gebhart/patrepeval huggingface dataset:
Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia (2004)

We recently identified a chronic lymphocytic leukemia (CLL) subgroup using the immunoglobulin variable heavy-chain (V(H)) gene V(H)3-21 with almost identical heavy-chain complementarity determining region 3s (HCDR3s) and preferential variable light-chain (V(L)) gene usage, suggesting recognition of a common antigen epitope in this subset. To further explore the B-cell receptors (BCRs) in CLL, we characterized 407 V(H) rearrangements amplified from 346 CLLs regarding V(H), diversity (D), and joining (J(H)) gene usage and performed multiple alignment of the HCDR3 sequences. These analyses revealed 3 small subsets (2 V(H)1-69 groups, 7 cases; and 1 V(H)1-2 group, 5 cases) with highly restricted HCDR3 features including identical V(H)/D/J(H) usage, HCDR3 lengths, and shared N-sequences, in addition to the V(H)3-21 group (22 cases). Furthermore, another 3 groups (9 V(H)1-3(+) cases, 3 V(H)1-18(+) cases, and 5 V(H)4-39(+) cases) had essentially identical V(H)/D/J(H) use and similar HCDR3 lengths but less conserved N-regions. Analysis in all 6 of these subgroups showed restriction in V(L) gene use, whereas no association between V(H) and V(L) usage was found in cases without HCDR3 similarities. Altogether, structurally similar HCDR3s associated with preferential V(L) gene usage implies selection of BCRs, especially in subsets showing high HCDR3 similarities, thus pointing to restricted antigen recognition sites and possibly involvement of specific antigens in CLL development.
Rapid characterisation of the inherent dispersibility of respirable powders using dry dispersion laser diffraction (2013)

Understanding and controlling powder de-agglomeration is of great importance in the development of dry powder inhaler (DPI) products. Dry dispersion laser diffraction measures particle size readily under controlled dispersing conditions, but has not been exploited fully to characterise inherent powder dispersibility. The aim of the study was to utilise particle size-dispersing pressure titration curves to characterise powder cohesivity and ease of de-agglomeration. Seven inhaled drug/excipient powders (beclometasone dipropionate, budesonide, fluticasone propionate, lactohale 300, salbutamol base, salmeterol xinafoate and tofimilast) were subjected to a range of dispersing pressures (0.2-4.5 Bar) in the Sympatec HELOS/RODOS laser diffractometer and particle size measurements were recorded. Particle size-primary pressure data were used to determine the pressures required for complete de-agglomeration. The latter were employed as an index of the cohesive strength of the powder (critical primary pressure; CPP), and the curves were modelled empirically to derive the pressure required for 50% de-agglomeration (DA₅₀). The powders presented a range of CPP (1.0-3.5 Bar) and DA₅₀ (0.23-1.45 Bar) which appeared to be characteristic for different mechanisms of powder de-agglomeration. This approach has utility as a rapid pre-formulation tool to measure inherent powder dispersibility, in order to direct the development strategy of DPI products.
Hyperhomocysteinaemia and atherothrombosis. (2000)

Homocysteine (Hcy) is a sulfhydryl amino acid derived from the metabolic conversion of methionine that is dependent on vitamins (folic acid, B12 and B6) as cofactors or cosubstrates. In 1969, McCully first reported the presence of severe atherosclerotic lesions in patients with severe hyperhomocysteinaemia and hypothesized the existence of a pathogenic link between hyperhomocysteinaemia and atherogenesis. Several case-control and cross-sectional studies confirmed the initial hypothesis of McCully, showing that also moderate hyperhomocysteinaemia is associated with a heightened risk of occlusive arterial disease. Less consistent results have been reported by prospective cohort studies of subjects who were healthy at the time of their enrollment, whereas prospective cohort studies of patients with overt coronary artery disease or other risk conditions consistently confirmed the association between moderate hyperhomocysteinaemia and the risk of cardiovascular morbidity and mortality. More recently, an association between moderate hyperhomocysteinaemia and heightened risk of venous thromboembolism has been documented, suggesting that hyperhomocysteinaemia might be involved not only in atherogenesis, but also in thrombogenesis. The mechanisms by which hyperhomocysteinaemia might contribute to atherogenesis and thrombogenesis are incompletely understood. The mainstay of treatment of hyperhomocysteinaemia is folic acid, alone or in combination with vitamins B12 and B6. Although it is quite clear that vitamins effectively reduce the plasma levels of total Hcy, we do not yet know whether they will decrease the risk of vascular disease. The results of ongoing randomized, placebo-controlled, double-blinded trials on the effects of vitamins on thrombotic risk will help in defining whether the relationship between hyperhomocysteinaemia and thrombosis is causal, and will potentially have a dramatic impact on the prevention of thromboembolic events.
C3-Symmetrical Supramolecular Architectures:  Fibers and Organic Gels from Discotic Trisamides and Trisureas (2002)

Hydrogen bonded C(3)-symmetrical molecules that associate into supramolecular stacks are described. Structural mutation on these molecules has been performed to elucidate the contribution of the different secondary interactions (hydrogen bonding, pi-pi stacking) to the self-assembly of the disks into chiral stacks. Twelve C(3)-symmetrical molecules have been investigated, six of which contain three central amide functionalities (1a-f) and six of which contain three central urea groups (2a-f). Peripheral groups of the disks are "small", "medium", or "large", half of them being achiral and the other half being chiral, to enable investigation of the supramolecular architectures with CD spectroscopy. In all of the cases, elongated, helical stacks are formed in apolar solution, except for the "medium" amide disks 1c/d. The elongated stacks of the C(3)-symmetrical disks form gels, which are visualized by AFM and SANS, and this confirms the directionality of the interactions. For the "large" urea disk, 2f, fibers with a length of up to 2 microm are observed. Temperature dependent and "sergeants-and-soldiers" CD measurements reveal that the urea stacks are much more rigid than the corresponding amide ones. In case of the "medium" urea disks, 2c/d, a true rigid rod, is formed. Where amide disks immediately reach their thermodynamic equilibrium, kinetic factors seem to govern urea aggregation. In a number of experiments aimed at reversibility with the urea stacks, hysteresis is observed, implying that these urea disks initially form a poorly defined stack, which subsequently transforms slowly into a well-defined, chiral architecture.
A high sensitivity z-axis torsional silicon accelerometer (2002)

This paper presents a high sensitivity silicon micromachined capacitive accelerometer fabricated using a three mask, dissolved wafer process. High electrical sensitivity is obtained by using high aspect-ratio comb fingers with narrow air gaps of 2 /spl mu/m and large overlap area of 12 /spl mu/m/spl times/300 /spl mu/m. Torsional suspension beams 150 /spl mu/m long with a cross-sectional area of 12 /spl mu/m/spl times/3 /spl mu/m are used to improve the mechanical gain (form factor). By using a varying overlap area method, the dynamic range, the pull-in voltage and the bandwidth are improved. The fabricated accelerometers yielded sensitivities of 263-300 mV/g, a nonlinearity less than 0.2% over a range of -4 g to +3 g, a full scale range of -4 g to +6 g and pull-in voltages greater than 8 V. A 3-dB cut-off frequency of 30 Hz was measured in air. The minimum resolution measured by the readout electronics was 0.077 g.
Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer (2014)

The multitude of rare genomic and transcriptomic events detected in a high-risk tumor cohort offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine.
Covalently attached multilayer assemblies of diazo-resins and porphyrins (1999)

Construction of highly stable covalently attached multilayer films containing porphyrins was achieved by UV irradiation of ionic self-assembled multilayer films of diazo-resins (DAR) and tetrasodium 5,10,15,20-tetraphenyl-21H,23H-porphine-P,P′,P″,P‴-tetrasulfonic acid (tpps4).
Triphasic decline of hepatitis C virus RNA during antiviral therapy (2007)

Triphasic responses can be predicted from a generalization of existent viral kinetic models through the inclusion of homeostatic proliferation of hepatocytes. This generalized model can also explain the viral kinetics seen in flat partial responders. Finally, the enhanced third phase in patients treated with IFN-alpha in combination with RBV versus patients treated with IFN-alpha alone can be explained by a mutagenic effect of RBV against HCV.
Regional distant sequence homology between amylases, α‐glucosidases and transglucanosylases (1988)

Amylases possess short, conserved regions near functional side chains. Sequence comparison extends this relationship to comprise a maltase and a cyclodextrin glucanotransferase. Similarity also exists with intestinal sucrase-isomaltase and fungal glucoamylase near identified essential carboxyl groups. Homology between COOH-terminal regions of glucoamylase and cyclodextrin glucanotranserase may indicate raw-starch binding areas. It is suggested that amylases, alpha-glucosidases, and transglucanosylases acting on 1,4- and 1,6-alpha-glucosidic linkages share key structural features in the active centres.
Epstein-Barr virus--associated diseases in humans. (2000)

It has been known for 30 years that Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, is the etiologic agent of acute infectious mononucleosis and is closely associated with the genesis of Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. Recent studies have demonstrated that EBV is also implicated in a variety of other diseases, such as EBV-associated hemophagocytic syndrome, chronic active EBV infection, T-cell lymphoma, natural killer cell leukemia/lymphoma, lymphoproliferative diseases in immunocompromised hosts, Hodgkin's disease, pyothorax-associated B-cell lymphoma, smooth-muscle tumors, and gastric carcinoma. Thus, the virus continues to attract worldwide attention, and it is now appropriate for a reappraisal of the relation between EBV and human diseases. This review summarizes the recent progress in research on EBV and the clinical findings of EBV-associated diseases and provides a basis for the development of new therapeutic strategies.
ElliPro: a new structure-based tool for the prediction of antibody epitopes (2008)

The results from ElliPro suggest that further research on antibody epitopes considering more features that discriminate epitopes from non-epitopes may further improve predictions. As ElliPro is based on the geometrical properties of protein structure and does not require training, it might be more generally applied for predicting different types of protein-protein interactions.
Chondroitin 4-sulfate covalently cross-links the chains of the human blood protein pre-alpha-inhibitor. (1991)

The human blood protein pre-alpha-inhibitor is composed of one heavy and one light protein chain. The chains are covalently linked to each other by a structure that has not previously been described, which we designate a protein-glycosaminoglycan-protein (PGP) cross-link. A combination of protein and carbohydrate analytical techniques indicates that the interchain linkage is mediated by a chondroitin 4-sulfate glycosaminoglycan that originates from a typical O-glycosidic link to Ser-10 of the light chain. The heavy chain is esterified, via the alpha-carbon of its C-terminal Asp, to C-6 of an internal N-acetylgalactosamine of the glycosaminoglycan chain. This PGP cross-link may be present in other proteins, but could have been overlooked due to the heterogeneous behavior of proteins containing glycosaminoglycan.
Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients (2014)

In patients with type 2 diabetes, empagliflozin-induced glycosuria improved β cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia. Chronic dosing shifted substrate utilization from carbohydrate to lipid. Trial registration. ClinicalTrials.Gov NCT01248364 (EudraCT no. 2010-018708-99). Funding. This study was funded by Boehringer Ingelheim.
Organophosphonate-Based PNA-Functionalization of Silicon Nanowires for Label-Free DNA Detection (2008)

We investigated hydroxyalkylphosphonate monolayers as a novel platform for the biofunctionalization of silicon-based field effect sensor devices. This included a detailed study of the thin film properties of organophosphonate films on Si substrates using several surface analysis techniques, including AFM, ellipsometry, contact angle, X-ray photoelectron spectroscopy (XPS), X-ray reflectivity, and current-voltage characteristics in electrolyte solution. Our results indicate the formation of a dense monolayer on the native silicon oxide that has excellent passivation properties. The monolayer was biofunctionalized with 12 mer peptide nucleic acid (PNA) receptor molecules in a two-step procedure using the heterobifunctional linker, 3-maleimidopropionic-acid-N-hydroxysuccinimidester. Successful surface modification with the probe PNA was verified by XPS and contact angle measurements, and hybridization with DNA was determined by fluorescence measurements. Finally, the PNA functionalization protocol was translated to 2 microm long, 100 nm wide Si nanowire field effect devices, which were successfully used for label-free DNA/PNA hybridization detection.
Computer Architecture: A Quantitative Approach, 2nd Edition (1996)

The computing world today is in the middle of a revolution: mobile clients and cloud computing have emerged as the dominant paradigms driving programming and hardware innovation today. The Fifth Edition of Computer Architecture focuses on this dramatic shift, exploring the ways in which software and technology in the cloud are accessed by cell phones, tablets, laptops, and other mobile computing devices. Each chapter includes two real-world examples, one mobile and one datacenter, to illustrate this revolutionary change.

	
		Updated to cover the mobile computing revolution
	
		Emphasizes the two most important topics in architecture today: memory hierarchy and parallelism in all its forms.
	
		Develops common themes throughout each chapter: power, performance, cost, dependability, protection, programming models, and emerging trends (What's Next)
	
		Includes three review appendices in the printed text. Additional reference appendices are available online.
	
		Includes updated Case Studies and completely new exercises.
Basic Fibroblast Growth Factor Released from a Platinum Coil with a Polyvinyl Alcohol Core Enhances Cellular Proliferation and Vascular Wall Thickness: An in Vitro and in Vivo Study (2003)

We suggest that FGF-core coils may be effective in inducing fibrotic changes inside aneurysms. These coils may be used as an embolic material to cure cerebral aneurysms.
Adenosine receptors and modulation of natural killer cell activity by purine nucleosides. (1990)

Natural killer (NK) cell activity is inhibited by the adenosine analogue tubercidin (Tub) and stimulated by the deoxyadenosine analogue 2-fluoro-1-beta-D-arabinofuranosyladenine 5'-monophosphate (F-ara-AMP) in the spleen lymphocytes from mice treated with the drugs in vivo (T. Priebe et al., Cancer Res., 48:4799, 1988). The present report demonstrates that the inhibition by Tub and stimulation by F-ara-AMP of NK cell activity are readily demonstrable in murine and human lymphocytes exposed to the drugs in vitro. In mouse spleen lymphocytes, NK cell activity is also inhibited by adenosine receptor A2 agonists, whereas potent A1 receptor agonists are more effective stimulators. Inhibition produced by adenosine, deoxyadenosine, and adenosine receptor agonists, but not by Tub, is partially prevented by the adenosine receptor antagonist 1,3-dipropyl-8-phenylxanthine amine congener. Agents that stimulate NK cell activity (deoxyadenosine, A1 receptor agonists, F-ara-AMP) do not increase further the 1.5-fold enhancement produced by a 10(-6) M concentration of 1,3-dipropyl-8-phenylxanthine amine congener. The nucleoside transport inhibitor, p-nitrobenzylthioinosine 5'-monophosphate, has no effect on NK cell activity or intracellular ribonucleotide pools; however, it partially prevents Tub 5'-triphosphate formation, ATP depletion, and NK cell inhibition in mouse spleen cells treated with Tub. p-Nitrobenzylthioinosine 5'-monophosphate also partially prevents the F-ara-AMP stimulation of NK cell activity, but it does not influence the effects of adenosine or deoxyadenosine. The results obtained with the adenosine receptor agonists suggest roles for both A1 and A2 receptors in regulating murine NK cell activity. Tub inhibition of NK cell activity does not appear to involve adenosine receptors; however, inhibition by the other agents may be mediated via an A2 receptor (stimulatory for adenylyl cyclase). Since p-nitrobenzylthioinosine 5'-monophosphate inhibited the stimulation of NK cell activity by F-ara-AMP, this stimulation may occur via an intracellular "P" site (inhibitory to adenylyl cyclase).
Solution Properties of Tadpole-type Cationic Amphiphilic Dendrimers Consisting of an Alkyl Chain, a Quaternary Ammonium, and a Poly(amidoamine) Dendron (2013)

Tadpole-type amphiphilic dendrimers consisting of an alkyl chain, a quaternary ammonium bromide (qb) and a poly(amidoamine) dendron (den) (CnqbdenGm, where n represents an alkyl chain with a length of 10,14, or 18 carbons; m is the generation number G of dendron taking the value -0.5, 0.5, or 1.5) were synthesized using N, N-dimethylethylenediamine as a central scaffold. Electrical conductivity, surface tension, pyrene fluorescence, and dynamic light scattering measurements were used to characterize the properties of the dendrimers. In addition, the effect of the alkyl chain length and the generation number of a dendron on these properties was evaluated through a comparison with those of the corresponding previously reported amphiphilic dendrimers with lactobionamide sugar terminal groups (CnqbdenGmLac) and conventional cationic monomeric surfactants (CnTAB). Both critical micelle concentration (cmc) and surface tension (except for C18 series) were lower than those of CnqbdenGmLac and CnTAB with the same alkyl chain length, indicating that the synthesized amphiphilic dendrimers have an excellent micelle-forming ability in solution and high adsorption ability at the air/water interface, in spite of the large bulky dendron structure. When the alkyl chain length and the generation number of the amphiphilic dendrimers were increased, the surface tension became high because of the curved long alkyl chain and the bulky structure of dendron. Further, CnqbdenGm formed micelles with a small size in solution, and the micelles of CnqbdenG(-0.5) had almost a constant size despite the changes in the concentration, while those of CnqbdenG0.5 and CnqbdenG1.5 became smaller with increasing concentration. The difference in the behavior results from the difference in the number of amide groups in the low- and high-generation dendrons.
Impaired receptor-mediated catabolism of low density lipoprotein in the WHHL rabbit, an animal model of familial hypercholesterolemia (1982)

The homozygous WHHL (Watanabe heritable hyperlipidemic) rabbit displays either no or only minimal low density lipoprotein (LDL) receptor activity on cultured fibroblasts and liver membranes and has therefore been proposed as an animal model for human familial hypercholesterolemia. To assess the impact of this mutation on LDL metabolism in vivo, we performed lipoprotein turnover studies in normal and WHHL rabbits using both native rabbit LDL and chemically modified LDL (i.e., methyl-LDL) that does not bind to LDL receptors. The total fractional catabolic rate (FCR) for LDL in the normal rabbit was 3.5-fold greater than in the WHHL rabbit. Sixty-seven percent of the total FCR for LDL in the normal rabbit was due to LDL receptor-mediated clearance and 33% was attributable to receptor-independent processes; in the WHHL rabbit, essentially all of the LDL was catabolized via receptor-independent processes. Despite a 17.5-fold elevated plasma pool size of LDL apoprotein (apo-LDL) in WHHL as compared to normal rabbits, the receptor-independent FCR-as judged by the turnover of methyl-LDL-was similar in the two strains. Thus, the receptor-independent catabolic processes are not influenced by the mutation affecting the LDL receptor. The WHHL rabbits also exhibited a 5.6-fold increase in the absolute rate of apo-LDL synthesis and catabolism. In absolute terms, the WHHL rabbit cleared 19-fold more apo-LDL via receptor-independent processes than did the normal rabbit and cleared virtually none by the receptor-dependent pathway. These results indicate that the homozygous WHHL rabbit shares a number of metabolic features in common with human familial hypercholesterolemia and should serve as a useful model for the study of altered lipoprotein metabolism associated with receptor abnormalities. We also noted that the in vivo metabolic behavior of human and rabbit LDL in the normal rabbit differed such that the mean total FCR for human LDL was only 64% of the mean total FCR for rabbit LDL, whereas human and rabbit methyl-LDL were cleared at identical rates. Thus, if human LDL and methyl-LDL had been used in these studies, the magnitude of both the total and receptor-dependent FCR would have been underestimated.
Mechanism-based isocoumarin inhibitors for trypsin-like serine proteases involved in blood coagulation (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism-based isocoumarin inhibitors for trypsin-like serine proteases involved in blood coagulationChih Min Kam, J. Clay Copher, and James C. PowersCite this: J. Am. Chem. Soc. 1987, 109, 16, 5044–5045Publication Date (Print):August 1, 1987Publication History Published online1 May 2002Published inissue 1 August 1987https://pubs.acs.org/doi/10.1021/ja00250a058https://doi.org/10.1021/ja00250a058research-articleACS PublicationsRequest reuse permissionsArticle Views188Altmetric-Citations14LEARN 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