gebhart/patrepeval huggingface dataset:
Synthesis of Sulfonamido‐Pseudopeptides: New Chiral Unnatural Oligomers (1994)

Chiral vinylogous aminosulfonic acids 1 can be used to synthesize the title compounds 2 by a straightforward iterative approach. The new chiral unnatural oligomers have defined conformational preferences in chloroform and may have interesting recognition and biological properties.
Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant tumor cells (2013)

Breast cancer (BC) can recur as metastatic disease many years after primary tumor removal, suggesting that disseminated tumor cells survive for extended periods in a dormant state that is refractory to conventional therapies. We have previously shown that altering the tumor microenvironment through fibrosis with collagen and fibronectin deposition can trigger tumor cells to switch from a dormant to a proliferative state. Here, we used an in vivo preclinical model and a 3D in vitro model of dormancy to evaluate the role of Src family kinase (SFK) in regulating this dormant-to-proliferative switch. We found that pharmacological inhibition of SFK signaling or Src knockdown results in the nuclear localization of cyclin-dependent kinase inhibitor p27 and prevents the proliferative outbreak of dormant BC cells and metastatic lesion formation; however, SFK inhibition did not kill dormant cells. Dormant cell proliferation also required ERK1/2 activation. Combination treatment of cells undergoing the dormant-to-proliferative switch with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis in a large fraction of the dormant cells and delayed metastatic outgrowth, neither of which was observed with either inhibitor alone. Thus, targeting Src prevents the proliferative response of dormant cells to external stimuli, but requires MEK1/2 inhibition to suppress their survival. These data indicate that treatments targeting Src in combination with MEK1/2 may prevent BC recurrence.
Show, Attend and Tell: Neural Image Caption Generation with Visual Attention (2015)

Inspired by recent work in machine translation and object detection, we introduce an attention based model that automatically learns to describe the content of images. We describe how we can train this model in a deterministic manner using standard backpropagation techniques and stochastically by maximizing a variational lower bound. We also show through visualization how the model is able to automatically learn to fix its gaze on salient objects while generating the corresponding words in the output sequence. We validate the use of attention with state-of-the-art performance on three benchmark datasets: Flickr8k, Flickr30k and MS COCO.
Nuclear localization signal of SV40 T antigen directs import of plasmid DNA into sea urchin male pronuclei in vitro (1996)

Nuclear import of plasmid DNA mediated by a nuclear localization signal (NLS) derived from SV40 T antigen was investigated in a cell-free extract. In vitro assembled sea urchin male pronuclei were incubated in a 100,000g supernatant of a zebrafish fertilized egg lysate, together with fluorescently labeled plasmid DNA bound to NLS or nuclear import deficient reverse NLS (revNLS) peptides. After 3 hr, DNA-NLS, but not DNA-revNLS, complexes were bound around the nuclear periphery. We demonstrate that nuclear import of DNA-NLS complexes is a two-step process involving binding to, and translocation across, the nuclear envelope. Binding is ATP-independent, occurs at 0 degree C and is Ca(2+)-independent. By contrast, translocation requires ATP hydrolysis, Ca2+, is temperature dependent and is blocked by the lectin wheat germ agglutinin. Both binding and translocation are competitively inhibited by albumin-NLS conjugates, require heat-labile cytosolic factors, and are inhibited by N-ethylmaleimide treatment of the cytosol. Binding and translocation are differentially affected by cytosol dilutions, suggesting that at least two distinct soluble fractions are required for nuclear import. The requirements for NLS-mediated nuclear import of plasmid DNA are similar to those for nuclear import of protein-NLS conjugates in permeabilized cells.
Cloning and characterization of a DNA region encoding a stress-sensitive restriction system from Corynebacterium glutamicum ATCC 13032 and analysis of its role in intergeneric conjugation with Escherichia coli (1994)

RP4-mediated transfer of mobilizable plasmids in intergeneric conjugation of Escherichia coli donors with Corynebacterium glutamicum ATCC 13032 is severely affected by a restriction system in the recipient that can be inactivated by a variety of exogenous stress factors. In this study a rapid test procedure based on intergeneric conjugal plasmid transfer that permitted the distinction between restriction-negative and restriction-positive C. glutamicum clones was developed. By using this procedure, clones of the restriction-deficient mutant strain C. glutamicum RM3 harboring a plasmid library of the wild-type chromosome were checked for their restriction properties. A complemented clone with a restriction-positive phenotype was isolated and found to contain a plasmid with a 7-kb insertion originating from the wild-type chromosome. This plasmid, termed pRES806, is able to complement the restriction-deficient phenotype of different C. glutamicum mutants. Sequence analysis revealed the presence of two open reading frames (orf1 and orf2) on the complementing DNA fragment. The region comprising orf1 and orf2 displayed a strikingly low G+C content and was present exclusively in C. glutamicum strains. Gene disruption experiments with the wild type proved that orf1 is essential for complementation, but inactivation of orf2 also resulted in a small but significant increase in fertility. These results were confirmed by infection assays with the bacteriophage CL31 from Corynebacterium lilium ATCC 15990.
Direct side-chain acylamination of 4-picoline 1-oxides and related compounds (1979)

The anhydro bases formed from the reaction of 4-picoline 1-oxides with N-substituted benzimidoyl chlorides and a strong base undergo a new molecular rearrangement to give mixtures of the side chain acylaminated (e.g.4) and acylaminoarylated products (e.g.5); 2-picoline 1-oxides behave similarly.
Properties of the factor Xa binding site on human platelets. (1978)

The affinity (Ka) of human coagulation Factor Xa for thrombin-treated (to stimulate the release reaction) platelets has been determined to be 3 to 4 x 10(10) M-1 by equilibrium binding studies using 125I-labeled Xa. The binding of Factor Xa to platelets results in an increase of 300,000-fold in the apparent enzymatic activity of Xa in the conversion of prothrombin to thrombin. The activity of platelet surface Xa is approximately 15-fold greater than that observed with optimum concentrations of bovine Factor V and phospholipids in place of platelets. Ca2+ is required for the Xa-platelet interaction; the optimum concentration is 2.5 mM. Related coagulation factors, including Factor X, Factor IXa, diisopropylphosphoryl Factor Xa, and prothrombin do not complete with Factor Xa for the Xa binding sites. The rate of thrombim formation at saturating amounts of Xa is directly proportional to the number of platelets from 1 x 10(7) to 5 x 10(8) platelets/ml. Factor Xa bound to platelets is not inactivated by antithrombin III. An antibody that inhibits both human and bovine coagulation Factor V activity blocks both Xa binding to released platelets and the rapid thrombin formation associated with this binding, suggesting that Factor V from platelets is involved in the Xa-platelet interaction.
How fast does an acetylcholine receptor channel open? Laser-pulse photolysis of an inactive precursor of carbamoylcholine in the microsecond time region with BC3H1 cells (1992)

The integrated function of the nervous system depends on specific and rapid transmission of signals between its constituent cells. The nicotinic acetylcholine receptor is the best known of a group of membrane-bound proteins responsible for such transmission; for this process to occur, a specific neurotransmitter, in this case acetylcholine, must bind to the receptor, which then forms transmembrane channels through which cations pass. The resulting change in transmembrane voltage determines whether or not a signal is transmitted. The question of how fast this process takes place in any neurotransmitter receptor has remained one of the interesting and most challenging in the field. To answer it, many attempts have been made to evaluate the rate constant for the opening of the acetylcholine receptor channel, but in almost all these studies the rate was measured after the receptor-mediated reaction, which involves the open channel and many intermediate states, had reached a quasi equilibrium. This resulted in a plethora of reported values for the rate constant that differ by a factor of up to 50-fold, even when the measurements were made with the same type of cell. The new approach described here involves the use of single cells of a mammalian cell line (BC3H1), containing muscle-type acetylcholine receptors, and the rapid introduction of neurotransmitter to the cell surface. The rapid delivery was achieved by converting a previously synthesized photolabile precursor of carbamoylcholine to carbamoylcholine, a stable amino-group-containing analogue of acetylcholine, with a single laser pulse and an observed photolysis rate of 7300 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatments of Generalized Pustular Psoriasis: A Multicenter Study in Japan (1999)

This study analyzed data from treatments of 385 cases of generalized pustular psoriasis (GPP) from 325 hospitals in Japan. Retinoid treatment was effective in 84.1% of patients, methotrexate in 76.2%, cyclosporine in 71.2%, oral PUVA therapy in 45.7%, and tonsillectomy in 16.7%. Short-term therapy with systemic corticosteroid for GPP during only the phase with severe systemic clinical findings may be also effective (75.4%). However, these treatments for GPP each differed in clinical effects, prognosis, and side effects. These findings may be useful in creating guidelines for treatment of generalized pustular psoriasis. Further studies based on these specific clinical effects are necessary.
MC-FDMA and MC-TDMA versus MC-CDMA and SS-MC-MA: performance evaluation for fading channels (2002)

The multi-carrier (MC) multiple access schemes MC-FDMA, MC-TDMA, MC-CDMA and the previously proposed SS-MC-MA scheme are investigated and compared for the suitability in the uplink and the downlink of a mobile radio system. By presenting a bandwidth efficiency plan for the different MC multiple access schemes in fading channels, the influence of the channel code rate, the system load, and the spreading code length is presented. Moreover, results with oneand two-dimensional pilot symbol aided channel estimation are shown for the various MC multiple access schemes considering typical multipath propagation scenarios in the uplink and the downlink.
Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease (2004)

Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in healthy middle-aged and elderly subjects. The increased mortality that has been reported in these settings may thus have a common aetiology. An autonomic imbalance in favour of the sympathetic system may interact with inflammatory processes to play a more important role in the process of atherosclerosis than previously thought.
Expression of proteins of Mycobacterium tuberculosis in Escherichia coli and potential of recombinant genes and proteins for development of diagnostic reagents (1987)

Recombinant plasmids containing DNA from Mycobacterium tuberculosis were transformed into Escherichia coli, and three colonies were selected by their reactivity with polyclonal antisera to M. tuberculosis. The three recombinant vectors contained DNA inserts of different sizes flanking a common 4.7-kilobase (kb) sequence. Each recombinant produced 35- and 53-kilodalton proteins (35K and 53K proteins, respectively) which were absent in the control E. coli. In Western blotting experiments, both proteins bound several antisera to M. tuberculosis but not antisera to other commonly isolated mycobacteria. Rabbits immunized with the recombinant 35K protein produced antisera which bound to both the 35K and 53K protein bands, a single 35K protein band present in a culture filtrate of M. tuberculosis, and single protein bands with differing molecular weights in whole-cell homogenates from other Mycobacterium spp. An additional recombinant vector containing a 2.2-kb subclone of the 4.7-kb sequence was constructed and, when used as a probe, demonstrated homology with various fragments of chromosomal digests of selected mycobacteria. Reactivity of this probe to Mycobacterium bovis and M. bovis BCG was indistinguishable from reactivity to M. tuberculosis. Immunoglobulin G reactivity to the 35K antigen was detected in antisera from 8 of 20 persons with active tuberculosis, 4 of 18 persons with leprosy, and none of 14 healthy controls. In contrast, reactivity to various proteins in M. tuberculosis culture filtrate was present in 18 of 20 patients with tuberculosis, 16 to 18 patients with leprosy, and 5 of 14 controls. The production of M. tuberculosis proteins by E. coli circumvents many difficulties encountered in the growth and manipulation of M. tuberculosis and may facilitate the development of better diagnostic and immunizing reagents.
Neratinib in combination with trastuzumab for the treatment of advanced breast cancer: A phase I/II study (2009)

1004 Background: Neratinib (HKI-272) is an orally administered irreversible pan-ErbB receptor tyrosine kinase inhibitor. In an ongoing phase II study, the preliminary objective response rate was 26% in patients with ErbB2+ advanced breast cancer with prior trastuzumab therapy. This study assessed the safety and preliminary efficacy of the combination of neratinib plus trastuzumab. Methods: Patients with advanced ErbB2+ breast cancer that progressed following trastuzumab therapy were enrolled. The primary endpoint was 16-week progression free survival rate (PFS). In part 1 (dose escalation), patients received neratinib 160 mg or 240 mg daily plus trastuzumab 4 mg/kg IV loading dose then 2 mg/kg weekly. In part 2, patients received weekly trastuzumab with neratinib 240 mg daily. Timed blood samples were collected for PK analyses. PK analysis is ongoing. Results: 45 patients (part 1 n = 8; part 2 n = 37) were enrolled (mean age 52 yr); 9 are active. In part 1, cohorts 1 and 2 were fully enrolled with 4 patients each. No dose limiting toxicities were observed. Most common AEs, any grade, were diarrhea (91%), nausea (51%), anorexia (40%), vomiting (38%), and asthenia (27%). Grade 3/4 AEs were diarrhea (13%), nausea (4%), vomiting (4%). Two patients receiving neratinib 240 mg reported AEs leading to withdrawal. No AEs of congestive heart failure and no significant drops of left ventricular ejection fraction were reported. Among 33 patients evaluable for efficacy, objective response rate was 27% (95% CI, 13% - 46%); 16-week PFS rate (for part 2) 47% (95% CI, 29% - 63%); median PFS was 19 weeks (95% CI 15 - 32 weeks). Conclusions: Neratinib plus trastuzumab was well tolerated with no significant or unexpected toxicities, and demonstrated clinical activity. [Table: see text]
Synthesis, resolution, and assignment of configuration of potent hypotensive retro-inverso bradykinin potentiating peptide 5a(BPP5a) analogues (1985)

The effect on the biological activity of an inverted amide group as an isosteric replacement for the Phe-Ala scissile bond of the BPP5a analogue [Phe3]BPP5a has been studied. The synthesis of the retroinverso pentapeptide [gPhe3,(R,S)-mAla4]BPP5a has been carried out in solution by coupling the pseudopeptide epimer HO-(R,S)-mAla-Pro-OBut to Glp-Lys(Boc)-gPhe-H·HCl, separation and identification of the resulting diastereoisomers [Lys2(Boc),gPhe3,(S)-mAla4,Pro5-OBut]BPP5a and [Lys2(Boc),gPhe3,(R)-mAla4,Pro5-OBut]BPP5a, and finally acidolytic cleavage. [gPhe3,(S)-mAla4]BPP5a, a moderate inhibitor of angiotensin converting enzyme (ACE)in vitro(I50= 14 × 10–5M), was obtained and proved to be more potent than BPP5a as a hypotensive in normotensive rats without manifesting the bradykinin potentiating action of the natural peptide.
Xeon Phi Core Microarchitecture (2013)

A processor core is the heart that determines the characteristics of a computer architecture. It is where the arithmetic and logic functions are mostly concentrated. The instruction set architecture (ISA) is implemented in this portion of the circuitry. Yet, in a modern-day architecture such as Intel Xeon Phi, less than 20 percent of the chip area is dedicated to the core. A survey of the development of the Intel Xeon Phi architecture will elucidate why its coprocessor core is designed the way it is.
Fast motion estimation within the H.264 codec (2003)

Three of the main reasons why the new H.264 (MPEG-4AVC) video coding standard has a significant performance benefit versus older standards are the adoption of variable block sizes, multiple reference frames, and the consideration of rate distortion optimization as a non-normative tool within the codec. Unfortunately these features incur a considerable increase in encoder complexity, mainly with regards to motion estimation and mode decision. In this paper, we extend and adapt the concept of the well-known enhanced predictive zonal search (EPZS) motion estimation algorithms, which is effectively used within other video coding standards into H.264. Simulation results demonstrate the efficiency of these algorithms of considerable reducing encoding complexity while incurring little, if any, loss in quality.
New tool for an old problem: can RNAi efficiently resolve the issue of genetic redundancy? (2004)

RNA interference (RNAi) has become a generally accepted tool for inhibiting gene expression in many laboratory organisms. Nagel et al.,(1) in a recent paper, give an example of how this tool can also be used to address the question of genetic redundancy. Their focus was on the redundancy in Drosophila melanogaster of the Enhancer of split gene complex [E(spl)-C] which comprises seven highly related genes. Their somewhat conflicting findings are probably the typical scenario for most RNAi experiments: some expected results and some surprises.
Regulatory CD56 bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis (2006)

Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.
A ready, convergent synthesis of the heptasaccharide GPI membrane anchor of rat brain Thy-1 glycoprotein (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA ready, convergent synthesis of the heptasaccharide GPI membrane anchor of rat brain Thy-1 glycoproteinUko E. Udodong, Robert Madsen, Carmichael Roberts, and Bert Fraser-ReidCite this: J. Am. Chem. Soc. 1993, 115, 17, 7886–7887Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/ja00070a048https://doi.org/10.1021/ja00070a048research-articleACS PublicationsRequest reuse permissionsArticle Views270Altmetric-Citations57LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
Retinoid Ligands Inhibit Cell Proliferation by Modulating Cell Cycle Regulators in Human Coronary Smooth Muscle Cells (2000)

P74 Retinoids inhibit vascular smooth muscle cell proliferation in vitro and intimal hyperplasia in vivo in rats. We examined the underlying mechanism of the antiproliferative effect of retinoids on human coronary smooth muscle cells (CASMC). The retinoids tested included: RAR ligands, all-trans retinoic acid (atRA) and Ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-propenyl]-benzoic acid (TTNPB); a RXR and RAR ligand 9-cis retinoic acid (9cRA); and the potent RXRα- ligand AGN4204. All retinoids inhibited DNA synthesis in CASMC stimulated with platelet derived growth factor and insulin (IC 50 : TTNPB 0.063μM, atRA 0.123μM, AGN4204 0.461μM, 9cRA 1.529μM, all p -7 M; AGN4204 and 9cRA, 2x10 -6 M all p -9 M; atRA, 2x10 -7 M; AGN4204, 2x10 -6 M, all p Kip1 , a major negative regulator of G1 cyclin/CDK activity (maximal effect: TTNPB and atRA, 2x10 -7 M; AGN4204 and 9cRA, 2x10 -6 M, all p
Flow cytometric analysis of DNA ploidy in primary non-small cell carcinoma of the lung in Korea (1993)

Flow cytometrically determined nuclear DNA content has been measured on 74 formalin-fixed, paraffin embedded specimens of non-small cell carcinoma of the lung. Of the 60 tumors that were successfully analyzed, 32 (53%) were diploid and 28 (47%) were aneuploid. The mean DNA index of aneuploid tumor was 1.5 +/- 0.25, ranging from 1.1 to 2.0. There was no significant correlation between DNA ploidy and the patient's clinical characteristics, histology of tumor, nodal status or tumor stage. Tumor ploidy was not found as a prognostic determinant in non-small cell carcinoma of the lung in this study.