gebhart/patrepeval huggingface dataset:
A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease (2014)

Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease.
Protection of Mice Against Dengue 2 Virus Encephalitis by Immunization with the Dengue 2 Virus Non-structural Glycoprotein NS1 (1987)

Immunization of mice with the dengue 2 virus (DEN 2)-specified non-structural protein NS1 provided significant protection against intracerebral challenge with the virus in the absence of detectable neutralizing or other anti-virion antibody. NS1, purified from lysates of infected Vero cells by immunoaffinity chromatography, expressed an antigenic site(s) common to each of the four DEN serotypes, and hyperimmunization of rabbits with NS1 stimulated production of complement-fixing (CF) antibody with broad DEN serotype specificity. However, cross-protection was not observed: mice immunized with DEN 2 NS1 developed little or no heterologous CF antibody and were not protected against challenge with neurovirulent DEN 1. Induction of a protective immune response by NS1 suggests that it be considered for incorporation into possible synthetic or recombinant DNA DEN vaccines.
Acute regression of advanced and retardation of early aortic atheroma in immunocompetent apolipoprotein-E (apoE) deficient mice by administration of a second generation [E1-, E3-, polymerase-] adenovirus vector expressing human apoE (2002)

Apolipoprotein E (apoE) is a 34 kDa glycoprotein with multiple actions that help protect against the development of atherosclerosis. Here, we have assessed the atheroprotective potential of an [E1(-), E3(-), polymerase(-)] adenovirus vector expressing human apoE, comparing intramuscular and intravenous (liver-directed) injections in hypercholesterolaemic apoE-deficient mice (apoE(-/-)). Intramuscular injections resulted in low expression of apoE and afforded no protection against atherogenesis. In contrast, 3 and 7 days after intravenous injections into young (6-8-week-old) apoE(-/-) mice, plasma levels of apoE were elevated and were accompanied by reductions in plasma cholesterol and normalization of lipoprotein profiles. Thereafter, plasma apoE was still detectable up to day 70, but gradually declined, although no humoral immune response was evoked, and there was a return to dyslipoproteinaemia. High levels of the vector genome were still present in livers of treated animals at 70 days, implying that decrease in apoE expression was due to cellular shutdown of the cytomegalovirus promoter. Importantly, liver-directed apoE gene transfer to these young mice retarded progression of atherosclerosis by 38% (treated, 8.21 +/- 1.05%; untreated, 13.26 +/- 0.98%, P < 0.05), during the 70 day study period. Moreover, when 10-month-old apoE(-/-) mice with advanced atherosclerosis were treated with the adenovirus vector, there was clear regression of aortic lesion area by 1 month [24.3 +/- 1.7% compared to 40.7 +/- 2.6% in baseline controls (P < 0.002)]. We conclude that the stability of the adenovirus vector genome in the livers of intravenously treated animals provides an ideal platform to evaluate liver-specific promoters for sustained transgene expression and control of atherosclerotic lesion pathology.
Foxp2 regulates neuronal differentiation and neuronal subtype specification (2014)

Mutations of the transcription factor FOXP2 in humans cause a severe speech and language disorder. Disruption of Foxp2 in songbirds or mice also leads to deficits in song learning or ultrasonic vocalization, respectively. These data suggest that Foxp2 plays important roles in the developing nervous system. However, the mechanism of Foxp2 in regulating neural development remains elusive. In the current study, we found that Foxp2 increased neuronal differentiation without affecting cell proliferation and cell survival in primary neural progenitors from embryonic forebrains. Foxp2 induced the expression of platelet-derived growth factor receptor α, which mediated the neurognic effect of Foxp2. In addition, Foxp2 positively regulated the differentiation of medium spiny neurons derived from the lateral ganglionic eminence and negatively regulated the formation of interneurons derived from dorsal medial ganglionic eminence by interacting with the Sonic hedgehog pathway. Taken together, our results suggest that Foxp2 regulates multiple aspects of neuronal development in the embryonic forebrain.
Expression of beta-arrestins and beta-adrenergic receptor kinases in the failing human heart. (1994)

The beta-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in beta-adrenergic receptor kinase (beta ARK) expression. beta ARK is thought to effect desensitization by acting in concert with an inhibitor protein, called beta-arrestin. Two isoforms have been identified both for beta ARK and for beta-arrestin. In the present study, we have investigated the expression of the individual isoforms of beta-arrestin and of beta ARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, beta-arrestin-1, beta-arrestin-2, beta ARK-1, and beta ARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for beta-arrestin-1 and beta-arrestin-2, a slight (< 50%) increase of the mRNA for beta ARK-2, and a threefold increase for beta ARK-1 mRNA. At the protein level, beta-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were approximately 350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. beta-Arrestin-2 levels were too low to be detectable using the same methods. beta ARK levels as determined by enzymatic activity were approximately 20 fmol/mg cytosolic protein (beta ARK-1 plus beta ARK-2) and thus almost 20-fold lower than those of beta-arrestin. beta ARK levels were increased approximately twofold in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Virulence studies of Aspergillus nidulans mutants requiring lysine or p-aminobenzoic acid in invasive pulmonary aspergillosis (1994)

To identify steps in fungal intermediary metabolism required by Aspergillus spp. during invasive pulmonary aspergillosis, we have developed murine models involving Aspergillus nidulans as the inoculum. The advantages of using A. nidulans over Aspergillus fumigatus or Aspergillus flavus, which are the most common agents of clinical disease, are the well-understood genetics of A. nidulans and a large range of mutants of this species which are affected in a variety of metabolic pathways. Comparison of the virulence of A. nidulans strains carrying mutations which block the biosynthesis of lysine (lysA2) and p-aminobenzoic acid (pabaA1) shows that lysA2 strains have reduced virulence while pabaA1 strains are entirely nonpathogenic. The pathogenicity of pabaA1 strains can be restored by supplementing the drinking water of animals with p-aminobenzoic acid. The results indicate that the availability of lysine in the lung is limited, and p-aminobenzoic acid is probably not available at all. Thus, models of invasive pulmonary aspergillosis involving A. nidulans can be used to identify metabolic pathways that may be essential for the pathogenicity of A. fumigatus, the predominant pathogenic species, suggesting potential new targets for antifungal therapy.
Combination of CO<sub>2</sub> Reforming and Partial Oxidation of Methane over NiO/MgO Solid Solution Catalysts (1998)

To overcome the explosions that can occur during the partial oxidation of methane, the latter exothermic reaction is coupled with an endothermic one, namely, the CO2 reforming of CH4. These combined reactions have been carried out over NiO/MgO solid solution, NiO/Al2O3, and NiO/SiO2 catalysts. About 90% conversion of CH4 and about 98% selectivities to CO and H2 were obtained at 790 °C and a GHSV(gas hourly space velocity) of 90 000 cm3 g-1 h-1 (O2/CO2/CH4 = 14.5/26.9/58.6), over a reduced NiO/MgO solid solution catalyst. Almost no change in activity and selectivity occurred during 50 h of reaction. Compared to the reduced NiO/MgO, the reduced NiO/SiO2 and NiO/Al2O3 catalysts provided lower activities and stabilities. The effects of the reaction temperature, space velocity, and feed gas composition for a ratio CH4/(CO2 + 2O2) = 1 were investigated. The increase in O2 in the feed gas resulted in a higher conversion of CH4, but the apparent conversion of CO2 passed through a maximum. The CH4 conversion decreased with increasing space velocity, while during the partial oxidation, because of the hot spots, it would have increased. This means that the coupling can, indeed, control the thermal behavior of the reactor.
European wind atlas (1989)

The aim of the European Wind Atlas is to establish the meteorological basis for the assessment of wind energy resources. The main objective is to provide suitable data for evaluating the potential wind energy output from large electricity producing wind turbine installations. In addition, the Wind Atlas provides data and guidelines for the meteorological aspects of the detailed siting of large and small wind turbines. The EUROPEAN WIND ATLAS IS: A DATA BANK of European Wind climate. It contains comprehensive statistics from more than 200 meteorological stations covering the intire EC - plus colour maps of the wind resources of each country in the EC. The statistical data are given also on a diskette for use with IBM compatible PC's. A HANDBOOK for regional wind resource assessment, and the local siting of wind turbines - including guidelines with computational procedures for the effects of shelter from buildings and other obstacles, the effects of varying surface roughnesses, and for the influence of hills and mountains on the wind climate and on the local wind power resources. A METHODOLOGY description. The computational procedures employed for the analysis of the meteorological data are described in full. These methods have applications for all parts of the world. The computer codes are available separately in the form of the Wind Atlas analysis and Application (PC-) Programme (WAsP). (author).
Antibody engineering: an overview. (1991)

We can now isolate and manipulate antibody genes. Mouse antibodies can be humanized, resulting in chimaeric or reshaped antibodies. Antibody engineering is useful in large scale production of antibodies, in production of active antibody fragments, bifunctional, single-domain and catalytic antibodies, and has lead to the production of novel expression systems useful in many other areas. It allows production of new antibody conjugates, e.g. antibody-toxin or antibody-enzyme linked proteins. Engineered antibodies have many potential applications e.g. imaging, therapy and biosensors.
A Novel Family of Sequence-specific Endoribonucleases Associated with the Clustered Regularly Interspaced Short Palindromic Repeats (2008)

Clustered regularly interspaced short palindromic repeats (CRISPRs) together with the associated CAS proteins protect microbial cells from invasion by foreign genetic elements using presently unknown molecular mechanisms. All CRISPR systems contain proteins of the CAS2 family, suggesting that these uncharacterized proteins play a central role in this process. Here we show that the CAS2 proteins represent a novel family of endoribonucleases. Six purified CAS2 proteins from diverse organisms cleaved single-stranded RNAs preferentially within U-rich regions. A representative CAS2 enzyme, SSO1404 from Sulfolobus solfataricus, cleaved the phosphodiester linkage on the 3'-side and generated 5'-phosphate- and 3'-hydroxyl-terminated oligonucleotides. The crystal structure of SSO1404 was solved at 1.6A resolution revealing the first ribonuclease with a ferredoxin-like fold. Mutagenesis of SSO1404 identified six residues (Tyr-9, Asp-10, Arg-17, Arg-19, Arg-31, and Phe-37) that are important for enzymatic activity and suggested that Asp-10 might be the principal catalytic residue. Thus, CAS2 proteins are sequence-specific endoribonucleases, and we propose that their role in the CRISPR-mediated anti-phage defense might involve degradation of phage or cellular mRNAs.
Cleaning of Silicon Surfaces by NF<sub>3</sub>-Added Hydrogen and Water-Vapor Plasma Downstream Treatment (1996)

Native oxide was removed from silicon surfaces by NF 3 -added hydrogen and water-vapor plasma downstream treatment. It took 45 s to remove native oxide from a 6-inch silicon wafer. Fourier transform infrared attenuated total reflection (FT-IR ATR) measurement revealed that the surface roughness after the downstream treatment was the same as that after wet cleaning with 2% HF solution. A silicon epitaxial layer was grown on the surface cleaned by the downstream treatment. Although process temperature was as low as 100°C, the present downstream treatment induced the same effect as in situ hydrogen annealing.
Structure-immunogenicity relationship of melittin and its N-terminal truncated analogs (1993)

Melittin is an amphipathic 26-residue peptide from bee venom. We showed previously that, in the murine system, melittin has one major B-cell epitope in the hydrophilic region of residues 21-26 and one T-cell epitope in the hydrophobic midregion of 11-19. In this paper we compared the immunogenicity and the biophysical properties of a series of melittin analogs which differ by stepwise two-residue truncation in the N-terminus of residues 2-10. All analogs retain the B- and T-cell epitopes of melittin. However, the analogs which have more than two residues deleted at the N-terminus are nonimmunogenic for antibody responses although they are immunogenic for T-cell responses. The analogs were found to differ in their hemolytic activity, helical content, and oligomer formation in different solvents. These results support the hypothesis that the immunogenicity of melittin for antibody response is associated with its binding to cell membranes followed with oligomer formation but its immunogenicity for T-cell response is not.
Fusogenics: A Recombinant Immunotoxin-Based Screening Platform to Select Internalizing Tumor-Specific Antibody Fragments (2010)

Antibody-based therapeutics play a vital role in the treatment of certain cancers; however, despite commercial success, various strategies are being pursued to increase their potency and hence improve patient outcomes. The use of antibodies to deliver a cytotoxic payload offers a promising alternative for more efficacious therapies. Immunotoxins are composed of an internalizing antibody fragment linked to a bacterial or plant toxin. Once internalized, the payload, such as Pseudomonas exotoxin A (PE), blocks protein synthesis and induces apoptosis. Typically, immunotoxins are developed by first isolating a tumor-specific antibody, which is then either chemically linked to a toxin or reengineered as a fusion protein. Here, the authors describe the development of Fusogenics, an immunotoxin-based screening method that selects internalizing tumor-specific antibodies using a functional assay. Selected immune library clones were characterized and shown to be selective against normal tissues and specific to tumor tissues. In summary, the Fusogenics immunotoxin platform represents a unique, single-step selection approach combining specificity and functionality to isolate novel internalizing tumor-specific antibody fragments with potential for direct clinical application in the treatment of cancer.
Synthesis and Biological Characterization of 1-Methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole Derivatives as Muscarinic Agonists for the Treatment of Neurological Disorders (2003)

Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M(1), M(2), and M(4) receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.
Improved E-model for monitoring quality of multi-party VoIP communications (2013)

Maintaining good Quality-of-Experience (QoE) is crucial for Voice-over-IP (VoIP) applications, particularly those operating across the public Internet. Accurate online estimation of QoE as perceived by end users allows VoIP applications take steps to improve QoE when it falls below acceptable levels. ITU-T recommendation G.107 introduced the E-model, which provides a means to assess QoE levels for two-party VoIP sessions. In this paper we provide an analysis of the accuracy of the E-model for multi-party VoIP sessions when all audio is processed by a centralised focus node. We analyse the impact of what we term the “Focus Transcoding Effect (FTE),” the “Focus Forwarding Effect (FFE),” and the number of end-points participating in the session. Through comparison to QoE metrics produced by the offline PESQ method for three common audio codecs, we show that the standard E-model does not provide accurate QoE assessment for multi-party VoIP sessions. We then introduce an improved Emodel for these codecs for multi-party VoIP sessions. We describe the implementation of the improved E-model in a QoE monitoring application, showing that it produces results similar to actual PESQ scores.
Satellite Constellation And Geometric Dilution Of Precision (1996)

T HE GPS satellite constellation is selected to satisfy many different conditions to provide worldwide three-dimensional navigation. The satellite constellation has been placed in an inclined orbit at 55 deg (formerly 63-deg inclination for earlier Block I satellites) to provide full Earth coverage, whereas a purely equatorial orbit cannot provide coverage above approximately 72° latitude at the GPS orbit altitude. The requirement for a minimum of four simultaneous pseudorange measurements with good geometry directly leads to a constellation of many satellites. A nongeosynchronous orbit was selected to permit the use of carrier phase/Doppler measurement profiles in addition to pseudorange measurements of code phase/delay. This objective was one of the reasons for the selection of the 12 sidereal hour orbit. This chapter discusses the operational satellite constellation of 24 satellites termed the GPS-24 (closely related to the previous Primary 21) constellation. The specific characteristics of this constellation are discussed in terms of the statistics of the numbers of satellites visible at different user latitudes and various elevation angles, the satellite ground tracks, and the signal Doppler shifts. The potential for the future augmentation of this GPS constellation by adding satellites in either the same planes or as geostationary satellites is also discussed. The chapter then continues with an analysis of the geometric dilution of precision (GDOP) and the related DOPs: PDOP, HDOP, VDOP, TDOP for position, horizontal, vertical, and time dilutions of precision. The bounds on the minimum value of these DOPs are analyzed for various numbers of satellites for both twoand three-dimensional problems with various constraints on elevation angle and user clock stability. Further discussion and development of the DOP concept is found in Chapter 11, this volume. The chapter concludes by describing the GDOP for the GPS-24 satellite constellation with a single satellite outage.
An Optimal Bloom Filter Replacement Based on Matrix Solving (2008)

We suggest a method for holding a dictionary data structure, which maps keys to values, in the spirit of Bloom Filters. The space requirements of the dictionary we suggest are much smaller than those of a hashtable. We allow storing n keys, each mapped to value which is a string of k bits. Our suggested method requires nk + o(n) bits space to store the dictionary, and O(n) time to produce the data structure, and allows answering a membership query in O(1) memory probes. The dictionary size does not depend on the size of the keys. However, reducing the space requirements of the data structure comes at a certain cost. Our dictionary has a small probability of a one sided error. When attempting to obtain the value for a key that is stored in the dictionary we always get the correct answer. However, when testing for membership of an element that is not stored in the dictionary, we may get an incorrect answer, and when requesting the value of such an element we may get a certain random value. Our method is based on solving equations in GF(2^k) and using several hash functions. Another significant advantage of our suggested method is that we do not require using sophisticated hash functions. We only require pairwise independent hash functions. We also suggest a data structure that requires only nk bits space, has O(n2) preprocessing time, and has a O(log n) query time. However, this data structures requires a uniform hash functions. In order replace a Bloom Filter of n elements with an error proability of 2^{-k}, we require nk + o(n) memory bits, O(1) query time, O(n) preprocessing time, and only pairwise independent hash function. Even the most advanced previously known Bloom Filter would require nk+O(n) space, and a uniform hash functions, so our method is significantly less space consuming especially when k is small.
Handbook of Optical Systems (2005)

Modulation Transfer Function 50 36.6.6 Visual Acuity 57 36.6.7 Resolution 58 36.6.8Stray Light 62 36.6.9Measuring the Performance of the Eye 62 36.7 Binocular Vision 63 36.7.1 Introduction 63 36.7.2 Convergence 65 36.7.3 Stereo Vision and Depth Discrimination 67 36.8Eye Defects 69 36.8.1 Introduction 69 36.8.2 Myopia 70 36.8.3 Hyperopia 70 36.8.4 Astigmatism 72 36.8.5 Aniseikonia 72 36.8.6 Color Aberrations 72 36.8.7 Spreading and Aging Effects 73 36.8.8 Cataract 75 36.9Correction of Eye Aberrations 75 36.9.1 Correcting Refraction by Spectacles 75 36.9.2 Binoculars with Corrected Oblique Astigmatism 36.9.3More Complicated Spectacle Shapes 82 36.9.4
Feedback suppression in reliable multicast protocol (2002)

Feedback implosion is one of the crucial issues confronting the scalability of reliable multicast protocols. Generally, there are two ways of solving this feedback implosion problem-timer-based and structure-based approaches. In the timer-based approach, when a receiver needs to send feedback, it multicasts the feedback to all receivers earlier than the other receivers, and hence suppresses others from returning feedback in response to the same event. The structure-based approach depends on intermediate network elements to consolidate feedback arising from the same event. It hence significantly reduces the number of feedback messages arriving at the sender from a single event. In this paper, we present an effective end-to-end NACK suppression algorithm which could solve the problem caused by correlative packet loss and independent packet loss among receivers.