gebhart/patrepeval huggingface dataset:
Cardiac performance during graded exercise in acute hypoxia (1975)

To evaluate the cardiocirculatory changes induced by acute hypoxic stress, rate corrected electro-mechanical systole (QS2)) left ventricular ejection time (LVET), and preejection period (PEP) were determined in 11 healthy males at sea level (SL) and after 2 h at a simulated altitude (HA) of 4,300 m. Recordings were made at rest and at 15 min of upright bicycle exercise at light and moderately heavy loads (40 and 75% of Vo2 max, respectively). Venous blood was withdrawn simultaneously for estimation of total plasma catecholamines (CATS). Exposure to HA produced a significant decrease in each interval at rest with differences narrowing progressively with exercise of increasing intensity. PEP/LVET ratio decreased progressively with graded exercise at SL indicating an enhancement of left ventricular performance that was directly related to the elevation in plasma CATS. Cardiac performance was augmented at rest during HA exposure, despite a normal level of CATS. However, during moderately heavy exercise at HA, when the plasma CATS were increased to twice the SL values, cardiac performance, as reflected by the PEP/LVET ratio, did not increase proportionately. It is postulated that the depressant effect of increased hypoxemia and acidosis during moderately heavy exercise in HA may override the cardiostimulatory influence of circulating CATS.
Therapeutic drug monitoring by reverse Iontophoresis (2012)

Therapeutic molecules possessing distinct pharmacokinetic variation, narrow therapeutic index and concentration dependent therapeutic/adverse effects demand constant monitoring. The current methods for blood sampling are invasive and possess low patient compliance. Human skin, selective and effective membrane to chemical permeation, offers an alternative route for the extraction of endogenous molecules in the body. Significant attention has been received in the application of reverse iontophoresis in extracting drugs/biomaterials from the subdermal region. This technique involves transiting of a low electric current across the skin usually with couple of skin electrodes to extract charged as well as neutral molecules. Electromigration and electroosmosis are the two basic mechanisms involved in transport of molecules. Several in vitro and in vivo experiments demonstrated the potential of reverse iontophoresis as a noninvasive tool in clinical chemistry and therapeutic drug monitoring. This technology is currently being used in device such as Glucowatch Biogrpaher which allows blood glucose detection across skin layers. Advances in technology and rapid progress in research has widely improved the opportunity of this system, and the recent trend indicates that several products are likely to be developed very soon. This review provides an overview about the recent developments in reverse iontophoresis for therapeutic drug monitoring.
Abstract 4995: Glucose-regulated protein 78 regulates crosstalk between apoptosis and autophagy to determine antiestrogen responsiveness (2012)

Abstract While over 70% of breast cancers express estrogen receptor α (ER+), drugs targeting these receptors such as Tamoxifen (TAM) or Faslodex (fulvestrant, ICI) often fail to cure these patients. Many ER+ patients fail to respond (de novo resistance) or lose drug responsiveness (acquired resistance), making endocrine resistance a major clinically relevant problem. The molecular mechanisms of endocrine therapy resistance still remain unclear. We show that antiestrogen resistant cells with an acquired resistant phenotype overexpress glucose-regulated protein 78 (GRP78), which is not observed in de novo resistance. Moreover, we show increased expression of GRP78 in MCF7/LCC9 (estrogen independent, ICI resistant, TAM cross-resistant) when compared to the MCF7/LCC1 (estrogen independent, TAM and ICI sensitive) breast cancer cells and tumors. These data reflect the response of aromatase inhibitor resistant breast cancers to second line antiestrogen therapy, and further support the hypothesis that antiestrogen resistance and estrogen independence are separate phenotypes. Targeting GRP78 with RNAi restored antiestrogen sensitivity in endocrine therapy resistant cells (MCF7-RR and MCF7/LCC9), whereas expressing GRP78 cDNA conferred resistance on antiestrogen sensitive breast cancer cells (MCF7 and MCF7/LCC1). We show that GRP78 integrates cellular signaling to inhibit apoptosis (as determined by cleaved caspase-7, cleaved PARP, and annexin V staining) and stimulate prosurvival autophagy (as determined by LC3-II, p62, and GFP-LC3 punctate). Moreover, GRP78-stimulated autophagy is dependent on TSC2/AMPK-mediated mTOR inhibition. Endocrine resistance induced by GRP78 overexpression is prevented through an inhibition of autophagy by ATG5 knockdown, while caspase inhibition prevented GRP78 RNAi-mediated therapy resensitization. Furthermore, knockdown of GRP78 and beclin 1 (BECN1) synergistically restores antiestrogen sensitivity in resistant cells. The use of GRP78 to integrate the cellular functions of apoptosis and autophagy to control cell fate raises the provocative question that this signaling may be widely applicable and represent a major stress response that explains how many different cell types could respond to stressors and acquire resistance to therapeutic interventions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4995. doi:1538-7445.AM2012-4995
Medical standards seen from the perspective of changes in academic society themes: investigation of a lawsuit concerning the prevention of venous thromboembolism. (2009)

The "standard of medical treatment at the time", can be discerned by tracing consensus agreement at session meetings. If the consensus from each session is recorded, a more detailed analysis can be made of the agreement reached by board members.
Transfer of Bruchid Resistance from the Common Bean to Other Starchy Grain Legumes by Genetic Engineering with the<i>α</i>-Amylase Inhibitor Gene (2010)

The field of plant genetic engineering has arisen from the laboratory and into the market place as a technology to provide farmers and consumers with improved crops. 1996 marks a turning point as the first genetically engineered crops to control agronomically important pests are registered for commercial sale. In most cases it has taken over a decade to develop commercially viable products. This book serves both as an update of current technologies that have been proven successful for engineering insect tolerant crops and an overview of new technologies that are being pursued for the development of new genetically engineered crops in the future. The book includes an introductory chapter on the world wide importance of insect problems in crops and the advantages of genetically engineered crops over traditional breeding; reviews insect control principles that are being develpoed for genetically engineered crops; and provides an overview of many new areas that wil lead to new insect control agents in the next decade.
Two types of Cassie-to-Wenzel wetting transitions on superhydrophobic surfaces during drop impact (2015)

Despite the fact that superhydrophobic surfaces possess useful and unique properties, their practical application has remained limited by durability issues. Among those, the wetting transition, whereby a surface gets impregnated by the liquid and permanently loses its superhydrophobicity, certainly constitutes the most limiting aspect under many realistic conditions. In this study, we revisit this so-called Cassie-to-Wenzel transition (CWT) under the broadly encountered situation of liquid drop impact. Using model hydrophobic micropillar surfaces of various geometrical characteristics and high speed imaging, we identify that CWT can occur through different mechanisms, and at different impact stages. At early impact stages, right after contact, CWT occurs through the well established dynamic pressure scenario of which we provide here a fully quantitative description. Comparing the critical wetting pressure of surfaces and the theoretical pressure distribution inside the liquid drop, we provide not only the CWT threshold but also the hardly reported wetted area which directly affects the surface spoiling. At a later stage, we report for the first time to our knowledge, a new CWT which occurs during the drop recoil toward bouncing. With the help of numerical simulations, we discuss the mechanism underlying this new transition and provide a simple model based on impulse conservation which successfully captures the transition threshold. By shedding light on the complex interaction between impacting water drops and surface structures, the present study will facilitate designing superhydrophobic surfaces with a desirable wetting state during drop impact.
Regulator of G protein–signaling proteins and addictive drugs (2010)

Regulator of G protein-signaling (RGS) proteins are a family of more than 30 intracellular proteins that negatively modulate intracellular signaling of receptors in the G protein-coupled receptor family. This family includes receptors for opioids, cannabinoids, and dopamine that mediate the acute effects of addictive drugs or behaviors and chronic effects leading to the development of addictive disease. Members of the RGS protein family, by negatively modulating receptor signaling, influence the intracellular processes that lead to addiction. In turn, addictive drugs control the expression levels of several RGS proteins. This review will consider the distribution and mechanisms of action of RGS proteins, particularly the R4 and R7 families that have been implicated in the actions of addictive drugs, how knowledge of these proteins is contributing to an understanding of addictive processes, and whether specific RGS proteins could provide targets for the development of medications to manage and/or treat addiction.
HANTAVIRUS PULMONARY SYNDROME IN CENTRAL BOLIVIA: RELATIONSHIPS BETWEEN RESERVOIR HOSTS, HABITATS, AND VIRAL GENOTYPES (2005)

In August 2002, two cases of hantavirus pulmonary syndrome (HPS) were confirmed in Mineros and Concepcion, within the Santa Cruz Department of Bolivia. Extensive alteration of the native ecosystem, from dense forest to pasture or sugarcane, had occurred in both regions. An ecologic assessment of reservoir species associated with the human disease identified a single hantavirus antibody-positive Oligoryzomys microtis from Mineros and three hantavirus antibody-positive Calomys callosus from Concepcion. In Mineros, the virus from the O. microtis was 90% similar to sequences published for Rio Mamore virus. Viral nucleotide sequences from two C. callosus were 87-88% similar to the sequence of Laguna Negra virus. The viral sequence from the C. callosus was 99% identical to viral sequences obtained from the HPS patient in this area, implicating C. callosus as the host and Laguna Negra virus as the agent responsible for the HPS case near Concepcion.
Multiple-beam propagation in an Anderson localized optical fiber (2013)

We investigate the simultaneous propagation of multiple beams in a disordered Anderson localized optical fiber. The profiles of each beam fall off exponentially, enabling multiple channels at high-density. We examine the influence of fiber bends on the movement of the beam positions, which we refer to as drift. We investigate the extent of the drift of localized beams induced by macro-bending and show that it is possible to design Anderson localized optical fibers that can be used for practical beam-multiplexing applications.
Investigating the Structure–Activity Relationship of 1,2,4-Triazine G-Protein-Coupled Receptor 84 (GPR84) Antagonists (2022)

G-protein-coupled receptor 84 (GPR84) is a proinflammatory orphan G-protein-coupled receptor implicated in several inflammatory and fibrotic diseases. Several agonist and antagonist ligands have been developed that target GPR84; however, a noncompetitive receptor blocker that was progressed to phase II clinical trials failed to demonstrate efficacy. New high-quality antagonists are required to investigate the pathophysiological role of GPR84 and to validate GPR84 as a therapeutic target. We previously reported the discovery of a novel triazine GPR84 competitive antagonist <b>1</b>. Here, we describe an extensive structure-activity relationship (SAR) of antagonist <b>1</b> and also present in silico docking with supporting mutagenesis studies that reveals a potential binding pose for this type of orthosteric antagonist. Lead compound <b>42</b> is a potent GPR84 antagonist with a favorable pharmacokinetic (PK) profile suitable for further drug development.
Lanthanum halide nanoparticle scintillators for nuclear radiation detection (2013)

Nanoparticles with sizes &amp;lt;10 nm were fabricated and characterized for their nanocomposite radiation detector properties. This work investigated the properties of several nanostructured radiation scintillators, in order to determine the viability of using scintillators employing nanostructured lanthanum trifluoride. Preliminary results of this investigation are consistent with the idea that these materials have an intrinsic response to nuclear radiation that may be correlated to the energy of the incident radiation.
Modulation of soleus stretch reflexes during walking in people with chronic incomplete spinal cord injury (2019)

In people with spasticity due to chronic incomplete spinal cord injury (SCI), it has been presumed that the abnormal stretch reflex activity impairs gait. However, locomotor stretch reflexes across all phases of walking have not been investigated in people with SCI. Thus, to understand modulation of stretch reflex excitability during spastic gait, we investigated soleus stretch reflexes across the entire gait cycle in nine neurologically normal participants and nine participants with spasticity due to chronic incomplete SCI (2.5-11 year post-injury). While the participant walked on the treadmill at his/her preferred speed, unexpected ankle dorsiflexion perturbations (6° at 250°/s) were imposed every 4-6 steps. The soleus H-reflex was also examined. In participants without SCI, spinal short-latency "M1", spinal medium latency "M2", and long-latency "M3" were clearly modulated throughout the step cycle; the responses were largest in the mid-stance and almost completely suppressed during the stance-swing transition and swing phases. In participants with SCI, M1 and M2 were abnormally large in the mid-late-swing phase, while M3 modulation was similar to that in participants without SCI. The H-reflex was also large in the mid-late-swing phase. Elicitation of H-reflex and stretch reflexes in the late swing often triggered clonus and affected the soleus activity in the following stance. In individuals without SCI, moderate positive correlation was found between H-reflex and stretch reflex sizes across the step cycle, whereas in participants with SCI, such correlation was weak to non-existing, suggesting that H-reflex investigation would not substitute for stretch reflex investigation in individuals after SCI.
Supplementary Table 3A-F from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib (2023)

Supplementary Table 3A-F from Genome-Wide siRNA Screen for Modulators of Cell Death Induced by Proteasome Inhibitor Bortezomib
Akt-dependent inhibition of glycogen synthase kinase 3-beta regulates viability and function of vascular endothelium in response to radiation (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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The vascular endothelium plays a critical role in the response of tumors and normal tissues to ionizing radiation. One of the main signal transduction pathways induced by radiation in endothelial cells is PI3K/Akt pathway. Since this pathway leads to the cell survival and promotes development of tumor vasculature, its inhibition enhances the cytotoxic effect of radiation in tumor vascular endothelium resulting in improved tumor control. Therefore, understanding of detailed molecular mechanism of radiation-induced activation of PI3K/Akt pathway in vascular endothelium is necessary for development of new radiosensitizing agents. Previously we have shown that phosphorylation of Akt at Ser473 in endothelium was increased within minutes of irradiation and that Akt-mediated signaling abrogated radiation-induced apoptosis. In this study we investigated radiation effect on Akt down-stream target, glycogen synthase kinase 3-beta (GSK3β). It was established that Akt negatively regulates pro-apoptotic function of GSK3β by phosphorylating GSK3β at Ser9. GSK3β was phosphorylated at Ser9 within minutes of exposure to ionizing radiation. This phosphorylation was diminished by overexpression of the nonfunctional double mutant Akt (T308A, S473A). Radiation treatment caused GSK3β translocation from membrane (active kinase) to cytoplasm (inhibited kinase). In the irradiated endothelial cells, overexpression of the nonfunctional mutant Akt or constitutively active mutant GSK3β (S9A) eliminated resistance to apoptosis leading to increased cell death, while addition of GSK3β antagonists or overexpression of mutant kinase dead GSK3β abrogated this effect. Overexpression of the nonfunctional mutant Akt demonstrated that radiation-induced Akt activation was responsible for endothelial cell migration and capillary tubule formation. In mouse angiogenesis models, microvascular response to ionizing radiation was enhanced by Akt inhibition and capillary-like tubule formation was aborted by GSK3β inhibitors. In summary, our results suggest that Akt signaling through its down-stream target GSK3β contributes to endothelial cell survival and capillary formation following ionizing radiation exposure. Therefore, GSK3β signaling pathway could present new molecular targets for the augmentation of cancer radiotherapy.
Node Numbering for Stabilizing Preconditioners Based on Incomplete LU Decomposition (2020)

Matrix-reordering strategies that reduce the occurrence of instabilities often associated with preconditioners based on incomplete LU decomposition are presented. Several example matrices, extracted from turbulent-flow simulations, and from structural mechanics, are used to demonstrate the occurrence of instabilities and to investigate the underlying cause. The current work demonstrates that appropriate schemes for reordering unknowns can provide a very effective strategy for stabilizing the preconditioner, thereby enabling a Krylov-subspace method to solve linear systems that were heretofore unsolvable. Several new numbering strate- gies are presented, one of which provides a tunable parameter to control the bandwidth of the renumbered matrix. Using the discussed methodology greatly increases the robustness and reliability of the simulations.
Comparing the Predictive Accuracy of Case Linkage Methods in Serious Sexual Assaults (2012)

Abstract The empirical support for linkage analysis is steadily increasing, but the question remains as to what method of linking is the most effective. We compared a more theory‐based, dimensional behavioural approach with a rather pragmatic, multivariate behavioural approach with regard to their accuracy in linking serial sexual assaults in a UK sample of serial sexual assaults (n = 90) and one‐off sexual assaults (n = 129). Their respective linkage accuracy was assessed by (1) using seven dimensions derived by non‐parametric Mokken scale analysis (MSA) as predictors in discriminant function analysis (DFA) and (2) 46 crime scene characteristics simultaneously in a naive Bayesian classifier (NBC). The dimensional scales predicted 28.9% of the series correctly, whereas the NBC correctly identified 34.5% of the series. However, a subsequent inclusion of non‐serial offences in the target group decreased the amount of correct links in the dimensional approach (MSA–DFA: 8.9%; NBC: 32.2%). Receiver operating characteristic analysis was used as a more objective comparison of the two methods under both conditions, confirming that each achieved good accuracies (AUCs = .74–.89), but the NBC performed significantly better than the dimensional approach. The consequences for the practical implementation in behavioural case linkage are discussed. Copyright © 2012 John Wiley &amp; Sons, Ltd.
Midterm Follow-Up of Cervical Disc Arthroplasty in Patients with Cervical Myelopathy (2015)

Introduction Cervical myelopathy secondary to cord compression may require surgical decompression with the aim of surgery being to arrest the progression of myelopathy and associated symptoms. Theoretical concerns have been raised regarding the use of cervical disc arthroplasty (CDA) in patients with myelopathy due to the fear that continued motion may cause continuing microtrauma to the cord. As such there is a paucity of reported data. We report the clinical results of anterior cervical decompression and CDA in patients with cervical myelopathy at our institution. Patients and Methods Patients who had undergone one- or two-level anterior cervical decompression and CDA for myelopathy were identified from the authors' institution's database. Prospectively collected data including neck disability index (NDI), visual analogue scale (VAS) for neck and arm pain, patient reported activity level, and hospital anxiety and depression scale were reviewed. Statistical analysis was performed for significance. Results Demographics: 40 patients. Mean age at surgery 51.3 years (range, 35–75). Operated levels, 63: 17 one- and 23 two-level procedures. Seven patients had cord compression at both levels; 21 had myelomalacia at one level and 3 at two levels. The average duration of preoperative symptoms was 37.5 months. Mean follow-up was 3.2 years (range, 1–7.4 years). Surgery: Surgery was performed using four different implants; 28 PRESTIGE LP Cervical Disc System (Medtronic, Minnesota, United States), 24 NUNEC Cervical Arthroplasty System (RTI Surgical, Inc., Florida, United States), 10 Discocerv (Scient́x-Alphatec Spine, France), and one DISCOVER Cervical Arthroplasty Disc Replacement System (DePuy Spine, Inc., Massachusetts, United States). Overall, 34 procedures were performed at C5/6, 21 at C6/7, 7 at C4/5, and 1 at C3/4. Outcomes: Mean NDI improved from 47.7 to 33.96 ( p &lt; 0.01), VAS arm 6.4 to 3.8 ( p &lt; 0.01), VAS neck 6.5 to 3.3 ( p &lt; 0.01), depression 8.9 to 7.1 ( p = 0.01), and anxiety 9.4 to 7.8 ( p = 0.06). A total of 26 patients (65%) reported same or better activity level, 27 (68%) would be satisfied with their current condition for life. A total of 29 (73%) said they would have the treatment again. Conclusion We report the clinical results of anterior cervical decompression and CDA in 40 patients with cervical myelopathy, with follow-up up to 7.4 years. Statistically significant improvements were seen in NDI and VAS scores. The level of improvement or maintenance of activity level is likely a reflection of a general patient reported activity measure being used rather than a specific myelopathy scale. We believe our results support further investigation of CDA in myelopathy.
A Hyperlinked Persistent Software Development Environment (2000)

this paper, we will present our initial ideas on the creation of an integrated environment for the development of persistent systems. Naturally, this development system will, by necessity, be resident within the total persistent environment. As such, a persistent object store provides the basis for the integrated programming environment. The result is an environment which differs significantly from those which have been developed as an adjunct to traditional programming practices in a file-based operating system. In this paper, we present our initial ideas on such an environment. In particular, we focus on potential uses for hyperlinking in the environment. 2