gebhart/patrepeval huggingface dataset:
Thrombelastography (2001)

Thrombelastography is a 'near patient' test of coagulation. It is easy to perform and can provide information on a patient's coagulation status within 30 min. Despite more than 25 years of clinical experience, however, several basic questions relating thromboelastograph (TEG) parameters to standard coagulation tests remain unanswered, and the value of the TEG is established only in the setting of orthotopic liver transplantation and cardiopulmonary bypass surgery. This review will focus on the principles and practise of the TEG(R), and data supporting the current accepted uses. Potential future uses will also be discussed including evaluation of hypercoagulable states, and investigating the mechanism of coagulopathies due to drugs or disease that standard tests have failed to unravel.
Fabrication of ultrasmall tunnel junctions by electron beam direct-writing (2001)

Fabrication of miniaturized tunnel junctions based on high-melting metals by the shadow evaporation technique is rather complicated. The thermal load of the suspended bridge mask during metal evaporation is assumed to be the most serious problem. As an alternative we have developed a preparation technique using e-beam direct-writing lithography in conjunction with material deposition by sputtering. To test the preparation process, we have fabricated single electron transistors (SETs) based on the metals Al and Nb, including mixed Al/Nb samples. For SETs made completely of Nb, we preferred Al0/sub x/ to the natural oxide NbO/sub x/ for barrier generation. The yield of functioning samples amounted to about 80%. By means of simple considerations we have estimated the tunnel capacitances to be of the order of a few 10/sup -16/ F, the tunnel resistance spread was less than one order of magnitude.
Retinoids and vertebrate development. (1994)

In conclusion, it is obvious that many of the abnormalities in pattern formation and organ formation that result from the exogenous addition of RA during embryogenesis are related at least in part to the ability of RA to change the pattern of expression of the clusters of homeobox genes in the mammalian embryo. The majority of experimental protocols to study RA-induced changes in embryonic development have utilized treatments with excess, exogenous RA, but it has not yet been proven that endogenous RA acts as a key signaling molecule in developing embryo. Thus, we need to develop an understanding of the metabolic enzymes that control the levels of the important endogenous retinoids, including RA, in the developing embryo. The continuing study of retinoids and their receptors will provide us with significant new information about the regulatory programs that control differentiation and development. Moreover, these studies will lead to discoveries relevant to the clinical use of retinoids in the areas of cancer prevention and treatment, and dermatology.
Regulatory Elements Governing Transcription in Specialized Myofiber Subtypes (2001)

Skeletal myofibers of vertebrates acquire specialized metabolic and physiological properties as a consequence of developmental cues in the embryo and different patterns of contractile activity in the adult. The myoglobin gene is regulated stringently in muscle fibers, such that high myoglobin expression is observed in mitochondria-rich, oxidative myofibers (Types I and IIa) compared with glycolytic fibers (Type IIb). Using germ-line transgenesis and somatic cell gene transfer methods, we defined discrete regions of the murine and human genes encoding myoglobin that are sufficient to confer muscle- and fiber type-specific expression to reporter genes. Mutational analysis confirms the importance of A/T-rich, MEF2-binding motifs in myoglobin gene regulation, as suggested by previous studies using different experimental approaches. In addition, we demonstrated a previously unsuspected role for an intragenic E-box motif as a negative regulatory element contributing to the tightly regulated variation in myoglobin gene expression among particular myofiber subtypes.
Percutaneous Radiofrequency Destruction of the Obturator Nerve for Treatment of Pain Caused by Coxarthrosis (1997)

Pain and restriction of movements in the hip joint due to coxarthrosis are common causes of patients' visits to their doctors. During the past few years, endoprosthetic surgery has been the most common surgical method for the treatment of this disease. Endoprosthetic operation is contraindicated for some patients in view of their excessive body weight or the presence of concurrent somatic diseases. In order to eliminate pain due to coxarthrosis, we have developed a new operation--percutaneous radiofrequency destruction of the obturator nerve--carried out at the point of its exit from the small pelvis through the obturator canal.
Drug Therapy and Memory Training Programs: A Double-Blind Randomized Trial of General Practice Patients With Age-Associated Memory Impairment (1994)

A double-blind randomized trial was performed involving 162 patients with age-associated memory impairment (AAMI) selected and followed by their general practitioners. Two intervention methods--a drug and a cognitive therapy--were assessed in combination. Three randomized parallel groups of 54 patients each, aged 55 years and over, were followed and treated for 3 months. After a placebo wash-out period of 10 days, one group received 2.4 g of piracetam, another group, 4.8g, and the third, a placebo. A total of 135 patients, 45 in each group, completed the study. Combined therapy was most effective in patients whose baseline performance on memory tests was lowest. The best results were observed with 4.8 g of piracetam, especially when training sessions began after 6 weeks of drug treatment. This result was confirmed by the global impression of the principal investigator.
The Etiology of Hepatocellular Carcinoma and Consequences for Treatment (2010)

Most patients with hepatocellular carcinoma (HCC) have liver cirrhosis, which develops following long periods of chronic liver disease. Cirrhosis is characterized by a decrease in hepatocyte proliferation, indicating an exhaustion of the regenerative capacity of the liver, and results in an increase in fibrous tissue and a destruction of liver cells, which may ultimately lead to the development of cancerous nodules. Half of all cases of HCC are associated with hepatitis B virus infection, with a further 25% associated with hepatitis C virus. Other risk factors for developing HCC include alcoholic liver disease, nonalcoholic steatohepatitis, intake of aflatoxin-contaminated food, diabetes, and obesity. There are multiple factors involved in the etiology of HCC, all of which have a direct impact on patient characteristics and disease course, and although a causative agent can often be identified, HCC remains an extremely complex condition associated with a poor prognosis. Additionally, the geographic variation in etiology means that information from different countries is needed in order to optimize surveillance methods and develop effective chemoprevention strategies. Unfortunately, there are still many gaps in our current understanding, and further research efforts are needed to fully elucidate the diverse mechanisms involved in the pathogenesis of HCC and offer optimal prevention strategies for those at risk.
Prediction of Docetaxel Response in Human Breast Cancer by Gene Expression Profiling (2005)

These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.
Further comments on the relation between hydraulic permeation and diffusion (1974)

Abstract We feel that the lengthy comments given here come down to a few simple points. For uniform, homogeneous swollen membranes the internal driving force for transport in hydraulic permeation experiments is a concentration gradient not a pressure gradient. Equation (1) is in error because it neglects the frame of reference term 1/(1 − ν 1 ). Equation (19) shows properly the connection between K 0 and the various diffusion coefficients. In the particular case discussed here and previously we see no evidence to say that a viscous flow mechanism is operative since we can explain all of the K 0 data in terms of reasonable diffusion coefficients if proper consideration is given to the frame of reference correction. This is not to say that in many other cases a viscous flow mechanism will not be present or even predominate.
Peptide YY: A Potential Therapy for Obesity (2005)

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.
Avoidance of security breach through selective permissions in android operating system (2012)

The current Android application framework has an "all or none" permission policy, viz., an application can be installed if and only if all the permissions are granted. Also, no provision exists to deny granted permissions after installation. Therefore, any application can misuse the granted permission. CyanogenMod addresses this issue by denying the unwanted permissions which might cause the application to crash. WhisperCore, has worked on this problem but the working model is unavailable at the moment. APEX, also is currently doing some research on this issue but there is no publicly available document. In this paper, the problem of misusing the granted permission n in Android is addressed and a novel idea of 'shadow manifest' is proposed. The proposed shadow manifest is implemented by creating a novel Content Provider, viz., SelPermProvider, which hosts the user permissions. In general, during the resource request phase, the system manifest is checked and the resources are allocated. But, in our implementation, the control is altered to flow through the shadow manifest after the system manifest is checked. If the query to shadow manifest is TRUE, then the resource is granted else a dummy or null value is returned. This facilitates the user to identify the malware and block the malware from achieving the intended task. Thus, the application is unaware of the indirect permission denial and continues to run normally. The user can decide which permission to restrict by checking a log of all recent permission requests, a facility provided in our app. The proposed shadow manifest has been implemented and tested using an application called 'Contacts_Retrieve'. It was found to successfully complete the application if the shadow manifest returned TRUE, and unsuccessfully complete otherwise.
Decomposition of 2-Isopropylnaphthalene Hydroperoxide into 2-Naphthol and Acetone in the Presence of Acetic Acid and H2O2 (1999)

Process conditions for the acid-catalyzed decomposition of 2-isopropylnaphthalene hydroperoxide (2-IPNHP) into 2-naphthol and acetone were investigated in the presence of acetic acid and H2O2 as the solvent and oxidizing reagent, respectively. 2-Naphthol and acetone are produced from 2-IPNHP by the ionic decomposition mechanism; however, reaction conditions that lead to the formation of radicals mainly favor the byproducts dimethyl-2-naphthylcarbinol (DMNC) and acetonaphthone (AN). The effects of the catalyst type and concentration on the 2-naphthol yield and on the product distribution were investigated by HClO4, H2SO4, H3PO4, and HCl. The catalytic activities of the acids in the decomposition of 2-IPNHP to produce 2-naphthol decreased in the order HClO4 > H2SO4 > HCl > H3PO4 depending on their acid strengths in acetic acid. The higher the catalyst concentration employed, the higher the 2-naphthol yield obtained. The high concentrations of 2-IPNHP did not lead to the hydroperoxide-induced decomposition reactions; instead they increased the ionic decomposition rate due to the polar character of 2-IPNHP. The increase in the DMNC concentration in the decomposition medium slightly decreased the 2-naphthol production rate and yield. The increase in temperature in the range of 22−40 °C increased the 2-naphthol production. The process conditions such as low acid strength, low catalyst concentration, and high temperature that lead to radical reactions increased the production of AN. The other byproduct DMNC was also oxidized to 2-IPNHP with H2O2 in the reactor. A 61% yield of 2-naphthol was obtained under the batch reactor conditions of 0.114 mol dm-3 HClO4 and 1.036 mol dm-3 initial 2-IPNHP concentrations at 22 °C.
Genome-Wide Assessment of Efficiency and Specificity in CRISPR/Cas9 Mediated Multiple Site Targeting in Arabidopsis (2016)

Simultaneous multiplex mutation of large gene families using Cas9 has the potential to revolutionize agriculture and plant sciences. The targeting of multiple genomic sites at once raises concerns about the efficiency and specificity in targeting. The model Arabidopsis thaliana is widely used in basic plant research. Previous work has suggested that the Cas9 off-target rate in Arabidopsis is undetectable. Here we use deep sequencing on pooled plants simultaneously targeting 14 distinct genomic loci to demonstrate that multiplex targeting in Arabidopsis is highly specific to on-target sites with no detectable off-target events. In addition, chromosomal translocations are extremely rare. The high specificity of Cas9 in Arabidopsis makes this a reliable method for clean mutant generation with no need to enhance specificity or adopt alternate Cas9 variants.
Broadband algorithms with the MicroUnity mediaprocessor (2002)

An important objective of the MicroUnity mediaprocessor is to allow the design of systems that replace hardwired functionality with software. One of the key design techniques that has been employed at the architectural level is an instruction set that processes 128-bit vectors of data of varying widths. This introduces the challenge of writing software that effectively uses the available vector processing across the broad range of algorithms of interest. In this paper we focus on a selected set of algorithms that illustrate many of the techniques we have developed for vector parallel programming on the mediaprocessor.
Role of cytokines in leukemic type growth of myelodysplastic CD34+ cells (1996)

The clonal growth of progenitor cells from myelodysplastic syndromes (MDS) can be subdivided into four growth patterns: (1) normal, (2) no growth or low plating efficiency, (3) low colony and high cluster number, and (4) normal or high colony number with a large number of clusters. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cytokines in leukemic-type growth of MDS progenitor cells, marrow CD34+ cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). The purified CD34+ cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. The clonal growth of MDS CD34+ cells supported by a combination of all of the above cytokines was subdivided into the two patterns of leukemic or nonleukemic, and then the role of individual or combined cytokines in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. Evidence we obtained showed that SCF plays a central role in the leukemic-type growth of MDS CD34+ cells and that G-CSF, GM-CSF; and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34+ cells. SCF is present in either normal or MDS plasma at a level of nanograms per milliliter, and this physiologic concentration of SCF can stimulate progenitor cells. This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at least in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF.
Optimizing the neural response to electrical stimulation and exploring new applications of neurostimulation (2015)

Electrical stimulation has been successful in treating patients who suffer from neurologic and neuropsychiatric disorders that are resistant to standard treatments. For deep brain stimulation (DBS), its official approved use has been limited to mainly motor disorders, such as Parkinson's disease and essential tremor. Alcohol use disorder, and addictive disorders in general, is a prevalent condition that is difficult to treat long-term. To determine whether DBS can reduce alcohol drinking in animals, voluntary alcohol consumption of alcohol-preferring rats before, during, and after stimulation of the nucleus accumbens shell were compared. Intake levels in the low stimulus intensity group (n=3, 100&mgr;A current) decreased by as much as 43% during stimulation, but the effect did not persist. In the high stimulus intensity group (n=4, 200&mgr;A current), alcohol intake decreased as much as 59%, and the effect was sustained. These results demonstrate the potent, reversible effects of DBS. Left vagus nerve stimulation (VNS) is approved for treating epilepsy and depression. However, the standard method of determining stimulus parameters is imprecise, and the patient responses are highly variable. I developed a method of designing custom stimulus waveforms and assessing the nerve response to optimize stimulation selectivity and efficiency. VNS experiments were performed in rats aiming to increase the selectivity of slow nerve fibers while assessing activation efficiency. When producing 50% of maximal activation of slow fibers, customized stimuli were able to activate as low as 12.8% of fast fibers, while the lowest for standard rectangular waveforms was 35.0% (n=4-6 animals). However, the stimulus with the highest selectivity requires 19.6nC of charge per stimulus phase, while the rectangular stimulus required only 13.2nC. Right VNS is currently under clinical investigation for preventing sudden unexpected death in epilepsy and for treating heart failure. Activation of the right vagal parasympathetic fibers led to waveform-independent reductions in heart rate, ejection ratio, and stroke volume. Customized stimulus design with response feedback produces reproducible and predictable patterns of nerve activation and physiological effects, which will lead to more consistent patient responses.
Effect of Redox Modulating NRF2 Activators on Chronic Kidney Disease (2014)

Chronic kidney disease (CKD) is featured by a progressive decline of kidney function and is mainly caused by chronic diseases such as diabetes mellitus and hypertension. CKD is a complex disease due to cardiovascular complications and high morbidity; however, there is no single treatment to improve kidney function in CKD patients. Since biological markers representing oxidative stress are significantly elevated in CKD patients, oxidative stress is receiving attention as a contributing factor to CKD pathology. Nuclear factor erythroid-2 related factor 2 (NRF2) is a predominant transcription factor that regulates the expression of a wide array of genes encoding antioxidant proteins, thiol molecules and their generating enzymes, detoxifying enzymes, and stress response proteins, all of which can counteract inflammatory and oxidative damages. There is considerable experimental evidence suggesting that NRF2 signaling plays a protective role in renal injuries that are caused by various pathologic conditions. In addition, impaired NRF2 activity and consequent target gene repression have been observed in CKD animals. Therefore, a pharmacological intervention activating NRF2 signaling can be beneficial in protecting against kidney dysfunction in CKD. This review article provides an overview of the role of NRF2 in experimental CKD models and describes current findings on the renoprotective effects of naturally occurring NRF2 activators, including sulforaphane, resveratrol, curcumin, and cinnamic aldehyde. These experimental results, coupled with recent clinical experiences with a synthetic triterpenoid, bardoxolone methyl, have brought a light of hope for ameliorating CKD progression by preventing oxidative stress and maintaining cellular redox homeostasis.
Helminth infection results in decreased virus-specific CD8+ cytotoxic T-cell and Th1 cytokine responses as well as delayed virus clearance. (1993)

During the time of egg deposition, schistosome-infected mice exhibit a downregulation in interleukin 2 and interferon gamma production toward parasite antigens, mitogens, and foreign nonparasite protein antigens. To determine whether this imbalance in cytokine response would impact on CD8+ cytotoxic T-lymphocyte (CTL) responses, as well as on immune clearance of viral infections, we challenged Schistosoma mansoni-infected BALB/c mice, when cytokine imbalance was prominent, with a recombinant vaccinia virus expressing human immunodeficiency virus type 1 gp160. In contrast to control vaccinia-infected animals, S. mansoni plus vaccinia-infected mice did not produce significant Th1 cytokine responses upon in vitro stimulation with recombinant gp120, consistent with previous results for nonparasite antigens. However, more striking was the downregulation of the virus-specific CTL response not previously studied. Spleen cells from vaccinia-infected control mice displayed strong CD8+ cytolytic activity against gp160-transfected fibroblasts and fibroblasts pulsed with a peptide (P18) representing a CTL epitope of gp160. In contrast, mice coinfected with S. mansoni and vaccinia manifested absent or markedly reduced in vitro CTL activity even in the presence of exogenous interleukin 2. To determine whether this immune dysregulation might impact on viral clearance, we measured virus titers in tissues as a function of time. Mice infected with vaccinia virus alone rapidly cleared the virus, whereas in animals coinfected with S. mansoni, viral clearance was delayed by as much as 3 weeks in the liver and by several days in the spleen and lungs. These observations suggest that helminth infection may influence immune responses to concurrent viral infections.