gebhart/patrepeval huggingface dataset:
Assembly of Phospholipids into Cellular Membranes: Biosynthesis, Transmembrane Movement and Intracellular Translocation (1988)

Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary ...Read More
Autoimmune T-Cell Response to the CD4 Molecule in HIV-Infected Patients (1998)

In a previous study, we demonstrated that by downregulating plasma membrane CD4 and increasing its processing, human immunodeficiency (HIV)-1-gp120 unveils hidden CD4 epitopes, inducing an in vitro anti-CD4-specific T-cell response. We report herein that this mechanism may potentially have important implications in HIV immunopathogenesis, because it could take part in the severe depletion of CD4+ cells that characterizes acquired immune deficiency syndrome (AIDS) and be related to disease progression. Freshly isolated peripheral blood lymphocytes (PBMC) from about 1/4 of a conspicuous cohort of HIV-infected patients responded to CD4 and this response was correlated with beta2-microglobulin levels, widely recognized as marker for progression of HIV infection. Moreover, we provide evidence that a CD4-specific T cell priming can occur in vivo, following a gp120 or anti-CD4 monoclonal antibody (mAb)-mediated CD4 molecule downregulation on antigen-presenting cells (APC). To our knowledge, this is the first study indicating that an autoimmune T-cell response is linked to HIV infection and that it could have an important impact on the immunopathogenesis of this disease.
Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation (1997)

The objective of this review is to summarize recent findings on the safety profiles of three natural cyclodextrins (alpha-, beta- and gamma-CDs) and several chemically modified CDs. To demonstrate the potential of CDs in pharmaceutical formulations, their stability against non-enzymatic and enzymatic degradations in various body fluids and tissue homogenates and their pharmacokinetics via parenteral, oral, transmucosal, and dermal routes of administration are outlined. Furthermore, the bioadaptabilities of CDs, including in vitro cellular interactions and in vivo safety profiles, via a variety of administration routes are addressed. Finally, the therapeutic potentials of CDs are discussed on the basis of their ability to interact with various endogenous and exogenous lipophiles or, especially for sulfated CDs, their effects on cellular processes mediated by heparin binding growth factors.
pH-Dependent Conformational Changes in Proteins and Their Effect on Experimental pKas: The Case of Nitrophorin 4 (2012)

The acid-base behavior of amino acids is an important subject of study due to their prominent role in enzyme catalysis, substrate binding and protein structure. Due to interactions with the protein environment, their pK(a)s can be shifted from their solution values and, if a protein has two stable conformations, it is possible for a residue to have different "microscopic", conformation-dependent pK(a) values. In those cases, interpretation of experimental measurements of the pK(a) is complicated by the coupling between pH, protonation state and protein conformation. We explored these issues using Nitrophorin 4 (NP4), a protein that releases NO in a pH sensitive manner. At pH 5.5 NP4 is in a closed conformation where NO is tightly bound, while at pH 7.5 Asp30 becomes deprotonated, causing the conformation to change to an open state from which NO can easily escape. Using constant pH molecular dynamics we found two distinct microscopic Asp30 pK(a)s: 8.5 in the closed structure and 4.3 in the open structure. Using a four-state model, we then related the obtained microscopic values to the experimentally observed "apparent" pK(a), obtaining a value of 6.5, in excellent agreement with experimental data. This value must be interpreted as the pH at which the closed to open population transition takes place. More generally, our results show that it is possible to relate microscopic structure dependent pKa values to experimentally observed ensemble dependent apparent pK(a)s and that the insight gained in the relatively simple case of NP4 can be useful in several more complex cases involving a pH dependent transition, of great biochemical interest.
Phosphatidylcholine‐phospholipase C mediates the induction of nerve growth factor in cultured glial cells (1995)

Addition of phosphatidylcholine-hydrolyzing phospholipase C (PC-PLC) to cultured glial cells increased the levels of nerve growth factor (NGF) mRNA and the amount of cell-secreted NGF. The effect of PC-PLC was 2.5 times higher than that elicited by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate. In cells in which protein kinase C (PKC) was fully inhibited or downregulated, the effect of PC-PLC was reduced-though still evident-and similar to that exerted by sphingosine. Results thus indicate that PC-PLC induces the synthesis of NGF by glial cells by a PKC-dependent and PKC-independent mechanisms.
Advances in the use of hydroxyurea (2009)

Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD. Hydroxyurea has proven clinical efficacy for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. Salutary effects on hematological parameters include increases in fetal hemoglobin (HbF), hemoglobin, and MCV; also significant decreases occur in WBC, ANC, reticulocytes, LDH, and bilirubin. Treatment with hydroxyurea is usually considered for patients with recurrent vaso-occlusive events, but additional indications for treatment may include laboratory markers of disease severity and evidence of chronic organ dysfunction. Ten years ago, the US Food and Drug Administration approved hydroxyurea for adult patients with clinically severe SCD; however, its use in children remains off-label. Despite the large body of evidence regarding its efficacy and safety, hydroxyurea is currently prescribed only sparingly for patients with SCD and therefore has only limited effectiveness for this disorder; barriers to its use need to be identified and overcome.
Mouse embryonic stem cells carrying one or two defective Msh2 alleles respond abnormally to oxidative stress inflicted by low-level radiation (1998)

Chronic oxidative stress may play a critical role in the pathogenesis of many human cancers. Here, we report that mouse embryonic stem (ES) cells deficient in DNA mismatch repair responded abnormally when exposed to low levels of ionizing radiation, a stress known to generate oxidative DNA damage. ES cells derived from mice carrying either one or two disrupted Msh2 alleles displayed an increased survival following protracted exposures to low-level ionizing radiation as compared with wild-type ES cells. The increases in survival exhibited by ES cells deficient in DNA mismatch repair appeared to have resulted from a failure to efficiently execute cell death (apoptosis) in response to radiation exposure. For each of the ES cell types, prolonged low-level radiation treatment generated oxidative genome damage that manifested as an accumulation of oxidized bases in genomic DNA. However, ES cells from Msh2(+/-) and Msh2(-/-) mice accumulated more oxidized bases as a consequence of low-level radiation exposure than ES cells from Msh2(+/+) mice. The propensity for normal cells with mismatch repair enzyme deficiencies, including cells heterozygous for inactivating mismatch repair enzyme gene mutations, to survive promutagenic genome insults accompanying oxidative stresses may contribute to the increased cancer risk characteristic of the hereditary nonpolyposis colorectal cancer syndrome.
Total Synthesis of (+)- and (-)-K252a (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal Synthesis of (+)- and (-)-K252aJohn L. Wood, Brian M. Stoltz, and Hans-Juergen DietrichCite this: J. Am. Chem. Soc. 1995, 117, 41, 10413–10414Publication Date (Print):October 1, 1995Publication History Published online1 May 2002Published inissue 1 October 1995https://pubs.acs.org/doi/10.1021/ja00146a039https://doi.org/10.1021/ja00146a039research-articleACS PublicationsRequest reuse permissionsArticle Views2310Altmetric-Citations72LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Privacy and authentication: An introduction to cryptography (1979)

This paper presents a tutorial introduction to contemporary cryptography. The basic information theoretic and computational properties of classical and modern cryptographic systems are presented, followed by cryptanalytic examination of several important systems and an examination of the application of cryptography to the security of timesharing systems and computer networks. The paper concludes with a guide to the cryptographic literature.
Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak (2020)

The mean estimate of R<sub>0</sub> for the 2019-nCoV ranges from 2.24 to 3.58, and is significantly larger than 1. Our findings indicate the potential of 2019-nCoV to cause outbreaks.
Singlet Fission for Dye-Sensitized Solar Cells:  Can a Suitable Sensitizer Be Found? (2006)

We discuss possible improvements in the efficiency of dye-sensitized photovoltaic cells using dyes capable of singlet fission into two triplets, thus producing two electron-hole pairs from a single photon. It is pointed out that, in addition to derivatives of large alternant hydrocarbons, those of biradicals are also likely candidates for a favorable ordering of excited-state energy levels, E(T2), E(S1) > 2E(T1). A large number of potentially favorable structures has been examined by the semiempirical Pariser-Parr-Pople method and some also by the time-dependent density functional theory method. Several likely candidates have been identified for experimental examination.
Sensitivity and Specificity of Single-Nucleotide Polymorphism Scanning by High-Resolution Melting Analysis (2004)

High-resolution melting analysis with the dye LCGreen I identifies heterozygous single-base changes in PCR products with a sensitivity and specificity comparable or superior to nonhomogeneous techniques. The error rate of scanning depends on the PCR product size and the type of base change, but not on the position of the SNP. The technique requires only PCR reagents, the dye LCGreen I, and 1-2 min of closed-tube, post-PCR analysis.
Robust Relational Parsing over Biomedical Literature: Extracting Inhibit Relation (2001)

We describe the design of a robust parser for identifying and extracting biomolecular relations from the biomedical literature. Separate automata over distinct syntactic domains were developed for extraction of nominal-based relational information versus verbal-based relations. This allowed us to optimize the grammars separately for each module, regardless of any specific relation resulting in significantly better performance. A unique feature of this system is the use of text-based anaphora resolution to enhance the results of argument binding in relational extraction. We demonstrate the performance of our system on inhibition-relations, and present our initial results measured against an annotated text used as a gold standard for evaluation purposes. The results represent a significant improvement over previously published results on extracting such relations from Medline: Precision was 90%, Recall 57%, and Partial Recall 22%. These results demonstrate the effectiveness of a corpus-based linguistic approach to information extraction over Medline.
Conducting polymer-hydrogels for medical electrode applications (2010)

Conducting polymers hold significant promise as electrode coatings; however, they are characterized by inherently poor mechanical properties. Blending or producing layered conducting polymers with other polymer forms, such as hydrogels, has been proposed as an approach to improving these properties. There are many challenges to producing hybrid polymers incorporating conducting polymers and hydrogels, including the fabrication of structures based on two such dissimilar materials and evaluation of the properties of the resulting structures. Although both fabrication and evaluation of structure-property relationships remain challenges, materials comprised of conducting polymers and hydrogels are promising for the next generation of bioactive electrode coatings.
miRNAs and sports: tracking training status and potentially confounding diagnoses (2016)

We provide evidence that the mode and the extent of training are important confounding factors for a miRNA based disease diagnosis.
Comamonas testosteroni colony phenotype influences exopolysaccharide production and coaggregation with yeast cells (1996)

A Comamonas testosteroni strain was isolated from activated sludge on the basis of its ability to coaggregate with yeast cells. On agar plates the following two types of colonies were formed: colonies with a mucoid appearance and colonies with a nonmucoid appearance. On plates this strain alternated between the two forms, making sectored colonies. In liquid medium with constant agitation no such change was observed. In the absence of agitation and in contact with a glass surface a culture with predominantly nonmucoid-colony-forming cells very rapidly shifted to a culture dominated by mucoid-colony-forming cells. In liquid medium the reverse was observed under stress conditions imposed by hydrogen peroxide, sodium dodecyl sulfate, or starvation. Nonmucoid cells formed very rapidly settling flocs with yeast cells, while coaggregation of mucoid cells with yeast cells did not occur. These findings may be relevant to the behavior of activated sludge microbial communities.
Dynamical Movement Primitives: Learning Attractor Models for Motor Behaviors (2012)

Nonlinear dynamical systems have been used in many disciplines to model complex behaviors, including biological motor control, robotics, perception, economics, traffic prediction, and neuroscience. While often the unexpected emergent behavior of nonlinear systems is the focus of investigations, it is of equal importance to create goal-directed behavior (e.g., stable locomotion from a system of coupled oscillators under perceptual guidance). Modeling goal-directed behavior with nonlinear systems is, however, rather difficult due to the parameter sensitivity of these systems, their complex phase transitions in response to subtle parameter changes, and the difficulty of analyzing and predicting their long-term behavior; intuition and time-consuming parameter tuning play a major role. This letter presents and reviews dynamical movement primitives, a line of research for modeling attractor behaviors of autonomous nonlinear dynamical systems with the help of statistical learning techniques. The essence of our approach is to start with a simple dynamical system, such as a set of linear differential equations, and transform those into a weakly nonlinear system with prescribed attractor dynamics by means of a learnable autonomous forcing term. Both point attractors and limit cycle attractors of almost arbitrary complexity can be generated. We explain the design principle of our approach and evaluate its properties in several example applications in motor control and robotics.
Microstreaming effects on particle concentration in an ultrasonic standing wave (2003)

Abstract It is shown that the magnitude of Rayleigh microstreaming convective drag on microparticles in water in a 3.2‐MHz ultrasonic standing wave can be comparable to the lateral direct radiation force in the nodal plane (DRF 1 ) and can significantly influence the microparticle aggregation. The transducer of a single half‐wavelength chamber was excited to give a single particle aggregate. The estimated sound pressure amplitude was 0.5 MPa. Particle image velocimetry (PIV) measurements gave the average microstreaming velocity in the nodal plane as 450 μm·s −1 , which is comparable to the 340‐μm·s −1 value calculated from Rayleigh's theory. Movement of 25‐μm latex particles was primarily determined by DRF 1 , while that of smaller 1.0 μm, particles was determined by Rayleigh microstreaming. A 15‐μm latex particle velocity map, simulated from microstreaming data, the measured velocity map of 25‐μm particles, and the cube‐dependent relationship between DRF 1 's on particles of different sizes, was in reasonable agreement with a measured velocity map. Further evidence for the importance of microstreaming came from the result that velocities for 1‐ and 25‐μm particles were of similar magnitude, but were opposite in direction.
Mitochondrion as a Novel Target of Anticancer Chemotherapy (2000)

Mitochondrial membrane permeabilization is a critical event in the process leading to physiologic or chemotherapy-induced apoptosis (programmed cell death). This permeabilization event is, at least in part, under the control of the permeability transition pore complex (PTPC). Oncoproteins from the Bcl-2 family and tumor suppressor proteins from the Bax family interact with PTPC to inhibit or facilitate membrane permeabilization, respectively. Conventional chemotherapeutic agents elicit mitochondrial permeabilization in an indirect fashion by induction of endogenous effectors that are involved in the physiologic control of apoptosis. However, an increasing number of experimental anticancer drugs, including lonidamine, arsenite, betulinic acid, CD437, and several amphipathic cationic alpha-helical peptides, act directly on mitochondrial membranes and/or on the PTPC. Such agents may induce apoptosis in circumstances in which conventional drugs fail to act because endogenous apoptosis induction pathways, such as those involving p53, death receptors, or apical caspase activation, are disrupted. However, stabilization of the mitochondrial membrane by antiapoptotic Bcl-2-like proteins reduces the cytotoxic potential of most of these drugs. Targeting of specific PTPC components may overcome this Bcl-2-mediated apoptosis inhibition. One strategy involves cross-linking of critical redox-sensitive thiol groups within the PTPC; another involves the use of ligands to the mitochondrial benzodiazepine receptor. Thus, the design of mitochondrion-targeted cytotoxic drugs may constitute a novel strategy for overcoming apoptosis resistance.
An Automated Procedure for Blood Phenylalanine (1965)

Abstract The fluorometric analysis of phenylalanine described by McCaman and Robins has been adapted to automation. The procedure may be used on 20-µl. whole-blood samples which may be stored on filter paper for elution. The procedure is rapid, reproducible, and accurate, making it useful for screening large populations for phenylketonuria.
Facts and theories concerning the mechanisms of carcinogenesis (1991)

Carcinogenesis can be induced experimentally by exposure to exogenous agents or it can occur spontaneously without intentional or active intervention. Carcinogenesis can be actively induced by chemicals, radiation, infectious biological agents, transgenesis, or selective breeding. In the human and occasionally when testing potential carcinogens in animals, cancer may result from passive exposure to carcinogens encountered in the ambient environment or from changes in the internal milieu of the animal. Many carcinogens alter the structure of DNA resulting in carcinogenesis, but a significant number of carcinogens do not appear to act through this mechanism. When the action of specific carcinogenic agents is considered in relation to the stages of cancer development, initiation, promotion, and progression, the mechanism of the induction of carcinogenesis by DNA-reactive agents that alter genomic structure can be reconciled with those agents that do not act in this manner. As some cells are fortuitously initiated by uncontrolled variables such as irradiation and through changes in normal processes, the stimulation of growth and altered genetic expression by nongenotoxic agents may result indirectly in cancer development. The final stage of carcinogenesis, progression, can occur spontaneously, enhanced by formation and propagation of genetic errors due to increased cellular proliferation associated with the promotion stage. In addition, chemical and viral agents that lack the capacity for initiation and promotion may actively convert cells in the stage of promotion to the stage of progression. Therefore, the diverse mechanisms of action of carcinogenic agents in relation to their effects on specific stages in the natural history of cancer development allow for greater congruence of many of the theories of carcinogenesis. The influence of the roles of nongenotoxic carcinogenic agents and the potential role of progressor agents on the carcinogenesis process allow a more accurate identification of the potential risk that specific carcinogenic agents pose for increasing human cancer.
Dnase2a Deficiency Uncovers Lysosomal Clearance of Damaged Nuclear DNA via Autophagy (2014)

Deficiencies in DNA-degrading nucleases lead to accumulation of self DNA and induction of autoimmunity in mice and in monogenic and polygenic human diseases. However, the sources of DNA and the mechanisms that trigger immunity remain unclear. We analyzed mice deficient for the lysosomal nuclease Dnase2a and observed elevated levels of undegraded DNA in both phagocytic and nonphagocytic cells. In nonphagocytic cells, the excess DNA originated from damaged DNA in the nucleus based on colocalization studies, live-cell imaging, and exacerbation by DNA-damaging agents. Removal of damaged DNA by Dnase2a required nuclear export and autophagy-mediated delivery of the DNA to lysosomes. Finally, DNA was found to accumulate in Dnase2a(-/-) or autophagy-deficient cells and induce inflammation via the Sting cytosolic DNA-sensing pathway. Our results reveal a cell-autonomous process for removal of damaged nuclear DNA with implications for conditions with elevated DNA damage, such as inflammation, cancer, and chemotherapy.
L'autre oreille: Le pouvoir mystique de la musique au Moyen-Orient (1990)

« Dans le santā’, les soufis ecoutent un autre son qui vient du trone divin... Toi tu ecoutes la forme de la musique, mais eux, ils ont une autre oreille ! »Mowlānā Jalāloddīn Rūmī Dans la culture islamique, la reflexion sur la musique est dominee par la question de son pouvoir sur le corps et l’âme. Ce pouvoir est au centre des discussions et des mythes, en particulier dans la pensee soufie. En dehors des ouvrages scientifiques, la plupart des traites consacres a la musique commencent d’un c...