gebhart/patrepeval huggingface dataset:
Urologists' referral attitude for sacral neuromodulation for treating refractory idiopathic overactive bladder syndrome: Discrete choice experiment (2013)

Besides absolute contraindications, other non-critical parameters such as cardiac pacemaker or diabetes mellitus influence urologists' decision to refrain from referral for SNM. We believe that the use of decision tools will help urologists identifying patients benefiting from SNM and therefore we call for broad dissemination of such tools into clinical practice.
The Mammary Progenitor Marker CD61/β3 Integrin Identifies Cancer Stem Cells in Mouse Models of Mammary Tumorigenesis (2008)

The cells of origin and mechanisms that underpin tumor heterogeneity in breast cancer are poorly understood. Here, we have examined three mouse models of mammary tumorigenesis (MMTV-wnt-1, MMTV-neu, and p53(+/-)) for changes in their epithelial cell hierarchy during the preneoplastic and neoplastic stages of tumor progression. In preneoplastic tissue, only MMTV-wnt-1 mice showed a perturbation in their epithelial subpopulations. In addition to an expanded mammary stem cell pool, repopulating cells capable of yielding extensive mammary outgrowths in vivo were revealed in the committed luminal progenitor population. These findings indicate that wnt-1 activation induces the appearance of aberrant progenitor cells, and suggest that both mammary stem and progenitor cells can serve as the cellular targets of wnt-1-induced tumorigenesis. In tumors arising in MMTV-wnt-1 tumors, the luminal epithelial progenitor marker CD61/beta3 integrin identified a cancer stem cell (CSC) population that was highly enriched for tumorigenic capability relative to the CD61(-) subset. CD61 expression also defined a CSC subset in 50% of p53(+/-)-derived tumors. No CSCs, however, could be identified in the more homogeneous MMTV-neu/erbB2 model, suggesting an alternative model of tumorigenesis. Overall, our findings show the utility of the progenitor marker CD61 in the identification of CSCs that sustain specific mammary tumors.
[6]‐Gingerol induces bone loss in ovary intact adult mice and augments osteoclast function via the transient receptor potential vanilloid 1 channel (2012)

Daily feeding of 6-gingerol to skeletally mature female mice caused trabecular osteopenia, and the mechanism appeared to be activation of osteoclast formation via the TRPV1 channel.
Measurement and modeling of human T cell kinetics (2003)

The ability to measure, describe and interpret T cell kinetics is pivotal in understanding normal lymphocyte homeostasis and diseases that affect T cell numbers. Following in vivo labeling of dividing cells with 6,6-D(2)-glucose in eight healthy volunteers, peripheral blood T cells were sorted by CD4, CD8 and CD45 phenotype. Enrichment of deuterium in DNA was measured by gas chromatography-mass spectrometry. A novel model of T cell kinetics, allowing for heterogeneity within T cell pools, was used to analyze data on acquisition and loss of label and calculate proliferation and disappearance rates for each subpopulation. Proliferation rates for CD45RO(+)CD8(+) cells and CD45RO(+)CD4(+) cells were 5.1% and 2.7% /day, respectively (equivalent doubling times: 14 and 26 days). CD45RA(+)CD8(+) lymphocytes and CD45RA(+)CD4(+) lymphocytes had slower proliferation rates, 0.5% and 0.6% / day, respectively (doubling time about 4 months). Disappearance rates of labeled cells were similar for all cell types (7%-12% / day) and exceeded corresponding proliferation rates. This disparity may be understood conceptually in terms of either phenotypic heterogeneity (rapid versus slow turnover pools), or history (recently divided cells are more likely to die). The new kinetic model fits the data closely and avoids the need to postulate a large external source of lymphocytes to maintain equilibrium.
1-Alkyl-4-acylpiperazines as a New Class of Imidazole-Free Histamine H3 Receptor Antagonists (2004)

With the aim of identifying structurally novel, centrally acting histamine H(3) antagonists, arrays of monoacyldiamines were screened. This led to the discovery of a series of 1-alkyl-4-acylpiperazines which were potent antagonists at the human histamine H(3) receptor. The most potent amides had antagonist potencies in the subnanomolar range.
Brute Force Vulnerability Testing Technology Based on Data Mutation (2011)

Protocol plays a profound role among networked computers in security issues. With the development of computer network engineering, protocol has become increasingly intricate in both data format and interaction behavior, which means that more potential defects exist in protocol software implementations. These factors make protocol vulnerable to malicious attacks and raise the security requirements to an ever high level. After over ten-year progress, however, the vulnerability testing methods have not been unified to an agreement. Especially, the problems in automated test cases generation remain to be solved. This paper proposes a novel brute force vulnerability testing technique, generating test data by mutating captured protocol messages. And to formalize the perturbing process, regular expression is introduced into the approach for constructing test case templates. In addition, a multi-protocol test tool called PVD is developed to implement the test system architecture. Finally, the authors carry on a complete vulnerability testing campaign on Asterisk 1.4 SIP (Session Initiation Protocol) server, as the result, finding a number of protocol defects and achieving fairly efficient test results.
A phase I/II trial of intratumoral endoscopic ultrasound injection of ONYX-015 with intravenous gemcitabine in unresectable pancreatic carcinoma. (2003)

This study indicates that ONYX-015 injection via EUS into pancreatic carcinomas by the transgastic route with prophylactic antibiotics is feasible and generally well tolerated either alone or in combination with gemcitabine. Transgastric EUS-guided injection is a new and practical method of delivering biological agents to pancreatic tumors.
Graphite Fiber Brush Anodes for Increased Power Production in Air-Cathode Microbial Fuel Cells (2007)

To efficiently generate electricity using bacteria in microbial fuel cells (MFCs), highly conductive noncorrosive materials are needed that have a high specific surface area (surface area per volume) and an open structure to avoid biofouling. Graphite brush anodes, consisting of graphite fibers wound around a conductive, but noncorrosive metal core, were examined for power production in cube (C-MFC) and bottle (B-MFC) air-cathode MFCs. Power production in C-MFCs containing brush electrodes at 9600 m2/m3 reactor volume reached a maximum power density of 2400 mW/m2 (normalized to the cathode projected surface area), or 73 W/m3 based on liquid volume, with a maximum Coulombic efficiency (CE) of 60%. This power density, normalized by cathode projected area, is the highest value yet achieved by an air-cathode system. The increased power resulted from a reduction in internal resistance from 31 to 8 Q. Brush electrodes (4200 m2/m3) were also tested in B-MFCs, consisting of a laboratory media bottle modified to have a single side arm with a cathode clamped to its end. B-MFCs inoculated with wastewater produced up to 1430 mW/m2 (2.3 W/m3, CE = 23%) with brush electrodes, versus 600 mW/m2 with a plain carbon paper electrode. These findings show that brush anodes that have high surface areas and a porous structure can produce high power densities, and therefore have qualities that make them ideal for scaling up MFC systems.
IL-12 Gene as a DNA Vaccine Adjuvant in a Herpes Mouse Model: IL-12 Enhances Th1-Type CD4+ T Cell-Mediated Protective Immunity Against Herpes Simplex Virus-2 Challenge (1999)

IL-12 has been shown to enhance cellular immunity in vitro and in vivo. Recent reports have suggested that combining DNA vaccine approach with immune stimulatory molecules delivered as genes may significantly enhance Ag-specific immune responses in vivo. In particular, IL-12 molecules could constitute an important addition to a herpes vaccine by amplifying specific immune responses. Here we investigate the utility of IL-12 cDNA as an adjuvant for a herpes simplex virus-2 (HSV-2) DNA vaccine in a mouse challenge model. Direct i.m. injection of IL-12 cDNA induced activation of resting immune cells in vivo. Furthermore, coinjection with IL-12 cDNA and gD DNA vaccine inhibited both systemic gD-specific Ab and local Ab levels compared with gD plasmid vaccination alone. In contrast, Th cell proliferative responses and secretion of cytokines (IL-2 and IFN-gamma) and chemokines (RANTES and macrophage inflammatory protein-1alpha) were significantly increased by IL-12 coinjection. However, the production of cytokines (IL-4 and IL-10) and chemokine (MCP-1) was inhibited by IL-12 coinjection. IL-12 coinjection with a gD DNA vaccine showed significantly better protection from lethal HSV-2 challenge compared with gD DNA vaccination alone in both inbred and outbred mice. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vivo CD4+ T cell deletion. Thus, IL-12 cDNA as a DNA vaccine adjuvant drives Ag-specific Th1 type CD4+ T cell responses that result in reduced HSV-2-derived morbidity as well as mortality.
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists (2009)

GOrilla is an efficient GO analysis tool with unique features that make a useful addition to the existing repertoire of GO enrichment tools. GOrilla's unique features and advantages over other threshold free enrichment tools include rigorous statistics, fast running time and an effective graphical representation. GOrilla is publicly available at: http://cbl-gorilla.cs.technion.ac.il
Hemispheric Processing and Methylphenidate Effects in Attention-Deficit Hyperactivity Disorder (1994)

To advance our understanding of attention-deficit hyperactivity disorder and medication effects we draw upon the evidence for (1) a neurotransmitter imbalance between norepinephrine and dopamine in attention-deficit hyperactivity disorder and (2) an asymmetric neural control system that links the dopaminergic pathways to left hemispheric processing and links the noradrenergic pathways to right hemispheric processing. It appears that attention-deficit hyperactivity disorder may involve a bihemispheric dysfunction characterized by reduced dopaminergic and excessive noradrenergic functioning. In turn, favorable medication effects may be mediated by a restoration in neurotransmitter balance and by increased control over the allocation of attentional resources between hemispheres.
Formation of Branched ZnO Nanowires from Solvothermal Method and Dye-Sensitized Solar Cells Applications (2008)

Branched ZnO nanowires have been fabricated on conductive glass substrates via a solvothermal method for dye-sensitized solar cells (DSCs). The 1D branched nanostructures can afford a direct conduction pathway instead of interparticle hops while using nanoparticles. Furthermore, the short-circuit current density and the energy conversion efficiency of the branched ZnO nanowire DSCs are 4.27 mA/cm2 and 1.51%, which are twice as high as the bare ZnO nanowire ones. The improvement was a consequence of the enlargement of the internal surface area within the photoelectrode and allowed us to achieve higher dye adsorption to significantly enhance the performance of the DSCs.
Recombinant rat stem cell factor synergizes with recombinant human granulocyte colony-stimulating factor in vivo in mice to mobilize peripheral blood progenitor cells that have enhanced repopulating potential (1993)

Splenectomized mice treated for 7 days with pegylated recombinant rat stem cell factor (rrSCF-PEG) showed a dose-dependent increase in peripheral blood progenitor cells (PBPC) that have enhanced in vivo repopulating potential. A dose of rrSCF-PEG at 25 micrograms/kg/d for 7 days produced no significant increase in PBPC. However, when this dose of rrSCF-PEG was combined with an optimal dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 200 micrograms/kg/d), a synergistic increase in PBPC was observed. Compared with treatment with rhG-CSF alone, the combination of rrSCF-PEG plus rhG-CSF resulted in a synergistic increase in peripheral white blood cells, in the incidence and absolute numbers of PBPC, and in the incidence and absolute numbers of circulating cells with in vivo repopulating potential. These data suggest that low doses of SCF, which would have minimal, if any, effects in vivo, can synergize with optimal doses of rhG-CSF to enhance the mobilization of PBPC stimulated by rhG-CSF alone.
Next‐generation‐sequencing‐based risk stratification and identification of new genes involved in structural and sequence variations in near haploid lymphoblastic leukemia (2013)

Near haploidy (23-29 chromosomes) is a numerical cytogenetic aberration in childhood acute lymphoblastic leukemia (ALL) associated with particularly poor outcome. In contrast, high hyperdiploidy (51-67 chromosomes) has a favorable prognosis. Correct classification and appropriate risk stratification of near haploidy is frequently hampered by the presence of apparently high hyperdiploid clones that arise by endoreduplication of the original near haploid clone. We evaluated next-generation-sequencing (NGS) to distinguish between "high hyperdiploid" leukemic clones of near haploid and true high hyperdiploid origin. Five high hyperdiploid ALL cases and the "high hyperdiploid" cell line MHH-CALL-2, derived from a near haploid clone, were tested for uniparental isodisomy. NGS showed that all disomic chromosomes of MHH-CALL-2, but none of the patients, were of uniparental origin, thus reliably discriminating these subtypes. Whole-exome- and whole-genome-sequencing of MHH-CALL-2 revealed homozygous non-synonymous coding mutations predicted to be deleterious for the protein function of 63 genes, among them known cancer-associated genes, such as FANCA, NF1, TCF7L2, CARD11, EP400, histone demethylases, and transferases (KDM6B, KDM1A, PRDM11). Only eight of these were also, but heterozygously, mutated in the high hyperdiploid patients. Structural variations in MHH-CALL-2 include a homozygous deletion (MTAP/CDKN2A/CDKN2B/ANRIL), a homozygous inversion (NCKAP5), and an unbalanced translocation (FAM189A1). Together, the sequence variations provide MHH-CALL-2 with capabilities typically acquired during cancer development, e.g., loss of cell cycle control, enhanced proliferation, lack of DNA repair, cell death evasion, and disturbance of epigenetic gene regulation. Poorer prognosis of near haploid ALL most likely results from full penetrance of a large array of detrimental homozygous mutations.
Could low grade bacterial infection contribute to low back pain? A systematic review (2015)

We found that bacteria were common in the spinal disc material of people undergoing spinal surgery. There was moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change associated with disc herniation and modest evidence for causation. However, further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain.
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) Dyes Modified for Extended Conjugation and Restricted Bond Rotations (2000)

Five new, constrained, aryl-substituted 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) dyes (3f,g and 4h-j) were prepared and investigated to see if they have more favorable fluorescence characteristics than the unconstrained systems 2 that were prepared in previous studies. Dye types 3 and 4 have relatively rigid conformations caused by the heteroatom (3f and 3g) or ethylene bridge (4h-j) linkers that preclude free rotation of the substituted-benzene molecular fragments. In the event, the new dye types 3 and 4 have longer lambda(max abs) (620-660 nm) and lambda(max)(fluor) (630-680 nm) values than compounds 2. They also exhibit higher extinction coefficients (>100 000 M(-1) cm(-1), except for 3g). Their fluorescent quantum yields are high (up to 0.72 for 4j), with the exception of compound 3g, which has a quantum yield of only 0.05. The redox properties of dyes 3 and 4 have also been examined.
Cre- lox -Based System for Multiple Gene Deletions and Selectable-Marker Removal in Lactobacillus plantarum (2006)

The classic strategy to achieve gene deletion variants is based on double-crossover integration of nonreplicating vectors into the genome. In addition, recombination systems such as Cre-lox have been used extensively, mainly for eukaryotic organisms. This study presents the construction of a Cre-lox-based system for multiple gene deletions in Lactobacillus plantarum that could be adapted for use on gram-positive bacteria. First, an effective mutagenesis vector (pNZ5319) was constructed that allows direct cloning of blunt-end PCR products representing homologous recombination target regions. Using this mutagenesis vector, double-crossover gene replacement mutants could be readily selected based on their antibiotic resistance phenotype. In the resulting mutants, the target gene is replaced by a lox66-P(32)-cat-lox71 cassette, where lox66 and lox71 are mutant variants of loxP and P(32)-cat is a chloramphenicol resistance cassette. The lox sites serve as recognition sites for the Cre enzyme, a protein that belongs to the integrase family of site-specific recombinases. Thus, transient Cre recombinase expression in double-crossover mutants leads to recombination of the lox66-P(32)-cat-lox71 cassette into a double-mutant loxP site, called lox72, which displays strongly reduced recognition by Cre. The effectiveness of the Cre-lox-based strategy for multiple gene deletions was demonstrated by construction of both single and double gene deletions at the melA and bsh1 loci on the chromosome of the gram-positive model organism Lactobacillus plantarum WCFS1. Furthermore, the efficiency of the Cre-lox-based system in multiple gene replacements was determined by successive mutagenesis of the genetically closely linked loci melA and lacS2 in L. plantarum WCFS1. The fact that 99.4% of the clones that were analyzed had undergone correct Cre-lox resolution emphasizes the suitability of the system described here for multiple gene replacement and deletion strategies in a single genetic background.
Intracerebroventricular Infusion of Nerve Growth Factor in Three Patients with Alzheimer’s Disease (1998)

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer's disease. We have treated 3 patients with Alzheimer's disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
Glutathione metabolism as a determinant of therapeutic efficacy: a review. (1984)

Glutathione, as the chief nonprotein intracellular sulfhydryl, affects the efficacy and interactions of a variety of antineoplastic interventions, mainly through nucleophilic thioether formation or oxidation-reduction reactions. Thus, glutathione plays a role in the detoxification and repair of cellular injury by such diverse agents as mechlorethamine, melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, daunorubicin, and mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone). Glutathione may play a similar role in host and tumor cell responses to radiation, hyperthermia, and the reactive reduction products of oxygen secreted by inflammatory cells. Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate. It seems likely that alterations in glutathione metabolism of tumor or host as a result of one therapeutic intervention may affect the outcome of concurrent treatments. Knowledge of these interactions may be useful in designing combination therapy for neoplastic disease.
Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation (2013)

Insulin and cortisol play a key role in the regulation of energy homeostasis, appetite, and satiety. Little is known about the action and interaction of both hormones in brain structures controlling food intake and the processing of neurovisceral signals from the gastrointestinal tract. In this study, we assessed the impact of single and combined application of insulin and cortisol on resting regional cerebral blood flow (rCBF) in the insular cortex. After standardized periods of food restriction, 48 male volunteers were randomly assigned to receive either 40 IU intranasal insulin, 30 mg oral cortisol, both, or neither (placebo). Continuous arterial spin labeling (CASL) sequences were acquired before and after pharmacological treatment. We observed a bilateral, locally distinct rCBF increase after insulin administration in the insular cortex and the putamen. Insulin effects on rCBF were present regardless of whether participants had received cortisol or not. Our results indicate that insulin, but not cortisol, affects blood flow in human brain structures involved in the regulation of eating behavior.