gebhart/patrepeval huggingface dataset:
Engineered Escherichia coli Silver-Binding Periplasmic Protein That Promotes Silver Tolerance (2012)

Silver toxicity is a problem that microorganisms face in medical and environmental settings. Through exposure to silver compounds, some bacteria have adapted to growth in high concentrations of silver ions. Such adapted microbes may be dangerous as pathogens but, alternatively, could be potentially useful in nanomaterial-manufacturing applications. While naturally adapted isolates typically utilize efflux pumps to achieve metal resistance, we have engineered a silver-tolerant Escherichia coli strain by the use of a simple silver-binding peptide motif. A silver-binding peptide, AgBP2, was identified from a combinatorial display library and fused to the C terminus of the E. coli maltose-binding protein (MBP) to yield a silver-binding protein exhibiting nanomolar affinity for the metal. Growth experiments performed in the presence of silver nitrate showed that cells secreting MBP-AgBP2 into the periplasm exhibited silver tolerance in a batch culture, while those expressing a cytoplasmic version of the fusion protein or MBP alone did not. Transmission electron microscopy analysis of silver-tolerant cells revealed the presence of electron-dense silver nanoparticles. This is the first report of a specifically engineered metal-binding peptide exhibiting a strong in vivo phenotype, pointing toward a novel ability to manipulate bacterial interactions with heavy metals by the use of short and simple peptide motifs. Engineered metal-ion-tolerant microorganisms such as this E. coli strain could potentially be used in applications ranging from remediation to interrogation of biomolecule-metal interactions in vivo.
Safety and Efficacy of Bronchial Thermoplasty in Symptomatic, Severe Asthma (2007)

BT is associated with a short-term increase in asthma-related morbidity. However, there is preliminary evidence of long-lasting improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 00214539).
Synthesis of 6-[N-Alkyl-N-(4-hidroxybutyl)amino]pyrimidine Derivatives- Simplified Analogues of Acyclonucleosides (1994)

The synthesis of some 6-alkylaminopyrimidine derivatives bearing a 4- hydroxybutyl chain as sugar mimic is described. These new compounds can be regarded as simplified, ring-opened analogues of purine acyclonucleosides. © 1994, Taylor &amp; Francis Group, LLC. All rights reserved.
Interaction of ligands with the opiate receptors of brain membranes: Regulation by ions and nucleotides (1978)

This study shows that nucleotides, as well as ions, regulate the opiate receptors of brain. GMP-P(NH)P and Na + reduce the amount of steady-state specific [ 3 H]dihydromorphine binding and increase the rate of dissociation of the ligand from the opiate receptor. In contrast, Mn 2+ decreases the rate of ligand dissociation and antagonizes the ability of Na + to increase dissociation. The effects of GMP-P(NH)P on steady-state binding and dissociation are not reversed by washing. Only GTP, GDP, ITP, and IMP-P(NH)P, in addition to GMP-P(NH)P, increase the rate of dihydromorphine dissociation. The site of nucleotide action appears to have high affinity: &lt;1 μM GMP-P(NH)P produces half-maximal increases in ligand dissociation. GMP-P(NH)P- and Na + -directed increases in dissociation have also been found for the opiate agonists [ 3 H]etorphine, [ 3 H]Leu-enkephalin, and [ 3 H]Met-enkephalin and the opiate antagonist [ 3 H]naltrexone. Mn 2+ -directed decreases in dissociation have been found for the agonist [ 3 H]-etorphine and the antagonist [ 3 H]naltrexone. Although the plasma membrane receptors for a number of other neuro-transmitters and hormones are also regulated by guanine nucleotides, the opiate receptors appear unique because only they show nucleotide regulation of both agonist and antagonist binding.
Assessment of Chemical Coverage of Kinome Space and Its Implications for Kinase Drug Discovery (2008)

More than 500 compounds chosen to represent kinase inhibitor space have been screened against a panel of over 200 protein kinases. Significant results include the identification of hits against new kinases including PIM1 and MPSK1, and the expansion of the inhibition profiles of several literature compounds. A detailed analysis of the data through the use of affinity fingerprints has produced findings with implications for biological target selection, the choice of tool compounds for target validation, and lead discovery and optimization. In a detailed examination of the tyrosine kinases, interesting relationships have been found between targets and compounds. Taken together, these results show how broad cross-profiling can provide important insights to assist kinase drug discovery.
Reduction of paediatric in-patient cardiac arrest and death with a medical emergency team: preliminary results (2005)

Introduction of a medical emergency team service was coincident with a reduction of cardiac arrest and mortality and a slight increase in admissions to intensive care.
[(E)-1-[123I]Iodo-1-penten-5-yl]triphenylphosphonium iodide: convenient preparation of a potentially useful myocardial perfusion agent (1984)

A rapid iodination method has been developed for the synthesis of the new 123I-labeled phosphonium cation [(E)-1-iodo-1-penten-5-yl]triphenylphosphonium iodide by I+ treatment of the corresponding trans-vinylboronic acid. This new model myocardial perfusion agent is obtained after purification in 25-50% yield in less than 1 h. High myocardial uptake (5 min, 2.38% dose/g) with prolonged retention (3 h, 2.21% dose/g) was observed in rats. In addition, heart/blood ratios were high and continued to increase over a 1-day period (5 min, 17:1; 60 min, 23:1; 3 h, 27:1; 1 day, 158:1). In rats, the liver uptake was moderate (5 min, 1.40% dose/g; 60 min; 0.25% dose/g). Excellent myocardial images were obtained in a dog.
Saccharomyces cerevisiae Contains Two Functional Citrate Synthase Genes (1986)

The tricarboxylic acid cycle occurs within the mitochondria of the yeast Saccharomyces cerevisiae. A nuclear gene encoding the tricarboxylic acid cycle enzyme citrate synthase has previously been isolated (M. Suissa, K. Suda, and G. Schatz, EMBO J. 3:1773-1781, 1984) and is referred to here as CIT1. We report here the isolation, by an immunological method, of a second nuclear gene encoding citrate synthase (CIT2). Disruption of both genes in the yeast genome was necessary to produce classical citrate synthase-deficient phenotypes: glutamate auxotrophy and poor growth on rich medium containing lactate, a nonfermentable carbon source. Therefore, the citrate synthase produced from either gene was sufficient for these metabolic roles. Transcription of both genes was maximally repressed in medium containing both glucose and glutamate. However, transcription of CIT1 but not of CIT2 was derepressed in medium containing a nonfermentable carbon source. The significance of the presence of two genes encoding citrate synthase in S. cerevisiae is discussed.
Scale-Up of an Oil/Water Cream Containing 40% Diethylene Glycol Monoethy Ether (2000)

The purpose of this study was to scale up an oil/water (o/w) cream formulation containing 40% diethylene glycol monoethyl ether (DGME), developed via 300-g laboratory batches in a 2(5-2) fractional factorial design, to 7-kg batch sizes in a Brogli-10 homogenizer. The o/w cream was manufactured via a standard phase-inversion process in the Brogli-10 homogenizer. Partitioning studies of DGME were conducted in test tubes at ambient temperature and after 24 hr at 70 degrees C in a convection oven. Phase height was measured by vernier calipers. Microscopy studies of excipients with and without treatment with water or a DGME/water mixture were conducted with a Nikon microscope after equilibration at 35 degrees C for 24 hr. During creation of the 7-kg pilot-scale batches, congealed material was observed between the sweep agitation blade and the discharge port, where the Brogli-10 homogenizer is not temperature jacketed. Factors that increased the amount of congealed material were higher temperatures during primary emulsification and longer cooling times. Partitioning studies revealed that DGME resides in the aqueous external phase of this formulation. Microscopy studies revealed that DGME in the external phase of this cream has a profound impact on the solubility of certain solid, waxy excipients (e.g., cetyl alcohol and polyoxyethylene-2-stearyl ether) at 35 degrees C. From this study, it appears that DGME resides in the external phase of the o/w cream. During manufacturing, it is hypothesized that the presence of DGME in the external phase alters the solubility of certain solid, waxy excipients in the formula such that they no longer primarily reside in the internal oil phase. On cooling, these materials precipitate or congeal in the external phase. The fractional factorial experimental design at the 300-g laboratory scale did not predict the issues encountered during scale-up. Differences between laboratory scale and pilot plant scale that explain why this phenomenon was not seen during laboratory scale are differences in cooling times, nonjacketed or "cold spots" in the Brogli-10 homogenizer, and a low proportion of congealed material in relation to the total batch size (< 1.5%).
Study of the impact of the T877A mutation on ligand‐induced helix‐12 positioning of the androgen receptor resulted in design and synthesis of novel antiandrogens (2009)

Antiandrogen flutamide, an antagonist of the wild-type androgen receptor (AR), is used in the clinics for treating metastatic prostate cancer. However, the T877A mutated AR is paradoxically activated by hydroxyflutamide, an active form of flutamide. Despite of crystallographic studies, how the T877A mutation results in antagonist-agonist conversion of hydroxyflutamide remains a puzzle. Here, started from a structural model of the apo form of AR ligand-binding domain (AR-LBD), we have investigated the impact of the T877A mutation on ligand-induced helix-12 positioning by replica-exchange molecular dynamics (REMD) simulations with an unique protocol, which is capable of simulating the H12 dynamics and keeping the main body of AR-LBD unchanged. Specifically, (i) we have computationally demonstrated that on the binding of hydroxyflutamide, the apo form of H12 rearranges into the agonistic form in the T877A mutant, but into the antagonistic forms in the wild-type receptor, shedding light on hydroxyflutamide agonism/antagonism; (ii) By REMD simulations, we have predicted antiandrogen SC184 is a non-agonist of the T877A mutant. This was confirmed by luciferase assays; and (iii) on the basis of the binding modes of hydroxyflutamide and SC184 from the simulations, we designed a novel flutamide derivative called SC333, which was subsequently predicted to be a pure antagonist of the T877A mutant. We then synthesized and experimentally confirmed SC333 is a pan-antiandrogen effective against the wild-type and the T877A and W741C mutated ARs, showing low micromolar cytotoxicity in LNCaP cells. Importantly, we demonstrated that distribution of the H12 conformations from REMD simulations is correlated with ligand agonist/antagonist activity.
Linear and nonlinear filtering in mathematical finance: an overview (2009)

This paper presents a brief overview of Kalman filtering and its applications in mathematical finance. Results of recent empirical studies with market data are presented for stochastic volatility modelling and yield curve modelling. The paper also outlines rigorous as well as heuristic approaches to filtering of nonlinear time series.
Antifungal Activity Against Allergic Fungal Sinusitis Organisms (1996)

A review of more than 50 allergic fungal sinusitis (AFS) patients indicates that most patients experience postoperative recurrences once weaned from oral steroids, leaving a glaring need for improved treatment. Topical antifungal therapy has not been described for AFS, but it could potentially lower fungal antigen loads via postoperative irrigations. No information exists to direct the choice of antifungal agent. The purpose of this study was to identify the appropriate drug to use for postoperative irrigations in AFS patients. Twenty-two fungal cultures grown from 15 AFS patients were studied for in vitro susceptibility to five common antifungal drugs: ketoconazole, amphotericin B, itraconazole, nystatin, and fluconazole. Results demonstrated that ketoconazole and amphotericin B were the most effective. Clinical trials are indicated to evaluate the efficacy of these drugs as a supplement to current AFS treatment.
A simple animal model of hyperammonemia (1989)

Rats were fed a standard diet or the standard diet supplemented with ammonium acetate (20% w/w) for up to 100 days. The effect of the ingestion of the high-ammonium diet on some aspects of nitrogen metabolism in rats was studied. Ammonia levels in blood increased approximately 3-fold; in brain, liver and muscle the increases were 36, 34 and 50%, respectively. Urea levels in blood and urea excretion increased approximately 2-fold. There was no increase of carbamyl phosphate synthase. Liver glutamine synthase activity increased by 58% and glutamate dehydrogenase by 40%, whereas glutaminase was not affected. Glutamine content in brain was twice that of controls. This new animal model to study hyperammonemia offers several advantages over others: it is simpler, is bloodless, requires no animal manipulation and permits long-term studies.
Fidelity of end joining in mammalian episomes and the impact of Metnase on joint processing (2014)

Our careful re-examination of fidelity of NHEJ repair in mammalian cells carrying a 3' cohesive overhang at the ends revealed that the repair is efficient and highly accurate, and predominant over HRR. However, the background of the cells is important in establishing accuracy; with human cells perhaps surprisingly much more prone to generate deletions at the repaired junctions, if/when Metnase is abundantly expressed.
Emerging antibody products and Nicotiana manufacturing (2011)

Antibody based products are not widely available to address multiple global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. Nicotiana-based manufacturing of antibody products may now begin to address these challenges as a result of revolutionary advances in transient expression and altered glycosylation pathways. This review provides examples of emerging antibody-based products (mucosal and systemic) that could be competitive and commercially viable when the attributes of Nicotiana-based manufacturing (large scale, versatile, rapid, low cost) are utilized.
Patient-Specific Volume Conductor Modeling for Non-Invasive Imaging of Cardiac Electrophysiology (2008)

We propose a general workflow to numerically estimate the spread of electrical excitation in the patients' hearts. To this end, a semi-automatic segmentation pipeline for extracting the volume conductor model of structurally normal hearts is presented. The cardiac electrical source imaging technique aims to provide information about the spread of electrical excitation in order to assist the cardiologist in developing strategies for the treatment of cardiac arrhythmias. The volume conductor models of eight patients were extracted from cine-gated short-axis magnetic resonance imaging (MRI) data. The non-invasive estimation of electrical excitation was compared with the CARTO maps. The development of a volume conductor modeling pipeline for constructing a patient-specific volume conductor model in a fast and accurate way is one essential step to make the technique clinically applicable.
Cytokine regulation of C3 and C5 production by the human type II pneumocyte cell line, A549. (1990)

A growing body of literature suggests that a variety of cell products (e.g., cytokines, C components, etc.) likely play an important role during inflammation and host defense by locally regulating the diverse functions of recruited (i.e., immunologic cells) as well as tissue cells. Previously, a number of investigations have demonstrated the ability of immunologic cells to produce C components in vitro, and further studies have identified a variety of cytokines that can regulate C component production by these cells. Recently, we have demonstrated the ability of lung tissue cells, including epithelial cells and fibroblasts, to synthesize and secrete numerous C components and complement regulatory proteins in vitro. Additionally, we have demonstrated that C component production can be modulated by a variety of factors including endotoxin and serum. In our studies we investigated the effects of specific cytokines, i.e., IL and IFN, on the production of the third (C3) and fifth (C5) C components by the continuous cell line of human type II pneumocytes (A549). Specifically, using sensitive ELISA we demonstrated that A549 pneumocytes exposed to IL-1 alpha, IL-1 beta, or IL-2 induced a dose-dependent, more than twofold, increase in C3 production and a 50% decrease in C5 production when compared to control (untreated) A549 cells. Interestingly, IFN-alpha significantly decreased both C3 and C5 production, i.e., 38 and 71%, respectively, in a dose-dependent manner. IFN-gamma had no effect on C3 production, but significantly decreased C5 production by A549 pneumocytes by 84%. These data not only demonstrate that cytokines have the capability to modulate C3 and C5 production by human type II pneumocytes in vitro, but that C3 and C5 production by these cells can be regulated independently by different cytokines. In vivo, cytokine modulation of C component production by local tissue cells likely plays an important role in the regulation of inflammation and host defense within the lung.
Simultaneous training of negatively correlated neural networks in an ensemble (1999)

This paper presents a new cooperative ensemble learning system (CELS) for designing neural network ensembles. The idea behind CELS is to encourage different individual networks in an ensemble to learn different parts or aspects of a training data so that the ensemble can learn the whole training data better. In CELS, the individual networks are trained simultaneously rather than independently or sequentially. This provides an opportunity for the individual networks to interact with each other and to specialize. CELS can create negatively correlated neural networks using a correlation penalty term in the error function to encourage such specialization. This paper analyzes CELS in terms of bias-variance-covariance tradeoff. CELS has also been tested on the Mackey-Glass time series prediction problem and the Australian credit card assessment problem. The experimental results show that CELS can produce neural network ensembles with good generalization ability.
Surfuranes. X. Reagent for the facile cleavage of secondary amides (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurfuranes. X. Reagent for the facile cleavage of secondary amidesJ. A. Franz and J. C. MartinCite this: J. Am. Chem. Soc. 1973, 95, 6, 2017–2019Publication Date (Print):March 1, 1973Publication History Published online1 May 2002Published inissue 1 March 1973https://pubs.acs.org/doi/10.1021/ja00787a054https://doi.org/10.1021/ja00787a054research-articleACS PublicationsRequest reuse permissionsArticle Views299Altmetric-Citations21LEARN 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
Single-feed dual-frequency rectangular microstrip antenna (2002)

A novel design of a dual-frequency rectangular microstrip antenna with embedded spur lines and integrated reactive loading has been demonstrated. The present design uses a new resonant mode of TM/sub /spl beta/0/ (0</spl beta/<1) and the fundamental TM/sub 10/ mode for dual-frequency operation. The two operating frequencies have the same polarization planes and similar broadside-radiation characteristics with a tunable frequency range of about 1.1 to 1.6. The proposed dual-frequency antenna is suitable for applications in which a low frequency ratio of the two operating frequencies is required.
A Facile Synthesis of 1,2,3,4-Tetrahydroisoquinolines Through Cyclization ofO,N-Acetals (1987)

A mild and efficient method for the synthesis of 1,2,3, 4-tetrahydroisoquinolines by a modified Pictet-Spengler reaction involving Lewis acid-mediated cyclization of O,N-acetals is described.
Inflammatory and Neuroimmunomodulatory Changes in Acute Cerebral Ischemia (2009)

Neuronal death produced by cerebral ischemia activates innate immunity by Toll-like receptors and triggers inflammatory response. This response is necessary to remove cell debris and to start regenerative process. However, inflammatory response could exacerbate cerebral damage and it is involved in secondary brain damage. Therefore, organisms have developed different mechanisms to regulate inflammatory response. An accurate balance between inflammation and anti-inflammation is necessary to assure the removal of cell debris and to avoid secondary cell damage. New therapeutic targets could be designed to obtain a correct modulation of the immune system and to reduce cerebral brain damage after cerebral ischemia. In this paper, we review the function of the immune system in cerebral ischemia, particularly inflammation and immunomodulation.
The relationship between KRAS gene mutations and HLA class I antigen downregulation in the metastasis of non-small cell lung cancer (2013)

KRAS codon 12 mutations appear to be important in the downregulation of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS pathway might provide a new treatment target for NSCLC.
Transplantation hematopoiesis (2001)

Hematopoietic reconstitution after transplantation relies on a small number of hematopoietic stem cells that selectively migrate from the bloodstream to the hematopoietic microenvironment. In the first phase of engraftment, an extreme proliferative demand causes a limited stem cell fraction and its progeny to divide continuously, showing a significant telomere shortening. When all hematopoietic compartments are fully reconstituted, progenitor cell replication stabilizes and the stem cell pool reverts to a quiescent state. In transplant recipients, the hematopoietic microenvironment and stem cell reservoir remain defective for a prolonged period. However, in most patients donor-derived polyclonal hemopoiesis results, and the system is not exhausted but is capable of sustained normal counts and eventually overcomes stressed conditions.