gebhart/patrepeval huggingface dataset:
Free Radical Theory Of Aging (1993)

SummaryAging is the accumulation of changes responsible for both the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. The production of these changes can be attributed to the environment and disease and to an inborn aging process (es). Past improvements in general living conditions have decreased the chances for death so that they are now near limiting values in the developed countries. In these countries the aging process is the major cause of disease and death after about age 28. The free radical theory of aging postulates that aging changes are caused by free radical reactions. Support for this theory is extensive; it includes: 1) studies on the origin and evolution of life, 2) studies of the effect of ionizing radiation on living things, 3) dietary manipulation of endogenous free radical reactions, 4) the plausible explanation it provides for aging phenomena, and 5) the growing number of studies that implicate free radical reactions in the pathogenesis of specific diseases. On the basis of present data the healthy active life span may be increased by 5-10 or more years by keeping body weight down, at a level compatible with a sense of well-being while ingesting diets adequate in essential nutrients but designed to minimize random free radical reactions in the body.
High-power 1.3 μm superluminescent diode (1989)

Superluminescent diodes with high output power (10 mW at 175 mA), wide spectral width (28 nm), low spectral modulation depth (&amp;lt;15%), wide frequency modulation bandwidth (570 MHz), and high single-mode fiber coupling efficiency (40%) are reported. The structure is based on a buried crescent laser structure with an antireflection coating and a ‘‘short-circuit’’ absorber to suppress lasing.
CHARACTERISTICS OF POST TRAUMA ANERGIC T CELLS AND THEIR CLINICAL RELEVANCE. (1997)

De, A. K.; Kodys, K.; Pellegrini, J.; Puyana, J. C.; Miller-Graziano, C. Author Information
Protective and pathological roles of nitric oxide in endotoxin shock (1992)

Inhibition of both constitutive and inducible NO synthases during endotoxaemia is deleterious. This can be overcome by replacing NO intravenously with a donor of NO. Selective inhibition of the inducible NO synthase may, however, be beneficial in shock.
Strain accommodation and interfacial structure of AlN interlayers in GaN (2009)

Abstract The strain accommodation mechanisms at AlN interlayers in GaN, grown by radio‐frequency plasma assisted molecular beam epitaxy, are studied using transmission electron microscopy techniques and atomistic modelling. Interlayers of various thicknesses grown within GaN epilayers deposited on both sapphire and silicon substrates have been employed. Interlayers of thickness below 6 nm do not exhibit line defects although local roughness of the upper interlayer interface is observed as a result of the Al adatom kinetics and higher interfacial energy compared to the lower interface. Above 6 nm, introduction of a ‐type misfit and threading dislocations constitutes the principal relaxation mechanism. Due to strain partitioning between AlN and GaN, threading dislocations adopt inclined zig‐zag lines thus contributing to the relief of alternating compressive‐tensile elastic strain across the AlN/GaN heterostructure. The observed dislocation configurations are consistent with a model of independent motion by climb or ancillary glide in response to their localized three‐dimensional strain environment. (© 2009 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
An Introduction to the Crystallogenesis of Biological Macromolecules (1999)

The word ‘crystal’ is derived from the Greek root ‘krustallos’ meaning ‘clear ice’. Like ice, crystals are chemically well defined, and many among of them are of transparent and glittering appearance, like quartz, which was for a long time the archetype. Often they are beautiful geometrical solids with regular faces and sharp edges, which probably explains why crystallinity, even in the figurative meaning, is taken as a symbol of perfection and purity. From the physical point of view, crystals are regular three-dimensional arrays of atoms, ions, molecules, or molecular assemblies. Ideal crystals can be imagined as infinite and perfect arrays in which the building blocks (the asymmetric units) are arranged according to well-defined symmetries (forming the 230 space groups) into unit cells that are repeated in the three-dimensions by translations. Experimental crystals, however, have finite dimensions. An implicit consequence is that a macroscopic fragment from a crystal is still a crystal, because the orderly arrangement of molecules within such a fragment still extends at long distances. The practical consequence is that crystal fragments can be used as seeds (Chapter 7). In laboratory-grown crystals the periodicity is never perfect, due to different kinds of local disorders or long-range imperfections like dislocations. Also, these crystals are often of polycrystalline nature. The external forms of crystals are always manifestations of their internal structures and symmetries, even if in some cases these symmetries may be hidden at the macroscopic level, due to differential growth kinetics of the crystal faces. Periodicity in crystal architecture is also reflected in their macroscopic physical properties. The most straightforward example is given by the ability of crystals to diffract X-rays, neutrons, or electrons, the phenomenon underlying structural chemistry and biology (for introductory texts see refs 1 and 2), and the major aim of this book is to present the methods employed to produce three-dimensional crystals of biological macromolecules, but also two-dimensional crystals (Chapter 12), needed for diffraction studies. Other properties of invaluable practical applications should not be overlooked either, as is the case of optical and electronic properties which are at the basis of non-linear optics and modern electronics (for an introduction to physical properties of molecular crystals see ref. 3).
Passive immunization of mice againstCandida albicans (1968)

Three similar groups of mice were given either pooled immune serum from vaccinated mice, normal mouse serum or normal saline. The animals were then challenged simultaneously with a single intravenous dose of 1 × 105 viable units of C. albicans.Passive immunization conferred demonstrable protection, inasmuch as the length of survival of those animals that died was considerably extended, and 33% of the animals survived the entire period of observation.
A Combinatorial Approach to Materials Discovery (1995)

A method that combines thin film deposition and physical masking techniques has been used for the parallel synthesis of spatially addressable libraries of solid-state materials. Arrays containing different combinations, stoichiometries, and deposition sequences of BaCO(3), Bi(2)O(3), CaO, CuO, PbO, SrCO(3), and Y(2)O(3) were generated with a series of binary masks. The arrays were sintered and BiSrCaCuO and YBaCuO superconducting films were identified. Samples as small as 200 micrometers by 200 micrometers in size were generated, corresponding to library densities of 10,000 sites per square inch. The ability to generate and screen combinatorial libraries of solid-state compounds, when coupled with theory and empirical observations, may significantly increase the rate at which novel electronic, magnetic, and optical materials are discovered and theoretical predictions tested.
Mechanisms by which indigenous microorganisms colonize gastrointestinal epithelial surfaces. (1983)

Indigenous microorganisms are known to associate with epithelial surfaces in the gastrointestinal tracts of birds and mammals of many species. In general, the mechanisms by which microorganisms associate with the epithelia are poorly understood. In some cases, in associating with epithelial surfaces, the microbial species involved undoubtedly colonize (i. e., multiply on) them. Some examples of such microorganisms are strains of certain Lactobacillus, and Candida (Torulopsis) species that associate with gastric surfaces, and strains of segmented, filamentous and of oxygen-intolerant anaerobic bacteria of numerous species that associate with intestinal surfaces in mice and rats. Several properties of the microbial cells involved may be important for them to be able to colonize epithelial habitats. Some such properties are a capacity for the cells to adhere to structures on the epithelium, or to be motile and able to move into the mucous gel present on most gastrointestinal surfaces. In addition, microorganisms that can colonize surface microhabitats on gastric or intestinal epithelia must be able to thrive in the environments and nutritional circumstances found in such habitats. In this respect, a capacity to multiply well in environments containing high concentrations of hydrogen ion is important for microbial cells to be able to colonize gastric surfaces, while a capacity enzymatically to digest mucinous glycoproteins and use the degradation products as carbon, energy and nitrogen sources may be important for microorganisms to be able to colonize most gastric or epithelial surfaces. These and related issues are examined in this paper.
Cholesterol-lowering efficacy of a microencapsulated bile salt hydrolase-activeLactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolaemic adults (2011)

Several studies have reported limited or no reduction in serum cholesterol in response to probiotic formulations. Recently, probiotics have shown promise in treating metabolic disease due to improved strain selection and delivery technologies. The aim of the present study was to evaluate the cholesterol-lowering efficacy of a yoghurt formulation containing microencapsulated bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, taken twice per d over 6 weeks, in hypercholesterolaemic adults. A total of 114 subjects completed this double-blind, placebo-controlled, randomised, parallel-arm, multi-centre study. This interventional study included a 2-week washout, 2-week run-in and 6-week treatment period. Subjects were randomised to consume either yoghurts containing microencapsulated L. reuteri NCIMB 30242 or placebo yoghurts. Over the intervention period, subjects consuming yoghurts containing microencapsulated L. reuteri NCIMB 30242 attained significant reductions in LDL-cholesterol (LDL-C) of 8·92 % ( P = 0·016), total cholesterol (TC) of 4·81 % ( P = 0·031) and non-HDL-cholesterol (HDL-C) of 6·01 % ( P = 0·029) over placebo, and a significant absolute change in apoB-100 of − 0·19 mmol/l ( P = 0·049). Serum concentrations of TAG and HDL-C were unchanged over the course of the study. Present results show that consumption of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurt is efficacious and safe for lowering LDL-C, TC, apoB-100 and non-HDL-C in hypercholesterolaemic subjects. The efficacy of microencapsulated BSH-active L. reuteri NCIMB 30242 yoghurts appears to be superior to traditional probiotic therapy and akin to that of other cholesterol-lowering ingredients.
Maraviroc (UK-427,857), a Potent, Orally Bioavailable, and Selective Small-Molecule Inhibitor of Chemokine Receptor CCR5 with Broad-Spectrum Anti-Human Immunodeficiency Virus Type 1 Activity (2005)

Maraviroc (UK-427,857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Maraviroc demonstrated potent antiviral activity against all CCR5-tropic HIV-1 viruses tested, including 43 primary isolates from various clades and diverse geographic origin (geometric mean 90% inhibitory concentration of 2.0 nM). Maraviroc was active against 200 clinically derived HIV-1 envelope-recombinant pseudoviruses, 100 of which were derived from viruses resistant to existing drug classes. There was little difference in the sensitivity of the 200 viruses to maraviroc, as illustrated by the biological cutoff in this assay (= geometric mean plus two standard deviations [SD] of 1.7-fold). The mechanism of action of maraviroc was established using cell-based assays, where it blocked binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry. Maraviroc did not affect CCR5 cell surface levels or associated intracellular signaling, confirming it as a functional antagonist of CCR5. Maraviroc has no detectable in vitro cytotoxicity and is highly selective for CCR5, as confirmed against a wide range of receptors and enzymes, including the hERG ion channel (50% inhibitory concentration, >10 microM), indicating potential for an excellent clinical safety profile. Studies in preclinical in vitro and in vivo models predicted maraviroc to have human pharmacokinetics consistent with once- or twice-daily dosing following oral administration. Clinical trials are ongoing to further investigate the potential of using maraviroc for the treatment of HIV-1 infection and AIDS.
"Do Animals Have Accents?" (2017)

In this paper we unpack the use of conversational agents, or so-called intelligent personal assistants (IPAs), in multi-party conversation amongst a group of friends while they are socialising in a café. IPAs such as Siri or Google Now can be found on a large proportion of personal smartphones and tablets, and are promoted as 'natural language' interfaces. The question we pursue here is how they are actually drawn upon in conversational practice? In our work we examine the use of these IPAs in a mundane and common-place setting and employ an ethnomethodological perspective to draw out the character of the IPA-use in conversation. Additionally, we highlight a number of nuanced practicalities of their use in multi-party settings. By providing a depiction of the nature and methodical practice of their use, we are able to contribute our findings to the design of IPAs.
Hormone regulation of human prostate in organ culture. (1993)

We have established organ cultures of human prostate for in vitro analysis of the hormone responsiveness of prostatic carcinoma. Tissue samples were obtained from total prostatectomies for localized cancer. Normal prostate tissues with age-related hyperplastic changes were obtained from cystoprostatectomies of bladder cancer patients representing the same age group, and they wer cultivated as controls. The explants of prostates were cultured for 7 days in basal medium containing 5% dextran charcoal-treated fetal calf serum, insulin (0.08 IU/ml), and dexamethasone (10(-7) M) with or without dihydrotestosterone (DHT) (10(-7) M) or estradiol (10(-9) M). Control prostates showed involutive changes of morphology when cultured in basal medium. These changes were prevented by DHT, which also maintained a strong epithelial immunostaining for PSA (prostate specific antigen), which was used as a marker for tissue-specific functions. The concentration of PSA in the medium was high. The rate of [3H]thymidine incorporation into DNA was stimulated by DHT in some cultures of control prostates, but no increase was seen in the others. Androgen stimulation of [3H]thymidine incorporation was consistently inhibited by the antihormone cyproterone acetate. The main morphological response of cultured control prostates to estradiol was induction of squamous metaplasia. This was associated with increased incorporation of [3H]thymidine, which was radioautographically localized to the basal layer of epithelium. Estradiol effects were counteracted by the antihormone toremifene. The expression of androgen receptor mRNA and protein in cultured control prostate was demonstrated by Northern blotting and immunohistochemistry, respectively. Also, the expression of estrogen receptor was demonstrated by the polymerase chain reaction analysis of total mRNA from cultured control and cancer prostate. The cultured explants of prostate cancer maintained the overall morphology of the original carcinoma. However, the presence of DHT improved the morphology of cancerous acini in all better differentiated carcinomas (3 grade I and 5 grade II), and corresponding responses to DHT were observed in the rate of DNA labeling with [3H]thymidine. In 2 of 3 grade I carcinomas, DHT increased DNA synthesis, but in grade II cancers the patterns of hormone responses were more variable. The poorly differentiated grade III prostatic carcinomas did not respond to either hormone as measured by [3H]thymidine uptake, and no hormone effects could be seen in morphology. Immunostaining for PSA differed from that in control prostates: besides cancerous acini, the surrounding stroma was also intensively stained, which suggests unpolarized and impaired secretion of PSA by the cancer cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing (2014)

Adeno-associated virus (AAV) capsid engineering is an emerging approach to advance gene therapy. However, a systematic analysis on how each capsid amino acid contributes to multiple functions remains challenging. Here we show proof-of-principle and successful application of a novel approach, termed AAV Barcode-Seq, that allows us to characterize phenotypes of hundreds of different AAV strains in a high-throughput manner and therefore overcomes technical difficulties in the systematic analysis. In this approach, we generate DNA barcode-tagged AAV libraries and determine a spectrum of phenotypes of each AAV strain by Illumina barcode sequencing. By applying this method to AAV capsid mutant libraries tagged with DNA barcodes, we can draw a high-resolution map of AAV capsid amino acids important for the structural integrity and functions including receptor binding, tropism, neutralization and blood clearance. Thus, Barcode-Seq provides a new tool to generate a valuable resource for virus and gene therapy research.
Exact evaluation of Catmull-Clark subdivision surfaces at arbitrary parameter values (1998)

In this paper we disprove the belief widespread within the computer graphics community that Catmull-Clark subdivision surfaces cannot be evaluated directly without explicitly subdividing. We show that the surface and all its derivatives can be evaluated in terms of a set of eigenbasis functions which depend only on the subdivision scheme and we derive analytical expressions for these basis functions. In particular, on the regular part of the control mesh where Catmull-Clark surfaces are bi-cubic B-splines, the eigenbasis is equal to the power basis. Also, our technique is both easy to implement and efficient. We have used our implementation to compute high quality curvature plots of subdivision surfaces. The cost of our evaluation scheme is comparable to that of a bi-cubic spline. Therefore, our method allows many algorithms developed for parametric surfaces to be applied to Catmull-Clark subdivision surfaces. This makes subdivision surfaces an even more attractive tool for free-form surface modeling.
Clozapine-Induced Sialorrhea Treated With Sublingual Ipratropium Spray (2004)

*Freedom Trail Clinic, MGH Schizophrenia Program, Boston MA; †Harvard Medical School, Boston, MA [email protected]
Responses of ewes to B. melitensis Rev1 vaccine administered by subcutaneous or conjunctival routes at different stages of pregnancy. (1989)

An experiment to determine the innocuousness and the humoral immune response of B. melitensis Rev1 vaccine was carried out in pregnant ewes. Thirty-three ewes were vaccinated on day 55 of pregnancy: 9 ewes received 2 X 10(9) Rev1 of French origin by the subcutaneous route, 9 ewes were conjunctivally vaccinated with 5 X 10(8) of the same strain, 7 ewes were subcutaneously vaccinated with 10(9) Rev1 of Spanish origin and 8 ewes received 1.8 X 10(9) Spanish strain Rev1 by conjunctival route. Another group (8 animals) were subcutaneously vaccinated with a reduced dose (10(6) of the French strain between days 90 and 120 of pregnancy. Finally, 20 ewes were vaccinated on day 120 of pregnancy with the French strain of which 11 received 10(9) Rev1 by the subcutaneous route and 9 were conjunctivally vaccinated with the same dose. Rev1 strain was isolated from the vaginal discharge of a significantly higher number of ewes vaccinated subcutaneously than in conjunctivally vaccinated ewes (24/35 versus 9/26 respectively; P less than 0.001). No difference between the two vaccine strains was recorded in the number of ewes excreting Rev1. Ewes subcutaneously vaccinated on day 55 of pregnancy aborted more frequently than conjunctivally vaccinated ewes (11/16 versus 2/17, respectively), hence a significantly reduced (P less than 0.001) length of pregnancy. Although 10 of the 11 animals subcutaneously vaccinated on day 120 of pregnancy excreted Rev1 strain, only one aborted. There was no significant effect of the time of vaccination on both abortions and length of pregnancy in ewes conjunctivally vaccinated with the French strain.(ABSTRACT TRUNCATED AT 250 WORDS)
[Semi-synthesis and proposed structure of platelet-activating factor (P.A.F.): PAF-acether an alkyl ether analog of lysophosphatidylcholine]. (1979)

We have studied the molecular structure of platelet-activating factor" (P.A.F.), a mediator of inflammation obtained from blood leukocytes, macrophages, and platelets themselves. We have semi-synthetized a substance that possesses all the known physicochemical and biological characteristics of P.A.F. from hog leukocytes. This was performed by successive methylation, hydrogenation, and acetylation of lysophosphatidylethanolamine plasmalogen. We therefore propose the following structure for P.A.F.: 1-0-alkyl-2-acetyl-glyceryl-3-phosphorylcholine. This molecular structure is not yet described among the numerous substances capable of inducing platelet aggregation and release.
Human apolipoprotein E. Determination of the heparin binding sites of apolipoprotein E3. (1986)

The interaction of human apolipoprotein (apo-) E3 with heparin was examined using heparin-Sepharose as a model system. The approach taken to determine the region of apo-E that is responsible for binding to heparin was to identify apo-E monoclonal antibodies that inhibited heparin binding, to determine the epitopes of the inhibiting antibodies, and finally to examine the heparin binding of fragments containing the inhibiting antibody epitopes. Three antibodies, designated 1D7, 6C5, and 3H1, were found to inhibit binding, suggesting that multiple heparin binding sites were present on apo-E. The epitopes of the inhibiting antibodies were determined by immunoblot analysis of synthetic or proteolytic fragments of apo-E. Measurement of the heparin binding activity of fragments containing epitopes of the inhibiting antibodies demonstrated that apo-E3 contains two heparin binding sites. The first site is located in the vicinity of residues 142-147 and coincides with the 1D7 epitope. The second binding site is contained in the carboxyl-terminal region of apo-E and is inhibited by 3H1, the epitope of which is located between residues 243 and 272. The epitope of the third inhibiting antibody, 6C5, is located at the amino terminus of apo-E; however, this antibody inhibits the second heparin binding site located in the carboxyl-terminal region. A head-to-tail association of apo-E, in which the 6C5 epitope and the second heparin binding site would be in close proximity, is proposed to account for this observation. In the lipid-free state both heparin binding sites on apo-E are expressed; however, when apo-E is complexed to phospholipid or on the surface of a lipoprotein particle, only the first binding site (residues 142-147) is expressed.