thiol oligonucleotide derivatives were covalently linked to sulfhydryl- and bromoacetyl-polyacrylamide supports with greater than 95% end-attachment efficiencies. These polyacrylamide-oligonucleotide supports were further derivatized with anionic residues to provide multi-functional supports which show low non-specific binding for non-complementary nucleic acids. While all the polyacrylamide-oligonucleotide supports capture complementary oligonucleotides with high affinity, the pore size was found to be a critical parameter in sandwich hybridization reactions. The superior hybridization characteristics of the Trisacryl support was ascribed to a combination of its macroporous nature, hydrophilicity and the terminal attachment of its capture oligonucleotides.
Choroidal Vascularity Index in Vogt-Koyanagi-Harada Disease: An EDI-OCT Derived Tool for Monitoring Disease Progression (2016)

Choroidal vascularity index can be used potentially to study and analyze the structural changes in choroid. It can be a useful tool to explain the changes in the CT in different retinochoroidal disorders. Choroidal vascularity index also can be used for longitudinal follow-up in patients with VKH disease and other inflammatory disease involving the choroid.