gebhart/patrepeval huggingface dataset:
Contribution of Known and Unknown Susceptibility Genes to Early-Onset Diabetes in Scandinavia (2002)

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with > or =2 members with onset of diabetes < or =45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302). Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G mitochondrial DNA mutation were detected by single-strand conformation polymorphism and direct sequencing. To increase homogeneity, we analyzed a subsample of five families with autosomal dominant inheritance of EOD (greater than or equal to two members with age at diagnosis < or =35 years). The highest NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and 16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. Our data also point at putative chromosomal regions, which could harbor novel genes that contribute to EOD.
Mapping the Domain(s) Critical for the Binding of Human Tumor Necrosis Factor-α to Its Two Receptors (1995)

The extracellular domains of the two human tumor necrosis factor (TNF) receptors critical for binding TNF-alpha were examined by deletion mapping. The ligand binding capability of full-length and truncated recombinant soluble TNF receptors (TNFRs) was assessed by ligand blot analysis and their binding affinity determined by Scatchard analysis. The results showed that deletion of the fourth cysteine-rich domain of the p55 receptor (TNFR-1) did not alter ligand binding affinity significantly. Deletion of domains 3 and 4 of TNFR-1 resulted in no ligand binding, suggesting that domain 3, but not 4, of TNFR-1 binds directly to ligand. Deletion of domain 4 of TNFR-2 resulted in drastically reduced protein yield and 3-fold reduction in ligand binding affinity, while deletion of both domains 4 and 3 yielded no protein. Thus, the domain 4 of TNFR-2, but not that of TNFR-1, appears to be involved directly in binding TNF, although it is also possible that the domain 4 of TNFR-2 is involved in the correct folding of other domains. These results suggest that the modes of interaction between TNF-alpha and its dual receptors are different, providing opportunity to modulate each receptor specifically for research and therapeutic purposes.
Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia. (1994)

Severe congenital neutropenia (Kostmann syndrome) is characterized by profound absolute neutropenia and a maturation arrest of marrow progenitor cells at the promyelocyte-myelocyte stage. Marrow cells from such patients frequently display a reduced responsiveness to granulocyte-colony-stimulating factor (G-CSF). G-CSF binds to and activates a specific receptor which transduces signals critical for the proliferation and maturation of granulocytic progenitor cells. Here we report the identification of a somatic point mutation in one allele of the G-CSF receptor gene in a patient with severe congenital neutropenia. The mutation results in a cytoplasmic truncation of the receptor. When expressed in murine myeloid cells, the mutant receptor transduced a strong growth signal but, in contrast to the wild-type G-CSF receptor, was defective in maturation induction. The mutant receptor chain may act in a dominant negative manner to block granulocytic maturation.
Surface Acoustic Wave Nebulization Facilitating Lipid Mass Spectrometric Analysis (2012)

Surface acoustic wave nebulization (SAWN) is a novel method to transfer nonvolatile analytes directly from the aqueous phase to the gas phase for mass spectrometric analysis. The lower ion energetics of SAWN and its planar nature make it appealing for analytically challenging lipid samples. This challenge is a result of their amphipathic nature, labile nature, and tendency to form aggregates, which readily precipitate clogging capillaries used for electrospray ionization (ESI). Here, we report the use of SAWN to characterize the complex glycolipid, lipid A, which serves as the membrane anchor component of lipopolysaccharide (LPS) and has a pronounced tendency to clog nano-ESI capillaries. We also show that unlike ESI SAWN is capable of ionizing labile phospholipids without fragmentation. Lastly, we compare the ease of use of SAWN to the more conventional infusion-based ESI methods and demonstrate the ability to generate higher order tandem mass spectral data of lipid A for automated structure assignment using our previously reported hierarchical tandem mass spectrometry (HiTMS) algorithm. The ease of generating SAWN-MS(n) data combined with HiTMS interpretation offers the potential for high throughput lipid A structure analysis.
Gelucire: A versatile polymer for modified release drug delivery system (2018)

Poly ethylene glycol (PEG) ester surfactants are synthesized by reacting polyethylene glycol with fatty acid. The polyethylene glycol comprises the hydrophilic part of the surfactant and the fatty acid is the lipophilic part. By varying the molecular weight of the PEG and the fatty acid, surfactants covering wide range of hydrophilic lipophilic balance (HLB) values can be produced. Gelucire is the family of vehicle derived from mixtures of mono, di and triglycerides with PEG esters of fatty acids. These are available with range of properties depending on their HLB and melting point range (33–65 °C). They have a wide variety of application in oral and topical formulations. The applications of oral formulation include solubility and bioavailability enhancement, sustain drug release, taste masking and active pharmaceutical ingredient (API) protection from oxygen, light and humidity. The applications of topical formulations include stabilization of creams, lotions and gels, thickener, superior penetration of drug through skin. Gelucire containing only PEG esters are generally used in the preparation of fast release formulations. Gelucire containing only glycerides or a mixture of glycerides and PEG esters are used in the preparation of sustained release formulations. Owing to their extreme hydrophobicity and low density, are considered as appropriate carriers for designing sustained release drug delivery systems. In this review manuscript, applications of various grades of gelucire are compiled in the form of tables and discussed critically. A current literature on patents on gelucire based formulations was also discussed.
Immunological determinants of nerve growth factor involved in p140trk (Trk) receptor binding (1994)

Monoclonal anti-NGF antibodies that specifically inhibit the biological activity of mouse beta-NGF were used to study the structural determinants involved in the interaction of NGF with its receptors gp75LNGFR and Trk. None of the three antibodies--N60, M15, and 27/21--showed any reactivity toward denatured NGF. Three experimental methods--radioimmunoassay (RIA), enzyme-linked immunoassay (ELISA), and slot blots--detected no significant cross reactivity between the antibodies and BDNF or NT-3. RIA showed that M15 and N60 recognize the same or an overlapping antigenic site, but 27/21 recognizes a different epitope. Only 27/21, and not N60 or M15, immunoprecipitated beta-NGF crosslinked to LNGFR receptor. Thus, the epitope recognized by 27/21 does not overlap the LNGFR receptor binding site. N60, M15, and 27/21 all block binding of NGF to Trk in a manner consistent with competitive inhibition. Purified Fab fragments of N60 and M15 gave similar results to the intact antibodies. The other subunits present in the 7S complex of NGF, i.e. the alpha and gamma subunits, competitively inhibited binding of antibodies to beta-NGF. Only the gamma subunit inhibited phosphorylation of Trk and biological activity of beta-NGF. These findings suggest that the M15, N60, and 27/21 antibodies bind to a specific site on the surface of NGF where they competitively inhibit binding to the Trk NGF receptor. The region encompassing the N-terminus, the C-terminus, and the loop on the surface of beta-NGF containing residues 60-80 is proposed as important for binding to the Trk receptor.
Storing and releasing light in a gas of moving atoms (2003)

We propose a scheme of storing and releasing pulses or cw beams of light in a moving atomic medium illuminated by two stationary and spatially separated control lasers. The method is based on electromagnetically induced transparency but in contrast to previous schemes, storage and retrieval of the probe pulse can be achieved at different locations and without switching off the control laser.
Development of Des-Fatty Acyl-Polymyxin B Decapeptide Analogs with Pseudomonas aeruginosa-Specific Antimicrobial Activity (2009)

Twelve N-terminal analogs of des-fatty acyl-polymyxin B (Des-FA-[X(1)]-PMB, X=various amino acids or peptides) were synthesized and examined for their antimicrobial activity against Escherichia coli (E. coli), Salmonella Typhimurium (S. Typhimurium) and Pseudomonas aeruginosa (P. aeruginosa). It was found that Des-FA-[Dap(1)]-, Des-FA-[Ser(1)]-, Des-FA-[Dab-Dab-Dab(1)]- and Des-FA-[Arg-Arg-Arg(1)]-PMB had potent activity only against P. aeruginosa, with MIC values of 0.5-1 nmol/ml. Analogs in which X was Lys, Arg, Leu or Ala did not have increased antimicrobial activity against the three bacterial species tested compared with the lead compounds Des-FA-[Dab(1)]-PMB and polymyxin B (PMB). Des-FA-[Trp(1)]-PMB and Des-FA-[Phe(1)]-PMB had reduced activity against P. aeruginosa. The results indicate that compact hydrophilic amino acids (C3) or basic tripeptides at the N-terminal provide specificity for bactericidal activity towards P. aeruginosa. For LPS-binding activity, Des-FA-[Dab-Dab-Dab(1)]-PMB and Des-FA-[Arg-Arg-Arg(1)]-PMB showed activity comparable to PMB, while Des-FA-[Ala-Ala-Ala(1)]-PMB showed very low activity. Reduced acute toxicity of Des-FA-[Dap(1)]-PMB and Des-FA-[Trp(1)]-PMB was demonstrated by a mouse tail intravenous administration test, with LD(50) values of 23.5 and 19.0 micromol/kg, respectively, in contrast to PMB (LD(50), 4.8 micromol/kg).
Considerations for extraction of monoclonal antibodies targeted to different subcellular compartments in transgenic tobacco plants (2008)

Monoclonal antibody production from transgenic tobacco plants offers many advantages over other heterologous production systems, creating the prospect of production at a scale that will allow new prophylactic and therapeutic applications in global human and animal health. However, information on the major processing factors to consider for large-scale purification of antibodies from transgenic plants is currently limited, and is in urgent need of attention. The purpose of this project was to investigate methods for the initial extraction of recombinant immunoglobulin G (IgG) antibodies from transgenic tobacco leaf tissue. Three different transgenic plant lines were studied in order to establish the parameters for optimal extraction of monoclonal antibodies that accumulate in the apoplasm, at the plasma membrane or within the endoplasmic reticulum. For each transgenic line, seven techniques for physical extraction were compared. The factors that determine the optimal extraction of antibodies from plants have a direct influence on the initial choice of expression strategy, and so must be considered at an early stage. The use of small-scale techniques that are applicable to large-scale purification was a particularly important consideration. The optimal extraction technique varied with the target location of IgG in the plant cell, and the dependence of antibody yield on the physical extraction methodology employed, the pH of the extraction buffer and the extraction temperature was demonstrated in each case. The addition of detergent to the extraction buffer may improve the yield, but this was found to be dependent on the site of accumulation of IgG within the plant cell.
Clostridium difficilein Long-Term–Care Facilities for the Elderly (2002)

Antimicrobial agents are among the most frequently prescribed medications in long-term-care facilities (LTCFs). Therefore, it is not surprising that Clostridium difficile colonization and C. difficile-associated diarrhea (CDAD) occur commonly in elderly LTCF residents. C. difficile has been identified as the most common cause of non-epidemic acute diarrheal illness in nursing homes, and outbreaks of CDAD in LTCFs have also been recognized. This position paper reviews the epidemiology and clinical features of CDAD in elderly residents of LTCFs and, using available evidence, provides recommendations for the management of C. difficile in this setting.
Microbubble contrast agents: a new era in ultrasound (2001)

Contrast agents are widely used in imaging, but until recently they had little place in ultrasonography. This has changed with the introduction of microbubbles—small (typically 3 μm in diameter) gas filled bubbles that are usually injected intravenously. Injecting a gas into the circulation may seem potentially hazardous, but extensive clinical experience has shown that the tiny volume of air or gas given (under 200 μl) is not dangerous, and the safety of microbubbles compares well to that of conventional agents in radiography and magnetic resonance imaging.1 Although microbubbles were originally designed simply to improve conventional ultrasound scanning, recent discoveries have opened up powerful emerging applications. This article describes some of these applications in radiology and cardiology and discusses the potential of microbubbles for therapy.

We prepared this review from contributions from researchers with special knowledge of the use of microbubbles in radiology, cardiology, and treatment. We combined our personal experience in research over several years with a review of recent literature on the subject.

Microbubbles work by resonating in an ultrasound beam, rapidly contracting and expanding in response to the pressure changes of the sound wave. By a fortunate coincidence, they vibrate particularly strongly at the high frequencies used for diagnostic ultrasound imaging. This makes them several thousand times more reflective than normal body tissues. In this way they enhance both grey scale images and flow mediated Doppler signals. As well as being useful in itself, the resonance that microbubbles produce has several special properties that can be exploited to improve diagnoses. Just as with a musical instrument, multiple harmonic signals—or overtones—are produced. Ultrasound scanners can be tuned to “listen” to these harmonics, producing strong preferential imaging of the microbubbles in an image. The selective excitation produced can also destroy microbubbles relatively easily, an effect that can be useful …
Characterization and Regulation of the Trehalose Synthesis Pathway and Its Importance in the Pathogenicity of Cryptococcus neoformans (2006)

The disaccharide trehalose has been found to play diverse roles, from energy source to stress protectant, and this sugar is found in organisms as diverse as bacteria, fungi, plants, and invertebrates but not in mammals. Recent studies in the pathobiology of Cryptococcus neoformans identified the presence of a functioning trehalose pathway during infection and suggested its importance for C. neoformans survival in the host. Therefore, in C. neoformans we created null mutants of the trehalose-6-phosphate (T6P) synthase (TPS1), trehalose-6-phophate phosphatase (TPS2), and neutral trehalase (NTH1) genes. We found that both TPS1 and TPS2 are required for high-temperature (37 degrees C) growth and glycolysis but that the block at TPS2 results in the apparent toxic accumulation of T6P, which makes this enzyme a fungicidal target. Sorbitol suppresses the growth defect in the tps1 and tps2 mutants at 37 degrees C, which supports the hypothesis that these sugars (trehalose and sorbitol) act primarily as stress protectants for proteins and membranes during exposure to high temperatures in C. neoformans. The essential nature of this pathway for disease was confirmed when a tps1 mutant strain was found to be avirulent in both rabbits and mice. Furthermore, in the system of the invertebrate C. elegans, in which high in vivo temperature is no longer an environmental factor, attenuation in virulence was still noted with the tps1 mutant, and this supports the hypothesis that the trehalose pathway in C. neoformans is involved in more host survival mechanisms than simply high-temperature stresses and glycolysis. These studies in C. neoformans and previous studies in other pathogenic fungi support the view of the trehalose pathway as a selective fungicidal target for use in antifungal development.
Origin of Mechanoluminescence from Cu-Doped ZnS Particles Embedded in an Elastomer Film and Its Application in Flexible Electro-mechanoluminescent Lighting Devices (2015)

Mechanically driven light emission from particles embedded in elastomer films has recently attracted interest as a strong candidate for next-generation light sources on display devices because it is nondestructive, reproducible, real-time, environmentally friendly, and reliable. The origin of mechanoluminescence (ML) obtained from particles embedded in elastomer films have been proposed as the trapping of drifting charge carriers in the presence of a piezoelectric field. However, in this study, we propose a new origin of ML through the study of the microstructure of a Cu-doped ZnS particles embedded in an elastomer composite film with high brightness using transmission electron microscopy (TEM) to clearly demonstrate the origin of ML with respect to the microstructure of ML composite films. The TEM characterization of the ML composite film demonstrated that the Cu-doped ZnS particles were fully encapsulated by a 500 nm thick Al layer, which acts as an electron source for ML emission. Furthermore, we fabricated a flexible electro-mechanoluminescence (EML) device using a Cu-doped ZnS particles embedded in a flexible elastomer composite film. Our research results on a new emission mechanism for ML and its application in flexible light generating elastomer films represent an important step toward environmentally benign and ecofriendly flexible electro-mechanoluminescent lighting devices.
Surface Acoustic Wave Chemical Sensor Arrays:  New Chemically Sensitive Interfaces Combined with Novel Cluster Analysis To Detect Volatile Organic Compounds and Mixtures (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface Acoustic Wave Chemical Sensor Arrays: New Chemically Sensitive Interfaces Combined with Novel Cluster Analysis To Detect Volatile Organic Compounds and MixturesAntonio J. Ricco, Richard M. Crooks, and Gordon C. OsbournView Author Information Microsensor R&D and Vision Science Departments, Sandia National Laboratories, Albuquerque, New Mexico 87185-1425, and Department of Chemistry, Texas A&M University, College Station, Texas 77843-3255 Cite this: Acc. Chem. Res. 1998, 31, 5, 289–296Publication Date (Web):May 2, 1998Publication History Received24 June 1997Published online2 May 1998Published inissue 1 May 1998https://pubs.acs.org/doi/10.1021/ar9600749https://doi.org/10.1021/ar9600749research-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views856Altmetric-Citations103LEARN 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-Alertsclose SUBJECTS:Isotherms,Materials,Mathematical methods,Sensors,Thin films Get e-Alerts
Selenoprotein P in serum as a biochemical marker of selenium status (1995)

Some characteristics of a radioimmunoassay of selenoprotein P (a major selenoprotein in human serum) are described. Polyclonal antibodies generated in rabbits were used and goat anti-rabbit-IgG antiserum was used as a second antibody. Depending on the concentration of selenoprotein P, 1-10 microliters of human serum were used in the assay. The relative standard deviation for the concentration of selenoprotein P was 6.3% between assays and 7.7% within assays. Different animal sera gave no significant interference, indicating that the antibodies did not react with non-human analogues of selenoprotein P. No indication of cross-reactivity could be found concerning extracellular glutathione peroxidase (another selenoprotein in serum). Addition of increasing amounts of normal human serum and partially purified selenoprotein P to the radioimmunoassay resulted in parallel curves. Incubation at 4 degrees C gave somewhat higher binding of labelled selenoprotein P than incubation at room temperature. The epitope, recognized by the antibodies, was apparently stable after storage of serum (in the frozen state for years, and in the cold for months). No significant amount of selenoprotein P could be demonstrated in red blood cells, and analysis of haemolysed whole blood gave expected data. Investigations of selenium status in different study groups indicated that in most cases the concentration of selenoprotein P in serum was positively correlated to that of glutathione peroxidase and serum selenium. In an intervention study, where subjects decreased their selenium intake to 50%, the serum levels of glutathione peroxidase and selenium decreased, but no significant decrease of selenoprotein P could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
Security problems in the TCP/IP protocol suite (1989)

The TCP/IP protocol suite, which is very widely used today, was developed under the sponsorship of the Department of Defense. Despite that, there are a number of serious security flaws inherent in the protocols, regardless of the correctness of any implementations. We describe a variety of attacks based on these flaws, including sequence number spoofing, routing attacks, source address spoofing, and authentication attacks. We also present defenses against these attacks, and conclude with a discussion of broad-spectrum defenses such as encryption.