gebhart/patrepeval huggingface dataset:
Regulation of Signaling Protein Function and Trafficking by the hsp90/hsp70-Based Chaperone Machinery (2003)

Nearly 100 proteins are known to be regulated by hsp90. Most of these substrates or "client proteins" are involved in signal transduction, and they are brought into complex with hsp90 by a multiprotein hsp90/hsp70-based chaperone machinery. In addition to binding substrate proteins at the chaperone site(s), hsp90 binds cofactors at other sites that are part of the heterocomplex assembly machinery as well as immunophilins that connect assembled substrate*hsp90 complexes to protein-trafficking systems. In the 5 years since we last reviewed this subject, much has been learned about hsp90 structure, nucleotide-binding, and cochaperone interactions; the most important concept is that ATP hydrolysis by an intrinsic ATPase activity results in a conformational change in hsp90 that is required to induce conformational change in a substrate protein. The conformational change induced in steroid receptors is an opening of the steroid-binding cleft so that it can be accessed by steroid. We have now developed a minimal system of five purified proteins-hsp90, hsp70, Hop, hsp40, and p23- that assembles stable receptor*hsp90 heterocomplexes. An hsp90*Hop*hsp70*hsp40 complex opens the cleft in an ATP-dependent process to produce a receptor*hsp90 heterocomplex with hsp90 in its ATP-bound conformation, and p23 then interacts with the hsp90 to stabilize the complex. Stepwise assembly experiments have shown that hsp70 and hsp40 first interact with the receptor in an ATP-dependent reaction to produce a receptor*hsp70*hsp40 complex that is "primed" to be activated to the steroid-binding state in a second ATP-dependent step with hsp90, Hop, and p23. Successful use of the five-protein system with other substrates indicates that it can assemble signal protein*hsp90 heterocomplexes whether the substrate is a receptor, a protein kinase, or a transcription factor. This purified system should facilitate understanding of how eukaryotic hsp70 and hsp90 work together as essential components of a process that alters the conformations of substrate proteins to states that respond in signal transduction.
Disabled early recruitment of antioxidant defenses in Friedreich's ataxia (2001)

Friedreich's ataxia (FRDA) results from a generalized deficiency of mitochondrial iron-sulfur protein activity ascribed to mitochondrial iron overload. However, iron overload appears to be a late event in the disease. Here we show that neither superoxide dismutases nor the import iron machinery was induced by an endogenous oxidative stress in FRDA patients' fibroblasts in contrast to control cells. Superoxide dismutase activity was not induced in the heart of conditional frataxin-KO mice either. This suggests that continuous oxidative damage to iron-sulfur clusters, resulting from hampered superoxide dismutase signaling, is causative of the mitochondrial deficiency and long term mitochondrial iron overload occurring in FRDA.
Correlation of retinal arterial wall thickness with atherosclerosis predictors in type 2 diabetes without clinical retinopathy (2016)

Microvasuclar thickness was greater in patients with diabetes than in controls. Furthermore, WT was positively correlated with HbA1c, total cholesterol and low-density lipoprotein cholesterol levels and IMT in the diabetic group. These results suggest that retinal artery wall measurements can be potential surrogate markers of early diabetic microangiopathy.
A reference genome for common bean and genome-wide analysis of dual domestications (2014)

Common bean (Phaseolus vulgaris L.) is the most important grain legume for human consumption and has a role in sustainable agriculture owing to its ability to fix atmospheric nitrogen. We assembled 473 Mb of the 587-Mb genome and genetically anchored 98% of this sequence in 11 chromosome-scale pseudomolecules. We compared the genome for the common bean against the soybean genome to find changes in soybean resulting from polyploidy. Using resequencing of 60 wild individuals and 100 landraces from the genetically differentiated Mesoamerican and Andean gene pools, we confirmed 2 independent domestications from genetic pools that diverged before human colonization. Less than 10% of the 74 Mb of sequence putatively involved in domestication was shared by the two domestication events. We identified a set of genes linked with increased leaf and seed size and combined these results with quantitative trait locus data from Mesoamerican cultivars. Genes affected by domestication may be useful for genomics-enabled crop improvement.
Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer. (2003)

This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols.
ChemInform Abstract: Structure‐Activity Relations. Part 13. Inhibitors of Cyclic Nucleotide Phosphodiesterase and Anaphylaxis. Inhibition by a Series of Substituted Benzamidotetrazoles (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Influence of Temperature and Humidity on Laser in situ Keratomileusis Outcomes (2001)

ABSTRACT PURPOSE: The influence of ambient factors on the results of refractive surgery is not well-known. This study evaluated the influence of temperature and humidity on laser in situ keratomileusis (LASIK) outcomes. METHODS: Two hundred thirty-seven patients who underwent LASIK at the Clivan Instituto de Oftalmologia in Salvador - Bahia - Brazil, between May 1999 and March 2000, were evaluated. A total of 156 (65.8%) patients were female. Mean age was 30.3 ± 7.6 years. Refractive errors: 197 patients (83.12%) had compound myopic astigmatism, 17 patients (7.17%) had myopia, 11 patients (4.64%) had compound hyperopic astigmatism, and 12 patients (5.07%) had other. Results at 15 and 60 days after LASIK were compared according to different levels of temperature and humidity in the operating room during the procedure. RESULTS: Patients whose spherical equivalent refraction varied between -0.50 to +0.50 D at 15 days after LASIK had surgery performed when the temperature was 25.1 ± 1.4° C and humidity was 45.1 ± 4.2%; for the others, temperature was 24.7 ± 1.5° C (P = .12) and humidity was 43.0 ± 4.0% (P = .002). The linear regression coefficient showed that lower temperature levels were associated with lower spherical equivalent refractions at 60 days after LASIK (r p 2 = .14; P = .03) but not at 15 days after LASIK (P = .98). The evaluation of humidity indicated an influence at 15 days after LASIK (r p 2 = .44; P = .04), as well as at 60 days (r p 2 = .45; P = .0002). CONCLUSION: Operating room environment may influence LASIK outcomes; humidity may be more significant than temperature. [J Refract Surg 2001;17(suppl):S202-S2041
Genetic Diversity among Botulinum Neurotoxin-Producing Clostridial Strains (2006)

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore-forming rod-shaped bacteria that have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and death in humans and other animal species. A collection of 174 C. botulinum strains was examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine the genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT/A to BoNT/G). Analysis of the16S rRNA gene sequences confirmed previous identifications of at least four distinct genomic backgrounds (groups I to IV), each of which has independently acquired one or more BoNT genes through horizontal gene transfer. AFLP analysis provided higher resolution and could be used to further subdivide the four groups into subgroups. Sequencing of the BoNT genes from multiple strains of serotypes A, B, and E confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven toxin genes of the serotypes were compared and showed various degrees of interrelatedness and recombination, as was previously noted for the nontoxic nonhemagglutinin gene, which is linked to the BoNT gene. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for the treatment of botulism.
Out-of-band and adjacent-channel interference reduction by analog nonlinear filters (2015)

In a perfect world, we would have ‘brick wall’ filters, no-distortion amplifiers and mixers, and well-coordinated spectrum operations. The real world, however, is prone to various types of unintentional and intentional interference of technogenic (man-made) origin that can disrupt critical communication systems. In this paper, we introduce a methodology for mitigating technogenic interference in communication channels by analog nonlinear filters, with an emphasis on the mitigation of out-of-band and adjacent-channel interference. Interference induced in a communications receiver by external transmitters can be viewed as wide-band non-Gaussian noise affecting a narrower-band signal of interest. This noise may contain a strong component within the receiver passband, which may dominate over the thermal noise. While the total wide-band interference seen by the receiver may or may not be impulsive, we demonstrate that the interfering component due to power emitted by the transmitter into the receiver channel is likely to appear impulsive under a wide range of conditions. We give an example of mechanisms of impulsive interference in digital communication systems resulting from the nonsmooth nature of any physically realizable modulation scheme for transmission of a digital (discontinuous) message. We show that impulsive interference can be effectively mitigated by nonlinear differential limiters (NDLs). An NDL can be configured to behave linearly when the input signal does not contain outliers. When outliers are encountered, the nonlinear response of the NDL limits the magnitude of the respective outliers in the output signal. The signal quality is improved in excess of that achievable by the respective linear filter, increasing the capacity of a communications channel. The behavior of an NDL, and its degree of nonlinearity, is controlled by a single parameter in a manner that enables significantly better overall suppression of the noise-containing impulsive components compared to the respective linear filter. Adaptive configurations of NDLs are similarly controlled by a single parameter and are suitable for improving quality of nonstationary signals under time-varying noise conditions. NDLs are designed to be fully compatible with existing linear devices and systems and to be used as an enhancement, or as a low-cost alternative, to the state-of-art interference mitigation methods.
Physics of Relativistic Perfect Fluids (1997)

A criterion is presented and discussed to detect when a divergence-free perfect fluid energy tensor in the space-time describes an evolution in local thermal equilibrium. This criterion is applied to the class II Szafron-Szekeres perfect fluid space-times solutions, giving a very simple characterization of those that describe such thermal evolutions. For all of them, the significant thermodynamic variables are explicitly obtained. Also, the specific condition is given under which the divergence-free perfect fluid energy tensors may be interpreted as an ideal gas. 1 Physical fluids and energetic evolutions. The inverse problem In the absence of nuclear or chemical reactions, and independent of the external constraints to which it may be submitted, a material medium is considered here as physically characterized by the specification of its molecular components. In a domain Ω of the space-time, and in the absence of exterior constraints, every initial configuration of a material medium gives rise to a particular evolution. And, to every one of these evolutions in Ω an energy tensor [1] Tf corresponds univocally. Due to the absence of exterior constraints, the energy tensors so obtained are divergence-free, ∇ · Tf = 0. Thus, a set Tf ≡ {Tf} of energy tensors is associated to every medium f, namely those of all its possible unconstrained evolutions in the space-time domain Ω. We have the diagram of Figure 1. The energetic description of a particular evolution of the medium f by the energy tensor Tf, consists, and only consists, of the specification of the energy density ρf, the energy flow density qf and the stress tensor tf of this evolution of f in Ω.
Localization and Sequence Analysis of Yeast Origins of DNA Replication (1983)

The precise and uniform duplication of a cell's genome is essential to its normal growth. Focal points for the orchestration of this central process are provided by specific loci within the genome that function as sites of initiation of DNA replication. In this paper we present results that allow us to address the structural characteristics of DNA replication origins in yeast.
Computing the visibility graph via pseudo-triangulations (1995)

We show that the k free bitangents of a collection of n pairwise disjoint convex plane sets can be computed in time O(k + n log n) and O(n) working space. The algorithm uses only one advanced data structure, namely a splittable queue. We introduce (weakly) greedy pseudo-triangulations, whose combinatorial properties are crucial for our method.
Onsite Design, Analysis, and Automation Maximizes Efficiency of Fracturing Operations (1989)

ABSTRACT Recent advances in onsite data acquisition and automation of field equipment have led to the development of a new fracturing treatment control center. This mobile control center combines design, monitoring, and analysis capabilities with the ability to automatically and remotely control, from within the same unit, all of the fracturing equipment on location. By using a computer system with increased processing power, and a sophisticated data communications network, many new capabilities are provided: All fracturing equipment on location can be monitored and/or controlled from inside the control center using a variety of operator interface screens. Set points are sent from the control center to each piece of equipment through a single communications line. More than 1200 measured and/or calculated job parameters, ranging from blender suction pressure to fracture geometry predictions, can be displayed on color monitors during the job. All data are stored internally and can be accessed at any time. Commonly used mainframe computer programs have been downloaded into the control center and can be executed in a background environment. This provides for analysis, design and, if necessary, redesign capabilities while the job is in progress. This paper describes the system and presents field case histories to illustrate the practical use of the increased computing power and automatic and remote controls now available to help improve the efficiency of the fracturing treatment.
Human carboxypeptidase M (1989)

A membrane-bound neutral carboxypeptidase B-like enzyme was solubilized from human placental microvilli with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) and purified to homogeneity by ion-exchange chromatography and affinity chromatography on arginine-Sepharose. It gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent Mr of 62,000 with or without reduction. The enzyme is a glycoprotein as shown by its high affinity for concanavalin A-Sepharose and reduction in mass to 47,600 daltons after chemical deglycosylation. It has a neutral pH optimum, is activated by CoCl2, and inhibited by o-phenanthroline, 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, or cadmium acetate, indicating it is a metallopeptidase. The enzyme cleaves arginine or lysine from the COOH terminus of synthetic peptides (e.g. Bz-Gly-Arg, Bz-Gly-Lys, Bz-Ala-Lys, dansyl-Ala-Arg, where Bz is benzoyl and dansyl is 5-dimethylaminonaphthalene-1-sulfonyl) as well as from several biologically active substrates: dynorphin A(1-13), Met5-Arg6-enkephalin (Km = 46 microM, kcat = 934 min-1), bradykinin (Km = 16 microM, kcat = 147 min-1), Met5-Lys6-enkephalin (Km = 375 microM, kcat = 663 min-1), and Leu5-Arg6-enkephalin (Km = 63 microM, kcat = 106 min-1). Although the enzyme shares some properties with other carboxypeptidase B-like enzymes, it is structurally, catalytically, and immunologically distinct from pancreatic carboxypeptidase A or B, human plasma carboxypeptidase N, and carboxypeptidase H ("enkephalin convertase"). To denote that the enzyme is membrane-bound, and to distinguish it from other known carboxypeptidases, we propose the name "carboxypeptidase M." Because of its localization on the plasma membrane and optimal activity at neutral pH, carboxypeptidase M could inactivate or modulate the activity of peptide hormones either before or after their interaction with plasma membrane receptors.
Novel Gamma-Chain Cytokines as Candidate Immune Modulators in Immune Therapies for Cancer (2010)

Cytokines that signal through the common-gamma chain are potent growth factors for T cells and natural killer cells. Interleukin (IL)-2, the gammac prototype, can mediate antitumor effects as a single agent or in the context of multimodality regimens but is limited by side effects and a propensity for expansion of regulatory T cells. IL-7, IL-15, and IL-21 each possess properties that can be exploited in the context of immunotherapy for cancer. Each has been demonstrated to mediate potent vaccine adjuvant effects in tumor models, and each can enhance the effectiveness of adoptive immunotherapies. Although the overlap among the agents is significant, IL-7 is uniquely immunorestorative and preferentially augments reactivity of naive populations, IL-15 potently augments reactivity of CD8 memory cells and natural killer cells, and IL-21 preferentially expands the inflammatory Th17 subset and may limit terminal differentiation of effector CD8 cells. Clinical trials of IL-7 and IL-21 have already been completed and, so far, demonstrate safety and biologic activity of these agents. Clinical trials of IL-15 are expected soon. Ultimately, these agents are expected to be most effective in the context of multimodal immunotherapy regimens, and careful clinical trial design will be needed to efficiently identify the proper doses, regimens, and settings in which to exploit their biologic properties for therapeutic gain.
Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality (1997)

This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.
Constitutive Expression of Pea Defense Gene DRR206 Confers Resistance to Blackleg (Leptosphaeria maculans) Disease in Transgenic Canola (Brassica napus) (1999)

To identify genes effective against the blackleg fungus Leptosphaeria maculans (Phoma lingam), we have transformed canola (Brassica napus) with four pea (Pisum sativum) genes under constitutive control by the cauliflower mosaic virus 35S promoter: PR10.1, chitinase, DRR206, and defensin. Transgenic lines containing single-copy T-DNA insertions for each gene were screened for both seedling (cotyledonary) and adult plant resistance. Lines for which pea DRR206 mRNA was expressed showed decreased disease scores, compared with non-expressing transgenic lines. Transgenic plants expressing pea defensin showed a slight enhancement of resistance, while for PR10 and chitinase transgenics there was little or no enhancement of resistance. Resistance to L. maculans cosegregated with DRR206 transgenes. Extracts from DRR206 and defensin transgenic plants inhibited fungal germination in vitro. DRR206 transgenic plants also demonstrated decreased hyphal growth at inoculation sites. While the precise function of DRR206 remains to be determined, these results suggest that it does play an important role in defense against fungi.
Speech in Celebration of IEC 100th Anniversary 2006 (2006)

Dear IEC colleagues: At this special moment of IEC 100th anniversary, please allow me on behalf of Standardization Administration of the People's Republic of China (SAC) to convey my best regards to colleagues working in the field of electric and electronic standardization. Also, my highly respect will be given to all people who have devoted into or are making contribution to IEC development.……
Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin (1992)

Terfenadine is a nonsedating H1-antagonist that when overdosed, used with hepatic compromise, or when given with ketoconazole results in accumulation of parent terfenadine, prolongation of the QT interval, and torsades de pointes in susceptible patients. Nine subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral erythromycin (500 mg every 8 hours). All subjects increased metabolite concentrations after the addition of erythromycin for 1 week. The maximum concentration of metabolite increased by a mean of 107% and the mean metabolite area under the concentration-time curve increased by 170%. Three subjects accumulated unmetabolized terfenadine after administration of erythromycin for 1 week. Electrocardiographic data revealed changes in QT intervals and ST-U complexes in a subset of subjects who accumulated terfenadine. We conclude that erythromycin alters the metabolism of terfenadine, leading to accumulation of terfenadine in certain individuals that is associated with altered cardiac repolarization.