gebhart/patrepeval huggingface dataset:
Mutation of the Highly Conserved Tryptophan in the Serpin Breach Region Alters the Inhibitory Mechanism of Plasminogen Activator Inhibitor-1 (2003)

We have demonstrated that interactions within the conserved serpin breach region play a direct role in the critical step of the serpin reaction in which the acyl-enzyme intermediate must first be exposed to hydrolyzing water and aqueous deacylation. Substitution of the breach tryptophan in PAI-1 (Trp175), a residue found in virtually all known serpins, with phenylalanine altered the kinetics of the reaction mechanism and impeded the ability of PAI-1 to spontaneously become latent without compromising the inherent rate of cleaved loop insertion or partitioning between the final inhibited serpin-proteinase complex and hydrolyzed serpin. Kinetic dissection of the PAI-1 inhibitory mechanism using multiple target proteinases made possible the identification of a single rate-limiting intermediate step coupled to the molecular interactions within the breach region. This step involves the initial insertion of the proximal reactive center loop hinge residue(s) into beta-sheet A and facilitates translocation of the distal P'-side of the cleaved reactive center loop from the substrate cleft of the proteinase. Substitution of the tryptophan residue raised the kinetic barrier restricting the initial loop insertion event, significantly retarding the rate-limiting step in tPA reactions in which strong exosite interactions must be overcome for the reaction to proceed.
The Tissue Factor Region That Interacts with Substrates Factor IX and Factor X (2000)

The enzymatic activity of coagulation factor VIIa is controlled by its cellular cofactor tissue factor (TF). TF binds factor VIIa with high affinity and, in addition, participates in substrate interaction through its C-terminal fibronectin type III domain. We analyzed surface-exposed residues in the C-terminal TF domain to more fully determine the area on TF important for substrate activation. Soluble TF (sTF) mutants were expressed in E. coli, and their ability to support factor VIIa-dependent substrate activation was measured in the presence of phospholipid vesicles or SW-13 cell membranes. The results showed that factor IX and factor X interacted with the same TF region located proximal to the putative phospholipid surface. According to the degree of activity loss of the sTF mutants, this TF region can be divided into a main region (residues Tyr157, Lys159, Ser163, Gly164, Lys165, Lys166, Tyr185) forming a solvent-exposed patch of 488 A(2) and an extended region which comprises an additional 7-8 residues, including the distally positioned Asn199, Arg200, and Asp204. Some of the identified TF residues, such as Trp158 and those within the loop Lys159-Lys165, are near the factor VIIa gamma-carboxyglutamic acid (Gla) domain, suggesting that the factor VIIa Gla-domain may also participate in substrate interaction. Moreover, the surface identified as important for substrate interaction carries a net positive charge, suggesting that charge interactions may significantly contribute to TF-substrate binding. The calculated surface-exposed area of this substrate interaction region is about 1100 A(2), which is approximately half the size of the TF area that is in contact with factor VIIa. Therefore, a substantial portion of the TF surface (3000 A(2)) is engaged in protein-protein interactions during substrate catalysis.
Effectiveness of commercially-available antibiotic-impregnated implants (2006)

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them.
Modulus and Damping of Soils by the Resonant-Column Method (1978)

The resonant-column method, a relatively nondestructive test employing wave propagation in cylindrical specimens, is used to obtain modulus and damping of soils as functions of vibratory strain amplitude and other factors such as ambient confining stress and void ratio. Descriptions of the apparatus, calibration procedures, testing procedures, and aids for data reduction are given for apparatus which propagate either rod compression waves or shear waves or both. Data reduction aids include graphs for a wide range of apparatus conditions and include a computer program that covers all admissable boundary conditions.
Adrenergic lipolysis in guinea pig is not a beta 3-adrenergic response: comparison with human adipocytes (1994)

beta 3-Adrenoceptor agonists are potent lipolytic activators in rats, but they are only weak stimulators in human adipocytes, indicating interspecies differences in the adrenergic regulation of lipid mobilization. Like human but not rat adipocytes, guinea pig fat cells were poorly responsive to the beta 3-agonists BRL-37344, CGP-12177, SR-58611, and ICI-215001, acid metabolite of ICI-D7114. In guinea pigs, the beta 1-agonist dobutamine was more lipolytic than the beta 2-agonist procaterol. Anatomic location of fat deposits was without major influence on the beta-adrenergic responsiveness. Weak responses to beta 3-agonists were found whatever the sex or the age (from 2 days to 16 mo) of the animals. Even in the interscapular brown adipose tissue, which is well known in rats for its beta 3-adrenergic responsiveness, a blunted response to BRL-37344 was observed. The alpha 2-adrenergic antilipolytic effect and receptor number were smaller in guinea pig than in human adipocytes, but the beta-adrenergic receptor number was similar in the two species. Thus guinea pig adipocytes resemble human fat cells when their weak beta 3-adrenergic responsiveness is considered.
High frequency of clonal chromosome abnormalities in prostatic neoplasms sampled by prostatectomy or ultrasound‐guided needle biopsy (2000)

Cancer of the prostate remains poorly characterized cytogenetically. This is due in part to methodological problems and in part to the paucity of radical prostatectomies, until now the main source of material for cytogenetic analyses. We have improved existing techniques for the culturing of prostatic neoplasms removed by radical prostatectomy or sampled by ultrasound-guided needle biopsy. Successful short-term cultures were obtained from all 10 prostatectomy samples and from all 10 ultrasound-guided needle biopsies, always with a pure epithelial morphology. Of the 19 cases yielding a sufficient number of high-quality metaphases for chromosome banding analysis, the single atypical epithelial hyperplasia had a normal karyotype, whereas both prostatic intraepithelial neoplasias and 12 of 16 (75%) invasive carcinomas were shown to have clonal abnormalities. Ten of the 12 (83%) karyotypically abnormal invasive carcinomas presented structural chromosomal rearrangements. A recurrent deletion, del(10)(p13), was seen in three tumors; in one of them the terminal nature of the deletion was confirmed by two-color FISH. A del(17)(p11) was seen in one PIN lesion, but since the analysis of exons 4–8 of the TP53 tumor suppressor gene revealed no mutations, there probably was no inactivation of the second TP53 allele. Our study thus leads to the following main conclusions. First, better culturing methods allow the detection of abnormal karyotypes in a much higher percentage of prostatic neoplasms than has hitherto been possible. Second, ultrasound-guided needle biopsies of prostatic neoplasms are a sufficient source of material for cytogenetic analysis. Third, a terminal deletion of the short arm of chromosome 10, del(10)(p13), seems to identify a subgroup of prostatic cancer. Genes Chromosomes Cancer 28:211–219, 2000. © 2000 Wiley-Liss, Inc.
Role of Kynurenines in the Central and Peripherial Nervous Systems (2005)

Kynurenine (KYN) is an intermediate in the pathway of the metabolism of tryptophan to nicotinic acid. KYN is formed in the mammalian brain (40%) and is taken up from the periphery (60%), indicating that it can be transported across the blood-brain barrier (BBB). In the brain, KYN can be converted to two other components of the pathway: the neurotoxic quinolinic acid (QUIN) and the neuroprotective kynurenic acid (KYNA). QUIN is probably the most widely studied metabolite of KYN, because it may cause excitotoxic neuronal cell loss and convulsions by interacting with the N-methyl-D-aspartate (NMDA) receptor complex, a type of glutamate receptor. KYNA is another metabolite of KYN; its synthesis is catalysed by KYN aminotransferases. This is the only known endogenous NMDA receptor inhibitor, which can act at the glycine site on the receptor complex. Furthermore, KYNA non-competitively inhibits alpha7 nicotinic acetylcholine presynaptic receptors (nAChRs), inhibiting glutamate release, and regulates the expression of alpha4beta2 nAChR. It is well-known that the activation of excitatory amino acid (EAA) receptors can play a role in a number of neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease, stroke and epilepsy. Various studies have been made of whether the EAA receptor antagonist KYNA can exert a therapeutic effect in these neurological disorders. It has been established that KYNA has only a very limited ability to cross the BBB. Other KYNA derivatives have been synthesised (e.g. glucosamine-KYNA, 4-chloro-KYNA and 7-chloro-KYNA), which are well transported across the BBB and act on the glutamate receptors. Moreover, it has been demonstrated that probenecid, a known inhibitor of the transport of organic acids (e.g. KYNA), increases the cerebral concentration of KYNA. There is another new perspective to the maintenance of a high level of KYNA in the brain: the use of enzyme inhibitors, which can block the synthesis of the neurotoxic QUIN. These are some of the most promising possibilities as novel therapeutic strategies for the treatment of neurodegenerative diseases, in which the hyperactivation of amino acid receptors could be involved. The presence and importance of KYN derivatives in the periphery are also discussed in the light of recent publications.
Electronic design of a multichannel programmable implant for neuromuscular electrical stimulation (1999)

An advanced stimulator for neuromuscular stimulation of spinal cord injured patients has been developed. The stimulator is externally controlled and powered by a single encoded radio frequency carrier and has four independently controlled bipolar stimulation channels. It offers a wide range of reprogrammability and flexibility, and can be used in many neuromuscular electrical stimulation applications. The implant system is adaptable to patient's needs and to future developments in stimulation algorithms by reprogramming the stimulator. The stimulator is capable of generating a wide range of stimulation waveforms and stimulation patterns and therefore is very suitable for selective nerve stimulation techniques. The reliability of the implant has been increased by using a forward error detection and correction communication protocol and by designing the chip for structural testability based on scan test approach. Implemented testability scheme makes it possible to verify the complete functionality of the implant before and after implantation. The stimulators architecture is designed to be modular and therefore its different blocks can be reused as standard building blocks in the design and implementation of other neuromuscular prostheses. Design for low-power techniques have also been employed to reduce power consumption of the electronic circuitry.
α‐Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes (2004)

Cone snails comprise approximately 500 species of venomous molluscs, which have evolved the ability to generate multiple toxins with varied and often exquisite selectivity. One class, the alpha-conotoxins, is proving to be a powerful tool for the differentiation of nicotinic acetylcholine receptors (nAChRs). These comprise a large family of complex subtypes, whose significance in physiological functions and pathological conditions is increasingly becoming apparent. After a short introduction into the structure and diversity of nAChRs, this overview summarizes the identification and characterization of alpha-conotoxins with selectivity for neuronal nAChR subtypes and provides examples of their use in defining the compositions and function of neuronal nAChR subtypes in native vertebrate tissues.
Planar micro-optic solar concentrator (2010)

We present a new approach to solar concentration where sunlight collected by each lens in a two-dimensional lens array is coupled into a shared, planar waveguide using localized features placed at each lens focus. This geometry yields a thin, flat profile for moderate concentration systems which may be fabricated by low-cost roll manufacture. We provide analyses of tradeoffs and show optimized designs can achieve 90% and 82% optical efficiency at 73x and 300x concentration, respectively. Finally, we present preliminary experimental results of a concentrator using self-aligned reflective coupling features fabricated by exposing molded SU-8 features through the lens array.
Bagging, boosting, and C4.S (1996)

Breiman's bagging and Freund and Schapire's boosting are recent methods for improving the predictive power of classifier learning systems. Both form a set of classifiers that are combined by voting, bagging by generating replicated bootstrap samples of the data, and boosting by adjusting the weights of training instances. This paper reports results of applying both techniques to a system that learns decision trees and testing on a representative collection of datasets. While both approaches substantially improve predictive accuracy, boosting shows the greater benefit. On the other hand, boosting also produces severe degradation on some datasets. A small change to the way that boosting combines the votes of learned classifiers reduces this downside and also leads to slightly better results on most of the datasets considered.
Microglial secreted cathepsin B induces neuronal apoptosis (2001)

Activated microglia release a number of substances that can influence neuronal signalling and survival. Here we report that microglia stimulated with the peptide chromogranin A (CGA), secreted the cysteine protease, cathepsin B. Conditioned medium from CGA exposed microglia was neurotoxic to the HT22 hippocampal cell line and to primary cultures of cerebellar granule neurones. In both neuronal cell types, the neurotoxicity could be significantly attenuated with z-FA-fmk or by depletion of microglial conditioned medium with cathepsin B antibody. Conditioned medium from activated microglia or cathepsin B alone induced neuronal apoptosis and caspase 3 activation. Our data indicate that CGA-activated microglia can trigger neuronal apoptosis and that this may be mediated through the secretion of cathepsin B. Since cathepsins may also play a role in the amyloidogenic processing of amyloid precursor protein, these results may have significance for tissue damage and neuronal loss in the neuropathology of Alzheimer's disease.
Surface‐Modified Upconverting Microparticles and Nanoparticles for Use in Click Chemistries (2010)

A method is described for modifying the surface of upconverting microparticles (UCmuPs) and nanoparticles (UCNPs) such that they become amenable to click chemistry. Respective reagents are presented and used in both kinds of particles, either directly or in combination with tetraethoxysilane. The particles also were labeled by using the click reaction, a) with fluorophores to yield materials that have emission colors that depend on the wavelength of excitation; b) with maleinimido groups (so to obtain labels for thiols), and c) with biotin (to make them useful for affinity studies based on the biotin-streptavidin system). We believe that both the UCmuPs and UCNPs have the potential of being used in numerous areas including upconversion imaging, biolabeling, and derivatization, but also in encoding and security.
Reduction of rat myocardial ischemia and reperfusion injury by sialyl Lewis x oligosaccharide and anti-rat P-selectin antibodies (1996)

Polymorphonuclear leukocytes (PMN) are directly involved in development of ischemic myocardial injury. Adhesion of PMN to endothelial cells is an initial step that triggers a sequential process leading to acute inflammatory responses. Interaction between P-selectin and its oligosaccharide ligand, sialyl Lewis x (sLex), plays an important role in the early stage of the adhesion. To examine the role of P-selectin in various animal disease models especially in rats, we have cloned rat E- and P-selectin cDNAs and established monoclonal antibodies against these rat selectins. In this report, we describe the generation and characterization of anti-rat P-selectin antibodies (ARPs). These antibodies detect cell surface P-selectin on thrombin-stimulated rat platelets. More importantly, intravenous administration of ARP2-4 reduced infarction developed after 30 min of ischemia followed by 24 h of reperfusion in a rat myocardial injury model. In addition, similar protective effect was also observed by administration of a sLex-oligosaccharide. These results indicate that cell adhesion mediated via P-selectin is involved in the development of ischemia and reperfusion injury in rat heart.
Qubit-photon interactions in a cavity: Measurement-induced dephasing and number splitting (2006)

We theoretically study measurement-induced dephasing of a superconducting qubit in the circuit QED architecture and compare the results to those obtained experimentally by Schuster et al. [Phys. Rev. Lett. 94, 123602 (2005)]. Strong coupling of the qubit to the resonator leads to a significant ac Stark shift of the qubit transition frequency. As a result, quantum fluctuations in the photon number populating the resonator cause dephasing of the qubit. We find good agreement between the predicted line shape of the qubit spectrum and the experimental results. Furthermore, in the strongly dispersive limit, where the Stark shift per photon is large compared to the cavity decay rate and the qubit linewidth, we predict that the qubit spectrum will be split into multiple peaks, with each peak corresponding to a different number of photons in the cavity.
Incidence of breast carcinoma-related lymphedema (1998)

The definitive study to determine the incidence of lymphedema has not been performed to date. There has been no prospective study in which patients have been followed at intervals with accurate measurement techniques over the long term.
(Invited) Dilute-Nitride-Antimonide Materials Grown by MOVPE for Multi-Junction Solar Cell Application (2015)

We have investigated the growth by metalorganic vapor phase epitaxy (MOVPE) of multinary (four- and five- element) dilute-nitride-antimonide materials on GaAs substrates. The lowest background carbon concentration (~ 5 × 10 16 cm -3 ) is observed in dilute-nitride materials grown at high temperature which do not contain Sb (i.e. InGaAsN). An increased depletion region width significantly improves the solar cell performance over that found from dilute-nitride cells grown at lower growth temperatures (~525 o C). The device performance of the single-junction solar cells with the low carbon background InGaAsN base region (InGaAsN/Ge double-junction solar cell) exhibit short-circuit current density, open-circuit voltage, fill factor, and efficiency values of 26.05 (28.46) mA/cm 2 , 0.67 (0.9) V, 75.85 (72.8) %, and 13.2 (18.54) %, with anti-reflecting coating (ARC), respectively.
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease (1998)

The efficacy and safety of donepezil as a treatment for patients with mild to moderate Alzheimer's disease (AD) was investigated in a multicenter, double-blind study. Patients were randomly assigned to treatment with placebo (n = 162), 5 mg/d donepezil (n = 154), or 10 mg/d donepezil (n = 157) for 24 weeks followed by a 6-week, single-blind placebo washout. The primary efficacy measures were the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog) and the Clinician's Interview Based Assessment of Change-Plus (CIBIC plus), with the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB), and patient rated Quality of Life (QoL) used as secondary measures. Cognitive function, as measured by the ADAS-cog, was significantly improved in the 5- and 10-mg/d donepezil groups as compared with the placebo group at weeks 12, 18, and 24. Clinician's global ratings on the CIBIC plus also improved in both the 5- and 10-mg/d donepezil groups relative to placebo. At the end of the 6-week placebo washout phase, ADAS-cog scores and CIBIC plus ratings were not significantly different for the three groups. Significant treatment benefits were also observed consistently in both the 5- and 10-mg/d groups on the MMSE and the CDR-SB, but there was no consistent effect on the patient-rated QoL. Cholinergic side effects (primarily diarrhea, nausea, and vomiting) were reported more often in the 10-mg/d group than either the 5-mg/d or placebo groups. Side effects were transient and generally mild in severity. These data indicate that donepezil is a well-tolerated drug that improves cognition and global function in patients with mild to moderate AD.
Global zoom/pan estimation and compensation for video compression (1991)

An algorithm is presented for estimating and compensating camera zooms and pans. It models the global motion in each frame with just two parameters: a zoom factor and a two-dimensional pan vector both based on local displacement vectors found by conventional means (such as block matching). Since motion by objects in the scene obscures global motion, the algorithm can iterate to refine its estimate. Simulations suggest the algorithm is robust and accurate, and can significantly reduce both the energy of the motion compensated residual image as well as the zeroth-order entropy of the local displacement vector field.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Zesto: A cycle-level simulator for highly detailed microarchitecture exploration (2009)

For academic computer architecture research, a large number of publicly available simulators make use of relatively simple abstractions for the microarchitecture of the processor pipeline. For some types of studies, such as those for multi-core cache coherence designs, a simple pipeline model may suffice. For detailed microarchitecture research, such as those that are sensitive to the exact behavior of out-of-order scheduling, ALU and bypass network contention, and resource management (e.g., RS and ROB entries), an over-simplified model is not representative of modern processor organizations. We present a new timing simulator that models a modern x86 microarchitecture at a very low level, including out-of-order scheduling and execution that much more closely mirrors current implementations, a detailed cache/memory hierarchy, as well as many x86-specific microarchitecture features (e.g., simple vs. complex decoders, micro-op decomposition and fusion, microcode lookup overhead for long/complex x86 instructions).