gebhart/patrepeval huggingface dataset:
Charge induced pattern formation on surfaces: Segregation in cylindrical micelles of cationic-anionic peptide-amphiphiles (2005)

Micelles, vesicles, and films composed of two species of incompatible heterogeneous molecules exhibit full internal segregation of the component species. This macroscopic segregation can be inhibited by oppositely charging the two different molecular species. The degree of compatibility achieved by the charges leads to either fully homogenous mixtures or to local segregation and the possible formation of regular patterns. We investigate the induction of periodic surface patterns by the presence of opposite charges in flat films and cylindrical micelles. In the strong segregation limit the incompatibility between species can be described by a line tension parameter gamma. The size of the patterns formed is of the order of a characteristic size L approximately (gamma/sigma(2))(1/2), where sigma is the surface charge density. The pattern symmetry on flat surfaces is function only of the fraction of area covered by the components, f: lamellar for 0.34<f<0.66 and hexagonal otherwise. In cationic and anionic mixtures aggregated into cylindrical micelles the symmetry and size of the surface charged domains depends also on the radius R of the cylinder. For large radii the patterns are similar to those in the plane, but for small radii only lamellar patterns are formed. At high salt concentration the surface domain size jumps discontinuously to an infinite value, resulting in macroscopic phase segregation.
Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 5. Conformationally mobile analogs derived by furan ring opening (1979)

Synthesis and antitetrabenazine activity of 4-[2-(arylmethyl)phenyl]piperidines and 4-(benzyloxy)-4-phenylpiperidines, prepared as simplified and possibly more readily synthesized analogues of 3-phenylspiro[isobenzofuran-1 (3H),4'-piperidine], are reported. Several 4-[2-(arylmethyl)phenyl]piperidines display antitetrabenazine activity comparable to imipramine or amitriptyline but are two- to fourfold less active than analogous 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Structure--activity relationships for 4-[2p(arylmethyl)phenyl]piperidines are generally similar to the profile established for 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Significant antitetrabenazine activity is associated only with derivatives where the arylmethyl group is ortho to the piperidine ring. 4-(Benzyloxy)-4-phenylpiperidines and 4-[2-(arylmethyl)phenyl]-4-piperidinols and the corresponding methyl ethers and esters display weak to modest antitetrabenazine activity. 4-[2-(Arylmethyl)phenyl]-1,2,3,6-tetrahydropyridine derivatives, at best, exhibit modest antitetrabenazine activity, with the exception of 4-[2-(phenylmethyl)phenyl]-1,2,3,6-tetrahydropyridine which is approximately equipotent with amitriptyline. The results of these investigations allow certain speculations to be made with respect to the role of the furan ring in the 3-arylspiro[isobenzofuran-1(3H),4'-piperidines] and antitetrabenazine activity.
Molecular and cellular studies of X-linked severe combined immunodeficiency. (1996)

X-linked severe combined immunodeficiency (XSCID) is characterised by a failure of both humoral and cellular immunity resulting in recurrent and opportunistic infections. Affected individuals have no T cells and normal or elevated numbers of B cells, indicating a defect in T cell development. At the start of this study the gene involved in XSCID had been mapped to the region Xq 13.1-21.1. In an attempt to reduce the extent of this region, the positions of polymorphic microsatellite loci, mapping to Xq 13.2-21.1, were refined. In 1993 the gene responsible for XSCID was cloned and identified as the IL-2 receptor γ chain which was also found to be a subunit of the IL-4, IL-7, IL-9 and IL- 15 receptors and denoted γc. This new information made it possible to screen a number of XSCID patients for mutations in the γc gene using single strand conformation polymorphism (SSCP) analysis. Mutations were identified in 14 individuals and this information has also aided carrier status assignment in a number of families. Expression of mutant γc at both the mRNA and surface protein levels was investigated in a number of EBV transformed B cell lines and also primary lymphocytes from patients. Surface expression as detected by a monoclonal antibody appeared to be disrupted in the majority of XSCID cases studied. Since the γc chain is a subunit of the IL-7 receptor and IL-7 is known to have a role in T cell development, an assay for IL-7 receptor function in XSCID patients was developed. This assay utilised a whole blood culture system and IL-6 production by monocytes in response to IL-7 was measured. The preliminary results obtained may help to elucidate the role of the γc chain in T cell development. The work presented here reflects the advancement of this field from gene cloning to the development of an understanding of the role of the XSCID gene product in both the normal and disease states.
[Biotransformation of tramadol in man and animal (author's transl)]. (1981)

Following p.o. administration of 14C-labelled rac.-1-(e)-(m-methoxyphenyl)-2-(e)-dimethylaminomethyl-cyclohexan-1-(a)-ol hydrochloride (tramadol hydrochloride, CG 315, Tramal) to mice, hamsters, rats, guinea pigs, rabbits, dogs and man the metabolic pathways were investigated and the results compared. After synthesis of the reference substances the metabolites were identified by co-chromatography using both TLC (thin-layer chromatography) and HPLC (high-performance liquid chromatography) methods, by co-crystallization and by gas chromatography-mass spectrometry. In all species the main metabolic pathways are N- and O-demethylation (phase I reactions) and conjugation of O-demethylated compounds (phase II reactions). 11 metabolites are known, 5 arising by phase I reactions (M1 to M5) and 6 by phase II reactions (glucuronides and sulfates of M1, M4 and M5). The 5 phase I metabolites are mono-O-demethyl-tramadol (M1), mono-N-demethyl-tramadol (M2), di-N-demethyl-tramadol (M3), tri-N,O-demethyl-tramadol (M4) and di-N,O-demethyl-tramadol (M5). The biotransformation scheme of tramadol is qualitatively identical in man, dog, rabbit, guinea pig, rat, hamster and mouse. In all species M1 and M1-conjugates, M5 and M5-conjugates and M2 are the main metabolites, whereas M3, M4 and M4-conjugates were only formed in minor quantities. Following p.o. administration to man and animals 14C-tramadol are rapidly and almost completely absorbed. The unchanged drug and metabolites are mainly excreted via kidneys. The cumulative renal excretion of total radioactivity accounts for approximately 90% in man and varies from 86 to 100% in mouse, hamster, rat, guinea pig, rabbit and dog; the residual of the applied radioactivity appears in the feces. Apparently tramadol is metabolized much more rapidly in animals than in man. For that reason there are appreciable differences between man and animals in the amount of tramadol excreted unchanged in the urine (about 30% and 1% of the p.o. dose, respectively). After incubation with beta-glucuronidase and arylsulfatase at least 81% of the excreted radioactivity could be extracted from the urine of man animals (with the exception of the guinea pig and the rabbit). In man all extractable metabolites were identified.
Patterns of gene action in plant development revealed by enhancer trap and gene trap transposable elements. (1995)

The crucifer Arabidopsis thaliana has been used widely as a model organism for the study of plant development. We describe here the development of an efficient insertional mutagenesis system in Arabidopsis that permits identification of genes by their patterns of expression during development. Transposable elements of the Ac/Ds system carrying the GUS reporter gene have been designed to act as enhancer traps or gene traps. A novel selection scheme maximizes recovery of unlinked transposition events. In this study 491 plants carrying independent transposon insertions were generated and screened for expression patterns. One-half of the enhancer trap insertions and one-quarter of the gene trap insertions displayed GUS expression in seedlings or flowers, including expression patterns specific to organs, tissues, cell types, or developmental stages. The patterns identify genes that act during organogenesis, pattern formation, or cell differentiation. Transposon insertion lines with specific GUS expression patterns provide valuable markers for studies of Arabidopsis development and identify new cell types or subtypes in plants. The diversity of gene expression patterns generated suggests that the identification and cloning of Arabidopsis genes expressed in any developmental process is feasible using this system.
Crystal structures and stereospecific propylene polymerizations with chiral hafnium metallocene catalysts (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCrystal structures and stereospecific propylene polymerizations with chiral hafnium metallocene catalystsJohn A. Ewen, Luc Haspeslach, Jerry L. Atwood, and Hongming ZhangCite this: J. Am. Chem. Soc. 1987, 109, 21, 6544–6545Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/ja00255a068https://doi.org/10.1021/ja00255a068research-articleACS PublicationsRequest reuse permissionsArticle Views630Altmetric-Citations205LEARN 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
Preventing a decrease in the palatability of round‐baled silage by preserving it as fermented total mixed ration (2009)

Abstract The first and second cuttings of orchardgrass ( Dactylis glomerata L.) were harvested without wilting to produce round‐baled silages. The palatability of fermented total mixed ration (TMR) was compared to that of fresh TMR, for which these round‐baled silages were the only roughage source. The fermented TMR was prepared from the silages opened after 40 days of the harvest, and was preserved as fermented TMR in drum silos until the palatability test. The fresh TMR was prepared from the silages opened after 132 days (first cutting) or 80 days (second cutting) of the harvest. The fermented TMR tended to show better palatability by animals than fresh TMR when the TMR were prepared from the first‐cutting silages, however, there was no palatability difference between the two TMR when they were prepared from the second‐cutting silages. Although the chemical compositions of the silages used for the two TMR were mostly similar, the butyric acid content in the first‐cutting silages was higher for fresh TMR (0.45%) than for fermented TMR (0.05%). The butyric acid content in the second‐cutting silages was less than 0.03% for both TMR. It was thus suggested that enhanced butyric fermentation during the preservation of the first‐cutting silages decreased the palatability of fresh TMR. The results indicate that if the round‐baled silage is of low fermentative quality for reasons such as ensiling under insufficient wilting conditions, the decrease in palatability can be suppressed by preserving it as fermented TMR before further enhancement of butyric fermentation in the silages.
Advanced glycation endproducts: what is their relevance to diabetic complications? (2006)

Glycation is a major cause of spontaneous damage to proteins in physiological systems. This is exacerbated in diabetes as a consequence of the increase in glucose and other saccharides derivatives in plasma and at the sites of vascular complications. Protein damage by the formation of early glycation adducts is limited to lysine side chain and N‐terminal amino groups whereas later stage adducts, advanced glycation endproducts (AGEs), modify these and also arginine and cysteine residues. Metabolic dysfunction in vascular cells leads to the increased formation of methylglyoxal which adds disproportionately to the glycation damage in hyperglycaemia. AGE‐modified proteins undergo cellular proteolysis leading to the formation and urinary excretion of glycation free adducts. AGEs may potentiate the development of diabetic complications by activation of cell responses by AGE‐modified proteins interacting with specific cell surface receptors, activation of cell responses by AGE free adducts, impairment of protein–protein and enzyme–substrate interactions by AGE residue formation, and increasing resistance to proteolysis of extracellular matrix proteins. The formation of AGEs is suppressed by intensive glycaemic control, and may in future be suppressed by thiamine and pyridoxamine supplementation, and several other pharmacological agents. Increasing expression of enzymes of the enzymatic defence against glycation provides a novel and potentially effective future therapeutic strategy to suppress protein glycation.
Multiple forms of ram and bull sperm hyaluronidase revealed by using monoclonal antibodies (1988)

Two monoclonal anti-sperm hyaluronidase-producing cell lines were isolated following inoculation of mice with ram sperm hyaluronidase monomer. Both lines produced antibodies of the IgG1 class; these bound to ram hyaluronidase after 'Western blotting' but did not recognize the native enzyme. Whereas the 1A4 antibody was specific for ram hyaluronidase, and did not react with 'blotted' bull, boar or rabbit hyaluronidase, the 1D6 antibody recognized bull as well as ram hyaluronidase. The antibodies could be used for immunocytochemical localization of hyaluronidase in fixed spermatozoa. However, although some form of denaturation was required to unmask or form the epitopes with which the antibodies reacted, the degree and type of fixation required was critical, for the epitopes were readily destroyed; in particular, they were very sensitive to chemical modification such as glutaraldehyde treatment. It could be demonstrated that, like ram, bull spermatozoa contained an extended oligomeric family of hyaluronidase forms, apparently the result of intermolecular disulphide cross-linking of monomers. In spermatozoa of both species, the enzyme was confined to the anterior acrosomal region of the head.
The Involvement of Immune Semaphorins in the Pathogenesis of Inflammatory Bowel Diseases (IBDs) (2015)

Altered % of Tregs expressing sema3A in patients with inflammatory bowel diseases (IBD) is partially responsible for their failure in preventing CD4+ effector T cell induced inflammation in IBD in peripheral blood. The increased expression of sema4A in bowel biopsies from CD and UC patients is suggestive of its central role in regulating local tissue inflammation in the bowel.
Platelet-associated complement factor H in healthy persons and patients with atypical HUS (2009)

Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates that platelets are intimately involved in aHUS pathogenesis. It has been reported that a releasable pool of platelet CFH originates from alpha-granules. We observed that platelet CFH can arise from endogenous synthesis in megakaryocytes and that platelets constitutively lacking alpha-granules contain CFH. Electron and high-resolution laser fluorescence confocal microscopy revealed that CFH was present throughout the cytoplasm and on the surface of normal resting platelets with no evident concentration in alpha-granules, lysosomes, or dense granules. Therapeutic plasma transfusion in a CFH-null aHUS patient revealed that circulating platelets take up CFH with similar persistence of CFH in platelets and plasma in vivo. Washed normal platelets were also observed to take up labeled CFH in vitro. Exposure of washed normal platelets to plasma of an aHUS patient with CFH autoantibodies produced partial platelet aggregation or agglutination, which was prevented by preincubation of platelets with purified CFH. This CFH-dependent response did not involve P-selectin mobilization, indicating a complement-induced platelet response distinct from alpha-granule secretion.
Accurate Inclusion Mass Screening (2008)

Verification of candidate biomarker proteins in blood is typically done using multiple reaction monitoring (MRM) of peptides by LC-MS/MS on triple quadrupole MS systems. MRM assay development for each protein requires significant time and cost, much of which is likely to be of little value if the candidate biomarker is below the detection limit in blood or a false positive in the original discovery data. Here we present a new technology, accurate inclusion mass screening (AIMS), designed to provide a bridge from unbiased discovery to MS-based targeted assay development. Masses on the software inclusion list are monitored in each scan on the Orbitrap MS system, and MS/MS spectra for sequence confirmation are acquired only when a peptide from the list is detected with both the correct accurate mass and charge state. The AIMS experiment confirms that a given peptide (and thus the protein from which it is derived) is present in the plasma. Throughput of the method is sufficient to qualify up to a hundred proteins/week. The sensitivity of AIMS is similar to MRM on a triple quadrupole MS system using optimized sample preparation methods (low tens of ng/ml in plasma), and MS/MS data from the AIMS experiments on the Orbitrap can be directly used to configure MRM assays. The method was shown to be at least 4-fold more efficient at detecting peptides of interest than undirected LC-MS/MS experiments using the same instrumentation, and relative quantitation information can be obtained by AIMS in case versus control experiments. Detection by AIMS ensures that a quantitative MRM-based assay can be configured for that protein. The method has the potential to qualify large number of biomarker candidates based on their detection in plasma prior to committing to the time- and resource-intensive steps of establishing a quantitative assay.
Fc Receptors are Critical for Autoimmune Inflammatory Damage to the Central Nervous System in Experimental Autoimmune Encephalomyelitis (2002)

Multiple sclerosis (MS) is simulated by various forms of experimental autoimmune encephalomyelitis, in which T cells, antibodies, cytokines and complementary factors interact with the central nervous system (CNS) myelin proteins and lead to inflammatory damage. We investigated the role of Fc receptors (FcRs), which link the cellular and humoral branches of the immune system, in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), using two different FcRgamma knockout DBA/1 mice. The first knockout were the FcRgamma chain-deficient mice, which lack FcgammaRI, FcgammaRIII and Fc(epsilon)RI, while the second knockout mice lack only FcgammaRII. The lack of FcgammaRII enhanced the disease susceptibility with associated increased CNS demyelination. While FcRgamma+/+ DBA/1 mice also developed pronounced CNS infiltration and myelin destruction, FcRgamma-/- littermates were protected despite initial peripheral autoimmune responses to MOG. In vitro analyses revealed equivalent potentials of fluid phase phagocytosis of myelin and MOG in bone-marrow macrophages derived from both FcRgamma+/+ and FcRgamma-/- mice, while MOG-immunoglobulin (Ig)G immune complexes were only internalized by FcRgamma+/+ macrophages. This was associated with cellular activation in FcRgamma+/+ but not FcRgamma-/- macrophages, as assessed by the activation of intracellular mitogen activated protein (MAP)-kinase signalling elements. We propose that protection from EAE in FcRgamma-deficient mice is due to the inefficient antigen processing/presentation of myelin proteins during the induction of secondary immune responses locally in the CNS, which leads to demyelination. This demonstrates the importance of FcR in the promotion of autoimmune inflammation of the CNS and highlights the therapeutic possibility of treatment of MS with FcR-directed modalities.
CD40{middle dot}FasL inhibits human T cells: evidence for an auto-inhibitory loop-back mechanism (2007)

A chimeric CD40.FasL (CD40-CD95L) protein was designed with the combined capacities to bind to two surface receptors on activated T cells, CD40 ligand (CD40L; CD154) and Fas receptor (CD95). CD40.FasL, once tethered to the cell surface via one of its ends, can transmit a signal via its other end. In principle, simultaneous triggering from both ends is possible, and thus there is the intriguing potential for 'auto-inhibition' if such dual triggering occurs on the same cell itself. Several lines of evidence support this mechanism: (i) CD40.FasL is cytotoxic to Fas receptor-positive cell lines of different cell lineages, (ii) CD40.FasL's function is potentiated when there is enforced expression of CD40L on target cells, (iii) CD40.FasL inhibition does not require intercellular contact, as demonstrated by soft agar clone formation and cell dilution analysis and (iv) introduction of exogenous CD40 into the system interferes with CD40.FasL inhibition. Taken together, these data are consistent with a 'loop-back' inhibitory mechanism within individual activated (CD40L and Fas receptor expressing) T cells causing suicide of these T cells. Significantly, this type of fusion protein provides a unique way to confine immunoinhibition to activated T cells.
A social skills training group for early adolescents (1979)

A programme of 15 weekly group sessions designed to teach social skills is described together with some theoretical justifications for the choice of methods used. The group members were early adolescents, age range 10·5 to 14 years, with a wide spectrum of psycho‐social problems, but having in common inadequate social skills to tackle their problems at an interpersonal level. Originally all had been referred to a hospital based Child Guidance Clinic. Two groups using the format described have been run, and clinical assessment suggests the groups have been effective in teaching social skills. The relative contribution made by the structured learning programme, direct feedback, and small group dynamics is discussed. Methods of objectively assessing outcome are discussed, and a pilot attempt to measure change is described.
A gene map of the human genome. (1996)

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.