gebhart/patrepeval huggingface dataset:
Cell cycle inhibition by the anti-angiogenic agent TNP-470 is mediated by p53 and p21 WAF1/CIP1 (2000)

Angiogenesis has been demonstrated to be essential for tumor growth and metastasis, and inhibition of angiogenesis is emerging as a promising strategy for treating cancer. Among the most potent inhibitors of angiogenesis is the fumagillin family of natural products. An analog of fumagillin, known as TNP-470 or AGM-1470, has been undergoing clinical trials for treating a variety of cancers. TNP-470 has been shown to block endothelial cell cycle progression in the late G(1) phase. Although the direct molecular target for TNP-470 has been identified as the type 2 methionine aminopeptidase (MetAP2), how inhibition of this enzyme leads to cell cycle arrest has remained unclear. We report that treatment of endothelial and other drug-sensitive cell types leads to the activation of the p53 pathway, causing an accumulation of the G(1) cyclin-dependent kinase inhibitor p21(WAF1/CIP1). The requirement of p53 and p21(WAF1/CIP1) for the cell cycle inhibition by TNP-470 is underscored by the observation that cells deficient in p53 and p21(WAF1/CIP1) are resistant to TNP-470. These results shed significant light on the mechanism of cell cycle inhibition by TNP-470 and suggest an alternative method of activating p53 in endothelial cells to halt angiogenesis and tumor progression.
Portable devices used to detect endotracheal intubation during emergency situations (1998)

Although no clinical comparative study of commercial devices to detect endotracheal intubation exists, the syringe device (TubeChek) has most of the characteristics necessary for a device to be considered ideal in emergency situations in the prehospital setting. It is simple, inexpensive, easy to handle and operate, disposable, does not require maintenance, gives reliable results for patients with and without cardiac arrest, and can be used for almost all age groups. The device may yield false-negative results, most commonly in the presence of copious secretions and in cases of accidental endobronchial intubation. Regardless of the device used, clinical judgment and direct visualization of the endotracheal tube in the trachea are required to unequivocally confirm proper endotracheal tube placement.
Single-Cell Chemical Lysis Method for Analyses of Intracellular Molecules Using an Array of Picoliter-Scale Microwells (2008)

Analyzing the intracellular contents and enzymatic activities of single cells is important for studying the physiological and pathological activities at the cellular level. For this purpose, we developed a simple single-cell lysis method by using a dense array of microwells of 10-30-pL volume fabricated by poly(dimethylsiloxane) (PDMS) and a commercially available cell lysis reagent. To demonstrate the performance of this single-cell lysis method, we carried out two different assays at the single-cell level: detection of proteins by antibody conjugated microbeads and measurement of protease activity by fluorescent substrates. The results indicated that this method readily enabled us to monitor protein levels and enzymatic activities in a single cell. Because this method required only an array of PDMS microwells and a fluorescence microscope, the simplicity of this platform opens a way to explore the biochemical characteristics of single cells even by those who are not familiar with microfluidic technology.
Modeling of Piezoelectric Tube Actuators (2004)

A new dynamic model is presented for piezoelectric tube actuators commonly used in high-precision instruments. The model captures coupling between motions in all three axes such as bending motion due to a supposedly pure extension of the actuator. Both hysteresis and creep phenomena are included in the overall actuator model permitting modeling nonlinear sensitivity in the voltage to displacement response. Experimental data on hysteresis and creep are presented to support the modeling. Experiments and model predictions show that due to coupling a voltage Vz corresponding to vertical displacement will produce lateral displacement that acts as a disturbance to the main lateral response. The resonance frequency for the lateral dynamics is inherently lower than that of the longitudinal dynamics. Therefore, Vz is expected to contain frequencies that may excite the lateral resonance. Accordingly, this out of bandwidth disturbance will not be well compensated for either in open or closed loop control of the actuator. In order to preserve performance in open loop actuator control and stability and performance in closed loop control, a large reduction in the bandwidth of vertical motion would be required to avoid exciting the first bending mode.
A review of signals used in sleep analysis (2013)

This article presents a review of signals used for measuring physiology and activity during sleep and techniques for extracting information from these signals. We examine both clinical needs and biomedical signal processing approaches across a range of sensor types. Issues with recording and analysing the signals are discussed, together with their applicability to various clinical disorders. Both univariate and data fusion (exploiting the diverse characteristics of the primary recorded signals) approaches are discussed, together with a comparison of automated methods for analysing sleep.
EDTA: An Antimicrobial and Antibiofilm Agent for Use in Wound Care (2014)

Significance: Methods employed for preventing and eliminating biofilms are limited in their efficacy on mature biofilms. Despite this a number of antibiofilm formulations and technologies incorporating ethylenediaminetetraacetic acid (EDTA) have demonstrated efficacy on in vitro biofilms. The aim of this article is to critically review EDTA, in particular tetrasodium EDTA (tEDTA), as a potential antimicrobial and antibiofilm agent, in its own right, for use in skin and wound care. EDTA's synergism with other antimicrobials and surfactants will also be discussed. Recent Advances: The use of EDTA as a potentiating and sensitizing agent is not a new concept. However, currently the application of EDTA, specifically tEDTA as a stand-alone antimicrobial and antibiofilm agent, and its synergistic combination with other antimicrobials to make a “multi-pronged” approach to biofilm control is being explored. Critical Issues: As pathogenic biofilms in the wound increase infection risk, tEDTA could be considered as a potential “stand-alone” antimicrobial/antibiofilm agent or in combination with other antimicrobials, for use in both the prevention and treatment of biofilms found within abiotic (the wound dressing) and biotic (wound bed) environments. The ability of EDTA to chelate and potentiate the cell walls of bacteria and destabilize biofilms by sequestering calcium, magnesium, zinc, and iron makes it a suitable agent for use in the management of biofilms. Future Direction: tEDTA's excellent inherent antimicrobial and antibiofilm activity and proven synergistic and permeating ability results in a very beneficial agent, which could be used for the development of future antibiofilm technologies.
Molecular characterization of the acyl-coenzyme A:isopenicillin N acyltransferase gene (penDE) from Penicillium chrysogenum and Aspergillus nidulans and activity of recombinant enzyme in Escherichia coli (1990)

The final step in the biosynthesis of beta-lactam antibiotics in Penicillium chrysogenum and Aspergillus nidulans involves removal of the L-alpha-aminoadipyl side chain from isopenicillin N (IPN) and exchange with a nonpolar side chain. The enzyme catalyzing this reaction, acyl-coenzyme A:isopenicillin N acyltransferase (acyltransferase), was purified from P. chrysogenum and A. nidulans. Based on NH2-terminal amino acid sequence information, the acyltransferase gene (penDE) from P. chrysogenum and A. nidulans were cloned. In both organisms, penDE was located immediately downstream from the isopenicillin N synthetase gene (pcbC) and consisted of four exons encoding an enzyme of 357 amino acids (approximately 40 kilodaltons [kDa]). The DNA coding sequences showed approximately 73% identity, while the amino acid sequences were approximately 76% identical. Noncoding DNA regions (including the region between pcbC and penDE) were not conserved. Acyltransferase activity from Escherichia coli producing the 40-kDa protein accepted either 6-aminopenicillanic acid or IPN as the substrate and made a penicillinase-sensitive antibiotic in the presence of phenylacetyl coenzyme A. Therefore, a single gene is responsible for converting IPN to penicillin G. The active form of the enzyme may result from processing of the 40-kDa monomeric precursor to a heterodimer containing subunits of 11 and 29 kDa.
Symbolic layout compaction review (1988)

Symbolic layout and compaction is reaching a mature status. This is demonstrated, in part, by the recent or imminent introductions of a number of commercial symbolic layout and compaction systems. The two most frequently used symbolic layout compaction approaches, constraint graph compaction and virtual grid compaction, are reviewed in this paper. The current status of these two approaches is presented by looking at the results of the ICCD87 compaction benchmark session.
Utilization of Alternate Substrates by the First Three Modules of the Epothilone Synthetase Assembly Line (2002)

The epothilones, a family of macrolactone natural products produced by the myxobacterial species Sorangium cellulosum, are of current clinical interest as antitumor agents. Inspection of the structure of the epothilones suggests a hybrid polyketide/nonribosomal peptide biosynthetic origin, and the recent sequencing of the epothilone biosynthetic gene cluster has validated this proposal. Here we have examined unnatural substrates with the first two enzymes of the biosynthetic pathway, EpoA and EpoB, to investigate the enzymatic construction of alternate heterocyclic structures and the subsequent elongation of these products by the third enzyme of the pathway, EpoC. The epothilone biosynthetic machinery can utilize serine to install an oxazole in place of a thiazole in the epothilone structure and will tolerate functionalized donor groups from the EpoA-ACP domain to produce epothilone fragments modified at the C21 position. These studies with the early enzymes of the epothilone biosynthesis cluster suggest that combinatorial biosynthesis may be a viable means for producing a variety of epothilone analogues that incorporate diversity into the heterocycle starter unit.
Treg and CTLA-4: Two intertwining pathways to immune tolerance (2013)

Both the CTLA-4 pathway and regulatory T cells (Treg) are essential for the control of immune homeostasis. Their therapeutic relevance is highlighted by the increasing use of anti-CTLA-4 antibody in tumor therapy and the development of Treg cell transfer strategies for use in autoimmunity and transplantation settings. The CTLA-4 pathway first came to the attention of the immunological community in 1995 with the discovery that mice deficient in Ctla-4 suffered a fatal lymphoproliferative syndrome. Eight years later, mice lacking the critical Treg transcription factor Foxp3 were shown to exhibit a remarkably similar phenotype. Much of the debate since has centered on the question of whether Treg suppressive function requires CTLA-4. The finding that it does in some settings but not in others has provoked controversy and inevitable polarization of opinion. In this article, I suggest that CTLA-4 and Treg represent complementary and largely overlapping mechanisms of immune tolerance. I argue that Treg commonly use CTLA-4 to effect suppression, however CTLA-4 can also function in the non-Treg compartment while Treg can invoke CTLA-4-independent mechanisms of suppression. The notion that Foxp3 and CTLA-4 direct independent programs of immune regulation, which in practice overlap to a significant extent, will hopefully help move us towards a better appreciation of the underlying biology and therapeutic significance of these pathways.
An ankle-foot emulation system for the study of human walking biomechanics (2006)

Although below-knee prostheses have been commercially available for some time, today's devices are completely passive, and consequently, their mechanical properties remain fixed with walking speed and terrain. A lack of understanding of the ankle-foot biomechanics and the dynamic interaction between an amputee and a prosthesis is one of the main obstacles in the development of a biomimetic ankle-foot prosthesis. In this paper, we present a novel ankle-foot emulator system for the study of human walking biomechanics. The emulator system is comprised of a high performance, force-controllable, robotic ankle-foot worn by an amputee interfaced to a mobile computing unit secured around his waist. We show that the system is capable of mimicking normal ankle-foot walking behaviour. An initial pilot study supports the hypothesis that the emulator may provide a more natural gait than a conventional passive prosthesis
Hypoglycemic Effects of Propolis to the Streptozotocin Induced Diabetic Rats (2005)

To evaluate the hypoglycemic effect of propolis, streptozotocin (STZ) induced diabetic rats were divided into 4 groups such as, diabetic control group, low dose of propolis (0.1 ml) group, medium dose of propolis (0.3 ml) group and high dose of propolis (0.9 ml) group and feeded with propolis extracts for 30 days. After experiment, oral glucose tolerance test (Oral GTT) was carried, and 16 hours fasting blood sugar levels, body weights, blood lipid levels were measured. Finally, pancreatic histopathological study was performed. In conclusion, the propolis is effective to the treatment diabetes due to the reduction of the blood sugar level and the regeneration of the damaged -cells shown in streptozotocininduced diabetic rats.
Role of neurotrophin-trk interactions in oncology: the anti-tumor efficacy of potent and selective trk tyrosine kinase inhibitors in pre-clinical tumor models. (1999)

The increasing knowledge of the pathogenic mechanisms involved in cancer cell growth has enabled the implementation of mechanism based drug design approaches rather than the more conventional nonspecific approaches. Drugs that interfere with cellular signal transduction pathways are currently a major focus in development of newer therapeutic technologies in oncology. The therapeutic utility of potent and selective tyrosine kinase inhibitors in oncologic applications has become widely recognized for several years, however targeting neurotrophin receptors as a molecular target driven approach has only recently been realized. This review presents the hypothesis of the neurotrophin-trk receptors as a viable molecular target for medicinal chemical intervention in tumor biology, followed by an overview of the pre-clinical studies which culminated in the advancement of the first potent trk tyrosine kinase inhibitor CEP-2563 (KT-8391), and the orally active K-252a analog, CEP-701 (KT-5555) into clinical evaluation.
Synthesis and properties of N-(2,3,5-tri-O-acetyl-D-ribofuranosyl)maleimide (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and properties of N-(2,3,5-tri-O-acetyl-D-ribofuranosyl)maleimideArthur L. Schwartz and Leon M. LernerCite this: J. Org. Chem. 1975, 40, 1, 24–28Publication Date (Print):January 1, 1975Publication History Published online1 May 2002Published inissue 1 January 1975https://pubs.acs.org/doi/10.1021/jo00889a005https://doi.org/10.1021/jo00889a005research-articleACS PublicationsRequest reuse permissionsArticle Views248Altmetric-Citations7LEARN 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
Small-Molecule Antiviral β- d - N 4 -Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance (2019)

Coronaviruses (CoVs) have emerged from animal reservoirs to cause severe and lethal disease in humans, but there are currently no FDA-approved antivirals to treat the infections. One class of antiviral compounds, nucleoside analogues, mimics naturally occurring nucleosides to inhibit viral replication. While these compounds have been successful therapeutics for several viral infections, mutagenic nucleoside analogues, such as ribavirin and 5-fluorouracil, have been ineffective at inhibiting CoVs. This has been attributed to the proofreading activity of the viral 3'-5' exoribonuclease (ExoN). β-d-<i>N</i><sup>4</sup>-Hydroxycytidine (NHC) (EIDD-1931; Emory Institute for Drug Development) has recently been reported to inhibit multiple viruses. Here, we demonstrate that NHC inhibits both murine hepatitis virus (MHV) (50% effective concentration [EC<sub>50</sub>] = 0.17 μM) and Middle East respiratory syndrome CoV (MERS-CoV) (EC<sub>50</sub> = 0.56 μM) with minimal cytotoxicity. NHC inhibited MHV lacking ExoN proofreading activity similarly to wild-type (WT) MHV, suggesting an ability to evade or overcome ExoN activity. NHC inhibited MHV only when added early during infection, decreased viral specific infectivity, and increased the number and proportion of G:A and C:U transition mutations present after a single infection. Low-level NHC resistance was difficult to achieve and was associated with multiple transition mutations across the genome in both MHV and MERS-CoV. These results point to a virus-mutagenic mechanism of NHC inhibition in CoVs and indicate a high genetic barrier to NHC resistance. Together, the data support further development of NHC for treatment of CoVs and suggest a novel mechanism of NHC interaction with the CoV replication complex that may shed light on critical aspects of replication.<b>IMPORTANCE</b> The emergence of coronaviruses (CoVs) into human populations from animal reservoirs has demonstrated their epidemic capability, pandemic potential, and ability to cause severe disease. However, no antivirals have been approved to treat these infections. Here, we demonstrate the potent antiviral activity of a broad-spectrum ribonucleoside analogue, β-d-<i>N</i><sup>4</sup>-hydroxycytidine (NHC), against two divergent CoVs. Viral proofreading activity does not markedly impact sensitivity to NHC inhibition, suggesting a novel interaction between a nucleoside analogue inhibitor and the CoV replicase. Further, passage in the presence of NHC generates only low-level resistance, likely due to the accumulation of multiple potentially deleterious transition mutations. Together, these data support a mutagenic mechanism of inhibition by NHC and further support the development of NHC for treatment of CoV infections.
Animal models of migraine: looking at the component parts of a complex disorder (2006)

Animal models of human disease have been extremely helpful both in advancing the understanding of brain disorders and in developing new therapeutic approaches. Models for studying headache mechanisms, particularly those directed at migraine, have been developed and exploited efficiently in the last decade, leading to better understanding of the potential mechanisms of the disorder and of the action for antimigraine treatments. Model systems employed have focused on the pain-producing cranial structures, the large vessels and dura mater, in order to provide reproducible physiological measures that could be subject to pharmacological exploration. A wide range of methods using both in vivo and in vitro approaches are now employed; these range from manipulation of the mouse genome in order to produce animals with human disease-producing mutations, through sensitive immunohistochemical methods to vascular, neurovascular and electrophysiological studies. No one model system in experimental animals can explain all the features of migraine; however, the systems available have begun to offer ways to dissect migraine's component parts to allow a better understanding of the problem and the development of new treatment strategies.
Genome-wide loss of heterozygosity analysis from laser capture microdissected prostate cancer using single nucleotide polymorphic allele (SNP) arrays and a novel bioinformatics platform dChipSNP. (2003)

Oligonucleotide arrays that detect single nucleotide polymorphisms were used to generate genome-wide loss of heterozygosity (LOH) maps from laser capture microdissected paraffin-embedded samples using as little as 5 ng of DNA. The allele detection rate from such samples was comparable with that obtained with standard amounts of DNA prepared from frozen tissues. A novel informatics platform, dChipSNP, was used to automate the definition of statistically valid regions of LOH, assign LOH genotypes to prostate cancer samples, and organize by hierarchical clustering prostate cancers based on the pattern of LOH. This organizational strategy revealed apparently distinct genetic subsets of prostate cancer.
Selective delivery of an anticancer drug with aptamer-functionalized liposomes to breast cancer cells in vitro and in vivo (2013)

Selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. To address this need, DNA aptamers have attracted significant attention as possible targeting ligands. However, while their use in targeting cancer cells <i>in vitro</i> has been reported, their effectiveness has rarely been established <i>in vivo</i>. Here we report the development of a liposomal drug delivery system for targeted anticancer chemotherapy. Liposomes were prepared containing doxorubicin as a payload, and functionalized with AS1411, a DNA aptamer with strong binding affinity for nucleolin. AS1411 aptamer-functionalized liposomes increased cellular internalization and cytotoxicity to MCF-7 breast cancer cells as compared to non-targeting liposomes. Furthermore, targeted liposomal doxorubicin improved antitumor efficacy against xenograft MCF-7 breast tumors in athymic nude mice, attributable to their enhanced tumor tissue penetration. This study suggests that AS1411 aptamer-functionalized liposomes can recognize nucleolin overexpressed on MCF-7 cell surface, and therefore enable drug delivery with high specificity and selectivity.