gebhart/patrepeval huggingface dataset:
Development of RA101348, a Potent Cyclic Peptide Inhibitor of C5 for Complement-Mediated Diseases (2014)

Abstract The involvement of complement in the pathogenesis of serious, life-threatening diseases underscores the importance in developing therapeutics to intervene in this cascade. Specifically, dysregulation of the complement system is central in multiple hematologic conditions. Antibody blockade of the C5 component of complement has been approved as a treatment for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS), validating C5 as a therapeutic target for these conditions. Ra Pharma has developed a macrocyclic peptide platform capable of yielding potent inhibitors of protein-protein interactions. Recently, we developed a short cyclic peptide that binds complement C5 with high affinity (KD = 2.6 nM) and inhibits its cleavage into C5a and C5b by a novel mechanism. At low nanomolar concentrations, RA101348 blocks the formation of the terminal complement complex (TCC) in vitro, as demonstrated in RBC lysis assays for both alternative and classical complement activation pathways. Inhibition of in vivo complement activity was evaluated in cynomolgus monkeys following single- and multi-dose subcutaneous (SC) administration. RA101348 exhibited high SC bioavailability, and low, single doses inhibited complement activity by 90-100%. The effect is durable owing to an in vivo terminal half-life of approximately 72 hrs. Repeat dosing for 7 days was well tolerated in monkeys at up to 100-fold above projected human therapeutic doses and resulted in sustained inhibition of complement activity. RA101348 is a novel therapeutic approach for inhibiting the activity of C5 for the treatment of disorders caused or associated with complement dysregulation. It offers the potential to enable self-administration of therapeutics for patients with PNH and other complement disorders. Disclosures Ricardo: Ra Pharmaceuticals: Employment. Arata:Ra Pharmaceuticals: Employment. DeMarco:Ra Pharmaceuticals: Employment. Dhamnaskar:Ra Pharmaceuticals: Employment. Hammer:Ra Pharmaceuticals: Employment. Josephson:Ra Pharmaceuticals: Employment. Seyb:Ra Pharmaceuticals: Employment. Tobe:Ra Pharmaceuticals: Employment. Wang:Ra Pharmaceuticals: Employment. Zheng:Ra Pharmaceuticals: Employment. Treco:Ra Pharmaceuticals: Employment.
Transient expression of RSVCAT in transgenic zebrafish made by electroporation. (1993)

We report the fish use of an exponential decay electroporation system to introduce foreign DNA into fertilized zebrafish embryos. The plasmid RSVCAT (Rous sarcoma viral promoter (RSV) upstream from the chloramphenicol acetyltransferase gene (CAT)) was linearized and introduced into fertile zebrafish embryos by electroporation no later than the four-cell stage. Conditions for the procedure were empirically derived, and 68% of the treated animals survived through hatching to at least 6 days after fertilization and well beyond. Dot-blot analysis on DNA extracted from individual hatching fry demonstrated that 65% of the animals tested carried the foreign construct. Enzyme assays on the soluble proteins of treated animals were positive for chloramphenicol acetyltransferase activity. These data demonstrate that the foreign construct was being transiently expressed in the developing tissues of the embryo. The simplicity of this technique will greatly enhance the ability to analyze gene promoter regulation in vivo in transgenic zebrafish. The ability of the electroporated DNA to integrate into the host genome and to generate stable lines of transgenic fish is discussed.
Novel Penetration Enhancers for Skin Applications: A Review (2012)

The use of topical formulation is popular over the past decade due to extensive researches made in the field of transdermal drug delivery. As a result, an increasing number of drugs are being added to the list of therapeutic agents that can be delivered to systemic circulation through the skin. Commonly available dosage forms for the topical application are creams, ointments, gels, patches etc. The therapeutic benefits of the above topical formulations are limited due to barrier property of stratum corneum (SC). The use of chemical penetration enhancers (CPEs) is one of the long standing approach to overcome the barrier property of SC. Numerous class of novel compounds have been evaluated for penetration enhancement activity, including soft enhancement for percutaneous absorption (SEPA), for example, 2 N-nonyl-1,3- dioxolanes, N-acetyle prolinate esters (such as pentyl- and octyl-N-acetyle prolinate), alkyldiloxanes (e.g., 1-Alkyl-3-b-D glucopyranosyl-1,1,3,3-tetramethyl disiloxanes), transcarbam (such as 5-(dodecyloxycarbonyl) pentylammonium-5- (dodecyloxycarbonyl) pentylcarbamate), iminosulfurane (like N-hexyl,N-benzoyl-S,S-dimethylimino-sulfuranes), capsaicin derivatives (e.g., Nonivamide), cinnamene compounds (such as cinnamic acid, cinnamaldehyde etc), terpenes (like clove and basil oil) and synergestic combination of penetration enhancers (SCOPE). We briefly describe about the anatomy of skin. Potential mechanisms of action of above novel PEs along with adverse reactions associated with traditional PEs are also considered in this review.
OBJECT-ORIENTED CONCEPTUAL MODELING TECHNIQUES TO DESIGN AND IMPLEMENT A SOUND AND ROBUST ORACLE ENVIRONMENT (2000)

The paper will introduce the advantages of using the Object-Oriented Model for conceptual modeling, as a kind of knowledge model to capture information system properties. Next, the paper will explain how to properly implement such a system description in an advanced ORACLE environment, using ORACLE v7 as server and Developer/2000 as execution model tool. The main contribution is the definition of a precise mapping between OO notions at the conceptual model level, and ORACLE structures for implementation at the programming level. This allows us to connect OO modeling with a sound and functionally equivalent relational implementation in Oracle. 1.
Limits of Emmetropization and Developmental Vision Disorders (1999)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text E. L. Smith, L. Hung, and R. S. Harwerth, "Limits of Emmetropization and Developmental Vision Disorders," in Vision Science and its Applications, 1999 OSA Technical Digest Series (Optica Publishing Group, 1999), paper SuA1. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Mitigation of Inter-Cell Interference Utilizing Carrier Allocation in Visible Light Communication System (2012)

It is necessary in visible light communication where different information from adjacent cells is distinguishable without inter-cell interference for indoor localization-based services and positioning systems. In order to mitigate inter-cell interference, a carrier allocation-visible light communication system, adopting various carriers among the system's respective cells, is suggested. The effects of inter-cell interference for a single channel and the proposed systems are investigated by experimentation with simultaneous transmissions of QPSK signals.
A composite kernel to extract relations between entities with both flat and structured features (2006)

This paper proposes a novel composite kernel for relation extraction. The composite kernel consists of two individual kernels: an entity kernel that allows for entity-related features and a convolution parse tree kernel that models syntactic information of relation examples. The motivation of our method is to fully utilize the nice properties of kernel methods to explore diverse knowledge for relation extraction. Our study illustrates that the composite kernel can effectively capture both flat and structured features without the need for extensive feature engineering, and can also easily scale to include more features. Evaluation on the ACE corpus shows that our method outperforms the previous best-reported methods and significantly out-performs previous two dependency tree kernels for relation extraction.
Experimental and numerical study of a hydrogen fuelled I.C. engine fitted with the hydrogen assisted jet ignition system (2007)

The use of hydrogen as an engine fuel poses several challenges as well as opportunities in engine design and control. These challenges are mainly due to hydrogen&apos;s high flame temperatures at near stoichiometric mixtures, as well as the reactant volume fraction which can reduce the engine power output significantly. However, the wide flammability limits of hydrogen combustion in air means that a large part of the engine operation regime can be achieved without the use of the engine throttle or exhaust after treatment. This paper presents results of experiments and computations for a research single cylinder pressure boosted hydrogen fuelled internal combustion engine (H2ICE) fitted with the Hydrogen Assisted Jet Ignition system (HAJI) and running extremely lean mixtures.
Asmarines G and H and Barekol, Three New Compounds from the Marine Sponge <i>Raspailia</i> sp. (2003)

Four asmarines, the known A and F and two new ones G and H, four diterpenes, the known chelodane, barekoxide, and zaatirin and a new one, barekol, and methyl 3-oxo-cholan-24-oate were isolated from the Kenyan sponge Raspailia sp. The structures of all these compounds were established on the basis of MS and NMR data, and the absolute configuration of barekol was determined from the CD measurements of its keto-derivative. The (15)N chemical shifts of the N atoms of the heterocycles of the asmarines were measured from (15)N HMBC experiments, and the influence of various structural features on the delta(N) values studied.
Design of transparent conductive coatings and filters (1992)

There are currently four types of transparent electrically conductive filters available. These are (1) a free-standing conducting inductive mesh, (2) a substrate coated with a conducting inductive mesh, (3) a conducting substrate, and, (4) a substrate coated with a continuous conducting coating. Each can be designed to provide high visible, near infrared, and/or far infrared transmittance and high radio frequency (RF) and microwave reflectance. Itek has developed theoretical models to predict the performance of each filter type at optical and very long wavelengths as a function of pertinent design features such as conductivity, electronic mobility, thickness, mesh period and line width. The temperature dependence is explicitly included. This paper presents Itek’s methods for predicting the performance of these four filter types at both optical and RF frequencies.
A schema for interprocedural modification side-effect analysis with pointer aliasing (2001)

The first interprocedural modification side-effects analysis for C (MOD C ) that obtains better than worst-case precision on programs with general-purpose pointer usage is presented with empirical results. The analysis consists of an algorithm schema corresponding to a family of MOD C algorithms with two independent phases: one for determining pointer-induced aliases and a subsequent one for propagating interprocedural side effects. These MOD C algorithms are parameterized by the aliasing method used. The empirical results compare the performance of two dissimilar MOD C algorithms: MOD C ( FSAlias ) uses a flow-sensitive, calling-context-sensitive interprocedural alias analysis; MOD C ( FIAlias uses a flow-insensitive, calling-context-insensitive alias analysis which is much faster, but less accurate. These two algorithms were profiled on 45 programs ranging in size from 250 to 30,000 lines of C code, and the results demonstrate dramatically the possible cost-precision trade-offs. This first comparative implementation of MOD C analyses offers insight into the differences between flow-/context-sensitive and flow-/context-insensitive analyses. The analysis cost versus precision trade-offs in side-effect information obtained are reported. The results show surprisingly that the precision of flow-sensitive side-effect analysis is not always prohibitive in cost, and that the precision of flow-insensitive analysis is substantially better than worst-case estimates and seems sufficient for certain applications. On average MOD C ( FSAlias ) for procedures and calls is in the range of 20% more precise than MOD C ( FIAlias ); however, the performance was found to be at least an order of magnitude slower than MOD C ( FIAlias ).
A Population Study of Plasma Neuropeptide Y: Correlations with Components of the Metabolic Syndrome (1996)

The positive correlation between LDL-cholesterol and NPY in women, independent of age, and components of the metabolic syndrome, makes it a possible gender-specific cardiovascular riskmarker.
Slow-wave sleep and the risk of type 2 diabetes in humans (2008)

There is convincing evidence that, in humans, discrete sleep stages are important for daytime brain function, but whether any particular sleep stage has functional significance for the rest of the body is not known. Deep non-rapid eye movement (NREM) sleep, also known as slow-wave sleep (SWS), is thought to be the most "restorative" sleep stage, but beneficial effects of SWS for physical well being have not been demonstrated. The initiation of SWS coincides with hormonal changes that affect glucose regulation, suggesting that SWS may be important for normal glucose tolerance. If this were so, selective suppression of SWS should adversely affect glucose homeostasis and increase the risk of type 2 diabetes. Here we show that, in young healthy adults, all-night selective suppression of SWS, without any change in total sleep time, results in marked decreases in insulin sensitivity without adequate compensatory increase in insulin release, leading to reduced glucose tolerance and increased diabetes risk. SWS suppression reduced delta spectral power, the dominant EEG frequency range in SWS, and left other EEG frequency bands unchanged. Importantly, the magnitude of the decrease in insulin sensitivity was strongly correlated with the magnitude of the reduction in SWS. These findings demonstrate a clear role for SWS in the maintenance of normal glucose homeostasis. Furthermore, our data suggest that reduced sleep quality with low levels of SWS, as occurs in aging and in many obese individuals, may contribute to increase the risk of type 2 diabetes.
Heritabilities and Genetic, Environmental and Phenotypic Correlations of Carcass Traits in a Population of Diverse Biological Types and their Implications in Selection Programs (1982)

Genetic, environmental and phenotypic relationships among four growth and 12 carcass traits of 2,453 crossbred steers representing 16 different sire breeds were analyzed. Heritabilities were: birth weight .43; gain to weaning .07; feedlot gain .57; retail product (kg) .58, (percentage) .63; fat trim (kg) .47, (percentage) .57; bone (kg) .57, (percentage) .53; kidney fat (kg) .77, (percentage) .82; fat thickness .41; rib eye area .56; marbling .40 and Warner-Bratzler shear .31. The genetic and environmental correlations differed greatly in magnitude and sign among different trait combinations. Genetic regressions of component tissues on side weight showed that genetic aspects of higher growth rate led to increased growth of lean relative to fat. In contrast, environmental increases in growth rate led to relatively more fat deposition. Expected response was evaluated for six selection criteria at age constant and weight constant bases. When selection for growth rate was evaluated at a constant age, retail product and bone percentages declined and fat trim percentage increased because of increased carcass weight. The trends were reversed when adjusted to a constant slaughter weight. This suggests that selection for increased growth rate results in later maturing lean types. Selection response in fat thickness followed the pattern of response in fat trim percentage and response in rib eye area followed the response in retail product percentage, as expected from the high genetic correlations between these traits. Selection criteria, except gain to weaning, that increased retail product percentage also decreased marbling, but the decline generally was small. Mass selection for rate of gain and against external fat in record of performance programs will improve lean yield of carcasses when evaluated at a constant weight, removing the need for expensive and time consuming progeny tests, unless changes in other carcass traits are desired.
On Some Modern Uses of the Electron in Logic and Memory (1997)

The electron plays a role in many facets of modern life—lighting, heating, welding and so on. Here, I concentrate on the use of electrons primarily in logic and memory. I generally skip the early history—that of electronic tubes—and start instead with the modern integrated circuit and then go on to explore possible alternatives to the now-dominant silicon MOSFET technology. (MOSFET stands for metal oxide semiconductor field-effect transistor.) This approach is enforced not only by space considerations, but also by the fact that the passing years have erased triodes, power pentodes, klystrons, traveling-wave tubes and the like from my memory. Not that they are no longer used; clones of the 6L6, EL34 and KT88 are still used in some of the best audio amplifiers. Microwaves and power applications still rely heavily on tubes. Cathode-ray tubes are still the standard display, although their days may be numbered—at least at the large and small ends. Electron microscopes and lithography tools are, in a sense, large demountable vacuum tubes. (They are the subject of Murray Gibson's article on page 56 in this special issue.) However, over the past 40 years, the vacuum tube has been displaced by solid-state devices as the basis of most computer, low-power amplifier, communications and control circuits. (See figure 1, which shows a computer processing unit.)
Cyclin-dependent kinase 1–dependent activation of APC/C ubiquitin ligase (2016)

Error-free genome duplication and segregation are ensured through the timely activation of ubiquitylation enzymes. The anaphase-promoting complex or cyclosome (APC/C), a multisubunit E3 ubiquitin ligase, is regulated by phosphorylation. However, the mechanism remains elusive. Using systematic reconstitution and analysis of vertebrate APC/Cs under physiological conditions, we show how cyclin-dependent kinase 1 (CDK1) activates the APC/C through coordinated phosphorylation between Apc3 and Apc1. Phosphorylation of the loop domains by CDK1 in complex with p9/Cks2 (a CDK regulatory subunit) controlled loading of coactivator Cdc20 onto APC/C. A phosphomimetic mutation introduced into Apc1 allowed Cdc20 to increase APC/C activity in interphase. These results define a previously unrecognized subunit-subunit communication over a distance and the functional consequences of CDK phosphorylation. Cdc20 is a potential therapeutic target, and our findings may facilitate the development of specific inhibitors.
Sensitive assay for cholesterol in biological membranes reveals membrane‐specific differences in kinetics of cholesterol oxidase (1995)

Quantification of cholesterol in biological membranes from a variety of sources is an important step toward understanding cholesterol's roles in membrane function. We extend to biological membranes the fluorometric/enzymatic approach (cholesterol oxidase) to measure cholesterol, originally described for whole cells (Heider and Boyett [1978] J. Lipid Res., 19:514-518; Gamble et al. [1978] J. Lipid Res., 19:1068-1070) and serum (Huang et al. [1975] Clin Chem., 21:1605-1608). This method has a detection limit of 0.3 microgram cholesterol. As revealed by comparison with high-performance liquid chromatography, the fluorometric/enzymatic method with biological membranes is accurate (within 4% and 8% for intestinal and hepatic plasma membranes, respectively). The assay may be completed within 3 to 4 hours and requires neither lipid extraction nor chromatographic techniques. Kinetics of the cholesterol oxidase reaction are membrane-specific, and first-order rate constants (k) are positively correlated with membrane order.
Absorbance signals from resting frog skeletal muscle fibers injected with the pH indicator dye, phenol red. (1990)

Singly dissected twitch fibers from frog muscle were studied on an optical bench apparatus after micro-injection with the pH indicator dye, phenol red. Dye-related absorbances in myoplasm, denoted by A0(lambda) and A90(lambda), were estimated as a function of wavelength lambda (450 nm less than or equal to lambda less than or equal to 640 nm) with light polarized parallel (0 degrees) and perpendicular (90 degrees) to the fiber axis respectively. At all lambda, A0(lambda) was slightly greater than A90(lambda), indicating that some of the phenol red molecules were bound to oriented structures accessible to myoplasm. The phenol red "isotropic" signal, [A0(lambda) + 2A90(lambda)]/3, a quantity equal to the average absorbance of all the dye molecules independent of their orientation, had a spectral shape that was red-shifted by approximately 10 nm in comparison with in vitro dye calibration curves measured in 140 mM KCl. The red-shifted spectrum also indicates that some phenol red molecules were bound in myoplasm. A quantitative estimate of indicator binding was obtained from measurements of the dye's apparent diffusion constant in myoplasm, denoted by Dapp. The small value of Dapp, 0.37 x 10(-6) cm2 s-1 (at 16 degrees C), can be explained if approximately 80% of the dye was bound to myoplasmic sites of low mobility. To estimate the apparent myoplasmic pH, denoted by pHapp, the isotropic absorbance of phenol red was fitted by in vitro calibration spectra. pHapp was found to be independent of dye concentration (0.2-2 mM), but varied widely (range, 6.8-7.5; mean value, 7.17) among fibers judged from functional characteristics to be normal. When fibers were subjected to acid or alkaline loads by exposure to Ringer's solution containing, respectively, dissolved CO2 or NH3, the changes in pHapp were in agreement with those expected from pH micro-electrode studies. It is concluded that in spite of the several indications for the presence of bound phenol red inside muscle cells, the pHapp signal from the indicator is useful for monitoring changes in myoplasmic pH in response to physiological and pharmacological manipulations.
Development of strain sensors utilizing giant magnetoresistive and tunneling magnetoresistive devices (2003)

This study investigates magnetic layer structures suitable for devices measuring mechanical responses such as stress, strain and pressure. The sensors are based either on giant magnetoresistiance (GMR) structures or on magnetic tunneling junctions (MTJ's) both intentionally prepared with highly magnetostrictive free layer materials. Results for magnetostrictive Fe<sub>50</sub>Co<sub>50</sub> materials or amorphous Co- or Fe-based alloys serving as sensing (or “free”) layers are discussed in view of possible applications. In general, gauge factors in the range of 300-600 have been obtained for strain sensors based on MTJ's, whereas gauge factors of 2-4 are typical for metal based thin film, and 40-180 for piezoresistive strain gauges.