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BackgroundNonsteroidal anti-inflammatory drugs are commonly used to treat postoperative and chronic pain. Animal studies suggest these drugs act in part by blocking...Full Text Available

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The main goal of local drug delivery is to increase the concentration of a specific therapeutic agent in a target tissue with minimal nontarget distribution. Compared to systemic therapy, local drug delivery provides a high level of therapeutic efficacy with minimal systemic effects. The current primary imaging modality for drug delivery has been x-ray angiography, but it has major limitations including anatomical ambiguity and inability to visualize the targeted tissues. Due to these inherent problems, MR guidance has been explored as an alternative imaging modality for guiding and monitoring of drug therapy. Recently, interventional MR (XMR) systems have been implemented that have both dual x-ray and MRI capabilities in a single suite and allow for real-time interventional procedures to ...

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To capitalize on the response of tumor cells to ionizing radiation, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced...Full Text Available

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Magnetic particles have become very promising materials for drug delivery. However, preparation of magnetite particles with high surface area, biocompatibility, strong magnetic response, and suitable particle size still remains a major challenge. In this report, magnetite nanocrystal clusters with high surface areas were fabricated through a solvothermal process by introducing ammonium acetate as a porogen and trisodium citrate as a surface modification agent. The porosity, which was controlled by the reactant concentration, has been investigated in detail. The surface area of the nanocrystal clusters was as high as 141?m(2) g(-1) . Ibuprofen, as a model drug, was entrapped into the magnetite carriers. The interfacial interaction between the carboxylic groups on the drug molecules and the carboxylate groups on the carriers enhanced the loading efficiency. Low cytotoxicity in MCF-7 cell and in vitro constant ...

UK PubMed Central (United Kingdom)

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants [such as peroxynitrite (OONO⁻)]...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available

UK PubMed Central (United Kingdom)

The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA...Full Text Available

UK PubMed Central (United Kingdom)

σ-Receptor (σR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of σR ligands in rats trained to self-administer...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Drug particle size distribution has a profound impact to the content uniformity in low-dose solid drug products. We derived theoretically the skewness of potency distribution as a function of particle size distribution and target dose. It was demonstrated that both skewness and coefficient of variation diverge simultaneously with inverse square root of the target dose. This scaling relation was observed in recent experiment and was verified by Monte Carlo (MC) simulation, which was employed for the first time to solve for the full potency distribution from a random retrieving model. When tested against the criteria from USP uniformity of dosage units, MC simulation showed a striking anisotropic distribution of the data. This suggests a full-scale consideration of the potency distribu...

British Library Electronic Table of Contents (United Kingdom)

PP2B is a Ca2+/calmodulin-dependent protein phosphatase that is ubiquitously expressed in mammals. Among other actions, it is an effector mechanism in NMDA-mediated glutamate neurotransmission as well as a regulator of GSK3? and MAPK signaling cascades. Because all of these mechanisms have demonstrable roles in the control of circadian rhythyms, we hypothesized that PP2B would be a key regulator of rhythm generation and entrainment, and that through inhibition of its phosphatase activity, the circadian system would be affected by immunosuppressant drug therapy. We report here that immunosuppressant drugs (cyclosporin A, FK506) (1) block the circadian responses to light that underlie photic entrainment; (2) produce circadian phase shifts with a characteristic nonphotic profile; and (3) disr...

Science.gov (United States)

Forty-one patients were treated with epidural neurolysis using 50 % ethyl alcohol 2 ml. Thirty eight patients were suffering from cancer pain and three patients were complaining of chronic benign pain. Alcohol block was repeated 2.3 times (mean) in the same patient. Thirty patients were followed after the treatment. Forty-seven percent of the patients reported 70 % or greater pain relief and 20 % of the patients reported about 50 % pain relief. Duration of pain relief was from 9 days to 203 days with a mean duration of 54 days. Adverse effects were reported 43 % of the patients. There is no miserable adverse effect. Adverse effect reported most was pain with epidural injection of drugs after the alcohol block had been performed. PMID:8544293

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Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...

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Isolation of functional and intact mitochondria from solid tissue is crucial for studies that focus on the elucidation of normal mitochondrial physiology and/or mitochondrial dysfunction in conditions such as aging, diabetes, and cancer. There is growing recognition of the importance of mitochondria both as targets for drug development and as off-target mediators of drug side effects. Unfortunately, mitochondrial isolation from tissue is generally carried out using homogenizer-based methods that require extensive operator experience to obtain reproducible high-quality preparations. These methods limit dissemination, impede scale-up, and contribute to difficulties in reproducing experimental results over time and across laboratories. Here we describe semiautomated methods to disrupt tissue ...

British Library Electronic Table of Contents (United Kingdom)

Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which ha...

British Library Electronic Table of Contents (United Kingdom)

A promising drug target currently under investigation to improve cognitive deficits in neuropsychiatric and neurological disorders is the neuronal nicotinic alpha7 acetylcholine receptor (a7nAChR). Improving cognitive impairments in diseases such as Alzheimer's (AD) and schizophrenia remains a large unmet medical need, and the a7nAChR has many properties that make it an attractive therapeutic target. The a7nAChR is a ligand gated ion channel that has particularly high permeability to Ca^2^+ and is expressed in key brain regions involved in cognitive processes (e.g., hippocampus). The a7nAChRs are localized both pre-synaptically, where they can regulate neurotransmitter release, and post-synaptically where they can activate intracellular signaling cascades and influence downstream processes...

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Designer natriuretic peptides (NPs) represent an active area of drug development. In canine and human studies, the designer natriuretic peptide CD-NP demonstrated more desirable therapeutic potential than recombinant B-type NP (BNP), which is known as nesiritide and is approved for treatment of acute decompensated heart failure. However, why CD-NP is more effective than BNP is not known. We previously reported that CD-NP is a poorer activator of human guanylyl cyclase-A (GC-A) and a better activator of human guanylyl cyclase-B than BNP. Here, guanylyl cyclase bioassays were used to compare the susceptibility of CD-NP verses ANP, BNP, CNP and DNP to inactivation by human kidney membranes. The half time (t(1/2)) for CD-NP inactivation was increased by factors of 13, 3 and 4 compared to ANP, BNP and CNP, respectively, when measured in the same assay. Surprisingly, DNP failed to undergo complete inactivation and was the most degradation resistant of the peptides ...

Scientific Electronic Library Online (English)

Abstract in english Previous studies have shown that women are more emotionally expressive than men. It is unclear, however, if women are also more susceptible to the emotional modulation of behavior imposed by an affective stimulus. To investigate this issue, we devised a task in which female subjects performed six sequential trials of visual target detection following the presentation of emotional (mutilation and erotic) or neutral pictures (domestic utensils and objects) and compared the (more) data obtained in the present study with those described in a previous study with male subjects. The experiment consisted of three blocks of 24 pictures and each block had an approximate duration of 4 min. Our sample consisted of 36 subjects (age range: 18 to 26 years) and each subject performed all blocks. Trials following the presentation of mutilation pictures (283 ms) had significantly slower reaction times ...

Science.gov (United States)

Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats were trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ...

British Library Electronic Table of Contents (United Kingdom)

Summary DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kin...

British Library Electronic Table of Contents (United Kingdom)

The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.

Energy Technology Data Exchange (ETDEWEB)

New technologies make multi-megajoule glass lasers economically feasible. Laser architectures using harmonic switchout, target plane holographic injection, phase conjugation, continuous apodization and higher amplifier efficiencies have been devised. A plan for a multi-megajoule laser which can be built for an acceptable cost relies on manufacturing economies of scale and the demonstration of the new technologies presented here. These include continuous pour glass production, rapid harmonic crystal growth, switching of large blocks of power using larger capcaitors packed more economically and by using large identical parts counts.

International Nuclear Information System (INIS)

The herbicide atrazine is a known immunotoxicant and an inhibitor of human natural killer (NK) cell lytic function. The precise changes in NK cell lytic function following atrazine exposure have not been fully elucidated. The current study identifies the point at which atrazine exerts its affect on the stepwise process of human NK cell-mediated lyses of the K562 target cell line. Using intracellular staining of human peripheral blood lymphocytes, it was determined that a 24-h in vitro exposure to atrazine did not decrease the level of NK cell lytic proteins granzyme A, granzyme B or perforin. Thus, it was hypothesized that atrazine exposure was inhibiting the ability of the NK cells to bind to the target cell and subsequently inhibit the release of lytic protein from the NK cell. To test this hypothesis, flow cytometry and fluorescent microscopy were employed to analyze NK cell-target cell co-cultures following atrazine ...

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Our inability to associate distant regulatory elements with the genes that they regulate has largely precluded their examination for sequence alterations contributing to human disease. One major obstacle is the large genomic space surrounding targeted genes in which such elements could potentially reside. In order to delineate gene regulatory boundaries we used whole-genome human-mouse-chicken (HMC) and human-mouse-frog (HMF) multiple alignments to compile conserved blocks of synteny (CBS), under the hypothesis that these blocks have been kept intact throughout evolution at least in part by the requirement of regulatory elements to stay linked to the genes that they regulate. A total of 2,116 and 1,942 CBS>200 kb were assembled for HMC and HMF respectively, encompassing 1.53 and 0.86 Gb of human sequence. To support the existence of complex long-range regulatory domains within these CBS we analyzed the prevalence and ...

Science.gov (United States)

Background: Determinants of warfarin use and anticoagulation levels in atrial fibrillation (AF) patients have not been clarified thoroughly. Methods and Results: A total of 6,324 patients with non-valvular AF and congestive heart failure, hypertension, age, diabetes, prior stroke (CHADS(2)) score ?1 were used to investigate determinants of warfarin use, and 6,932 patients with AF receiving warfarin were used to investigate determinants of international normalized ratio (INR) of prothrombin time. Target INR levels for non-valvular AF patients were 1.6-2.6 for patients aged ?70 years and 2-3 for patients aged transient ischemic attack (TIA), and had higher CHADS(2) scores than those not receiving warfarin. Determinants of warfarin use were age (?60 years), AF type (persistent and permanent), and comorbidities (congestive heart failure, diabetes mellitus, and prior stroke or TIA). Use of antiplatelet drugs was a negative determinant of warfarin ...

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PMID:20636852

UK PubMed Central (United Kingdom)

There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density...Full Text Available

International Nuclear Information System (INIS)

Effects of ethanol in vitro on membrane vesicles were evaluated by monitoring "3"6Cl"- influx. Different assay parameters were tested to determine increased or decreased action of ethanol on GABA-activated chloride channels. The ability of 30 mM ethanol to augment "3"6Cl"- flux was seen at 0 degree C, in the absence of GABA, and at 34 degree C in the presence of GABA, using two different assay procedures. Picrotoxin blocked the direct effects of ethanol suggesting GABA_a involvement. Endogenous GABA in the medium surrounding the microsacs was assayed at different temperatures both in the presence and absence of GABA and ethanol. The direct effect of ethanol did not appear to involve the action of endogenous GABA. In addition to temperature effects on the assay, time of membrane storage also influenced ethanol action. Microsacs stored on ice for 2 hours or more lost their ability to respond to ethanol but not to GABA, pentobarbital or flunitrazepam. When these ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...

British Library Electronic Table of Contents (United Kingdom)

The present study was carried out to exploit the feasibility of using polymeric nanosponges as an alternative carrier for targeting econazole nitrate (EN) to the skin through topical hydrogel formulation. Nanosponges prepared by emulsion solvent diffusion method were evaluated for various physicochemical parameters and in vitro drug release. The nanosponges of EN were discrete free flowing nanosized particles with perforated orange peel like morphology as visualized by SEM. The nanosponge formulated using PVA:EC (3:2) displayed highest in vitro release after 12 ?h in phosphate buffer (pH 6.8) that fitted matrix model. Selected nanosponge was formulated as Carbopol 934 NF hydrogel using varying concentrations of permeation enhancers propylene glycol and N-methyl-2-pyrrolidone. The EN nanosp...

British Library Electronic Table of Contents (United Kingdom)

Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...

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This task within the EU R and D for ITER was aimed at the development of basic manufacturing solutions for the high heat flux plasma facing components such as the divertor targets, the baffles and limiters. More than 50 representative small-scale mock-ups have been manufactured with beryllium, carbon and tungsten armour using various joining technologies. High heat flux testing of 20 of these mock-ups showed the carbon mono-blocks to be the most robust solution, surviving 2000 cycles at absorbed heat fluxes of up to 24 MW m{sup -2}. With flat armour tiles rapid joint failures occurred at 5-16 MW m{sup -2} depending on joining technology and armour material. These test results serve as a basis for the selection of manufacturing options and materials for the prototypes now being ordered. (orig.) 11 refs.

Science.gov (United States)

The widespread use of tobacco and alcohol among adolescents might be related to the ability of nicotine and ethanol to facilitate social interactions. To investigate the neurobehavioral mechanisms underlying the prosocial effects of nicotine and ethanol, we focused on social play behavior, the most characteristic social activity in adolescent rats. Social play behavior is rewarding, and it is modulated through opioid, cannabinoid and dopaminergic neurotransmission, which are also involved in the reinforcing properties of nicotine and ethanol. We found that nicotine and ethanol increased social play, without affecting locomotion or social exploration. Their effects depended on the level of social activity of the partner, and were comparable in familiar and unfamiliar environments. At doses that increased social play, nicotine and ethanol had no anxiolytic effects in the elevated plus-maze. By contrast, the prototypical anxiolytic drug diazepam reduced social play at ...

Science.gov (United States)

The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two ...

International Nuclear Information System (INIS)

The first essential before embarking on the radiation-hardening of electrical insulation - mostly magnet coils - in any beam line application is to obtain a reliable estimate of the dose to the components. These are examples ( switchyards at SLAC and LAMPF) where the degree of hardness specified was much higher than was required. Although experience shows that the cost premium for substantial radiation - hardening is of the order of 10%, it has also become clear that well - designed beam line have negligible losses: hardening is required only in the vicinity of targets, collimators or other beam - intercepting devices. Where the beam is deliberately scraped, local shielding will minimize the associated radiation in the surroundings. Electron machines have their own special problems due to synchrotron radiation, so certainly coils and other electrical equipment should be kept away from the beam bend - plane. Because proton beams interact with thick ...

UK PubMed Central (United Kingdom)

Nearly every drug may cause changes to ocular tissues through a variety of mechanisms. Medication overdoses, drug–drug interactions but also chronic administration of medications at...Full Text Available

UK PubMed Central (United Kingdom)

The sale of consumer products over the Internet has grown rapidly, including the sale of drugs. While the growth in online drug sales by reputable pharmacies is a trend that may provide benefits to...Full Text Available

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... derived and which describes fundamentally flux enhancement across an artificial membrane or skin: Keywords: Transdermal drug delivery system. ...

UK PubMed Central (United Kingdom)

AIMSTo evaluate the intraregional differences in drug prescribing to children and adolescents.METHODSPrescriptions reimbursed...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

The magnetic separation technology using sub-microsized ferromagnetic particle is indispensable in many areas of medical biosciences. For example, ferromagnetic particles (200-500 nm) are widely used for cell sorting in stem cell research with the use of cell surface-specific antigens. Nanosized ferromagnetic particles (10-20 nm) have been suggested as more suitable in drug delivery studies given their efficiency of tissue penetration, however, the magnetic separation method for them has not been established. One of the major reasons is that magnetic force acting on the object particles decreases drastically as a particle diameter becomes small. In this study, magnetic force acting on the targets was enhanced by the combination of superconducting magnet and the filter consisting of ferromagnetic particle. By doing so, we confirmed that Fe{sub 3}O{sub 4} of 20 nm in diameter was trapped in the magnetic filter under an external magnetic field of ...

Science.gov (United States)

Current antidotal regimens for organophosphorus compound (OP) poisoning consist of a combination of pretreatment with a spontaneously reactivating AChE inhibitor such as pyridostigmine bromide, and postexposure therapy with anticholinergic drugs such as atropine sulfate and oximes such as 2-PAM chloride (Gray, 1984). Although these antidotal regimens are effective in preventing lethality of animals from OP poisoning, they do not prevent postexposure incapacitation, convulsions, performance deficits, or, in many cases, permanent brain damage (Dunn and Sidell, 1989). These problems stimulated the development of enzyme bioscavengers as a pretreatment to sequester highly toxic OPs before they reach their physiological targets. Several studies over the last two decades have demonstrated that exogenously administered human serum butyrylcholinesterase (Hu BChE) can be used successfully as a safe, efficacious, and single prophylactic treatment to ...

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PMID:21704560

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Abstract Not Provided

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Dyslipidemia

KoreaScience (Korea)

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A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-(2,3-3H)aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and ...

Science.gov (United States)

The goal of the present work was to determine the impact of N3-methyladenine (3-mA), an important lesion generated by many environmental agents and anticancer drugs, on in vivo DNA replication and in vitro RNA transcription. Due to 3-mA chemical instability, the stable isostere 3-methyl-3-deazaadenine (3-m-c(3)A) was site specifically positioned into an oligodeoxynucleotide. The oligomer was, then incorporated into a vector system that is rapidly converted to ssDNA inside yeast cells and requires DNA replication opposite the lesion for plasmid clonal selection. For control purposes, an adenine or a stable apurinic/apyrimidinic (AP)-lesion was placed at the same site. The presence of each lesion in the oligonucleotide was confirmed by MALDI-TOF analysis. Plasmids were then transfected into yeast cells. While the AP-site dramatically reduced plasmid replication in all strains, the 3-m-c(3)A had a slight effect in the rad30 background which significantly increased ...

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Short communication. 3 refs.

Science.gov (United States)

PMID:15922238

British Library Electronic Table of Contents (United Kingdom)

Control of human filarial infections currently depends on chemotherapeutic strategies predominantly directed at microfilariae. Doxycycline therapy in an extended daily dose regimen sterilizes and kills adult stages, but the utility of this drug for routine field use remains an issue of concern. No macrofilaricidal drugs with efficacy after one or two doses are available for use, delaying the achievement of the elimination or eradication of onchocerciasis and lymphatic filariasis. Moxidectin, a macrocyclic lactone, is currently in clinical trials for onchocerciasis. A few other drugs that have already been approved for use in veterinary practice or in human medicine for other indications are available for investigation. Early drug discovery pipelines are poorly populated and the process of ...

DEFF Research Database (Denmark)

Udgivelsesdato: 2002-Mar

Science.gov (United States)

BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, ...

International Nuclear Information System (INIS)

As an engineered barrier system in the geological disposal of high-level waste, multibarrier system is considered. Multibarrier system consists of the vitrified waste, the overpack and the buffer. Bentonite is one of the potential material as the buffer because of its low water permeability, self-sealing properties, radionuclides adsorption and retardation properties, thermal conductivity, chemical buffering properties, overpack supporting properties, stress buffering properties, etc. As the construction technology of the buffer, the block installation method and in-situ compaction method, etc, are being investigated. The block installation method is to emplace the buffer blocks manufactured in advance at the ground facility, and construction processes of the block installation method at the underground will be simplified compared with the in-situ compaction method. However, the ...

Energy Technology Data Exchange (ETDEWEB)

Three blocks of non-welded tuff, one nominally one cubic foot (trial block) and the other two, nominally one cubic metre (1 m{sup 3}), were excavated from the Busted Butte Test Facility on the Nevada Test Site and transported to the Atomic Energy of Canada Limited Whiteshell Laboratories in Pinawa, Manitoba. The trial block and one of the 1-m{sup 3} blocks were used for unsaturated flow experiments. The remaining 1-m{sup 3} block is being used for saturated flow experiments and will be reported on separately. After a vertical flow of synthetic transport solution was set up under unsaturated conditions, a suite of conservative and chemically reactive radionuclide tracers was injected at volumetric flow rates of 20 mL/hr in the trial block, and 10 mL/hr in the 1-m{sup 3} block. The duration of the migration experiment in the trial ...

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A procedure for lowering an offshore rig support block into water, one with water displacement elements, including transfering a structure ready for installation from construction supports onto the grillage that has been set up on the slide, and then lowering the structure together with the grillage into the water. With the goal of dereasing the volume of hydrotechnical operations, the slides have been extended only to the waterline, and the water-displacing elements of the support block are mounted or the structure in a manner whereby the following conditions are fulfilled: Msigmaless than or equal toM /SUB wi/ sigma-W/Lless than or equal toq where Msigma, M /SUB w/ - are the mass moments of the support block and bouyancy forces correspond to the threshhold; sigma and W - the weight force and bouyancy; L - the support length of the block on the grillage; q - the allowable linear load for the support ...

Science.gov (United States)

... Accession Number : ADB119274. Title : Transdermal Drug Delivery System. Stage 1. Volume 1. Descriptive Note : Final rept. 15 Aug 85-14 Oct 87,. ...

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... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (115) Inhalants (12) K Ketamine (1) L LSD ( ...

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... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (112) Inhalants (12) K Ketamine (1) L LSD ( ...

UK PubMed Central (United Kingdom)

IntroductionResearch is an essential tool in facing the challenges of scaling up interventions and improving access to services. As in many other countries, the translation of research...Full Text Available

UK PubMed Central (United Kingdom)

A knowledge-based expert system has been developed to support human decision makers who assess drug products for inclusion in the Saskatchewan Formulary. Formulary inclusion and deletion decisions...Full Text Available

UK PubMed Central (United Kingdom)

The main aim of the present study was to evaluate potential of ternary complexation (comprising of drug, cyclodextrin and polymer) as an approach for taste masking. For this purpose famotidine with...Full Text Available

UK PubMed Central (United Kingdom)

Wild-type viruses from the ViroLogic phenotype-genotype database were evaluated to determine the upper confidence limit of the drug susceptibility distributions, or “biological cutoffs,”...Full Text Available

UK PubMed Central (United Kingdom)

Few data exist about the impact of computerized prescribing systems on outpatient medication errors (MEs) and adverse drug events (ADEs). We compared the rates of MEs and ADEs in handwritten sites versus...Full Text Available

UK PubMed Central (United Kingdom)

Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available

UK PubMed Central (United Kingdom)

SummaryEpigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available

UK PubMed Central (United Kingdom)

ObjectivesWe undertook a meta-analysis to assess outcomes for drug-eluting (DES) and bare metal stents (BMS) in percutaneous coronary intervention (PCI) for unprotected...Full Text Available

UK PubMed Central (United Kingdom)

Our understanding of the development of neurotransmitter systems in the central nervous system has increased greatly over the past three decades and it has become apparent that drug effects...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundParticulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the...Full Text Available

UK PubMed Central (United Kingdom)

The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the...Full Text Available

UK PubMed Central (United Kingdom)

Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission...Full Text Available

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... The pharmacologist/toxicologist and the statistician will jointly determine if a statistical review is needed and when the review should be done. ...

UK PubMed Central (United Kingdom)

The study of blocking factors requires in vitro assay of cell mediated immunity that parallels the in vivo response. By microcytotoxicity testing, progressor and immune peripheral blood lymphocytes...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

An improved lockout assembly for locking a circuit breaker in a selected off or on position is provided. The lockout assembly includes a lock block and a lock pin. The lock block has a hollow interior which fits over the free end of a switch handle of the circuit breaker. The lock block includes at least one hole that is placed in registration with a hole in the free end of the switch handle. A lock tab on the lock block serves to align and register the respective holes on the lock block and switch handle. A lock pin is inserted through the registered holes and serves to connect the lock block to the switch handle. Once the lock block and the switch handle are connected, the position of the switch handle is prevented from being changed by the lock tab bumping up against a stationary housing portion of the circuit breaker. When the lock pin ...

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pT181 is a naturally-occurring 4437 basepair (bp) plasmid isolated from Staphylococcus aureus which encodes inducible resistance to tetracycline (Tc). The DNA sequence data has identified three open reading frames (ORFs). The largest ORF B, has been found to be responsible for the Tc resistance phenotype of pT181. Since most Tc resistance systems appear to be regulated by an effector protein and a repressor protein, several Bal 31 deletion mutants of pT181 were constructed and analyzed in an effort to identify the elements involved in Tc resistance. Two transcomplementing groups of mutants were identified within the tet gene. The mechanism of Tc resistance was studied by assaying the accumulation of (7-/sup 3/H) Tc by Tc sensitive cells, and uninduced and induced pT181-containing cells. A sharp decrease in accumulation of the drug after an initial increase was observed in Tc induced pT181-containing cells. In vivo labeling of Bacillus subtilis minicells containing ...

Science.gov (United States)

... Blocks world, eight puzzle, eight queens, labeling line drawings (constraint satisfaction), magic squares, missionaries and cannibals, monkey and ...

Energy Technology Data Exchange (ETDEWEB)

This invention relates to an automatically-operating wedge block for maintaining intimate structural contact over wide temperature ranges, including cryogenic use. The wedging action depends on the relative thermal expansion of two materials having very different coefficients of thermal expansion. The wedge block expands in thickness when cooled to cryogenic temperatures and contracts in thickness when returned to room temperature.

International Nuclear Information System (INIS)

Homidium bromide and isometamidium chloride are used extensively in the treatment of bovine trypanosomiasis in Africa, but no specific and sensitive method to detect the drug in plasma has been published yet. Comparing the methods of other investigators it was found that they could not overcome the protein binding of these drugs which reduced the available and determined drug to 10% of the real concentrations. These techniques overcome the protein binding by enzyme digestion and an alteration of the pH before adding the sample directly on clean-up columns. Drug recover rates above 80% were obtained. For the detection, the HPLC was employed using a C18 reversed phase analytical column and UV detection, determining both drugs as intact molecules. (author).

British Library Electronic Table of Contents (United Kingdom)

The electroless nickel plating/poly(dl-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(dl-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder dif...

Science.gov (United States)

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared ...

Energy Technology Data Exchange (ETDEWEB)

This paper describes a newly developed software for manifold block design. Manifold block has become indispensable as an important component part to hydraulic systems since the 1970 {prime} s. However, its design is complicated and difficult. The reasons are firstly that hydraulic circuits have to be densely placed and secondary there is no means to correct a failure in the design or manufacture. Considering these points, the experiments of design engineers and the habitual design processes are analyzed, and a support system for manifold block design was developed by using a super-mini computer. With this system, the correctness of a design became to be proved. The software is easy to operate, and it can retrieve past design data, and it is extendible to the production line. 4 refs., 7 figs., 4 tabs.

Science.gov (United States)

Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the ...

International Nuclear Information System (INIS)

Ewing's sarcoma is a small round-cell tumor typically arising in the bones, rarely in soft tissues, of children and adolescents. Ewing's sarcoma has retained the most unfavorable prognosis of all primary musculoskeletal tumors. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. In addition, the preferred method of tumor resection has changed; limb salvage has nearly replaced amputation of the affected limb. Limb salvage procedures can be performed in place of amputation without compromising patient survival rates. Recent studies have revealed that the pathognomonic translocations involving the EWS gene on chromosome 22 and an ETS-type gene, which is most commonly the Fli1 gene on chromosome 11, are implicated in more than 95% of Ewing's sarcomas, ...

Energy Technology Data Exchange (ETDEWEB)

Concentrating solar power (CSP) technologies continue to mature and are being deployed worldwide. Power towers will likely play an essential role in the future development of CSP due to their potential to provide dispatchable solar electricity at a low cost. This Power Tower Technology Roadmap has been developed by the U.S. Department of Energy (DOE) to describe the current technology, the improvement opportunities that exist for the technology, and the specific activities needed to reach the DOE programmatic target of providing competitively-priced electricity in the intermediate and baseload power markets by 2020. As a first step in developing this roadmap, a Power Tower Roadmap Workshop that included the tower industry, national laboratories, and DOE was held in March 2010. A number of technology improvement opportunities (TIOs) were identified at this workshop and separated into four categories associated with power tower subsystems: solar collector field, ...

Energy Technology Data Exchange (ETDEWEB)

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and laser post-ionization secondary neutral mass spectrometry (laser-SNMS) have been used to image and quantify targeted compounds, intrinsic elements and molecules with subcellular resolution in single cells of both cell cultures and tissues. Special preparation procedures for analyzing cell cultures and tissue materials were developed. Cancer cells type MeWo, incubated with boronated compounds, were sandwiched between two substrates, cryofixed, freeze-fractured and freeze-dried. Also, after injection with boronated compounds, different types of mouse tissues were extracted, prepared on a special specimen carrier and plunged with high velocity into LN{sub 2}-cooled propane for cryofixation. After trimming, these tissue blocks were freeze-dried. The measurements of the K/Na ratio demonstrated that for both cell cultures and tissue materials the special preparation techniques used were ...

International Nuclear Information System (INIS)

Purpose: Previous data suggest that the PKC? catalytic V5 (PKC?-V5) heptapeptide (HEPT) (FEQFLDI) binds HSP27 and blocks HSP27-mediated radio- or chemoresistance. Here we investigated further the in vivo function of the PKC?-V5 HEPT. Methods and Materials: Labeling of HEPT with Cy5.5 or fluorescein isothiocyanate was performed to evaluate in vitro or in vivo distribution of HEPT. A clonogenic survival assay, flow cytometry, and Western blotting of cleaved caspase-3 were performed to determine in vitro sensitization effects of HEPT plus ionizing radiation (IR) versus IR alone or those of HEPT plus cisplatin(Cis) versus Cis alone. A nude mouse xenografting system was also applied to detect in vivo sensitizing effects of HEPT. Results: HEPT efficiently bound to HSP27 and showed sensitization after combined treatment with IR versus treatment with Cis alone in NCI-H1299 lung carcinoma cells, with higher HSP27 expression, which was similar to that of combined treatment ...

J-STORE (Japan)

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UK PubMed Central (United Kingdom)

All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available

International Nuclear Information System (INIS)

Three blocks of non-welded tuff, one nominally one cubic foot (trial block) in volume and the other two, nominally one cubic meter (1 m3) in volume, were excavated from the Busted Butte Test Facility on the Nevada Test Site in 1999 and transported to the Atomic Energy of Canada Limited Whiteshell Laboratories in Pinawa, Manitoba. The trial block and one of the 1-m3 blocks were used for radionuclide migration experiments under unsaturated conditions; the remaining 1-m3 block was used for similar migration experiments under saturated conditions. After a vertical flow of synthetic transport solution was set up under unsaturated conditions, a suite of conservative and chemically reactive radionuclide tracers was injected at volumetric flow rates of 20 mL/hr in the trial block, and 10 mL/hr in two locations on the upper surface of the 1-m3 block. ...

International Nuclear Information System (INIS)

Based on the instrumental wavelength dispersive X-ray fluorescence technique of analysis (W D-X R F), the inorganic elements in four samples of commercial medicines drugs were analyzed. The samples were used without any chemical separation of the elements or chemical pre-treatment. Eleven elements could be identified, namely Si, P, S, Cl, K, Ca, Ti, Mn, Fe, Cu and Zn. However, Si, Ti and Mn have not been mentioned in the printed instructions for the use of the medicines drugs by the producers. (author)

Science.gov (United States)

... drugs, foods, environmental conditions, and behavioral disorders (1,8,10,17,18,24,29). In addition, we designed a self-rated ...

UK PubMed Central (United Kingdom)

Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often...Full Text Available

UK PubMed Central (United Kingdom)

Standardization of herbal formulations is essential in order to assess the quality of drugs, based on the concentration of their active principles. This article reports on standardization of Ajmodadi...Full Text Available

Medline Plus

Enter Search terms A-Z Index Home Food Drugs Medical Devices Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Radiation-Emitting Products Tobacco ...

British Library Electronic Table of Contents (United Kingdom)

Background/Objectives: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. Methods: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. Results: While BNP values on admission were poorly informative, subsequent BNP measurements (11 +- 6 h after admission) were significantly increased in patients with CS comp...

Science.gov (United States)

uv irradiation (365 nm) of air-saturated methanol solutions of 20 drugs absorbing in the 300 to 400 nm region gave rise to oxygen uptake, as determined with a polarographic oxygen electrode. The drugs were tested for photosensitizing capability by either a Type I (free radical) or a Type II (single molecular oxygen) mechanism. This testing was done by the inclusion of either acrylamide or 2,5-dimethylfuran in the irradiated drug solution, with observation of the subsequent polymerization or oxidation, respectively. Phenothiazine and thiazide derivatives appear capable of photosensitization by both mechanisms; promethazine, trifluoperazine, and furosemide show relatively high reactivity. Diazepam (weak), hexachlorophene, aminacrine, pyrilamine, tetracycline, demeclocyline, quinine, and anthracene (strong) react only by a Type II mechanism, with a photosensitizing efficiency increasing in the order given. A correlation ...

UK PubMed Central (United Kingdom)

PurposeTo identify the extent of persistence (period of time of continuous therapy with the drug prescribed) of glaucoma patients treated with prostaglandins (latanoprost, bimatoprost,...Full Text Available

UK PubMed Central (United Kingdom)

Monitoring describes the prospective supervision, observation, and testing of an ongoing process. The result of monitoring provides reassurance that the goal has been or will be achieved, or suggests...Full Text Available

UK PubMed Central (United Kingdom)

Immunomodulatory drugs lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide to improve its potency and reduce its side effects. Lenalidomide...Full Text Available

UK PubMed Central (United Kingdom)

Purpose:This study investigated the penetration of lidocaine around and through a sutured incision following the application of iontophoretic and passive patches...Full Text Available

UK PubMed Central (United Kingdom)

Invasive fungal infections can be devastating, particularly in immunocompromised patients, and difficult to treat with systemic drugs. Furthermore, systemic administration of those medications...Full Text Available

UK PubMed Central (United Kingdom)

ObjectiveEpidemiological studies indicate that experimentation with addictive drugs and onset of addictive disorders is primarily concentrated in adolescence and...Full Text Available

Science.gov (United States)

... is reduced: 1) by lack of oxygen, 2) in hypercapnia associated with closed rooms or tents, 3) by use of sleeping drugs, antipyretics, insulin, and 4 ...

UK PubMed Central (United Kingdom)

RationaleProcedures for studying the effects of medications on satiation will assist the development of obesity medications.ObjectivesFull Text Available

Science.gov (United States)

... 36 7 Corrugated Steel Pipe Concept Layout--Elevation ..... 37 viii ... revetment. 3. Land Use ... Corner modules and capping blocks are available. ...

Science.gov (United States)

... Those functions are fundamental routines to build a power model for more complex circuits or functional blocks. ... 21 of 54 6. Memory Power Model ...

Science.gov (United States)

the Missionaries and Cannibals, Fool's Disk, the Blocks World. and the 8-Puzzle. Also ...... place the sets of missionaries and cannibals by ob- ...

Science.gov (United States)

9-foot 9-inch blocks of concrete with asphaltic-filled expansion joints. The concrete was placed on 4 to 6 inches of gravel or #4 stone. ...

Science.gov (United States)

... irispectors to operate or Soviet territory. They exr-essed this reluctarice ir interniat ionai law terms, claimirig that inspect ior act ivit ies ...

UK PubMed Central (United Kingdom)

More data about TACE and pTACE seem necessary to better define the global treatment strategy for HCC. Aim of our analysis was to evaluate the role of TACE, either with lipiodol (traditional) or drug-eluting...Full Text Available

UK PubMed Central (United Kingdom)

Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

The heterogeneous solid catalyst, mercaptopropylsilica (MPS), has been prepared by a modified procedure in water and its structure confirmed by solid state carbon-13 CP-MAS NMR spectrum. This catalyst has been efficiently utilized for the synthesis of a wide variety of tri-, tetrasubstituted imidazoles and their bis-analogues at room temperature. The protocol was further explored for the synthesis of the drug trifenagrel.

UK PubMed Central (United Kingdom)

BackgroundAs the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images...Full Text Available

International Nuclear Information System (INIS)

In this study the development of a methodology to detect illicit drugs and plastic explosives is described with the objective of being applied in the realm of public security. For this end, non-destructive assay with neutrons was used and the technique applied was the real time neutron radiography together with computerized tomography. The system is endowed with automatic responses based upon the application of an artificial intelligence technique. In previous tests using real samples, the system proved capable of identifying 97% of the inspected materials.

UK PubMed Central (United Kingdom)

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available

UK PubMed Central (United Kingdom)

The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown....Full Text Available

Science.gov (United States)

The synthesis and structures of acyclic and macrocyclic thio-, seleno- and telluro-ether complexes of the metallic and metalloid elements of Groups 13-16 reported since 2000 are described. The diverse structures range from discrete monomers through to infinite 1-, 2- or 3-D polymers. The coordination chemistry in this area is quite different to familiar d-block chemistry and the underlying factors are explored. PMID:21706103

Energy Technology Data Exchange (ETDEWEB)

The purpose of this invention is to assure operating reliability of a Mandrel head in tubes of various diameters. This goal is achieved in that it is equipped with movable expanding sectors, which are installed on a rigid conical plunger dye. It is also equipped with spring-loaded conical slides blocks which are installed on a shaft. The upper ends of the sectors of the sectorial head are attached by hinges to a rigid cone shaped plunger dye. The lower ends are installed with the possibility of interacting with the slide blocks.

Energy Technology Data Exchange (ETDEWEB)

A special purpose hardware machine, which simulates up to one half-million gates and 2m byte RAM ICS at a 5 millisecond clock speed is described. This is accomplished with a hardware logic (HAL) simulator. This performance is achieved with 32 distributed special parallel processors, which utilize block oriented simulation technique. The technique promises a good cost hardware logic simulator. 7 references.

International Nuclear Information System (INIS)

... reactions selenium 74 target selenium 77 target strontium 84 target strontium

UK PubMed Central (United Kingdom)

In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Experimental and computational investigations were performed in order to better understand the mechanical response of rigid targets with various geometries to the detonation of shallow buried explosives. The motion of the targets was measured by use of high-speed digital video photography. This work involved flat targets, targets that were downwardly convex, and targets that were downwardly concave with explosive charges located at various positions beneath the targets. It was observed that, in general, angled hulls - whether downwardly concave or convex - tended to reduce the amount of momentum imparted to the center of mass of the targets. Computations were performed by use of an arbitrary Langrangian-Eulerian treatment in a nonlinear finite element code. A model based on quasi-static te...

Science.gov (United States)

... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...

Science.gov (United States)

By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...

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British Library Electronic Table of Contents (United Kingdom)

The cephalosporin class antibacterial agent, cefazolin, was intercalated into layered double hydroxides (LDHs) in order to improve the drug efficiency as well as to achieve the controlled release property. Cefazolin molecules were incorporated into LDH through conventional ion exchange reaction. X-ray diffraction pattern analyses confirmed that cefazolin molecules were intercalated between the interlayer spaces of LDH. Fourier-transform infrared spectra and high performance liquid chromatographs clearly showed that the drug molecules were stabilized in LDH lattice through electrostatic interaction and released without any changes in their chemical integrity. Antibacterial activity of the cefazolin-LDH nanohybrid was also examined by an in vitro test, such as the minimal inhibitory concentr...

British Library Electronic Table of Contents (United Kingdom)

A qualitative method, involving supported liquid?liquid extraction (SLE) and ultra high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS?MS), was developed for the rapid tentative identification of various drugs of abuse in urine. In this study, 28 drugs and metabolites were covered by the screening procedure. Before analysis, urine samples were extracted by SLE and good extraction recoveries were obtained for most investigated compounds. The UHPLC strategy was then selected for the rapid separation of amphetamines, cocaine, opiates and related compounds in urine. Using columns packed with sub-2??m particles, analysis time was reduced down to 2?min, while maintaining acceptable performance. Finally, the detection was by tandem MS operating in the single reaction...

British Library Electronic Table of Contents (United Kingdom)

The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug (NSAID) plaster for knee osteoarthritis among Japanese patients. An open-labeled, randomized, controlled, multiclinic trial was performed involving outpatient clinic groups. Two comparative groups?plaster NSAIDs and oral NSAIDs?were randomly allocated. The drugs used were limited to the current top three in both groups in Japan. Treatments were assessed after four?weeks and compared with the baseline scores. Outcomes were evaluated by two psychometric measures: Japanese knee osteoarthritis measure, and pain with the visual analogue scale. The total number of patients included in the final evaluation was 165 (87 for the plaster group and 78 for the oral group). Between these two groups there were ...

British Library Electronic Table of Contents (United Kingdom)

The aim of this study is to evaluate the specificities of the irradiation of drugs in frozen aqueous solution. The structures of the degradation products were determined to gain insight into the radiolysis mechanisms occurring in frozen aqueous solutions. Metoclopramide hydrochloride and metoprolol tartrate were chosen as models. The frozen solutions were irradiated at dry ice temperature by high energy electrons at various doses. The drug purity (chemical potency) and the radiolysis products were quantified by HPLC-DAD. Characterization of the degradation products was performed by LC-APCI-MS-MS. The structures of the radiolysis products detected in irradiated frozen aqueous solutions were compared to those detected in solid-state and aqueous solutions (previous studies). For both metoclop...

KoreaScience (Korea)

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Energy Technology Data Exchange (ETDEWEB)

No abstract prepared.

Science.gov (United States)

Mineral deposition or alteration is commonly found at fracture-block interfaces is fissured, geothermal reservoirs. In response to pressure reduction in the fissures such mineralization, if less permeable than the matrix rock, will retard the flow of fluid from the blocks to the fissures and is termed fracture skin in this paper. The problem of fluid flow to a production well in a double-porosity reservoir with fracture skin was analyzed theoretically. One of the findings of the analysis was that fully transient block-to-fissure flow can be approximated by pseudo-steady state flow if fracture skin permeability is sufficiently low. Type curves generated by numerical inversion of Laplace transform solutions are used to cooroborate the results of a finite-difference model of steam transport to a well in a naturally fissured, geothermal reservoir with fracture skin.

Energy Technology Data Exchange (ETDEWEB)

A numerical investigation for forced convection in a constant-temperature parallel plate channel with porous cavity and block alternately emplaced on the bottom plate is presented in this work. The Brinkman-Forchheimer-extended Darcy model, which accounts for the effects of impermeable boundary and inertia, is used to characterize the flow field inside the porous region. Solutions of the coupled governing equations are carried out through the stream function-vorticity analysis. The characteristics of fluid flow and forced convection heat transfer have been obtained by the examinations of various governing parameters, such as the Reynolds number, Darcy number, inertial parameter, Prandtl number, and two geometric parameters. Several interesting phenomena such as the heat transfer augmentation in the channel were presented and discussed. The results of this investigation indicate that the size of recirculation caused by porous block will have a ...

Science.gov (United States)

We report on the formation of current blocking regions by O2 plasma treatment to reduce current crowding at the active region above the p-type electrodes of GaN-based vertical light emitting diodes (LEDs). The forward voltage and reverse current (at -5 V) of the plasma-treated LEDs slightly increase with increasing aging time. The output power (at 350 mA) of the plasma-treated LEDs is enhanced by 26% as compared to that of reference LEDs and is comparable to that of LEDs with SiO2 current blocking layers. It is shown that the output power (at 700 mA) of the plasma-treated LEDs is degraded by less than 2% of the initial value after 500 h.

Energy Technology Data Exchange (ETDEWEB)

The use of vacuum multifoil (VMF) container for thermal insulation in long-life thermal batteries was investigated in a proof-of-concept demonstration. An InvenTek-designed VMF container 4.9 inches in diameter by 10 inches long was used with an internally heated aluminum block, to simulate a thermal-battery stack. The block was heated to 525 C or 600 C and allowed to cool while monitoring the temperature of the block and the external case at three locations with time. The data indicate that it should be possible to build an equivalent-sized thermal battery that should last up to six hours, which would meet the requirements for a long-life sonobuoy application.

CERN Document Server

In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.

UK PubMed Central (United Kingdom)

Background:The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who...Full Text Available

UK PubMed Central (United Kingdom)

The study involved 110 randomly selected dairy farms located in the Ontario, Canada counties of Bruce, Grey, Huron, Oxford, Perth, Waterloo and Wellington. Herds were classified as "intensive" and "extensive"....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxicity and biological activity of dioxins and related chemicals. The...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

The present study discusses the contribution of the adoption of more rigorous and objective criteria to the selection and analysis of information sources, leading to more scientific rigour when registering phytotherapic drugs. To this end, it is herein proposed the adoption of a previously tested and acknowledged methodology, namely the Systematic Revision, as a standard for phytotherapic drug analyses. In order to show differences brought about by the Systematic Revision during the registration procedures of phytotherapic drugs, the case of the Maytenus ilicifolia (known popularly in Brazil as 'espinheira-santa') is presented. As it is well known, the use of ionizing radiation is expanding, especially in medicine and pharmacy. Therefore, gamma radiation was applied to the microbiological quality control of phytotherapic matrices. Results indicated a positive contribution of Systematic Revision to the ...

UK PubMed Central (United Kingdom)

Objective:This article examines relationships between reproductive onset and lifetime history of smoking, regular smoking, and nicotine dependence, and cannabis and other illicit...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundRifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month...Full Text Available

UK PubMed Central (United Kingdom)

The safety, pharmacokinetics, and distribution in tissue of an amphotericin B (AmB)-cholesteryl sulfate colloidal dispersion (ABCD) were compared with those of micellar amphotericin B-deoxycholate (m-AmB)....Full Text Available

UK PubMed Central (United Kingdom)

Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous...Full Text Available

UK PubMed Central (United Kingdom)

The juxtacapsular BNST (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of...Full Text Available

UK PubMed Central (United Kingdom)

Treatment of functional bowel disorders of irritable bowel-type (IBS) in children remains a difficult task because of a lack of drugs with low adverse event profile. We here report the results of a...Full Text Available

UK PubMed Central (United Kingdom)

Buccal bioadhesive films, releasing topical drugs in the oral cavity at a slow and predetermined rate, provide distinct advantages over traditional dosage forms. The aim of present study was to prepare...Full Text Available

UK PubMed Central (United Kingdom)

The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years)...Full Text Available

UK PubMed Central (United Kingdom)

Dimethyl sulfoxide (DMSO) is commonly used in biological studies to dissolve drugs and enzyme inhibitors with low solubility. While DMSO is generally thought of as being relatively inert, it...Full Text Available

UK PubMed Central (United Kingdom)

Opioids have been regarded for millennia as among the most effective drugs for the treatment of pain. Their use in the management of acute severe pain and chronic pain related to advanced medical...Full Text Available

UK PubMed Central (United Kingdom)

Telbivudine is a novel nucleoside drug recently approved for the treatment of patients with chronic hepatitis B. Its nonclinical safety was evaluated in a comprehensive program of studies, including...Full Text Available

UK PubMed Central (United Kingdom)

AimsThe efficacy of topical glucocorticosteroids in rhinitis and asthma is likely to depend on drug retention in the airway mucosa. With fluticasone propionate, retention may be...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying...Full Text Available

UK PubMed Central (United Kingdom)

Integration of solid-state biosensors and lipid bilayer membranes is important for membrane protein research and drug discovery. In these sensors, it is critical that the solid-state sensing...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundArtemisinin-based combination therapy, currently considered the therapy of choice for uncomplicated Plasmodium falciparum malaria in endemic countries,...Full Text Available

UK PubMed Central (United Kingdom)

Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug...Full Text Available

UK PubMed Central (United Kingdom)

Disruption of circadian rhythms may be involved in the pathophysiology of psychiatric disorders, including drug addiction. Recently, we detected the significant association between prokineticin 2 receptor...Full Text Available

UK PubMed Central (United Kingdom)

The development of azole resistance in Candida albicans is most problematic in patients with AIDS who receive long courses of drug for therapy or prevention of oral candidiasis. Recently,...Full Text Available

UK PubMed Central (United Kingdom)

The nicotinic acetylcholine receptor (AChR) controls signal transmission between cells in the nervous system. Abused drugs such as cocaine inhibit this receptor. Transient kinetic investigations indicate...Full Text Available

UK PubMed Central (United Kingdom)

African trypanosomes exert significant morbidity and mortality in man and livestock. Only a few drugs are available for the treatment of trypanosome infections and therefore, the development of new...Full Text Available

UK PubMed Central (United Kingdom)

ObjectiveTo evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in...Full Text Available

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Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed. (orig.)

British Library Electronic Table of Contents (United Kingdom)

Abstract Objective: This study aims to gain an overview of hot topics related to research focused on Chinese herbal drugs by authors inside China and outside of China in the past 10 years. Methods: PubMed/MEDLINE was utilized in order to investigate and select research that was published on ?Chinese herbal drugs?? from 1998 to 2007, by authors located both inside and outside of China (MeSH terms were downloaded and ranked). MeSH terms that frequently appeared were identified and co-word analysis was carried out for two groups: (1) authors located in China, and (2) authors based outside of China, respectively. The hot topics concerning research into Chinese herbal drugs were concluded after cluster analysis and related document analysis. Results: For authors in the China group versus those ...

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The D2 antidopaminergic drug Domperidone was evaluated singly and in combination with synthetic adrenocorticoid and an H2 antihistamine for its ability to reduce the acute emetic effects of /sup 60/Co whole-body radiation. Random-source adult male dogs were fasted 12 hours, fed a standard meal, injected 44 minutes later and irradiated 47 minutes after that. Four groups of dogs were radiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim+Thi), and dexamethasone + domperidone + cimetidine (Dex+Dom+Cim). Drug quantities for dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 ka, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset times, offset times, and number of episodes were recorded. The ED50 of Dex+Dom+Cim was higher than Con. Dom ...

UK PubMed Central (United Kingdom)

Dysregulation of glutamate neurotransmission may play a role in cognitive deficits in schizophrenia. Manipulation of glutamate signaling using drugs acting at metabotropic glutamate receptors...Full Text Available

UK PubMed Central (United Kingdom)

1 The influence of the nonsteroidal anti-inflammatory drug naproxen on glucose metabolism and on tolbutamide pharmacokinetics and pharmacodynamics has been studied in ten maturity-onset diabetics. 2...Full Text Available

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Antivenoms are the currently available agents for treatment of snake venom intoxication in humans. The development of therapeutic strategies employing more generally available drugs could improve treatment of invenomation by reducing hypersensitive reacti...

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The hypothesis that the antiarrhythmic drug amiodarone slows down the heart rate by its inhibitory action on the intracellular conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3) was investigated....Full Text Available

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The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs...Full Text Available

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Experiments were performed to investigate the involvement of the cell membrane in the excision DNA repair process in Escherichia coli. Two membrane-binding drugs, procaine and phenethyl alcohol (PEA), inhibited liquid-holding recovery (LBR) in u.v.-irradiated E. coli wild-type and recA strains. In uvrB and polA strains where, after u.v.-irradiation, LHR was absent the two drugs had no effect. Both drugs markedly reduced the removal of u.v.-induced thymine dimers in the DNA of wild-type cells (H/r30). Analysis by alkaline sucrose gradients revealed that PEA inhibited the incision step in excision repair. In contrast, procaine had no effect on incision but apparently inhibited the late steps in excision repair. PEA dissociated DNA from the cell membrane, whereas procaine did not. The results suggest that the two drugs PEA and procaine inhibit LHR and the excision repair process operating on u.v.-induced ...

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Acetaminophen (APAP), a widely used analgesic and antipyretic that is considered to be relatively safe at recommended doses, is the leading cause of drug-induced liver failure in the United States....Full Text Available

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Aims:To investigate the relationship between the duration of comatose state, severity of rhabdomyolysis and frequency of peripheral nerve injury (PNI) in patients following...Full Text Available

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Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several...Full Text Available

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We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs....Full Text Available

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The main objective of Phase I of this SBIR project was to demonstrate the feasibility for successful development of an antimicrobial wound dressing based on a hydrogel sustained release matrix. This goal has been achieved. In vitro studies of drug diffusi...

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Oligopeptidic drugs such as β-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model...Full Text Available

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Albumin is a multifunctional transport protein that binds a wide variety of endogenous substances and drugs. Insulins with affinity for albumin were engineered by acylation of the epsilon-amino group...Full Text Available

UK PubMed Central (United Kingdom)

Albendazole binds to parasite's tubulin inhibiting its glucose absorption. Its common adverse effects are nausea, vomiting, constipation, thirst, dizziness, headache, hair loss and pruritus. Although...Full Text Available

UK PubMed Central (United Kingdom)

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism; its activity is regulated by a plethora of physiological conditions, exercises and many anti-diabetic drugs. Recent...Full Text Available

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BackgroundA relevant problem in drug design is the comparison and recognition of protein binding sites. Binding sites recognition is generally based on geometry often combined with...Full Text Available

UK PubMed Central (United Kingdom)

This study examines the longitudinal relationship between personal and sexual partner incarceration and subsequent HIV risk behaviors among drug-involved men and their primary female sexual...Full Text Available

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...2010-04-01 false Sodium pentobarbital injection. 522.1704 Section...DRUGS § 522.1704 Sodium pentobarbital injection. (a)(1) Specifications. Sodium pentobarbital injection is sterile and...

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Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 g/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. Copyright Copyright 2009 John Wiley & Sons, Ltd.

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How does complex social behavior evolve? What are the developmental building blocks of division of labor and specialization, the hallmarks of insect societies? Studies have revealed the developmental...Full Text Available

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PURPOSEThe purpose of this study was to compare the linear sintering behavior of presintered zirconia blocks of various densities. The mechanical properties of the resulting sintered...Full Text Available

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BackgroundUnderstanding the interactions between ion channels and blockers remains an important goal that has implications for delineating the basic mechanisms of ion channel function...Full Text Available

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A series of studies conducted to identify the factors that block and unblock problem solving is described. Through the construction of an isomorph of the classic "water jar" problems developed by A. S. Luchins (1942) as a dynamic graphic micro-world, several factors involved in producing blocked states were identified. Subjects included 10 individuals and 10 pairs of subjects. By comparing the behavior of individuals tackling the "missionaries and cannibals" problem to that of pairs of subjects solving this problem, a study identified means by which problem solvers operating in a social context are able to overcome blocks that discourage individuals. These studies point to the importance of "reflection" (evaluation of problem-solving results) for flexible problem solving. This research suggests that teaching students to analyze what they have done will help them develop flexibility in using a new approach when ...

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Liquid pipeline codes generally stipulate placement of block valves along liquid transmission pipelines such as on each side of major river crossings where environmental hazards could cause or are foreseen to potentially cause serious consequences. Codes, however, do not stipulate any requirement for block valve spacing for low vapour pressure petroleum transportation, nor for remote pipeline valve operations to reduce spills. A review of pipeline codes for valve requirement and spill limitation in high consequence areas is thus presented along with a criteria for an acceptable spill volume that could be caused by pipeline leak/full rupture. A technique for deciding economically and technically effective pipeline block valve automation for remote operation to reduce oil spilled and control of hazards is also provided. In this review, industry practice is highlighted and application of the criteria for maximum permissible ...

UK PubMed Central (United Kingdom)

Neutral endopeptidase 24.11 (NEP, CD10) is a cell-surface enzyme expressed by prostatic epithelial cells that cleaves and inactivates neuropeptides implicated in the growth of androgen-independent prostate...Full Text Available

UK PubMed Central (United Kingdom)

Local anesthetics are able to induce pain relief by binding to the sodium channels of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Ropivacaine...Full Text Available

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Vegetable oils such as soybean oil will be converted to novel polymers using hydroformylation and other catalytic processes. These polymers can be used in the construction, automotive, packaging, and electronic sectors.

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Under a cooperative agreement, the Bureau of Mines, Magma Copper Co., and ASARCO, Inc., tested backfilled ground support systems at two elevations in Magma's San Manuel, AZ, mine. The tests were mainly for guidance in designing the loading crosscuts of th...

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A procedure has been developed for judging one-pile foundations for wind turbines. It appears that these foundations are good alternatives for block foundations. It is recommended to develop a program for testing one-pile foundations and to carry out a further research into their dynamic behavior.

UK PubMed Central (United Kingdom)

Several theories have proposed a functional role for synchronous neuronal firing in generating the neural code of a sensory perception. Synchronous neural activity develops during a critical...Full Text Available