gebhart/patrepeval huggingface dataset:
Making prophecies with decision predicates (2011)

We describe a new algorithm for proving temporal properties expressed in LTL of infinite-state programs. Our approach takes advantage of the fact that LTL properties can often be proved more efficiently using techniques usually associated with the branching-time logic CTL than they can with native LTL algorithms. The caveat is that, in certain instances, nondeterminism in the system's transition relation can cause CTL methods to report counter examples that are spurious with respect to the original LTL formula. To address this problem we describe an algorithm that, as it attempts to apply CTL proof methods, finds and then removes problematic nondeterminism via an analysis on the potentially spurious counterexamples. Problematic nondeterminism is characterized using decision predicates , and removed using a partial, symbolic determinization procedure which introduces new prophecy variables to predict the future outcome of these choices. We demonstrate---using examples taken from the PostgreSQL database server, Apache web server, and Windows OS kernel---that our method can yield enormous performance improvements in comparison to known tools, allowing us to automatically prove properties of programs where we could not prove them before.
Bioinformatic analysis of protein structure–function relationships: case study of leukocyte elastase (ELA2) missense mutations (2006)

Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood. The HNE mutations presumably cause loss of enzyme activity, consequently leading to compromised immune system function. To understand the structural basis for the disease, we implemented methods from bioinformatics to analyze all the known HNE missense mutations at both the sequence and structural level. Our results demonstrate that the 32 different mutations have diverse effects on HNE structure and function, affecting structural disorder and aggregation tendencies, stability maintaining contacts, and electrostatic properties. A large proportion of the mutations are located at conserved amino acids, which are usually essential in determining protein structure and function. The majority of the disease-causing HNE missense mutations lead to major structural changes and loss of stability in the protein. A few mutations also affect functional residues, leading into decreased catalytic activity or altered ligand binding. Our analysis reveals the putative effects of all known missense mutations in HNE, thus allowing the structural basis of cyclic and congenital neutropenia to be elucidated. We have employed and analyzed a set of some 30 different methods for predicting the effects of amino acid substitutions. We present results and experience from the analysis of the applicability of these methods in the analysis of numerous genes, proteins, and diseases to reveal protein structure–function relationships and disease genotype–phenotype correlations. Hum Mutat 27(12), 1230–1243, 2006. © 2006 Wiley-Liss, Inc.
A recombinant multivalent combination vaccine protects againstChlamydiaand genital herpes (2006)

Chlamydia trachomatis and Herpes simplex virus type 2 (HSV-2) genital infections pose a considerable public health challenge worldwide. Considering the high incidence of coinfections by the two pathogens, a combination vaccine that can be administered as a single regimen would be highly desirable. Recombinant Vibrio cholerae ghosts (rVCG) offer an attractive approach for the induction of humoral and cellular immune responses against human and animal pathogens. In this study, we evaluated a bivalent combination vaccine formulation comprising rVCG expressing chlamydial MOMP and HSV-2 glycoprotein D in mice for immunogenicity and protective efficacy against genital challenge with either pathogen. Mice immunized with the combination vaccine elicited secretory IgA and IgG2a antibodies to both chlamydial and HSV-2 antigens in serum and vaginal secretions. Robust antigen-specific mucosal and systemic T helper type 1 responses were induced in mice as measured by increased interferon-gamma levels produced by immune T cells in response to restimulation with target antigen in vitro. In addition, mice immunized with the combination vaccine were prophylactically protected from genital challenge with high doses of live Chlamydia and HSV-2. Thus, the combination vaccine regimen delivered by rVCG elicited adequate immune effectors that simultaneously protected against the individual pathogens.
An Aged Rat Model of Partial Androgen Deficiency: Prevention of Both Loss of Bone and Lean Body Mass by Low-Dose Androgen Replacement (2000)

The aim of this study was to evaluate the effects of different doses of androgen replacement, both on body composition and bone, in an aged male orchidectomized rat model. Testosterone was administered by 0.5, 1, and 2.5-cm sc SILASTIC implants (release of, respectively, 11.5, 23, and 55 μg/day) to aged (12 months old, ± 550 g) male orchidectomized Wistar rats during a 15-week experimental period.
[Supersynthesis of flavins in microorganisms and its molecular mechanism (review of the literature)]. (1988)

The present review discusses the significance of fundamental research into regulation of flavin biosynthesis for development of the knowledge about mechanisms of overproduction of these compounds and their manufacturing. The pathways of riboflavin, FMN and FAD biosyntheses and their regulation in some bacteria, yeasts and fungi are considered, as well as the recent advances in flavin biotechnology. The modern trends in microbial and enzymatic production of flavins are discussed.
Characterization of Semiquinone Free Radicals Formed from Stilbene Catechol Estrogens (1989)

Electron spin resonance spectroscopy has been used to detect, characterize, and to infer structures of o-semiquinones derived from stilbene catechol estrogens. Radicals were generated enzymatically using tyrosinase and were detected as their Mg2+ complexes. It is suggested that initial hydroxylation of stilbene estrogen gives a catechol estrogen in situ; subsequent two-electron oxidation of the catechol to the quinone, followed by reverse disproportionation, leads to the formation of radicals. Consistent with this mechanism, o-phenylenediamine, a quinone trapping agent, inhibits formation of o-semiquinones. A competing mechanism of radical production involves autoxidation of the catechol. Hydroxyl radicals are shown to be produced in this system via a mechanism involving reduction of iron and copper complexes by stilbene catechols. Possible differences in the reactivity of stilbene ortho- and para-semiquinones are discussed.
Vaccine-Induced Effector-Memory CD8+ T Cell Responses Predict Therapeutic Efficacy against Tumors (2012)

CD8(+) T cells have the potential to attack and eradicate cancer cells. The efficacy of therapeutic vaccines against cancer, however, lacks defined immune correlates of tumor eradication after (therapeutic) vaccination based on features of Ag-specific T cell responses. In this study, we examined CD8(+) T cell responses elicited by various peptide and TLR agonist-based vaccine formulations in nontumor settings and show that the formation of CD62L(-)KLRG1(+) effector-memory CD8(+) T cells producing the effector cytokines IFN-γ and TNF predicts the degree of therapeutic efficacy of these vaccines against established s.c. tumors. Thus, characteristics of vaccine-induced CD8(+) T cell responses instill a predictive determinant for the efficacy of vaccines during tumor therapy.
Tri-lithium borate (Li3BO3); a new highly regenerable high capacity CO2 adsorbent at intermediate temperature (2017)

A lithium-borate oxide, Li<sub>3</sub>BO<sub>3</sub>, is proposed as a next generation high capacity CO<sub>2</sub> adsorbent operative over the intermediate temperature range of 500 to 650 °C.
Wideband fading channel capacity with training and partial feedback (2005)

We consider the capacity of a wideband fading channel with partial feedback, subject to an average power constraint. A doubly block Rayleigh fading model is assumed with finite coherence time (L channel uses) and a large number of independent, finite bandwidth coherence bands (sub-channels). Without feedback, it is known that uniformly spreading the signal power beyond a critical number of coherence bands decreases the capacity. Here we assume that the transmitter probes a subset of subchannels during each coherence time by transmitting pilot sequences for channel estimation. For each sub-channel probed, one bit of feedback indicates whether or not the transmitter should continue to transmit information symbols. Our problem is to optimize jointly the training (both length and power), number of sub-channels probed (probing bandwidth), and feedback threshold to maximize the achievable rate (lower bound on ergodic capacity) taking into account the sub-channel estimation error. Optimizing the probing bandwidth balances diversity against the quality of sub-channel estimate. We show that the achievable rate increases as S log L, where S is the Signal-to-Noise Ratio, and exceeds the capacity with impulsive signaling (given by S) when L exceeds a (positive) threshold value. Moreover, the optimal probing bandwidth scales as S L log2 L. In contrast, without feedback the optimal probing bandwidth for the probing scheme scales as SL1/3 and the achievable rate converges to S, where the gap diminishes as SL−1/3.
Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer (2007)

Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided. During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline ( P = .05) and the rate of PSA change ( P <.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level. Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.
Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies (2010)

Recently, several newer diagnostic tools have become available. The American and European Neurogastroenterology and Motility Societies undertook this review to provide guidelines on the indications and optimal methods for the use of transit measurements in clinical practice. This was based on evidence of validation including performance characteristics, clinical significance, and strengths of various techniques. The tests include measurements of: gastric emptying with scintigraphy, wireless motility capsule, and (13)C breath tests; small bowel transit with breath tests, scintigraphy, and wireless motility capsule; and colonic transit with radioopaque markers, wireless motility capsule, and scintigraphy. Based on the evidence, consensus recommendations are provided for each technique and for the evaluations of regional and whole gut transit. In summary, tests of gastrointestinal transit are available and useful in the evaluation of patients with symptoms suggestive of gastrointestinal dysmotility, since they can provide objective diagnosis and a rational approach to patient management.
Multiple Sclerosis (2000)

More than 100 years has passed since Charcot, Carswell, Cruveilhier, and others described the clinical and pathological characteristics of multiple sclerosis.1 This enigmatic, relapsing, and often eventually progressive disorder of the white matter of the central nervous system continues to challenge investigators trying to understand the pathogenesis of the disease and prevent its progression.2 There are 250,000 to 350,000 patients with multiple sclerosis in the United States.3 Multiple sclerosis typically begins in early adulthood and has a variable prognosis. Fifty percent of patients will need help walking within 15 years after the onset of disease.4 Advanced magnetic resonance imaging (MRI) . . .
Molecular Pathways: Targeting ATR in Cancer Therapy (2015)

The human ATR gene encodes a kinase that is activated by DNA damage and replication stress as a central transducer of a checkpoint signaling pathway. Once activated, ATR phosphorylates multiple substrates, including the kinase Chk1, to regulate cell-cycle progression, replication fork stability, and DNA repair. These events promote cell survival during replication stress and in cells with DNA damage. Accordingly, there has been the tantalizing possibility that ATR inhibitors would be therapeutically useful, especially if they were more effective in tumor versus normal cells. Indeed, multiple studies have demonstrated that alterations that promote tumorigenesis, such as defects in the ATM-p53 pathway, constitutive oncogene activation, and acquisition of the alternative lengthening of telomeres pathway, render tumor cells sensitive to ATR inhibitor monotherapy and/or increase the synergy between ATR inhibitors and genotoxic chemotherapies. Now, nearly two decades after the discovery of ATR, two highly selective and potent ATR inhibitors, AZD6738 and VX-970, are in early-phase clinical trials either as monotherapies or paired with a variety of genotoxic chemotherapies. These trials will generate important insights into the effects of ATR inhibition in humans and the potential role of inhibiting this kinase in the treatment of human malignancies.
Troubleshooting Nuclear Medicine Instrumentation Problems (1982)

Etude des problemes, de leurs causes et de leurs solutions, des equipements diagnostiques suivants: camera a scintillation, detecteur a scintillation, et systemes informatiques
Real-time optical biopsy and analysis of breast cancer using clinical optical coherence tomography (2007)

10508 Background: Advances in high-resolution, real-time, optical imaging have enabled optical coherence tomography (OCT) for non-excisional optical biopsies of breast tissue. OCT is the optical analogue to ultrasound imaging, with resolution approaching that of histology. In breast tissue, regions of tumor, tumor margins, abnormal ducts, and foci of tumor cells can be identified based on increased scattering and morphological appearance. We have developed a portable clinical OCT system along with image criteria for identifying breast cancer in real-time during needle-biopsy and surgical-biopsy procedures. Methods: Over 4,000 depth-resolved OCT axial scans were extracted from over 50 cross-sectional OCT images from 9 ex vivo specimens of ductal carcinoma in situ (DCIS) of the human breast. OCT image data was acquired in real-time within 6 hours of surgical resection using a state-of-the-art OCT system with micron resolution. Imaged sites were marked for registration with hematoxylin and eosin-stained histology. Axial scan data was analyzed using frequency-domain analysis techniques to classify regions as tumor, stroma, or adipose tissue. OCT images of tissue types were compared with histological observations. Results: Real-time OCT images of microscopic breast cancer morphology showed strong correlations with corresponding histology, including regions of tumor, tumor margins, ducts, and adipose tissue. Computational frequency-domain analysis of depth-resolved axial scan data classified tissue types as tumor, stroma, and adipose with 91% sensitivity and 87% specificity. Conclusions: Optical biopsy of breast cancer with OCT is feasible for imaging at resolutions approaching histology. Frequency- domain analysis of axial scan data can be used to classify breast tissue types with a sensitivity and specificity that are comparable to or surpasses that of conventional mammography and ultrasound imaging of human DCIS. Clinical OCT imaging has the potential for real-time guidance and diagnostics in needle- or surgical-biopsy of breast cancer. No significant financial relationships to disclose.
Effects of adriamycin on enzymes of adenine nucleotide metabolism in heart cell cultures. (1985)

Effects of adriamycin (ADM) treatment on rat heart cells in culture were examined. ADM treatment (lug/ml) for 3 hr, 48 to 51hr of culture age, had no effect on oxygen consumption, myosin content or myosin ATPase activity. In contrast, the activities of creatine kinase, adenylate kinase and adenosine deaminase were significantly lower in ADM-treated cells than in corresponding controls at 72 and 96 hr of culture age. Fall in the activities of these key enzymes of adenine nucleotide metabolism would lead to disturbances in energy metabolism, and results in the functional impairment of heart cells.
Identification of α‐fetoprotein‐derived peptides recognized by cytotoxic T lymphocytes in HLA‐A24+ patients with hepatocellular carcinoma (2005)

Alpha-fetoprotein (AFP) has been proposed as a potential target forT-cell-based immunotherapy for hepatocellular carcinoma (HCC), but the number of its epitopes that have been identified is limited and the status of AFP-specific immunological responses in HCC patients has not been well-characterized. To address the issue, we examined the possibility of inducing AFP-specific cytotoxic T cells (CTLs) using novel HLA-A*2402-restricted T-cell epitopes (HLA, human leukocyte antigen) derived from AFP and then analyzed the relationship between its frequency of occurrence and clinical features associated with patients having HCC. Five AFP-derived peptides containing HLA-A*2402 binding motifs and showing high binding affinity to HLA-A*2402 induced CTLs to produce IFN-gamma and kill an AFP-producing hepatoma cell line. The frequency of AFP-specific CTLs was 30-190 per 1 x 10(6) peripheral blood mononuclear cells, which was the same as that of other immunogenic cancer associated antigen-derived epitopes. Analyses of the relationships between AFP-specific CTL responses and clinical features of patients with HCC revealed that AFP epitopes were more frequently recognized by CTLs in patients with advanced HCC correlating to tumor factors or the stage of TNM classification. The analyses of CTL responses before and after HCC treatments showed that the treatments changed the frequency of AFP-specific CTLs. In conclusion, we identified five HLA-A*2402-restricted T-cell epitopes derived from AFP. The newly identified AFP epitopes could be a valuable component of HCC immunotherapy and for analyzing host immune responses to HCC.
The A‐subunit of surface‐bound Shiga toxin stimulates clathrin‐dependent uptake of the toxin (2005)

Shiga toxin can be internalized by clathrin-dependent endocytosis in different cell lines, although it binds specifically to the glycosphingolipid Gb3. It has been demonstrated previously that the toxin can induce recruitment of the toxin-receptor complex to clathrin-coated pits, but whether this process is concentration-dependent or which part of the toxin molecule is involved in this process, have so far been unresolved issues. In this article, we show that the rate of Shiga toxin uptake is dependent on the toxin concentration in several cell lines [HEp-2, HeLa, Vero and baby hamster kidney (BHK)], and that the increased rate observed at higher concentrations is strictly dependent on the presence of the A-subunit of cell surface-bound toxin. Surface-bound B-subunit has no stimulatory effect. Furthermore, this increase in toxin endocytosis is dependent on functional clathrin, as it did not occur in BHK cells after induction of antisense to clathrin heavy chain, thereby blocking clathrin-dependent endocytosis. By immunofluorescence, we show that there is an increased colocalization between Alexa-labeled Shiga toxin and Cy5-labeled transferrin in HeLa cells upon addition of unlabeled toxin. In conclusion, the data indicate that the Shiga toxin A-subunit of cell surface-bound toxin stimulates clathrin-dependent uptake of the toxin. Possible explanations for this phenomenon are discussed.
Evidence That Levels of Presenilins (PS1 and PS2) Are Coordinately Regulated by Competition for Limiting Cellular Factors (1997)

Mutations in two related genes, PS1 and PS2, account for the majority of early onset cases of familial Alzheimer's disease. PS1 and PS2 are homologous polytopic membrane proteins that are processed endoproteolytically into two fragments in vivo. In the present report we examine the fate of endogenous PS1 and PS2 after overexpression of human PS1 or PS2 in mouse N2a neuroblastoma cell lines and human PS1 in transgenic mice. Remarkably, in N2a cell lines and in brains of transgenic mice expressing human PS1, accumulation of human PS1 derivatives is accompanied by a compensatory, and highly selective, decrease in the steady-state levels of murine PS1 and PS2 derivatives. Similarly, the levels of murine PS1 derivatives are diminished in cultured cells overexpressing human PS2. To define the minimal sequence requirements for "replacement" we expressed familial Alzheimer's disease-linked and experimental deletion variants of PS1. These studies revealed that compromised accumulation of murine PS1 and PS2 derivatives resulting from overexpression of human PS1 occurs in a manner independent of endoproteolytic cleavage. Our results are consistent with a model in which the abundance of PS1 and PS2 fragments is regulated coordinately by competition for limiting cellular factor(s).