gebhart/patrepeval huggingface dataset:
Discriminant Analysis Indicates a Single Sperm Protein (SP22) Is Predictive of Fertility Following Exposure to Epididymal Toxicants (1997)

In a previous study, we found that ethane dimethanesulphonate (EDS) compromised the fertilizing ability of proximal cauda epididymal sperm from the rat within 4 days of exposure, an effect that persisted in castrated, testosterone (T)-implanted animals, establishing direct action on the epididymis. This EDS-induced reduction in fertilizing ability was highly correlated with a quantitative decrease in specific sperm protein. Here we sought to determine whether the fertility of proximal cauda epididymal sperm recovered from animals exposed to a variety of male reproductive toxicants could be predicted by assessing quantitative changes in specific sperm protein(s), or whether more common endpoints (e.g., sperm motility, sperm morphology, serum and epididymal tissue T, cauda epididymal sperm reserves) also are required to predict fertility. Intact adult male rats were dosed with EDS (25 or 50 mg/kg), chloroethylmethanesulphonate (CEMS; 12.5 or 18.75 mg/kg), or epichlorohydrin (EPI; 3 or 6 mg/kg) daily for 4 days. Castrated, T-implanted rats were dosed with hydroxyflutamide (HFLUT; 12.5 or 25 mg/kg) daily for 5 days. On day 5, proximal cauda epididymal sperm were inseminated in utero into receptive, cervically stimulated adult females, and on day 9, fertility (implants/corpora lutea) was assessed. Fertility-was decreased by the higher dose of each toxicant (P < 0.05) and also by the lower dose of EPI and HFLUT. Likewise, an acidic 22 kDa sperm protein (SP22) was decreased quantitatively (P < 0.05) in silver-stained two-dimensional gels by the higher dose of each toxicant as well as by the lower dose of EPI and HFLUT. Although sperm motility and serum T were altered by specific exposures, these endpoints were not useful in predicting fertility. In contrast, SP22 was highly correlated (P < 0.0001; r2 = 0.83) with fertility. Indeed, the amount of SP22 correctly predicted 90% and 94% of the fertile (> 50% fertility) and subfertile (< 50 fertility) animals, respectively, when discriminant analysis was performed. Thus, the amount of SP22 in a cauda epididymal sperm sample may be a useful predictor of fertility in toxicant-treated animals.
Molecular Dynamics Modeling of Clay Minerals. 1. Gibbsite, Kaolinite, Pyrophyllite, and Beidellite (1997)

A molecular dynamics model for clays and the oxide minerals is desirable for studying the kinetics and thermodynamics of adsorption processes. To this end, a valence force field for aluminous, dioctahedral clay minerals was developed. Novel aspects of this development include the bending potential for octahedral O−Al−O angles, which uses a quartic polynomial to create a double-well potential with minima at both 90° and 180°. Also, atomic point charges were derived from comparisons of ab initio molecular electrostatic potentials with X-ray diffraction-based deformation electron densities. Isothermal−isobaric molecular dynamics simulations of quartz, gibbsite, kaolinite, and pyrophyllite were used to refine the potential energy parameters. The resultant force field reproduced all the major structural parameters of these minerals to within 1% of their experimentally determined values. Transferability of the force field to simulations of adsorption onto clay mineral surfaces was tested through simulations of Na+, Ca2+, and hexadecyltrimethylammonium (HDTMA+) in the interlayers of beidellite clays. The new force field worked rather well with independently derived nonbonded parameters for all three adsorbates, as indicated by comparisons between experimental and molecular-dynamics-predicted d(001) layer spacings of the homoionic beidellites.
Suppressive Immunization with DNA Encoding a Self-Peptide Prevents Autoimmune Disease: Modulation of T Cell Costimulation (1999)

Usually we rely on vaccination to promote an immune response to a pathogenic microbe. In this study, we demonstrate a suppressive from of vaccination, with DNA encoding a minigene for residues 139-151 of myelin proteolipid protein (PLP139-151), a pathogenic self-Ag. This suppressive vaccination attenuates a prototypic autoimmune disease, experimental autoimmune encephalomyelitis, which presents clinically with paralysis. Proliferative responses and production of the Th1 cytokines, IL-2 and IFN-gamma, were reduced in T cells responsive to PLP139-151. In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN-gamma were reduced. A mechanism underlying the reduction in severity and incidence of paralytic autoimmune disease and the reduction in Th1 cytokines involves altered costimulation of T cells; loading of APCs with DNA encoding PLP139-151 reduced the capacity of a T cell line reactive to PLP139-151 to proliferate even in the presence of exogenous CD28 costimulation. DNA immunization with the myelin minigene for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in the spleen. Suppressive immunization against self-Ags encoded by DNA may be exploited to treat autoimmune diseases.
Human beta-fibrinogen gene expression. Upstream sequences involved in its tissue specific expression and its dexamethasone and interleukin 6 stimulation. (1990)

The synthesis of fibrinogen in the liver is drastically enhanced during the inflammatory process. Two factors are involved: glucocorticoids and the hepatocyte stimulating factor which is identical with interleukin 6 (Il6), also called interferon beta 2. The function of the 5'-flanking region of the human beta-fibrinogen (beta-Fg) gene has been studied by deletion analysis with the chloramphenicol acetyltransferase (CAT) gene as a transient expression vector. In this analysis, a fragment containing 150 base pairs (bp) upstream from the cap site is sufficient to drive expression of the CAT gene in the hepatoma cells HepG2, but not in HeLa cells. The beta-Fg gene is induced by dexamethasone and Il6 in HepG2. We identify a domain located between -2900 and -1500 bp upstream from the transcription start point involved in dexamethasone sensibility. This distal regulatory region can confer hormone inductibility to a heterologous promoter and exert its effect in either orientation. The sequence located between -150 and -82 bp upstream from the transcription start point is responsive for the Il6-stimulated expression. This 68-bp sequence contains probably all the cis-acting Il6-responsive element of the human beta-Fg gene.
Systematic analysis of structural data as a research technique in organic chemistry (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSystematic analysis of structural data as a research technique in organic chemistryFrank H. Allen, Olga Kennard, and Robin TaylorCite this: Acc. Chem. Res. 1983, 16, 5, 146–153Publication Date (Print):May 1, 1983Publication History Published online1 May 2002Published inissue 1 May 1983https://pubs.acs.org/doi/10.1021/ar00089a001https://doi.org/10.1021/ar00089a001research-articleACS PublicationsRequest reuse permissionsArticle Views1246Altmetric-Citations895LEARN 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-Alertsclose Get e-Alerts
Prioritizing test cases for regression testing (2000)

Test case prioritization techniques schedule test cases in an order that increases their effectiveness in meeting some performance goal. One performance goal, rate of fault detection , is a measure of how quickly faults are detected within the testing process; an improved rate of fault detection can provide faster feedback on the system under test, and let software engineers begin locating and correcting faults earlier than might otherwise be possible. In previous work, we reported the results of studies that showed that prioritization techniques can significantly improve rate of fault detection. Those studies, however, raised several additional questions: (1) can prioritization techniques be effective when aimed at specific modified versions; (2) what tradeoffs exist between fine granularity and coarse granularity prioritization techniques; (3) can the incorporation of measures of fault proneness into prioritization techniques improve their effectiveness? This paper reports the results of new experiments addressing these questions.
Can Relative Binding Free Energy Predict Selectivity of Reversible Covalent Inhibitors? (2017)

Reversible covalent inhibitors have many clinical advantages over noncovalent or irreversible covalent drugs. However, apart from selecting a warhead, substantial efforts in design and synthesis are needed to optimize noncovalent interactions to improve target-selective binding. Computational prediction of binding affinity for reversible covalent inhibitors presents a unique challenge since the binding process consists of multiple steps, which are not necessarily independent of each other. In this study, we lay out the relation between relative binding free energy and the overall reversible covalent binding affinity using a two-state binding model. To prove the concept, we employed free energy perturbation (FEP) coupled with λ-exchange molecular dynamics method to calculate the binding free energy of a series of α-ketoamide analogues relative to a common warhead scaffold, in both noncovalent and covalent binding states, and for two highly homologous proteases, calpain-1 and calpain-2. We conclude that covalent binding state alone, in general, can be used to predict reversible covalent binding selectivity. However, exceptions may exist. Therefore, we also discuss the conditions under which the noncovalent binding step is no longer negligible and propose to combine the relative FEP calculations with a single QM/MM calculation of warhead to predict the binding affinity and binding kinetics. Our FEP calculations also revealed that covalent and noncovalent binding states of an inhibitor do not necessarily exhibit the same selectivity. Thus, investigating both binding states, as well as the kinetics will provide extremely useful information for optimizing reversible covalent inhibitors.
Gene specific siRNA selector (2004)

Small interfering RNA (siRNA) is used in functional genomics applications to decrease the expression of a target gene, which may yield a biological effect that suggests a function for the target gene. The siRNA design tool scans a target gene for candidate siRNA sequences that satisfy user-adjustable rules. Selected candidates are then screened to identify those siRNA sequences that are specific to the gene of interest.
Acute myeloid leukemia therapeutics (2013)

Acute myeloid leukemia remains a difficult disease to cure and novel therapeutic approaches are needed. To this end, we developed CD123 chimeric antigen receptor (CAR) redirected T cells which exhibited potent antileukemic activity. We discuss what we learned during the development of CD123 CARs and future directions for this immunotherapy.
Hepatitis C Virus Infection Sensitizes Human Hepatocytes to TRAIL-Induced Apoptosis in a Caspase 9-Dependent Manner (2008)

Apoptosis of infected cells represents a key host defense mechanism against viral infections. The impact of apoptosis on the elimination of hepatitis C virus (HCV)-infected cells is poorly understood. The TRAIL has been implicated in the death of liver cells in hepatitis-infected but not in normal liver cells. To determine the impact of TRAIL on apoptosis of virus-infected host cells, we studied TRAIL-induced apoptosis in a tissue culture model system for HCV infection. We demonstrated that HCV infection sensitizes primary human hepatocytes and Huh7.5 hepatoma cells to TRAIL induced apoptosis in a dose- and time-dependent manner. Mapping studies identified the HCV nonstructural proteins as key mediators of sensitization to TRAIL. Using a panel of inhibitors targeting different apoptosis pathways, we demonstrate that sensitization to TRAIL is caspase-9 dependent and mediated in part via the mitochondrial pathway. Sensitization of hepatocytes to TRAIL-induced apoptosis by HCV infection represents a novel antiviral host defense mechanism that may have important implications for the pathogenesis of HCV infection and may contribute to the elimination of virus-infected hepatocytes.
miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression. (2010)

Lipoapoptosis of pancreatic beta cells caused by elevated circulating free fatty acids (FFAs) has now been recognized to be a pivotal factor contributing to beta cellular dysfunction and beta-mass lose in type 2 diabetes. Although recent studies suggested an important role for the ceramide pathway in the late destructive phase of lipid overload in the pancreatic beta cells, the overall underlying mechanisms leading to lipoapoptosis, however, remained poorly understood. mir-375 was recently characterized to be a pancreatic islet-specific miRNA implicated in the regulation of insulin secretion and beta-mass turnover. In the present study we further examined its effect on palmitate-induced lipoapoptosis in NIT-1 cells, a NOD-derived beta-cell line. It was found that NIT-1 cells with ectopic mir-375 expression were much more susceptible to palmitate-induced lipoapoptosis. In contrast, knockdown of endogenous pri-mir-375 expression by a modified antisense oligo, 2'-O-me-375, almost completely protected NIT-1 cells from palmitate-induced lipoapoptosis. We further demonstrated that mir-375 could target V1 mRNA and repress its translation. Consistent with this assumption, NIT-1 cells transfected with 2'-O-me-375 showed significant higher levels of V1 protein after palmitate induction. Together, our data suggest that mir-375 could be a potential therapeutic target for prevention and intervention of beta-cell dysfunction and beta-mass lose in type 2 diabetes.
Comparison of the DNA Sequences Involved in Replication and Packaging of the Filamentous Phages IKe and Ff (M13, fd, and fl) (1987)

The product of gene II of the distantly related, filamentous, single-stranded DNA phages IKe and Ff (M13, fd, and f1) is the only phage-encoded protein that is required for the replication of their double-stranded replicative form DNA. With the aid of recombinant plasmids containing the origins of viral strand replication [(+)-origins] of both IKe and Ff, we demonstrated that initiation but not termination of viral strand replication by gene II protein is restricted to its cognate (+)-origin. If the (+)-origins of IKe and Ff are present in the same orientation, fusion origins are generated upon gene II protein-instructed replication as a result of initiation at one origin and termination at the other. These fusion origins are only functional in the presence of the gene II protein encoded by the phage from which the sequence lying at the 3' side of the gene II protein cleavage site is derived. The nucleotides that determine the specificity of the replication initiation process are located between positions +17 and +49, or +17 and +40, with respect to the gene II protein cleavage site of IKe and Ff, respectively. The DNA sequence that forms the recognition signal for cleavage by gene II protein is probably located within the sequence that starts 3 nucleotides before and terminates 17 nucleotides after the cleavage site. Efficient packaging by phage IKe of plasmid DNA strands that contain the morphogenetic signal of Ff, or vice versa, indicates that, despite their only partial homology, the morphogenetic signals of IKe and Ff are interchangeable.
Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1 (2008)

We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1.
European protocol for neutron dosimetry for external beam therapy (1981)

A common basis for neutron dosimetry will be one of the essential requirements for the comparison of clinical results obtained at the increasing number of fast-neutron radiotherapy facilities. Co-operation between the physicists involved in fast-neutron radiotherapy has been established in Europe by the High LET Therapy Project Group under the sponsorship of the European Organization for Research on Treatment of Cancer, EORTC. In September 1978, the clinical group decided that the physicists should intensify their contacts and organize a formal co-operation. For this purpose a European Clinical Neutron Dosimetry Group, abbreviation ECNEU, was established. In the United States all groups involved in or planning fast neutron therapy have directly or indirectly participated in the Fast Neutron Beam Dosimetry Physics Task Group 18 of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM). Protocols for neutron dosimetry for radiotherapy have been drafted for the European (Broerse and Mijnheer, 1976) and the American groups (Eenmaa and Wootton, 1978). The main items of the two drafts were recently summarized by Broerse et al. (1979). Both groups, ECNEU and Task Group 18, have introduced a number of improvements which resulted in the final draft of the American protocol (AAPM, 1980) and the present contribution. Both protocols quote ICRU Report 26 (1977) as the main source of information on methodology and basic physical data for neutron dosimetry. It should be emphasized that efforts are continuing to improve the data base of neutron dosimetry.
Interval cancers following breast cancer screening in Singaporean women (2002)

Our study reports on the interval cancers arising in the subsequent 3 years in women screened as part of the Singapore Breast Cancer Screening Programme that commenced in 1994. Women, the majority of Chinese ethnicity, were either invited or not invited by random allocation to be screened. All women, other than those identified with breast cancer at screening, whether invited or not, were followed for 3 years, and information on all breast cancers arising in this period was obtained through the national registry. In particular, the cancers arising from those women who were deemed free of the disease at screening were noted. The mammographs taken at screening of those women who developed such an interval cancer were rereviewed by 3 radiologists. In the 28,099 women who were screened and deemed free of disease, 59 interval cancers were reported with annual rates of 2.1, 10.6 and 10.8 per 10,000 women-years in the succeeding 3-year periods. In 39,425 women who were invited but declined screening, the rates were 17.0, 15.5 and 11.7, while the corresponding rates from 97,294 women not invited were 12.8, 13.3 and 13.0. Whereas the annual incidence at 1 year in women who have been screened is much lower than those in the 2 groups who were not screened, it is of a similar magnitude by 2 years. This suggests that locally an optimal screening interval may be close to 1 year. The rereview of the mammograms of those 59 women with interval cancers suggested that the maximum possible number of these that might have been detected at screening was 10 (17%).
Emulation of the human torso dynamic effects during walking gait (2002)

An approach consisting of the identification of a minimal mechanical system which is capable to emulate the dynamic effects of the human torso during walking gait is presented. A 3D dynamic simulation of a virtual manikin with 27 degrees of freedom (DOFs) is carried out in order to identify the effort wrench exerted by the torso on the lower limbs. An analysis of the six components of this wrench shows that some components are dependant. A systemic study of two, three and four DOFs mechanisms based on general state equation formalism leads to an interesting result. Indeed, four DOFs are necessary and sufficient to emulate the dynamic effects. We also show the efficiency and generality of the proposed approach.
Homogeneous-Phase Electron-Transfer Reactions of Polyoxometalates (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHomogeneous-Phase Electron-Transfer Reactions of Polyoxometalates†I. A. WeinstockView Author Information USDA Forest Service, Forest Products Laboratory, One Gifford Pinchot Drive, Madison, Wisconsin 53705, and the Department of Chemistry, Emory University, 1515 Pierce Drive, Atlanta, Georgia 30322 Cite this: Chem. Rev. 1998, 98, 1, 113–170Publication Date (Web):January 22, 1998Publication History Received23 September 1997Revised12 November 1997Published online22 January 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/cr9703414https://doi.org/10.1021/cr9703414research-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views4110Altmetric-Citations309LEARN 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-Alertsclose SUBJECTS:Anions,Kinetic parameters,Oxidation,Redox reactions,Transfer reactions Get e-Alerts