gebhart/patrepeval huggingface dataset:
Quantitative 2D HSQC NMR determination of polymer structures by selecting suitable internal standard references (2006)

A new analytical method based on the 2D HSQC NMR sequence is presented, which can be applied for quantitative structural determination of complicated polymers. The influence of T1 and T2 relaxations, off-resonance effects, coupling constants and homonuclear couplings are discussed. It was found that the T2 values measured on polymeric samples with the conventional HSQC-CPMG sequence could not be used to correct the errors caused by T2 relaxations during the polarization transfer delay. A unique way of selecting the proper internal standard reference signal(s) is therefore proposed to eliminate the major errors caused by T2 relaxations, resonance offsets, coupling constant deviations and homonuclear couplings. Two polymer samples, a cellulose triacetate and an acetylated lignin, have been used to illustrate the principles. The methodology developed in this work is robust to instrument miss-setting and it can find wide-spread applications in areas where a quantitative analysis of structurally complicated polymers is necessary.
Mapping the future of common diseases: lessons from psoriasis (2006)

Psoriasis (OMIM*177900) is a common, chronic, hyperproliferative inflammatory disorder of the skin affecting approximately 2% of Caucasians. Despite the prevalence of psoriasis in general population, significant differences in the incidence among Japanese, Eskimos, West Africans, north American blacks and American natives are well known. The cause for these variations are likely to be both genetic and environmental. Independent genomewide scans have suggested the involvement of a large number of chromosomal regions (loci), but so far only poor susceptibility genes have been suggested. We discuss genetic basis of the disease, results and interpretations of relevant studies, with particular regard to study design and future perspectives. Indeed to date, mapping genes which contribute to complex diseases is one of the major challenge in the post-genomic era.
On the Origin and Progression of Ductal Carcinoma in the Human Breast2 (1973)

When 60 whole human breasts with and without coincident infiltrating ductal carcinoma were analyzed by a quantitative, three-dimensional subgross method correlated with histopathology, the smallest solitary, independent foci of ductal carcinoma in situ were observed in the terminal ductal-lobular units. If these independent foci are early stages of primary carcinoma, then a reasonable hypothesis is that ductal carcinoma in situ usually arises in these units, rather than in larger ducts. This hypothesis suggests that terminal ducts and/or lobules with atypical populations of .epithelial cells may be precancerous to common ductal breast cancer. A process of progressive lobular and ductular distension and unfolding, with concomitant coalescence of ductular lumens, probably explains the conversion of lobular structure (i.e., ductules) into larger ovoid and circular profiles. These profiles are of such magnitude that they sometimes falsely appear to be ducts in conventional, two-dimensional histologic slides.
Oligonucleotide inhibition of IL2Rα mRNA transcription by promoter region collinear triplex formation in lymphocytes (1991)

The promoter region of the IL2R alpha gene 5' flanking sequence contains enhancer elements crucial for binding nuclear factors which upregulate transcription following T lymphocyte activation. A 3' exonuclease resistant oligonucleotide (3'A-IL28p, terminated by a free amine group at its 3' end) was designed to bind to the IL2R alpha promoter region from -273 to -246, forming a collinear triplex spanning the kappa B enhancer (-266 to -256) as well as most of the serum response element (CArG box, -251 to -244). The binding site specificity of this oligonucleotide was demonstrated in electrophoretic mobility shift assays and by inhibition of restriction endonuclease (HinfI) cleavage within the segment of the target DNA predicted to form a triplex with the oligonucleotide. Intact normal lymphocytes, preincubated for 2h with 3'A-IL28p, accumulated less IL2Ralpha mRNA relative to other mRNAs (c-myc, beta-actin, IL2R beta, IL-6) for up to 12h after PHA stimulation, than did lymphocytes treated with a control oligomer of similar composition but different sequence. Nuclear run-on studies demonstrated that the rate of IL2R alpha mRNA synthesis relative to c-myc and beta-actin was also selectively diminished by treatment with 3'A-IL28p. These experiments suggest that transcription of individual genes can be selectively modulated in living cells by sequence specific collinear triplex formation in regulatory enhancer sequences.
Markers of endothelial dysfunction in lacunar infarction and ischaemic leukoaraiosis (2003)

Patients with cerebral small vessel disease (SVD) can present as isolated lacunar infarction or with diffuse white matter changes, with the imaging appearance of leukoaraiosis. Endothelial dysfunction, which can lead to breakdown of the blood-brain barrier, impaired cerebral autoregulation and prothrombotic changes, is believed to be important in mediating disease. Circulating levels of intercellular adhesion molecule 1 (ICAM1), thrombomodulin (TM), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are markers of endothelial activation and damage, and may provide insights into disease pathogenesis or differences between phenotypes. We therefore measured these markers in a prospective series of patients with lacunar stroke. One hundred and ten white Caucasian patients with previous lacunar stroke and 50 community control subjects were studied. Markers of endothelial function were measured on venous blood samples. Patients were classified on brain imaging into two groups: isolated lacunar infarction (n = 47) and ischaemic leukoaraiosis, defined as a clinical lacunar stroke and leukoaraiosis on brain imaging (n = 63). The number of lacunes and severity of leukoaraiosis were also scored on MRI. ICAM1, TM and TFPI were elevated in cerebral SVD subjects compared with controls (P <or= 0.006). The ischaemic leukoaraiosis group had a different endothelial marker profile, with lower levels of TFPI (P = 0.01) and a higher TF/TFPI ratio (P = 0.01) compared with the isolated lacunar infarction group. TM levels were associated with the number of lacunes (P = 0.008) and the leukoaraiosis score (P = 0.03), but TF levels and the TF/TFPI ratio were associated only with the extent of leukoaraiosis (P <or= 0.02). These results suggest that there is evidence of chronic endothelial dysfunction in cerebral SVD, and endothelial prothrombotic changes may be important in mediating the ischaemic leukoaraiosis phenotype. Therapies which help to stabilize the endothelium may have a role in this group of patients.
Macrophage accumulation at a site of renal inflammation is dependent on the M-CSF/c-fms pathway (2002)

Production of macrophage-colony stimulating factor (M-CSF), the major macrophage growth factor, is increased in tissues during inflammation. Therefore, we determined whether M-CSF, acting through its receptor c-fms, contributes to macrophage accumulation at a site of tissue injury. Daily treatment with anti-c-fms or control antibody was given to mice with renal inflammation resulting from unilateral ureteric obstruction (UUO). Following UUO, kidney M-CSF mRNA increased in association with macrophage accumulation (days 1, 5, and 10) and local macrophage proliferation (days 5 and 10). Anti-c-fms treatment caused a minor inhibition of monocyte recruitment at day 1, reduced macrophage accumulation by 75% at day 10, but did not affect blood monocyte counts or the CD4 and CD8 lymphocytic infiltrate. Prevention of macrophage accumulation by anti-c-fms treatment was associated with a 90% reduction in local macrophage proliferation at days 5 and 10 without evidence of increased macrophage apoptosis. Therefore, M-CSF/c-fms signaling plays a key role in macrophage accumulation during tissue injury.
Sensitivity of human subjects to head-related transfer-function phase spectra (1999)

Head-related transfer functions (HRTFs) for human subjects in anechoic space were modeled with modified phase spectra, including minimum-phase-plus-delay, linear-phase, and reversed-phase-plus-delay functions. The overall (wide-band) interaural time delay (ITD) for the modeled HRTFs was made consistent with that of the empirical HRTFs by setting the position-dependent, frequency-independent delay in the HRTF for the lagging ear. Signal analysis of the minimum-phase-plus-delay reconstructions indicated that model HRTFs deviate from empirical HRTF measurements maximally for contralateral azimuths and low elevations. Subjects assessed the perceptual validity of the model HRTFs in a four-interval, two-alternative, forced-choice discrimination paradigm. Results indicate that monaural discrimination performance of subjects was at chance for all three types of HRTF models. Binaural discrimination performance was at chance for the linear-phase HRTFs, was above chance for some locations for the minimum-phase-plus-delay HRTFs, and was above chance for all tested locations for the reversed-phase-plus-delay HRTFs. An analysis of low-frequency timing information showed that all of these results are consistent with efficient use of interaural time differences in the low-frequency components of the stimulus waveforms. It is concluded that listeners are insensitive to HRTF phase spectra as long as the overall ITD of the low-frequency components does not provide a reliable cue. In particular, the minimum-phase-plus-delay approximation to the HRTF phase spectrum is an adequate approximation as long as the low-frequency ITD is appropriate. These results and conclusions are all limited to the anechoic case when the HRTFs correspond to brief impulse responses limited to a few milliseconds.
Computationally Guided Directed Evolution of O-GlcNAcase into a Reagent Specific for [beta]-O-GlcNAc (2013)

Protein glycosylation with O-linked N-Acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues in nucleocytoplasmic proteins. Alterations in the glycosylation pattern of O-GlcNAc has been shown to play a role in many different cellular processes and O-GlcNAcylation is often found at sites that are also known to be phosphorylated. Unlike phosphorylation, the addition and removal O-GlcNAc are regulated by only two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (O-GlcNAcase or OGA). So far, no obvious consensus sequence has been found for sites of O-GlcNAcylation; additionally, O-GlcNAcase acts on all O-GlcNAcylated proteins, seemingly independent of their sequence. Despite the importance of this modification, very little is known about the structural relationship between these enzymes and their substrates. Nor is it clear, how only a single hydrolase is capable of removing O-GlcNAc from all GlcNAcylated proteins, independent of the protein sequence. Here a combination of computational and experimental techniques is employed to develop an understanding of the interactions between an inactive point mutant of OGA and its substrate, in an aim to designing an OGA-based receptor with enhanced affinity for O-GlcNAc. The key interactions involved in binding have been identified computationally, and are separated into residues which are directly responsible for the specificity of the complex (hot residues) and those whose mutation may increase the affinity (tepid residues). An inactive human OGA, which was engineered using site directed mutagenesis to knock out the nucleophile, was used to construct a combinatorial library in bacteriophage by saturation mutagenesis of the tepid residues. This library has been screened leading to the discovery of a single clone showing high affinity and specificity for O-GlcNAc. Reagents of this type are termed Lectenz®, and may be important diagnostic tools for the detection of enzyme substrates, such as O-GlcNAcylated proteins. In addition, five models of O-GlcNAcylated peptides in complex with a bacterial OGA were generated and assessed in terms of conformational dynamics and binding contributions in an aim to understand how OGA recognizes O-GlcNAc in situ. The results show that each of the five glycopeptides bind to OGA in a similar fashion, forming OGA-peptide interactions primarily, but not exclusively, with peptide backbone atoms, thus explaining the lack of sensitivity to peptide sequence. Nonetheless, differences in peptide sequences, particularly at the -1 to -4 positions, lead to variations in predicted affinity, consistent with observed experimental variations in enzyme kinetics. The potential exists therefore to employ the present analysis to guide the development glycopeptide-specific inhibitors, or conversely, the conversion of OGA into reagents that could target specific O-GlcNAcylated peptide sequences.
The development of selective and biocompatible coatings for solid phase microextraction (2003)

Abstract The development of solid phase microextraction (SPME) has seen huge growth since its conception as a new approach to sample preparation in the early 1990s. In comparison to existing technologies such as liquid‐liquid or solid phase extraction (LLE and SPE, respectively), the technique offers many advantages, including simplicity, speed, solventless extraction, and a convenient format. However, an important aspect in the future application and growth of SPME is the development of new extraction coatings. The objective of this review is to present an overview of the advances in coating development for solid phase microextraction (SPME). More specifically, this review will focus on the use of molecular recognition elements in SPME coatings to provide enhanced extraction selectivity and their applicability to the direct analysis of complex samples, such as biological fluids. The work will also include short overviews of emerging extraction phase technologies such as molecularly imprinted polymers (MIPs) and restricted access materials (RAM). The biocompatibility of RAMs has been combined with SPME and highlighted in several examples for more targeted and direct extraction possibilities in complex samples. The ability to perform direct and selective extraction of analytes from complex samples will extend SPME into the field of bioanalysis. Lastly, the future outlook for SPME and potential new applications for these fibers will be discussed.
ALBERT: A Lite BERT for Self-supervised Learning of Language Representations (2019)

Increasing model size when pretraining natural language representations often results in improved performance on downstream tasks. However, at some point further model increases become harder due to GPU/TPU memory limitations and longer training times. To address these problems, we present two parameter-reduction techniques to lower memory consumption and increase the training speed of BERT. Comprehensive empirical evidence shows that our proposed methods lead to models that scale much better compared to the original BERT. We also use a self-supervised loss that focuses on modeling inter-sentence coherence, and show it consistently helps downstream tasks with multi-sentence inputs. As a result, our best model establishes new state-of-the-art results on the GLUE, RACE, and \squad benchmarks while having fewer parameters compared to BERT-large. The code and the pretrained models are available at https://github.com/google-research/ALBERT.
Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells. (1987)

The function of exogenous murine recombinant IL-1 alpha as a T lymphocyte-activating molecule was examined. IL-1 did not induce IL-2 release or responsiveness in purified T cells regardless of their state of activation: unprimed lymphocytes, freshly sensitized lymphocytes, or memory cells derived from the blasts. Nor did IL-1 synergize with mitogens, or with antigens, to stimulate proliferation. For example the combinations of IL-1 plus Ia+ peritoneal macrophages, or IL-1 plus Con A, were less than 5% as effective in triggering T cell growth as a low dose (1%) of dendritic cells. However, when IL-1 was added at the onset of culture, the response to limiting doses of dendritic cells was increased 3- to 10-fold in several systems: the syngeneic and allogeneic MLR, Con A- and periodate-induced polyclonal mitogenesis, and T-dependent antibody formation against foreign red cells. The amplifying effect of IL-1 could be obtained if the dendritic cells but not the responding lymphocytes were exposed to IL-1 before use as accessory cells. Optimal activation of dendritic cells required a dose of 5 U/ml (50 pM) and 18 h of exposure, and was not due to carryover of IL-1 into the lymphocyte culture. IL-2, IL-3, and cachectin/TNF did not amplify dendritic cell function, while IFN-gamma diminished it. The enhanced function of IL-1-treated dendritic cells was due to an enhanced clustering with helper T lymphocytes in the first day of the MLR response. Therefore IL-1 does not seem to act as an activating factor for most peripheral T lymphocytes. Instead, IL-1 enhances the function of accessory dendritic cells and represents the first molecule that has been shown to enhance the immune response at this critical level.
A Reliable Routing Architecture and Algorithm for Network-on-Chip (2015)

The Network-on-Chip (NoC) is Network-version of System-on-Chip (SoC) means that on-chip communication through packet based networks. In NOC topology, routing algorithm and switching are main terminology. The routing algorithm is one of the key factors in NoC architecture. The routing algorithm which defines as the path taken by a packet between the source and the destination. The paper proposes a novel algorithm for a Network-on-Chip, which is based on packet switching. Using square mesh techniques used for 16 nodes based NoC design and simulation. The node is equal to row and column. Paper discusses internal architecture of NoC using addressable memory and simulate on XILINX 14.1 ISE MODELSIM. Keywords : Network-on-Chip, Static routing, Parallelism Cite this Article Anurag Shrivastava, Sudhir Kumar Sharma. A reliable routing architecture and algorithm for network-on-chip, Journal of Electronic Design and Technology . 2015; 6(3): 40–48p.
An observation on excimer formation in pyrenyl-labelled polystyrene: concentrated solution and solvent-plasticized film (1999)

Excimer formation of pyrenyl labels attached to polystyrene has been studied in concentrated solution and solvent-plasticized film. The ratio of excimer to monomer intensities (Ie/Im) is found to vary tortuously with increasing concentration (C) and display a critical concentration point at Cg ≈ 0.80 g ml−1. While C < Cg, the sharp decrease of Ie/Im is ascribed to entanglements of polymer chains. In the region C > Cg, Ie/Im increases slowly because of static excimer formation. © 1999 Society of Chemical Industry
Gold-Catalyzed Organic Transformations (2008)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTGold-Catalyzed Organic TransformationsZigang Li, Chad Brouwer, and Chuan He*View Author Information Department of Chemistry, The University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637* To whom correspondence should be addressed. Phone: 773-702-5061. Fax: 773-702-0805. E-mail: [email protected]Cite this: Chem. Rev. 2008, 108, 8, 3239–3265Publication Date (Web):July 10, 2008Publication History Received23 January 2008Published online10 July 2008Published inissue 1 August 2008https://pubs.acs.org/doi/10.1021/cr068434lhttps://doi.org/10.1021/cr068434lreview-articleACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views21196Altmetric-Citations1800LEARN 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:Alcohols,Catalysts,Cyclization,Gold,Hydrocarbons Get e-Alerts
Rationale for folate receptor alpha targeted therapy in “high risk” endometrial carcinomas (2008)

Advanced and recurrent endometrial cancers account for the majority of deaths from this disease with limited therapeutic options. High grade, and nonendometrioid histology, pathologically characterize the endometrial tumors associated with adverse outcome and are classified as "high risk". The identification of molecular prognostic factors that might be targeted for therapy among "high risk" endometrial cancers is an active area of investigation. We hypothesize that the FRalpha, highly expressed in endometrial cancer cells, is a potential target for this disease. Our objectives were to determine if FRalpha overexpression is associated with adverse prognostic factors and worse outcome. Three hundred and thirty-two endometrial cancer cores were arrayed onto a tissue microarray and stained using a FRalpha-specific monoclonal antibody. Staining was scored as absent or weak and moderate or strong. Forty-one percent of 310 evaluable cases stained moderate/strong. Moderate/strong FRalpha staining was significantly associated with other poor prognostic factors including: advanced stage, nonendometrioid histology and high grade. An association was observed between moderate/strong FRalpha staining and recurrence (p < 0.0014). These findings support further exploring a role for FRalpha targeted approaches for therapy and diagnostics in endometrial cancer.
Factor-stimulated RNA polymerase II transcribes at physiological elongation rates on naked DNA but very poorly on chromatin templates. (1992)

We used an in vitro assay system based on HeLa cell core transcription components to examine transcript elongation by RNA polymerase II on either naked DNA or chromatin templates as a function of the three known elongation factors, IIS, TFIIF, and TFIIX. We demonstrate for the first time that mammalian RNA polymerase II can achieve physiological elongation rates on naked DNA templates in vitro. The addition of TFIIF alone gave this rate, although IIS was required to minimize the block to elongation at intrinsic termination sites. However, IIS and TFIIF provided only a slight increase in the very poor elongation efficiency of RNA polymerase II on chromatin templates. The addition of TFIIX to reactions containing IIS and TFIIF reduced the elongation rate on naked DNA templates but slightly increased the elongation efficiency on chromatin. The ability of elongation factors either separately or in combination to stimulate transcription on naked DNA and chromatin templates was also examined.