gebhart/patrepeval huggingface dataset:
PHARMACOKINETIC RATIONALE FOR DOSING EVERY 2 WEEKS VERSUS 4 WEEKS WITH INTRAVITREAL RANIBIZUMAB, BEVACIZUMAB, AND AFLIBERCEPT (VASCULAR ENDOTHELIAL GROWTH FACTOR TRAP-EYE) (2011)

The theoretical increase in trough binding levels when anti-VEGF drugs are dosed every 2 weeks most likely explains the clinical benefit observed in patients who received biweekly injections after their poor response to monthly therapy. The short-term use of biweekly dosing may be an attractive treatment option for those eyes that show a treatment response within 2 weeks of an injection, but rebound with increased macular fluid after a month. In the future, VTE should provide higher trough levels of anti-VEGF binding activity and eliminate the need for biweekly dosing in those eyes with VEGF-mediated exudation that appear unresponsive to monthly ranibizumab or bevacizumab.
The Logic of China-ASEAN FTA: Economic Statecraft of "Peaceful Ascendancy" (2005)

The regional political and economic order in East Asia1 has undergone a significant transformation since the end of the Cold War. One of the most important changes is China's growing clout and influence in this region. Several important factors contribute to this development: China's rapid and sustained economic growth (on average 9 percent per year over the past two decades), Japan's relative decline as a result of its decade-long recession, the 1997-98 Asian Financial Crisis that decimated several high-flying Asian economies, and the stretching-thin of the United States' military resources and political capital due to the war on terror, the daunting task of rebuilding Iraq, and the challenge posed by a nuclear North Korea.
Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. (2002)

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.
Evolutionary ordered neural network with a linked-list encoding scheme (2002)

The paper proposes an evolutionary design of a neural network architecture, with a one dimensional linked list encoding scheme. In this scheme, neurons are arranged in one dimensional array, and the order information of neurons play important roles in genetic operation. Due to one dimensional structure, encoding from neural network architecture to genotype becomes easy, and genetic operation can be easily applied. To avoid the permutation problem, we choose evolutionary programming (EP) rather than genetic algorithm (GA), i.e., we apply mutation operators only in order to generate offspring. The proposed scheme is applied to XOR and 3 parity problems, and optimal neural network architecture can be found with this encoding scheme.
Calculation of ion mobilities from electrospray ionization high-field asymmetric waveform ion mobility spectrometry mass spectrometry (2001)

Careful analysis is made of the accuracies possible when gaseous ion mobilities are determined from data obtained by combining electrospray ionization (ESI), high-field asymmetric waveform ion mobility spectrometry (FAIMS) at atmospheric pressure and room temperature, and mass spectrometry (MS). New results are reported for the mobilities of positive and negative amino acid ions in air at elevated values of E/N, the ratio of the electric field strength to the gas number density.
Structural Basis for Interaction of FGF-1, FGF-2, and FGF-7 with Different Heparan Sulfate Motifs, (2001)

Stromal cell-derived FGF-7 binds and activates only the resident FGFR2IIIb in epithelial cells while FGF-1 and FGF-2 exhibit a broader interaction with multiple isoforms of FGFR. Here we report the structure of FGF-7 that has been solved to 3.1 A resolution by molecular replacement with the structure of a dual function chimera of FGF-7 and FGF-1 (FGF-7/1) which was resolved to 2.3 A. Comparison of the FGF-7 structure to that of FGF-1 and FGF-2 revealed the strongly conserved Calpha backbone among the three FGF polypeptides and the surface hydrophobic patch that forms the primary receptor-binding domain. In contrast, a decrease and dispersion of the positive surface charge density characterized the heparin-binding domain of FGF-7 defined by homology to that of FGF-1 and FGF-2 in complexes with heparin. A simple heparin hexasaccharide that cocrystallized with FGF-1 and FGF-2 and protected both against protease in solution failed to exhibit the same properties with FGF-7. In contrast to FGF-1 and FGF-2, protection of FGF-7 was enhanced by heparin oligosaccharides of increased length with those exhibiting a 3-O-sulfate being the most effective. Protection of FGF-7 required interaction with specifically the fraction of crude heparin retained on antithrombin affinity columns. Conversely, heparin enriched by affinity for immobilized FGF-7 exhibited anti-factor Xa activity similar to that purified on an antithrombin affinity matrix. In contrast, an FGF-1 affinity matrix enriched the fraction of crude heparin with low anti-factor Xa activity. The results provide a structural basis to suggest that the unique FGF-7 heparin-binding (HB) domain underlies a specific restriction in respect to composition and length of the heparan sulfate motif that may impact specificity of localization, stability, and trafficking of FGF-7 in the microenvironment, and formation and activation of the FGFR2IIIb kinase signaling complex in epithelial cells.
The cationic polymerization of t‐butyl vinyl ether at low temperature and the conversion into polyvinyl alcohol of poly‐t‐butyl vinyl ether (1962)

Abstract The stereospecific polymerization of t ‐butyl vinyl ether (tBVE) catalyzed by BF 3 ·O(C 2 H 5 ) 2 in homogeneous system is studied. The stereoregular polymer is obtained at low temperature in solvents of low dielectric constant. In homogeneous polymerization, a more highly stereoregular polymer can be obtained than in heterogeneous polymerization, but in the heterogeneous system the polymer having a higher molecular weight is formed. These results are approximately the same as in the case of iso butyl vinyl ether. As one of the characteristics of tBVE polymerization, the stereoregularity of the polymer is greatly affected by its solubility in the solvent used. Polyvinyl alcohol (PVA) and polyvinyl acetate (PVAc) can be obtained from the isotactic and atactic poly‐ t ‐butyl vinyl ether. The infrared spectra of isotactic PVAc are the same as those of the atactic PVAc, while there are some differences between the isotactic and atactic PVA so obtained. In the case of isotactic PVA contrary to that of atactic PVA the crystalline band near 1140 cm −1 is very week even after heating.
Dermatoporosis: A Chronic Cutaneous Insufficiency/Fragility Syndrome (2007)

We propose to group the different manifestations and implications of this syndrome under the umbrella term of 'dermatoporosis', because we think it will help to capture the understanding of health professionals that, as osteoporosis, 'dermatoporosis' should be prevented and treated to avoid complications. Dermatologists should be aware of this emerging syndrome and function as key players in prevention and therapy. Randomized clinical trials should demonstrate which intervention may best prevent and/or reverse dermatoporosis.
The Rate of Saponification of Acetates of Unsaturated Alcohols (1952)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Rate of Saponification of Acetates of Unsaturated AlcoholsR. Thomas Myers, A. R. Collett, and C. L. LazzellCite this: J. Phys. Chem. 1952, 56, 4, 461–463Publication Date (Print):April 1, 1952Publication History Published online1 May 2002Published inissue 1 April 1952https://pubs.acs.org/doi/10.1021/j150496a012https://doi.org/10.1021/j150496a012research-articleACS PublicationsRequest reuse permissionsArticle Views233Altmetric-Citations16LEARN 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 options Get e-Alerts
Insulin-Like Growth Factor I Activates c-Jun N-Terminal Kinase in MCF-7 Breast Cancer Cells1 (2000)

Insulin-like growth factor I (IGF-I) is an important mediator of breast cancer cell growth, although the signaling pathways important for IGF-I-mediated effects in breast cancer cells are still being elucidated. We had demonstrated previously that increased intracellular cAMP in MCF-7 breast cancer cells inhibited cell growth and IGF-I-induced gene expression, as determined using a reporter gene assay. This effect of cAMP on IGF-I signaling was independent of IGF-I-induced activation of the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1 and -2). To determine whether this effect of cAMP may be mediated via another mitogen-activated protein kinase, the ability of IGF-I to activate the c-Jun N-terminal kinases (JNKs) was investigated. Treatment of MCF-7 cells with 100 ng/ml IGF-I increased the level of phosphorylated JNK, as determined by Western blot analysis. JNK phosphorylation was not evident until 15 min after treatment with IGF-I, and peak levels of phosphorylation were present at 30-60 min. This was in contrast to ERK phosphorylation, which was present within 7.5 min of IGF-I treatment. Determination of JNK activity using an immune complex assay demonstrated a 3.3- and 3.5-fold increase in JNK1 and -2 activity, respectively, 30 min after treatment with 100 ng/ml IGF-I. The use of PD98059, which inhibits activation of ERK1 and -2, and LY 294002, an inhibitor of phosphatidylinositol 3-kinase, demonstrated that IGF-I-induced activation of JNK1 is independent of ERK and phosphatidylinositol 3-kinase activation. In contrast, increasing intracellular cAMP with forskolin resulted in abrogation of IGF-I-induced JNK activity. In summary, these data demonstrate that IGF-I activates the JNKs in MCF-7 breast cancer cells and, taken together with the results of our previous study, suggest that JNK may contribute to IGF-I-mediated gene expression and, possibly, cell growth in MCF-7 breast cancer cells.
GPCRHomology Model Development and Application (2010)

Abstract G‐protein‐coupled receptors (GPCRs) are a very important class of proteins for drug discovery. Exciting progress has been made recently in the determination of X‐ray crystal structures. However, despite this, structural coverage of the receptor family is still thin. We lack direct structural knowledge of many important subfamilies, we have only modest detail of the conformational changes associated with receptor activation and we lack robust crystallographic systems for the rapid determination of ligand binding modes. As a consequence, the ability to build and apply homology models for drug discovery at these targets is very valuable. The accuracy of the models has improved in parallel with the increase in available structural data and the models have been successfully applied to a wide range of lead generation and optimization problems.
Fiber-optic sensors for continuous clinical monitoring (1992)

Optical sensors are prepared by attaching an indicating layer to the distal tip of an optical fiber. Light is sent down the optical fiber and is modulated by the indicating layer. The degree of modulation of the returned light is a direct measure of the amount of a particular chemical species in contact with the fiber tip. A variety of sensor designs can be employed along with a diverse array of supporting instrumentation. An overview of the various optical transduction mechanisms, instrumentation, and problems associated with optical sensors for continuous clinical monitoring is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Broadening the horizons for yellow fever (2005)

The vaccine against yellow fever is one of the safest and most effective ever developed. With an outstanding record in humans, has this live attenuated vaccine been overlooked as a promising vector for the development of vaccines against pathogens outside its own genus? Recent studies, including a report by Tao et al. on page 201 of this issue, have sparked renewed interest.
Interacting with paper on the DigitalDesk (1993)

In the 1970’s Xerox PARC developed the “desktop metaphor, ” which made computers easy to use by making them look and act like ordinary desks and paper. This led visionaries to predict the “paperless office ” would dominate within a few years, but the trouble with this prediction is that people like paper too much. It is portable, tactile, universally accepted, and easier to read than a screen. Today, we continue to use paper, and computers produce more of it than they replace. Instead of trying to use computers to replace paper, the DigitalDesk takes the opposite approach. It keeps the paper, but uses computers to make it more powerful. It provides a Computer Augmented Environment for paper. The DigitalDesk is built around an ordinary physical desk and can be used as such, but it has extra capabilities. A video camera is mounted above the desk, pointing down at the work surface. This camera’s output is fed through a system that can detect where the user is pointing, and it can read documents that are placed on the desk. A computer-driven electronic projector is also mounted above
Transforming growth factor-β1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells (2005)

Transforming growth factor-beta1 (TGF-beta1) is abundantly expressed in pulmonary hypertension, but its effect on the pulmonary circulation remains unsettled. We studied the consequences of TGF-beta1 stimulation on freshly isolated human pulmonary artery smooth muscle cells (HPASMC). TGF-beta1 initially promoted differentiation, with upregulated expression of smooth muscle contractile proteins. TGF-beta1 also induced expression of Nox4, the only NAD(P)H oxidase membrane homolog found in HPASMC, through a signaling pathway involving Smad 2/3 but not mitogen-activated protein (MAP) kinases. TGF-beta1 likewise increased production of reactive oxygen species (ROS), an effect significantly reduced by the NAD(P)H oxidase flavoprotein inhibitor diphenylene iodonium (DPI) and by Nox4 siRNAs. In the absence of TGF-beta1, Nox4 was present in freshly cultured cells but progressively lost with each passage in culture, paralleling a decrease in ROS production by HPASMC over time. At a later time point (72 h), TGF-beta1 promoted HPASMC proliferation in a manner partially inhibited by Nox4 small interfering RNA and dominant negative Smad 2/3, indicating that TGF-beta1 stimulates HPASMC growth in part by a redox-dependent mechanism mediated through induction of Nox4. HPASMC activation of the MAP kinases ERK1/2 was reduced by the NAD(P)H oxidase inhibitors DPI and 4-(2-aminoethyl)benzenesulfonyl fluoride, suggesting that TGF-beta1 may facilitate proliferation by upregulating Nox4 and ROS production, with transient oxidative inactivation of phosphatases and augmentation of growth signaling cascades. These findings suggest that Nox4 is the relevant Nox homolog in HPASMC. This is the first observation that TGF-beta1 regulates Nox4, with important implications for mechanisms of pulmonary vascular remodeling.
Advances In Power Sources For Wireless Sensor Nodes (2004)

In young Asian children, the axial length and vitreous chamber depth increased, but the elongation slowed with age. There was a U-shaped growth curve for lens thickness and an inverted U-shaped curve for anterior chamber depth. The findings of early lens thinning followed by thickening suggest a two-phase growth of the lens.
The Effect of the JNK Inhibitor, JIP Peptide, on Human T Lymphocyte Proliferation and Cytokine Production (2008)

Although JNK is a potential target for treating chronic inflammatory diseases, its role in T lymphocyte function remains controversial. To overcome some of the previous limitations in addressing this issue we have used the recently described transactivator of transcription-JNK-interacting protein (TAT-JIP) peptide, a specific inhibitor that was derived from the minimal JNK-binding region of the scaffold protein, JNK-interacting protein 1 (JIP-1), coupled to the short cell-permeable HIV TAT sequence. Pretreatment of purified human T lymphocytes with the TAT-JIP peptide inhibited the phosphorylation of endogenous jun activated by PHA-PMA. This was associated with a corresponding inhibition of lymphoproliferation, and of IL-2, IFN-gamma, lymphotoxin, and IL-10 cytokine production. Similar results were also found using mouse splenic T cells. Examination of the specificity of TAT-JIP revealed that although the peptide was more selective than the pharmacological inhibitor, SP600125, it also inhibited cyclin-dependent kinase 2, p70 ribosomal protein S6 kinase, and serum and glucocorticoid-regulated kinase activity. Nevertheless, these data demonstrate for the first time the ability of the TAT-JIP peptide to inhibit the JNK pathway and the phosphorylation of jun in intact cells, thereby preventing the activation of the transcription factor, AP-1, and the production of Th1 and Th2 cytokines. Thus JNK could potentially be a target for the development of drugs for the treatment of autoimmune inflammatory diseases.
Rapid Deadenylation and Poly(A)-Dependent Translational Repression Mediated by the Caenorhabditis elegans tra-2 3′ Untranslated Region in Xenopus Embryos (2000)

The 3' untranslated region (3'UTR) of many eukaryotic mRNAs is essential for their control during early development. Negative translational control elements in 3'UTRs regulate pattern formation, cell fate, and sex determination in a variety of organisms. tra-2 mRNA in Caenorhabditis elegans is required for female development but must be repressed to permit spermatogenesis in hermaphrodites. Translational repression of tra-2 mRNA in C. elegans is mediated by tandemly repeated elements in its 3'UTR; these elements are called TGEs (for tra-2 and GLI element). To examine the mechanism of TGE-mediated repression, we first demonstrate that TGE-mediated translational repression occurs in Xenopus embryos and that Xenopus egg extracts contain a TGE-specific binding factor. Translational repression by the TGEs requires that the mRNA possess a poly(A) tail. We show that in C. elegans, the poly(A) tail of wild-type tra-2 mRNA is shorter than that of a mutant mRNA lacking the TGEs. To determine whether TGEs regulate poly(A) length directly, synthetic tra-2 3'UTRs with and without the TGEs were injected into Xenopus embryos. We find that TGEs accelerate the rate of deadenylation and permit the last 15 adenosines to be removed from the RNA, resulting in the accumulation of fully deadenylated molecules. We conclude that TGE-mediated translational repression involves either interference with poly(A)'s function in translation and/or regulated deadenylation.
Semi-synthetic aequorin. An improved tool for the measurement of calcium ion concentration (1988)

The photoprotein aequorin isolated from the jellyfish Aequorea emits blue light in the presence of Ca2+ by an intramolecular process that involves chemical transformation of the coelenterazine moiety into coelenteramide and CO2. Because of its high sensitivity to Ca2+, aequorin has widely been used as a Ca2+ indicator in various biological systems. We have replaced the coelenterazine moiety in the protein with several synthetic coelenterazine analogues, providing semi-synthetic Ca2+-sensitive photoproteins. One of the semi-synthetic photoproteins, derived from coelenterazine analogue (II) (with an extra ethano group), showed highly promising properties for the measurement of Ca2+, namely (1) the rise time of luminescence in response to Ca2+ was shortened by approx. 4-fold compared with native aequorin and (2) the luminescence spectrum showed two peaks at 405 nm and 465 nm and the ratio of their peak heights was dependent on Ca2+ concentration in the range of pCa 5-7, thus allowing the determination of [Ca2+] directly from the ratio of two peak intensities. Coelenterazine analogue (I) (with a hydroxy group replaced by an amino group) was also incorporated into apo-aequorin, yielding a Ca2+-sensitive photoprotein, which indicates that an electrostatic interaction between the phenolate group in the coelenterazine moiety and some cationic centre in apo-aequorin is not important in native aequorin, contrary to a previous suggestion.
Towards intent-driven bidterm suggestion (2009)

In online advertising, pervasive in commercial search engines, advertisers typically bid on few terms, and the scarcity of data makes ad matching difficult. Suggesting additional bidterms can significantly improve ad clickability and conversion rates. In this paper, we present a large-scale bidterm suggestion system that models an advertiser's intent and finds new bidterms consistent with that intent. Preliminary experiments show that our system significantly increases the coverage of a state of the art production system used at Yahoo while maintaining comparable precision.
Sulfenylation of some pyrroles and indoles (1991)

Abstract Methylsulfenylation of 1‐substituted pyrroles and indoles was observed using 1‐(methylthio)morpholine and an acid catalyst or with methylsulfenyl chloride and excess pyridine. 1‐Substituents which are activating or weakly deactivating towards electrophilic substitution such as alkyl, 2‐cyanoethyl, dimethylamino, trialkylsilyl, 2‐chloroethyl and 2‐phenylsulfonylethyl were used. The 2‐chloroethyl and 2‐phenylsulfonylethyl groups which can be removed with a strong base can be used to obtain 1 H ‐methylthiopyrroles and indoles. 1‐Phenylsulfonyl and 1‐acetyl substituents are too strongly deactivating for these sulfenylations to be successful. Mono and disubstituted pyrroles and monosubstituted indoles can be isolated from these reactions, however, because the methylthio group is activating towards electrophilic substitution the main advantage of these reactions is the synthesis of tri and tetrasubstituted pyrroles and disubstituted indoles. 1‐Methyl‐2,3,4,5‐tetra‐methylthiopyrrole and 1‐methyl‐2,3‐dimethylthioindole are oxidized to the corresponding 3,4‐disulfoxide and 3‐sulfoxide and with excess oxidizing agent to the tetrasulfone and disulfone, respectively.
Prophylactic Antibiotics in Clean Orthopaedic Surgery (1974)

A double-blind prospective study involving 1,591 clean orthopaedic surgical procedures was performed to test the effectiveness of preoperative and intraoperative antibiotics in reducing the postoperative infection rate. The antibiotic and placebo groups were analyzed for factors known to predispose to infection. A decrease in the over-all postoperative infection rate from 5 per cent in the placebo group to 2.8 per cent in the antibiotic group was found.