gebhart/patrepeval huggingface dataset:
Differences among Monte Carlo codes in the calculations of voxel values for radionuclide targeted therapy and analysis of their impact on absorbed dose evaluations (2009)

Several updated Monte Carlo (MC) codes are available to perform calculations of voxel S values for radionuclide targeted therapy. The aim of this work is to analyze the differences in the calculations obtained by different MC codes and their impact on absorbed dose evaluations performed by voxel dosimetry. Voxel S values for monoenergetic sources (electrons and photons) and different radionuclides (90Y, 131I, and 188Re) were calculated. Simulations were performed in soft tissue. Three general-purpose MC codes were employed for simulating radiation transport: MCNP4C, EGSnrc, and GEANT4. The data published by the MIRD Committee in Pamphlet No. 17, obtained with the EGS4 MC code, were also included in the comparisons. The impact of the differences (in terms of voxel S values) among the MC codes was also studied by convolution calculations of the absorbed dose in a volume of interest. For uniform activity distribution of a given radionuclide, dose calculations were performed on spherical and elliptical volumes, varying the mass from 1 to 500 g. For simulations with monochromatic sources, differences for self-irradiation voxel S values were mostly confined within 10% for both photons and electrons, but with electron energy less than 500 keV, the voxel S values referred to the first neighbor voxels showed large differences (up to 130%, with respect to EGSnrc) among the updated MC codes. For radionuclide simulations, noticeable differences arose in voxel S values, especially in the bremsstrahlung tails, or when a high contribution from electrons with energy of less than 500 keV is involved. In particular, for 90Y the updated codes showed a remarkable divergence in the bremsstrahlung region (up to about 90% in terms of voxel S values) with respect to the EGS4 code. Further, variations were observed up to about 30%, for small source-target voxel distances, when low-energy electrons cover an important part of the emission spectrum of the radionuclide (in our case, for 131I). For 90Y and 188Re, the differences among the various codes have a negligible impact (within few percents) on convolution calculations of the absorbed dose; thus either one of the MC programs is suitable to produce voxel S values for radionuclide targeted therapy dosimetry. However, if a low-energy beta-emitting radionuclide is considered, these differences can affect also dose depositions at small source-target voxel distances, leading to more conspicuous variations (about 9% for 1311) when calculating the absorbed dose in the volume of interest.
Synthesis and evaluation of 2,5-dihydrochorismate analogues as inhibitors of the chorismate-utilising enzymes (2009)

A library of 2,5-dihydrochorismate analogues were designed as inhibitors of the chorismate-utilising enzymes including anthranilate synthase, isochorismate synthase, salicylate synthase and 4-amino-4-deoxychorismate synthase. The inhibitors were synthesised in seven or eight steps from shikimic acid, sourced from star anise. The compounds exhibited moderate but differential inhibition against the four chorismate-utilising enzymes.
Polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with obesity phenotypes in a large family-based association study (2006)

Intronic variants of the LRP5 gene are markedly associated with obesity. We hypothesise that such an association may be due to the role of LRP5 in the WNT signalling pathway or lipid metabolism. Further functional studies are needed to elucidate the exact molecular mechanism underlying our finding.
Self-Aligned Supported Lipid Bilayers for Patterning the Cell−Substrate Interface (2009)

Supported lipid bilayers capture the fluidity and chemical properties of cellular membranes. In this report, we introduce a method for creating surfaces that contain multiple, aligned regions of supported membranes of different compositions at scales of micrometers and smaller. This method uses the design of a diffusional barrier to increase the resolution that can be achieved directly using traditional bilayer patterning techniques, such as laminar flow. We demonstrate the use of this platform for presenting ligands to the T Cell Receptor and LFA-1 that are tethered to separate, closely juxtaposed regions of bilayer, capturing an important aspect of the natural organization observed between T cells and Antigen Presenting Cells. Our results present a novel platform for the study of spatial separation of extracellular ligands and its impact on cell signals.
Interventions to improve return to work in depressed people (2014)

A combination of a work-directed intervention and a clinical intervention probably reduces the number of sickness absence days, but at the end of one year or longer follow-up, this does not lead to more people in the intervention group being at work. The intervention may also reduce depressive symptoms and probably increases work functioning more than care as usual. Specific work-directed interventions may not be more effective than usual work-directed care alone. Psychological interventions may reduce the number of sickness absence days, compared with care as usual. Interventions to improve clinical care probably lead to lower sickness absence and lower levels of depression, compared with care as usual. There was no evidence of a difference in effect on sickness absence of one antidepressant medication compared to another. Further research is needed to assess which combination of work-directed and clinical interventions works best.
Low Incidence of Antibodies to Recombinant Human Tissue-Type Plasminogen Activator in Treated Patients (1990)

Sera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients' serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.
Immunosuppression-free transplantation reconsidered from a regenerative medicine perspective (2012)

Recent groundbreaking progress in regenerative medicine has shown its potential to meet the two major needs of solid organ transplantation, namely the achievement of an immunosuppression-free state (IFS) and the identification of a new, potentially inexhaustible source of organs. This review illustrates how regenerative medicine technology may contribute to the achievement of IFS. There are three possible strategies: organ bioengineering, immuno-isolation and thymus bioengineering. The goal of organ bioengineering is to manufacture organs ex vivo from autologous cells. Immuno-isolation technology implements strategies aiming to prevent recognition of nonself antigens by the host immune system. Thymus organoids have been bioengineered with scaffold-seeding methods to allow deletion of T-cell clones responsible for allograft rejection. Despite the several hurdles that must be overcome, regenerative medicine technologies offer alternative strategies aimed at establishing immediate, stable and durable IFS in solid organ graft recipients.
Lipopeptide immunization without adjuvant induces potent and long‐lasting B, T helper, and cytotoxic T lymphocyte responses against a malaria liver stage antigen in mice and chimpanzees (1997)

We have employed a 26-amino-acid synthetic peptide based on Plasmodium falciparum liver stage antigen-3 to evaluate improvements in immunogenicity mediated by the inclusion of a simple lipid-conjugated amino acid during peptide synthesis. Comparative immunization by the peptide in Freund's adjuvant or by the lipopeptide in saline shows that the addition of a palmitoyl chain can dramatically increase T helper (Th) cell responses in a wide range of major histocompatibility complex (MHC) class II haplotypes, to the extent that responses were induced in mice otherwise unable to respond to the non-modified peptide injected with Freund's adjuvant, and that the increased immunogenicity of the lipopeptide led to high and longer lasting antibody production (studied up to 8 months). B and T cell responses induced by the lipopeptide were reactive with native parasite protein epitopes, and a lipopeptide longer than ten amino acids was endogenously processed to associate with MHC class I and elicit cytotoxic T lymphocyte (CTL) responses. Finally, the lipopeptide was safe and highly immunogenic in chimpanzees, whose immune system is very similar to that of humans. Our results suggest that relatively large synthetic peptides, carefully chosen from pertinent areas of proteins and incorporating a simple palmitoyl-lysine, can induce not only CTL, but also strong Th and antibody responses in genetically diverse populations. Lipopeptides engineered in this way are simple to produce and purify under GMP conditions, they are well tolerated by apes, and with the enhanced immunogenicity without the need for adjuvant that we report here, they offer a quick and relatively low-cost route to provide material for human malaria vaccination trials.
Solid-Phase Chemical-Enzymic Synthesis of Glycopeptides and Oligosaccharides (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSolid-Phase Chemical-Enzymic Synthesis of Glycopeptides and OligosaccharidesMatthias Schuster, Peng Wang, James C. Paulson, and Chi-Huey WongCite this: J. Am. Chem. Soc. 1994, 116, 3, 1135–1136Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://doi.org/10.1021/ja00082a047RIGHTS & PERMISSIONSArticle Views839Altmetric-Citations194LEARN 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 InReddit PDF (234 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Development of support matrices for affinity chromatography of thyroid hormone receptors. (1981)

Certain cellular responses to thyroid hormones appear to be mediated by non-histone chromatin protein receptors. Purification of these proteins is important for an investigation of the detailed mechanisms of their regulatory role. In the present studies, we report the development of an affinity chromatographic system that can be used to purify thyroid hormone receptors solubilized from nuclei. Amine-substituted hormone analogs were prepared with D and L isomers of T3; these bind to the receptor. This finding supports the hypothesis that thyroid hormones fit into the receptor with the amino groups accessible from outside the binding site. Although L-triiodothyronine (LT3) (the naturally occurring isomer) binds more tightly (relative Kd = 1.0 nM) to the nuclear receptor than D-triiodothyronine (DT3) (relative Kd = 2.0 nM), the amine-substituted analog of DT3 binds more tightly than the LT3 analog (DT3 analog, relative Kd = 40 nM; LT3 analog, relative Kd = 1500 nM). Agarose-based gels containing DT3 and LT3 covalently coupled by their amino groups were also prepared. Binding of receptor to these gels was biospecific in that it could be inhibited by prior incubation of the receptors with LT3. In addition, as predicted by the analog studies, the DT3 affinity gels were more effective than LT3 gels in adsorbing receptor. Elution of receptor from the LT3-derived gels was achieved in a predicted volume and concentration of counter-ligand in elution buffer. These results suggest that affinity chromatography can be applied to the purification of thyroid hormone receptors.
Where Does Parkinson Disease Pathology Begin in the Brain? (2002)

The substantia nigra is not the induction site in the brain of the neurodegenerative process underlying Parkinson disease (PD). Instead, the results of this semi-quantitative study of 30 autopsy cases with incidental Lewy body pathology indicate that PD in the brain commences with the formation of the very first immunoreactive Lewy neurites and Lewy bodies in non-catecholaminergic neurons of the dorsal glossopharyngeus-vagus complex, in projection neurons of the intermediate reticular zone, and in specific nerve cell types of the gain setting system (coeruleus-subcoeruleus complex, caudal raphe nuclei, gigantocellular reticular nucleus), olfactory bulb, olfactory tract, and/or anterior olfactory nucleus in the absence of nigral involvement. The topographical parcellation of the nuclear grays described here is based upon known architectonic analyses of the human brainstem and takes into consideration the pigmentation properties of a few highly susceptible nerve cell types involved in PD. In this sample and in all 58 age- and gender-matched controls, Lewy bodies and Lewy neurites do not occur in any of the known prosencephalic predilection sites (i.e. hippocampal formation, temporal mesocortex, proneocortical cingulate areas, amygdala, basal nucleus of Meynert, interstitial nucleus of the diagonal band of Broca, hypothalamic tuberomamillary nucleus).
E-beam direct write (EBDW) as complementary lithography (2010)

193nm Optical lithography has powered the industry's growth for the last 10 years and multiple patterning is poised to extend 193nm even further. There is a growing trend in Logic design for manufacturing, with high-volume manufacturing (HVM) firms adopting a layout style using unidirectional single-pitch straight lines in poly and metal layers. These layouts lend themselves to a complementary lithography approach. First, unidirectional lines are patterned with Optical lithography. Second, these lines are "cut" to form the desired layout. In this paper, we present EBDW as a complement to optical lithography for line-cutting. We show how e-beam multiple-column architecture, optimized for line-cutting, is the best for patterning critical layers at advanced nodes as Complementary Lithography.
Matching sets of parse trees for answering multi-sentence questions (2013)

The problem of answering multi-sentence questions is addressed in a number of products and services-related domains. A candidate set of answers, obtained by a keyword search, is re-ranked by matching the set of parse trees of an answer with that of the question. To do that, a graph representation and learning technique for parse structures for paragraphs of text have been developed. Parse Thicket (PT) as a set of syntactic parse trees augmented by a number of arcs for inter-sentence word-word relations such as co-reference and taxonomic relations is introduced. These arcs are also derived from other sources, including Speech Act and Rhetoric Structure theories. The proposed approach is subject to evaluation in the product search and recommendation domain, where search queries include multiple sentences. An open source plugin for SOLR is developed so that the proposed technology can be easily integrated with industrial search engines.
Antibiotics as Probes of Ribosome Structure: Binding of Chloramphenicol and Erythromycin to Polyribosomes; Effect of Other Antibiotics (1974)

Antibiotics were used as probes of ribosome topology and function. Studies of [(14)C]chloramphenicol and [(14)C]erythromycin binding to ribosomes and polyribosomes revealed the following features. The requirement of high K(+) concentration (150 mM) for [(14)C]chloramphenicol binding to NH(4)Cl-washed ribosomes resulted from the washing procedure. Neither native 70S ribosomes nor polyribosomes require K(+) greater than 30 mM for [(14)C]chloramphenicol binding. Whereas [(14)C]chloramphenicol binds to both ribosomes and polyribosomes, [(14)C]erythromycin binds essentially only to ribosomes. After removal of peptidyl-transfer ribonucleic acid (tRNA) from polyribosomes, [(14)C]erythromycin could then be bound. The effects of a number of antibiotics on [(14)C]chloramphenicol binding to ribosomes and polyribosomes was assessed. It was found that most of the macrolides (erythromycin, carbomycin, spiramycin III, niddamycin, oleandomycin, and tylosin) and streptogramins A and B (vernamycin A, PA114A, vernamycin Balpha, and PA114B) inhibited chloramphenicol binding to NH(4)Cl-washed and native 70S ribosomes, but not to polyribosomes. After removal of peptidyl-tRNA from polyribosomes, [(14)C]chloramphenicol binding was then inhibited. In contrast, sparsomycin and althiomycin inhibited chloram-phenicol binding to polyribosomes, but not to ribosomes. After removal of peptidyl-tRNA from polyribosomes, sparsomycin and althiomycin were then ineffective. The presence of peptidyl-tRNA on polyribosomes apparently is required for binding of sparsomycin and althiomycin, but prevents binding of most macrolides and streptogramins. The lincosaminides (lincomycin and celesticetin) and methymycin (a small macrolide) inhibited [(14)C]chloramphenicol binding to NH(4)Cl-washed and native 70S ribosomes best, but also inhibited the binding to polyribosomes. The amino nucleosides and other antibiotics tested do not seem to interact strongly with the major chloramphenicol-binding site. These results provide knowledge of the interrelationships between antibiotic and substrate ribosome binding sites which should eventually contribute to a map of ribosomal topology.
Statistical and Mechanistic Approaches to Understanding the Gas-Phase Fragmentation Behavior of Methionine Sulfoxide Containing Peptides (2004)

Recently, we carried out a statistical analysis of a 'tryptic' peptide tandem mass spectrometry database in order to identify sequence-dependent patterns for the gas-phase fragmentation behavior of protonated peptide ions, and to improve the models for peptide fragmentation currently incorporated into peptide sequencing and database search algorithms [Kapp, E. A., Schutz, F., Reid, G. E., Eddes, J. S., Moritz, R. L., O'Hair, R. A. J., Speed, T. P. and Simpson, R. J. Anal. Chem. 2003, 75, 6251-6264.]. Here, we have reexamined this database in order to determine the effect of a common post-translational or process induced modification, methionine oxidation, on the appearance and relative abundances of the product ions formed by low energy collision induced dissociation of peptide ions containing this modification. The results from this study indicate that the structurally diagnostic neutral loss of methane sulfenic acid (CH3SOH, 64Da) from the side chain of methionine sulfoxide residues is the dominant fragmentation process for methionine sulfoxide containing peptide ions under conditions of low proton mobility, i.e., when ionizing proton(s) are sequestered at strongly basic amino acids such as arginine, lysine or histidine. The product ion abundances resulting from this neutral loss were found to be approximately 2-fold greater than those resulting from the cleavage C-terminal to aspartic acid, which has previously been shown to be enhanced under the same conditions. In close agreement with these statistical trends, experimental and theoretical studies, employing synthetic "tryptic" peptides and model methionine sulfoxide containing peptide ions, have determined that the mechanism for enhanced methionine sulfoxide side chain cleavage proceeds primarily via a 'charge remote' process. However, the mechanism for dissociation of the side chain for these ions was observed to change as a function of proton mobility. Finally, the transition state barrier for the charge remote side chain cleavage mechanism is predicted to be energetically more favorable than that for charge remote cleavage C-terminal to aspartic acid.
The physical layer of UTRA TDD (2002)

The third generation mobile radio system UTRA that has been specified in the Third Generation Partnership Project (3GPP) consists of an FDD and a TDD mode. This paper presents the physical layer of the UTRA TDD mode, which is based on TD-CDMA. Important system features are explained in detail. The physical layer is responsible for the transmission of transport blocks over the air interface. This includes forward error correction, multiplexing of different transport channels on the same physical resources, rate matching, modulation, spreading and RF processing.
The role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo (1999)

A highly conserved TGF-&bgr; signaling pathway is involved in the establishment of the dorsoventral axis of the vertebrate embryo. Specifically, Bone Morphogenetic Proteins (Bmps) pattern ventral tissues of the embryo while inhibitors of Bmps, such as Chordin, Noggin and Follistatin, are implicated in dorsal mesodermal and neural development. We investigated the role of Tolloid, a metalloprotease that can cleave Chordin and increase Bmp activity, in patterning the dorsoventral axis of the zebrafish embryo. Injection of tolloid mRNA into six dorsalized mutants rescued only one of these mutants, mini fin. Through chromosomal mapping, linkage and cDNA sequence analysis of several mini fin alleles, we demonstrate that mini fin encodes the tolloid gene. Characterization of the mini fin mutant phenotype reveals that Mini fin/Tolloid activity is required for patterning ventral tissues of the tail: the ventral fin, and the ventroposterior somites and vasculature. Gene expression studies show that mfn mutants exhibit reduced expression of ventrally restricted markers at the end of gastrulation, suggesting that the loss of ventral tail tissues is caused by a dorsalization occurring at the end of gastrulation. Based on the mini fin mutant phenotype and the expression of tolloid, we propose that Mini fin/Tolloid modifes the Bmp activity gradient at the end of gastrulation, when the ventralmost marginal cells of the embryo are in close proximity to the dorsal Chordin-expressing cells. At this time, unimpeded Chordin may diffuse to the most ventral marginal regions and inhibit high Bmp activity levels. In the presence of Mini fin/Tolloid, however, Chordin activity would be negatively modulated through proteolytic cleavage, thereby increasing Bmp signaling activity. This extracellular mechanism is amplified by an autoregulatory loop for bmp gene expression.