gebhart/patrepeval huggingface dataset:
Identification of Amino Acid Residues Critical for Catalysis and Cosubstrate Binding in the Flavonol 3-Sulfotransferase (1995)

The comparison of the deduced amino acid sequences of plant and animal sulfotransferases (ST) has allowed the identification of four well conserved regions, and previous experimental evidence suggested that regions I and IV might be involved in the binding of the cosubstrate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). Moreover, region IV is homologous to the glycine-rich phosphate binding loop (P-loop) motif known to be involved in nucleotide phosphate binding in several protein families. In this study, the function of amino acid residues within these two regions was investigated by site-directed mutagenesis of the plant flavonol 3-ST. In region I, our results identify Lys59 as critical for catalysis, since replacement of this residue with alanine resulted in a 300-fold decrease in specific activity, while a 15-fold reduction was observed after the conservative replacement with arginine. Photoaffinity labeling of K59R and K59A with [35S]PAPS revealed that Lys59 is not required for cosubstrate binding. However, the K59A mutant had a reduced affinity for 3'-phosphoadenosine 5'-phosphate (PAP)-agarose, suggesting that Lys59 may participate in the stabilization of an intermediate during the reaction. In region IV, all substitutions of Arg276 resulted in a marked decrease in specific activity. Conservative and unconservative replacements of Arg276 resulted in weak photoaffinity labeling with [35S]PAPS and the R276A/T73A and R276E enzymes displayed reduced affinities for PAP-agarose, suggesting that the Arg276 side chain is required to bind the cosubstrate. The analysis of the kinetic constants of mutant enzymes at residues Lys277, Gly281, and Lys284 allowed to confirm that region IV is involved in cosubstrate binding.
Retargeted Clostridial Neurotoxins as Novel Agents for Treating Chronic Diseases (2011)

Botulinum neurotoxin (BoNT) A and B are used to treat neuropathic disorders; if retargeted, these agents could be used to treat medical conditions that involve secretion from nonneuronal cells. Here, we report novel strategies for successfully retargeting BoNTs, and also tetanus neurotoxin (TeNT), to primary human blood monocyte-derived macrophages where BoNT/B inhibited the release of tumor necrosis factor-α, a cytokine that plays a key role in inflammation. Furthermore, mice treated with retargeted BoNT/B exhibited a significant reduction in macrophage (MΦ) recruitment, indicating that these toxins can be used to treat chronic inflammation.
Development and Application of a Continuous Microwave Reactor for Organic Synthesis (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDevelopment and Application of a Continuous Microwave Reactor for Organic SynthesisTeresa Cablewski, Alan F. Faux, and Christopher R. StraussCite this: J. Org. Chem. 1994, 59, 12, 3408–3412Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/jo00091a033https://doi.org/10.1021/jo00091a033research-articleACS PublicationsRequest reuse permissionsArticle Views6082Altmetric-Citations185LEARN 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
Myasthenia gravis and myasthenic syndromes. (1992)

Epidemiology, pathophysiology, thymus pathology, antibodies and therapies in myasthenia gravis MG) are reviewed. Congenital MG and the Lambert-Eaton myasthenic syndrome (LEMS) are also discussed.
PREVENTION OF THE LOCALIZED AND GENERALIZED SHWARTZMAN REACTIONS BY AN ANTICOMPLEMENTARY AGENT, COBRA VENOM FACTOR (1971)

Both localized and generalized Shwartzman reactions were induced in the same rabbits by simultaneous administration of preparatory intravenous and intradermal doses of endotoxin followed in 24 hr by the provocative dose. Control rabbits with more than 80% positive responses showed corresponding changes of platelet, white blood cell, fibrinogen, and hemolytic complement levels. Circulating fibrinogen and fibrin degradation products were detected shortly after the preparatory dose and persisted for at least 3 days. Rabbits given cobra venom anticomplementary factor showed hypocomplementemia (less than 10% of normal), leukocytosis, and elevated fibrinogen levels. After the administration of endotoxin, only one of 15 CVF-treated animals developed a Shwartzman reaction and that was mild. These rabbits showed only minor changes of platelet and fibrinogen levels throughout the experiment although their white blood cell responses were similar to those of the control group. No detectable fibrinogen and fibrin degradation products appeared in circulation, and the hemolytic complement activity increased gradually beginning with the preparatory dose of endotoxin. Thus depletion of terminal complement components (mainly C3) in rabbits is protective against the development of both localized and generalized Shwartzman reactions; its mechanism of action is probably through the sparing of platelets by inhibiting platelet-endotoxin interaction. The essential role of the complement system in Shwartzman reaction indicates that this coagulopathy probably represents a manifestation of immunologic injury.
A family of beta 7 integrins on human mucosal lymphocytes. (1992)

The heterodimeric protein complex recognized by the human mucosal lymphocyte 1 (HML-1) monoclonal antibody is expressed on 95% of intraepithelial lymphocytes but on only 1-2% of peripheral blood lymphocytes [Cerf-Bensusson, N., Jarry, A., Brousse, N., Lisowska-Grospierre, B., Guy-Grand, D. & Griscelli, C. (1987) Eur. J. Immunol. 17, 1279-1285]. We purified the smaller HML-1 subunit (105 kDa under nonreducing conditions) from hairy-cell leukemia cells and determined the N-terminal amino acid sequence of this chain. The 17 residues determined were identical to the deduced amino acid sequence encoded by an integrin beta 7 cDNA clone [Yuan, Q., Jiang, W.-M., Krissansen, G.W. & Watson, J.D. (1990) Int. Immunol. 2, 1097-1108]. Biochemical analysis of the larger HML-1 subunit (175 kDa under nonreducing conditions) suggested that it was a distinct member of the cleaved group of integrin alpha chains, which we designated alpha E. The beta 7 chain also was associated with the integrin alpha 4 subunit, suggesting that the HML-1 antigen (alpha E beta 7) and alpha 4 beta 7 constitute a beta 7 integrin family on mucosal lymphocytes. Interestingly, regulation of the expression of the HML-1 antigen was reciprocal to that of lymphocyte function-associated molecule 1 in the presence of transforming growth factor beta 1. We suggest that these beta 7 integrins may play a specific role in mucosal localization or adhesion and that the expression of the HML-1 antigen might be regulated by transforming growth factor beta 1 produced at or near epithelial tissues.
Effects of the TREM-1 pathway modulation during empyema in rats. (2010)

The modulation of the TREM-1 pathway by the use of LP17 appears to be beneficial during empyema in rats in attenuating pleural and systemic inflammatory responses.
Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws (2006)

99Tc(m)-MDP three-phase bone scans who could be used as a screening test to detect subclinical osteonecrosis in patients who have received bisphosphonates. CT scans and MRI are useful in defining the features and extent of osteolytic lesions.
Tumor Content of the Antiapoptosis Molecule Survivin and Recurrence of Bladder Cancer (1999)

To the Editor: Transitional-cell carcinoma of the bladder is the fourth most common cancer among American men, with approximately 50,000 new cases and 10,500 deaths from the disease every year. Fif...
Carbonic Anhydrase in the Scleractinian Coral Stylophora pistillata (2008)

Carbonic anhydrases (CA) play an important role in biomineralization from invertebrates to vertebrates. Previous experiments have investigated the role of CA in coral calcification, mainly by pharmacological approaches. This study reports the molecular cloning, sequencing, and immunolocalization of a CA isolated from the scleractinian coral Stylophora pistillata, named STPCA. Results show that STPCA is a secreted form of alpha-CA, which possesses a CA catalytic function, similar to the secreted human CAVI. We localized this enzyme at the calicoblastic ectoderm level, which is responsible for the precipitation of the skeleton. This localization supports the role of STPCA in the calcification process. In symbiotic scleractinian corals, calcification is stimulated by light, a phenomenon called "light-enhanced calcification" (LEC). The mechanism by which symbiont photosynthesis stimulates calcification is still enigmatic. We tested the hypothesis that coral genes are differentially expressed under light and dark conditions. By real-time PCR, we investigated the differential expression of STPCA to determine its role in the LEC phenomenon. Results show that the STPCA gene is expressed 2-fold more during the dark than the light. We suggest that in the dark, up-regulation of the STPCA gene represents a mechanism to cope with night acidosis.
Understanding Low Speed Pre-Ignition Phenomena across Turbo-Charged GDI Engines and Impact on Future Engine Oil Design (2015)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;Recent advances in the powertrain design of gasoline engines to meet environmental regulations have posed new challenges to the engine oil development. Smaller displacement engines, often with turbochargers, developed to meet higher fuel economy standards demand higher performance engine oils in conventional areas (oxidation and deposit control, fuel economy), and completely new areas (Low-Speed Pre-ignition [LSPI], turbocharger performance). Formulating engine oils which can simultaneously meet these competing demands will become more complex with increasing performance requirements.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;Of particular interest for upcoming engine oil development is the phenomenon of low speed pre-ignition (LSPI). LSPI is an abnormal combustion event in which lubricating oil has been observed to play a role. This phenomenon is restricting automakers when operating their engines at high loads and low speed, which in turn is preventing the engine from operating at the most efficient conditions with respect to emissions and fuel economy.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;Currently there are a number of different LSPI engine tests, using different hardware, operating conditions, and criteria to determine when LSPI events have occurred. In this presentation, a comparison of different LSPI tests will be made based on Oronite's extensive research work in this area. This comparison will highlight the differences in test severity and appetite while examining similar lubricant systems across different engine platforms and test conditions.&lt;/div&gt;&lt;/div&gt;
EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells (2009)

In the previous studies, (-)-epigallocatechin-3-gallate (EGCG) has been shown to have anticarcinogenic effects via modulation in protein expression of p53. Using p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of EGCG resulted in dose-dependent inhibition of cellular proliferation, which suggests that the interaction of EGCG with p53 may not fully explain its inhibitory effect on proliferation. Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents. EGCG has multiple beneficial activities similar to those associated with CR. One key enzyme thought to be activated during CR is AMP-activated kinase (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated AMPK in both p53 positive and negative human hepatoma cells. The activation of AMPK suppressed downstream substrates, such as mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and a general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the decision between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based on these results, we have demonstrated that EGCG has a potential to be a chemoprevention and anti-lipogenesis agent for human hepatoma cells.
CCLXXXVIII.—The aryl and alkyl sulphonamides (1923)

P. W. Clutterbuck and J. B. Cohen, J. Chem. Soc., Trans., 1923, 123, 2507 DOI: 10.1039/CT9232302507
Kinetics of Ion Transport in Perovskite Active Layers and Its Implications for Active Layer Stability (2015)

Solar cells fabricated using alkyl ammonium metal halides as light absorbers have the right combination of high power conversion efficiency and ease of fabrication to realize inexpensive but efficient thin film solar cells. However, they degrade under prolonged exposure to sunlight. Herein, we show that this degradation is quasi-reversible, and that it can be greatly lessened by simple modifications of the solar cell operating conditions. We studied perovskite devices using electrochemical impedance spectroscopy (EIS) with methylammonium (MA)-, formamidinium (FA)-, and MA(x)FA(1-x) lead triiodide as active layers. From variable temperature EIS studies, we found that the diffusion coefficient using MA ions was greater than when using FA ions. Structural studies using powder X-ray diffraction (PXRD) show that for MAPbI3 a structural change and lattice expansion occurs at device operating temperatures. On the basis of EIS and PXRD studies, we postulate that in MAPbI3 the predominant mechanism of accelerated device degradation under sunlight involves thermally activated fast ion transport coupled with a lattice-expanding phase transition, both of which are facilitated by absorption of the infrared component of the solar spectrum. Using these findings, we show that the devices show greatly improved operation lifetimes and stability under white-light emitting diodes, or under a solar simulator with an infrared cutoff filter or with cooling.
Proton relaxation enhancement in tissue due to ingested manganese chloride: time course and dose response in the rat. (1984)

MnCl2, a potential NMR contrast agent, was force fed by cannula to 27 fasted rats in an attempt to establish the efficacy of this route of administration. The animals were sacrificed and the relaxation times (T1 and T2) of liver, spleen, kidney, heart, and skeletal muscle were determined in vitro. One group of rats was subject to a range of doses (8.3-333.3 mg/kg) and sacrificed at 90 minutes. Another group received a single large dose (500 mg/kg) with animals sacrificed at intervals from 15-225 minutes. The single large dose caused a rapid and prolonged reduction in liver T1 (-93% of normal) and to a lesser degree affected the other organs. The dose response data shows that liver T1 is also affected at significantly lower dosages than the other tissues tested. These results suggest the oral route as a possible alternative to IV Mn+2. Further studies with inorganic and organic manganese are indicated.
OFDM with code division multiplexing and transmit antenna diversity for mobile communications (2002)

We investigate the potential of code division multiplexing (CDM) and transmit antenna diversity in coded orthogonal frequency division multiplexing (OFDM) systems. The CDM component applied to OFDM systems can additionally exploit diversity in frequency and time selective mobile radio channels. For coded OFDM and OFDM-CDM systems we propose an antenna concept based on transmit diversity achieved by shifting the phase of the signal on the individual antennas. We show the design of such an antenna diversity concept and present the performance improvements due to CDM and transmit antenna diversity in coded OFDM systems for typical indoor and outdoor multipath channels.
Perspectives in the treatment of pancreatic adenocarcinoma (2015)

Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.
Are there ways to attenuate arterial calcification and improve cardiovascular outcomes in chronic kidney disease? (2014)

The risk of cardiovascular mortality among patients with end-stage renal disease is several times higher than general population. Arterial calcification, a marker of atherosclerosis and a predictor of cardiovascular mortality, is common in chronic kidney disease (CKD). The presence of traditional cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and advanced age cannot fully explain the high prevalence of atherosclerosis and arterial calcification. Other factors specific to CKD such as hyperphosphatemia, excess of calcium, high dose active vitamin D and prolonged dialysis vintage play important roles in the development of arterial calcification. Due to the significant health risk, it is prudent to attempt to lower arterial calcification burden in CKD. Treatment of hyperlipidemia with statin has failed to lower atherosclerotic and arterial calcification burden. Data on diabetes and blood pressure controls as well as smoking cessation on cardiovascular outcomes in CKD population are limited. Currently available treatment options include non-calcium containing phosphate binders, low dose active vitamin D, calcimimetic agent and perhaps bisphosphonates, vitamin K and sodium thiosulfate. Preliminary data on bisphosphonates, vitamin K and sodium thiosulfate are encouraging but larger studies on efficacy and outcomes are needed.
Reversal of human allergic T helper 2 responses by engagement of signaling lymphocytic activation molecule (1997)

Allergen-specific Th2 cells accumulate at high frequencies in the skin of patients with atopic dermatitis (AD), where they contribute to the induction and maintenance of the lesions that are characteristic for the disease. Attenuation of these lesions in response to successful therapy is associated with a reduction in IL-4-producing Th2 cells and the appearance of IFN-gamma-producing Th cells. In this study, we demonstrate that engagement of the signaling lymphocytic activation molecule (SLAM) by an agonistic mAb, during allergen-specific expansion of highly polarized Th2 cell populations derived from skin biopsies of AD patients, results in the generation of stable populations of IFN-gamma-producing cells. SLAM-mediated reversal of Th cell phenotype has important biologic consequences, because supernatants of these activated, allergen-specific Th cells fail to induce IgE synthesis by purified B cells costimulated by anti-CD40 mAbs. Thus, highly polarized, allergen-specific Th2 cell populations derived from the skin of AD patients can be reversed into Th cell populations that contain IFN-gamma-producing cells and that do not support IgE synthesis. These results define a new mechanism to promote Th0/Th1 differentiation and suggest a potential role for anti-SLAM mAbs in the treatment of Th2-mediated allergic diseases.
『대한매일신보』의 ‘국문" 정책과 번안소설의 대중성 연구 - 〈국치전〉과 〈매국노〉를 중심으로 (2007)

This thesis has two purposes; One is to analyze the National letter, so called Kukmun(國文) policy of the...
Electric-Field Assisted Growth and Self-Assembly of Intrinsic Silicon Nanowires (2005)

Electric-field assisted growth and self-assembly of intrinsic silicon nanowires, in-situ, is demonstrated. The nanowires are seen to respond to the presence of a localized DC electric field set up between adjacent MEMS structures. The response is expressed in the form of improved nanowire order, alignment, and organization while transcending a gap. This process provides a simple yet reliable method for enhanced control over intrinsic one-dimensional nanostructure placement and handling.