gebhart/patrepeval huggingface dataset:
In vitro and In vivo Models for the Reconstruction of Intercellular Signalinga, (1998)

A critical need in both tissue-engineering applications and basic cell culture studies is the development of synthetic extracellular matrices (ECMs) and experimental systems that reconstitute three-dimensional cell-cell interactions and control tissue formation in vitro and in vivo. We have fabricated synthetic ECMs in the form of fiber-based fabrics, highly porous sponges, and hydrogels from biodegradable polymers (e.g., polyglycolic acid) and tested their ability to regulate tissue formation. Both cell seeding onto these synthetic ECMs and subsequent culture conditions can be varied to control initial cell-cell interactions and subsequent cell growth and tissue development. Three-dimensional tissues composed of cells of interest, matrix produced by these cells, and the synthetic ECM (until it degrades) can be created with these systems. For example, smooth muscle cells can be grown on polyglycolic acid fiber-based synthetic ECMs to produce tissues with cell densities in excess of 10(8) cells/mL. These tissues contain extensive elastin and collagen, and the smooth muscle cells within the tissue express the contractile phenotype (e.g., alpha-actin staining). Similar approaches can be used to grow a number of other tissues (e.g., dental pulp) that resemble the native tissue. These engineered tissues may provide novel experimental systems to study the role of three-dimensional intercellular signaling in tissue development and may also find clinical application as replacements to lost or damaged tissues.
Race-Conscious Diversity Admissions Programs: Furthering a Compelling Interest (1997)

This Article argues that narrowly tailored, race-conscious admissions programs can be employed to achieve a more diverse student body and consequently a more enlightened and egalitarian society. An admissions body which looks beyond traditional academic indicators and explores the whole person of each applicant will matriculate a group of students with a wide variety of race, gender, class and other backgrounds, thereby fostering a robust exchange of ideas among these students. Pointing to the enduring precedential value of Bakke as well as the ideological makeup of the Supreme Court, this Article asserts that the Courts would likely uphold a program aimed at promoting diversity. The Article concludes by describing the ideal diversity program and why Asian Americans, in particular, should support these programs
Synthesis and antitumor activity of 10-alkyl-10-deazaminopterins. A convenient synthesis of 10-deazaminopterin (1982)

Requirements for large-scale synthesis of the potent antitumor drug 10-deazaminopterin have led to development of a facile synthesis of this compound and its 10-alkyl analogues. The lithium diisopropyl amide generated dianions of appropriate p-alkylbenzoic acids were alkylated with 3-methoxyallyl chloride. The resulting 4-(p-carboxyphenyl)-1-methoxy-1-butenes were brominated at pH 7-8 to afford the 2-bromo-4-(p-carboxyphenyl)butyraldehydes. Condensation with 2,4,5,6-tetraminopyrimidine and subsequent in situ oxidation of the resulting dihydropteridines yielded crystalline 10-alkyl-10-deaza-4-amino-4-deoxypteroic acids. The pteroic acids were coupled with diethyl glutamate via the mixed anhydride method, followed by saponification at room temperature, to give the target 10-deazaminopterins. The 10-alkyl compounds were approximately equipotent to 10-deazaminopterin as growth inhibitors of folate-dependent bacteria. Their abilities to inhibit Lactobacillus casei and L1210 derived dihydrofolate reductases were also similar. Transport properties in vitro were suggestive of an improved therapeutic index for the 10-alkyl analogues. Against L1210 in mice, the percent increase in life span at the LD10 dosage was +151% (methotrexate), +178% (10-deazaminopterin), +235% (10-methyl analogue), and +211% (10-ethyl analogue). 10,10-Dimethyl-10-deazaminopterin was less effective at an equimolar dosage, but the ILS at the maximum dose tested (72 mg/kg) was +135%. It was far less toxic than the other analogues possibly because of enhanced clearance.
XKvalidator (2002)

The role of XML in data exchange is evolving from one of merely conveying the structure of data to one that also conveys its semantics. In particular, several proposals for key and foreign key constraints have recently appeared, and aspects of these proposals have been adopted within XMLSchema.In this paper, we examine the problem of checking keys and foreign keys in XML documents using a validator based on SAX. The algorithm relies on an indexing technique based on the paths found in key definitions, and can be used for checking the correctness of an entire document (bulk checking) as well as for checking updates as they are made to the document (incremental checking). The asymptotic performance of the algorithm is linear in the size of the document or update. Furthermore, experimental results demonstrate reasonable performance.
Millimeter-Wave Propagation: Characterization and modeling toward fifth-generation systems. [Wireless Corner] (2016)

The World Radiocommunication Conference 2015 (WRC-15) identified a number of frequency bands between 24 and 86 GHz as candidate frequencies for future cellular networks. In this article, an extensive review of propagation characteristics and challenges related to the use of millimeter wave (mm-wave) in future wireless systems is presented. Reference to existing path-loss models including atmospheric and material attenuation in recommendations of the International Telecommunication Union (ITU) in Geneva, Switzerland, is given, and the need for new multidimensional models and measurements is identified. A description of state-of-the-art mm-wave channel sounders for single and multiple antenna measurements is followed by a discussion of the most recent deterministic, semideterministic, and stochastic propagation and channel models. Finally, standardization issues are outlined with recommendations for future research.
Distinct Activation Signals Determine whether IL-21 Induces B Cell Costimulation, Growth Arrest, or Bim-Dependent Apoptosis (2004)

IL-21 costimulates B cell proliferation and cooperatively with IL-4 promotes T cell-dependent Ab responses. Somewhat paradoxically, IL-21 also induces apoptosis of B cells. The present study was undertaken to more precisely define the expression of the IL-21R, using a novel mAb, and the circumstances by which IL-21 promotes B cell growth vs death. The IL-21R was first detected during T and B cell development, such that this receptor is expressed by all mature lymphocytes. The IL-21R was further up-regulated after B and T activation, with the highest expression by activated B cells. Functional studies demonstrated that IL-21 substantially inhibited proliferation and induced Bim-dependent apoptosis for LPS or CpG DNA-activated B cells. In contrast, IL-21 induced both costimulation and apoptosis for anti-CD40-stimulated B cells, whereas IL-21 primarily costimulated B cells activated by anti-IgM or anti-IgM plus anti-CD40. Upon blocking apoptosis using C57BL/6 Bim-deficient or Bcl-2 transgenic B cells, IL-21 readily costimulated responses to anti-CD40 while proliferation to LPS was still inhibited. Engagement of CD40 or the BCR plus CD40 prevented the inhibitory effect by IL-21 for LPS-activated B cells. Collectively, these data indicate that there are three separable outcomes for IL-21-stimulated B cells: apoptosis, growth arrest, or costimulation. We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells.
Type 2 Diabetes (2009)

Type 2 diabetes (T2D) is the most common form of diabetes, a metabolic disorder characterized by hyperglycemia resulting from defects in insulin action, insulin secretion, or both. Early diagnosis of T2D and the high-risk category of pre-diabetes may help reduce the associated public health and clinical burden. Available diagnostic strategies include fasting plasma glucose, oral glucose tolerance test, and casual plasma glucose in the presence of symptoms of hyperglycemia. Potential use of hemoglobin A1c as part of the strategy for screening and diagnosis has been recently proposed. Those with risk factors for T2D should be targeted including patients with overweight/obesity, those with family history of T2D, those aged 45 years and older, race/ethnic minorities (such as Native Americans, African Americans, Latinos, and Asian Americans), women with history of gestational diabetes, and those with metabolic syndrome abnormalities (high blood pressure, low HDL cholesterol, and high triglycerides). Lifestyle modification (i.e., weight loss through diet and increased physical activity) has proven effective in reducing incident T2D in high-risk groups. Prevention trials using pharmacological therapy (metformin, α-glucosidase inhibitors, or thiazolidinediones) have also reported a significant lowering of the incidence of T2D. As a chronic condition, T2D requires continuous care to prevent damage to various organs, including the eyes, kidney, nervous system, and cardiovascular system. Appropriate glycemic control, blood pressure and lipid management, nutrition and physical activity, taking into account functional status and comorbidities, are needed to prevent microvascular and macrovascular complications. A variety of oral antihyperglycemic agents, which target different mechanisms in the pathogenesis of T2D, are as follows: insulin sensitizers, insulin secretagogues, α-glucosidase inhibitors, and the new dipeptidyl peptidase (DPP)-IV inhibitors. Injectable agents for the treatment of insulin-deficient T2D include traditional insulin preparations, newer insulin analogs, amylin, and incretin mimetics. Additional aspects of T2D management in the older adult include the assessment of geriatric syndromes and psychosocial screening. Efforts to improve T2D care following recommended guidelines are still very much needed.
Ribosomal frameshifting efficiency and gag/gag-pol ratio are critical for yeast M1 double-stranded RNA virus propagation (1992)

About 1.9% of ribosomes translating the gag open reading frame of the yeast L-A double-stranded RNA virus positive strand undergo a -1 frameshift and continue translating in the pol open reading frame to make a 170-kDa gag-pol fusion protein. The importance of frameshifting efficiency for viral propagation was tested in a system where the M1 (killer toxin-encoding) satellite RNA is supported by a full-length L-A cDNA clone. Either increasing or decreasing the frameshift efficiency more than twofold by alterations in the slippery site disrupted viral propagation. A threefold increase caused by a chromosomal mutation, hsh1 (high shifter), had the same effect. Substituting a +1 ribosomal frameshift site from Ty1 with the correct efficiency also allowed support of M1 propagation. The normal -1 frameshift efficiency is similar to the observed molar ratio in viral particles of the 170-kDa gag-pol protein to the 70-kDa gag gene product, the major coat protein. The results are interpreted in terms of a packaging model for L-A.
Synthesis and antiinflammatory activity of 6,11-dihydro-11-oxodibenzo[b,e]thiepinalkanoic acids and related compounds (1978)

Acetic acid derivatives of tricyclic systems, such as 6,11-dihydro-11-oxodibenzo[b,e]thiepin, 4,10-dihydro-4-oxo-thieno[2,3-c][1]benzothiepin, dibenzo[b,f]thiepin, dibenz[b,f]oxepin, etc., were synthesized and assayed for antiinflammatory activity. One of the compounds, 6,11-dihydro-11-oxodibenzo[b,e]thiepin-3-acetic acid (52), was chosen for evaluation in man on the basis of high antiinflammatory activity in both short- and long-term animal assays and a low gastric irritation liability in rats and dogs.
Divalent Cations and Heparin/Heparan Sulfate Cooperate to Control Assembly and Activity of the Fibroblast Growth Factor Receptor Complex (1996)

Polypeptides of the fibroblast growth factor (FGF) family are ubiquitous bioregulators within tissues whose activity is controlled by heparan sulfates within the pericellular matrix. FGF and the ectodomain of their transmembrane tyrosine kinase receptors (FGFR) exhibit heparin-binding domains that when juxtaposed in a FGF middle dotFGFR complex can accommodate a single, potentially bivalent, decameric polysaccharide chain in a ternary complex. Here we show that the interaction of heparin with FGF ligands is not affected by divalent cations. In contrast, the high affinity interaction (apparent Kd = 10 nM) of heparin with FGFR requires Ca2+ or Mg2+ at physiological concentrations. Divalent cations maintain FGFR in a heparan sulfate-dependent state in respect to FGF binding and an FGF- and heparan sulfate-dependent state in respect to autophosphorylation. A model is proposed where divalent cations and heparan sulfate cooperate to maintain FGFR in a conformation that restricts trans-phosphorylation between intracellular kinase domains. The restriction is overcome by FGF or constitutively as a common consequence of diverse mutations in FGFR associated with skeletal and craniofacial abnormalities.
Measures, markers, and mediators: Toward a staging system for clinical sepsis. A Report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25–26, 2000 (2003)

Advances in the understanding and management of patients with sepsis will necessitate more rigorous approaches to disease description and stratification. Models should be developed, tested, and modified through clinical studies rather than through consensus.
Rebound intragastric hyperacidity after abrupt withdrawal of histamine H2 receptor blockade. (1991)

In a series of 24 hour studies, intragastric acidity and plasma gastrin concentration were measured simultaneously in 46 healthy subjects before, during, and 24 to 48 hours after abrupt withdrawal of a histamine H2 receptor antagonist regimen. For 34 days subjects were given either cimetidine 800 mg at night (n = 8), ranitidine 150 mg twice daily (n = 10), ranitidine 300 mg at night (n = 12), nizatidine 300 mg at night (n = 8), or famotidine 40 mg at night (n = 8). All subjects responded to H2 blockade by a decrease in 24 hour intragastric acidity. Withdrawal of H2 blockade resulted in a significant rise in median nocturnal integrated intragastric acidity in 42 of 46 subjects (+36%; 95% CI +19, +55%) compared with prestudy values, but this rise was not associated with a significant change in the median integrated plasma gastrin concentration (+1%; 95% CI -12, +13%). A statistically significant rise in nocturnal acidity was observed after all regimens, except after dosing with famotidine. After stopping, median daytime integrated acidity and plasma gastrin concentrations in the whole group were raised, but not significantly: values were +15% (95% CI +4, +34%) and +5% (95% CI -2, +12%), respectively. A statistically significant increase in daytime acidity was observed only after dosing with ranitidine. In conclusion, intragastric hyperacidity occurs in most subjects after abrupt withdrawal of a histamine H2 receptor blocker, but this phenomenon is not associated with hypergastrinaemia.
The South and the Democratic Coalition (2006)

The presidential election of 2000 was not only one of the most closely contested in American history, but it was also an election that displayed significant regional differences in voting patterns. The Democrats won the popular vote by 0.5 per cent of the total, lost in the Electoral College (EC) by five votes, and yet won 79 per cent of the EC votes in (what might be called) the “Old North” and 66 per cent of those votes in the “West”. The Democratic defeat resulted from their winning a mere 29 per cent of EC votes in the Border states and not a single vote in the South. Not the least of the remarkable features of this pattern of voting is that it is almost a mirror image of the result in 1880. That earlier election produced an even closer contest for the popular vote with the Republican plurality being a mere .0002 per cent of the total, although they won the EC by 59 votes. In 1880, however, the Democrats won only 5 per cent of the EC votes in the Old North and 20 per cent in the West, while at the same time they won every EC vote in both the Border states and the South.
Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity (2010)

These findings identify proinflammatory CD11c(+) ATMs as markers of insulin resistance in human obesity. In addition, the machinery of CD11c(+) ATMs indicates they metabolize lipid and may initiate adaptive immune responses.
Angiotensin IV Is a Potent Agonist for Constitutive Active Human AT1 Receptors (2002)

The octapeptide hormone, angiotensin II (Ang II), exerts its major physiological effects by activating AT(1) receptors. In vivo Ang II is degraded to bioactive peptides, including Ang III (angiotensin-(2-8)) and Ang IV (angiotensin-(3-8)). These peptides stimulate inositol phosphate generation in human AT(1) receptor expressing CHO-K1 cells, but the potency of Ang IV is very low. Substitution of Asn(111) with glycine, which is known to cause constitutive receptor activation by disrupting its interaction with the seventh transmembrane helix (TM VII), selectively increased the potency of Ang IV (900-fold) and angiotensin-(4-8), and leads to partial agonism of angiotensin-(5-8). Consistent with the need for the interaction between Arg(2) of Ang II and Ang III with Asp(281), substitution of this residue with alanine (D281A) decreased the peptide's potency without affecting that of Ang IV. All effects of the D281A mutation were superseded by the N111G mutation. The increased affinity of Ang IV to the N111G mutant was also demonstrated by binding studies. A model is proposed in which the Arg(2)-Asp(281) interaction causes a conformational change in TM VII of the receptor, which, similar to the N111G mutation, eliminates the constraining intramolecular interaction between Asn(111) and TM VII. The receptor adopts a more relaxed conformation, allowing the binding of the C-terminal five residues of Ang II that switches this "preactivated" receptor into the fully active conformation.
Chromatin Remodeling, Measured by a Novel Real-Time Polymerase Chain Reaction Assay, Across the Proximal Promoter Region of the IL-2 Gene (2001)

The structure of chromatin and its remodeling following activation are important aspects of the control of inducible gene transcription. The IL-2 gene is induced in a cell specific-manner in T cells following an antigenic stimulus. We show, using a novel real-time PCR assay, that significant chromatin remodeling of the IL-2 proximal promoter region occurred upon stimulation of both the murine EL-4 T cell line and primary CD4(+) T cells. Chromatin remodeling appears to be limited to the first 300 bp of the proximal promoter region as measured by micrococcal nuclease and restriction enzyme accessibility. Time course studies indicated that chromatin remodeling was observed at 1.5 h postinduction and was maintained for up to 16 h. The remodeling is reversible upon removal of the stimulus. The region immediately upstream from the transcription start site, however, remains accessible for up to 16 h. Upon restimulation, remodeling occurs much more rapidly, consistent with a more rapid rise in IL-2 mRNA levels. Using a number of pharmacological inhibitors we show that remodeling is dependent on the presence of specific transcription factors, but not on the modification of histones. The development of this novel chromatin accessibility assay based on real-time PCR has allowed rapid, sensitive, and quantitative measurements on the IL-2 gene following cellular activation in both T cell lines and primary cells.
Unsymmetrically Substituted Piperazines. V. Piperazine Ureas (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUnsymmetrically Substituted Piperazines. V. Piperazine UreasRichard Baltzly, Samuel W. Blackman, and Walter S. IdeCite this: J. Am. Chem. Soc. 1954, 76, 4, 1165–1166Publication Date (Print):February 1, 1954Publication History Published online1 May 2002Published inissue 1 February 1954https://pubs.acs.org/doi/10.1021/ja01633a070https://doi.org/10.1021/ja01633a070research-articleACS PublicationsRequest reuse permissionsArticle Views113Altmetric-Citations2LEARN 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 Get e-Alerts
Soft, entirely photoplastic probes for scanning force microscopy (1999)

A new probe made entirely of plastic material has been developed for scanning probe microscopy. Using a polymer for the cantilever facilitates the realization of mechanical properties that are difficult to achieve with classical silicon technology. The new cantilever and tip presented here are made of an epoxy-based photoplastic. The fabrication process is a simple batch process in which the integrated tip and the lever are defined in one photolithography step. The simplicity of the fabrication step, the use of a polymer as material, and the ability to reuse the silicon mold lead to a soft low-cost probe for scanning force microscopy. Imaging soft condensed matter with photoplastic levers, which uses laser beam deflection sensing, exhibits a resolution that compares well with that of commercially available silicon cantilevers.
Common Neutralization Epitope in Minor Capsid Protein L2 of Human Papillomavirus Types 16 and 6 (1999)

Studies of virus neutralization by antibody are a prerequisite for development of a prophylactic vaccine strategy against human papillomaviruses (HPVs). Using HPV16 and -6 pseudovirions capable of inducing beta-galactosidase in infected monkey COS-1 cells, we examined the neutralizing activity of mouse monoclonal antibodies (MAbs) that recognize surface epitopes in HPV16 minor capsid protein L2. Two MAbs binding to a synthetic peptide with the HPV16 L2 sequence of amino acids (aa) 108 to 120 were found to inhibit pseudoinfections with HPV16 as well as HPV6. Antisera raised by immunizing BALB/c mice with the synthetic peptide had a cross-neutralizing activity similar to that of the MAb. The data indicate that HPV16 and -6 have a common cross-neutralization epitope (located within aa 108 to 120 of L2 in HPV16), suggesting that this epitope may be shared by other genital HPVs.