gebhart/patrepeval huggingface dataset:
Nanoparticle Technology for Drug Delivery Across the Blood-Brain Barrier (2002)

Nanoparticles (NP) are solid colloidal particles ranging in size from 1 to 1000 nm that are utilized as drug delivery agents. The use of NPs to deliver drugs to the brain across the blood-brain barrier (BBB) may provide a significant advantage to current strategies. The primary advantage of NP carrier technology is that NPs mask the blood-brain barrier limiting characteristics of the therapeutic drug molecule. Furthermore, this system may slow drug release in the brain, decreasing peripheral toxicity. This review evaluates previous strategies of brain drug delivery, discusses NP transport across the BBB, and describes primary methods of NP preparation and characterization. Further, influencing manufacturing factors (type of polymers and surfactants, NP size, and the drug molecule) are detailed in relation to movement of the drug delivery agent across the BBB. Currently, reports evaluating NPs for brain delivery have studied anesthetic and chemotherapeutic agents. These studies are reviewed for efficacy and mechanisms of transport. Physiological factors such as phagocytic activity of the reticuloendothelial system and protein opsonization may limit the amount of brain delivered drug and methods to avoid these issues are also discussed. NP technology appears to have significant promise in delivering therapeutic molecules across the BBB.
Binding of Peptides with Basic and Aromatic Residues to Bilayer Membranes (2003)

Electrostatic interactions with positively charged regions of membrane-associated proteins such as myristoylated alanine-rich C kinase substrate (MARCKS) may have a role in regulating the level of free phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in plasma membranes. Both the MARCKS protein and a peptide corresponding to the effector domain (an unstructured region that contains 13 basic residues and 5 phenylalanines), MARCKS-(151-175), laterally sequester the polyvalent lipid PI(4,5)P2 in the plane of a bilayer membrane with high affinity. We used high resolution magic angle spinning NMR to establish the location of MARCKS-(151-175) in membrane bilayers, which is necessary to understand the sequestration mechanism. Measurements of cross-relaxation rates in two-dimensional nuclear Overhauser enhancement spectroscopy NMR experiments show that the five Phe rings of MARCKS-(151-175) penetrate into the acyl chain region of phosphatidylcholine bilayers containing phosphatidylglycerol or PI(4,5)P2. Specifically, we observed strong cross-peaks between the aromatic protons of the Phe rings and the acyl chain protons of the lipids, even for very short (50 ms) mixing times. The position of the Phe rings implies that the adjacent positively charged amino acids in the peptide are close to the level of the negatively charged lipid phosphates. The deep location of the MARCKS peptide in the polar head group region should enhance its electrostatic sequestration of PI(4,5)P2 by an "image charge" mechanism. Moreover, this location has interesting implications for membrane curvature and local surface pressure effects and may be relevant to a wide variety of other proteins with basic-aromatic clusters, such as phospholipase D, GAP43, SCAMP2, and the N-methyl-d-aspartate receptor.
Respiratory Sinus Arrhythmia (1996)

These results support our hypothesis that RSA benefits the pulmonary gas exchange and may improve the energy efficiency of pulmonary circulation by "saving heartbeats."
Community-Acquired Methicillin-ResistantStaphylococcus aureusCarrying Panton-Valentine Leukocidin Genes: Worldwide Emergence (2003)

Infections caused by community-acquired (CA)-methicillin--resistant Staphylococcus aureus (MRSA) have been reported worldwide. We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa by performing polymerase chain reaction for 24 virulence factors and the methicillin-resistance determinant. The genetic background of the strain was analyzed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The CA-MRSA strains shared a type IV SCCmec cassette and the Panton-Valentine leukocidin locus, whereas the distribution of the other toxin genes was quite specific to the strains from each continent. PFGE and MLST analysis indicated distinct genetic backgrounds associated with each geographic origin, although predominantly restricted to the agr3 background. Within each continent, the genetic background of CA-MRSA strains did not correspond to that of the hospital-acquired MRSA.
Calcium-Binding Proteins S100A8 and S100A9 as Novel Diagnostic Markers in Human Prostate Cancer (2005)

Our data suggest that enhanced expression of S100A8, S100A9, and RAGE is an early event in prostate tumorigenesis and may contribute to development and progression or extension of prostate carcinomas. Furthermore, S100A9 in serum may serve as useful marker to discriminate between prostate cancer and BPH.
Rapid Transport of Muco-Inert Nanoparticles in Cystic Fibrosis Sputum Treated with N -Acetyl Cysteine (2011)

NAC facilitated rapid diffusion of PEG-coated, muco-inert nanoparticles in CF sputum. Our results provide a promising strategy to improve drug and gene carrier penetration in CF sputum, offering hope for improved therapies for CF.
<title>Architectural approaches for multimedia processors</title> (1997)

This paper presents an overview on architectures for multimedia purposes. Emphasis is given on flexible, programmable processors to enable processing of different standardized or proprietary multimedia applications. Several parallelization strategies to enhance performance especially for video coding are described. This includes architectures like SIMD, MIMD and associative controlling. Exploitation of instruction-level parallelism by use of techniques like VLIW and packed-arithmetic extends this discussion. Reference to design examples from the literature is given. To help develop cost-effective architectures for a set of applications, two methods for modeling hardware and algorithms are explained. Instrumentation of algorithms implemented in software is discussed as a method to determine characteristics and features of given algorithms. Additionally, a more general approach is presented that analyzes different parallelization potentials for a class of algorithms. These are mapped on a simple hardware model using only a few parameters for performance evaluation. Limitations of software instrumentation and the presented modeling approach are discussed.
Familial Thoracic Aortic Aneurysms and Dissections (2001)

A major locus for familial TAAs and dissections maps to 5q13-14, with the majority (9 of 15) of the families identified demonstrating evidence of linkage to this locus. The condition is genetically heterogeneous, with 6 families not demonstrating evidence of linkage to any loci previously associated with aneurysm formation.
Control and prevention of tuberculosis in Britain (1988)

The epidemiology of tuberculosis relevant to methods of prevention and control and the organisation of tuberculosis services in Britain are described. Active case finding is conducted among higher risk groups which include middle aged and elderly native born males, tuberculosis contacts, immigrants from Asia and Africa, and inmates of certain institutions. Regimens of short-course chemotherapy are used which are highly effective in treatment. Guidelines for the selection of individuals for chemoprophylaxis are given. Programmes for the management of patients and staff in hospitals and schools are outlined. BCG vaccination is give to high risk groups including hospital workers, travellers to areas of high prevalence, contacts, immigrants form Asia and Africa, and infants born in Britain of parents of the above immigarant ethnic groups. Mass vaccination of schoolchildren aged 10–14 years remains effective but predications about declining risks of infection in Britain among young persons suggest that routine vaccination of schoolchildren may be stopped in the near future.
Site of Deposition of C3 in Arthus Reactions of C4 Deficient Guinea Pigs (1973)

Summary The site of C3 deposition in the direct Arthus reaction induced in a strain of guinea pigs with a nonoperative classical complement pathway but a functional alternate complement pathway (C4 deficient animals) was examined. The area of hemorrhage, induration, and erythema was identical in these animals and controls. The lesions in homozygous C4 deficient animals showed normal infiltration of neutrophils and normal deposition of C3 by immuno-fluorescent visualization; thus the alternate complement pathway could successfully mediate this inflammatory event.
Mixed alkylation (methylation and ethylation) of adenosine by diazoethane in aqueous 1,2-dimethoxyethane (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMixed alkylation (methylation and ethylation) of adenosine by diazoethane in aqueous 1,2-dimethoxyethaneLee M. Pike, M. Khurshid A. Khan, and Fritz RottmanCite this: J. Org. Chem. 1974, 39, 25, 3674–3676Publication Date (Print):December 1, 1974Publication History Published online1 May 2002Published inissue 1 December 1974https://pubs.acs.org/doi/10.1021/jo00939a013https://doi.org/10.1021/jo00939a013research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
MEMS Accelerometer Based Nonspecific-User Hand Gesture Recognition (2011)

This paper presents three different gesture recognition models which are capable of recognizing seven hand gestures, i.e., up, down, left, right, tick, circle, and cross, based on the input signals from MEMS 3-axes accelerometers. The accelerations of a hand in motion in three perpendicular directions are detected by three accelerometers respectively and transmitted to a PC via Bluetooth wireless protocol. An automatic gesture segmentation algorithm is developed to identify individual gestures in a sequence. To compress data and to minimize the influence of variations resulted from gestures made by different users, a basic feature based on sign sequence of gesture acceleration is extracted. This method reduces hundreds of data values of a single gesture to a gesture code of 8 numbers. Finally, the gesture is recognized by comparing the gesture code with the stored templates. Results based on 72 experiments, each containing a sequence of hand gestures (totaling 628 gestures), show that the best of the three models discussed in this paper achieves an overall recognition accuracy of 95.6%, with the correct recognition accuracy of each gesture ranging from 91% to 100%. We conclude that a recognition algorithm based on sign sequence and template matching as presented in this paper can be used for nonspecific-users hand-gesture recognition without the time consuming user-training process prior to gesture recognition.
A model for testing recombinogenic sequences in the mouse germline (1996)

Homologous recombination is a conserved process of genetic exchange generated by homologous pairing of nucleotides. Species diversity and gene evolution are dependent on the outcomes of recombination during germ cell development, yet systems to study mammalian germline recombination, especially those with applications to human genetics, are not well developed. We report on a transgenic mouse system designed to study recombination within test sequences in the male germline utilizing an intron-interrupted lacZ reporter gene. beta-galactosidase positive sperm are detected and quantitated by flow cytometry using fluorogenic substrates. Examination of recombination within a 1.7 kb repeat of test sequences derived from the human glycophorin breakpoint cluster region detects approximately 0.04-0.09% fluorescent sperm. Confirmation that these sperm result from recombination in the germline comes from histochemical staining of testicular cells, examination of spliced mRNA, and PCR analysis of sorted sperm populations. The system is readily adaptable to studies of other sequences reported to have elevated levels of recombination, including those implicated in human genetic disease. Investigations of the molecular basis for genomic instability at specific chromosomal locations may yield important insights into mechanisms of chromosomal loss and rearrangements.
THE NATURAL HISTORY OF MULTIPLE SCLEROSIS: A GEOGRAPHICALLY BASED STUDY (1989)

Controversy exists regarding the predictive value of the early clinical course of multiple sclerosis (MS). Three parameters often considered are the attack rate, the first interattack interval and the rate at which disability develops in the early years of the disease. We have recorded the time to reach successive levels of disability defined by the Kurtzke Disability Status Scale (DSS) in 1,099 MS patients followed at University Hospital, London, Canada between 1972 and 1984. Our population is particularly suitable because of its size, the high degree of ascertainment of cases in the community, and the regular follow-up provided. Life table analysis was used to compare survival in patients stratified according to the above three parameters using DSS 6 as end point. Significant differences were evident in the survival distributions. Despite the extensive interindividual variation in the rate at which disability developed, the early course of MS may be useful in determining the relative risk of rapid progression.
STING Agonists Induce an Innate Antiviral Immune Response against Hepatitis B Virus (2014)

Chronicity of hepatitis B virus (HBV) infection is due to the failure of a host to mount a sufficient immune response to clear the virus. The aim of this study was to identify small-molecular agonists of the pattern recognition receptor (PRR)-mediated innate immune response to control HBV infection. To achieve this goal, a coupled mouse macrophage and hepatocyte culture system mimicking the intrahepatic environment was established and used to screen small-molecular compounds that activate macrophages to produce cytokines, which in turn suppress HBV replication in a hepatocyte-derived stable cell line supporting HBV replication in a tetracycline-inducible manner. An agonist of the mouse stimulator of interferon (IFN) genes (STING), 5,6-dimethylxanthenone-4-acetic acid (DMXAA), was found to induce a robust cytokine response in macrophages that efficiently suppressed HBV replication in mouse hepatocytes by reducing the amount of cytoplasmic viral nucleocapsids. Profiling of cytokines induced by DMXAA and agonists of representative Toll-like receptors (TLRs) in mouse macrophages revealed that, unlike TLR agonists that induced a predominant inflammatory cytokine/chemokine response, the STING agonist induced a cytokine response dominated by type I IFNs. Moreover, as demonstrated in an HBV hydrodynamic mouse model, intraperitoneal administration of DMXAA significantly induced the expression of IFN-stimulated genes and reduced HBV DNA replication intermediates in the livers of mice. This study thus proves the concept that activation of the STING pathway induces an antiviral cytokine response against HBV and that the development of small-molecular human STING agonists as immunotherapeutic agents for treatment of chronic hepatitis B is warranted.
Nucleotide sequences of Saccharomycopsis fibuligera genes for extracellular beta-glucosidases as expressed in Saccharomyces cerevisiae (1988)

We isolated two genes for extracellular beta-glucosidase, BGL1 and BGL2, from the genomic library of the yeast Saccharomycopsis fibuligera. Gene products (BGLI and BGLII) were purified from the culture fluids of Saccharomyces cerevisiae transformed with BGL1 and BGL2, respectively. Molecular weights of BGLI and BGLII were estimated to be 220,000 and 200,000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The two beta-glucosidases showed the same enzymatic characteristics, such as thermo-denaturation kinetics and dependencies on pH and temperature, but quite different substrate specificities: BGLI hydrolyzed cellobiose efficiently, but BGLII did not. This result is consistent with the observation that the S. cerevisiae transformant carrying BGL1 fermented cellobiose to ethanol but the transformant carrying BGL2 did not. Southern blot analysis revealed that the two beta-glucosidase genes were derived from Saccharomycopsis fibuligera and that the nucleotide sequences of the two genes are closely related. The complete nucleotide sequences of the two genes were determined. BGL1 and BGL2 encode 876- and 880-amino-acid proteins which were shown to be highly similar to each other. The putative precursors begin with hydrophobic segments that presumably act as signal sequences for secretion. Amino acid analysis of the purified proteins confirmed that BGL1 and BGL2 encode BGLI and BGLII, respectively.
Use of Piezoelectric-Excited Millimeter-Sized Cantilever Sensors To Measure Albumin Interaction with Self-Assembled Monolayers of Alkanethiols Having Different Functional Headgroups (2006)

In this paper, we describe a new modality of measuring human serum albumin (HSA) adsorption continuously on CH3-, COOH-, and OH-terminated self-assembled monolayers (SAMs) of C11-alkanethiols and the direct quantification of the adsorbed amount. A gold-coated piezoelectric-excited millimeter-sized cantilever (PEMC) sensor of 6-mm2 sensing area was fabricated, where resonant frequency decreases upon mass increase. The resonant frequency in air of the detection peak was 45.5 +/- 0.01 kHz. SAMs of C11-thiols (in absolute ethanol) with different end groups was prepared on the PEMC sensor and then exposed to buffer solution containing HSA at 10 microg/mL. The resonant frequency decreased exponentially and reached a steady-state value within 30 min. The decrease in resonant frequency indicates that the mass of the sensor increased due to HSA adsorption onto the SAM layer. The frequency change obtained for the HSA adsorption on CH3-, COOH-, and OH-terminated SAM were 520.8 +/- 8.6 (n = 3), 290.4 +/- 6.1 (n = 2), and 210.6 +/- 8.1 Hz (n = 3), respectively. These results confirm prior conclusions that albumin adsorption decreased in the order, CH(3) > COOH > OH. Observed binding rate constants were 0.163 +/- 0.003, 0.248 +/- 0.006, and 0.381 +/- 0.001 min(-1), for methyl, carboxylic, and hydroxyl end groups, respectively. The significance of the results reported here is that both the formation of self-assembled monolayers and adsorption of serum protein onto the formed layer can be measured continuously, and quantification of the adsorbed amount can be determined directly.
Deflections at Sea (1973)

The possibility of utilizing bathymetric data is explored for determining or interpolating deflections of the vertical at sea if gravimetric anomalies are not available or do not have sufficient density. A Pacific atoll where 23 astrogeodetic deflections of the vertical ranging from −24″ to 29″ in the meridian and from −19″ to 22″ in the prime vertical have been observed is studied as a test case to determine the accuracy with which the given deflection values can be reproduced. Sixteen of the deflections were used as indicators of the unknown density distribution in order to choose from several tentative models of the area the one with the smallest residuals. With this model, a crude combination of five point masses, the observed deflection values at the remaining seven stations could be reproduced with an rms error of less than 1.5″ in each component.
The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation (2005)

A previously unknown signal transduction pathway is important in human cognitive development.
Cell surface morphology identifies microglia as a distinct class of mononuclear phagocyte (1995)

To investigate differences among brain-derived microglia and other classes of immune cells, we compared the morphologies and growth properties of mononuclear phagocytes isolated from tissues of the newborn rat. Scanning EM shows that microglia from postnatal rat brain are covered with spines (typically > 20 per cell body) in a distinctive manner which contrasts the smooth surfaces of bone marrow cells and the ruffled surfaces of tissue macrophages from spleen, liver, and peritoneum. The spine-bearing surface of microglia is a specific cell marker, for it does not change with age or after exposure to cytokines or other immunostimulants. Approximately 99% of mononuclear phagocytes cultured from normal adult rat brain are spinous microglia. Five days after injury to rat brain, cells at sites of Wallerian degeneration are essentially all spinous ones while nearly 30% of cells found within areas of infarction or penetrating trauma are invading macrophages. In a similar way, nearly all cells isolated from normal, postmortem adult human brain are spine-bearing microglia (> 99% homogeneity). Brains from patients with amyotrophic lateral sclerosis contain only spinous microglia whereas cells from HIV-1 infected brains include significant numbers of invading ruffled macrophages. Cultured microglia, unlike cultured bone marrow precursors, monocytes, or tissue macrophages, spontaneously develop long, thin processes that extend hundreds of microns in length. Microglia retract these processes after exposure to fetal bovine serum, laminin, or such immunostimulants as recombinant murine interferon gamma (rmIFN gamma) and lipopolysaccharide. Of all types of mononuclear phagocytes tested, only microglia differentiate into quiescent ramified cells when in contact with astrocytes. Thus, microglia represent a unique class of cell maintained, in part, by astroglia as dormant, ramified mononuclear phagocytes in mature CNS. Application of cell surface criteria described here will allow study of distinct populations of mononuclear phagocytes associated with neurologic disorders.