gebhart/patrepeval huggingface dataset:
Antiarrhythmic drugs for atrial fibrillation: focus on dronedarone (2009)

Patients with atrial fibrillation have an increased risk of stroke and heart failure, as well as impairment of their quality of life. Most trials have primarily focused on the prevention of stroke and heart failure, and the improvement of symptoms in these patients. More recently, a rate-control strategy has been reported to be a noninferior strategy compared with a rhythm-control strategy in atrial fibrillation patients. Many different classes of antiarrhythmic drugs have been used for rhythm control, with inconsistent results and adverse effects on mortality and morbidity. Of the available antiarrhythmic drugs, amiodarone is the single most effective drug in the prevention of atrial fibrillation recurrences and maintaining sinus rhythm; however, it is vastly limited by its various systemic side effects, especially those observed with long-term use. However, recent trial data from a new antiarrhythmic agent, dronedarone, suggest that this drug may be a safe alternative to amiodarone; however, its long-term efficacy and safety still require exploration.
Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation. (1997)

This study investigates the significance of the glucose-6-phosphate dehydrogenase (G6PD) catalyzed oxidative and the transketolase (TK) catalyzed nonoxidative pentose cycle (PC) reactions in the tumor proliferation process by characterizing tumor growth patterns and synthesis of the RNA ribose moiety in the presence of respective inhibitors of G6PD and TK. Mass spectra analysis of 13C-labeled carbons revealed that these PC reactions contribute to over 85% of de novo ribose synthesis in RNA from [1,2-(13)C]glucose in cultured Mia pancreatic adenocarcinoma cells, with the fraction synthesized through the TK pathway predominating (85%). Five days of treatment with the TK inhibitor oxythiamine (OT) and the G6PD inhibitor dehydroepiandrosterone-sulfate (0.5 microM each) exerted a 39 and a 23% maximum inhibitory effect on cell proliferation in culture, which was increased to 60% when the two drugs were administered in combination. In vivo testing of 400 mg/kg OT or dehydroepiandrosterone-sulfate in C57BL/6 mice hosting Ehrlich's ascitic tumor cells revealed a 90.4 and a 46% decrease in the final tumor mass after 3 days of treatment. RNA ribose fractional synthesis through the TK reaction using metabolites directly from glycolysis declined by 9.1 and 23.9% after OT or the combined treatment, respectively. Nonoxidative PC reactions play a central regulating role in the carbon-recruiting process toward de novo nucleic acid ribose synthesis and cell proliferation in vitro and in vivo. Therefore, enzymes or substrates regulating the nonoxidative synthesis of ribose could also be the sites to preferentially target tumor cell proliferation by new anticancer drugs.
Flexible Ion‐Conducting Composite Membranes for Lithium Batteries (2015)

The use of metallic lithium anodes enables higher energy density and higher specific capacity Li‐based batteries. However, it is essential to suppress lithium dendrite growth during electrodeposition. Li‐ion‐conducting ceramics (LICC) can mechanically suppress dendritic growth but are too fragile and also have low Li‐ion conductivity. Here, a simple, versatile, and scalable procedure for fabricating flexible Li‐ion‐conducting composite membranes composed of a single layer of LICC particles firmly embedded in a polymer matrix with their top and bottom surfaces exposed to allow for ionic transport is described. The membranes are thin (&lt;100 μm) and possess high Li‐ion conductance at thicknesses where LICC disks are mechanically unstable. It is demonstrated that these membranes suppress Li dendrite growth even when the shear modulus of the matrix is lower than that of lithium. It is anticipated that these membranes enable the use of metallic lithium anodes in conventional and solid‐state Li‐ion batteries as well as in future LiS and LiO 2 batteries.
Biostatistical modeling using traditional variables and genetic biomarkers for predicting the risk of prostate carcinoma recurrence after radical prostatectomy (1997)

This equation allows patients at high risk for PSA recurrence to be identified shortly after radical surgery. These patients at high risk for serologic recurrence and eventual progression may be considered for currently accepted adjuvant therapy or enrollment in clinical trials for the newer investigational therapies for locally advanced prostate carcinoma.
Magnetic and corrosion characteristics of Nd-Fe-B magnet with various surface coatings (1997)

Various surface coatings, including duplex Ni(undercoat)/Cr(topcoat), multilayer Ni/Cu/Ni/Cr, Zn, bright Ni, bright Au, and black epoxy were applied to improve the corrosion resistance of the Nd-Fe-B magnet. The corrosion behavior of the surface-coated magnets was studied using Normal and Acetic Acid Salt Spray Tests. The influence of coating and corrosion on the magnetic properties was also investigated. It was found that the duplex Ni/Cr coating provided the best corrosion protection with little deterioration in the magnetic properties during the corrosion process.
Studies in Subjects with Long-Term Nonprogressive Human Immunodeficiency Virus Infection (1995)

In persons who remain free of disease for many years despite HIV infection the viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact.
Depression and Cardiovascular Sequelae in Postmenopausal Women (2004)

A large proportion of older women report levels of depressive symptoms that are significantly related to increased risk of CVD death and all-cause mortality, even after controlling for established CVD risk factors. Whether early recognition and treatment of subclinical depression will lower CVD risk remains to be determined in clinical trials.
The Infecting Dose ofChlamydia muridarumModulates the Innate Immune Response and Ascending Infection (2004)

Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.
Pim-1: A serine/threonine kinase with a role in cell survival, proliferation, differentiation and tumorigenesis (2001)

Pim-1 belongs to a family of serine/threonine protein kinases that are highly conserved through evolution in multicellular organisms. Originally identified from moloney murine leukemia virus (MuLV)-induced T-cell lymphomas in mice, Pim-1 kinase is involved in the control of cell growth, differentiation and apoptosis. Expression of Pim-1 kinase can be stimulated by a variety of growth factors and regulated at four different levels: transcriptional, post-transcriptional, translational and post-translational. Several signal transduction pathways may be associated with the regulation of Pim-1's expression; accumulating data support that the expression of Pim-1 protein is mediated through activation of JAK/STATs. Recent studies of Pim family kinases indicate that Pim-1 kinase plays important roles outside of the hematopoietic system as well.
Revision of the Nomenclature for the Bacillus thuringiensis Pesticidal Crystal Proteins (1998)

The crystal proteins of Bacillus thuringiensis have been extensively studied because of their pesticidal properties and their high natural levels of production. The increasingly rapid characterization of new crystal protein genes, triggered by an effort to discover proteins with new pesticidal properties, has resulted in a variety of sequences and activities that no longer fit the original nomenclature system proposed in 1989. Bacillus thuringiensis pesticidal crystal protein (Cry and Cyt) nomenclature was initially based on insecticidal activity for the primary ranking criterion. Many exceptions to this systematic arrangement have become apparent, however, making the nomenclature system inconsistent. Additionally, the original nomenclature, with four activity-based primary ranks for 13 genes, did not anticipate the current 73 holotype sequences that form many more than the original four subgroups. A new nomenclature, based on hierarchical clustering using amino acid sequence identity, is proposed. Roman numerals have been exchanged for Arabic numerals in the primary rank (e.g., Cry1Aa) to better accommodate the large number of expected new sequences. In this proposal, 133 crystal proteins comprising 24 primary ranks are systematically arranged.
Correlation of hormone receptors with pathological features in human breast cancer (1980)

Correlations have been found between certain pathologic features and estrogen and progesterone receptors status of mammary carcinoma. Well-differentiated carcinomas were more frequently receptor positive than poorly differentiated tumors. An increasing degree of lymphocytic and plasmacytic infiltrate in the tumor was associated with a decreasing incidence of estrogen receptor activity. In addition, elastosis in primary carcinomas has been correlated with response to endocrine therapy in patients with advanced disease. With increasing amounts of elastosis in the primary tumor, there was an increase in the response rate. Also, patients with estrogen receptor positive tumors with no elastosis showed a response rate similar to that of estrogen receptor-negative tumors. Hormone receptor analysis is most valuable when considered with other factors.
In the Absence of Endogenous Gamma Interferon, Mice Acutely Infected withNeospora caninumSuccumb to a Lethal Immune Response Characterized by Inactivation of Peritoneal Macrophages (2001)

Following infection with Neospora caninum, BALB/c mice were shown to be resistant to an acute infection but developed a latent chronic infection. However, BALB/c background gamma interferon (IFN-gamma)-deficient mice were sensitive to the acute infection. Since the immune response in IFN-gamma-deficient mice is scantly known, we examined the function of macrophages, major histocompatibility complex (MHC) class II expression, T-cell responses, and serum cytokine levels in the mice. All IFN-gamma-deficient mice died within 9 days of infection with N. caninum, whereas those treated with exogenous IFN-gamma lived longer. Although N. caninum invaded various organs in both types of mice at the early stage of infection, the parasite was not detected in the brains of resistant hosts until 21 days postinfection (dpi). Peritoneal macrophages from IFN-gamma-deficient mice were activated by exogenous IFN-gamma associated with inhibition of parasite growth and nitric oxide production as were those from BALB/c mice. IFN-gamma-deficient mice failed to increase MHC class II expression on macrophages. Moreover, BALB/c mice induced T-cell proliferation while IFN-gamma-deficient mice did not. However, in vivo treatment with exogenous IFN-gamma induced up-regulated MHC class II expression in IFN-gamma-deficient mice. BALB/c mice treated with an antibody to CD4 showed an increase in morbidity and mortality after parasite infection. In serum, significant levels of IFN-gamma and interleukin-4 (IL-4) were detected in resistant hosts, whereas IL-10 was detected in IFN-gamma-deficient mice. The levels of IL-12 in IFN-gamma-deficient mice were higher than those in BALB/c mice at 7 dpi. The present study indicates that early IFN-gamma production has a crucial role in the activation of peritoneal macrophages for the induction of protective immune responses against N. caninum.
Evidence of a locus for schizophrenia and related disorders on the short arm of chromosome 5 in a large pedigree (1996)

We attempted to identify a locus for schizophrenia and related disorders in 24 nuclear families of schizophrenic probands using a predefined classification system for affected cases that included those disorders most clearly identified as sharing a genetic relationship with schizophrenia--schizoaffective disorder and schizotypal personality disorder. Initially, we evaluated 8 markers on chromosome 5 on the first 12 families with available genotyping and diagnostic assessments and, assuming autosomal dominant transmission, found a lod score of 2.67 for the D5S111 locus (5p14.1-13.1) in one large nuclear family (no. 17; sibship: n = 12; schizophrenia: n = 3; schizotypal personality disorder: n = 2); the other 11 families were much smaller, less complete, and provided little additional information. Other branches of no. 17 were then assessed and the 2-point lod score for family 17 rose to 3.72; using multipoint analysis the lod score in 17 was 4.37. When only schizophrenia was used to define affectedness, the positive evidence for linkage to D5S111 was greatly reduced. Sensitivity analysis indicated that the lod score is heavily dependent upon the predefined diagnostic criteria. Our studies of other families of schizophrenic probands eventually totalled 23, but linkage to D5S111 in these yielded a -2.41 lod score. The results provide evidence for genetic linkage of the D5S111 locus to schizophrenia and related disorders in one family. It may be of interest that over several generations, almost all the ancestors of family 17 could be traced back to a small, relatively isolated, hill region of Puerto Rico.
Early Epidermal Destruction with Subsequent Epidermal Hyperplasia Is a Unique Feature of the Papilloma-Independent Squamous Cell Carcinoma Phenotype in PKCε Overexpressing Transgenic Mice (2005)

Protein kinase C epsilon (PKCepsilon) overexpressing transgenic (PKCepsilon Tg) mice develop papilloma-independent squamous cell carcinomas (SCC) elicited by 7,12-dimethylbenz[a]anthracene (DMBA) tumor initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) tumor promotion. We examined whether epidermal cell turnover kinetics was altered during the development of SCC in PKCepsilon Tg mice. Dorsal skin samples were fixed for histological examination. A single application of TPA resulted in extensive infiltration of polymorphonuclear neutrophils (PMNs) into the epidermis at 24 h after TPA treatment in PKCepsilon Tg mice while wild-type (WT) mouse skin showed focal infiltration by PMNs. Complete epidermal necrosis was observed at 48 h in PKCepsilon Tg mice only; at 72 h, epidermal cell regeneration beginning from hair follicles was observed in PKCepsilon Tg mice. Since the first TPA treatment to DMBA-initiated PKCepsilon Tg mouse skin led to epidermal destruction analogous to skin abrasion, we propose the papilloma-independent phenotype may be explained by death of initiated interfollicular cells originally destined to become papillomas. Epidermal destruction did not occur after multiple doses of TPA, presumably reflecting adaptation of epidermis to chronic TPA treatment. Prolonged hyperplasia in the hair follicle may result in the early neoplastic lesions originally described by Jansen et al. (2001) by expanding initiated cells in the hair follicles resulting in the subsequent development of SCC.
Adiabatic-rapid-passage multiphoton Bragg atom optics (2012)

The combination of adiabatic rapid passage and multiphoton Bragg diffraction (ARPMB pulses) to efficiently transfer many photon recoils of momentum ($\ensuremath{\hbar}k$) to cold-atom clouds is theoretically and experimentally investigated. This method is insensitive to perturbations of the pulse intensity or detuning. In particular, the theoretically calculated velocity acceptance can be up to $80%$ of one recoil velocity ${v}_{r}$, the theoretical maximum in Bragg diffraction. We experimentally demonstrate ARPMB pulses with transfer efficiency of 99.7$%$ per $\ensuremath{\hbar}k$ using $10\ensuremath{\hbar}k$ pulses, limited by spontaneous emission losses, and Mach-Zehnder interferometers with $80%$ contrast.
Chronic morphine augments G(beta)(gamma)/Gs(alpha) stimulation of adenylyl cyclase: relevance to opioid tolerance. (1998)

In the current study, we investigated the neurochemical basis for the previously reported predominance of stimulatory mu-opioid signaling in guinea pig longitudinal muscle/myenteric plexus (LMMP) preparations after chronic in vivo morphine exposure. As expected, recombinant Gsalpha (rGsalpha) dose-dependently stimulated adenylyl cyclase (AC) activity in LMMP membranes obtained from opioid naive as well as tolerant LMMP tissue. However, the magnitude of the increase was significantly greater in the latter than in the former. The Gbetagamma blocking peptide QEHA (50 microM) essentially abolished stimulation by rGsalpha in LMMP membranes obtained from both opioid naive and tolerant animals. Interestingly, after partial blockade by lower QEHA concentrations, the incremental AC stimulation by rGsalpha in tolerant LMMP membranes was no longer observed, indicating augmented Gbetagamma stimulatory responsiveness. Concomitant changes in the content of AC isoform protein are consistent with these biochemical observations. After chronic systemic morphine, AC protein is augmented significantly (56%). This increment is most likely to be composed of AC isoforms that are stimulated by Gbetagamma. This is the first demonstration in a complex mammalian tissue that persistent activation of opioid receptors results in augmented Gbetagamma/Gsalpha AC stimulatory interactiveness. The relevance of such changes to the manifestation of opioid tolerance is discussed.
Dehydroepiandrosterone Can Inhibit the Proliferation of Myeloma Cells and the Interleukin-6 Production of Bone Marrow Mononuclear Cells from Patients with Myeloma (2005)

The serum levels of an adrenal sex hormone, dehydroepiandrosterone sulfate (DHEA-S), are significantly more decreased in human myelomas compared with the reduction brought by physiologic decline with age. In order to clarify the effect of DHEA on myeloma cells, we investigated whether DHEA and DHEA-S could inhibit interleukin-6 (IL-6) production of bone marrow mononuclear cells and the proliferation of myeloma cells from patients with myeloma. DHEA-S and DHEA suppressed IL-6 production from a bone marrow stromal cell line, KM-102, as well as in bone marrow mononuclear cells from patients with myeloma. Furthermore, DHEA inhibited in vitro growth of the U-266 cell line and primary myeloma cells from the patients, as well as the in vivo growth of U-266 cells implanted i.p. in severe combined immunodeficiency-hIL6 transgenic mice. DHEA up-regulated the expression of peroxisome proliferator-activated receptor (PPAR), PPAR beta, but not PPARgamma or PPARalpha, and the expression of IkappaBalpha gene in myeloma cells and bone marrow stromal cells, which could explain the suppressive effect of DHEA on IL-6 production through the down-regulation of NF-kappaB activity. Therefore, these data revealed that DHEA-S, as well as DHEA, had a direct effect on myeloma and bone marrow stromal cells to inhibit their proliferation and IL-6 production, respectively.
Nature screen: an efficient method for screening natural populations of Drosophila for targeted P-element insertions. (1994)

The efficiency of molecular techniques is making it increasingly necessary to rely on reverse genetics to understand the function of genes. Tissue-specific libraries allow one to identify numerous genes that can be cloned, sequenced, and mapped and whose temporal and tissue-specific pattern of expression are well characterized but whose function remains unknown. In such cases, it is desirable to generate targeted mutations to examine the phenotype of loss-of-function lesions. Here we describe a method for identifying naturally occurring variants of Drosophila melanogaster with specific genes tagged by a nearby P element. Imprecise P-element excision can then be used to generate a series of small deletions in or near the gene. In the method described here, large numbers of wild-caught males were crossed to balancer females, and inserts were identified in pooled samples by the polymerase chain reaction with one primer from each target gene and one primer from the P-element terminal repeat. We present the calculations for the probability of successfully tagging a gene and show that it is greatly improved by simultaneously screening inserts into several genes. If a large natural population is available, a nature screen is faster and easier than inducing P-element transposition in the laboratory, but the resulting lines, being genetically heterogeneous, may require more subsequent work to isolate. Using this method to screen the genomes of approximately 10,400 males, we found P-element inserts in close proximity to 3 of 10 genes that were screened.
Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer's disease: A positron emission tomography study (2000)

We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's disease (AD) and 14 age-matched controls by positron emission tomography (PET) and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had repeat PET scans. The k3 values were calculated as an index of acetylcholinesterase activity in a three-compartment analysis using the metabolite corrected arterial input function. Twenty-eight of the 30 AD patients (14 each in the early and late onset subgroups) were retained in the study so as to equalize the range and average severity of cognitive impairment within the early and late onset subgroups. The k3 values were significantly reduced in the neocortex, hippocampus, and amygdala in the early onset AD patients, although the k3 values were significantly reduced only in the temporoparietal cortex and amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat AD patients showed further reduction of cortical k3 values in the second PET scans, with a mean interval of 2 years, suggesting a progressive loss of the ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD patients, there was a highly significant correlation between the cortical k3 values and Mini-Mental State Examination scores, supporting the cholinergic hypothesis in AD.