gebhart/patrepeval huggingface dataset:
The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic (2007)

In addition to their well-known critical role in energy metabolism, mitochondria are now recognized as the location where various catabolic and anabolic processes, calcium fluxes, various oxygen-nitrogen reactive species, and other signal transduction pathways interact to maintain cell homeostasis and to mediate cellular responses to different stimuli. It is important to consider how pharmacological agents affect mitochondrial biochemistry, not only because of toxicological concerns but also because of potential therapeutic applications. Several potential targets could be envisaged at the mitochondrial level that may underlie the toxic effects of some drugs. Recently, antiviral nucleoside analogs have displayed mitochondrial toxicity through the inhibition of DNA polymerase-gamma (pol-gamma). Other drugs that target different components of mitochondrial channels can disrupt ion homeostasis or interfere with the mitochondrial permeability transition pore. Many known inhibitors of the mitochondrial electron transfer chain act by interfering with one or more of the respiratory chain complexes. Nonsteroidal anti-inflammatory drugs (NSAIDs), for example, may behave as oxidative phosphorylation uncouplers. The mitochondrial toxicity of other drugs seems to depend on free radical production, although the mechanisms have not yet been clarified. Meanwhile, drugs targeting mitochondria have been used to treat mitochondrial dysfunctions. Importantly, drugs that target the mitochondria of cancer cells have been developed recently; such drugs can trigger apoptosis or necrosis of the cancer cells. Thus the aim of this review is to highlight the role of mitochondria in pharmacotoxicology, and to describe whenever possible the main molecular mechanisms underlying unwanted and/or therapeutic effects.
Toxin II from Anemonia sulcata-the first sequence of a coelenterate toxin. (1976)

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>
Nitric Oxide Modulates Oxygen Sensing by Hypoxia-inducible Factor 1-dependent Induction of Prolyl Hydroxylase 2 (2006)

The transcription factor complex hypoxia-inducible factor 1 (HIF-1) plays a crucial role in cellular adaptation to low oxygen availability. O(2)-dependent HIF prolyl hydroxylases (PHDs) modify HIF-1alpha, which is sent to proteasomal degradation under normoxia. Reduced activity of PHDs under hypoxia allows stabilization of HIF-1alpha and induction of HIF-1 target gene expression. Like hypoxia, nitric oxide (NO) was found to inhibit normoxic PHD activity leading to HIF-1alpha accumulation. In contrast under hypoxia, NO reduced HIF-1alpha levels due to enhanced PHD activity. Herein, we studied the role of NO in regulating PHD expression and the consequences thereof for HIF-1alpha degradation. We report a biphasic response of HIF-1alpha and PHDs to NO treatment both under normoxia and hypoxia. In the early phase, NO inhibits PHD activity that leads to HIF-1alpha accumulation, whereas in the late phase, increased PHD levels reduce HIF-1alpha. NO induces expression of PHD2 and -3 mRNA and protein under normoxia and hypoxia in a strictly HIF-1-dependent manner. NO-treated cells with elevated PHD levels displayed delayed HIF-1alpha accumulation and accelerated degradation of HIF-1alpha upon reoxygenation. Subsequent suppression of PHD2 and -3 expression using small interfering RNA revealed that PHD2 was exclusively responsible for regulating HIF-1alpha degradation under NO treatment. In conclusion, we identified the induction of PHD2 as an underlying mechanism of NO-induced degradation of HIF-1alpha.
Filtered Arc Evaporation (1993)

Arc evaporation has been extensively used in the deposition of wear resistant coatings and metallisation. The methods used to improve the quality of arc evaporated films by macroparticle filtering are reviewed. The use of passive filtering, and internal and external magnetic fields are discussed. The technique of filtering using the magnetic plasma duct is reviewed in detail with emphasis on the properties of deposited films. The filtered arc technique is seen to be a useful method for the deposition of metal, nitride, and oxide films.
Evidence for Msh2 haploinsufficiency in mice revealed by MNU-induced sister-chromatid exchange analysis (2000)

The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC, Msh2Delta7N. Chromosome aberration frequencies were similar in bone marrow of Msh2(+/+), Msh2(+/-)and Msh2(-/-)mice and no differential effects of in vivo X-irradiation were noted. By contrast, the induction of sister-chromatid exchanges (SCEs) by methyl nitrosourea (MNU) was reduced in Msh2(-/-)and Msh2(+/-)cells to approximately 20% and approximately 45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene.
Narrow-linewidth widely tunable hybrid external cavity laser using Si<sub>3</sub>N<sub>4</sub>/SiO2 microring resonators (2016)

We report on the characteristics of a tunable hybrid external cavity laser using silicon nitride microring resonators. A wavelength tuning range covering from 1530nm to 1580nm is demonstrated with a side mode suppression ratio larger than 45dB. Typical linewidth values are 65kHz.
Smart card applications in integrated transit fare, parking fee and automated toll payment systems-the MAPS concept (2002)

The concept for a multimodal access and payment system (MAPS) promising to provide a common mechanism for the payment of transit fares, parking fees, tolls and other transportation-related items is described. MAPS will focus on the use of smart card technology and smart cards interfaced to RF transponders on vehicles to relieve the traffic congestion and air pollution problems which are becoming increasingly severe in urban areas. MAPS smart cards will maintain logs of the actual transportation modes used on employee journeys to and from work. Trips made as passengers in ride share or high occupancy vehicles will also be recorded on the smart cards. These logs can be used for the purposes of measuring the effectiveness of corporate traffic congestion and air pollution mitigation programs and in certifying compliance with regulations in these areas. Profile information on primary and alternate travel itineraries and modes will be maintained in the smart cards. This information can be used in future extensions of MAPS to supply users with traffic and transit information, updated schedules and alternate routing specific to their trip.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Double MgO-based Perpendicular Magnetic-Tunnel-Junction Spin-valve Structure with a Top Co2Fe6B2 Free Layer using a Single SyAF [Co/Pt]n Layer (2018)

A new perpendicular spin-transfer-torque magnetic-tunnel-junction (p-MTJ) spin-valve was developed to achieve a high tunneling magnetoresistance (TMR) ratio. It had a double MgO-based spin-valve structure with a top Co<sub>2</sub>Fe<sub>6</sub>B<sub>2</sub> free layer and incorporated a single SyAF [Co(0.4 nm)/Pt(0.3 nm)]<sub>3</sub> layer and a new buffer layer of Co(0.6)/Pt(0.3)/Co(0.4). It had a TMR ratio of 180% and anisotropy exchange field (H <sub>ex</sub> ) of 3.44 kOe after ex-situ annealing of 350 °C for 30 min under a vacuum below 10<sup>-6</sup> torr and a perpendicular magnetic field of 3 tesla, thereby ensuring a memory margin and avoiding read disturbance failures. Its high level of performance was due to the face-center-cubic crystallinity of the MgO tunneling barrier being significantly improved by decreasing its surface roughness (i.e., peak-to-valley length of 1.4 nm).
Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex (1986)

Highly purified branched-chain 2-oxo acid dehydrogenase complex (BCOADC) oxidizes 4-methylthio-2-oxobutyrate and 2-oxobutyrate, with Km values of 67 microM and 18 microM respectively. The Vmax. for oxidation of these substrates is 27% and 53% respectively of that for 3-methyl-2-oxobutyrate. Highly purified pyruvate dehydrogenase complex (PDC) oxidizes 2-oxobutyrate (Km 100 microM; Vmax. 49% of that for pyruvate) but not 4-methylthio-2-oxobutyrate, whereas 2-oxoglutarate dehydrogenase complex will not utilize either 2-oxo acid as substrate. BCOADC kinase is inhibited by both 4-methylthio-2-oxobutyrate and 2-oxobutyrate, with half-maximal inhibition by 45 microM and 50 microM respectively. Phosphorylation of BCOADC in isolated adipocytes is inhibited by both 4-methylthio-2-oxobutyrate and 2-oxobutyrate, consistent with their inhibitory action of BCOADC kinase. Phosphorylation of PDC is decreased by 2-oxobutyrate, but not by 4-methylthio-2-oxobutyrate.
Jaudio: An Feature Extraction Library. (2005)

[TODO] Add abstract here.
Potential benefits of student- and junior doctor-led textbooks (2015)

Juniors can be a motivated, dynamic, innovative group, capable of significant contributions to the medical textbook literature. This initiative has generated a sustainable infrastructure to facilitate junior-led publishing, and has the capacity for expansion to accommodate new initiatives and ideas.
Effective Immunity to Dental Caries: Studies of Active and Passive Immunity to Streptococcus mutans in Malnourished Rats (1976)

The present studies suggest that rat dams passively transfer IgG to their offspring via milk. Furthermore, rat dams hyperimmunized to S mutans after intravenous administration of this bacterium have serum-precipitating antibody to S mutans group-specific antigen. This serum precipitin was also observed in serums of their offspring during the suckling period and was detectable for a week after weaning. When these offspring were infected with S mutans on the day of weaning, significantly fewer smooth surface lesions developed in them than in infected rats reared on nonimmunized mothers. These results suggest that anti-S mutans antibody, perhaps of the IgG2a class, is passively transferred from mother to offspring via the milk. Furthermore, this antibody is probably important in protection against S mutans infection. In this regard, recent studies by Lehner, Challacombe, and Caldwell have suggested that crevicular fluid transudating serum antibodies are important in the prevention of dental caries in rhesus monkeys. From our studies and others, it is becoming clear that at least two sources and classes of antibody are important in caries immunity. Secretory IgA, produced and secreted into saliva after local injection can be correlated with protection. At the same time, serum antibody (presumably IgG) either passively or actively derived also gives immune protection. Further studies must clarify the precise role of these Ig's and their possible synergistic activity with other specific immune factors in saliva in order to determine the mechanism(s) involved in effective caries immunity.
A randomized phase II study of perifosine (P) plus imatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST) (2009)

10563 Background: P inhibits activation of the Akt pathway which results in apoptosis and block cancer cell proliferation. Since AKT is a molecule downstream of Kit, its inhibition may overcome Kit-dependent imatinib resistance. We performed a phase II trial to assess antitumor activity of perifosine in patients with advanced GIST who were refractory to imatinib mesylate. Methods: Pts with Kit(+) advanced GIST who have PD on IM were eligible. Pts continued their current dose of IM and were randomized to one of two dosing schedules of P (Arm A: 100 mg p.o. qd x 28 + IM or Arm B: 900 mg [300 mg p.o tid] qweekly + qd IM). A Bayesian approach was utilized to assess a target response rate or 20% with an unacceptable toxicity rate of 15% or less. Response was measured at q8 wk intervals by RECIST and Choi criteria. The primary endpoint was to determine the efficacy of P with IM in pts with advanced GIST with PD while receiving IM. Results: From 8/2005 to 7/2008, 41 pts were accrued. After 1 pt exclusion and 2 cross-overs, 22 pts were in Arm A and 18 pts in Arm B. Median age was 58 (range, 32–82), 51% were male, and median ECOG PS was 1. The most common primary site of disease and metastasis was the stomach (29%) and liver (66%), respectively. KIT genotype was available for 22 pts(54%); 5(12%) WT, 13(32%) exon 11 mutations, and 4(10%) exon 9 mutations. The median number of cycles was 2 (range, 1–24). By Choi and RECIST, 30 pts(73%) and 36 pts(87%) were available for response, respectively. No CR was identified but the PR rate was 4/36 (11%) by Choi (4 PR, 9 SD) and 0/36 (0%) by RECIST (16 SD). 4/5 (80%) of pts with WT KIT appeared to benefit (Choi: 1 PR, 3 SD; RECIST: 4 SD). Median PFS and OS for 40 pts were 2.2 months and 18.3 months. No difference in PFS was noted for the 2 schedules. Toxicity was assessed in 39 pts; 46 grade 3 events and 4 grade 4 events (ALT elevation, blurred vision, fatigue, and mood alteration) were noted. The most common grade 3 event was fatigue (20%). Three pts (7%) were removed from the study for toxicity (Arm A:1 pt, Arm B:2 pts). Conclusions: The addition of P to IM has minimal activity in IM-refractory GIST although its activity in GIST with WT KIT may be further investigated. No significant financial relationships to disclose.
<title>Electromechanics of ionoelastic beams as electrically controllable artificial muscles</title> (1999)

Presented are theoretical and experimental results on electrically controlled static and dynamic flexing and deformation of iono-elastic beams made with ionic-polymer metal composite (IPMC) artificial muscles. These composite materials have the capability of large motion sensing and actuation in a biomimetic fashion. The essence of the underlying iono-elastic response of such materials is due to Coulombic electro-dynamic charge interaction amongst a dispersed phase of metallic particles that are charged either positively or negatively, mobile phase of a cation such as hydrogen ions H<SUP>+</SUP> (Protons) or Li+, Hydroxyl anions OH<SUP>-</SUP>, and a fixed anionic phase such as an assembly of sulfonates SO<SUB>3</SUB><SUP>-</SUP> elastically attached to the backbone polymer network macromolecules. The mathematical model presented is analogous to classical Euler-Bernoulli's beam theory modified to accommodate a non-homoeneous distributed electrically-induced moment due to the presence of a non-homogeneous electric field in an elastic material. The presentation may be extended to materials governed by hyper- elasticity such as in rubber elasticity. Analytical solution obtained agree reasonably well with our experimental results on Cationic Polymer-Platinum Composites (CPPC) which are also reported in this paper.
An Efficient Model for Cooperative Caching in Mobile Information Systems (2011)

Data availability in mobile information systems is lower than in traditional information systems due to its limitations of wireless communication such as low bandwidth, instability, and easy disconnection. Cooperative data caching is an attractive approach to this problem. This paper proposes an efficient approach for cooperative caching in mobile information systems. We use references to share data among client's caches. We evaluated and demonstrated the effectiveness of our approach by experiments on simulation datasets.
Absolute vs. comparative end-of-life age (1996)

Conventional insulation statistics typically use test averages of a normal, log normal, or Weibull distribution to compare the quality of different materials or constructions. None of these numbers characterizes an age at end of life with a near 100% reliability, which is necessary to predict when failure occurs. This is a major fundamental and misleading aspect in the manner in which life and age data is reported. The distributed nature of insulation aging and failure requires taking into account the length of samples to report age at end of life. This implies that probability of failure at any time should be reported as a function of cable length. Simply reporting an average probability of failure can endanger human life and have negative economic consequences. This paper shows test data and a method of calculating end of life that provides high reliability operation of aircraft wire that is aging from root-cause stresses. The authors believe this paper treats a major refinement which is essential for realistic prediction of insulation end of life, for instance in the control of reliable operation of aircraft electrical wiring. This technique is now being used in maintenance scheduling of active aircraft and is hoped to influence future revisions of standards.
Deadlock detection in distributed databases (1987)

The problem of deadlock detection in distributed systems has undergone extensive study. An important application relates to distributed database systems. A uniform model in which published algorithms can be cast is given, and the fundamental principles on which distributed deadlock detection schemes are based are presented. These principles represent mechanisms for developing distributed algorithms in general and deadlock detection schemes in particular. In addition, a hierarchy of deadlock models is presented; each model is characterized by the restrictions that are imposed upon the form resource requests can assume. The hierarchy includes the well-known models of resource and communication deadlock. Algorithms are classified according to both the underlying principles and the generality of resource requests they permit. A number of algorithms are discussed in detail, and their complexity in terms of the number of messages employed is compared. The point is made that correctness proofs for such algorithms using operational arguments are cumbersome and error prone and, therefore, that only completely formal proofs are sufficient for demonstrating correctness.
Fabrication of thick silicon dioxide layers for thermal isolation (2004)

This paper reports a method of fabricating very thick (10-100 m) silicon dioxide layers for thermal isolation without the need for very long deposition or oxidation. Deep reactive ion etching (DRIE) is used to create high-aspect-ratio trenches and silicon pillars, which are then oxidized and/or refilled with LPCVD oxide to create oxide layers as thick as the DRIE allows. Stiffeners are used to provide support for the pillars during oxidation. Thermal tests show that such thick silicon dioxide layers can effectively thermally isolate heated structures from neighboring structures within a distance of hundreds of microns. The thermal conductivity of the thick SiO 2 is measured to be 1.1 W (m K) -1 . Such SiO 2 diaphragms of thickness 50-60 m can sustain an extrinsic shear stress up to 3-5 MPa.
Elevation of lung glutathione by oral supplementation of L‐2‐oxothiazolidine‐4‐carboxylate protects against oxygen toxicity in protein‐energy malnourished rats (1992)

The objectives of this study were to investigate whether oral supplementation of L-2-oxothiazolidine-4-carboxylate (OTC) is effective for increasing tissue glutathione (GSH) concentrations in rats fed a diet very low (0.5%) in protein-a model of wasting malnutrition-and to determine the efficacy of OTC for protection against pulmonary oxygen toxicity. Weanling rats, fed a 0.5 or 15% protein diet for 2 wk, were given an oral supplement of OTC, and tissue GSH concentrations were measured over a 24 h period. OTC supplementation to rats fed 0.5% protein significantly increased GSH concentrations in liver and lung, but not in kidney and blood, when compared with the 0.5% protein unsupplemented group. The liver GSH concentration in the 0.5% protein OTC-supplemented group was higher than the 15% control group. Daily supplementation of OTC protected rats from pulmonary oxygen toxicity during 4 days of 85% oxygen exposure as determined by lung-to-body weight ratios and in vivo proton magnetic resonance imaging. Although hyperoxia exposure increased lung GSH concentrations in all groups, OTC supplementation was effective for increasing lung GSH concentration in rats fed the 0.5% protein diet. This study demonstrated that oral administration of OTC to wasting malnourished rats is an effective procedure to increase GSH concentration rapidly in target organs such as lung, and that daily supplementation of a low dose of OTC has a sustained effect to protect against pulmonary oxygen toxicity during 4 days of hyperoxia exposure.
<scp>MORPHIT</scp>: an observational study on morphine titration in the postanesthetic care unit in children (2013)

Our study of morphine titration for children shows that our protocol was effective for pain control with a significant decrease in pain scores over time. No serious complications were encountered. More studies on larger cohorts of patients are needed to confirm the efficacy and safety of this protocol.
Sevoflurane (1975)

Laboratory screening of a series of halogenated methyl isopropyl ethers revealed sevoflurane (fluoromethyl-1,1,1,3,3,3,-hexafluroro-2-propyl ether) as a potent nonexplosive inhalational anesthetic agent. Sevoflurance, a pleasant-smelling liquid, boils at 58.5 degrees C at 760 torr and has a vapor pressure of 200 torr at 25 degrees C. It is nonflammable in air and has lower flammability limits of 11 vols percent in O2 and 10 vols percent in N2O. Sevoflurane exhibits limited chemical reactivity in vitro; it is subject to slight but measurable hydrolysis, and reacts with soda lime to form traces of related ethers. It provides rapid anesthetic induction and recovery consistent with its low distribution coefficients (blood:gas, 0.6; corn oil:gas, 41.6; olive oil:gas, 53.4). In dogs, anesthetic concentrations of sevoflurane did not produce spontaneous cardiac arrhythmias and did not sensitize the heart to epinephrine. Electroencephalographic patterns were similar to those observed during anesthesia with halothane. In rats, small increases in the urinary excretion of inorganic fluoride ion occurred during the first 24 hours after anesthesia. Subacute studies in dogs and rats, using closed-circle absorption with soda lime, revealed no toxicologically significant changes in animals anesthetized frequently for 2 weeks. Sevoflurane appears to be a unique volatile anesthetic agent worthy of further study.
Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care (2017)

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET.