gebhart/patrepeval huggingface dataset:
Ginkgo biloba extract EGb 761 increases stress resistance and extends life span of Caenorhabditis elegans. (2002)

EGb 761, a standardized extract of Ginkgo biloba leaves, has been used in clinical trials for its beneficial effects on brain functions. In mammals, EGb 761 has been shown to enhance cognition, stress resistance, and longevity, but its molecular and cellular mechanisms are not known. In the present investigation, we used the model organism Caenorhabditis elegans to evaluate pharmacological effects of EGb 761 on aging. We tested the theory that EGb 761 augments the natural antioxidant system of C elegans, and thus increases stress resistance and longevity. We found that treatment of the wild-type worms with EGb 761 extended their median life span by 8%. Amongst several purified components of EGb 761, the flavonoid tamarixetin showed the most dramatic effect: it extended the median life span by 25%. Furthermore, EGb 761 increased the wild type's resistance to acute oxidative and thermal stress by 33% and 25%, respectively. Treatment of the prematurely aging mutant worms mev-1 with EGb 761 increased their resistance to acute oxidative and thermal stress by 33% and 11%, respectively. It appears that oxidative stress, a major determinant of life span, as well as other types of stress, can be successfully counteracted by the Ginlkgo biloba extract EGb 761.
Generation of Anti-complement “Prodrugs” (2003)

Expression of biologically active molecules as fusion proteins with antibody Fc can substantially extend the plasma half-life of the active agent but may also influence function. We have previously generated a number of fusion proteins comprising a complement regulator coupled to Fc and shown that the hybrid molecule has a long plasma half-life and retains biological activity. However, several of the fusion proteins generated had substantially reduced biological activity when compared with the native regulator or regulator released from the Fc following papain cleavage. We have taken advantage of this finding to engineer a prodrug with low complement regulatory activity that is cleaved at sites of inflammation to release active regulator. Two model prodrugs, comprising, respectively, the four short consensus repeats of human decay accelerating factor (CD55) linked to IgG4 Fc and the three NH2-terminal short consensus repeats of human decay accelerating factor linked to IgG2 Fc have been developed. In each, specific cleavage sites for matrix metalloproteinases and/or aggrecanases have been incorporated between the complement regulator and the Fc. These prodrugs have markedly decreased complement inhibitory activity when compared with the parent regulator in vitro. Exposure of the prodrugs to the relevant enzymes, either purified, or in supernatants of cytokine-stimulated chondrocytes or in synovial fluid, efficiently cleaved the prodrug, releasing active regulator. Such agents, having negligible systemic effects but active at sites of inflammation, represent a paradigm for the next generation of anti-C therapeutics.
The application of electromagnetic surface waves to wireless energy transfer (2015)

The use of guided electromagnetic waves for the wireless transmission of electrical energy has long been the subject of scientific investigation. While attention is presently focused on the near-field inductive and far-field radiative techniques there is ongoing interest, as well, in the possibility of using a terrestrial transmission line mode for wireless power transfer. A history of surface wave theory development is provided, along with comments about the basic functionality of Tesla's original designs.
Current Perspectives on the Therapeutic Utility of VR1 Antagonists (2004)

This review gives a brief overview of the expression patterns, molecular pharmacology and physiological roles of the vanilloid receptor 1 (VR1). Particular emphasis is given to the therapeutic utility of VR1 modulators. Small molecule agonists of VR1, including capsaicin and RTX, are currently utilized for a number of clinical syndromes, including intractable neuropathic pain, spinal detrusor hyperreflexia, and bladder hypersensitivity; however, antagonists of VR1 have yet to reach the clinic. While the classic VR1 antagonist, capsazepine has proven a useful tool for unraveling the molecular pharmacology of VR1, in vivo studies with this compound have had limited success due to poor pharmacokinetic properties and species selectivity issues. With the cloning of VR1 in 1997, the pharmaceutical community has been provided a molecular target for high throughput screening and small molecule lead discovery and optimization. As a result, resurgence in the interest of VR1 antagonists has given way to many new pharmacological agents that may provide better tools to probe VR1 physiology, and ultimately yield promising therapeutic agents.
A method to detect and characterize point mutations in transcribed genes: amplification and overexpression of the mutant c-Ki-ras allele in human tumor cells. (1985)

A significant percentage of human tumors contain activated ras oncogenes that have acquired oncogenic potential as a result of somatic point mutations at codon 12 or 61 of the encoded ras gene product. We report here a method to detect and characterize mutations in ras genes that is based on the ability of pancreatic ribonuclease (RNase A; EC 3.1.27.5) to cleave RNA heteroduplexes containing single-base mismatches. Using this method, we show that certain human tumor cells contain mutant c-Ki-ras genes, and we define the nature and position of these mutations. At the same time, we describe the presence and estimate the expression of both normal and mutant c-Ki-ras alleles in the same tumor cells. This method should be useful for the diagnostic detection and characterization of single point mutations in expressed genes.
Soluble Epidermal Growth Factor Receptor (SEG-FR) and Cancer Antigen 125 (CA125) as Screening and Diagnostic Tests for Epithelial Ovarian Cancer (2005)

Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecologic cancers in the United States. Because women who are diagnosed with early stage disease have a better prognosis than women diagnosed with late stage disease, early detection represents a potentially practical approach to reduce the mortality associated with EOC. Unfortunately, no single screening test has proven to be effective for this purpose, and a valid and feasible screening program to detect early stage EOC in the general population has not yet been devised. Consequently, research has focused on coupling two or more screening modalities to improve program validity and feasibility. Serum cancer antigen 125 (CA125) and a soluble isoform of the epidermal growth factor receptor (p110 sEGFR) have been studied individually as biomarkers of ovarian cancer. In this study, we compare serum CA125 levels and sEGFR concentrations in women with EOC to women with benign gynecologic conditions of ovarian and non-ovarian origin. We show that serum sEGFR concentrations are lower in patients with EOC than in women with benign gynecologic conditions, whereas serum CA125 levels are higher in patients to EOC compared with women with benign gynecologic conditions. These data also reveal that age and serum sEGFR concentrations modify the association between CA125 levels and EOC versus benign gynecologic disease. Hence, age- and sEGFR-dependent CA125 cutoff thresholds improve the ability of CA125 to discern EOC patients from women with benign ovarian tumors and non-ovarian gynecologic conditions. Our analyses show that parallel testing with fixed sEGFR and CA125 cutoff thresholds optimizes sensitivity to detect EOC, whereas serial testing with age- and sEGFR-dependent CA125 cutoff thresholds optimizes test specificity, and overall accuracy to discern patients with EOC from women with benign ovarian and non-ovarian gynecologic conditions. The combined use of serologic sEGFR and CA125, thus, has improved utility for screening and diagnosing EOC, which may increase the positive predictive value of a multimodal screening program that incorporates these biomarkers to detect and subsequently differentiate benign from malignant ovarian tumors.
Learning conversations (1998)

article Free Access Share on Learning conversations Authors: Rachel Bellamy View Profile , Kristina Woolsey View Profile Authors Info & Claims ACM SIGCHI BulletinVolume 30Issue 2April 1998 pp 108–112https://doi.org/10.1145/279044.279170Published:01 April 1998Publication History 2citation205DownloadsMetricsTotal Citations2Total Downloads205Last 12 Months31Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Kinetics of Mg2+ unblock of NMDA receptors: implications for spike‐timing dependent synaptic plasticity (2004)

The time course of Mg(2+) block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg(2+) unblock were found to be non-instantaneous and complex, consisting of a prominent fast component (time constant approximately 100 micros) and slower components (time constants 4 and approximately 300 ms), the relative amplitudes of which depended on the timing of the depolarizing pulse. Fitting a kinetic model to these data indicated that Mg(2+) not only blocks the NMDAR channel, but reduces both the open probability and affinity for glutamate, while enhancing desensitization. These effects slow the rate of NMDAR channel opening in response to depolarization in a time-dependent manner such that the slower components of Mg(2+) unblock are enhanced during depolarizations at later times after glutamate application. One physiological consequence of this is that brief depolarizations occurring earlier in time after glutamate application are better able to open NMDAR channels. This finding has important implications for spike-timing-dependent synaptic plasticity (STDP), where the precise (millisecond) timing of action potentials relative to synaptic inputs determines the magnitude and sign of changes in synaptic strength. Indeed, we find that STDP timing curves of NMDAR channel activation elicited by realistic dendritic action potential waveforms are narrower than expected assuming instantaneous Mg(2+) unblock, indicating that slow Mg(2+) unblock of NMDAR channels makes the STDP timing window more precise.
Analysis of the role of M24 protein in group A streptococcal adhesion and colonization by use of omega-interposon mutagenesis (1994)

We recently concluded that M protein mediates adherence of group A streptococci to HEp-2 tissue culture cells, because the N-terminal half of M protein blocked adherence and M+ strains attached in greater numbers than M- streptococci. To further assess the role of M protein in adhesion, an M-, isogenic mutant of M type M-, isogenic mutant of M type 24 group A streptococci was constructed by insertional inactivation of the emm24 gene with the omega-interposon flanked by emm24 gene sequences. Southern blot analysis confirmed that the omega-element inserted only into emm24. The M- isogenic mutant M24-omega 3 did not react with antiserum to M24 protein, not did it survive in whole human blood. Electron micrographs of M24-omega 3 showed a diminution of surface fibrillae and reduced binding of plasma components compared with the parent strain. The adhesion of the M+ parent to HEp-2 cells and to mouse oral epithelial cells was dramatically greater than the adhesion of the M24-omega 3 mutant, although there was no difference between the two in adhesion to human buccal cells. In addition, the parent strain was dramatically more effective than the M24-omega 3 mutant in colonizing the oral cavity of mice. These results indicate that the M24 protein can serve as an adhesin in streptococcal attachment to human cells in tissue culture and is important in the colonization of mouse mucosal surfaces.
Phase I study of temozolomide and escalating doses of oral etoposide for adults with recurrent malignant glioma (2003)

Abstract BACKGROUND Although temozolomide is active against recurrent malignant glioma, responses in many patients are modest and short‐lived. Temozolomide may prove more effective in combination with other agents. Therefore, combination oral chemotherapy for these patients is a particularly attractive approach. METHODS The authors conducted a Phase I study of temozolomide in combination with escalating doses of oral etoposide (VP‐16) to determine the maximum tolerated doses of these two agents when given together. The temozolomide dose was fixed at 150 mg/m 2 per day on Days 1–5. The oral VP‐16 was escalated in cohorts of 3 to 6 patients by numbers of days of VP‐16 administered: 50 mg/m 2 per day, Days 1–5 (dose level 1), Days 1–8 (dose level 2), Days 1–12 (dose level 3), Days 1–16 (dose level 4), and Days 1–20 (dose level 5). Therapy was given in 28‐day cycles. RESULTS Of the 29 patients enrolled, 26 were fully evaluable and 3 were partially evaluable for toxicity. The 29 patients received a total of 92 cycles. The median age of the patients was 49 years (range, 28–76 years). Diagnoses included glioblastoma ( n = 19), gliosarcoma ( n = 3), anaplastic astrocytoma ( n = 5), and anaplastic oligoastrocytoma ( n = 2). The median time from diagnosis to disease recurrence was 8 months (3–188 months). Twenty patients were treated at the first disease recurrence, seven at the second, and two at the third. Twenty‐four patients (83%) were receiving anticonvulsants and 24 were receiving dexamethasone. All patients had received previous radiation, and 25 of 29 had been treated with chemotherapy previously. Of the 3 patients at dose level 1, none had dose‐limiting toxicity (DLT). Of the 6 patients at dose level 2, 1 patient had DLT: Grade 3 thrombocytopenia resulting in a &gt; 2‐week delay in starting the next cycle of chemotherapy. Of the 6 patients at dose level 3, 1 patient had DLT: death due to pneumonia. There were 2 DLTs in the 7 patients at dose level 4: fever, neutropenia, and herpes zoster infection in 1 patient and death due to pneumonia in another. Seven patients had been started at dose level 5 when DLT was established at dose level 4: of the 5 fully evaluable and 2 partially evaluable patients at dose level 5, there was no DLT. CONCLUSIONS The maximum tolerated dose of temozolomide and oral VP‐16 in this heavily treated group of patients with recurrent malignant glioma is temozolomide 150 mg/m 2 per day for 5 days and oral VP‐16 50 mg/m 2 per day for 12 days. Cancer 2003;97:1963–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11260
Presynaptic Molecular Determinants of Quantal Size (2016)

The quantal hypothesis for the release of neurotransmitters at the chemical synapse has gained wide acceptance since it was first worked out at the motor endplate in frog skeletal muscle in the 1950's. Considering the morphological identification of synaptic vesicles (SVs) at the nerve terminals that appeared to be homogeneous in size, the hypothesis proposed that signal transduction at synapses is mediated by the release of neurotransmitters packed in SVs that are individually uniform in size; the amount of transmitter in a synaptic vesicle is called a quantum. Although quantal size-the amplitude of the postsynaptic response elicited by the release of neurotransmitters from a single vesicle-clearly depends on the number and sensitivity of the postsynaptic receptors, accumulating evidence has also indicated that the amount of neurotransmitters stored in SVs can be altered by various presynaptic factors. Here, I provide an overview of the concepts and underlying presynaptic molecular underpinnings that may regulate quantal size.
Bicondylar St. Georg Sledge Knee Arthroplasty (1990)

Fifty-three bicondylar St. Georg sledge knee arthroplasties in 44 patients were reviewed. These patients had a mean follow-up period of 5.9 years (range, three to ten years). Function was assessed using the d'Aubigné scale coupled with measurement of range of motion (ROM) and stability. Pain relief was substantial (75%), and functional ability improved commensurately. ROM improved from a preoperative average of 83 to a postoperative 123. Three (5.7%) arthroplasties failed and were subsequently revised, while three (6.8%) of the knees examined at review have static radiolucent lines at the tibial bone-cement interface. The remaining 44 knees examined (93.2%) showed no signs of impending failure and have sustained their functional result. The polyethylene tibial components are not metal backed, and it is of interest that bone-cement interface failure has been unusual. This operation is a somewhat exacting procedure, but with the correct choice of patient and technique, a predictable result can be expected.
Improving main memory utilization for array-based datacube computation (1998)

Computing datacubes requires multidimensional aggregations for all possible combinations of each dimension. In thii paper, we present a method to improve main memory utilization efficiency for an array-based algorithm for datacube computation in a MOLAP context. The problem with the array-based algorithm is in its sparsity, where a large pre portion of array cells are empty. ,The algorithm proposed in [ZDN97] reduces this space inefficiency by compressing arrays on disk. We improve on this algorithm by performing compression of arrays in main memory as well as on disk using a hashing method, which allocates main memory according to the number of non-empty array cells. We further improve the algorithm using a dynamic main memory allocation strategy. The algorithm by [ZDN97] computes the multiple aggregate views simultaneously, which consumes a lot of main memory space. We propose a main memory allocation method that minimizes the main memory requirement by dynamically allocating main memory only to necessary aggregate views at run time. These savings in main memory resources result in the reduction of disk I/O cost. We evaluate the performance of the proposed method by disk I/O analysis and demonstrate that the improved MOLAP algorithm compares well with a ROLAP algorithm.
Efficient and Selective Formation of Macrocyclic Disubstituted Z Alkenes by Ring‐Closing Metathesis (RCM) Reactions Catalyzed by Mo‐ or W‐Based Monoaryloxide Pyrrolide (MAP) Complexes: Applications to Total Syntheses of Epilachnene, Yuzu Lactone, Ambrettolide, Epothilone C, and Nakadomarin A (2013)

The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z), and nakadomarin A (15-membered ring: up to 97% Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule.
Destructive adsorption of chlorinated hydrocarbons on ultrafine (nanoscale) particles of calcium oxide (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDestructive adsorption of chlorinated hydrocarbons on ultrafine (nanoscale) particles of calcium oxideOlga Koper, Yong Xi Li, and Kenneth J. KlabundeCite this: Chem. Mater. 1993, 5, 4, 500–505Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/cm00028a017https://doi.org/10.1021/cm00028a017research-articleACS PublicationsRequest reuse permissionsArticle Views364Altmetric-Citations81LEARN 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
Release of Bound Procyanidins from Cranberry Pomace by Alkaline Hydrolysis (2010)

Procyanidins in plant products are present as extractable or unextractable/bound forms. We optimized alkaline hydrolysis conditions to liberate procyanidins and depolymerize polymers from dried cranberry pomace. Alkaline extracts were neutralized (pH 6-7) and then procyanidins were extracted with ethyl acetate and analyzed by normal phase high performance liquid chromatography. Alkaline hydrolysis resulted in an increase in low molecular weight procyanidins, and the increase was greater at higher temperature, short time combinations. The most procyanidins (DP1-DP3) were extracted at 60 degrees C for 15 min with each concentration of NaOH. When compared to conventional extraction using homogenization with acetone/water/acetic acid (70:29.5:0.5 v/v/v), treatment with NaOH increased procyanidin oligomer extraction by 3.8-14.9-fold, with the greatest increase being DP1 (14.9x) and A-type DP2 (8.4x) procyanidins. Alkaline treatment of the residue remaining after conventional extraction resulted in further procyanidin extraction, indicating that procyanidins are not fully extracted by conventional extraction methods.
A Web-Based Cross-Sectional Epidemiological Survey of Complex Regional Pain Syndrome (2009)

Complex regional pain syndrome is a severe disabling pain disorder that results in physical as well as emotional and financial consequences to patients. The disease complexity requires coordination of multidisciplinary care that can be achieved by educational efforts directed to general practitioners.