gebhart/patrepeval huggingface dataset:
PTPROt: An Alternatively Spliced and Developmentally Regulated B-Lymphoid Phosphatase That Promotes G0/G1 Arrest (1999)

Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways. By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen). This PTP, termed PTPROt (truncated), is a tissue-specific alternatively-spliced form of a human epithelial PTP, PTPRO (PTPU2/GLEPP1). Whereas the epithelial PTPRO includes an approximately 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain. PTPROt cDNAs encode functional approximately 47-kD and approximately 43-kD PTPs, which are most abundant in normal naive quiescent B cells and decreased or absent in germinal center B cells and germinal center-derived diffuse large B-cell lymphomas. Because PTPROt was predominantly expressed in naive quiescent B cells, the enzyme's effects on cell-cycle progression were examined. When multiple stable PTPROt sense, antisense, and vector only B-cell transfectants were grown in reduced serum and synchronized with nocodazole, PTPROt sense clones exhibited markedly increased G0/G1 arrest. Taken together, these data implicate PTPROt in the growth control of specific B-cell subpopulations.
Effect of Cr3+ and SO42- on the Structure of Rust Layer Formed on Steels by Atmospheric Corrosion (2002)

The effect of chromium ion (Cr3+) and sulfate ion (SO42-) on the structure of the rust layer formed by thin electrolyte-film corrosion of low-alloy steels has been examined. By using X-ray diffraction spectroscopy, it was found that coexistence of Cr3+ and SO42- in the electrolyte film covering the steel surface quickly forms the Cr-goethite (α-(Fe 1-X, CrX)OOH) layer which has been known as the final protective rust layer. Scanning vibrating electrode measurements showed that the rust layer formed under the electrolyte film containing Cr3+ and SO42- possesses higher protective ability against the aggressive chloride environment. Mössbauer spectroscopy revealed that most of the Cr-goethite formed by corrosion of the Fe-5at%Cr alloy under thin electrolyte-film containing SO42- was the superparamagnetic ultra-fine Cr-goethite. It can be said that the Cr-goethites possess the high protective ability against aggressive corrosives.
A lentiviral microRNA-based system for single-copy polymerase II-regulated RNA interference in mammalian cells (2005)

The advent of RNA interference has led to the ability to interfere with gene expression and greatly expanded our ability to perform genetic screens in mammalian cells. The expression of short hairpin RNA (shRNA) from polymerase III promoters can be encoded in transgenes and used to produce small interfering RNAs that down-regulate specific genes. In this study, we show that polymerase II-transcribed shRNAs display very efficient knockdown of gene expression when the shRNA is embedded in a microRNA context. Importantly, our shRNA expression system [called PRIME (potent RNA interference using microRNA expression) vectors] allows for the multicistronic cotranscription of a reporter gene, thereby facilitating the tracking of shRNA production in individual cells. Based on this system, we developed a series of lentiviral vectors that display tetracycline-responsive knockdown of gene expression at single copy. The high penetrance of these vectors will facilitate genomewide loss-of-function screens and is an important step toward using bar-coding strategies to follow loss of specific sequences in complex populations.
Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma (2009)

Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population. (Current Controlled Trials number, ISRCTN75169762.)
Tumor-Targeting Properties of Novel Antibodies Specific to the Large Isoform of Tenascin-C (2006)

These data suggest that the F16 antibody, specific to domain A1 of tenascin-C, is a promising building block for the development of antibody-based pharmaceuticals in view of its excellent tumor-targeting performance and the strong expression of the antigen in a variety of primary and metastatic tumors.
Pharmaceutical Point of View on Parenteral Nutrition (2013)

Parenteral nutrition--a form of administering nutrients, electrolytes, trace elements, vitamins, and water--is a widely used mode of therapy applied in many diseases, in patients of different ages both at home and in hospital. The success of nutritional therapy depends chiefly on proper determination of the patient's energetic and electrolytic needs as well as preparation and administration of a safe nutritional mixture. As a parenterally administered drug, it is expected to be microbiologically and physicochemically stable, with all of the components compatible with each other. It is very difficult to obtain a stable nutritional mixture due to the fact that it is a complex, two-phase drug. Also, the risk of incompatibility between mixture components and packaging should be taken into consideration and possibly eliminated. Since parenteral nutrition is a part of therapy, simultaneous use of drugs may cause pharmacokinetic and pharmacodynamic interactions as well as those with the pharmaceutical phase. The aim of this paper is to discuss such aspects of parenteral nutrition as mixture stability, methodology, and methods for determining the stability of nutritional mixtures and drugs added to them.
Trp89 in the lid ofHumicola lanuginosa lipase is important for efficient hydrolysis of tributyrin (1994)

To determine whether Trp89 located in the lid of the lipase (EC 3.1.1.3) from Humicola lanuginosa is important for the catalytic property of the enzyme, site-directed mutagenesis at Trp89 was carried out. The kinetic properties of wild type and mutated enzymes were studied with tributyrin as substrate. Lipase variants in which Trp89 was changed to Phe, Leu, Gly or Glu all showed less than 14% of the activity compared to that of the wild type lipase. The Trp89Glu mutant was the least active with only 1% of the activity seen with the wild type enzyme. All Trp mutants had the same binding affinity to the tributyrin substrate interface as did the wild type enzyme. Wild type lipase showed saturation kinetics against tributyrin when activities were measured with mixed emulsions containing different proportions of tributyrin and the nonionic alkyl polyoxyethylene ether surfactant, Triton DF-16. Wild type enzyme showed a Vmax = 6000 +/- 300 mmol.min-1.g-1 and an apparent Km = 16 +/- 2% (vol/vol) for tributyrin in Triton DF-16, while the mutants did not show saturation kinetics in an identical assay. The apparent Km for tributyrin in Triton DF-16 was increased as the result of replacing Trp89 with other residues (Phe, Leu, Gly or Glu). The activities of all mutants were more sensitive to the presence of Triton DF-16 in the tributyrin substrate than was wild type lipase. The activity of the Trp89Glu mutant was decreased to 50% in the presence of 2 vol% Triton DF-16 compared to the activity seen with pure tributyrin as substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
CHC+RT: Coherent Hierarchical Culling for Ray Tracing (2015)

Abstract We propose a new technique for in‐core and out‐of‐core GPU ray tracing using a generalization of hierarchical occlusion culling in the style of the CHC++ method. Our method exploits the rasterization pipeline and hardware occlusion queries in order to create coherent batches of work for localized shader‐based ray tracing kernels. By combining hierarchies in both ray space and object space, the method is able to share intermediate traversal results among multiple rays. We exploit temporal coherence among similar ray sets between frames and also within the given frame. A suitable management of the current visibility state makes it possible to benefit from occlusion culling for less coherent ray types like diffuse reflections. Since large scenes are still a challenge for modern GPU ray tracers, our method is most useful for scenes with medium to high complexity, especially since our method inherently supports ray tracing highly complex scenes that do not fit in GPU memory. For in‐core scenes our method is comparable to CUDA ray tracing and performs up to 5.94 × better than pure shader‐based ray tracing.
Treatment of Chronic Insomnia by Restriction of Time in Bed (1987)

A treatment of chronic insomnia is described that is based on the recognition that excessive time spent in bed is one of the important factors that perpetuates insomnia. Thirty-five patients, with a mean age of 46 years and a mean history of insomnia of 15.4 years, were treated initially by marked restriction of time available for sleep, followed by an extension of time in bed contingent upon improved sleep efficiency. At the end of the 8-week treatment program, patients reported an increase in total sleep time (p less than 0.05) as well as improvement in sleep latency, total wake time, sleep efficiency, and subjective assessment of their insomnia (all p less than 0.0001). Improvement remained significant for all sleep parameters at a mean of 36 weeks after treatment in 23 subjects participating in a follow-up assessment. Although compliance with the restricted schedule is difficult for some patients, sleep restriction therapy is an effective treatment for common forms of chronic insomnia.
The role of the pineal in the control of the daily patterns of neurohypophysial hormone secretion (1993)

Plasma concentrations of neurohypophysial hormones show clear rhythms over 24 hr which can be suppressed by exposure to constant light, an observation consistent with pineal involvement. A study has therefore been performed on the changes in the hormone levels in the hypothalamus, posterior pituitary, and plasma over 24 hr in control, pinealectomised, and sham pinealectomised animals to determine if the pineal could play a role. Water intake, urine excretion, packed cell volume, plasma osmolality, and electrolytes were also monitored. Pinealectomy had little effect on fluid balance, but after 8 weeks for oxytocin and 2 weeks for vasopressin the morning values (0700-0800) for the circulating concentrations of the hormones were significantly higher in the pinealectomized group compared with the combined sham operated and unoperated groups (pineal intact). By contrast, the pituitary vasopressin was significantly lower in the pinealectomised group. The increase in plasma oxytocin and vasopressin seen over the hours of daylight and accompanying fall in plasma osmolality seen in the pineal intact group were absent in the pinealectomised group. Similarly, the evening fall in pituitary hormone concentrations and increase in hypothalamic hormone content were absent in the pinealectomised animals. After 10 days of exposure to constant light, the fall in plasma osmolality in the pineal-intact animals over the day was no longer significant; instead a significant increase in plasma osmolality and sodium was seen in the pinealectomised group. Exposure to constant light, while altering the patterns of neurohypophysial activity in the pineal intact group, had little effect on the pinealectomised animals.
Recommendations for revised response criteria for malignant lymphoma (2006)

7507 Background: Standardized response criteria are needed to interpret and compare clinical trials, and for approval of new therapeutic agents by regulatory agencies. Methods: The International Working Group (IWG) criteria (Cheson et al, JCO 17:1244, 1999) were widely adopted but were reevaluated because of limitations identified, and recent advances, notably FDG-PET, immunohistochemistry (IHC) and flow cytometry. Results: We propose the following modifications for non-Hodgkin’s lymphoma (NHL) and Hodgkin lymphoma (HL). For predictably PET avid histologies (PA)(e.g., diffuse large B-cell NHL (DLBCL), HL, follicular (FL) and mantle cell lymphoma (MCL), PET pretreatment is strongly encouraged to define sites of disease, but not required. For histologies not predictably PET+ (NPA), PET should only be done if response is an endpoint. Although PET performed after ≥1 cycles of chemotherapy correlates with treatment efficacy, in the absence of data that altering therapy because of PET results improves outcome, mid-treatment PET should only be done in a clinical trial. PET is essential to assess response in DLBCL and HL, but only in FL and MCL if response is the endpoint. For NPA histologic subtypes, PET should only be used if PET+ prior to therapy and response is a major endpoint. Present data are inadequate to recommend PET for routine post-treatment surveillance. The new definition for CR includes: 1) no signs or symptoms of disease; 2) PET- in a PA lymphoma, or negative CT in NPA lymphoma. 3) Normal bone marrow by morphology, or if indeterminate, negative by IHC, flow and/or molecular genetic studies. CR unconfirmed (CRu) is no longer included. PR is defined as 1) ≥ 50% decrease in tumor size, but PET+ at prior PA sites, or 2) ≥ 50% decrease in tumor size, but CT+ and PET- if PET- prior to treatment. Bone marrow is irrelevant if positive pre-treatment. Stable disease is neither PR nor progressive disease, PET+ only at prior sites of disease. Progressive/ relapsed disease requires ≥ 50% increase in disease or new lesions that are PET+ if PA lymphoma. PET does not replace a biopsy before initiating new therapy. Conclusions: We hope these revised recommendations will be adopted by study groups and regulatory agencies to facilitate the development of new and more effective therapies to improve patient outcome. No significant financial relationships to disclose.
Identification of Insulin‐Producing Cells Derived from Embryonic Stem Cells by Zinc‐Chelating Dithizone (2002)

ES cell-derived DTZ-positive cellular clusters possess characteristics of the endocrine pancreas, including insulin secretion. Further, DTZ staining is a useful method for the identification of differentiated pancreatic islets developed from EBs in vitro.
Rat Extramedullary Adipose Tissue as a Source of Osteochondrogenic Progenitor Cells (2002)

Human liposuction aspirates contain pluripotent adipose-derived mesodermal stem cells that have previously been shown to differentiate into various mesodermal cell types, including osteoblasts and chondrocytes. To develop an autologous research model of bone and cartilage tissue engineering, the authors sought to determine whether rat inguinal fat pads contain a similar population of osteochondrogenic precursor cells. It was hypothesized that the rat inguinal fat pad contains adipose-derived multipotential cells that resemble human adipose-derived mesodermal stem cells in their osteochondrogenic capacity. To test this, the authors assessed the ability of cells isolated from the rat inguinal fat pad to differentiate into osteoblasts and chondrocytes by a variety of lineage-specific histologic stains. Rat inguinal fat pads were isolated and processed from Sprague-Dawley rats into a fibroblast-like cell population. Cell cultures were placed in pro-osteogenic media containing dexamethasone, ascorbic acid, and beta-glycerol phosphate. Osteogenic differentiation was assessed at 2, 4, and 6 weeks. Alkaline phosphatase activity and von Kossa staining were performed to assess osteoblastic differentiation and the production of a calcified extracellular matrix. Cell cultures were also placed in prochondrogenic conditions and media supplemented with transforming growth factor-beta1, insulin, transferrin, and ascorbic acid. Chondrogenic differentiation was assessed at 2, 7, and 14 days by the presence of positive Alcian blue staining and type II collagen immunohistochemistry. Cells placed in osteogenic conditions changed in structure to a more cuboidal shape, formed bone nodules, stained positively for alkaline phosphatase activity, and secreted calcified extracellular matrix by 2 weeks. Cells placed in chondrogenic conditions formed cartilaginous nodules within 48 hours that stained positively for Alcian blue and type II collagen. The authors identified the rat inguinal fat pad as a source of osteochondrogenic precursors and developed a straightforward technique to isolate osteochondrogenic precursors from a small animal source. This relatively easily obtained source of osteochondrogenic cells from the rat may be useful for study of tissue engineering strategies and the basic science of stem cell biology.
Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors (2020)

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a global health emergency. An attractive drug target among coronaviruses is the main protease (M<sup>pro</sup>, also called 3CL<sup>pro</sup>) because of its essential role in processing the polyproteins that are translated from the viral RNA. We report the x-ray structures of the unliganded SARS-CoV-2 M<sup>pro</sup> and its complex with an α-ketoamide inhibitor. This was derived from a previously designed inhibitor but with the P3-P2 amide bond incorporated into a pyridone ring to enhance the half-life of the compound in plasma. On the basis of the unliganded structure, we developed the lead compound into a potent inhibitor of the SARS-CoV-2 M<sup>pro</sup> The pharmacokinetic characterization of the optimized inhibitor reveals a pronounced lung tropism and suitability for administration by the inhalative route.
Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites (1997)

The circumsporozoite protein (CSP) is a target for effector Ab and cell mediated immunity against malaria parasites; DNA vaccination can induce both types of effector response. The immunogenicity and efficacy of two DNA plasmids expressing different amounts of Plasmodium berghei CSP were evaluated by immunizing BALB/c mice i.m. or epidermally and by varying the number of immunizations (one to three doses) and the interval between immunizations. Expanding the interval gave the strongest effect, increasing efficacy and antibody boosting, and, in the case of epidermal vaccination, promoting a switch in CSP-specific IgG isotypes from IgG1 to a balance with IgG2a. The strongest humoral immune response and the greatest level of protection were induced by vaccinating epidermally with high expresser plasmid, using a gene gun to administer three doses at 6-wk intervals. For this group, the mean, repeat-specific, prechallenge antibody titer among mice not infected after challenge was significantly higher than that in infected mice, but the mean prechallenge titers for antibody reactive with whole sporozoites were not significantly different. The interval-dependent induction of IgG2a antibodies by epidermal vaccination contradicts the widely held belief that antibody responses induced by this method are restricted to those that are Th2 dependent.
Constant-dispersion grism spectrometer for channeled spectra (1990)

A new spectrometer design is presented in which the angular dispersion with respect to wave number is nearly constant. The spectrometer is a type of grism, a series combination of grating and prism, in which the constant parts of the dispersion terms add to one another but the slopes of the dispersions tend to cancel one another. A systematic method is presented for optimizing the grating and prism parameters. Expressions are given for the blaze efficiency and effective groove width of a transmission grating with generalized triangular grooves. A cross-dispersion technique is presented, eliminating overlapping grating orders. A design example is given for the visible region from 0.45 to 0.80 μm with essentially constant wave-number dispersion and a peak transmission of approximately 95%. This grism is well suited for measuring channeled spectra as generated by an optical stellar interferometer.
Stepped-frequency radar design and signal processing enhances ground penetrating radar performance (1996)

This thesis presents a theoretical analysis and applied evaluation of the stepped- frequency radar technique and shows that significant performance benefits can be achieved in ground penetrating radar (GPR) applications. These benefits are successfully demonstrated in field trials of a newly designed stepped-frequency GPR system.An original contribution has been made in establishing a unified characterisation of the performance of GPR for constant Q materials. This enables the maximum penetration depth of a GPR system to be characterised as a fixed number of wavelengths which is constant for any frequency. Similarly, the resolution is expressed as a fixed number of wavelengths which is also constant with frequency. These expressions prove to be a useful design tool in characterising GPR performance independently of frequency, and in selecting the waveform parameters for a defined application.A rigorous theoretical study of the stepped-frequency radar technique is undertaken, which demonstrates the synthesis of an impulse waveform using an IDFT-based matched filter with minimum-phase. It is concluded that a physically realisable stepped-frequency radar has far-reaching benefits in the form of higher processed mean energy than an impulse radar with the same frequency bandwidth.A 1-2 GHz stepped-frequency GPR prototype has been completely designed and built to test the above theories. The primary application for this system design is the high-resolution mapping of thin coal seam structures in open-cut coal mines. The 1-2 GHz frequency band is selected to meet the performance requirements of one metre penetration and five centimetre resolution in coal.A novel technique is presented which corrects the broadband quadrature receiver errors in the stepped-frequency radar prototype. It is shown that the technique suppresses the Hermit,Ian images by more than 50 dB below the target responses.The external loop gain of the system is measured to be 156 ± 6 dB for bow-tie antennas and 166 ± 6 dB for horn antennas. These figures represent the maximum power loss that the radiated signal, integrated over a defined ten millisecond interval, can tolerate between the transmit and receive antennas, for a defined signal-to-noise ratio of 10 dB. The performances of typical impulse GPR systems are noted in the literature to lie between 100-130 dB under similar conditions.The system is successfully field tested at various sites, including two open-cut coal mines. The resulting images from these sites demonstrate a penetration depth of at least 80 centimetres and a resolving power of better than 8 centimetres.