gebhart/patrepeval huggingface dataset:
Human extracellular recombinant phospholipase A2 induces an inflammatory response in rabbit joints (1991)

Phospholipase A2 (PLA2) enzymes hydrolyze membrane phospholipids liberating fatty acid and lysophospholipid. This event is thought to be the rate-limiting step in the generation of the lipid proinflammatory mediators, the eicosanoids and possibly platelet-activating factor. For this reason, extracellular forms of PLA2 have been postulated to be a component of the inflammatory cascade in certain biologic settings. In the synovial fluid of patients with inflammatory arthritides, substantial amounts of PLA2 activity have been found, and subsequently, one enzyme was purified, cloned, and expressed. Here we show that the pure recombinant enzyme free of any proinflammatory contaminants elicits a dramatic inflammatory, arthritogenic response when injected into the joint space of healthy rabbits. Within 24 h, extensive leukocyte infiltration and hyperplasia of the synovial lining cells were observed, and prostaglandin production in the joint space increased. In comparison, pancreatic PLA2(2) had little activity in this system, whereas a very inflammatory cobra venom enzyme was intermediate in its effects. In view of the presence of the enzyme in inflamed joints, the fact that its synthesis and secretion can be induced by proinflammatory cytokines and its proinflammatory biologic activity, we suggest that synovial PLA2 plays an exacerbating role in acute episodes in chronic inflammatory conditions such as rheumatoid arthritis.
Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration (2006)

Null mutations in the progranulin gene (PGRN) were recently reported to cause tau-negative frontotemporal dementia linked to chromosome 17. We assessed the genetic contribution of PGRN mutations in an extended population of patients with frontotemporal lobar degeneration (FTLD) (N=378). Mutations were identified in 10% of the total FTLD population and 23% of patients with a positive family history. This mutation frequency dropped to 5% when analysis was restricted to an unbiased FTLD subpopulation (N=167) derived from patients referred to Alzheimer's Disease Research Centers (ADRC). Among the ADRC patients, PGRN mutations were equally frequent as mutations in the tau gene (MAPT). We identified 23 different pathogenic PGRN mutations, including a total of 21 nonsense, frameshift and splice-site mutations that cause premature termination of the coding sequence and degradation of the mutant RNA by nonsense-mediated decay. We also observed an unusual splice-site mutation in the exon 1 5' splice site, which leads to loss of the Kozac sequence, and a missense mutation in the hydrophobic core of the PGRN signal peptide. Both mutations revealed novel mechanisms that result in loss of functional PGRN. One mutation, c.1477C>T (p.Arg493X), was detected in eight independently ascertained familial FTLD patients who were shown to share a common extended haplotype over the PGRN genomic region. Clinical examination of patients with PGRN mutations revealed highly variable onset ages with language dysfunction as a common presenting symptom. Neuropathological examination showed FTLD with ubiquitin-positive cytoplasmic and intranuclear inclusions in all PGRN mutation carriers.
Porous scaffolds of gelatin–hydroxyapatite nanocomposites obtained by biomimetic approach: Characterization and antibiotic drug release (2005)

Gelatin-hydroxyapatite (HA) nanocomposite porous scaffolds were fabricated biomimetically, and their feasibility as a drug-delivery carrier for tissue-regeneration and wound-healing treatments was addressed. The composite sols were prepared by the precipitation of HA up to 30 wt % within a gelatin solution with the use of calcium and phosphate precursors, and the porous scaffold was obtained by casting the sols and further freeze drying. The obtained bodies were crosslinked with carbodiimide derivatives to retain chemical and thermal integrity. The apatite precipitates were observed to be a poorly crystallized carbonate-substituted HA. The nanocomposite scaffolds had porosities of approximately 89-92% and exhibited a bimodal pore distribution, that is, the macropores (approximately 300-500 microm) of the framework structure, and micropores (approximately 0.5-1 microm) formed on the framework surface. Transmission electron microscopy (TEM) observation revealed the precipitation of highly elongated HA nanocrystals on the gelatin network. The well-developed porous structure and organized nanocomposite configurations were in marked contrast to the directly mixed gelatin-HA powder conventional composites. For drug-release tests, tetracycline, an antibiotic drug, was entrapped within the scaffold, and the drug-release profile was examined with processing parameters, such as HA amount in gelatin, crosslinking degree, and initial drug addition. The drug entrapment decreased with increasing HA amount, but increased with increasing crosslinking degree and initial drug addition. The crosslinking of the gelatin was the prerequisite to sustaining and controlling the drug releases. Compared to pure gelatin, the gelatin-HA nanocomposites had lower drug releases, because of their lower water uptake and degradation. All the nanocomposite scaffolds released drugs in proportion to the initial drug addition, suggesting their capacity to deliver drugs in a controlled manner. Based on the findings of the well-developed morphological feature and controlled drug-release profile, the gelatin-HA nanocomposite porous scaffolds are suggested to be potentially useful for hard-tissue regeneration.
Prostate cancer, prostate-specific antigen, and the polymerase chain reaction (1995)

Journal Article Prostate cancer, prostate-specific antigen, and the polymerase chain reaction Get access E P Diamandis E P Diamandis Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 41, Issue 2, 1 February 1995, Pages 177–179, https://doi.org/10.1093/clinchem/41.2.177 Published: 01 February 1995
Cache Coherence in Distributed Systems (Thesis) (1986)

members of the "systems group" I the Ami's crowd, the staff at the East Coast 6-Day Advanced Course, and many others to whom I apologize for the lack of space and my momentary lapse of memory.Each contributed something tangible, valuable, and irreplaceable to my path through
Synthesis of hazard-free multi-level logic under multiple-input changes from binary decision diagrams (1994)

We describe a new method for directly synthesizing a hazard-free multilevel logic implementation from a given logic specification. The method is based on free/ordered Binary Decision Diagrams (BDD's), and is naturally applicable to multiple-output logic functions. Given an incompletely-specified (multiple-output) Boolean function, the method produces a multilevel logic network that is hazard-free for a specified set of multiple-input changes. We assume an arbitrary (unbounded) gate and wire delay model under a pure delay (PD) assumption, we permit multiple-input changes, and we consider both static and dynamic hazards. This problem is generally regarded as a difficult problem and it has important applications in the field of asynchronous design. The method has been automated and applied to a number of examples. The results we have obtained are very promising.
Platelet Release Reaction During Clotting of Native Human Platelet-Rich Plasma (1972)

SummaryDuring clotting of PRP, 20 to 80% of the platelet serotonin, adenine nucleotides, βN-acetyl-glucosaminidase, β-glucuronidase, and β-galactosidase were released to serum in a soluble form. Other enzymes, such as lactate dehydrogenase, pyruvate kinase, and hexokinase were retained. Small amounts of acid phosphatase were lost from the platelets in a particulate form. These results agreed well with those obtained previously on the action of thrombin on washed platelets. It is concluded that, during clotting, platelets do not lyse initially, but release only those substances stored in intracellular granules, a process previously described as the platelet release reaction.
Acylcarnitines in amniotic fluid: Application to the prenatal diagnosis of propionic acidaemia (1993)

Acylcarnitines were assayed in amniotic fluid by isotope dilution tandem mass spectrometry. Control values for propionylcarnitine, C4 and C5 acylcarnitines were established. Propionylcarnitine was elevated by a factor of 5 relative to controls in the amniotic fluid of three pregnancies affected with propionic acidaemia. This may provide a convenient new method for prenatal diagnosis of propionic acidaemia. One pregnancy at risk for propionic acidaemia but unaffected according to methylcitrate analysis had an intermediate level of propionylcarnitine, indicating the need for further studies to determine the range of concentration in probable heterozygotes.
Purification and Characterization of a Reduced Nicotinamide Adenine Dinucleotide Phosphate-linked Aldehyde Reductase from Brain (1970)

The presence of a nonspecific NADPH-linked aldehyde reductase (alcohol: NADP oxidoreductase, EC 1.1.1.2) was observed in various areas of bovine brain in vitro.In the midbrain, hypothalamus, and pons, the rate of NADPH oxidation, with p-nitrobenzaldehyde as substrate, was approximately 4.0 nmoles per min per mg of protein; but somewhat lower values were obtained when other regions of the brain were studied.It was found that the enzyme was localized primarily in the soluble supernatant fraction of rat brain homogenates.The enzyme from bovine brain was purified approximately 120-fold and was found to catalyze the reduction of a number of aldehydes, including substituted benzaldehydes, substituted phenylacetaldehydes, and some long chain aliphatic aldehydes.Short chain aliphatic aldehydes such as acetaldehyde or propionaldehyde were not reduced by the enzyme.With p-nitrobenzaldehyde as substrate, NADPH, but not NADH, was oxidized by bovine brain aldehyde reductase.The pH optimum for the enzyme was found to be 6.75 for aldehyde reduction, whereas the rate of oxidation of p-hydroxyphenylethanol, with NADP as cosubstrate, was optimal at pH 9.7.K, values for various substrates ranged from 3.7 X 1OV M to 1.4 X 1O-4 M. K, values for various substituted benzaldehydes were correlated with the electropositive nature of the carbonyl carbon atom by the Hammet a-p relationship.Oxidation of NADPH by the partially purified enzyme was inhibited approximately 50% by 0.1 mM concentrations of amytal, phenobarbital, or chlorpromazine.The enzyme activity was not altered, however, by 10 mM pyrazole. Bernheim(I), Blashko, Richter, and Schlossman (a), and Blashko (3) proposed that aldehydes were formed as intermediaates of biogenic amine metabolism.
<sup>13</sup>C-NMR Sequence Analysis. 23. Synthesis and NMR Spectroscopic Characterization of Polyoxamides with Alternating and Random Sequences of Aliphatic Diamines (1984)

Abstract Three classes of polyoxamides were prepared: homopolymers derived from α-, ω-diaminoalkanes, and 4,4′-diaminodiphenyl-methane, copolymers with an alternating sequence of two different aliphatic diamines and copolymers with a random sequence of two different diamines. For their syntheses a new class of monomers, the diamine bisoxamide diethyl esters, were prepared from α,ω-diamines and oxalic acid chloride ethyl ester. The 22.63 MHz 13C-NMR spectra of the polyoxamide solution in fluorosulfonic acid permitted sequence analysis because the carbonyl signals are sensitive to the nature of the neighboring diamine units. In contrast, 9.12 MHz 15N-NMR spectra did not give any sequence information. The thermal stability of the polyoxamides was investigated, but differential scanning calorimetry did not give useful information on the crystallinity of the polyoxamides because of their thermal degradation.
Silent Cerebral Microbleeds on T2*-Weighted MRI (2002)

The findings suggest that microbleeds on T2*-weighted MRI are an indicator of advanced small artery disease of the brain with an increased risk for bleeding. This result should be taken into consideration when treating patients with stroke, and further studies are required.
An Update on Canine Adenovirus Type 2 and Its Vectors (2010)

Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd) have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2) biology and gives an overview of the generation of early region 1 (E1)-deleted to helper-dependent (HD) CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors.
Safety and antitumor activity of chimeric antigen receptor modified T cells in patients with chemotherapy refractory metastatic pancreatic cancer. (2015)

3007 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive microenvironment with a scarcity of effector T cells. Adoptive T cell therapy to restore anti-tumor immunity has demonstrated promise in several advanced malignancies. However, its role in PDAC remains to be established. This Phase I study was performed to determine the safety and feasibility of administering autologous T cells genetically modified with a chimeric antigen receptor (CAR) that recognizes mesothelin overexpressed on PDAC. Methods: Patients (ECOG 0-1; adequate organ function) with chemotherapy refractory metastatic PDAC ( > 1 prior chemotherapy) were treated with autologous T cells engineered using in vitro transcribed mRNA to transiently express a mesothelin-specific CAR that includes both CD3-zeta and 4-1BB co-stimulatory domains. CAR T cells were infused 3 times per week for 3 weeks. The primary endpoint was to determine safety and manufacturing feasibility. Secondary endpoints were to measure clinical and immune responses. Results: 10 patients were enrolled (6 treated, 2 withdrew due to progressive disease prior to treatment, 1 manufacturing failure, 1 did not complete apheresis necessary for manufacturing). 53 of 54 (98%) planned CAR T cell infusions were administered without dose limiting toxicity. Infusions were well tolerated without evidence of cytokine release syndrome, pleuro-pericarditis or peritonitis. Treatment-related grade > 3 toxicities included abdominal pain (1) and back pain (1). CAR T cells were transiently detected in the peripheral blood after infusion. Two of six patients experienced stable disease by RECIST 1.1 with disease control off therapy seen in one patient for > 4 months. The change in SUVmax of all lesions for each patient detected on 18FDG-PET/CT imaging performed before and 1 month after beginning treatment was -1.9% (95% CI: -25.5% to 21.7%). In one patient, abnormal 18FDG avidity seen in liver metastases at baseline was no longer detected at 1 month after therapy. Conclusions: Mesothelin-redirected CAR T cell therapy is well tolerated and shows preliminary evidence of antitumor efficacy in PDAC. Clinical trial information: NCT01897415.
Adjunctive Use of Tafluprost with Timolol Provides Additive Effects for Reduction of Intraocular Pressure in Patients with Glaucoma (2009)

As adjunctive therapy to timolol, tafluprost achieved a consistently greater reduction in IOP compared with vehicle, and was well tolerated.
Suppression of serum tumour necrosis factor-alpha by thalidomide does not lead to reversal of tumour vascular collapse and anti-tumour activity of 5,6-dimethylxanthenone-4-acetic acid. (1999)

The antitumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA), developed in this laboratory as a potent analogue of flavone acetic acid (FAA), has a novel antitumour action involving both immune and vascular components. DMXAA induces the synthesis of tumour necrossi factor-alpha (TNF) and it has been hypothesised that this mediates its selective reduction of tumour blood flow and consequent induction of tumour necrosis. Unexpectedly, the drug thalidomide, while reducing the serum TNF response to DMXAA, potentiates its antitumour effect. We have investigated this in the MDAH-MCa-4 mammary carcinoma model, comparing it to previous data with the Colon 38 adenocarcinoma. We have related DMXAA-induced blood flow changes in the MCa-4 tumour to tumour growth delay, serum TNF and extractable TNF from tumour tissue. We have also compared the effect of thalidomide (387 mumol/kg) on DMXAA (80 mumol/kg) with that of a monoclonal anti-TNF antibody (50 micrograms/mouse). We find that tumour blood flow reduction is strongly correlated with tumour growth delay. Coadministration of anti-TNF antibody abolishes serum TNF levels and slightly reduces the antitumour effects of DMXAA. While tumour growth delay is not correlated with serum induced TNF levels, it is related to tumour TNF levels. We conclude that while the data are consistent with TNF being the principal mediator of the action of DMXAA, serum TNF levels do not reflect the antitumour response.
Serum interleukin‐6 levels reflect the disease status of colorectal cancer (2003)

Serum IL-6 levels correlated with disease status of colorectal cancer but could not be regarded as an independent predictor for prognosis.
Proteomic Profiling Identifies Afamin as a Potential Biomarker for Ovarian Cancer (2007)

Afamin shows potential complementarity with CA-125 in longitudinal monitoring of patients with ovarian cancer, justifying prospective larger-scale investigation. Changes in specific isoforms may provide further information.
Macroscopic Interferometry: Rethinking Depth Estimation with Frequency-Domain Time-of-Flight (2016)

A form of meter-scale, macroscopic interferometry is proposed using conventional time-of-flight (ToF) sensors. Today, ToF sensors use phase-based sampling, where the phase delay between emitted and received, high-frequency signals encodes distance. This paper examines an alternative ToF architecture, inspired by micron-scale, microscopic interferometry, that relies only on frequency sampling: we refer to our proposed macroscopic technique as Frequency-Domain Time of Flight (FD-ToF). The proposed architecture offers several benefits over existing phase ToF systems, such as robustness to phase wrapping and implicit resolution of multi-path interference, all while capturing the same number of subframes. A prototype camera is constructed to demonstrate macroscopic interferometry at meter scale.
White Matter Lesions Are Associated With Progression of Medial Temporal Lobe Atrophy in Alzheimer Disease (2006)

Our findings suggest that the presence and the progression of WML are associated with progression of MTA in AD. WML may be a predictor of the course of the disease and a potential treatment target in AD.
Kinematic Inversion of Robotic Manipulators in the Presence of Redundancies (1989)

A general algorithm for the solution of the inverse kinematic problem of robotic manipulators in the presence of redundan cies is presented in this article. Redundancies are handled using a constrained nonlinear least-square minimization approach in which a positive definite performance index is minimized subject to the associated kinematic closure equa tions. The arising nonlinear problem is solved as a sequence of linear quadratic programs. The algorithm is aimed at providing an efficient and general solution that avoids the production of undesirable effects such as non-conservative joint motions. Numerical stability of the procedure is en hanced by use of the Newton-Gauss method. Examples are given using the six-axis PUMA and seven-axis CYBOTECH P-15, each performing a task for which five degrees of free dom are required to orient and position an axially-symmetric peg through a continuous path.
A lidocaine-prilocaine cream for superficial skin surgery and painful lesions (1980)

A eutectic mixture of lidocaine and prilocaine in a water emulsion cream base produces effective superficial dermal analgesia when applied under occlusive dressing for 60 minutes. On the genitals, lips and oral mucosa, the application time can be reduced. The cream was found to be an effective alternative to conventional infiltration anesthesia for dermabrasion and superficial surgical procedures. It is especially useful in children for the removal of molluscum contagiosum and prior to venepuncture. The preparation is also an effective pain reliever when used on certain ulcerations.
Computational paradigms using oscillatory networks based on state-transition devices (2017)

In this paper we review recent work on computational paradigms involving coupled relaxation oscillators built using metal-insulator-transition (MIT) devices. Such oscillators made using MIT devices based on Vanadium-Dioxide thin films are very compact and can be realized in hardware. Networks of such oscillators have interesting phase and frequency dynamics which can be programmed to solve computationally hard problems.
Optimizing Volumetric Sweep Efficiency in Waterfloods by Integrating Streamlines, Design of Experiments, and Hydrocarbon F-F Curves (2010)

Abstract Waterflooding is by far the most commonly used method to improve oil recovery. Success of a waterflood depends on its ability to sweep remaining oil efficiently. Incorrect or insufficient design may lead to increases in cost associated with water cycling and poor sweep. Most waterflood management is restricted to classical methods (e.g., surveillance or pattern balancing) or sensitivity studies centered on finite difference simulation. Most of the time, conventional methods fail to account for subsurface heterogeneity, while optimizing sweep via conventional modeling is time consuming in waterfloods with large number of wells or a relatively high-resolution numerical grid. We propose a practical and efficient approach for rapid and full-field optimization of waterfloods. Our method focuses on optimizing volumetric sweep efficiency using streamlines. We introduce two new concepts: the Hydrocarbon F-Φ Curve and Hydrocarbon Lorenz Coefficient (LC-HC). We show that these concepts can be easily derived from streamline simulation and can be used for optimum waterflood management. The LC-HC serves as a unique measure of the flow – or dynamic – heterogeneity, and we show that minimizing LC-HC results in optimal volumetric sweep efficiency. The method is straightforward: we evaluate the sensitivity of LC-HC to variations in operating conditions in a design of experiment (DoE) study, describe the LC-HC as a function of those operating conditions using response surface methods, then select the operating conditions that minimize LC-HC (maximize sweep efficiency). The main advantages of our method are its speed, flexibility to start optimizing at any arbitrary time regardless of the history, and ability to handle large problems. The new approach requires running a streamline simulator only a few time steps, so multi-million cell models are optimized in minutes. We verified our approach with several synthetic examples. An example shows that a 100,000 cell, complex reservoir with 13 wells, and 29 completions can be optimized in less than 4 hours, leading to significant increase in recovery efficiency and reduced water cycling. We then apply the method to a model of the Brugge field, the SPE comparative problem on recovery optimization. Improved production response illustrates the power of the new method.