gebhart/patrepeval huggingface dataset:
The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent (2018)

In spite of impressive response rates in multiple cancer types, immune checkpoint inhibitors (ICIs) are active in only a minority of patients. Alternative strategies currently aim to combine immunotherapies with conventional agents such as cytotoxic chemotherapies. Here, we performed a study of PD-1 or PDL-1 blockade in combination with reference chemotherapies in four fully immunocompetent mouse models of cancer. We analyzed both the <i>in vivo</i> antitumor response, and the tumor immune infiltrate 4 days after the first treatment. <i>in vivo</i> tumor growth experiments revealed variable responsiveness to ICIs between models. We observed enhanced antitumor effects of the combination of immunotherapy with chemotherapy in the MC38 colon and MB49 bladder models, a lack of response in the 4T1 breast model, and an inhibition of ICIs activity in the MBT-2 bladder model. Flow cytometry analysis of tumor samples showed significant differences in all models between untreated and treated mice. At baseline, all the tumor models studied were predominantly infiltrated with cells harboring an immunosuppressive phenotype. Early alterations of the tumor immune infiltrate after treatment were found to be highly variable. We found that the balance between effector cells and immunosuppressive cells in the tumor microenvironment could be altered with some treatment combinations, but this effect was not always correlated with an impact on <i>in vivo</i> tumor growth. These results show that the combination of cytotoxic chemotherapy with ICIs may result in enhanced, similar or reduced antitumor activity, in a model- and regimen-dependent fashion. The present investigations should help to select appropriate combination regimens for ICIs.
Reflex neuromodulation of bladder function elicited by posterior tibial nerve stimulation in anesthetized rats (2014)

Although posterior tibial nerve stimulation (PTNS) has been shown in both clinical and animal studies to elicit bladder-inhibitory reflexes, our understanding of the role of posterior tibial nerve (PTN) afferents that elicit these responses is significantly limited. To this end, we investigated the effects of frequency-dependant PTNS in urethane-anesthetized rats undergoing repeated urodynamic fills. Nerve stimulation trials (10 min) resulted in statistically significant inhibition of the urinary bladder, both during and after nerve stimulation (P < 0.05). PTNS applied at 5 Hz resulted in both acute and prolonged changes that corresponded to 38.0% and 34.1% reductions in the bladder contraction frequency, respectively. In contrast, PTNS applied at 10 Hz could only elicit an acute decrease (22.9%) in bladder activity. Subsequent electrical activation of individual PTN branches (lateral or medial plantar nerves) confirmed that these bladder reflexes are mediated by specific subsets of the PTN trunk. Both acute and prolonged inhibition of the bladder were achieved by electrical stimulation of the lateral plantar (10 and 20 Hz) and medial plantar (5 and 10 Hz) nerves. Finally, we report a bladder-excitatory reflex that is elicited by electrical activation of either the PTN trunk or lateral plantar nerve at 50 Hz. This study shows that multiple bladder reflexes are tuned to specific subsets of nerve afferents and stimulation frequencies, each of which provide novel insights into the physiological effects of PTNS.
Sound compilation of reals (2014)

Writing accurate numerical software is hard because of many sources of unavoidable uncertainties, including finite numerical precision of implementations. We present a programming model where the user writes a program in a real-valued implementation and specification language that explicitly includes different types of uncertainties. We then present a compilation algorithm that generates a finite-precision implementation that is guaranteed to meet the desired precision with respect to real numbers. Our compilation performs a number of verification steps for different candidate precisions. It generates verification conditions that treat all sources of uncertainties in a unified way and encode reasoning about finite-precision roundoff errors into reasoning about real numbers. Such verification conditions can be used as a standardized format for verifying the precision and the correctness of numerical programs. Due to their non-linear nature, precise reasoning about these verification conditions remains difficult and cannot be handled using state-of-the art SMT solvers alone. We therefore propose a new procedure that combines exact SMT solving over reals with approximate and sound affine and interval arithmetic. We show that this approach overcomes scalability limitations of SMT solvers while providing improved precision over affine and interval arithmetic. Our implementation gives promising results on several numerical models, including dynamical systems, transcendental functions, and controller implementations.
Thermal-Electrochemical Modeling of Battery Systems (2000)

A general form of the thermal energy equation for a battery system is derived based on first principles using the volume‐averaging technique. A thermal‐electrochemical coupled modeling approach is presented to simultaneously predict battery electrochemical and thermal behaviors. This approach couples the thermal energy equation with the previous multiphase micro‐macroscopic electrochemical model via the heat generation and temperature‐dependent physicochemical properties. The thermal‐electrochemical model is multidimensional and capable of predicting the average cell temperature as well as the temperature distribution inside a cell. Numerical simulations are performed on a Ni‐MH battery to demonstrate the significance of thermal‐electrochemical coupling and to investigate the effects of thermal environment on battery electrochemical and thermal behaviors under various charging conditions. © 2000 The Electrochemical Society. All rights reserved.
Functional Domains of Transcription Factor hGABP( 1/E4TF1-53 Required for Nuclear Localization and Transcription Activation (1996)

Transcription factor E4TF1 is the human homolog of GABP and has been renamed hGABP (human GABP). hGABP is composed of two types of subunits; hGABP beta1/E4TF1-53 and the ets-related protein hGABP alpha/E4TF1-60. Both bind together to form an (alpha)2(beta1)2 heterotetrameric complex on DNA and activate transcription at specific promoters in vitro. Tetramer formation depends on two regions of hGABP beta1; the N-terminal region containing the Notch/ankyrin-type repeats is necessary for binding to hGABP alpha and the C-terminal region is necessary for homodimerization. In this report, we constructed various deletion mutants of hGABP beta1 in order to delimit the functional regions required for nuclear localization and transcription activity. We found that hGABP beta1 localization in the nucleus is dependent on a region located between amino acids 243 and 330 and that the presence of hGABP beta1 influences the efficiency of hGABP alpha transport into the nucleus. Next, we demonstrated that the hGABP complex composed of alpha and beta1 subunits activates transcription from the adenovirus early 4 promoter in vivo. This transcription activation needs the C-terminal region of hGABP beta1 and is consistent with results obtained with the in vitro assay. Furthermore, site-directed mutagenesis analysis of the C-terminal region reveals that the alpha-helix structure and the leucine residues are important for formation of a heterotetrameric complex with hGABP alpha in vitro and for transcription activation in vivo. These results suggest that hGABP beta1 stimulates transcription as part of a heterotetrameric complex with hGABP alpha in vivo.
Reviews of Books (1985)

Reviews of Books Get access The History of Parliament. The House of Commons 1558—1603. Edited by P. W. HASLER (3 vols. London: HMSO for History of Parliament Trust, 1981. £95 the set). PENRY WILLIAMS PENRY WILLIAMS New CollegeOxford Search for other works by this author on: Oxford Academic Google Scholar The English Historical Review, Volume C, Issue CCCXCV, April 1985, Pages 346–348, https://doi.org/10.1093/ehr/C.CCCXCV.346 Published: 01 April 1985
A Novel Inhibitor of Cyclin-Cdk Activity Detected in Transforming Growth Factor β-Arrested Epithelial Cells (1994)

Transforming growth factor beta (TGF-beta) is a potent inhibitor of epithelial cell growth. Cyclins E and A in association with Cdk2 have been shown to play a role in the G1-to-S phase transition in mammalian cells. We have studied the effects of TGF-beta-mediated growth arrest on G1/S cyclins E and A. Inhibition of cyclin A-associated kinase by TGF-beta is primarily due to a decrease in cyclin A mRNA and protein. By contrast, while TGF-beta inhibits accumulation of cyclin E mRNA, the reduction in cyclin E protein is minimal. Instead, we find that the activation of cyclin E-associated kinase that normally accompanies the G1-to-S phase transition is inhibited. A novel inhibitor of cyclin-Cdk complexes was detected in TGF-beta-treated cell lysates. Inhibition is mediated by a heat-stable protein that targets both Cdk2 and Cdc2 kinases. In G0-arrested cells, a similar inhibitor of Cdk2 kinase was detected. These data suggest the existence of an inhibitor of cyclin-dependent kinases induced under different conditions to mediate antiproliferative responses.
A microsatellite linkage map of the porcine genome. (1994)

We report the most extensive genetic linkage map for a livestock species produced to date. We have linked 376 microsatellite (MS) loci with seven restriction fragment length polymorphic loci in a backcross reference population. The 383 markers were placed into 24 linkage groups which span 1997 cM. Seven additional MS did not fall into a linkage group. Linkage groups are assigned to 13 autosomes and the X chromosome (haploid n = 19). This map provides the basis for genetic analysis of quantitative inheritance of phenotypic and physiologic traits in swine.
Genome editing using the endogenous type I CRISPR-Cas system in Lactobacillus crispatus (2019)

CRISPR-Cas systems are now widely used for genome editing and transcriptional regulation in diverse organisms. The compact and portable nature of class 2 single effector nucleases, such as Cas9 or Cas12, has facilitated directed genome modifications in plants, animals, and microbes. However, most CRISPR-Cas systems belong to the more prevalent class 1 category, which hinges on multiprotein effector complexes. In the present study, we detail how the native type I-E CRISPR-Cas system, with a 5'-AAA-3' protospacer adjacent motif (PAM) and a 61-nucleotide guide CRISPR RNA (crRNA) can be repurposed for efficient chromosomal targeting and genome editing in <i>Lactobacillus crispatus</i>, an important commensal and beneficial microbe in the vaginal and intestinal tracts. Specifically, we generated diverse mutations encompassing a 643-base pair (bp) deletion (100% efficiency), a stop codon insertion (36%), and a single nucleotide substitution (19%) in the exopolysaccharide priming-glycosyl transferase (<i>p-gtf</i>). Additional genetic targets included a 308-bp deletion (20%) in the prophage DNA packaging <i>Nu1</i> and a 730-bp insertion of the green fluorescent protein gene downstream of enolase (23%). This approach enables flexible alteration of the formerly genetically recalcitrant species <i>L. crispatus</i>, with potential for probiotic enhancement, biotherapeutic engineering, and mucosal vaccine delivery. These results also provide a framework for repurposing endogenous CRISPR-Cas systems for flexible genome targeting and editing, while expanding the toolbox to include one of the most abundant and diverse systems found in nature.
Photonic bandgap defect laser (2003)

We form a microcavity laser using two-dimensional photonic crystals embedded in a half wavelength thick waveguide. Modes localized to a single defect in the photonic crystal can be theoretically shown to have mode volumes as small 2(/spl lambda//2n)/sup 3/ and near unity spontaneous emission coupling factors. The flexibility in design of the photonic crystal enables one to tailor the device for vertical emission or for coupling into an in-plane waveguide. These type of devices may be useful for high density, low threshold optical sources in compact optical systems. The added versatility in being able to etch the laser cavity may also help develop low threshold laser sources in material systems in which high index contrast epitaxial mirrors do not exist. The defect laser cavities were formed in the InGaAsP material system in order to reduce the non-radiative surface recombination rate. The active region consists of four quantum wells (QW) designed for 1.55 /spl mu/m peak emission at room temperature.
Funding Kenyan health centres: experiences of implementing direct facility financing and local budget management (2014)

Fresh ice stalactites were observed beneath sea ice in Antarctica. They are hollow, tapering, inverted cones having a base diameter between 10 and 20 centimeters and a tip diameter of 4 to 10 centimeters extending downward about 100 centimeters. The stalactites form when dense, chilled brine drains downward from the ice sheet into seawater of norma1 salinity and near-freezing temperature.
Gene-for-gene interactions of five cloned avirulence genes from Xanthomonas campestris pv. malvacearum with specific resistance genes in cotton (1986)

A total DNA clone bank of a strain of Xanthomonas campestris pv. malvacearum (Xcm) was constructed in the cosmid vector pSa747 and transfected into Escherichia coli. The Xcm strain carries at least nine identifiable avirulence (A) genes. Clones in E. coli were mated individually into a recombination-proficient Xcm isolate carrying no known A genes. Screening was for incompatibility on congenic cotton host lines that differ by single specific resistance (R) genes. Ten different cosmid clones conferring race-specific avirulence were recovered. In most cases, the same A gene clone was recovered independently several times. Using the congenic host lines and the merodiploid transconjugant pathogen strains, five of the A genes were shown to specifically interact, gene-for-gene, with individual R genes in the congenic cotton lines. Some A/R gene interactions appeared qualitatively different from others, suggesting that the physiological mechanism(s) of gene-for-gene specified incompatibility may be unique to the interactive gene pair. All A genes appeared to be chromosomally determined, three were found linked on a single 32-kilobase clone, and the rest were spaced more than 31 kilobases apart. Colinearity of the cosmid inserts with the Xcm recipient (carrying no known A genes) chromosome was demonstrated in two of the three tested. This and other evidence suggests that at least some A genes in bacteria may have the equivalent of virulence (a) alleles. The genetics of race specificity in this phytopathogenic bacterium appeared in all respects to be identical to that found in phytopathogenic fungi.
Flexible and Stretchable Energy Storage: Recent Advances and Future Perspectives (2016)

Energy-storage technologies such as lithium-ion batteries and supercapacitors have become fundamental building blocks in modern society. Recently, the emerging direction toward the ever-growing market of flexible and wearable electronics has nourished progress in building multifunctional energy-storage systems that can be bent, folded, crumpled, and stretched while maintaining their electrochemical functions under deformation. Here, recent progress and well-developed strategies in research designed to accomplish flexible and stretchable lithium-ion batteries and supercapacitors are reviewed. The challenges of developing novel materials and configurations with tailored features, and in designing simple and large-scaled manufacturing methods that can be widely utilized are considered. Furthermore, the perspectives and opportunities for this emerging field of materials science and engineering are also discussed.
Tissue Engineering of Ligaments (2004)

Tissue engineering is emerging as a significant clinical option to address tissue and organ failure by implanting biological substitutes for the compromised tissues. As compared to the transplantation of cells alone, engineered tissues offer the potential advantage of immediate functionality. Engineered tissues can also serve as physiologically relevant models for controlled studies of cells and tissues designed to distinguish the effects of specific signals from the complex milieu of factors present in vivo. A high number of ligament failures and the lack of adequate options to fully restore joint functions have prompted the need to develop new tissue engineering strategies. We discuss the requirements for ligament reconstruction, the available treatment options and their limitations, and then focus on the tissue engineering of ligaments. One representative tissue engineering system involving the integrated use of adult human stem cells, custom-designed scaffolds, and advanced bioreactors with dynamic loading is described.
Durable Gold-Coated Fused Silica Capillaries for Use in Electrospray Mass Spectrometry (1995)

A simple procedure for preparing gold-coated silica capillaries for use in electrospray ionization mass spectrometry is described. The tip of the capillary is mechanically tapered to a fine point, and a thin film of gold is vapor deposited on the outer surface following treatment with an organofunctional silane. The performance characteristics of these durable capillaries as continuous infusion sources are examined, and their utility in on-line capillary electrophoresis mass spectrometry is demonstrated.
Immunohistochemical study on the aggregation of ubiquitin in the central nervous system of the transgenic mice expressing a human Cu/Zn SOD mutation (2003)

In the present study, we performed immunohistochemical techniques to investigate the changes in ubiquitin expression in the central nervous system of the transgenic mice expressing a human superoxide dismutase 1 mutation (SOD1)G93A. Sections of brains from control mice showed virtually no immunostaining for ubiquitin, whereas sections from SOD1G93A transgenic mice contained numerous granular or linear deposits of ubiquitin. A high density of the processes containing ubiquitin was detected all around the gray matter of the spinal cord of the mutant transgenic mice. Ubiquitin immunoreactivity was also detected in the cerebellum, brainstem and midbrain of transgenic mice. The first demonstration of the distribution of ubiquitin in the whole brains of the transgenic mice may provide clues for understanding the neuronal degeneration mechanism in amyotrophic lateral sclerosis and other neurodegenerative diseases.
Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurones in vivo by glutamate receptors. (1995)

1. Vasopressin-secreting neurones in the rat hypothalamic supraoptic nucleus display patterned spontaneous phasic activity, which is apparently maintained in vivo through yet unidentified neurotransmitter system(s). The present investigation used extracellular recording techniques in anaesthetized Long-Evans rats to evaluate whether the neurotransmitter mechanism underlying phasic firing is provided via a family of ionotropic glutamate receptors. 2. N-Methyl-D-aspartate (NMDA) reliably evoked bursts of activity in twenty-seven of twenty-eight phasic neurones. Amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainate also elicited pronounced excitations in twenty-one of twenty-one and and fourteen of fifteen phasic cells, respectively. 3. A rapid blockade of on-going phasic activity was consistently induced following brief applications of both NMDA and non-NMDA receptor antagonists; extended application of antagonists resulted in prolonged silent periods, during which phasic activity failed to recur for minutes. Neither saline nor a cholecystokinin receptor antagonist influenced cell firing. 4. In contrast to putative vasopressin cells, application of NMDA receptor ligands did not affect the spontaneous activity in most putative oxytocin-secreting neurones, whereas kainate and AMPA potently excited seven of nine and four of five putative oxytocin cells, respectively. 5. These results imply that the maintenance of spontaneous phasic discharges in vivo in supraoptic vasopressin-secreting neurones requires tonic synaptic activation involving both NMDA and non-NMDA glutamate receptors. In putative oxytocin-secreting neurones, spontaneous firing appears to be predominantly regulated by non-NMDA receptors. Glutamatergic innervations may be in a unique position to influence the genesis of patterned electrical activity in supraoptic vasopressin neurones.
Ovarian cancer screening with annual transvaginal sonography (2007)

TVS screening, when it was performed annually, was associated with a decrease in disease stage at detection and with case-specific ovarian cancer mortality, but it was not effective in detecting ovarian cancers in women who had normal ovarian volume.
The Impact of Atherosclerotic Arterial Remodeling on Percentage of Luminal Stenosis Varies Widely Within the Arterial System (1997)

Luminal stenosis can be based on large atherosclerotic plaques in compensatory enlarged segments or on relatively little plaques in shrunken segments. In the present study, the contribution of plaque formation and remodeling to luminal narrowing was compared among six types of arteries prone to symptomatic atherosclerosis. Cross-sections (n = 5195) were obtained at regular intervals from 329 arteries. For each artery, the cross-section that contained the least amount of plaque was considered to be the reference. For each cross-section, the percentage of lumen area decrease was expressed as a percentage of the lumen area at the reference site (luminal stenosis). Similarly, the area encompassed by the internal elastic lamina (IEL area) was expressed as a percentage of the IEL area at the reference site (relative IEL area). All cross-sections were categorized in three groups: relative IEL area > 105% (enlargement), 95% to 105% (no remodeling), and < 95% (shrinkage). The prevalence of enlargement (50% to 75%) was significantly higher compared with shrinkage (8% to 25%). Shrinkage was observed most frequently in the femoral arteries (25%) and infrequently in the renal arteries (8%). For all types of arteries, the relative IEL area correlated negatively with luminal stenosis (P < .001). Regression analysis of relative IEL area on luminal stenosis, however, showed significant differences in the first-order regression coefficients among artery types. On average, plaque increase was more compensated for by enlargement in the coronary, common carotid, and renal arteries compared with the arteries obtained from the lower extremities. Anatomic regional differences were observed in the impact of arterial wall remodeling on percent luminal stenosis in de novo atherosclerotic lesions.