gebhart/patrepeval huggingface dataset:
Late Airway Responses to Antigen Challenge in Sensitized Inbred Rats (1988)

We studied the magnitude and the time course of changes in pulmonary resistance (RL) after aerosol challenge with chicken ovalbumin (OA) of 15 sensitized, highly inbred Brown-Norway (BN) rats. Animals were actively sensitized and 2 wk later were challenged through the airways. Airway responses of sensitized animals were compared to those of 6 control animals challenged with sufficient methacholine (MCh) to at least double RL and to 4 unsensitized control rats challenged with OA. Ten of 15 rats in the experimental group displayed an early response (ER), defined as an increase in RL of at least 50% within 1 h of challenge. A late response (LR) was considered to have occurred when the value of RL exceeded the mean plus 2 standard deviations of all the measurements taken from 1 h after challenge to the end of the experiment. Two rats died less than 240 min after OA challenge with RL greater than 200% baseline. The remaining 13 were studied for a total duration that ranged from 390 to 720 min and of these animals 10 demonstrated LRs. Maximal RL during the LR after OA was 287 +/- 49% (SE) baseline (range, 129 to 760) versus 115 +/- 15% (75 to 176) for control animals after MCh (p less than 0.01) and 52 +/- 3% (51 to 142; p less than 0.01) for unsensitized control animals after OA. There was no correlation between the magnitude of ER and LR; 3 LRs occurred in the absence of detectable ERs. The median time to the peak of the LR was 450 min; median duration of LRs was 90 min (range, 30 to 135 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Improved Multilevel Hysteresis Current Regulation and Capacitor Voltage Balancing Schemes for Flying Capacitor Multilevel Inverter (2008)

This paper focuses on the development of multilevel hysteresis current regulation strategies. Two such strategies have been discussed and some modifications in their control tasks have been proposed to achieve more reliable and improved performance. In general, the multiband concept has been used while making the proposals. The hysteresis band size considerations have also been presented by taking into account the desired and existing system conditions. The proposed modulation schemes have been applied to a five-level flying-capacitor inverter, whose operation under hysteresis current control mode is much less established. A new method of flying-capacitor voltage balancing is proposed which ensures balanced flying-capacitor voltages and, at the same time, maintains the desired current profile. It uses a time-based approach for controlling the capacitor voltages and achieves appreciable voltage spectrum under wide range of load power factor conditions. The performance of the proposed strategies is confirmed through both simulation and experimental investigations.
Targeting HIV proteins to the major histocompatibility complex class I processing pathway with a novel gp120-anthrax toxin fusion protein (1997)

A challenge for subunit vaccines whose goal is to elicit CD8(+) cytotoxic T lymphocytes (CTLs) is to deliver the antigen to the cytosol of the living cell, where it can be processed for presentation by major histocompatibility complex (MHC) class I molecules. Several bacterial toxins have evolved to efficiently deliver catalytic protein moieties to the cytosol of eukaryotic cells. Anthrax lethal toxin consists of two distinct proteins that combine to form the active toxin. Protective antigen (PA) binds to cells and is instrumental in delivering lethal factor (LF) to the cell cytosol. To test whether the lethal factor protein could be exploited for delivery of exogenous proteins to the MHC class I processing pathway, we constructed a genetic fusion between the amino-terminal 254 aa of LF and the gp120 portion of the HIV-1 envelope protein. Cells treated with this fusion protein (LF254-gp120) in the presence of PA effectively processed gp120 and presented an epitope recognized by HIV-1 gp120 V3-specific CTL. In contrast, when cells were treated with the LF254-gp120 fusion protein and a mutant PA protein defective for translocation, the cells were not able to present the epitope and were not lysed by the specific CTL. The entry into the cytosol and dependence on the classical cytosolic MHC class I pathway were confirmed by showing that antigen presentation by PA + LF254-gp120 was blocked by the proteasome inhibitor lactacystin. These data demonstrate the ability of the LF amino-terminal fragment to deliver antigens to the MHC class I pathway and provide the basis for the development of novel T cell vaccines.
Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries (2020)

Abstract The emergence of coronavirus disease 2019 (COVID-19) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 have more superiority to inhibit the interaction between spike protein and angiotensin converting enzyme 2 receptor (ACE2). Most importantly, the antibodies from Bin2 can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.
Dihydrino Molecule Identification (1994)

Three sets of heat production and “ash” identification data are presented. An exothermic reaction is reported wherein the electrons of hydrogen and deuterium atoms are stimulated to relax to quantized potential energy levels below that of the “ground state” via electrochemical reactants K+ and K+; Pd2+ and Li+; or Pd and O2 of redox energy resonant with the energy hole that stimulates this transition. Calorimetry of pulsed current and continuous electrolysis of aqueous potassium carbonate (K+/K+ electrocatalytic couple) at a nickel cathode were performed. The excess output power of 41 W exceeded by a factor >8 the total input power given by the product of the electrolysis voltage and current. The product of the exothermic reaction is atoms having electrons of energy below the ground state, which are predicted to form molecules. The predicted molecules were identified by their lack of reactivity with oxygen, by separation from molecular deuterium by cryofiltration, and by mass spectroscopic analysis.
Association of Genetic Loci With Glucose Levels in Childhood and Adolescence (2011)

Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards.
Macromolecules Containing Bipyridine and Terpyridine Metal Complexes: Towards Metallosupramolecular Polymers (2002)

The ability of a broad range of N-heterocycles to act as very effective and stable complexation agents for several transition metal ions, such as cobalt(II), copper(II), nickel(II), and ruthenium(II), has long been known in analytical chemistry. This behavior was later utilized in supramolecular chemistry for the construction of highly sophisticated architectures, such as helicates, racks, and grids. The discovery of macromolecules by Staudinger in 1922 opened up avenues towards sophisticated materials with properties hitherto completely unknown. In the last few decades, the combination of macromolecular and supramolecular chemistry has been attempted by developing metal-complexing and metal-containing polymers for a wide variety of applications that range from filtration to catalysis. The stability of the polymer-metal complex is a fundamental requirement for such applications. In this respect, the use of bi- and terpyridines as chelating ligands is highly promising, since these molecules are known to form highly stable complexes with interesting physical properties with transition-metal ions. A large number of different structures have been designed for many different applications, but polymers based on the application of coordinative forces have been prepared in a few cases only. Furthermore, the synthetic procedures applied frequently resulted in low yields. During the last few years, strong efforts have been made in the direction of self-assembling and supramolecular polymers as novel materials with "intelligent" and tunable properties. In this review, an overview of this active area at the interface of supramolecular and macromolecular chemistry is given.
The Inflammasome as a Target of Modulation by DNA Viruses (2013)

The cellular innate immune response represents the initial reaction of a host against infecting pathogens. Host cells detect incoming microbes by way of a large and expanding array of receptors that react with evolutionarily conserved molecular patterns exhibited by microbial intruders. These receptors are responsible for initiating signaling that leads to both transcriptional activation of immunologically important genes as well as protease-dependent processing of cellular proteins. The inflammasome refers to a protein complex that functions as an activation platform for the cysteine protease caspase-1, which then processes inflammatory molecules such as IL-1β and IL-18 into functional forms. Assembly of this complex is triggered following receptor-mediated detection of pathogen-associated molecules. Receptors have been identified that are essential to inflammasome activation in response to numerous molecular patterns including virus-associated molecules such as DNA. In fact, the importance of cytoplasmic DNA as an immune stimulus is exemplified by the existence of at least nine distinct cellular receptors capable of initiating innate reactivity in response to this molecule. Viruses that employ DNA as genomic material include herpesviruses, poxviruses and adenoviruses. Each has been described as capable of inducing inflammasome-mediated activity. Interestingly, however, the cellular molecules responsible for these responses appear to vary according to host species, cell type and even viral strain. Secretion of IL-1β and IL-18 are important components of antimicrobial immunity and, as a result, pathogens have evolved factors to evade or counteract this response. This includes DNA-based viruses, many of which encode multiple redundant counteractive molecules. However, it is clear that such phenotypes are only beginning to be uncovered. The purpose of this review is to describe what is known regarding the activation of inflammasome-mediated processes in response to infection with well-examined families of DNA viruses and to discuss characterized mechanisms of manipulation and neutralization of inflammasome-dependent activity. This review aims to shed light on the biologically important phenomena regarding this virus–host interaction and to highlight key areas where important information is lacking.
Integrated change and configuration management (2007)

This paper provides a summary of the best-practice change-management and configuration-management processes that express a core which conforms to ITIL® and discusses how they are extended for the service provider domain. These customizable processes, coupled with an execution platform and a configuration-management database, form the essence of the IBM Tivoli® Change and Configuration Management Database (CCMDB)—the heart of the IBM strategy for information technology service management (ITSM). We provide an overview of ITSM best practices and present details of the best-practice processes developed by IBM for the CCMDB product. We also describe a number of insights gained from implementing these processes and discuss issues that are key to implementing them in a service provider environment.
Electrophysiologic and Anatomic Characterization of Sites Resistant to Electrical Isolation During Circumferential Pulmonary Vein Ablation for Atrial Fibrillation: A Prospective Study (2007)

Sites of EI after WEPV have a preferential distribution determined by anatomic features. CA on the intervenous ridge is required in a significant proportion of patients to achieve EI. Atrial folds and ridges increase myocardial thickness creating technical and anatomic challenges for achieving transmural lesions.
Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver (2009)

Thyrotoxicosis increases endogenous glucose production (EGP) and induces hepatic insulin resistance. We have recently shown that these alterations can be modulated by selective hepatic sympathetic and parasympathetic denervation, pointing to neurally mediated effects of thyroid hormone on glucose metabolism. Here, we investigated the effects of central triiodothyronine (T(3)) administration on EGP. We used stable isotope dilution to measure EGP before and after i.c.v. bolus infusion of T(3) or vehicle in euthyroid rats. To study the role of hypothalamic preautonomic neurons, bilateral T(3) microdialysis in the paraventricular nucleus (PVN) was performed for 2 h. Finally, we combined T(3) microdialysis in the PVN with selective hepatic sympathetic denervation to delineate the involvement of the sympathetic nervous system in the observed metabolic alterations. T(3) microdialysis in the PVN increased EGP by 11 +/- 4% (P = 0.020), while EGP decreased by 5 +/- 8% (ns) in vehicle-treated rats (T(3) vs. Veh, P = 0.030). Plasma glucose increased by 29 +/- 5% (P = 0.0001) after T(3) microdialysis versus 8 +/- 3% in vehicle-treated rats (T(3) vs. Veh, P = 0.003). Similar effects were observed after i.c.v. T(3) administration. Effects of PVN T(3) microdialysis were independent of plasma T(3), insulin, glucagon, and corticosterone. However, selective hepatic sympathectomy completely prevented the effect of T(3) microdialysis on EGP. We conclude that stimulation of T(3)-sensitive neurons in the PVN of euthyroid rats increases EGP via sympathetic projections to the liver, independently of circulating glucoregulatory hormones. This represents a unique central pathway for modulation of hepatic glucose metabolism by thyroid hormone.
Iterative Method Applied To Image Reconstruction And To Computer-Generated Holograms (1980)

This paper discusses an iterative computer method that can be used to solve a number of problems in optics. This method can be applied to two types of problems: (1) synthesis of a Fourier transform pair having desirable properties in both domains, and (2) reconstruction of an object when only partial information is available in any one domain. Illustrating the first type of problem, the method is applied to spectrum shaping for computer-generated holograms to reduce quantization noise. A problem of the second type is the reconstruction of astronomical objects from stellar speckle interferometer data. The solution of the latter problem will allow a great increase in resolution over what is ordinarily obtainable through a large telescope limited by atmospheric turbulence. Experimental results are shown. Other applications are mentioned briefly.
Antibody-targeted thrombolytic agents. (1990)

Plasminogen activator therapy for acute myocardial infarction has become standard medical practice. Bleeding complications, however, limit the utility of the currently available agents. This article reviews how the tools of immunology, molecular biology and protein engineering are being used to develop safer and more effective plasminogen activators.
Study of Rimantadine in the USSR: A Review of the Literature (1981)

The results of basic-science and clinical studies performed in the USSR with the drug rimantadine are summarized. In the investigations cited, the therapeutic and prophylactic efficacy of rimantadine against infection with influenza virus was tested, and rimantadine was shown to be clinically efficacious and free of toxicity, both in studies with volunteers and in persons with natural disease during epidemics of influenza. Administration of 50 mg of the drug for 15-30 days was effective for prevention of influenza, and administration, early in the course of illness, of dosage of 150 mg per day for three to five days resulted in a favorable clinical response. The combination of immunization and chemoprophylaxis was shown to be highly effective for the prevention of influenza.
Robotic Nd:YAG-Laser Welding System and Its Applications (2003)

In this paper, the robotic Nd:YAG-laser welding system operated by the Aerospace Manufacturing Technology Center of NRC-IAR is described. The system is an advanced laser processing system built around a 4000W Haas Nd:YAG-laser, which has fiber optics for laser beam transmission. An ABB 4400 industrial robot is used for holding the processing optics. Various beam configurations can be used for different processes, including welding, cutting and heat treatment, either with single beam or dual beam laser spots. The system is also equipped with a sophisticated MVS vision-tracking device, which enables reliable and repeatable processing conditions. A convenient electro-magnetic base equipped with different fixtures is available for accurate positioning of the parts. The system also comes with a state-of-art wire feeder specially designed for welding aluminum alloys and super alloys used in the aerospace industry. Welding can be run in manual or automatic mode, making the system suitable for both research and production work. Several applications of this welding system will be presented.
Experimental chronic subdural hematoma in mice (1987)

A new experimental model of chronic subdural hematoma in mice is described. A single intraperitoneal injection of 6-aminonicotinamide (25 mg/kg body weight) on the 5th postnatal day induced hydrocephalus in mice with almost 100% success. Approximately 60% of the mice spontaneously developed intracranial hemorrhage 20 days after the injection. About 1 week after the hemorrhage, a lens-shaped or spherical subdural hematoma was observed, accompanied by marked dilatation of the lateral ventricles and intraventricular hemorrhage. Histological examination revealed that the hematoma contained well-organized outer and inner membranes. Fresh hemorrhage surrounded by many hemosiderin-laden macrophages was seen at the margin of the hematoma adjacent to the organizing outer membrane, in which many fibroblasts and blood vessels were noted. The inner membrane of the hematoma was made up of several tiers of flattened cells with thin-walled blood vessels. The gross morphology and histology of these hematomas closely resembled those of human chronic subdural hematoma.
Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial. (2014)

Combined treatment with tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB, there­by improving patients' quality of life.
Graft Healing in the Bone Tunnel in Anterior Cruciate Ligament Reconstruction (2000)

The histologic sequence in the bone tunnel after anterior cruciate ligament reconstruction using the bone-patellar tendon-bone graft was investigated in this study. Eighteen adult mongrel dogs were used. After excision of the anterior cruciate ligament, the graft was routed through the bone tunnels and fixed with interference fit screws. After the dogs were sacrificed at intervals, the bone blocks containing the bone tunnels were isolated and processed for histologic examination. At the bone-bone interface, incorporation of the bone plug at each end of the graft was completed at 12 weeks. The structure of the tendon insertion of the grafted patellar tendon, consisting of four distinct zones, was observed without apparent necrotic and degenerative change for as long as 12 weeks. Between the tendon and the bone tunnel, a layer of hypercellular fibrous tissue gradually became mature with time. Thus, it appeared the morphologic characteristics and location of the reestablished attachment of the bone-patellar tendon-bone graft were more similar to those of the native anterior cruciate ligament compared with the graft to bone healing in the hamstring tendon graft.
A Pro504 → Ser Substitution in the β-Subunit of β-Hexosaminidase A Inhibits α-Subunit Hydrolysis of GM2Ganglioside, Resulting in Chronic Sandhoff Disease (1998)

The GM2 gangliosidoses are caused by mutations in the genes encoding the alpha- (Tay-Sachs) or beta- (Sandhoff) subunits of heterodimeric beta-hexosaminidase A (Hex A), or the GM2 activator protein (AB variant), a substrate-specific co-factor for Hex A. Although the active site associated with the hydrolysis of GM2 ganglioside, as well as part of the binding site for the ganglioside-activator complex, is associated with the alpha-subunit, elements of the beta-subunit are also involved. Missense mutations in these genes normally result in the mutant protein being retained in the endoplasmic reticulum and degraded. The mutations associated with the B1-variant of Tay-Sachs are rare exceptions that directly affect residues in the alpha-active site. We have previously reported two sisters with chronic Sandhoff disease who were heterozygous for the common HEXB deletion allele. Cells from these patients had higher than expected levels of mature beta-protein and residual Hex A activity, approximately 20%. We now identify these patients' second mutant allele as a C1510T transition encoding a beta-Pro504 --> Ser substitution. Biochemical characterization of Hex A from both patient cells and cotransfected CHO cells demonstrated that this substitution (a) decreases the level of heterodimer transport out of the endoplasmic reticulum by approximately 45%, (b) lowers its heat stability, (c) does not affect its Km for neutral or charged artificial substrates, and (d) lowers the ratio of units of ganglioside/units of artificial substrate hydrolyzed by a factor of 3. We concluded that the beta-Pro504 --> Ser mutation directly affects the ability of Hex A to hydrolyze its natural substrate but not its artificial substrates. The effect of the mutation on ganglioside hydrolysis, combined with its effect on intracellular transport, produces chronic Sandhoff disease.