gebhart/patrepeval huggingface dataset:
Coexistence of myasthenia gravis and serological markers of neurological autoimmunity in neuromyelitis optica (2008)

Abstract We systematically evaluated the frequency of neurological disorders and muscle and neural autoantibodies in 177 patients with neuromyelitis optica (NMO) and in 250 control subjects (173 healthy; 77 multiple sclerosis, MS, patients). An excess of myasthenia gravis (MG, 2%), and muscle‐type acetylcholine receptor antibody (11%) was detected among NMO patients. The presence of neural or muscle autoantibodies was more common in NMO patients (34%) than in MS patients or healthy controls (7%), P &lt; 0.0001. The coexistence of NMO and MG should be considered in atypical or refractory presentations of either disorder. © 2008 Wiley Periodicals, Inc. Muscle Nerve 39: 87–90, 2009
An adaptive, non-uniform cache structure for wire-delay dominated on-chip caches (2002)

Growing wire delays will force substantive changes in the designs of large caches. Traditional cache architectures assume that each level in the cache hierarchy has a single, uniform access time. Increases in on-chip communication delays will make the hit time of large on-chip caches a function of a line's physical location within the cache. Consequently, cache access times will become a continuum of latencies rather than a single discrete latency. This non-uniformity can be exploited to provide faster access to cache lines in the portions of the cache that reside closer to the processor. In this paper, we evaluate a series of cache designs that provides fast hits to multi-megabyte cache memories. We first propose physical designs for these Non-Uniform Cache Architectures (NUCAs). We extend these physical designs with logical policies that allow important data to migrate toward the processor within the same level of the cache. We show that, for multi-megabyte level-two caches, an adaptive, dynamic NUCA design achieves 1.5 times the IPC of a Uniform Cache Architecture of any size, outperforms the best static NUCA scheme by 11%, outperforms the best three-level hierarchy--while using less silicon area--by 13%, and comes within 13% of an ideal minimal hit latency solution.
Abstract 2308: Manufacturing and characterization of KTE-C19 in a multicenter trial of subjects with refractory aggressive non-Hodgkin's lymphoma (NHL) (ZUMA-1) (2016)

Abstract Introduction: KTE-C19 is an autologous anti-CD19 CAR T cell product that is being studied in a phase 2 multicenter trial (ZUMA-1, NCT02348216). We developed a robust and efficient manufacturing process to support this trial, and compared the characteristics of the starting lymphocytes to resultant CAR T cells. Methods: After apheresis and PBMC enrichment, cells were activated with anti-CD3 antibody and cultured in serum free medium. T cells were transduced with a retroviral vector encoding the CAR gene, expanded to achieve a target dose and cryopreserved. The product CAR T cells and the starting PBMCs were evaluated by flow cytometry. Results: 7 subjects were dosed in the phase 1 portion of the trial. KTE-C19 was successfully manufactured at a dose of 2 × 106/kg (minimum 1 × 106/kg) for all subjects. All lots contained mainly CD3+ T cells (median 97%; 94-99%). While there was inter-subject variability in PBMC and CAR T cell product characteristics, the CD8/CD4 T cell ratios in PBMC and corresponding CAR product were similar (Table 1). T cells in PBMC from patients with NHL contained a majority of effector memory (36%) and effector T cells (27%), however, T cells in KTE-C19 contained a majority of central memory (37%) and effector memory (42%) CAR+ T cells. These CAR T cells were active and objective responses occurred in 5/7 patients. Conclusions: A KTE-C19 dose was successfully produced for all subjects. The optimized manufacturing process generated clinically active CAR T cells with a less differentiated phenotype than T cells in the starting PBMC population. Less differentiated cells likely confer preferred product characteristics based on preclinical studies. This manufacturing process is robust and well suited for multicenter clinical trials. Table 1.Comparative analysis of T cells from KTE-C19 and PBMC from patients with refractory aggressive NHL.IDSampleNaïve (%)Central Memory (%)Effector Memory (%)Effector (%)CD8/CD4 ratioSubject 1KTE-C1911583014.6PBMC161246272.3Subject 2KTE-C1914473540.37PBMC26303490.27Subject 3KTE-C196345642.3PBMC4536552.9Subject 4KTE-C19111552222.0PBMC1224721.8Subject 5KTE-C1915403871.0PBMC91550261.1Subject 6KTE-C1919344252.3PBMC101359192.0Subject 7KTE-C19152645140.5PBMC121336390.5Median (Range)KTE-C1913 (6-15)37 (15-58)42 (30-56)5 (1-22)1.9 (0.4-4.6)PBMC10 (1-26)13 (2-30)36 (24-59)27 (9-72)1.9 (0.3-2.9) Citation Format: Marc Better, Vijay Chiruvolu, James Oliver, Maryam Sorkhabi, Jeff S. Aycock, Emily Lowe, Edmund Chang, Arianne Perez, Lynn Navale, John M. Rossi, Adrian Bot. Manufacturing and characterization of KTE-C19 in a multicenter trial of subjects with refractory aggressive non-Hodgkin's lymphoma (NHL) (ZUMA-1). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2308.
TRPV1 Antagonists as Analgesic Agents (2013)

The last decade (2001 - 2010), declared as the Decade of Pain Control and Research by the United States Congress, brought significantly advances in our understanding of pain biology. Unfortunately, this has not translated into additional effective treatments of chronic pain conditions. Chronic pain is a debilitating and complex clinical state usually associated with diabetic neuropathy, postherpetic neuralgia, low back pathology, fibromyalgia, and neurological disorders. Standard pain drugs, even narcotic opioid analgesic agents, often provide unsatisfactory pain relief while causing important side-effect such as sedation, tolerance, dependence, respiratory depression and constipation. Furthermore, the effective management of chronic pain needs a multidisciplinary management approach and still represents one of the most urgent unmet medical need. Recently, preclinical research has uncovered new molecular mechanisms underlying the generation and transduction of pain, many of which represent new targets for innovative pharmacological interventions. This review focuses on Transient Receptor Potential (TRP) Vanilloid Type 1 (TRPV1) channel as a target for treating chronic pain. TRPV1 is a multifunctional ion channel involved in thermosensation (heat) and taste perception. Importantly, TRPV1 also functions as a molecular integrator for a broad variety of seemingly unrelated noxious stimuli. Indeed, TRPV1 is thought to be a major transducer of the thermal hyperalgesia that follows inflammation and/or tissue injury. Desensitization to topical TRPV1 agonists (e.g. capsaicin creams and patches) has been in clinical use for decades to treat chronic painful conditions like diabetic neuropathy. Most recently, a number of potent, small molecule TRPV1 antagonists have been advanced into clinical trials for pain relief. Perhaps not unexpectedly given the prominent role of TRPV1 in thermosensation, some of these antagonists showed worrisome adverse effects (hyperthermia and impaired noxious heat sensation) in humans, leading to their withdrawal from clinical trials. However, recent reports of TRPV1 antagonists that do not affect core body temperature in preclinical species suggest a potential opportunity to reduce at least this important side effect.
Slow Human Immunodeficiency Virus (HIV) Infectivity Correlated with Low HIV Coreceptor Levels (2001)

The absolute number of CD4+ lymphocytes in blood is prognostic for disease progression, yet the cell surface density of CD4 receptors or chemokine receptors on a single cell has not previously been found to be predictive of human immunodeficiency virus (HIV) infectivity outcome. It has recently been shown that human leukocyte elastase (HLE) and its ligand alpha(1) proteinase inhibitor (alpha(1)PI; alpha(1)antitrypsin) act as HIV fusion cofactors. The present study shows that decreased HIV infectivity is significantly correlated with decreased cell surface density of HLE but not with decreased CD4 nor chemokine receptors. In vitro HIV infectivity outcome in this study was predicted by the surface density of HLE on mononuclear phagocytes but not on lymphocytes. The set point HLE surface density was in part determined by alpha(1)PI. Decreased circulating alpha(1)PI was correlated with increased cell surface HLE and with increased HIV infectivity. The correlation of HIV infectivity outcome with surface HLE and circulating alpha(1)PI supports the utility of these HIV cofactors in diagnostic analysis and therapeutic intervention.
[Studies on the pharmacokinetics of qinghaosu and two of its active derivatives in dogs]. (1986)

The pharmacokinetics of Qinghaosu and two of its active derivatives was studied by means of the RIA method developed in our laberatory. Artesunate was dissolved in a mixture of 5% NaHCO_3 and 0.9% saline and injected intravenously to 2 dogs at a dose of 6 mg/kg. The serum drug concentration-time course was found to fit a one compartment model with an elimination half-life of 0.45 h as shown in figure 1. The other pharmacokinetic parameters calculated was Cl_T=0.2 L/kg·h, Vd=0.15 L/kg.Artemether, another active derivative of Qinghaosu, was dissolved in peanut oil and given intramuscularly to dogs at doses of 10 mg/kg or 30 mg/kg. The drug was found to be easily absorbed. The serum concentration-time curve is depicted in figure 2. Peak concentrations were reached at 4.0 h after injection of 10 mg/kg and at 1.9 h after a dose of 30 mg/kg with peak serum levels of 0.7 and 3.7 μg/ml, respectively. The half-lives of the elimination phases were shown to be 4.0 h at the dose of 10 mg/kg and 6.5 h at the dose of 30 mg/kg. The data of the serum concentration time course of artemether was also treated by the statistical moment method. The MRT was found to be 7.0 h at the lower dose and 9.4 h at the higher dose.Qinghaosu was ground into very fine powder in a mortar and suspended in peanut oil. The suspension was injected intramuscularly to dogs at the dose of 10 mg/kg. Figure 3 shows that the absorption of Qinghaosu was rapid with peak level of 0.2 μg/ml at 2 h after administration. The half-life of the elimination phase was found to be 1.6 h and the MRT calculated by statistical moment method was 3.3 h.No Qinghaosu was detected by the RIA method in the serum of dogs given the drug rectally or orally.
A case of Crimean-Congo haemorrhagic fever in Greece, June 2008 (2008)

A 46-year-old woman with disseminated intravascular coagulation (DIC) died in a hospital in Alexandroupoli, in north-eastern Greece, in the end of June 2008. The woman was admitted to the hospital four days earlier, with fever, malaise, myalgia, chills and abdominal pain. One day before death, her condition deteriorated rapidly and she developed heavy hemorrhage from the genital tract, DIC and multi-organ failure. The patient reported a tick bite four days before admission, and that she had tried to remove the tick herself. No travel abroad was reported. She was engaged in agricultural activities in a rural area near the town of Komotini, in Rhodope prefecture, south of the Greek-Bulgarian border.
Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group. (1989)

Peripheral blood, bone marrow films, and bone marrow biopsy specimens from 110 patients, well characterised by clinical and laboratory studies, including electron microscopy, were reviewed, to determine proposals for the classification of chronic (mature) B and T cell leukaemias. On the basis of cytology and membrane phenotype the following disorders were defined: (i) B cell type: chronic lymphocytic leukaemia (CLL); CLL of mixed cell type, which includes cases with more than 10% and less than 55% prolymphocytes (CLL/PL), and a less well defined form with pleomorphic lymphocytes but less than 10% prolymphocytes; prolymphocytic leukaemia (PLL); hairy cell leukaemia (HCL); HCL variant; splenic lymphoma with circulating villous lymphocytes; leukaemic phase of non-Hodgkin's lymphoma (follicular lymphoma, intermediate, or mantle zone lymphoma and others); lymphoplasmacytic lymphoma with peripheral blood disease (mostly Waldenström's macroglobulinaemia); and plasma cell leukaemia. (ii) T cell type: T/CLL, which was differentiated from reactive T/lymphocytosis; T/PLL; adult T cell leukaemia/lymphoma; and Sézary's syndrome. The recognition of distinct entities within the B and T cell leukaemias seems to have clinical and epidemiological connotations. It is hoped that these proposals may serve as the basis for further work, discussion, and improved management of patients.
Targeting Visceral Fat by Intraperitoneal Delivery of Novel AAV Serotype Vector Restricting Off-Target Transduction in Liver (2017)

It is challenging to genetically manipulate fat in adults. We demonstrate that intraperitoneal (i.p.) injection of an engineered adeno-associated virus (AAV) serotype Rec2 leads to high transduction of multiple visceral fat depots at a dose of 1 to 2 orders lower than commonly used doses for systemic gene delivery. To target adipose tissue, we develop a single AAV vector harboring two expression cassettes: one using the CBA promoter to drive transgene expression and one using the liver-specific albumin promoter to drive a microRNA-targeting WPRE sequence that only exists in this AAV vector. This dual-cassette vector achieves highly selective transduction of visceral fat while severely restricting off-target transduction of liver. As proof of efficacy, i.p. administration of an adipose-targeting Rec2 vector harboring the leptin gene corrects leptin deficiency, obesity, and metabolic syndromes of <i>ob</i>/<i>ob</i> mice. This study provides a powerful tool to genetically manipulate fat for basic research and gene therapies of genetic and acquired diseases.
Biodegradable Amphiphilic Copolymers Based on Poly(ϵ-caprolactone)-Graft Chondroitin Sulfate as Drug Carriers (2008)

The goal of this study was to develop a new type of core-shell micelles based on biocompatible and biodegradable amphiphilic copolymers, named PCL-CS, using chondroitin sulfate (CS) as a hydrophilic segment and poly(epsilon-caprolactone) (PCL) as a hydrophobic segment. The copolymers, prepared from the various compositions between CS and PCL, were characterized by Fourier transform infrared spectrometer, proton nuclear magnetic resonance spectrometer, and differential scanning calorimeter. The PCL-CS copolymers could be assembled into micelles using a simple emulsion. With the fluorescent probe technique, the critical micelle concentrations were obtained in the range of 1.26 x 10(-3)-8.86 x 10(-3) mg/mL. The spherical images of micelles were visualized in the presence of polyvinyl alcohol (PVA) with the use of the transmission electron microscope. The particle sizes of micelles were all smaller than 300 nm, neither aggregate nor change in hydrodynamic sizes after 15 days staying in solutions containing salts or PVA by dynamic light scattering. The intracellular uptake of KB cells incubated with PCL-CS micelles was evidenced by confocal laser scanning microscope upon loading fluorescein isothiocyanate labeled bovine serum albumin as a probe.
The Application of Flow Diagnostics for Reservoir Management (2014)

Summary Flow diagnostics, as referred to herein, are computational tools derived from controlled numerical flow experiments that yield quantitative information regarding the flow behavior of a reservoir model in settings much simpler than would be encountered in the actual field. In contrast to output from traditional reservoir simulators, flow-diagnostic measures can be obtained within seconds. The methodology can be used to evaluate, rank, and/or compare realizations or strategies, and the computational speed makes it ideal for interactive visualization output. We also consider application of flow diagnostics as proxies in optimization of reservoir-management work flows. In particular, by use of finite-volume discretizations for pressure, time of flight (TOF), and stationary tracers, we efficiently compute general Lorenz coefficients (and variants) that are shown to correlate well with simulated recovery. For efficient optimization, we develop an adjoint code for gradient computations of the considered flow-diagnostic measures. We present several numerical examples, including optimization of rates, well placements, and drilling sequences for two- and three-phase synthetic and real field models. Overall, optimizing the diagnostic measures implies substantial improvement in simulation-based objectives.
Protection against blood–brain barrier disruption in focal cerebral ischemia by the type IV phosphodiesterase inhibitor BBB022: a quantitative study (1998)

We examined the effect of BBB022, a type IV phosphodiesterase inhibitor, on blood-brain barrier (BBB) integrity after transient middle cerebral artery occlusion (MCAo) in rats. Male Sprague-Dawley rats were anesthetized with halothane and subjected to 120 min of temporary MCAo by retrograde intraluminal insertion of a nylon suture coated with poly-L-lysine. The drug (BBB022 in saline, 1 mg kg-1 h-1, i.v.) or vehicle (0.9% saline, 1-2 ml kg-1 h-1) was administered by infusion after the onset of MCAo. Four animal groups were studied: Groups A and B were treated by infusion of vehicle or drug over 5 h, and groups C and D over 48 h. Damage to the BBB was judged by extravasation of Evans blue (EB) dye, which was administered i.v. at 3 h after the onset of MCAo in groups A and B; and at 46 h in groups C and D. Fluorometric quantitation of EB was performed 1 or 2 h later in six brain regions. In the 5-h infusion series (group B), BBB022 decreased dye extravasation in the ipsilateral cortex, striatum and hemisphere (hemisphere mean+/-S.E.M. : 41.2+/-5.4 vs. 82.4+/-9.2 microg/g, p=0.005) compared to the vehicle-treated group (A). The 48-h infusion of BBB022 (group D) also decreased dye extravasation in the ipsilateral cortex (7.4+/-2. 5 vs. 29.0+/-8.3 microg/g, p=0.05), striatum (17.2+/-2.2 vs. 50. 8+/-12.1 microg/g, p=0.03) and hemisphere (30.7+/-4.0 vs. 93.2+/-18 microg/g, p=0.01) compared to the vehicle-treated group (C). BBB022 also significantly improved the neurological score at 3 and 5 h after MCAo (in the 5-h infusion group) and at 60 min, 24 h and 48 h (in the 48-h infusion group) compared to the vehicle groups. These data indicate that BBB022 prevents ischemic damage to the BBB after focal cerebral ischemia in rats.
Distributed generation islanding-implications on power system dynamic performance (2003)

Distributed generation can potentially support unintentional system islands, isolated from the remainder of the system. These islands pose a significant risk to safety and equipment, and need to be quickly detected and eliminated. Islands are detected by sensitive under- and over-voltage and frequency functions, sometimes aided by active island destabilization techniques. Both the passive voltage and frequency trip point and active destabilization measures to counter islanding, however, can also adversely impact system dynamic performance. As DG penetration grows, attention will need to be directed to the balance between the need to eliminate Islands, and the impact of measures used to detect and eliminate islands on system performance when no islanding occurs.
The evaluation of osteoporosis : dual energy x-ray absorptiometry in clinical practice (1994)

Bone mass and bone structure instruments and measurement techniques commercial instruments - evaluation and quality control fan beam geometry lumbar spine lateral spine the hip the radius absorptiometry the growing skeleton clinical applications secondary forms of osteoporosis application of dual E-ray absorptiometry to densitometry bone loss at sites of implants.
Large Microwave Birefringence Liquid-Crystal Characterization for Phase-Shifter Applications (2008)

This work is concerned with the improvement of a microwave liquid-crystal phase shifter using a large birefringence nematic liquid crystal. This material is a eutectic mixture of isothiocyanatotolane molecules. Microwave dielectric properties are reported and compared to the data obtained with the 5CB cyanobiphenyl material in the 26–40 GHz frequency range using a rectangular waveguide. The phase-shifter design consists of a central cavity, where a liquid crystal is inserted, and two coplanar strip lines accesses. Its dimensions were calculated by electromagnetic simulation, using measured dielectric permittivities of the liquid crystal. The measurements were performed with a commercial Wiltron 3680 K probe test fixture. Phase-shift variations with and without bias voltage versus frequency are presented. As expected, the large-birefringence nematic liquid crystal exhibits a higher microwave dielectric anisotropy (Δε' = 1.06 against 0.34) and the tunability of the phase shifter strongly increases (1.8 deg·cm-1·GHz-1 against 0.8 deg·cm-1·GHz-1).
Inhibition by sodium cromoglycate of bronchoconstriction stimulated by respiratory heat loss: comparison of pressurised aerosol and powder. (1984)

The protective effect was examined of three doses (2, 10, and 20 mg) of sodium cromoglycate inhaled from a pressurised metered dose inhaler on the response to isocapnic hyperventilation of cold dry air in 10 asthmatic subjects. This was compared with the effect of cromoglycate powder (20 mg) inhaled from a Spincap and with placebo given on two occasions. The medications were inhaled on separate days, in random order and with the use of a double blind double dummy technique, 20 minutes before isocapnic hyperventilation of two fold increasing volumes of air (-15 degrees C, 0% humidity) to produce a 20% fall in the post-treatment FEV1. The response was expressed as the provocative dose of respiratory heat loss required to cause a fall in FEV1 of 15% (PD15, kcal/min). The mean baseline spirometric indices exceeded 85% of predicted normal values on each test day; both placebo treatments reduced the baseline FEV1 by comparison with all active treatments (p less than 0.0001). Comparison of the PD15 on the two placebo days confirmed excellent reproducibility. All doses of cromoglycate shifted the respiratory heat loss dose-response curve to the right of the placebo curve; PD15 after all active treatments exceeded PD15 after placebo (p less than 0.0001). There was no cromoglycate dose-response relationship between the three doses of aerosol (p greater than 0.05), or between any dose of aerosol and powder (p greater than 0.05). It is concluded that cromoglycate aerosol inhaled from a pressurised inhaler in a dose of 2 mg gives the same magnitude of protection against bronchoconstriction stimulated by airway cooling as 20 mg of pressurised aerosol or powder from a Spincap.
Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder (2006)

In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.
Loss of a Chance As a Cause of Action in Medical Malpractice Cases (1994)

Judicial treatment of the relationship between causation and the relatively new theory of loss of a chance in medical malpractice cases demonstrates this welter of confusion. In 1992, the Supreme Court of Missouri addressed whether loss of chance can constitute a cause of action under Missouri law. This Note will examine the Wollen decision as well as the myriad of cases addressing loss of chance.