gebhart/patrepeval huggingface dataset:
Rat Brain Tumor Models and the Statistical Evaluation of Survival Data in Experimental Neuro-Oncology (1998)

With the growing interest in gene therapy of brain tumors, there is a major need for suitable animal models that can be used to assess the efficacy of various approaches to genetically engineer brain tumor cells. This chapter will be selective rather than comprehensive, and will focus entirely on rat brain tumor models, their utility in evaluating the efficacy of various treatment modalities, and the statistical evaluation of survival data. Two recent reviews (1,2) provide much useful information about a number of the rat brain tumor models that will be discussed here, and interested readers are referred to these for additional details relating to the tumors described by us. Murine (3,4),canine (5,6),and feline (2,7) models have been described, but these will not be discussed. The rat is one of the most widely used of experimental animals (8,9) and rat brain tumor models have been used in experimental neuro-oncology since the mid-1970s (10). Druckrey (11), Benda, Schmidek, Swenberg, and Koestner (12–16) and their associates reported that central nervous system tumors could be induced selectively and reproducibly in adult rats that had been given repeated, weekly, intravenous (iv) injections of N-methylnitrosourea (NMU). Contemporaneous with this, Druckrey (11) and Swenberg (16) reported that brain tumors also could be induced in the progeny of pregnant rats that had been given a single iv injection of N-ethyl-N-nitrosourea (ENU). These studies led to the development of a number of brain tumor models that were easily reproduced, and that did not require the topical application of a chemical carcinogen to the brain. At about the same time, Bigner et al. (6) described the development of an avian sarcoma virus-induced rat brain tumor model, which also has proven to be useful. Some general principles relating to the use of rat brain tumor models will be presented, brief descriptions of the most widely used of these tumors will be reviewed, and their respective advantages and limitations will be discussed. Xenograft models (17), based on the intracerebral transplantation of human brain tumors into immunologically deficient nude rats, will not be discussed.
Human Functional States: An Exploratory Study of Performance and Role Stress in a Power Plant (2001)

The present study attempts to understand the functional competence of employees by developing a measure of and analyzing the factors affecting competence. A narrative inquiry method was used. Suggestions are made for a Human Resources Development strategy to improve the functional competence of the employees in a Power Plant in Sonebhadra, Uttar Pradesh, India.
An abstract-device interface for implementing portable parallel-I/O interfaces (2002)

We propose a strategy for implementing parallel I/O interfaces portably and efficiently. We have defined an abstract device interface for parallel I/O, called ADIO. Any parallel I/O API can be implemented on multiple file systems by implementing the API portably on top of ADIO, and implementing only ADIO on different file systems. This approach simplifies the task of implementing an API and yet exploits the specific high performance features of individual file systems. We have used ADIO to implement the Intel PFS interface and subsets of MPI-IO and IBM PIOFS interfaces on PFS, PIOFS, Unix, and NFS file systems. Our performance studies indicate that the overhead of using ADIO as an implementation strategy is very low.
The renin-angiotensin-aldosterone system in preeclampsia. A review. (1991)

The renin-angiotensin-aldosterone system plays an integral role in the (patho)physiology of pregnancy and pregnancy-induced hypertensive disease. The current review concerns the renin-angiotensin-aldosterone system in relation to other vasoactive substances in normal pregnancy and preeclampsia.
Fusion guide RNAs for orthogonal gene manipulation with Cas9 and Cpf1 (2017)

The bacteria-derived clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are powerful tools for genome engineering. Recently, in addition to Cas protein engineering, the improvement of guide RNAs are also performed, contributing to broadening the research area of CRISPR-Cas9 systems. Here we develop a fusion guide RNA (fgRNA) that functions with both Cas9 and Cpf1 proteins to induce mutations in human cells. Furthermore, we demonstrate that fgRNAs can be used in multiplex genome editing and orthogonal genome manipulation with two types of Cas proteins. Our results show that fgRNAs can be used as a tool for performing multiple gene manipulations.
Frequency and type of serious infections in fludarabine‐refractory B‐cell chronic lymphocytic leukemia and small lymphocytic lymphoma (2002)

BACKGROUND Treatments for fludarabine-refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are limited. Most new therapies being examined in fludarabine-refractory patients have shown a high frequency of serious infection. Little data exist regarding the frequency of infections in this population treated with noninvestigational best supportive care therapies. METHODS The infectious courses of 27 patients with fludarabine-refractory CLL/SLL were retrospectively reviewed. Fludarabine-refractoriness was defined as either relapse within six months of completion of or failure to respond to fludarabine treatment. Infections were documented after patients met National Cancer Institute criteria for further treatment. Serious infections were defined as infections mandating admission to the hospital for intravenous antibiotics. RESULTS Patient characteristics included: median age 67 years (range, 40–83), median 3 chemotherapy treatments (range, 1–8), and hypogammaglobulinemia in 73% of patients. Pneumocystis carinii prophylaxis was given to 89% of patients. Serious infections developed in 24 out of 27 patients (89%). Patients had a median of 2 admissions (range, 0–11) for serious infection occurring at a median of 4 months (range, 0–21) from onset of fludarabine-refractoriness. The median frequency of admission for infection was 0.17 per month. Most common sites for infection in decreasing frequency were: respiratory tract, urinary tract, blood/sepsis, and soft tissues. Bacteria caused 69 out of 88 infections (78.4%); viruses (varicella-zoster and herpes simplex) caused 11 out of 88 (12.5%); fungi caused 4 out of 88 (4.5%); and opportunistic infections caused 4 out of 88 (4.5%). Median survival was 13.0 months (range, 1–44+). CONCLUSIONS The frequency of serious infections in patients with fludarabine-refractory CLL/SLL is high. These findings are relevant to trials with new and highly effective agents for which the incidence of serious infections after treatment might otherwise appear to be prohibitively high. Cancer 2002;94:2033–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10437
Expression of Functional Prolactin Receptors in Nonpregnant Human Endometrium: Janus Kinase-2, Signal Transducer and Activator of Transcription-1 (STAT1), and STAT5 Proteins Are Phosphorylated after Stimulation with Prolactin (1998)

PRL is synthesized by decidualized endometrial stromal cells from the midsecretory phase in a nonconception cycle and throughout pregnancy. The exact role of PRL in the human endometrium remains to be elucidated; however, the pattern of expression supports a role for PRL during implantation and placentation. This study investigated the site and pattern of expression of PRL receptors in the nonpregnant human endometrium. In situ hybridization and immunohistochemistry localized expression of the receptor in the glandular epithelium and a subset of stromal cells of the endometrium. As judged by the intensity of staining, expression of the receptor was dramatically up-regulated during the secretory phase. Expression of the PRL receptor gene in the endometrium from the secretory phase of the menstrual cycle was confirmed by ribonuclease protection assay using 50 micrograms total ribonucleic acid. Phosphorylation of Janus kinase-2 (JAK2), STAT1 (signal transducer and activator of transcription-1), and STAT5 proteins in response to PRL was investigated to establish the signaling pathway of PRL in the human endometrium. Endometrial tissue was collected during the secretory phase of the menstrual cycle and incubated in the presence of 100 ng/mL human PRL for 0, 5, 10, and 20 min. JAK2 phosphorylation was induced by PRL at 5 min, whereas STAT1 and STAT5 phosphorylation was apparent 20 min after stimulation with PRL. Immunohistochemistry localized the JAK/STAT proteins in the glandular epithelial cells and a subset of stromal cells, as was observed for the PRL receptor. Secretory phase stromal and glandular cells cultured separately and in the presence or absence of 100 ng/mL PRL confirmed the PRL-induced phosphorylation of JAK2/STAT proteins, at least in the glandular compartment. These studies demonstrate an up-regulation of expression of functional PRL receptors during the secretory phase of the menstrual cycle. Further, decidual PRL through a paracrine mechanism may influence glandular epithelial function/secretions and direct gene transcription through the JAK/STAT pathway. The target genes activated by PRL in the glandular epithelium of the nonpregnant human endometrium remain to be elucidated.
Inflammation and the Microcirculation (2010)

Abstract The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells,...
Electronic damping of orthogonal bending modes in a cylindrical mast - Experiment (1981)

Covers advancements in spacecraft and tactical and strategic missile systems, including subsystem design and application, mission design and analysis, materials and structures, developments in space sciences, space processing and manufacturing, space operations, and applications of space technologies to other fields.
Techniques for Extracting Reliable Density and Porosity Data From Cuttings (2005)

Abstract The collection of core samples from a reservoir is essential for its proper characterization. Core data play very important roles in the following: log calibration, well treatment and performance prediction, reservoir modeling and simulation, and production and development planning. Coring is time-consuming, expensive and risky. It is difficult, if not impossible, to retrieve whole cores from horizontal and maximum reservoir contact (MRC) wells — which form the bulk of wells being drilled at present. As an alternative to coring, the use of cuttings has been proposed by many, as cuttings are always available from wells. Aside from some loss, contamination and depth-uncertainty (typically within 10 ft), cuttings show strong potential to represent all the formations encountered during the drilling of a well. This paper discusses the capabilities of various laboratory instruments to extract reliable density and porosity data from cuttings. The methodology used involves full characterization of a carbonate core plug using several laboratory tools followed by crushing the plug into cuttings of different mesh sizes. Samples of different mesh sizes were then scanned with a CT-scanner and bulk densities and porosities were calculated using advanced histogram-based analysis techniques. Results for individual cuttings sizes were compared against those for the whole plug. Additional data on the same cuttings were generated using micro-CT, Environmental Scanning Electron Microscope (ESEM), Nuclear Magnetic Resonance (NMR) spectrometer and APEX (Apparatus for Pore Examination) mercury porosimeter, which were also used for comparison. A set of procedures was developed for generating porosity data based on image processing of SEM and micro-CT generated images. The work helped establish the size of about 2.5 mm as the limit of detectability of medical-based CT-scanners to generate reliable density and porosity data from drilled cuttings. Comparison between the micro-CT and ESEM data showed the range of application for each tool in determining porosities from cuttings. Comparison between the pore size distributions generated by the NMR and APEX mercury porosity instruments and their visual comparisons with ESEM images provide important insights for the pore network modeling efforts.
Protein Misfolding and Human Disease (2006)

Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting in accumulation of misfolded proteins. Dependent on the properties of the protein and the efficiency of the PQC systems, the accumulated protein may be degraded or assembled into toxic oligomers and aggregates. To illustrate this concept, we discuss a number of very different protein misfolding diseases including phenylketonuria, Parkinson's disease, alpha-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute to the elucidation of the cell pathology and guide intervention and treatment strategies of many genetic and age-dependent diseases.
A New Generation of Modified Live-Attenuated Avian Influenza Viruses Using a Two-Strategy Combination as Potential Vaccine Candidates (2007)

In light of the recurrent outbreaks of low pathogenic avian influenza (LPAI) and highly pathogenic avian influenza (HPAI), there is a pressing need for the development of vaccines that allow rapid mass vaccination. In this study, we introduced by reverse genetics temperature-sensitive mutations in the PB1 and PB2 genes of an avian influenza virus, A/Guinea Fowl/Hong Kong/WF10/99 (H9N2) (WF10). Further genetic modifications were introduced into the PB1 gene to enhance the attenuated (att) phenotype of the virus in vivo. Using the att WF10 as a backbone, we substituted neuraminidase (NA) for hemagglutinin (HA) for vaccine purposes. In chickens, a vaccination scheme consisting of a single dose of an att H7N2 vaccine virus at 2 weeks of age and subsequent challenge with the wild-type H7N2 LPAI virus resulted in complete protection. We further extended our vaccination strategy against the HPAI H5N1. In this case, we reconstituted an att H5N1 vaccine virus, whose HA and NA genes were derived from an Asian H5N1 virus. A single-dose immunization in ovo with the att H5N1 vaccine virus in 18-day-old chicken embryos resulted in more than 60% protection for 4-week-old chickens and 100% protection for 9- to 12-week-old chickens. Boosting at 2 weeks posthatching provided 100% protection against challenge with the HPAI H5N1 virus for chickens as young as 4 weeks old, with undetectable virus shedding postchallenge. Our results highlight the potential of live att avian influenza vaccines for mass vaccination in poultry.
Variables Influencing Extraction of Nucleic Acids from Microbial Plankton (Viruses, Bacteria, and Protists) Collected on Nanoporous Aluminum Oxide Filters (2014)

Anodic aluminum oxide (AAO) filters have high porosity and can be manufactured with a pore size that is small enough to quantitatively capture viruses. These properties make the filters potentially useful for harvesting total microbial communities from water samples for molecular analyses, but their performance for nucleic acid extraction has not been systematically or quantitatively evaluated. In this study, we characterized the flux of water through commercially produced nanoporous (0.02 μm) AAO filters (Anotop; Whatman) and used isolates (a virus, a bacterium, and a protist) and natural seawater samples to test variables that we expected would influence the efficiency with which nucleic acids are recovered from the filters. Extraction chemistry had a significant effect on DNA yield, and back flushing the filters during extraction was found to improve yields of high-molecular-weight DNA. Using the back-flush protocol, the mass of DNA recovered from microorganisms collected on AAO filters was ≥ 100% of that extracted from pellets of cells and viruses and 94% ± 9% of that obtained by direct extraction of a liquid bacterial culture. The latter is a minimum estimate of the relative recovery of microbial DNA, since liquid cultures include dissolved nucleic acids that are retained inefficiently by the filter. In conclusion, we demonstrate that nucleic acids can be extracted from microorganisms on AAO filters with an efficiency similar to that achievable by direct extraction of microbes in suspension or in pellets. These filters are therefore a convenient means by which to harvest total microbial communities from multiple aqueous samples in parallel for subsequent molecular analyses.
Pharmacotherapy of actinic keratosis (2009)

Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation with the potential of progression to squamous cell carcinoma (SCC). When in limited numbers, clinically visible AKs are treated individually with ablative and/or surgical procedures (lesion-directed treatment), while multiple and sublinical AKs are treated with field-directed therapies that use ablative, nonablating and other topically applied treatment modalities. Owing to difficulties in predicting which AK will progress to SCC, the general rule is to treat all AKs. The goals of treatment are to eliminate the AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmetic outcomes. Prevention is the most important treatment modality for AKs. Avoidance of sun and artificial sources of ultraviolet light, applying sunscreen and self-examination are among the most effective preventive measures. Chemopreventive modalities such as retinoids, 2-(Difluoromethyl)-dl-ornithine (DFMO), perillyl alcohol, T4 endonuclease V, and dl-alpha-tocopherol are described. Lesion-directed treatment modalities include cryotherapy, surgery and electrodessication with or without curettage. Field-directed treatment modalities include nonablative and ablative laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod, 5-fluorouracil and diclofenac) and photodynamic therapy. And, finally, newer and investigational treatment modalities such as ingenol mebutate, resiquimod and betulinic acid are also being discussed.
Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses (2001)

Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pulmonary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was carried out to examine whether the structural changes in the blood-gas barrier caused by a prior bout of high-intensity short-term exercise capable of inducing EIPH would affect the arterial hypoxemia induced during a successive bout of exercise performed at the same workload. Two sets of experiments, double- and single-exercise-bout experiments, were carried out on seven healthy, sound Thoroughbred horses. Experiments were carried out in random order, 7 days apart. In the double-exercise experiments, horses performed two successive bouts (each lasting 120 s) of galloping at 14 m/s on a 3.5% uphill grade, separated by an interval of 6 min. Exertion at this workload induced arterial hypoxemia within 30 s of the onset of galloping as well as desaturation of Hb, a progressive rise in arterial PCO2, and acidosis as exercise duration increased from 30 to 120 s. In the single-exercise-bout experiments, blood-gas/pH data resembled those from the first run of the double-exercise experiments, and all horses experienced EIPH. Thus, in the double-exercise experiments, before the horses performed the second bout of galloping at 14 m/s on a 3.5% uphill grade, stress failure of pulmonary capillaries had occurred. Although arterial hypoxemia developed during the second run, arterial PO2 values were significantly (P < 0.01) higher than in the first run. Thus prior exercise not only failed to accentuate the severity of arterial hypoxemia, it actually diminished the magnitude of exercise-induced arterial hypoxemia. The decreased severity of exercise-induced arterial hypoxemia in the second run was due to an associated increase in alveolar PO2, as arterial PCO2 was significantly lower than in the first run. Thus our data do not support a role for structural changes in the blood-gas barrier related to the stress failure of pulmonary capillaries in causing the exercise-induced arterial hypoxemia in horses.
Management of acute asthma in childhood. (1993)

In children, acute asthma is one of the most common reasons for admission to hospital. Morbidity and mortality from asthma are unnecessarily high. It is essential that all those caring for asthma patients can accurately assess and treat an acute exacerbation of asthma.
Engineered VaginalLactobacillusStrain for Mucosal Delivery of the Human Immunodeficiency Virus Inhibitor Cyanovirin-N (2006)

Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women.