SUMMARYDendritic cells (DCs) in mucosal surfaces are early targets for human immunodeficiency virus-1 (HIV-1). DCs mount rapid and robust immune responses upon pathogen encounter....Full Text Available
PurposeClinical trials have commenced to evaluate the feasibility of targeting malignant gliomas with genetically engineered cytolytic T-cells (CTLs) delivered directly...Full Text Available
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
The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with non-classical cellular targets. Unfortunately, target-based drug discovery against...Full Text Available
p53 plays a critical role in tumor suppression. As a transcription factor, in response to stress signals, p53 regulates its target genes and initiates stress responses, including cell cycle arrest,...Full Text Available
Cytokinins are distributed through the vascular system and trigger responses of targetcells via receptor-mediated signal transduction. Perception and transduction of the signal can occur at the plasma...Full Text Available
Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, targetcellresponses are determined...Full Text Available
Smooth muscle cell (SMC) proliferation and migration are key processes that occur in the pathogenesis of atherosclerosis and post-angioplasty restenosis. In the present study, we designed locked nucleic...Full Text Available
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain ...
Motivation: Automatic recognition of cell identities is critical for quantitative measurement, targeting and manipulation of cells of model animals at single-cell resolution. It has been...Full Text Available
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...
Background: The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. ?g particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion). Results: The In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular ...
Human antibodies targeting prostate cancer cell surface epitopes may be useful for imaging and therapy. The objective of this study was to evaluate the tumor targeting of an internalizing human...Full Text Available
S100A4, a member of the Ca(2+)-activated S100 protein family, regulates the motility and invasiveness of cancer cells. Moreover, high S100A4 expression levels correlate with poor patient survival in several cancers. Although biochemical, biophysical, and structural data indicate that S100A4 is a noncovalent dimer, it is unknown if two functional S100A4 monomers are required for the productive recognition of protein targets and the promotion of cell invasion. To address this question, we created covalently linked S100A4 dimers using a glycine rich flexible linker. The single-chain S100A4 (sc-S100A4) proteins exhibited wild-type affinities for calcium and nonmuscle myosin-IIA, retained the ability to regulate nonmuscle myosin-IIA assembly, and promoted tumor cell invasion when expressed in S100A4-deficient colon carcinoma cells. Mutation of the two calcium-binding EF-hands in one ...
... they assisted in the 2000 attack on the USS Cole? ... List the types of targets that ETA has attacked. ... was at least partially responsible for the attack. ...
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...
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
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 targetcell 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 targetcell and subsequently inhibit the release of lytic protein from the NK cell. ...
The role of intermediate products of dioxygen reduction in cytotoxic effects ascribed to oxygen molecules was studied in vivo using various yeast mutants with changed response to oxygen stress. It has been documented that superoxide radical exerts its deleterious effects on yeast cells directly and the role of other oxygen species derived from it is hardly detectable. Yeast Saccharomyces cerevisiae, however, cannot be considered as a typical eukaryotic organism due to its inability of synthesizing polyunsaturated fatty acids (pufa). These fatty acids are known as main target molecules during oxidative stress and their peroxidation leads to cytotoxic effects. As fatty acid content could be easily manipulated in yeast, this organism was used to evaluate the contribution of pufa peroxidation process to the cytotoxic effects of oxygen. Results obtained show, that yeast cells containing linolenic acid as the ...
Elevated nuclear factor kappa B (NF-@kB) activity and interleukin-6 (IL-6) secretion participates in the pathology of several age and inflammatory-related diseases, including age-related macular degeneration (AMD), in which retinal pigment epithelial cells are the key target. Recent findings reveal that heat shock protein 70 (Hsp70) may affect regulation of NF-@kB. In the current study, effects of Hsp70 expression on NF-@kB RelA/p65 activity were evaluated in human retinal pigment epithelial cells (ARPE-19) by using celastrol, a novel anti-inflammatory compound. Anti-inflammatory properties of celastrol were determined by measuring expression levels of IL-6 and endogenous NF-@kB levels during lipopolysaccharide (LPS) exposure by using enzyme-linked immunosorbent assays (ELISA). Cell viabil...
Many hormones elicit effects on targetcells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time ...
Endoreduplication represents a cell cycle variant during which multiple rounds of DNA replication occur without subsequent chromosome separation and cytokinesis, resulting into a cellular increase of the DNA content. Although the DNA ploidy level of cells is controlled by external stimuli such as light, currently limited knowledge is available on how environmental signals regulate the endoreduplication cycle at the molecular level. Previously, we have demonstrated that the conversion from the mitotic cell cycle into an endoreduplication cycle is mediated by the atypical E2F transcription factor DEL1 that operates as a repressor of endocycle onset. Here, we identified DEL1 as a transcriptional target of the classical E2Fb and E2Fc transcription factors that antagonistically control DEL1 transcript levels through competition for a single E2F cis-acting binding site. Correspondingly with the reported ...
Despite the fact that humans are exposed to multiple forms of mercury (elemental, inorganic, and organic), most research on mercury toxicity has focused on methylmercury (MeHg) and on neurotoxic outcomes and mechanisms. Recent work has indicated that the immunotoxic effects of mercury compounds may be significant contributors to human disease as well as mechanistically relevant to other target organ toxicities. In this study, we compared the effects of inorganic Hg (iHg) to organic Hg species (MeHg and ethylmercury, EtHg) in human peripheral blood mononuclear cells (PBMCs) in vitro at sub-cytotoxic concentrations, using methods developed to characterize response of human PBMCs to iHg in vitro. PBMCs were isolated from six volunteer blood donors (three males and three females) and cultured ...
SUMMARYThe cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on targetcells. Structural studies of...Full Text Available
Target of rapamycin (TOR) kinases control cell growth through two functionally distinct multiprotein complexes. TOR complex 1 (TORC1) controls temporal cell growth and is sensitive to rapamycin, whereas...Full Text Available
Certain allelochemicals of the marine dinoflagellate Alexandrium tamarense cause lysis of a broad spectrum of target protist cells but the lytic mechanism is poorly defined. We first hypothesized that membrane sterols serve as molecular targets of these lytic compounds, and that differences in sterol composition among donor and targetcells may cause insensitivity of Alexandrium and sensitivity of targets to lytic compounds. We investigated Ca^2^+ influx after application of lytic fractions to a model cell line PC12 derived from a pheochromocytoma of the rat adrenal medulla to establish how the lytic compounds affect ion flux associated with lysis of target membranes. The lytic compounds increased permeability of the cell membrane for Ca^2^+ ions even during blockade of Ca^2^+ channels wit...
In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative ...
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 drug release behavior combined with ...
The role of IGF-I in the negative regulation of GH expression and release is demonstrated by in vitro and in vivo models; however, the targets and mechanisms of IGF-I...Full Text Available
The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles...Full Text Available
Many genetic processes depend on proteins interacting with specific sequences on DNA. Despite the large excess of nonspecific DNA in the cell, proteins can locate their targets rapidly. After initial...Full Text Available
Cytokinesis in animal and fungal cells utilizes a contractile actomyosin ring (AMR). However, how myosin II is targeted to the division site and promotes AMR assembly, and how the AMR coordinates with...Full Text Available
Senescence is regarded as a physiological response of cells to stress, including telomere dysfunction, aberrant oncogenic activation, DNA damage, and oxidative stress. This stress response has an antagonistically...Full Text Available
We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
RNA interference (RNAi) is an effective tool for studying gene function in oocytes, but no studies have targeted somatic cells of primary cultured cumulus cell-oocyte complexes (COCs). This...Full Text Available
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 targetcell 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 targetcell and subsequently inhibit the release of lytic protein from the NK cell. ...
The feasibility of containing genetically engineered bacteria with enhanced dehalogenating properties for in situ bioremediation was investigated. (1) An agarose matrix microbead protocol and a detection system for contained microorganisms or DNA were developed. Multiplex Polymerase Chain Reaction (PCR) allowed tracking of a consortium of encapsulated organisms or several gene targets from a single species. Gene sequences encoding the enzymes responsible for initiating the biodegradation of toluene, octane, and 2,4-D were detected by multiplex PCR and nucleic acid probes from similar to 1-10 biodegradative cells/g soil. Improved DNA extraction methods resulted in PCR reactions detecting similar to 6 cells/g soil. (2) The pcpB gene (for the broad-spectrum detoxicant pentachlorophenol (PCP) hydroxylase) isolated from Flavobacterium sp. strain ATCC 39723 was used in attempts to develop an improved ...
BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available
Chaperones (stress proteins) are essential proteins to help the formation and maintenance of the proper conformation of other proteins and to promote cell survival after a large variety of environmental...Full Text Available
Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into targetcells to simulate ionic conductances and synaptic inputs. This method is based...Full Text Available
BackgroundAmino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved...Full Text Available
The dielectrophoretic (DEP) crossover method has been applied to the detection of cellresponses to toxicants. Time and dose responses of the human cultured leukemia (HL-60) line were measured...Full Text Available
Cytokines produced by Th2 cells are responsible for the pathogenesis of asthma. Th1-biased immune responses caused by attenuated salmonella have the potential to relieve asthmatic symptoms. We evaluated...Full Text Available
Effector proteins expressed in the esophageal gland cells of cyst nematodes are delivered into plant cells through a hollow, protrusible stylet. Although evidence indicates that effector proteins function...Full Text Available
We investigate a method for gene delivery to vascular smooth muscle cells using ultrasound triggered delivery of plasmid DNA from electrostatically coupled cationic microbubbles. Microbubbles...Full Text Available
Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis....Full Text Available
A goal of our research is to identify biochemical factors that underlie the susceptibility of bone marrow cell populations to benzene metabolites so as to develop a mechanistically based chemoprotective...Full Text Available
We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic ...
The gastrin releasing peptide (GRP) receptor is becoming an increasingly attractive target for development of new radiolabeled peptides with diagnostic and therapeutic potential. The attractiveness of the GRP receptor as a target is based upon the functional expression of GRP receptors in several tumors of neuroendocrine origin including prostate, breast, and small cell lung cancer. This concise review outlines some of the efforts currently underway to develop new GRP receptor specific radiopharmaceuticals by employing a variety of radiometal chelation systems.
We have investigated the properties of nerve cell precursors in hydra by analyzing the differentiation and proliferation capacity of interstitial cells in the peduncle of Hydra oligactis, which is a region of active nerve cell differentiation. Our results indicate that about 50% of the interstitial cells in the peduncle can grow rapidly and also give rise to nematocyte precursors when transplanted into a gastric environment. If these cells were committed nerve cell precursors, one would not expect them to differentiate into nematocytes nor to proliferate apparently without limit. Therefore we conclude that cycling interstitial cells in peduncles are not intermediates in the nerve cell differentiation pathway but are stem cells. The remaining interstitial cells in the peduncle are ...
The cell types involved in the cellular immune response were studied with the GVH in vitro as a test system. Comparison of the activities of cells of different lymphoid organs in the...Full Text Available
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 ...
The response of a real time neutron dosemeter using a thin LiF target sandwiched between tow parallel surface barrier semiconductor detectors is studied for different neutron distributions and different angles of incidence. Calculations of the response function defined for a simultaneous detection by the two detectors of the particles emitted when the reaction "6Li(n,t)#alpha# occurs in the target are fulfilled by geometrical considerations of the reaction kinematics and the differential cross section variations. Finally, the efficiency of the studied detection systems is analyzed for dosimetric uses. (author).
Atrazine is one of the most commonly used herbicides in the United States. While effective on target plants, it has been associated with harmful health effects in non-target organisms such as fish, amphibians and mammals. In this study, growth effects on human liver cells were determined after exposure to increasing concentrations of this herbicide. Growth of immortalized human hepatoma HepG2 cells was inhibited by atrazine concentrations of 625 ppb after 72 h exposure and flow cytometry analysis demonstrated HepG2 cells exposed to 100 ppb atrazine accumulated in S phase after 48 h compared to untreated cells. Expression of cell cycle specific cyclin proteins was altered after atrazine exposure with cyclin E levels significantly decreased after a 24 h exposure and cyclin B levels decreased...
Humoral immune response to human epidermal growth factor receptor 2 (HER-2/neu or ErbB-2) has been detected in sera of breast cancer patients and shown to be an appropriate prognostic marker (Taylor et al., 2007). However, since Trastuzumab (Herceptin) is a widely used monoclonal antibody as cancer therapy agent for tumors over-expressing HER-2, there is a need for an efficient way to detect host-generated antibodies against HER-2 without the confounding effect of Herceptin. Here we describe a screening method developed to decipher between host antibodies against HER-2 and that of Herceptin. By producing a series of truncation mutants within the epitope of Herceptin, we were able to inhibit this binding. We demonstrated also that by a three amino acid substitution (PPF?SSS) we were able to abrogate Herceptin binding while generating a highly conserved HER-2 extracellular domain (ECD). By producing a stable cell line that expresses this mutated ...
Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from...Full Text Available
Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single-cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory-evoked responses were layer- and cell-type-specific but always
Nicotine is the main psychoactive ingredient in tobacco and its rewarding effects are considered primarily responsible for persistent tobacco smoking and relapse. Although dopamine has been extensively...Full Text Available
BackgroundAntigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy...Full Text Available
Calcium-activated chloride channels (CaCCs) are widely expressed in mammalian tissues, including intestinal epithelia, where they facilitate fluid secretion. Potent, selective CaCC inhibitors have not been available. We established a high-throughput screen for identification of inhibitors of a human intestinal CaCC based on inhibition of ATP/carbachol-stimulated iodide influx in HT-29 cells after lentiviral infection with the yellow fluorescent halide-sensing protein YFP-H148Q/I152L. Screening of 50,000 diverse, drug-like compounds yielded six classes of putative CaCC inhibitors, two of which, 3-acyl-2-aminothiophenes and 5-aryl-2-aminothiazoles, inhibited by >95% iodide influx in HT-29 cells in response to multiple calcium-elevating agonists, including thapsigargin, without inhibition of calcium elevation, calcium-calmodulin kinase II activation, or cystic fibrosis transmembrane conductance regulator chloride channels. ...
Antibodies directed against markers on cancer cells are gaining in importance for the purpose of targeting diagnostic and therapeutic agents. In the past, this approach has had very limited success principally because the classical methods for producing antibodies from blood serum of animals immunized with cancer cells or extracts were unsatisfactory. The situation has changed dramatically since 1975 following the design of procedures for 'immortalizing' antibody-producing cells (lymphocytes) by fusing them with cultured myeloma cells to form hybridomas which continuously secrete antibodies. Since these hybridomas produce antibodies coded for by a single antibody-producing cell, the antibodies are called monoclonal. Building on these advances in biomedical research, it is now possible to reproducibly manufacture monoclonal antibodies on a scale suitable for use ...
LEW anti-DA kidney and DA anti-LEW kidney sera were assayed using an indirect 125I anti-immunoglobulin-binding assay with kidney homogenate as target. This allowed the full spectrum of antibodies to...Full Text Available
The present work summarizes efforts on the simulation of natural convection cooling within the IFMIF target and test cell. The simulations have been performed with the STAR-CD code using the k-#omega# high-Reynolds number turbulence model. A dedicated thermohydraulic model has been devised including Lithium loop components. Nuclear heat production has been calculated by the Monte-Carlo code McDeLicious for different parts of the target and test cell walls and was used as input for the STAR-CD simulations. Helium atmospheres at several pressures from 0.1 to 10"-"5 MPa have been investigated. In order to limit the maximum temperature of the concrete walls to 80 deg. C it was necessary to add thermal insulation layers to the hot Lithium loop surfaces and a conceptual system of two cooling layers in different depths of the concrete walls.
A highly purified preparation of double-stranded RNA, obtained from virus-like particles in Penicillium cultures, was found to affert humoral immune responses in mice differentially depending on its...Full Text Available
The response of the dissimilatory metal-reducing bacterium Shewanella alga BrY to carbon and nitrogen starvation was examined. Starvation resulted in a gradual decrease in the mean cell volume from...Full Text Available
Osteoblasts are the primary cellsresponsible for bone formation. They also support osteoclast formation from bone marrow precursors in response to osteotropic factors by inducing receptor activator...Full Text Available
BackgroundCells dynamically adapt their gene expression patterns in response to various stimuli. This response is orchestrated into a number of gene expression modules consisting...Full Text Available
In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing...Full Text Available
The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available
Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...
In response to stress, cells start transcriptional and transcription-independent programs that can lead to adaptation or death. Here, we show that multiple inducers of autophagy, including nutrient...Full Text Available
Age-related alterations in the cellular composition of the B lineage are a major cause of the poor antibody response to vaccination and to infectious agents among the elderly population. The mechanisms...Full Text Available
Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering...Full Text Available
Several scientists have proposed that DNA repair deficiencies and the induction of a mutator phenotype are responsible for the generation of multiple mutagenic alterations in cancer cells. I propose...Full Text Available
BackgroundThe dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following...Full Text Available
Taste cells use multiple signaling mechanisms to generate appropriate cellular responses to discrete taste stimuli. Some taste stimuli activate G protein coupled receptors (GPCRs) that cause calcium...Full Text Available
MicroRNAs (miRs) can regulate many cellular functions, but their roles in regulating responses of vascular endothelial cells (ECs) to mechanical stimuli remain unexplored. We hypothesize that the physiological...Full Text Available
Cell suspension cultures of tomato, Lycopersicon esculentum Mill. cv VFNT-Cherry, produce phytochelatins (poly[γ-glutamylcysteinyl]glycines) when exposed to cadmium. The synthesis...Full Text Available
Acute inflammation is important for tissue repair; however, chronic inflammation contributes to neurodegeneration in Alzheimer’s disease (AD) and occurs when glial cells undergo prolonged...Full Text Available
The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in patients with impaired CD4+ T cell function, particularly those with AIDS. To identify...Full Text Available
In whole-cell recording, the conductance of the plasma membrane of protoplasts isolated from mesophyll cells of leaves of oat (Avena sativa) was greater for inward than outward current....Full Text Available
BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available
Rodent models have been extensively utilized to identify putative human immunotoxicants; however, even when immunotoxicity is established, uncertainty remains whether the effects are predictive of human...Full Text Available
Mechanical forces can regulate various functions in living cells. The cytoskeleton is a crucial element for the transduction of forces in cell-internal signals and subsequent biological responses. Accordingly,...Full Text Available
The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells...Full Text Available
In this paper, model analysis into the time-dependent transmembrane potential at the outer cell membrane is presented, for applied high-intensity electric pulses having durations in the nanosecond range or smaller. It is argued that the frequency-dependent dielectric response of cell membranes could be used to advantage for stronger bioeffects by employing shorter pulses. Our model calculations predict faster transmembrane voltages and larger electroporation densities for a given external energy with pulse durations in the subnanosecond regime. This temporal regime would be used, for example, in the electrotherapy of mixed cell ensembles having different dielectric response properties. PMID:21937300
Regulatory T (T reg) cells exert powerful down-modulatory effects on immune responses, but it is not known how they act in vivo. Using intravital two-photon laser scanning microscopy we determined that,...Full Text Available
The state of chromatin during the cell cycle was examined using synchronized cultures of CHO hamster cells. Results support Mazia's dynamic chromosome cycle model and indicate that DNA-interactive chemotherapeutic agents elicit different types of kinetic responses in treated cells, suggesting a degree of specificity of interaction between various alkylating and intercalating agents and the genome. Effects of sarkosyl crystals, heparin, and chemotherapeutic agents, neocarzinostatin and adriamycin, on chromation are discussed. (HLW)
Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization....Full Text Available
The target of rapamycin (TOR) pathway regulates cell growth and aging in various organisms. In Saccharomyces cerevisiae, silent information regulator 2 (Sir2) modulates cellular senescence. Moreover,...Full Text Available
Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary...Full Text Available
PrefaceCardiovascular effects of epoxyeicosatrienoic acids (EETs) include vasodilation, vascular smooth muscle cell anti-migratory actions, and anti-inflammatory actions. These...Full Text Available
Epidermal growth factor receptor (EGFR) related therapies – mainly tyrosine kinase inhibitors (TKIs) such as erlotinib and gefitinib, but also monoclonal antibodies targeting EGFR, for example,...Full Text Available
Rapamycin inhibits the mTOR (target of rapamycin) pathway and extends lifespan in multiple species. The tuberous sclerosis complex (TSC) protein is a negative regulator of mTOR. In humans, loss of the...Full Text Available
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
BackgroundCD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers....Full Text Available
As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc...Full Text Available
The cancer preventive action of (−)-epigallocatechin gallate (EGCG), found in green tea, is strongly supported by epidemiology and laboratory research data. However, the mechanism by...Full Text Available
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available
SUMMARYATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as...Full Text Available
Autophagic adapters including p62/SQSTM1 recognize polyubiquitinated autophagic targets such as toxic protein aggregates. Recently reporting in Molecular Cell, Filimonenko et al. provide evidence...Full Text Available
The NREL Sensitized Solar Cell (SSC) Core Program supports the Solar America Initiative by: (1) targeting new devices and processes for commercialization by 2015 that are less expensive, more efficient, highly reliable, and environmentally benign; (2) collaborating with DOE OS/BES to conduct basic research targeting breakthroughs in key areas, such as ultra-high efficiency and/or ultra-low cost materials and devices.
A technique for delivering genes carried by recombinant retroviruses into specific cell types could have numerous applications in oncology, developmental biology, and gene therapy. As a first step toward this remote goal the authors designed a procedure allowing in vitro celltargeting by retroviruses. Biotinylated antibodies against the viral envelope protein on one side, and against specific cell membrane markers on the other side, were bridged by streptavidin and used to link the virus to the host. The method was successfully used to infect human cells with ecotropic murine retroviruses by means of major histocompatibility complex class I and class II antigens and appears easily adaptable to other cell, membrane markers. Moreover, the sequential protocol they design, although allowing infection of human cells, requires less stringent ...
The infection of cultured human cells with baboon endogenous virus (BEV) frequently leads to an association of viral DNA with a specific genetic locus (termed BEVI, for baboon endogenous virus infection) on chromosome 6. Restriction endonuclease digestion of DNA from BEV-infected human cells and their derived somatic cell clones frequently revealed a common cellular DNA sequence in the proximity of one of the junctions between cellular DNA and the integrated virus. We propose that a short cellular DNA sequence, repeated on chromosome 6 and separated by unique DNA sequences, presents a high-affinity target for the integration of BEV in human cells. PMID:6401843
Immune function is critical in health and disease. The control and regulation of immune reactions is an area of intense investigation that has important implications for allogeneic hematopoietic cell transplantation. Immune reactions are regulated in a number of important ways. Compartmentalization of immune responses and the production of both pro-inflammatory and anti-inflammatory cytokines play a major role. More recently several populations of T cells that regulate immune responses termed regulatory T cells have been identified. This manuscript will focus on CD4^+CD25^+FoxP3^+ natural regulatory T cells (T"r"e"g) and @a@bTCR^+CD4^+NK1.1^+ natural killer T (NK-T) cells which both suppress graft vs host disease but appear to function by distinct mechanisms.
Dynamic deformation and recovery responses of red blood cells (RBCs) to a cyclically reversing shear flow generated in a 30-μm clearance, with the peak shear stress of 53, 108,...Full Text Available
Methods for improving the sensitivity of scintillation cells for radon concentration measurements were studied with emphasis on improving light collection efficiency. This allows the length and hence the volume of the cell to be increased. Variables studied were choice of scintillator material, its method of application and thickness, length of cell, cell material, type and configuration of reflectors, choice of photomultipliers, and factors affecting background. Response from various areas of the cell surface was studied with an alpha source and with radon filling. Coating the window with phosphor was found to be counter-productive. The optimum results obtained were with the inside of the cell (other than the window) covered with a thick layer of ZnS(Ag), or with a thick layer of reflective material coated with a thin layer of phosphor. ...
Methods for improving the sensitivity of scintillation cells for radon concentration measurements were studied with emphasis on improving light collection efficiency. This allows the length and hence the volume of the cell to be increased. Variables studied were choice of scintillator material, its method of application and thickness, length of cell, cell material, type and configuration of reflectors, choice of photomultipliers, and factors affecting background. Response from various areas of the cell surface was studied with an alphy source and with radon filling. Coating the window with phosphor was found to be counter-productive. The optimum results obtained were with the inside of the cell (other than the window) covered with a thick layer of ZnS(Ag), or with a thick layer of reflective material coated with a thin layer of phosphor. ...
The findings reported in this study highlight several important features of the development of hematopoietic stem cells after transplantation into irradiated recipients. First, they demonstrate the existence of a class of primitive multipotential stem cells that can function for a significant portion of the lifetime of a mouse (15 mo). In addition, they clearly show that these primitive stem cells can be infected with recombinant retroviruses and thus would be appropriate targets for gene therapy in somatic tissues. Second, our data indicate that the progeny of some, but not all, of the primitive stem cells have fully expanded into the various hematopoietic lineages by 2 mo after reconstitution. Finally, our analysis of the secondary recipients provides strong evidence suggesting that the primitive stem cell population can actually clonally expand. Our current ...
According to its relation to the dielectric response, the potential structure of CsH{sub 2}PO{sub 4} can successfully be modelled either as a three-well or as a single-well potential. The deviation from the Curie-Weiss law of the dielectric response has an intimate relationship to the low central potential in the unit cells, while ordering P atoms are assumed to drive its ferroelectric phase transition. (author)
The marine environment is becoming increasingly contaminated by environmental pollutants with the potential to damage DNA, with marine sediments acting as a sink for many of these contaminants. Understanding genotoxic responses in sediment-dwelling marine organisms, such as polychaetes, is therefore of increasing importance. This study is an exploration of species-specific and cell-specific differences in cell sensitivities to DNA-damaging agents in polychaete worms, aimed at increasing fundamental knowledge of their responses to genotoxic damage. The sensitivities of coelomocytes from three polychaetes species of high ecological relevance, i.e. the lugworm Arenicola marina, the harbour ragworm Nereis diversicolor and the king ragworm Nereis virens to genotoxic damage are compared, and dif...
A semiquantitative assay was developed and used to measure the effects of immune responses against 16 independent non-H-2 antigenic loci on erythropoietic stem cells. The assay compares repopulation in genetically anemic WBB6F1-W/Wv recipients that have normal immune responses, and in lethally irradiated WBB6F1 +/+ mice whose immune responses are suppressed by the irradiation. The differences in repopulating ability between these two types of recipients measure how immune responses affect erythropoietic stem cells. Stem cell repopulating abilities for the cells with antigens specified by the Thy-1, H-1, H-24, Ly-1, H-37, and H-17 loci were affected slightly, if at all. Repopulating abilities were moderately reduced by responses against antigens specified by H-15, 16, Ea-2, and Ly-2, 3 loci, and ...
The photocytotoxic effect of hypericin (Hyp) targeted by two different delivery techniques, namely, liposomes and anti-hepatocyte specific antigen (anti-HSA) was investigated. Optical absorption and steady-state fluorescence were used to analyze the conjugation of Hyp with anti-HSA model and to evaluate the encapsulation capacity and drug release in a liposome model. Particle size and thermal analysis of the prepared liposomes were performed using laser-light scattering and differential scanning calorimetry (DSC), respectively. Viability study of HepG2 cells exposed to Hyp in the two delivery systems, in the dark and following visible light irradiation, was performed in comparison to free Hyp. The intracellular uptake and localization of Hyp in HepG2 cells were analyzed by means of spectro...
In several vertebrate classes, the M?ller glia are capable of de-differentiating, proliferating, and acquiring a progenitor-like state in response to acute retinal injury or in response to exogenous growth factors. Our previous study has shown that M?ller cells can be activated and de-differentiated into retinal progenitors during Royal College of Surgeons (RCS) rats' degeneration, although the limited proliferation cannot maintain retinal function. We now report that rat retinal stem cells (rSCs) transplanted into RCS rats slowed the progression of retinal morphological degeneration and prevented the functional disruption. Further, we found that retinal progenitor cells labeled with Chx10 were increased significantly after rSCs transplantation, and most of them are mainly from activated M...
This study evaluates the frequency and functions of immunocompetent T cells at the clonal level in solid human lung tissue versus peripheral blood. Enzymatic digestion of slices of histologically normal...Full Text Available
Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic...Full Text Available
Abstract MicroRNAs (miRNAs) play important roles in global gene regulation. Researchers in recombinant protein production have proposed miRNAs as biomarkers and cell engineering targets. However, miRNA expression remains understudied in Chinese Hamster Ovary cells, one of the most commonly used host cell systems for therapeutic protein production. To profile highly conserved miRNA expression, we used the miRCURY- miRNA array for screening miRNAs in CHO cells. The selection criteria for further miRNA profiling included positive hybridization signals and experimentally validated predicted regulatory targets. On the basis of screening, we selected 16 miRNAs for quantitative RT-PCR profiling. We profiled miR expression in parental CHO DG44 and CHO K1 cell lines as well as four recombinant DG44...
The zinc-air battery/fuel cell is an old technology invented one hundred years ago. However, there is renewed interest in this technology in response to the growing need for clean energy technology. The zinc-air battery/fuel cell is more attractive than similar technologies because its characteristics include high power density, safe operation and storage, and low cost. Zinc-air battery/fuel cells can be made in milliwatts to mega watts to accommodate different applications. The zinc-air battery/fuel cell has four major designs, namely primary, mechanically rechargeable, continuous feed and electrically rechargeable zinc-air battery/fuel cells. Among the different designs, the most common is the air cathode. There are 3 generations of catalysts used in the air cathodes. This paper discussed the different designs of the zinc-air battery/fuel ...
We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)
Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 x 10^3/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/@mL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/@mL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreas...
Data are presented to support the hypothesis that the initial step in the morphologic transformation of irradiated rodent (BALB/3T3) cells is a frequent cellular event involving a large fraction of the irradiated population. This process appears to involve DNA damage, but not to represent a targeted mutation in specific structural gene(s). Morphologic transformation and immortalization appear to be distinct steps in the overall process of transformation. In contradistinction to rodent cells, immortalization is a very rare event in human diploid cells which is induced at extremely low frequencies. The hypothesis is presented that immortality develops among clones of cells bearing stable chromosomal rearrangements which emerge during the proliferation of a population of radiation damaged cells.
With an ageing population the demand for cheap, efficient implants is ever increasing. Laser surface treatment offers a unique means of varying biomimetic properties to determine generic parameters to predict cellresponses. This paper details how a KrF excimer laser can be employed for both laser-induced patterning and whole area irradiative processing to modulate the wettability characteristics and osteoblast cellresponse following 24h and 4 day incubation. Through white light interferometry (WLI) it was found that the surface roughness had considerably increased by up to 1.5mm for the laser-induced patterned samples and remained somewhat constant at around 0.1mm for the whole area irradiative processed samples. A sessile drop device determined that the wettability characteristics diffe...
We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092
Transforming growth factor beta (TGF-@b) has a crucial role in the differentiation of ectodermal cells to neural or epidermal precursors. TGF-@b and bone morphogenetic protein molecules (BMPs) are involved in many developmental processes, including cell proliferation and differentiation, apoptosis, mitotic arrest and intercellular interactions during morphogenesis. Additionally, the failure of central thymic tolerance mechanisms, leading to T cells with a skewed autoreactive response, is being described as a contributor in inflammatory processes in autoimmune diseases such as multiple sclerosis. Since TGF-@b and BMP proteins are crucial for the development of the neural system and the thymus, as well as for the differentiation of T cells, it is essential to further investigate their role i...
Daylight responsive dimming systems have been used in few buildings to date because they require improvements to improve reliability. The key underlying factor contributing to poor performance is the variability of the ratio of the photosensor signal to daylight workplane illuminance in accordance with sun position, sky condition, and fenestration condition. Therefore, this paper describes the integrated systems between automated roller shade systems and daylight responsive dimming systems with an improved closed-loop proportional control algorithm, and the relative performance of the integrated systems and single systems. The concept of the improved closed-loop proportional control algorithm for the integrated systems is to predict the varying correlation of photosensor signal to daylight workplane illuminance according to roller shade height and sky conditions for improvement of the system accuracy. In this study, the performance of the ...
Herpes simplex virus type-1 (HSV-1) entry into targetcell is initiated by the ionic interactions between positively charged viral envelop glycoproteins and a negatively charged cell surface heparan sulfate (HS). This first step involves the induction of HS-rich filopodia-like structures on the cell surface that facilitate viral transport during cell entry. Targeting this initial first step in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell induced filopodia. These MNSs were predicted to target the virus to compete for its binding to cellular HS through their partially negatively charged oxygen vacancies on their nanoscopic spikes, to affect viral entry and subsequent spread. Our results demonstrate that the partially ...
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies ...
Formaldehyde, a well-identified indoor pollutant, was recently classified as carcinogenic. New regulations for the air quality are expected and therefore there is a need for low-cost sensors, sensitive and selective with a fast response time for the detection of formaldehyde at ppb level. In the present work, we had developed a chemical sensor based on nano-porous matrices doped with Fluoral-P and optical methods of detection. The nano-porous matrices, elaborated via the Sol-Gel process, display nano-pores whose cavity is tailored for the trapping of the targeted pollutant. They provide a first selectivity with the discrimination of the pollutants by their size. A second selectivity is obtained with a molecular probe, Fluoral-P, which reacts specifically with formaldehyde leading to the 3,5- di-acetyl-1,4-dihydro-lutidine (DDL). The kinetics of formation of DDL was studied as function of many parameters such as the concentration of Fluoral-P in ...
Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the peptide or amino acid substitution of ...
Human embryonic stem (ES) cells can undergo spontaneously differentiation in standard culture conditions, demonstrating that the undifferentiated state is relatively unstable. The heterogeneous expression of SSEA3 observed within human ES colonies, provides a means to examine undifferentiated stem cell substates. Through functional testing of single cells we have shown that undifferentiated ES cells can be segregated into functionally discrete subpopulations on the basis of SSEA3 expression: SSEA3(High), SSEA(Low) and SSEA3(Negative). Human ES subpopulations were found to be interconvertible, but they possess distinct properties when challenged to differentiate along the neural lineage. These data suggest that ES cells with pluripotent/self-renewal capacities can exhibit different responses to induction of differentiation. PMID:21763622
A series of cyclic voltammetry, chronoamperometry and electrochemical impedance experiments have been carried out in order to investigate the effect of cathode composition and porosity on the electrochemical characteristics of strontium-doped lanthanum, praseodymium and gadolinium cobaltite cathodes. The impedance responses at different electrode potentials of the half cell and symmetric single cell setups are compared and analyzed by the equivalent circuit modeling method. The deconvolution of impedance spectra for single cell cathode and anode reactions contributions based on the results of simultaneous analysis of half cells and symmetric single cells has been made by differential impedance real part vs. ac frequency plot analysis method. Noticeable influence of cathode chemical composition, meso-porosity and macro-porosity on the electrochemical activity of ...
Reference is made to Cheng and Leblond (Amer. J. Anat.; 141:537 (1974)) who used tritiated thymidine to kill cells synthesising DNA in the crypts of the small intestine. Amongst their findings was that very low doses caused measurable cell killing and that the killing was not random throughout the crypt but occurred selectively at the crypt base where stem cells are presumably located. It is here reported that the presence of hypersensitive cells at the base of the crypts can be demonstrated after whole-body X- or gamma-irradiation, and the time sequence for the production and loss of the killed cells is described together with their dose-response relationship. The studies were conducted on mice. The data were expressed as surviving rather than killed cells, and it was established that the crypt are amongst the most sensitive of mammalian ...
The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is ...
Dose-response studies of the radiosensitivity of spermatogonial stem cells in various epithelial stages after irradiation with graded doses of fission neutrons of 1 MeV mean energy were carried out in the Cpb-N mouse. These studies on the stem cell population in stages IX-XI yielded simple exponential lines characterized by an average D0 value of 0.76 +/- 0.02 Gy. In the subsequent epithelial stages XII-III, a significantly lower D0 value of 0.55 +/- 0.02 Gy was found. In contrast to the curves obtained for stem cells in stages IX-III, the curves obtained in stages IV-VIII indicated the presence of a mixture of radioresistant and radiosensitive stem cells. In stage VII, almost no radioresistant stem cells appeared to be present and a D0 value for the radiosensitive stem cells of 0.22 +/- 0.01 Gy was derived. Previously, data were obtained on ...
The phosphatidylinositol pathway is implicated in the regulation of numerous cellular functions and responses to extracellular signals. An important branching point in the pathway is the phosphorylation...Full Text Available
The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer...Full Text Available
Interkingdom signaling is established in the gastrointestinal tract in that human hormones trigger responses in bacteria; here, we show that the corollary is true, that a specific bacterial signal,...Full Text Available
BackgroundSensitization to house dust mite allergens is strongly correlated with asthma. Der p 7 elicits strong IgE antibody and T-cellresponses in mite allergic...Full Text Available
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
BackgroundThe expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations...Full Text Available
Experience with visual objects leads to later improvements in identification speed and accuracy (“repetition priming”), but generally leads to reductions in neural activity in single-cell...Full Text Available
The CNS can exhibit features of inflammation in response to injury, infection or disease, whereby resident cells generate inflammatory mediators, including cytokines, prostaglandins, free radicals and...Full Text Available
BackgroundThe binding of peptide fragments of antigens to class II MHC is a crucial step in initiating a helper T cell immune response. The identification of such peptide epitopes...Full Text Available
Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It...Full Text Available
Unless relaxation of the stringent response is achieved, all nongrowing bacteria rapidly develop resistance to autolysis induced by a variety of agents, including all classes of cell wall synthesis...Full Text Available
BackgroundHIV-1 reverse transcriptase (RT) is a heterodimer composed of p66 and p51 subunits and is responsible for reverse transcription of the viral RNA genome into DNA. RT can...Full Text Available
Incubation of resting cells of Sphingobium indicum B90A, Sphingobium japonicum UT26, and Sphingobium francense Sp+ showed that they were able...Full Text Available
The sensations of sound and motion generated by the inner ear are controlled by the brain through extensive centripetal innervation originating within the brain stem. In the semicircular canals, brain...Full Text Available
B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated...Full Text Available
ET-743 (trabectedin; Yondelis) is approved in Europe for the treatment of soft tissue sarcomas. Emerging phase 1 and 2 clinical data have shown high response rates in myxoid liposarcoma in part owing...Full Text Available
A cell-free system which catalyzes the biosynthesis of terpene hydrocarbons when supplemented with mevalonate, Mn2+, and ATP was prepared from the scutellum-embryonic axis region of maize...Full Text Available
Retinoic acid inducible gene I (RIG-I) is a pattern recognition receptor (PRR) responsible for detection of nucleic acids from pathogens in the cytoplasm of infected cells and induction of type I interferon...Full Text Available
Cyclophilins (Cyps), the intracellular receptors for Cyclosporine A (CsA), are responsible for peptidyl-prolyl cis-trans isomerisation and for chaperoning several membrane proteins. Those functions...Full Text Available
We study the integration of multisensory and central input at the level of an identified fly motoneuron, the ventral cervical nerve motoneuron (VCNM) cell, which controls head movements of the animal....Full Text Available
In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard,...Full Text Available
Advanced Glycated End Products (AGEs) are formed by non-enzymatic protein glycation and are implicated in several physiological aspects including cell aging and diseases. Recent data indicate that bacteria...Full Text Available
The aim of this study was to survey the expression of an embryonic cytokine gene, MK, in the normal organs and neoplastic tissues of adults. Northern analysis showed that MK mRNA was exclusively expressed...Full Text Available
Murine cytomegalovirus (MCMV) is an important animal model of human cytomegalovirus (HCMV), a β-Herpesvirus that infects the majority of the world's population and causes disease in neonates...Full Text Available
Pregnant rats in 11d and 16d of their pregnancy were given one-off whole body exposure by "1"3"7Cs #gamma# rays to 0.2, 0.4, 0.9 and 2.0 Gy, respectively. Changes were observed in conditioned drinking response and cerebrum hippocampi cone cell number of the baby rats exposed to the #gamma# rays in different periods of their embryo development. As a result, that pregnant rats exposed to "1"3"7Cs #gamma# rays in different pregnant periods may induce significant decrease in cerebrum hippocampi cone cell number and achieving rate of conditioned drinking response of the babies. The dose-response relationship can be described by Y=a-b log_1_0D. The achieving rate of conditioned drinking response were significantly correlated to cerebrum hippocampi cone cell number in the babies, and the achieving rate of conditioned drinking ...
X-ray ablation of material from the first wall and other components of an ICF (Inertial Confinement Fusion) chamber is a major threat to the laser final optics. Material condensing on these optics after a shot may cause damage with subsequent laser shots. To ensure the successful operation of the ICF facility, removal rates must be predicted accurately. The goal for this dissertation is to develop an experimentally validated x-ray response model, with particular application to the National Ignition Facility (NIF). Accurate knowledge of the x-ray and debris emissions from ICF targets is a critical first step in the process of predicting the performance of the target chamber system. A number of 1-D numerical simulations of NIF targets have been run to characterize target output in terms of energy, angular distribution, spectrum, and pulse shape. Scaling of output characteristics with ...
A solar water splitting cell composed of WO3, Polymer Electrolyte Membrane (PEM) and Pt was constructed for producing hydrogen from deionized water in sunlight. Spectral responsivity measurements under various temperatures and bias voltages were conducted for the cell using the Incident Photon to Current Efficiency (IPCE) method. For comparison, a known WO3 Photo Electro Chemical (PEC) cell containing H3PO4 electrolyte, WO3/H3PO4/Pt, was tested using the same test method. The WO3/PEM-H2O/Pt cell showed better Quantum Efficiency (QE) performance compared to that obtained from the cell with the chemical electrolyte. For the first time, spectral responsivity of photo water splitting process without bias power was unveiled in the new WO3 cell, demonstrating the self-sustained photo electrolysi...
Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanisms that target cancer cells and regulate tumor microenvironment is essential in designing anticancer therapies. Here, we showed that serum amyloid-A (SAA) and cathelicidin (LL-37) stimulated M-CSF and MCP-1 expression with or without lipopolysaccharide (LPS) administration; conversely, lipoxin-A4 (LXA4) and annexin-A1 (ANXA1) inhibited LPS-induced M-CSF and MCP-1 production by human (HepG2) and mouse (H22) hepatocellular carcinoma cells (HCCs). The effects of LXA4, ANXA1, SAA ...
Optimization of nonviral gene delivery typically focuses on the design of particulate carriers that are endowed with desirable membrane targeting, internalization, and endosomal escape properties. Topographical control of cell transfectability, however, remains a largely unexplored parameter. Emerging literature has highlighted the influence of cell-topography interactions on modulation of many cell phenotypes, including protein expression and cytoskeletal behaviors implicated in endocytosis. Using high-throughput screening of primary human dermal fibroblasts cultured on a combinatorial library of microscale topographies, we have demonstrated an improvement in nonviral transfection efficiency for cells cultured on dense micropit patterns compared to smooth substrates, as verified with flow...
Calcium (Ca) plays an important role in regulating various cellular processes. In a variety of cell types, Ca signaling occurs within microdomains where channels deliver localized pulses of Ca which activate a nearby collection of Ca-sensitive receptors. The small number of channels involved ensures that the signaling process is stochastic. The aggregate response of several thousand of these microdomains yields a whole-cellresponse which dictates the cell behavior. Here, we study analytically the statistical properties of a population of these microdomains in response to a trigger signal. We apply these results to understand the relationship between Ca influx and Ca release in cardiac cells. In this context, we use a first passage time approach to show analytically how Ca release in the whole cell depends on the single ...
Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation ...
The histone chaperone Asf1 and the chromatin remodeler SWI/SNF have been separately implicated in derepression of the DNA damage response (DDR) genes in yeast cells treated with genotoxins that cause...Full Text Available
We studied the effect of booster injections and the long-term immune response after injections of an anti-human immunodeficiency virus type 1 (HIV-1) lipopeptide vaccine. This vaccine was injected alone...Full Text Available
The cytokinetic response of the solid Yoshida sarcoma to hyperthermia was examined at two tumour volumes, 1.0-1.5 ml and 3.0-3.5 ml. The tumour, growing on the feet of rats, was heated at 42 degrees...Full Text Available
Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) was used to identify the effects of GPC3 on the regulation of malignant behaviors of HCC. MHCC97-H, a highly metastatic human HCC cell line in which GPC3 mRNA and protein levels were detected as the highest among the 4 HCC cell lines assessed in this study, and was thus selected as a cell model for in vitro and in vivo experiments. The results showed that down-regulation of GPC3 can significantly inhibit the proliferative and invasive ability of MHCC97-H. Compared with the parental HCC cells, GPC3-silenced cells exhibited attenuated capacities in developing tumors in nude ...
A tk{sup +/-} mouse embryonic stem (ES) cell line, designated 1G2, has been created in which one allele of the thymidine kinase (tk) gene was inactivated by targeted homologous recombination. This line is an analog of the mouse lymphoma tk{sup +/-} L5178Y cell line, which is used widely to assess the mutagenicity of chemical agents. Treatment of 1G2 cells with the alkylating agent N-ethyl-N-nitrosourea (ENU) resulted in a dose-related increase in tribluorothymidine-resistant colonies. Mutant frequencies of 152 and 296 per 10{sup 6} cells were determined for 0.1 and 0.3 mg/ml doses of ENU, compared with a spontaneous mutant frequency of 15 per 10{sup 6} cells. The data indicate that tk{sup +/-} 1G2 ES cells may be useful for the creation of a transgenic mouse model for assessing in vivo mutation using an endogenous autosomal gene. 45 refs., 2 ...
BACKGROUND Accumulating evidence suggests that various epigenetic aberrations play definite roles in the pathogenesis of endometriosis. We investigated the histone acetylation status in endometriosis and the application of the histone deacetylase inhibitors (HDACIs) for the treatment of endometriosis. METHODS The levels of acetylated histones in the endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were evaluated. The effects of the HDACIs on cell proliferation, the cell cycle, apoptosis of ECSCs and NESCs, and the expression of genes related to these cellular events were investigated. The effects of HDACIs on histone acetylation in chromatin of the promoter region of the cell cycle regulatory genes in ECSCs were also investigated. RESULTS The acetylated histone levels were significantly lower in ECSCs than in NESCs (P endometriosis and that ...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only...
Purpose/Objective: The role of programmed cell death (apoptosis) as a cellular response to cancer therapy such as radiation or chemotherapy is the subject of much study, and manipulation of the apoptotic response in tumor cells may be valuable in the treatment of a variety of cancers. Both p53 dependent and independent apoptotic pathways have been identified; p53 is mutated in at least 50 % of human cancers and a majority of radiation resistant tumors contain p53 mutations. This study is designed to examine the induction of programmed cell death in a human colon carcinoma cell line that possesses two mutated p53 alleles. Ionizing radiation alone, or in combination with the chemotherapeutic drug 5-fluorouracil (5-FU), were used to elicit the apoptotic response. This study will focus on whether these treatments can induce a significant ...
The National Spallation Neutron Source (NSNS), in which neutrons are generated by bombarding a liquid mercury target with 1 GeV protons, will place extraordinary demands on materials performance. The target structural material will operate in an aggressive environment, subject to intense fluxes of high energy protons, neutrons, and other particles, while exposed to liquid mercury and to water. Components that require special consideration include the Hg liquid target container and protective shroud, beam windows, support structures, moderator containers, and beam tubes. In response to these demands a materials R and D program has been developed for the NSNS that includes: selection of materials; calculations of radiation damage; irradiations, post irradiation testing, and characterization; compatibility testing and characterization; design and implementation of a plan for monitoring of materials ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected ...
Inhibition of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is an appealing method for decreasing the immunoresistance and augmenting T cell-mediated immunotherapy. A major impediment to this strategy is the impact of conventional PI3K/mTOR pathway inhibitors on T cell function. In particular, rapamycin, is a well-known immunosuppressant that can decrease the activity of the PI3K/mTOR pathway in tumor cells, but also has a profound inhibitory effect on T cells. Here we show that Honokiol, a natural dietary product isolated from an extract of seed cones from Magnolia grandiflora, can decrease PI3K/mTOR pathway-mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical proinflammatory T cell functions. Specifically, we show that at doses sufficient to down-regulate ...
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...
The effect of UV radiation in the wavelength region 230 nm to 302 nm on the ability of an irradiated mammalian cell to reactivate UV-irradiated mammalian virus was tested. An action spectrum for radiation enhanced reactivation (RER) is presented. The shape of the action spectrum points to a combined nucleic acid-protein target for UV radiation effects on this cellular parameter. An analysis of the results of others involving the biochemical and photobiological events involved in RER does not allow us to distinguish which macromolecule is the major contributor to this effect. Studies involving an analogous phenomenon in bacteris (Weigle reactivation) imply that RER and WR amy involve similar mechanisms. (author).
Societatea Nationala Nuclearelectrica SA is the operator of the Cernavoda nuclear power plant and the second largest energy producer in Romania, after Hidroelectrica, ensuring 18% of the internal energy demand. The production of nuclear power differs from other industrial activities through the risks it involves and through the legacy it leaves to the future generations, i.e. the nuclear waste. Taking into account these considerations, public acceptance represents a constant preoccupation for nuclear companies around the world. Corporate Social Responsibility (CSR) is a new practice in the nuclear industry. After a long tradition of involvement in the life of the local community through the Social Program for Cernavoda, Nuclearelectrica has initiated a CSR campaign with the theme 'Welcome a tree in your family', addressed to pupils and high school students from Cernavoda. By this campaign, we aimed at creating relevance, not just green lots and to launch a chain of ...
BackgroundHIV infection causes a qualitative and quantitative loss of CD4+ T cell immunity. The institution of anti-retroviral therapy (ART) restores CD4+ T...Full Text Available
Retinal pigment epithelial (RPE) cells, derived from the neuroectoderm, biosynthesize the novel lipid mediator neuroprotectin D1 (NPD1) from docosahexaenoic acid (DHA) in response to oxidative...Full Text Available
It is shown that a simple algorithm which exactly segregates between adiabatic and non-adiabatic electrons in particle-in-cell simulations of drift modes yields excellent conservation properties (e.g. particle number, energy) compared to the conventional df scheme. The removal of the free streaming term in the evolution of the marker weight is shown to be responsible for the improved linear and nonlinear properties of the simulated plasma.
BackgroundThe differentiation of CD8+ T lymphocytes following priming of naïve cells is central in the establishment of the adaptive immune response. Yet, the...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available
31P nuclear magnetic resonance (NMR) spectroscopy was used to monitor the response of oil palm (Elaeis guineensis) and carrot (Daucus carota) cell suspensions...Full Text Available
Asynchronous Chinese hamster ovary (CHO) cells treated with conditioning hyperthermia (10 min at 45/sup 0/C) followed immediately by x irradiation with 4 Gy at room temperature display a decreased radiation response when either irradiated, or heated and irradiated again 24 h later. In addition, conditioning by 4 Gy of x radiation alone followed at 24 h by the combined heat and radiation treatment als resulted in a larger radiation D/sub 0/. Since the differential cell-cycle responses to heat- and x-ray-induced lethality are well established for CHO cells, the potential role of cell-cycle redistribution in the observed radiation desensitization was investigated by flow cytometry. At 24 h after the combined treatment, the fraction of the cells found in the G/sub 2/ + M portion of the DNA histograms was about three times that of the controls ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These data showed that ...
IMRT with inverse planning allows simultaneous integrated boost strategies that exploit the heterogeneous dose distribution within the planning target volumes (PTVs). In this scenario, the location of cold spots within the target becomes a crucial issue and has to be related to the distribution of the clonogenic cell density (CCD). The main aim of this work is to provide the means to calculate the optimal prescription dose in a relative inhomogeneous dose distribution. To achieve this, the prescription dose has to be assigned to obtain the same tumor control probability (TCP) as the ideal homogeneous distribution, taking into account different CCDs in different PTVs (i.e. visible and subclinical regions). An adapted formulation of the linear-quadratic model, within the F-factor formalism, has been derived to preserve a chosen TCP value for the whole target volume. The F-factor has been investigated to ...
This letter describes a new simple fabrication process, developed recently for blue response'' improvement in low-cost polycrystalline silicon solar cells. A selective emitter is created by heavily doping the emitter, followed by a wet etching-back of the cell area between the fingers. An improvement up to 17 mV in {ital V}{sub oc}, 1.5 mA/cm{sup 2} in {ital J}{sub sc}, and 1% (absolute value) in {eta} is obtained. Effective phosphorus gettering, self-alignment, and application in a low-cost full screenprinting technology are the main advantages of the proposed process.
A new scheme to accurately retain kinetic electron effects in particle-in-cell (PIC) simulations for the case of electrostatic drift waves is presented. The splitting scheme, which is based on exact separation between adiabatic and on adiabatic electron responses, is shown to yield more accurate linear growth rates than the standard df scheme. The linear and nonlinear elliptic problems that arise in the splitting scheme are solved using a multi-grid solver. The multi-grid particle-in-cell approach offers an attractive path, both from the physics and numerical points of view, to simulate kinetic electron dynamics in global toroidal plasmas.
A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different target genes in Drosophila somatic cells. A paralogous complex, tMAC, controls...Full Text Available
BackgroundAdipokines, e.g. TNFα, IL-6 and leptin increase insulin resistance, and consequent hyperinsulinaemia influences breast cancer progression. Beside its mitogenic...Full Text Available
...) Abstract: Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated strategies that have been developed for selectively labeling target molecules. More recently, two and ...
Interferon-γ (IFN-γ) has been shown to enhance anti-tumor immunity and inhibit the formation of bone-resorbing osteoclasts. We evaluated the role of IFN-γ in bone metastases,...Full Text Available
Leukocyte infiltration across an activated brain endothelium contributes to the neuroinflammation seen in many neurological disorders. Recent evidence shows that IL-17-producing T-lymphocytes (e.g.,...Full Text Available
One of several methods to build YSZ electrolyte of SOFC is plasma spraying. This system heats particle to a melting point and then pushing them into target and forming a deposition. This paper presents heating studies of YSZ particle in plasma jet. By simple model it is shown that the required time such those YSZ particle with grain size of 50 ?m to be melt is around 12 x 10-4 second. (author)
Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of cattle and the causative agent of enzootic bovine leukosis. Serum antibody in infected animals does not correlate with protection...Full Text Available
EOS Technologies has been commissioned to design and build a unique 2.4m astronomical telescope for the Magdalena Ridge Observatory. This telescope utilizes a high quality primary mirror and cell from a now decommissioned military application. This paper describes the project and gives an overview of the telescope design. The Magdalena Ridge Observatory (MRO) 2.4 meter telescope will be primarily utilized to observe, track, and characterize solar system astronomical targets, Earth satellites, space vehicles, and terrestrial military targets. The telescope's rapid tracking (slew rates are 10o/sec) will allow it to move to any target and acquire data within one minute of receipt of notice. In this way, the telescope will be used to capitalize on targets of opportunity that occur in asteroid studies (e.g., Near Earth Objects) and in astrophysics, such as gamma ray bursts and other ...
This R and D project is planed to supply domestic demands of Mo-99 through fission route, and consequently this project will be expected to rise up utilization of HANARO and KAERI's capability for marketing extension into domestic and oversea radiopharmaceutical market. HEU and LEU target types are decided and designed for fission Mo-99 production in domestic. Experimental study of target fabrication technology was performed and developed processing equipments. And conceptual design of target loading/unloading in/from HANARO device are performed. Tracer test of Mo-99 separation and purification process was performed, test results reach to Mo-99 recovery yield above 80% and decontamination factor above 1600. Combined Mo-99 separation and purification process was decided for hot test scheduled from next year, and performance test was performed. Conceptual design for modification of existing hot ...
The dynamics of planktonic cyanobacteria in eutrophicated freshwaters play an important role in formation of annual summer blooms, yet overwintering mechanisms of these water bloom forming cyanobacteria remain unknown. The responses to darkness and low temperature of three strains (unicellular Microcystis aeruginosa FACHB-905, colonial M.?aeruginosa FACHB-938, and a green alga Scenedesmus quadricauda FACHB-45) were investigated in the present study. After a 30-day incubation under darkness and low temperature, cell morphology, cell numbers, chlorophyll a, photosynthetic activity (ETRmax and I k), and malodialdehyde (MDA) content exhibited significant changes in Scenedesmus. In contrast, Microcystis aeruginosa cells did not change markedly in morphology, chlorophyll a, photosynthetic activi...
The giant alga Chara corallina generates action potentials (APs) in response to mechanical stimulation, injury, or direct electrical stimulation. Students examine the waveform characteristics of these APs using standard intracellular recording techniques. Intracellular recording is easier than with neurons because of the large size of the Chara cell. Students observe very negative resting potentials (up to -250 mV), large AP amplitudes with depolarizing peaks approaching 0 mV, AP durations of seconds, and refractory periods up to several minutes. Students calculate Nernst potentials for the ions distributed across the Chara cell membrane to hypothesize the ions responsible for the resting potential and for the depolarizing phase of the AP. These calculations suggest that K+ is responsible for the resting potential and that Ca2+ influx and Ca2+-activated Cl- efflux are ...
ABSTRACT-Here we identify release of annexin A2 into the culture medium in response to low dose X-ray radiation exposure and establish functional linkages to an established paracrine factor-mediated anchorage-independent growth response. Using a standard bicameral coculture model, we observe that annexin A2 levels associated with non-irradiated neighboring cells seeded in the lower chamber (annexin A2 silenced [shRNA] JB6 cells) are increased upon coculture with irradiated (10-50 cGy) JB6 cells seeded in the upper chamber, relative to coculture with sham exposed JB6 cells seeded in the upper chamber, suggesting that annexin A2 released into the medium is capable of communicating in a paracrine fashion. Using a previously established coculture model, we observed that the paracrine factor-mediated anchorage-independent growth response to low ...
Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and ...
Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...
We investigate optimal horizons for targeting inflation in response to different shocks and their properties. Our analysis is based on a well specified macroeconometric model of Norway. We find that optimal horizons are highly shock-specific and do not increase with concern for output and/or interest rate fluctuations beyond some shock-specific levels. Optimal horizons increase with the degree of persistence in shocks while they are not affected by the size of a shock unless the central bank is averse to interest rate volatility. In the face of multiple shocks, however, sizes as well as signs of shocks become important for optimal horizons even when the central bank is not averse to interest rate volatility. This is because shocks of different signs and sizes may amplify or outweigh each o...
The spectre of exclusionary medical service provision, restricted clinic access and physician targeting in sectarian-divided Iraq underscores the crucial and timely need for qualitative research into the inter-relationship between conflict, identity and health. In response, this paper provides a critical ethnography of obstetric service provision and patient access during Shia-Sunni hostilities in Gilgit Town, capital of Pakistans Northern Areas (2005). I analyse how services were embedded in and constrained by sectarian affiliation in ways that detrimentally impacted Sunni women patients and hospital staff, resulting in profoundly diminished clinic access, reduced physician coverage and a higher observed incidence of maternal morbidity and mortality. The paper first situates obstetric med...
The influence of headspace solid-phase microextraction (HS-SPME) variables, namely, sample concentration, salt concentration and sample amount, on the equilibrium headspace analysis of the main volatile flavor compounds released from soursop was investigated. A total of 35 volatile compounds, comprising 19 esters, six alcohols, three terpenes, two acids, two aromatics, two ketones and an aldehyde, were identified. The results indicated that all response-surface models were significantly (p<0.05) fitted for 10 target volatile flavor compounds. The results further indicated that more than 65% of the variation in the equilibrium headspace concentrations of target volatile flavor compounds could be explained by the final reduced models, with high R2 values ranging from 0.658 to 0.944. Multiple...
The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases. In addition, the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development, cell function, tissue repair, and drug discovery. However, these uses have been limited by the difficulty of in vitro differentiation. The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes. Using newly established rESCs, we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation...
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identify gene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
Objective: Atherosclerosis is an inflammatory disease, modulated by plaque stabilizing and de-stabilizing cell populations such as infiltrating monocytes and vascular smooth muscle cells (vSMCs). Transcription factors regulating proliferation and differentiation of atherosclerosis relevant cell types are of interest in this context. The forkhead box transcription factor FoxP1 modulates monocyte differentiation. We studied FoxP1 expression in atherosclerotic tissue, correlated FoxP1 expression with plaque characteristics and identified associations between FoxP1 and plaque proteins. Methods: 116 Atherosclerotic plaques from carotid endarterectomy samples were histologically classified (fibrous, fibroatheromatous, atheromatous) and subjected to semi-quantitative protein analysis. Macrophage,...
Invading melanoma spreads to local and unpredictable distant location at the early stages of its development. It is justifiable, therefore, to classify the disease as a systemic disorder. This requires a systemic treatment that reaches all melanoma cells irrespective of whether they are singly dispersed and in circulation or already forming solid tumours of various sizes. Targeted radiotherapy affects directly and selectively cancer cells provided an appropriate radionuclide and its carrier are chosen. Melanoma is a pigmented tumour. Methylene blue (MTB)) accumulates selectively in melanoma cells due to its exceptionally high affinity to melanin. MTB serves, therefore, as a carrier for radionuclides. "2"1"1At-MTB has proved to be particularly effective in treating disseminated melanoma when administered systemically and, at the same time, non-toxic to normal non-pigmented and pigmented organs. (authors)
Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA ...
Measurements using radioactive targets are important for the determination of key reaction path ways associated with the synthesis of the elements in nuclear astrophysics (sprocess), advanced fuel cycle initiative (transmutation of radioactive waste), and stockpile stewardship. High precision capture cross-section measurements are needed to interpret observations, predict elemental or isotopical ratios, and unobserved abundances. There are two new detector systems that are presently being commissioned at Los Alamos National Laboratory for very precise measurements of (n,{gamma}) and (n,f) cross-sections using small quantities of radioactive samples. DANCE (Detector for Advanced Neutron-Capture Experiments), a 4 {pi} gamma array made up of 160 BaF{sub 2} detectors, is designed to measure neutron capture cross-sections of unstable nuclei in the low-energy range (thermal to {approx}500 keV). The high granularity and high detection efficiency of DANCE, combined with ...
The Polarized Gamma-ray Observer (PoGOLite) is a balloon-borne instrument that will measure gamma-ray polarization in the energy range 25-80 keV from astronomical sources such as pulsars, accretion discs and jets from active galactic nuclei. The two additional parameters provided by such observations, polarization angle and degree, will allow these objects to be studied in a new way, providing information about their emission mechanisms and geometries. The instrument measures azimuthal scattering angles of photons within a close packed array of phoswich detector cells (PDCs) based on coincident detection of Compton scattering and photoelectric absorption. Each PDC comprises three different scintillating components and combines photon detection, active collimation and bottom anticoincidence into one single unit. The three parts are viewed by a photomultiplier tube (PMT) and pulse shape discrimination is used to identify signals from dierent parts. Surrounding the ...
In recent years it has become evident from epidemiological and experimental data that a large number of environmental factors, including diet, play a role in modifying the incidence of cancer. Cell culture systems in which oncogenic transformation serves as an end point are powerful tools for evaluating these questions. Using such systems it has been shown recently that pyrolysis products from charred surfaces of broiled meat and fish can transform hamster embryo cells in vitro as well as produce tumors in the animal. Our studies in vitro have demonstrated the oncogenic potential of ionizing radiation in both hamster and human cells and have established in hamster cells the dose response relationship at doses ranging from 1 to 600 rad for x-rays and 0.1 to 150 rad for neutrons. The present work was aimed at evaluating whether there exists a cocarcinogenic interaction between a ...
Abstract. Objective: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. Materials and methods: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines fro...
NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including ...
In this paper, the authors describe the characteristics of design seismic input motions and recently observed seismic records of base isolated buildings in Japan. First, we describe some seismic design spectra for building structures which were adopted. Then we show response spectra and energy spectra of observed records obtained during two recent major earthquakes (The 1995 Hyogo-ken Nanbu Earthquake and the 2003 Tokachi-oki Earthquake), which demonstrate the effectiveness of base isolation against large amplitude earthquake ground motion. We also introduce the responses of base isolated buildings during some earthquakes including the Tokachi-oki Earthquake. These data were gathered through questionnaires sent to many engineers who had conducted response observations of base isolated buildings. Last, an example of a base isolated building on soft ground is shown. We point out the importance of selecting the appropriate ...
The T cell receptor is a fundamental mediator of the adaptive immune responses, since TR ab on T cells recognize foreign structures (peptides derived from processed antigens) bound to the major histocompatibility complex (MHC) on APC cells. In the present study, we report the cloning of six TRB chains cDNA sequences from gilthead sea bream (Sparus aurata), a fish of high economical impact in South Mediterranean aquaculture. The V-BETA domains have the canonical features of known teleost and mammalian TR V-BETA domains and have been divided in four different subgroups. A multiple alignment of the six sea bream TRB chains with other known TRB sequences was assembled and showed the conservation of the four cysteine residues involved in disulphide bonds and of some amino acids with an importan...
Lung cancer is still difficult to treat by current chemotherapeutic procedures. We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis viridis, also has antitumor activity. The objective of this study was to investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic changes in A549 cells, and to identify the molecular pathways responsible for the anti-cancer action of R-MVL. We found that R-MVL induces A549 cells apoptosis in a dose-dependent manner by using MTT assay, fluorescent microscope (FM) and flow cytometry (FCM), and the IC50 was calculated to be 24.12??g/ml. Subsequently, 7 altered proteins in R-MVL-treated A549 cells were identified, including upregulated aldehyde dehydrogenase 1 and ?-actin, and five downregulated proteins: heat s...
The fuel cell control problem was studied. Attempts were made to control the output current of the fuel cell by starving it of hydrogen and oxygen. The motivation of this work was to increase efficiency by minimizing waste of fuel. The following findings were obtained: H2 starvation works better than O2 starvation; An optimal H2 to O2 ratio exists for combined H2&O2 starvation; The control scheme for H2&O2 starvation works well for 3 different disturbance tests and at 25 degrees C, 60 degrees C, and 80 degrees C; Fuel cell under reactant starvation is stable for at least 72 hrs.
Several challenges currently exist for rational design of functional tissue engineering constructs within the host, which include appropriate cellular integration, avoidance of bacterial infections, and low inflammatory stimulation. This work describes a novel class of biodegradable, amphiphilic polyanhydrides with many desirable protein-material and cell-material attributes capable of confronting these challenges. The biocompatible amphiphilic polymer films were shown to release laminin in a stable and controlled manner, promote neural cell adhesion and differentiation, and evade inflammatory responses of the immune system. Using high-throughput approaches, it was shown that polymer chemistry plays an integral role in controlling cell?film interactions, which suggests that these polyanhyd...
The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could ...
Human heat shock protein 27 (Hsp27, HspB1) is an anti-apoptotic protein characterized for its tumorigenic and metastatic properties, and now referenced as a major therapeutic target in many types of cancer. Hsp27 biochemical properties rely on a structural oligomeric and dynamic organization. Downregulation by small interfering RNA or inhibition with dominant-negative mutant have proven their efficiency to counteract the anti-apoptotic and protective properties of Hsp27. In this study, we report the isolation and characterization of Hsp27-targeted molecules interfering with its structural organization. Using the peptide aptamer (PA) strategy, we isolated PAs that specifically interact with Hsp27 and not with the other members of the small heat shock protein family. In mammalian cell cultur...
The DARWIN mission is an Infrared free flying interferometer mission based on the new technique of nulling interferometry. Its main objective is to detect and characterize other Earth-like planets, analyze the composition of their atmospheres and their capability to sustain life, as we know it. DARWIN is currently in definition phase. This PhD work that has been undertaken within the DARWIN team at the European Space Agency (ESA) addresses two crucial aspects of the mission. Firstly, a DARWIN target star list has been established that includes characteristics of the target star sample that will be critical for final mission design, such as, luminosity, distance, spectral classification, stellar variability, multiplicity, location and radius of the star. Constrains were applied as set by planet evolution theory and mission architecture. Secondly, a number of alternative mission architectures have been evaluated on the basis of interferometer ...
Electron and ion beam dynamics of the PF-1000 facility were investigated for the first time at its upper energy limit (?1 MJ) in relation to neutron emission, the pinch's plasma ('target') characteristics and some other parameters with the help of a number of diagnostics with ns temporal resolution. Special attention was paid to the temporal and the spatial cross correlations of different phenomena. Results of these experiments are in favour of a neutron emission model based on ion beam-plasma interaction with three important features: (1) the plasma target is hot and confined during a few 'inertial confinement times'; (2) the ions of the main part of the beam are magnetized and entrapped around the pinch plasma target for a period longer than the characteristic time of the plasma inductive storage system and (3) ion-ion collisions (both fusion collisions, due to head-on impacts and Coulomb collisions) are ...
An experimental and analytical study was performed to improve understanding of the dynamic impact behavior of carbon steel pipes. The test program addressed two types of pipe impact scenarios using both 2- and 4-in. Sch-80 pipes and elbows. Projectile-on-pipe tests simulated the behavior of a stationary target pipe which is impacted at its center by a larger, more rigid whipping pipe. These target pipes, which contained non-flowing water at about 290{degree}C temperature and ca 8.5 megapascals pressure, exhibited a peak deformation of up to 45% reduction in their diameter. For each test condition, the local deformation at the impact zone is a function of the peak impact force and impact velocity. Pipe-on-wall tests simulated the impact of an elbow at the free end of a cantilevered whipping pipe with a rigid barrier. The peak crush of the impact zone of the elbows was a function of peak impact force. Numerical analyses of dynamic impact tests ...
An experimental and computational study was undertaken to estimate the effects of pipe rupture and induced pipe whip impact on surround structures considered either as rigid or deformative such as concrete slabs. This program included sixteen tests using 3 inch schedule 80 (or 10) pipes made of carbon steel similar to A106 grade B. The study consisted of tests on rigid target and on concrete slab. The investigation of whip phase and impact phase was done separately for each test. For pipe impact on rigid targets, the impact forces are found to be directly related to the crush strength of the pipe and the general pipe deformation following the impact. For pipe impact on concrete slabs, the response of the target to the pipe impact needs to take into account the local effect such as penetration and localized damage on the slab. The test matrix covered a broad range of geometric parameters. It provides a ...
EPRI has sponsored an experimental program in the pipe whip impact and pipe rupture and depressurization areas. Sixteen pipe whip tests were performed with 3 in Schedule 80 (or 10) carbon steel pipes impacting on rigid target or concrete slab. The major testing parameters include distance, impact location, pipe rupture location, and concrete slab thickness and strength. The piping crushing at impact correlates with impact force and targetresponse behavior. Conservatism was established by comparing measured and calculated impact forces. The pipe rupture and depressurization tests were carried out using 6 in stainless steel and carbon steel pipes under either PWR or BWR fluid conditions. These tests are of axial crack with initial machined-in surface flaw. It was found that pipe rupture would occur only if a long unstable through-wall crack was embedded in a sufficiently long unstable part-through crack (in the pipe wall). ...
It is well known that composite armors, consisting of glass elements confined with metallic tampers, are extraordinarily effective against shaped charge attack. Early experiments showed that jets fired against glass targets appeared to be bombarded by tiny fragments that destroyed alignment and reduced residual jet penetration. This result was attributed to an elastic rebound effect in which the outward radial motion of the target around the jet periphery was supposed to be arrested by tensile hoop stresses which developed behind the divergent shock front. Glass fragments were then accelerated radially inward and these destabilized the jet. To sustain the large tensile hoop stresses required, the glass must not have been fractured by the initial shock, behind which the stress state is typically well above the Hugoniot elastic limit. Modeling the penetration of a jet into glass requires not only determining the spall strength, i.e., the tensile ...
Deep brain stimulation (DBS) has been used for relieving chronic pain in patients that have been through other existing options. The septum has been one of the targets for such treatment. The purpose of this study was to determine the inhibitory effect of electrical stimulation in the medial septum diagonal band of broca (MSDB) on neuronal activity in the spinal cord of rats anesthetized with sodium pentobarbital. While unilaterally stimulating the MSDB, wide dynamic range neurons in the lumbar region of the spinal cord were recorded in response to graded mechanical stimulation of the hind paws (brush, pressure, and pinch). Stimulation was at 1, 5, 10, and 20V, at 100Hz, and 0.1ms duration. Significant bilateral reduction was observed in response to pressure (ipsilaterally: 0.90+/-0.05, 0....
Insect attraction to host plants may be partly mediated by visual stimuli. In the present study, the responses of adult Hycleus apicicornis (Gur.) (Coleoptera: Meloidae) to plant models of different colours, different combinations of two colours, or three hues of blue of different shapes are compared. Single-colour models comprised the colours sky blue, bright green, yellow, red, white and black. Sky blue (reflecting light in the 440-500 nm region) is the most attractive, followed by white, which reflects light over a broader range (400-700 nm). On landing on sky blue targets, beetles exhibit feeding behaviour immediately. When different hues of blue (of different shapes) are compared, sky blue is preferred over turquoise, followed by dark blue, indicating that H. apicicornis is more attra...
The paper deals with the reliability-based design optimization (RBDO) of a riser support installed on a floating production storage and offloading (FPSO) unit under operation, extreme, damaged, and one line failure cases and installation loading conditions. The optimization problem is formulated such that probabilistic thickness variables described with random characteristics are determined by minimizing the weight of the riser support structure subjected to stress constraints for the given target reliability. The initial design model is generated based on actual FPSO riser support specifications. The finite element analysis is conducted using NASTRAN, and the probabilistic optimal solutions are obtained via the moving least squares method in the context of RBDO using a response surface me...
Nano photonic materials are synthetically manufactured crystals at the nano scale with the target of creating a microstructure with a special electro-magnetic periodicity. Such nano photonic materials have the ability to control light propagation and thus are capable of creating photonic bandgaps in the frequency domain. We propose using nano photonic crystals as sensors to detect microdamage in composite materials. We demonstrate using a simulation model that a nano photonic sensor attached to a composite bar experiences a significant change in its bandgap profile when damage is induced in the composite bar. The model predicts the frequency response of the nano photonic sensor using the transfer matrix method. A damage metric to evaluate the change in the frequency response is developed. Successful developments of nano photonic sensors allow damage identification at scales not attainable using current sensing technologies.
This paper reviews generation methods of artificial earthquake motion and proposes an improved method of generating input motions for use in vibration tests of equipment to prove aseismic performance. The improved method employs beat wave repetition characteristic that inherently appears in the component waves of recorded earthquakes decomposed by bandpass filter and algebraic function phase for the component waves. Typical motions generated by the improved method satisfies prescribed severe conditions such as targetresponse spectrum that are defined with a wideband frequency component and a limited maximum acceleration due to shaking table performance. The motions had never been generated by the conventional method.
The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...
This study focuses on comparing reports of nicotine withdrawal, craving, and depressive symptoms obtained using an Interactive Voice Response (IVR) system and several questionnaires. As part of a smoking cessation trial, daily reports of withdrawal, craving, and negative mood were collected using an IVR system for 7 days after participants attempted to quit smoking, and several pencil and paper questionnaires (i.e., the Minnesota Nicotine Withdrawal Scale, the Questionnaire on Smoking Urges, and the Center for Epidemiological Studies-Depression) were completed a week after the target quit date. The sample was composed of 378 daily smokers. Moderate to high correlations were found between the research questionnaires obtained at the end of the week and the corresponding daily IVR reports of ...
Measurement of serum biochemical parameters in response to metal exposures can be especially useful to help identify target organs of toxicity as well as the general health status of animals. Oreochromis niloticus were exposed to 5.0?mg/L?Zn, 1.0?mg/L?Cd, and 5.0?mg/L?Zn?+?1.0?mg/L?Cd mixture for 7 and 28?days, and alterations in serum enzyme activities and ion levels were measured. Significant changes in all the biochemical parameters were found to be time dependent. Following metal exposure, alkaline phosphatase activity was elevated at both exposure periods. No changes in activities of lactate dehydrogenase and lipase were observed in response to single or combined Zn and Cd exposure at 7?days while they increased at 28?days. Fish exposed to metals showed a decrease in cholinesterase ac...
Mitotic delay is described as a classical response to radiation; however, circadian rhythmicity in cell division in vivo has not been considered by many authors. The present study investigated the relation between fluctuations reported as mitotic delay and recovery in vivo and circadian oscillations in mitotic index in mouse corneal epithelium. One aspect involved single doses (approximately 600 rad) given to mice at different circadian stages. The normal circadian rhythm in cell division was never obliterated. Inhibition of mitosis was evident but unpredictable, ranging from 6 to 15 hr after irradiation. Recovery was evident only during the daily increase in mitotic index of controls. The classical interpretation of recovery from mitotic delay may be in an in vitro phenomenon not reflecting in vivo responses, which are apparently strongly circadian stage dependent. The second portion of the study ...
Low temperature Nonphotochemical Hole Burning (NPHB) Spectroscopy of the dye rhodamine 800 (MF680) was applied for the purpose of discerning differences between cultured normal and carcinoma ovarian surface epithelial (OSE) cells. Both the cell lines were developed and characterized at the Mayo Clinic (Rochester, MN), with the normal cell line having been transfected with a strain of temperature sensitive Simian Virus 40 Large T Antigen (SV40) for the purpose of extending the life of the cell culture without inducing permanent changes in the characteristics of the cell line. The cationic lipophilic fluorophore rhodamine 800 preferentially locates in in situ mitochondria due to the high lipid composition of mitochondria and the generation of a large negative membrane potential (relative to the cellular cytoplasm) for oxidative phosphorylation. Results presented for NPHB of MF680 ...
Low temperature Nonphotochemical Hole Burning (NPHB) Spectroscopy of the dye rhodamine 800 (MF680) was applied for the purpose of discerning differences between cultured normal and carcinoma ovarian surface epithelial (OSE) cells. Both the cell lines were developed and characterized at the Mayo Clinic (Rochester, MN), with the normal cell line having been transfected with a strain of temperature sensitive Simian Virus 40 Large T Antigen (SV40) for the purpose of extending the life of the cell culture without inducing permanent changes in the characteristics of the cell line. The cationic lipophilic fluorophore rhodamine 800 preferentially locates in in situ mitochondria due to the high lipid composition of mitochondria and the generation of a large negative membrane potential (relative to the cellular cytoplasm) for oxidative phosphorylation. Results presented for NPHB of MF680 ...
Extracellular ATP stimulates transmembrane ion fluxes in the mouse macrophage cell line J774. In the presence of Mg2+, nonhydrolyzable ATP analogs and other purine and pyrimidine nucleotides do not elicit this response, suggesting the presence of a specific receptor for ATP on the macrophage plasma membrane. One candidate for such a receptor is the ecto-ATPase expressed on these cells. We, therefore, investigated the role of this enzyme in ATP-induced /sup 86/Rb+ efflux in J774 cells. The ecto-ATPase had a broad nucleotide specificity and did not hydrolyze extracellular ATP in the absence of divalent cations. /sup 86/Rb+ efflux was not blocked by inhibition of the ecto-ATPase and did not require Ca2+ or Mg2+. In fact, ATP-stimulated /sup 86/Rb+ efflux was inhibited by Mg2+ and correlated with the availability of ATP4- in the medium. In the absence of divalent cations, the slowly hydrolyzable ATP analogs ...
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 ...
Innate immune responses are regulated by microorganisms and cell death, as well as by a third class of stress signal from the nervous and endocrine systems. The innate immune system also feeds back, through the production of cytokines, to regulate the function of the central nervous system (CNS), and this has effects on behaviour. These signals provide an extrinsic regulatory circuit that links physiological, social and environmental conditions, as perceived by the CNS, with transcriptional 'decision-making' in leukocytes. CNS-mediated regulation of innate immune responses optimizes total organism fitness and provides new opportunities for therapeutic control of chronic infectious, inflammatory and neuropsychiatric diseases.
Abstract Host-microorganism interactions in the intestinal tract are complex, and little is known about specific nonpathogenic microbial factors triggering host responses in the gut. In this study, mannose-specific interactions of Lactobacillus plantarum 299v with jejunal epithelium were investigated using an in situ pig Small Intestinal Segment Perfusion model. The effects of L. plantarum 299v wild-type strain were compared with those of two corresponding mutant strains either lacking the gene encoding for the mannose-specific adhesin (msa) or sortase (srtA; responsible for anchoring of cell surface proteins like Msa to the cell wall). A slight enrichment of the wild-type strain associated with the intestinal surface could be observed after 8 h of perfusion when a mixture of wild-type and...
Mycoplasma ovipneumoniae is associated with chronic non-progressive pneumonia of sheep and goats. As with many other mycoplasmas involved in animal diseases, protective immune responses have not been achieved with vaccines, even though antibody responses can be obtained. This study focuses on characterizing the interaction of M. ovipneumoniae with ovine PBMC using carboxy-fluorescein-succinimidyl-ester (CFSE) loading and flow cytometry to measure lymphoid cell division. M. ovipneumoniae induced a strong in vitro polyclonal suppression of CD4^+, CD8^+, and B blood lymphocyte subsets. The suppressive activity could be destroyed by heating to 60^oC, and partially impaired by formalin and binary ethyleneimine treatment that abolished its viability. The activity resided on the surface-exposed m...
To test the hypothesis that transduction of the channelrhodopsin-2 (ChR2) gene, a microbial-type rhodopsin gene, into retinal ganglion cells of genetically blind rats will restore functional vision, we recorded visually evoked potentials and tested the experimental rats for the presence of optomotor responses. The N-terminal fragment of the ChR2 gene was fused to the fluorescent protein Venus and inserted into an adeno-associated virus to make AAV2-ChR2V. AAV2-ChR2V was injected intravitreally into the eyes of 6-month-old dystrophic RCS (rdy/rdy) rats. Visual function was evaluated six weeks after the injection by recording visually evoked potentials (VEPs) and testing optomotor responses. The expression of ChR2V in the retina was investigated histologically. We found that VEPs could not b...
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 ...
CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after ...
Although the majority of men presenting with non-seminomatous germ cell tumours (NSGCT) are cured, late relapse (occurring more than 2 years after obtaining a complete response to treatment) is increasingly recognized. The typical patterns of disease spread have been well-documented, but the findings at late relapse are more variable and less well-described. We discuss the phenomenon of late relapse, the characteristics of teratoma differentiated (TD), and the issue of long-term imaging surveillance of patients with NSGCT. The potential sites of late relapse of NSGCT and the associated spectrum of imaging appearances are illustrated.
Although the majority of men presenting with non-seminomatous germ cell tumours (NSGCT) are cured, late relapse (occurring more than 2 years after obtaining a complete response to treatment) is increasingly recognized. The typical patterns of disease spread have been well-documented, but the findings at late relapse are more variable and less well-described. We discuss the phenomenon of late relapse, the characteristics of teratoma differentiated (TD), and the issue of long-term imaging surveillance of patients with NSGCT. The potential sites of late relapse of NSGCT and the associated spectrum of imaging appearances are illustrated.
Resistance and tolerance are two types of host defense mechanisms that increase fitness in response to fungi. Several genetic polymorphisms in pattern recognition receptors, most remarkably Toll-like receptors (TLRs), have been described to influence resistance and tolerance to aspergillosis in distinct clinical settings. TLRs on dendritic cells pivotally contribute in determining the balance between immunopathology and protective immunity to the fungus. Epithelial cells also contribute to this balance via selected TLRs converging on indoleamine-2,3-dioxygenase (IDO). Studies in experimental hematopoietic transplantation confirmed the dichotomy of pathways leading to resistance and tolerance to the fungus providing new insights on the relative contribution of the hematopoietic/nonhematopoi...
The objective of this research is to determine the role of DNA repair in mutagenesis and carcinogenesis in mammalian cells. Use of the host-cell reactivation viral suicide enrichment procedure was initiated in the isolation of repair-deficient mutants. Lightly mutagenized BHK cells were infected with irradiated Herpes simplex virus (HSV); several radiation-sensitive strains were isolated among the survivors of the infection. The characterization of these strains is progressing and the enrichments are continuing. That alterations in the frequency of mutation of C3H/10T 1/2 cells, occurring as a result of holding the cells in a confluent state following treatment with ethylmethane sulfonate, parallel the alterations in the frequency of neoplastic transformation was found. The repair capabilities of BHK cells were found to be intermediate in comparison to ...
Exogenous adenosine 5{prime}-triphosphate (ATP) mobilized intracellular calcium in human carcinoma A43l cells and in Swiss 3T3 and 3T6 mouse fibroblasts by increasing inositol trisphosphate similar to well down growth factors (platelet-derived growth factor (PDGF), epidermal growth factor (EGF), bradykinin (BK), serum). Calcium mobilization was examined by video imaging of fura-2 fluorescence is single cells, following the radioactive isotope {sup 45}Ca, and monitoring the decrease in fluorescence of cells loaded with chlortetracycline. Uridine 5{prime}-triphosphate, but not other nucleotides, mimicked ATP. Single-cell analysis revealed synchronous responses in 10 sec to ATP, BK or serum, while PDGF (3T3) and EGF (A431) produced slower signals with significant cell-to-cell variation. PDGF desensitized 3T3 cells to ATP and BK added 100 sec ...
Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast ...
Aim:To examine the electrophysiological effects of sophocarpine on action potentials (AP) and ionic currents of cardiac myocytes and to compare some of these effects with those of amiodarone.Methods:Langendorff perfusion set-up was used in isolated guinea pig heart, and responses to sophocarpine were monitored using electrocardiograph. Conventional microelectrode, voltage clamp technique and perforated patch were employed to record fast response AP (fAP), slow response AP (sAP) and ionic currents in guinea pig papillary muscle or rabbit sinus node cells.Results:Tachyarrhythmia produced by isoprenaline (15 ?mol/L) could be reversed by sophocarpine (300 ?mol/L). Sophocarpine (10 ?mol/L) decreased the amplitude by 4.0%, maximal depolarization velocity (Vmax) of the fAP by 24.4%...
Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and ...
We describe the isolation and genetic characterization of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced mutations in the phage P22 mnt repressor gene cloned in plasmid pBR322. Mutations in the mnt repressor gene or its operator on this plasmid, pPY98, confer a tetracycline resistance phenotype, whereas the wild-type plasmid confers tetracycline sensitivity. Cells carrying pPY98 were briefly exposed to MNNG to give 20 to 40% survival and a 50- to 100-fold increase in tetracycline-resistant cells. DNA sequence analysis showed that 29 to 30 MNNG-induced mutations were GC-to-AT transitions and one was an AT-to-GC transition. About 80% of the mutations are in three hotspots. This mutation spectrum is consistent with the proposed mechanism of mutagenic action of MNNG, which involves mispairing of an alkylated base, O/sup 6/-methylguanine. The mnt gene may be a useful target for determining mutagenic specificity at ...
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 ...
'Full text:' The use of fuel cell technology in military applications will depend on safe, high energy density systems being developed. An important part of using this technology is also the development of alternative hydrogen producing fuels with high energy densities and are easy to transport. Fuel cells are now a very large R and D effort for several military applications around the world. The major reason is because of the high power demands needed requires electrical energy sources that far exceed the capabilities of batteries currently being fielded for portable applications. Fuel cells are regarded as highly efficient, tactical energy converters that can be adapted for wide range of power requirements. They are potentially the lowest weight power source when coupled with batteries or capacitors to form hybrid systems. Generally electrical power is needed to support a number of applications from ultra-high power for ...
Radiotherapy with high-energy carbon ion beams can be more advantageous compared to photons because of better physical dose distribution and higher biological efficiency in tumour cell sterilization. Despite enhanced normal tissue sparing, damage incurred by normal cells at the beam entrance is unavoidable and may affect the progeny of surviving cells in the form of inheritable cytogenetic alterations. Furthermore, the quality of the beam along the Bragg curve is modified by nuclear fragmentation of projectile and target nuclei in the body. We present an experimental approach based on the use of a polymethylmethacrylate (PMMA) phantom that allows the simultaneous exposure to a particle beam of several biological samples positioned at various depths along the beam path. The device was used to measure the biological effectiveness of a 60 MeV/amu carbon-ion beam at inducing chromosomal aberrations in G{sub ...
Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ ...
ABSTRACT: Metabolomic analysis will provide the next large set of clues to further our understanding of human health and disease. A recent study has elucidated the significant differences in the metabolomes of adipocytes, serum and an adipocyte cell line after activation of two nuclear receptors, peroxisome proliferator activated receptor ?/? (PPAR?/?) and PPAR?. These findings hold great promise for explaining fundamental differences in the mechanisms of PPAR agonists and for identifying targets for the treatment of diabetes.See related research article: http://genomebiology.com/2011/12/8/R75. PMID:21861850
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.
Gas nitridation has shown excellent promise to form dense, electrically conductive and corrosion-resistant Cr-nitride surface layers on Ni-Cr base alloys for use as proton exchange membrane fuel cell (PEMFC) bipolar plates. Due to the high cost of nickel, Fe-base bipolar plate alloys are needed to meet the cost targets for many PEMFC applications. Unfortunately, nitridation of Fe-base stainless steel alloys typically leads to internal Cr-nitride precipitation rather than the desired protective surface nitride layer formation, due to the high permeability of nitrogen in these alloys. This paper reports the finding that it is possible to form a continuous, protective Cr-nitride (CrN and Cr2N) surface layer through nitridation of Fe-base stainless steel alloys. The key to form a protective Cr...
This study examined whether elevated intravascular pressure stimulates asynchronous Ca2+ waves in cerebral arterial smooth muscle cells and if their generation contributes to myogenic tone development. The endothelium was removed from rat cerebral arteries, which were then mounted in an arteriograph, pressurized (20 100 mmHg) and examined under a variety of experimental conditions. Diameter and membrane potential (VM) were monitored using conventional techniques; Ca2+ wave generation and myosin light chain (MLC20)/MYPT1 (myosin phosphatase targeting subunit) phosphorylation were assessed by confocal microscopy and Western blot analysis, respectively. Elevating intravascular pressure increased the proportion of smooth muscle cells firing asynchronous Ca2+ waves as well as event frequency. C...
The importance of cellular dosimetry in both diagnostic and therapeutic nuclear medicine is becoming increasingly recognized. Experimental range-energy relations for electrons and alpha particles, along with derived geometric reduction factors, are used to calculate cellular absorbed fractions for these radiations. The resulting absorbed fractions are employed to calculate cellular S-values for several radionuclides. Cellular absorbed fractions for monoenergetic electron sources with energies ranging from 0.1 keV to 1 MeV, distributed uniformly in the source region, are calculated for several target {l_arrow} source combinations including cell{l_arrow}cell, cell{l_arrow}cell surface, nucleus{l_arrow}nucleus, nucleus {l_arrow}cytoplasm and nucleus {l_arrow}cell surface. Similar data are also provided for monoenergetic alpha particle sources with energies ranging from 3 to 10 MeV. S-values are also ...
Abstract A Pseudomonas sp. isolate MSB1 efficiently inhibited the growth of Flavobacterium psychrophilum of different serotypes on agar medium. A significant difference in the inhibition was observed between isolates of the less virulent FpT serotype compared to the Fd and Th serotypes. In broth coculture experiments, a low number of cells of MSB1 inhibited and outcompeted the F.psychrophilum cells. Also cell-free culture supernatant of MSB1 clearly repressed the growth of F.psychrophilum. A chromoazurol S assay suggested that MSB1 produced efficient siderophores, which most probably were responsible for the iron deficiency in the supernatant. The limited growth of F.psychrophilum in the supernatant was found to be partly because of the lack of available iron, but the results also indicate...
Hybrid electric vehicles (HEV) need long-lived high-power batteries as energy storage devices. Batteries based on lithium-ion technology can meet the high-power goals but have been unable to meet HEV calendar-life requirements. As part of the US Department of Energy's Advanced Technology Development (ATD) Program, diagnostic studies are being conducted on 18650-type lithium-ion cells that were subjected to accelerated aging tests at temperatures ranging from 40 to 70 C. This article summarizes data obtained by gas chromatography, liquid chromatography, electron microscopy, X-ray spectroscopy and electrochemical techniques, and identifies cell components that are responsible for the observed impedance rise and power fade.
Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by [sup 89]Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses. (author).
Entorhinal grid cells in mammals fire as a function of animal location, with spatially periodic response patterns. This nonlocal periodic representation of location, a local variable, is unlike other neural codes. There is no theoretical explanation for why such a code should exist. We examined how accurately the grid code with noisy neurons allows an ideal observer to estimate location and found this code to be a previously unknown type of population code with unprecedented robustness to noise. In particular, the representational accuracy attained by grid cells over the coding range was in a qualitatively different class from what is possible with observed sensory and motor population codes. We found that a simple neural network can effectively correct the grid code. To the best of our kn...
A 33-year-old male of proven fertility suffered six attacks of malaria while resident in an African country. For this he received anti-malarial drugs. Semen analysis performed after the fourth attack, and repeated during the following 2 years after his return to Israel, revealed severe oligozoospermia, necrozoospermia and occasionally even azoospermia. Immunological examination of the patient revealed an inverse ratio of T-cell subsets and mast cell degranulation in response to palludrin. Twenty-five months after the last attack of malaria a significant improvement was found in semen quality and there was an increase in the ratio of T-helper to T-suppressor cytotoxic cells. These observations indicate that although malaria and its treatment may affect spermatogenesis, recovery may be expected eventually. PMID:3500921
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17b-estradiol (E2), although glycyrrhizin di...
HT-29 human colon tumor cells growing as spheroids have been evaluated as a model system for measuring the response of human colon tumor cell to antineoplastic agents. HT-29 cells have been capacity to form spheroids up to 1 mm or more in diameter when grown in spinner culture. The multicellular HT-29 spheroids develop hypoxic centers reflecting the cellular conditions found in human cancer treatment, i.e., nutritionally deficient hypoxic cells that are felt to be a significant source of both radiation and chemotherapy clinical treatment failures. Spheroids of increasing size were radiated and then dispersed into single cells for colony survival assay. Compared with irradiated single cell suspensions, the spheroid cells demonstrated a significant increase in radioresistance. Growing spheroids developed a complex ...
Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to ...
Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed ...
Elite suppressors or controllers (ES) are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated...Full Text Available
The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study,...Full Text Available
Cell-free extracts of Acremonium chrysogenum and Streptomyces clavuligerus oxidize the 3-methyl group of desacetoxycephalosporin C to a 3-hydroxymethyl group. The enzyme responsible for this reaction...Full Text Available
Werner syndrome (WS) is a rare disorder characterized by the premature onset of several pathologies associated with aging. The gene responsible for WS codes for a RecQ-type DNA helicase and is believed...Full Text Available
BackgroundThe Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against...Full Text Available
TH1 cytokine secretion was examined in response to synthetic peptides of the 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis in seven different...Full Text Available
BackgroundHerpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction...Full Text Available
The leukocyte-enriched p110γ and p110δ isoforms of PI3K have been shown to control in vitro degranulation of mast cells induced by cross-linking...Full Text Available
Intrahepatic cholangiocarcinoma is the second most common primary malignant hepatic neoplasm. We describe two cases of intrahepatic cholangiocarcinoma which initially presented as liver abscess both clinically and radiologically. Mucin-hypersecretion from the tumor cells and extensive necrosis or secondary bacterial infection was responsible for the radiologic appearance of a liver abscess.=20
Refeeding starved rats with an elemental diet resulted in a marked increase in crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect...Full Text Available
The heat resistance of spores of Bacillus subtilis formed at 30°C was enhanced by pretreatment at 48°C for 30 min, 60 min into sporulation, for all four strains examined....Full Text Available
From the dried fruiting bodies of the mushroom Armillaria luteo-virens, a dimeric lectin with a molecular mass of 29.4 kDa has been isolated. The purification procedure involved (NH{sub 4}){sub 2}SO{sub 4} precipitation, ion exchange chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The hemagglutinating activity of the lectin could not be inhibited by simple sugars but was inhibited by the polysaccharide inulin. The activity was stable up to 70 {sup o}C but was acid- and alkali-labile. Salts including FeCl{sub 3}, AlCl{sub 3}, and ZnCl{sub 2} inhibited the activity whereas MgCl{sub 2}, MnCl{sub 2}, and CaCl{sub 2} did not. The lectin stimulated mitogenic response of mouse splenocytes with the maximal response achieved by 1 {mu}M lectin. Proliferation of tumor cells including MBL2 cells, HeLa ...
The main drawback of Ni/YSZ anode supports for solid oxide fuel cell application is their low tolerance to reducing and oxidizing (RedOx) atmosphere changes, owing to the Ni/NiO volume variation. This work describes a structured approach based on design of experiments for optimizing the microstructure for RedOx stability enhancement. A full factorial hypercube design and the response surface methodology are applied with the variables and their variation range defined as: (1) NiO proportion (40-60wt% of the ceramic powders), (2) pore-former proportion (0-30wt% corresponding to 0-64vol.%), (3) NiO particle size (0.5-8mm) and (4) 8YSZ particle size (0.6-9mm). To obtain quadratic response models, 25 different compositions were prepared forming a central composite design. The measured responses...
Investigations into sexual differentiation and pheromone response in the fission yeast Schizosaccharomyces pombe are complicated by the need to first starve the cells of nitrogen. Most mating-related experiments are therefore performed on non-dividing cells. Here we overcome this problem by using two mutants that bypass the nutritional requirements and respond to the M-factor mating pheromone in rich medium. The first mutant lacks the cyr1 gene which encodes adenylate cyclase and these cells contain no measurable amounts of cAMP. When M-factor is added to a growing h+ cyr1- strain it causes a transient G1 arrest of cell division, transcription of mat1-Pm, and elongation of the cells to form shmoos. The second mutant contains the temperature-sensitive pat1-114 allele. At 30 degrees C this mutant was previously shown not only to bypass the nutritional signal but ...
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. ...
Autophagy is an intracellular recycling route in eukaryotes whereby organelles and cytoplasm are sequestered in vesicles, which are subsequently delivered to the vacuole for breakdown. The process is induced by various nutrient-responsive signaling cascades converging on the Autophagy-Related1 (ATG1)/ATG13 kinase complex. Here, we describe the ATG1/13 complex in Arabidopsis thaliana and show that it is both a regulator and a target of autophagy. Plants missing ATG13 are hypersensitive to nutrient limitations and senesce prematurely similar to mutants lacking other components of the ATG system. Synthesis of the ATG12-ATG5 and ATG8-phosphatidylethanolamine adducts, which are essential for autophagy, still occurs in ATG13-deficient plants, but the biogenesis of ATG8-decorated autophagic bodies does not, indicating that the complex regulates downstream events required for autophagosome enclosure and/or vacuolar delivery. Surprisingly, levels of the ...
Natural sunlight induces a genotoxic response in cultured CHO cells pre-treated with shale oil retort process water. Near ultraviolet light (NUV) component of the solar spectrum is the apparent radiation responsible for photoactivation. Cultured human skin fibroblasts are acutely sensitive to the genotoxic effects of photoactivated process water. The mutagenic potential of photoactivated process water in human cells is the same as that witnessed for an equivalent killing dose of the potent skin carcinogen FUV. DNA repair processes are involved in modulating genotoxic effects of this photo-induced process. The exact magnitude of the potential health-related and environmental risks resulting from photoactivation of retort process waters and other oil shale by-products is unassessed at this time. Our demonstration that a significant rate of mutation occurs in cultured human cells ...
Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of ...
The thermophotovoltaic (TPV) option was not selected for further deep space mission technology development in NASA for several reasons. Chief among them was the large radiator required to keep the photovoltaic cells at a sufficiently low operating temperature. This led to significant integration problems with the spacecraft and limited sensor view angles. It is clear that the issue of cell temperature is crucial for space applications because of radiator size and system impact. Many efforts have focused on matching cell band gap to appropriate emitters in the 1 to 2 {mu}m range, resulting in band gaps in the 0.5 to 0.8 eV range. However, low band gaps lead to low open circuit voltages ({approximately}0.25 to 0.45 V) caused by high intrinsic carrier concentrations (n{sub i}{sup 2}). Thus, in order to obtain high performance. Photovoltaic cell temperatures must be kept near room temperature. This leads to ...
PURPOSE: Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment thus requiring innovative and effective targeted therapies. The oncogene Astrocyte elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.EXPERIMENTAL DESIGN: IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual Fluorescence in situ hybridization was performed to detect loss of heterozygosity at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in ...
Species interactions research and monitoring was initiated in 1989 to investigate ecological interactions among fish in response to proposed supplementation of salmon and steelhead in the upper Yakima River basin. This is the eighth of a series of progress reports that address species interactions research and pre-supplementation monitoring of fishes in the Yakima River basin. Data have been collected prior to supplementation to characterize the ecology and demographics of non-target taxa (NTT) and target taxon, and develop methods to monitor interactions and supplementation success. Major topics of this report are associated with implementing NTT monitoring prescriptions for detecting potential impacts of hatchery supplementation, hatchery fish interactions, and monitoring fish predation indices. This report is organized into four chapters, with a general introduction preceding the first chapter. This annual report ...
The new guidelines for indoor air hygiene in school buildings are intended as a response to current requirements in school practice. The recommendations aim to help to avoid mistakes in modernising school buildings and to provide hygiene-specific support in planning of new school buildings. The guidelines are laid out as follows: (a) In the general section the targets of the guidelines and the target groups are addressed. The current indoor hygiene situation in German schools is described, followed by the parameters with regard to peripheral issues which will not be dealt with further; (b) Part A deals with the hygiene requirements in the practical running of schools. Besides general requirements for maintenance and operation the important issues of cleaning and ventilation are considered, as well as minor building works; (c) Part B provides an overview of important chemical and biological contaminants in schools; (d) Part ...
In many experiments involving fast neutrons generated in nuclear reactions initiated by accelerator produced charged particle beams, it is important to be able to determine accurately the neutron yield from the target. A detector suitable for such applications should have: a constant efficiency over a large energy range; a fast time response; and the ability to discriminate between gamma rays and neutrons. The authors have constructed a open-quotes black neutron detectorclose quotes based on the design of Poenitz that has these characteristics. At the Lowell Van de Graaff accelerator laboratory neutrons are produced via the "7Li(p,n)"7Be reaction using a pulsed proton beam which impinges on metallic lithium targets. The pulsed beam enables the detector to be used in a time-of-flight spectrometer. Use of BC501 liquid scintillator permits neutron-gamma discrimination. The scintillator is viewed by five RCA 48796 photo tubes. ...
Thermal (gas) nitridation of stainless steel alloys can yield low interfacial contact resistance (ICR), electrically conductive and corrosion-resistant nitride containing surface layers (Cr2N, CrN, TiN, V2N, VN, etc.) of interest for fuel cells, batteries, and sensors. This paper presents results of scale-up studies to determine the feasibility of extending the nitridation approach to thin 0.1mm stainless steel alloy foils for proton exchange membrane fuel cell (PEMFC) bipolar plates. Developmental Fe-20Cr-4V alloy and type 2205 stainless steel foils were treated by pre-oxidation and nitridation to form low-ICR, corrosion-resistant surfaces. As-treated Fe-20Cr-4V foil exhibited target (low) ICR values, whereas 2205 foil suffered from run-to-run variation in ICR values, ranging up to 2x the...
This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and ...
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 ...
No-carrier-added astatine radionuclides produced in the {sup 7}Li-irradiated lead matrix were separated from bulk lead nitrate target by complexing At with insulin, followed by dialysis. The method offers simultaneous separation of At from lead as well as its complexation with insulin. The At-insulin complex might be a potential radiopharmaceutical in the treatment of hepatocellular carcinoma. The stability of At-insulin complex was checked by dialysis against deionized water and Ringer lactate (RL) solution. It has been found that the half-life of At-insulin complex is about {approx}12 h, when dialyzed against deionized water and is only 6 h, when dialyzed against RL solution having the same composition as blood serum. The 6 h half-life of this Insulin-At complex is perfect for killing cancer cells from external cell surfaces as the half-life of internalization of insulin molecule inside the cell is ...
No-carrier-added astatine radionuclides produced in the "7Li-irradiated lead matrix were separated from bulk lead nitrate target by complexing At with insulin, followed by dialysis. The method offers simultaneous separation of At from lead as well as its complexation with insulin. The At-insulin complex might be a potential radiopharmaceutical in the treatment of hepatocellular carcinoma. The stability of At-insulin complex was checked by dialysis against deionized water and Ringer lactate (RL) solution. It has been found that the half-life of At-insulin complex is about #approx#12 h, when dialyzed against deionized water and is only 6 h, when dialyzed against RL solution having the same composition as blood serum. The 6 h half-life of this Insulin-At complex is perfect for killing cancer cells from external cell surfaces as the half-life of internalization of insulin molecule inside the cell is 7-12 h.
We have constructed a 27-kDa hTERT C-terminal polypeptide (hTERTC27) devoid of domains required for telomerase activity and demonstrated that it is capable of nuclear translocation/telomere-end targeting. Here we showed that expression of a low level of hTERTC27 renders hTERT positive HeLa cells sensitive to H(2)O(2)-induced oxidative stress and subsequent cell senescence. The senescence-associated gene, the cyclin/cdk inhibitor p21(Waf1), was up-regulated. This occurs without changing the expression of endogenous hTERT, causing significant telomere shortening or inhibiting telomerase activity. Results from this study suggest for the first time that in addition to telomerase activity, the C-terminus of hTERT also plays a role in hTERT-mediated cellular resistance to oxidative stress. PMID:12565825
Shewanella oneidensis MR-1 is a model environmental organism that possesses diverse respiratory capacities, including the ability to reduce soluble Cr(VI) to sparingly soluble, less toxic Cr(III). Effective bioremediation of Cr-contaminated sites requires knowledge of the molecular mechanisms and regulation of heavy metal resistance and biotransformation by dissimilatory metal-reducing bacteria. Towards this goal, our ERSP-funded work is focused on the identification and functional analysis of genes/proteins comprising the response pathways for chromate detoxification and/or reduction. Previous transcriptomic profiling and whole-cell proteomic analyses implicated the involvement of a functionally undefined DNA-binding response regulator (SO2426) and a putative azoreductase (SO3585) in the chromate stress response of MR-1. Here we describe a detailed functional analysis of SO2426 and SO3585 in order to ...
In attempting to detect and map out underground facilities, whether they be large-scale hardened deeply-buried targets (HDBT's) or small-scale tunnels for clandestine border or perimeter crossing, seismic imaging using reflections from the tunnel interface has been seen as one of the better ways to both detect and delineate tunnels from the surface. The large seismic impedance contrast at the tunnel/rock boundary should provide a strong, distinguishable seismic response, but in practice, such strong indicators are often lacking. One explanation for the lack of a good seismic reflection at such a strong contrast boundary is that the damage caused by the tunneling itself creates a zone of altered seismic properties that significantly changes the nature of this boundary. This report examines existing geomechanical data that define the extent of an excavation damage zone around underground tunnels, and the potential impact on rock ...
This report covers the first year of operation of a fuel cell power plant, installed by PPL Spectrum, Inc. (PPL) under contract with the United States Coast Guard (USCG), Research and Development Center (RDC). The fuel cell was installed at Air Station Cape Cod in Bourne, MA. The project had the support of the Massachusetts Technology Collaborative (MTC), the Department of Energy (DOE), and Keyspan Energy. PPL selected FuelCell Energy, Inc. (FCE) and its fuel cell model DFC{reg_sign}300 for the contract. Grant contributions were finalized and a contract between PPL and the USCG for the manufacture, installation, and first year's maintenance of the fuel cell was executed on September 24, 2001. As the prime contractor, PPL was responsible for all facets of the project. All the work was completed by PPL through various subcontracts, including the primary ...
Radio-biologists have pointed out a novel radiobiological phenomenon observed in many tumor and normal cell lines: hyper-radiosensitivity to very low-dose (H.R.S.) followed by induced radioresistance (I.R.R.) after a threshold dose of 0.1-0.3 Gy that depends on the cell line. Radioresistance at high dose (i.e. higher than 0.5 Gy) and metastatic potential of tumor cells are likely major factors of failure in radiotherapy. A careful review of literature suggests that: 1) radiotherapy does not increase the metastatic potential of tumor cells; 2) radioresistance at high dose and metastatic potential are not related. However, inside a given tumor cell line, highly metastatic clones may elicit more cells showing H.R.S; or are more radiosensitive at high dose than poorly metastatic ones. Recent data obtained from molecular techniques (comet and immunofluorescence ...
Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; ...
Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian ...
Abstract in english BACKGROUND: Severe pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock. OBJECTIVES: To investigate the protective effect of caffeic acid phenethye ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR). METHODS: Fifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma c (more) oncentrations of various cytokines, including TNF-?, IL-1?, IL-1?, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed. RESULTS: The LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain ...
Apoptosis is a pattern of cell death involving nuclear pycnosis, cytoplasmic condensation, and karyorrhexis. Apoptosis induced by continuous irradiation with gamma rays (externally given by a 137Cs source) or with beta rays (from tritiated water injected ip) was quantified in the crypts of two portions of mouse bowel, the small intestine and descending colon. The time-course change in the incidence of apoptosis after each type of radiation could be explained on the basis of the innate circadian rhythm of the cells susceptible to apoptotic death and of the excretion of tritiated water (HTO) from the body. For 6-h continuous gamma irradiation at various dose rates (0.6-480 mGy/h) and for 6 h after injection of HTO of various radioactivities (0.15-150 GBq per kg body wt), the relationships between dose and incidence of apoptosis were obtained. Survival curves were then constructed from the curves for dose vs incidence of apoptosis. For the ...
Schools have increasingly been targeted as appropriate sites for mental health promotion and teachers are considered well placed to identify issues concerning students' social and emotional well-being. Whilst teachers are now expected to be responsive to a wide range of student needs and circumstances, they receive little in their pre-service and subsequent teacher education to adequately prepare them for such realities. This paper reports the findings of a study that investigated teacher perspectives on student mental health and mental health education, including their sense of self-efficacy in relation to promoting and supporting children's mental well-being in schools. These findings highlight a complex interplay between teachers' constructions of 'mental health', the importance they pl...
This study is one element of a larger engineering study effort by WHC to examine the feasibility of irradiated fuel and sludge consolidation in the KW Basin in response to TPA Milestone (target date) M-34-00-T03. The study concludes that up to 11,500 fuel storage canisters could be accommodated in the KW Basin with modifications. These modifications would include provisions for multi-tiered canister storage involving the fabrication and installation of new storage racks and installation of additional decay heat removal systems for control of basin water temperature. The ability of existing systems to control radionuclide concentrations in the basin water is examined. The study discusses requirements for spent nuclear fuel inventory given the proposed multi-tiered storage arrangement, the impact of the consolidated mass on the KW Basin structure, and criticality issues associated with multi-tiered storage.
Abstract Male infertility continues to be a clinical challenge of increasing significance. While male factors such as decreased semen quality are responsible for 25% of all infertility issues, the etiology of suboptimal semen quality is poorly understood. Many physiological, environmental, and genetic factors have been implicated, including oxidative stress. Oxidative stress is induced by reactive oxygen species (ROS), or free radicals, and although ROS are required for critical aspects of sperm function, excessive levels of ROS can negatively impact sperm quality. The origin of ROS generation, and the etiologies of increased ROS in men with suboptimal sperm quality have only recently been elucidated, offering multiple targets for potential therapy. Here, we present a critical review of th...
Coumarin (1,2-benzopyrone) is occurring in food, and is also used in cosmetics. In order to perform a risk assessment for both oral and dermal exposure, we applied a physiologically based approach to model kinetics in humans by simulating both routes of exposure. The concentration-time profile in liver revealed a higher peak concentration (Cmax-hep) for the oral when compared to the dermal route. The area under the concentration-time curve in the liver (AUChep) was found the same for both routes if the same extent of absorption is assumed. Dose response information from published rat studies were used to identify the metric relevant for liver toxicity. Liver exposure levels resulting from doses and durations as outlined in the studies were simulated in a rat model. We obtained 31 data pair...
'Regional climate change: hydrology and land-use' is a topic that is being intensively discussed for quite a while already. At the same time, this topic demands consequences both on the level of politics and other decision makers. We scientists bear a particular responsibility for the analysis of existing data, targeted additional research to fill information gaps, and the critical evaluation and interpretation of the obtained results. The currently gathered sub-population of the scientific community is, albeit small, quite representative of a wide spectrum of activities and can very well offer a deeper insight into the current state-of-the-art. We deliberately organized the contributions such as to offer both overviews and results from detailed projects, as well as a close proximity of very well founded results with rather provocative hypotheses. (orig.)
As the number of devices is increasing in centralized monitoring and control rooms, Ashibetsu Mine of Mitsui Coal Mining Co. has carried out a study on the installation of a computer system for labor savings in the analysis and judgment of operators and for quick and accurate response for emergency in 1984. The target of the first stage was set to centralized monitoring of analog and on-off data using computers. The development plan included: the development of the first stage system of their mine based on the (A/D) 104 connected points and review of problems in 1985: and extension of equipment and revision of the entire system in 1986. The most favorable effect of the system installation is that effective monitoring is possible with display and that the data stored in the computer can be used later. (8 figs, 1 ref)
The marketing strategy developed for use in international markets by the S. M. Group International of Longueuil, Quebec, a company with interest and well-developed expertise in the environmental and energy sector, was described. The strategy is designed to aid in the selection of countries or regions of interest, in determining the sector of activity to be emphasized, in selecting a local partner or local business representatives, and in making contact locally with the people responsible for the development banks in the target countries in an effort to create awareness of the company. The company also tries, wherever possible, to promote its services to local governmental agencies through the industrial cooperation program of CIDA. Since development banks have a very conservative behaviour, past performances and constant provision of high quality services are of prime importance.
Root growth is a highly dynamic process influenced by genetic background and environment. This paper reports the development of R scripts that enable root growth kinematic analysis that complements a new motion analysis tool: PlantVis. Root growth of Arabidopsis thaliana expressing a plasma membrane targeted GFP (C24 and Columbia 35S:LTI6b-EGFP) was imaged using time-lapse confocal laser scanning microscopy. Displacement of individual pixels in the time-lapse sequences was estimated automatically by PlantVis, producing dense motion vector fields. R scripts were developed to extract kinematic growth parameters and report displacement to ?0.1 pixel. In contrast to other currently available tools, Plantvis-R delivered root velocity profiles without interpolation or averaging across the root s...
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...
This thesis deals with the evaluation of Solar Grade Silicon (SoG-Si) purified by different techniques, and also the fabrication and characterization of high efficiency and advanced bifacial solar cells. In the beginning of Chapter 1, various SoG-Si production methods relevant for this work are qualitatively described. The three feedstock materials used in this work are from the Fluidized Bed Reactor (FBR) process, metallurgical feedstock-I and feedstock-II process. In metallurgical feedstock-I, the lifetime of the minority charge carriers in multicrystalline silicon (mc-Si) samples at the grain boundaries are found to be higher than the grains themselves possibly due to lower resistivities in the grain boundaries. The efficiency of the best solar cell obtained using the mc-Si metallurgical feedstock-I is 16.1%. It has been identified that the fast light induced degradation, whose magnitude is lower than that of a reference ...
Abstract High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and ...
Ingestion of HTO during oocyte maturation and continued during pre-implantation time was found to depress decidual response. At birth these offspring also showed a decrease in brain cell number. When HTO was given during pregnancy only, the offspring at birth showed a similar deficit in brain cell number. Even so, we could not demonstrate a gross deficit in oocyte maturation when HTO was ingested during sexual maturity only; however, when further continued during pregnancy, the measured newborn parameters were most severely affected. In this group, cell-multiplication in the cerebrum was severely decreased, protein synthesis was decreased, and somatic growth was also highly significantly decreased. These experiments indicate that even a short-term exposure to HTO during early pregnancy (pre-implantation) alters normal development to such an extent that it is still observable at birth. During embryonic ...
H Power Enterprises of Canada was founded in 1997; currently, it has 40 employees and expect to grow to about 50 by mid-2000. The company is engaged in fuel cell technology development , manufacturing and marketing. The company has the advantage that its technology has been proven, products are already commercialized, and strategic alliances are already in place to make an assault on the market. The concept of proton exchange membrane fuel cell technology is explained in terms of efficiency, response time, power density, stack manufacturing cost, maintenance cost, stack life and compatible thermal loads. Individual products, their energy and operating efficiency, potential applications and potential markets are reviewed. It is estimated that for stationary fuel cells the market will be worth $ 30 billion by 2030. In the United States alone, remote residential cogeneration sites are estimated at 500,000. ...
Bulk nanocrystalline pure iron rods were fabricated by the equal channel angular pressure (ECAP) technique up to eight passes. The microstructure and grain size distribution, natural immersion and electrochemical corrosion in simulated body fluid, cellular responses and hemocompatibility were investigated in this study. The results indicate that nanocrystalline pure iron after severe plastic deformation (SPD) would sustain durable span duration and exhibit much stronger corrosion resistance than that of the microcrystalline pure iron. The interaction of different cell lines reveals that the nanocrystalline pure iron stimulates better proliferation of fibroblast cells and preferable promotion of endothelialization, while inhibits effectively the viability of vascular smooth muscle cells (VSMCs). The burst of red cells and adhesion of the platelets were also substantially suppressed ...
In the advance of fuel cell electric vehicles (EV), hybrid electric vehicles (HEV) can contribute to reduced emissions and energy consumption of personal cars as a short term solution. Trade-offs reveal better emission control for series hybrid vehicles, while parallel hybrid vehicles with different drive trains may significantly reduce fuel consumption as well. At present, costs and marketing considerations favor parallel hybrid vehicles making use of small, high power batteries. With ultra high power density cells in development, exceeding 1 kW/kg, high power batteries can be provided by adapting a technology closely related to consumer cell production. Energy consumption and emissions may benefit from regenerative braking and smoothing of the internal combustion engine (ICE) response as well, with limited additional battery weight. High power supercapacitors may assist the achievement of this goal. ...
Abstract Sam68 (Src-associated protein in mitosis 68-kDa) is a multifunctional protein, known to govern cellular signal transduction, transcription, RNA metabolism, proliferation, apoptosis, and HIV-1 replication. Although intrinsic mechanisms that modulate Sam68 function are beginning to emerge, the regulatory events contributing to its expression remain elusive. We previously reported that heat shock protein-22 (Hsp22) antagonizes Sam68 function in rev-response element (RRE)-mediated gene expression. We now demonstrate that Sam68 levels correlate inversely with Hsp22 in a variety of cells, including U87, Jurkat, 293T, and U-937. In U87 glioblastoma cells, which contained high levels of Hsp22 than other cell lines tested, Hsp22 knockdown dramatically increased both Sam68 mRNA and protein,...
Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-T27) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd++-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous 35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and ...
A new method is being developed to quickly screen for the human exposure potential to polycyclic aromatic hydrocarbons (PAHs) and organochlorines (OCs). The development involves two key elements: identifying suitable signals that represent intracellular changes that are specific to PAH and OC exposure, and constructing a device to guide the biological cell growth so that signals from individual cells are consistent and reproducible. We are completing the identification of suitable signals by using synchrotron radiation-based (SR) Fourier-transform infrared (FTIR) spectromicroscopy in the mid-infrared region (4000-400 cm-1). Distinct changes have been observed in the IR spectra after treatment of human cells in culture medium with PAHs and OCs. The potential use of this method for detecting exposure to PAHs and OCs has been tested and compared to a reverse transcription polymerase chain reaction (RT-PCR) assay that ...
This paper presents a new grid connected inverter for fuel cells. It consists of a two stage power conversion topology. Since the fuel cell operates with a low voltage in a wide voltage range (25 V-45 V) this volt- age must be transformed to around 350-400 V in order to invert this dc power into ac power to the grid. The proposed converter consists of an isolated dc-dc converter cascaded with a single phase H-bridge inverter. The dc-dc converter is a current-fed push-pull converter. A new dedicated voltage mode startup procedure has been developed in order to limit the inrush current during startup. The inverter is controlled as a power factor controller with resistor emulation.Experimental results of converter efficiency, grid performance and fuel cellresponse are shown for a 1 kW prototype. The proposed converter exhibits a high efficiency in a wide power range (higher than 92%) and the inverter ...
BACKGROUND AND PURPOSE Human K2P3.1 (TASK1) channels represent potential targets for pharmacological management of atrial fibrillation. K2P channels control excitability by stabilizing membrane potential and by expediting repolarization. In the heart, inhibition of K2P currents by class III antiarrhythmic drugs results in action potential prolongation and suppression of electrical automaticity. Carvedilol exerts antiarrhythmic activity and suppresses atrial fibrillation following cardiac surgery or cardioversion. The objective of this study was to investigate acute effects of carvedilol on human K2P3.1 (hK2P3.1) channels. EXPERIMENTAL APPROACH Two-electrode voltage clamp and whole-cell patch clamp electrophysiology was used to record hK2P3.1 currents from Xenopus oocytes, Chinese hamster o...
The temperature dependences of the Grueneisen parameter, heat capacity, bulk modulus and linear thermal expansion coefficient of sixteen III-V zincblende compounds are studied by first-principles response-function calculations. The fundamental relationships among these physical parameters are explored. Negative thermal expansions at lower temperature are found in most of these III-V phases except for the nitrides and boron compounds. By analyzing the cell-volume dependences of the phonon spectrum, it is found that the phases with a negative thermal expansion show a significant acoustic phonon weakening at the X-point in their phonon dispersion, while slight weakening is only seen around the L-point for those boron phases. There is no sign of phonon weakening in the nitrides. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)
Protein kinase C activity has been identified in the rat brown adipocyte. About 60% of this activity is found in the cytosolic fraction under basal conditions, and 12-O-tetradecanoylphorbol 13-acetate (TPA) causes a rapid shift from the cytosol to the particulate fraction. Norepinephrine and phenylephrine causes a similar redistribution that can be blocked by prazosin but not by alprenolol. {alpha}{sub 1}-Adrenergic agonists cause three- to fivefold stimulation of type 2 iodothyronine 5{prime}-deiodinase activity in brown adipocytes. TPA has no effect on basal deiodinase activity and reduces the response of the enzyme to {alpha}{sub 1}-adrenergic agonists. These results suggest that the translocation of protein kinase C from cytosol to particulate fraction is not sufficient to increase deiodinase activity but can modulate the {alpha}{sub 1}-adrenergic agonist-mediated responses in these cells.
The class of Spirochetes comprises a wide array of clinically important pathogens, including Treponema pallidum causing syphilis as well as Borrelia burgdorferi, the agent of Lyme disease (LD). Diseases caused by spirochetes are characterized by specific sequelae of host reactions, and also by characteristic antibody response patterns. Over the last decades, research on the interaction of spirochetes with the hosts immune system had a strong emphasis on outer membrane lipoproteins. In fact, these structures have been convincingly shown to activate immune cells via CD14 and Toll-like receptor (TLR)-2, and recent data also indicate an interaction with lipopolysaccharide (LPS)-binding protein (LBP). In particular, the interaction of B. burgdorferi with TLR-2 could not only be demonstrated in ...
In many species social behaviors are dependent on integration of chemosensory and hormonal cues. Many chemosensory stimuli are detected by the vomeronasal organ, which projects to many regions that contain steroid receptors, including the medial amygdala. In male hamsters, testosterone is known to acutely increase in response to chemosensory stimulation, and can facilitate sexual behavior by direct action within the medial amygdala. Conspecific stimuli activate the anterior (MeA) and posterior (MeP) medial amygdala, while heterospecific stimuli activate only MeA. Chemosensory stimuli with different social significance differentially activate the dorsal and ventral subdivisions of MeA and MeP. Therefore, it is likely that steroids differentially facilitate stimulation of the medial amygdala...
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 ...
Thermal (gas) nitridation of stainless steel alloys can yield low interfacial contact resistance (ICR), electrically conductive and corrosion-resistant nitride containing surface layers (Cr{sub 2}N, CrN, TiN, V{sub 2}N, VN, etc.) of interest for fuel cells, batteries, and sensors. This paper presents results of scale-up studies to determine the feasibility of extending the nitridation approach to thin 0.1 mm stainless steel alloy foils for proton exchange membrane fuel cell (PEMFC) bipolar plates. Developmental Fe-20Cr-4V alloy and type 2205 stainless steel foils were treated by pre-oxidation and nitridation to form low-ICR, corrosion-resistant surfaces. As-treated Fe-20Cr-4V foil exhibited target (low) ICR values, whereas 2205 foil suffered from run-to-run variation in ICR values, ranging up to 2 x the target value. Pre-oxidized and nitrided surface structure examination revealed ...
Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all ...
The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the only major protection to astronauts from harmful exposure. Unlike low-linear energy transfer (LET) {gamma} or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure, since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak. The Bragg curve does not necessarily represent the biological damage along the particle traversal, and the 'biological Bragg curve' is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Here we used a unique irradiation geometry to measure the biological response across the Bragg curve in human fibroblasts exposed to 577MeV/nucleon incident Fe ions in vitro. ...
Introduction The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis. Methods Expression of Tumor necrosis factor-alpha (TNF-?) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-? expression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-? and CD8+ cytotoxic T cells in immunofluorescence double staining experiments. Results: 94% (n?=?98/104) of the patients with CRC expressed TNF-?. High TNF-? express...
Abstract A facile and efficient single-step mineralization approach was exploited for achieving nanoscopic hydroxyapatite (HAP) crystal layer in chitosan porous matrix, wherein a mixed water-ethanol solvent was used to control the growth of minerals. The crystallographic structure, morphology, and mechanical properties of the scaffold were analyzed with XRD, FTIR, environmental scanning electric microscopy (ESEM), TEM, and compression tests. The behaviors and responses of MC3T3-E1 pre-osteoblast cells on the scaffolds were studied as well. The results showed that the scaffolds kept woodpile structure with predefined and controlled hierarchical structure after mineralization. The inorganic phase in the mineralized chitosan scaffolds was determined as pure rod-like HAP, which settled densely...
In the paper we investigate a mathematical model describing the growth of tumor in the presence of immune response of a host organism. The dynamics of tumour and immune cells is based on the generic Michaelis-Menten kinetics describing interaction and competition between the tumour and the immune system. The appropriate phenomenological equation modeling cell-mediated immune surveillance against cancer is of the predator-prey form and within a given choice of parameters exhibits bistability. Under the influence of spontaneous weak fluctuations, the model may be analyzed in terms of a stochastic differential equation bearing the form of an overdamped Langevin-like dynamics in the external quasi-potential represented by a double well. We analyze properties of the system within the range of parameters for which the potential wells are of the same depth and when the additional perturbation describing a periodic treatment is ...
A new band gap profile (exponential profile) for the active layer of the a-SiGe:H single junction cell has been designed and experimentally demonstrated. In this paper we compare its optical and electrical characteristics with the two more common profiles: the U- and V-shapes. As predicted by the simulations, the new profile combines the advantages of both profiles. Like the V-shape, the exponential shape reduces the amount of Ge in the i-layer, decreasing both the space charge defect density inside the i-layer and the recombination losses. It also improves the electric field. At the same time, the exponential shape generates the same current density as the U-shape.
Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of cervical carcinoma.
Discovery of better biomarkers for diagnosis, prognosis, and therapy-response prediction is the most critical task of a scientific quest aimed at developing newly designed, tailor-made therapies for patients with cancer. Consequently, a proteome wide analysis, in addition to genomic studies, is an absolute requirement for a complete functional understanding of tumor biology. Ultra-sensitive, high-performance Fourier transform ion cyclotron resonance (FTICR) mass spectrometry (MS) currently holds an important role in fulfilling the demands of biomarker discovery. In this review, we describe the applicability of FTICR MS for breast cancer proteomics, particularly for the analysis of complex protein mixtures obtained from a limited number of cells typically available from clinical specimens.
Cytophotometric measurements of DNA content after Feulgen's reaction and autoradiography after incubation with "3H-thymidine were performed to investigate the early stages of development of yellow lupin root nodule. The first response of the host plant to the contact with Rhizobium lupini was the enhancement of nuclear DNA endoreplication in root cortex cells. A conversion of the initially mixoploid nodule meristem into a diploid one during root nodule formation was found. Differentiation of bacteroid-containing tissue both from diploid and polyploid cells was observed. The highest content of nuclear DNA in the uninfected root cortex, nodule cortex and in bacteroid-containing tissue was 16 C. (author).
Viral infections are still common causes of morbidity and mortality in immunosuppressed patients after allogeneic hematopoietic stem cell transplantation. Infections caused by virus such as cytomegalovirus, adenovirus and Epstein-Barr virus are well-known. In addition, several other viruses such as polyomavirus and human herpesvirus 6 have been recently reported to be causes of significant complications. As the delay in recovery of virus-specific cellular immune response after transplant is associated with viral reactivation and viral disease, adoptive immunotherapy to restore virus-specific cellular immunity is an attractive option. Recent clinical trials showed the safety and effectiveness of adoptive immunotherapy against viral diseases. In this review, we summarize the current status o...
To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL ...
The performance of two-cell planar solid oxide fuel cell stacks using coal syngas, with and without hydrogen sulfide (H{sub 2}S), was studied. All cells were tested at 850 C with a constant current load of 15.2 A (current density of 0.22 A cm{sup -2} per cell) and 30% fuel utilization. The H{sub 2}S injection immediately and significantly affected the power degradation of the stack system regardless of the carrier fuel. Results for the test with only H{sub 2} and N{sub 2} in the presence of H{sub 2}S (119-120 ppm) indicated that the power decay and area-specific resistance (ASR) degradation values were lower than those for the tests where simulated syngas containing CO and increased water content was used. The results indicate that contact points in the stack contributed to the power degradation of the system. Other factors, including contamination from the upstream fuel gas tubing, may have contributed ...
The two-compartment radioassay for microbial kinetics based on continuous measurement of the {sup 14}CO{sub 2} released by bacterial metabolism of 14C-labeled substrate offers a valuable approach to testing the potency of antimicrobial drugs. By using a previously validated radioassay with gram-positive and gram-negative bacteria, a group of protein synthesis inhibitors was evaluated for their effect on microbial growth kinetics. All tested drugs induced changes in both the slopes and intercepts of the growth curves. An exponential growth model was applied to quantify the drug effect on the processes of bacterial {sup 14}CO{sub 2} liberation and cell generation. The response was measured in terms of a generation rate constant. A linear dependence of the generation rate constant on the dose of spectinomycin was observed with Escherichia coli. Sigmoidal-shaped curves were found in the assays of chloramphenicol and tetracycline. The implications ...
Self-grooming in response to the odors of conspecifics is a form of olfactory communication among meadow voles. The amount of time meadow voles spend self-grooming when they encounter the odors of conspecifics varies seasonally, with males targeting the odors of reproductively active females only during the breeding season. Other odor related behaviors in male voles such as odor preferences for conspecifics and the attractiveness of their odors to conspecifics vary seasonally as well. For male meadow voles, these behaviors are mediated by seasonal variations in testosterone (T) and prolactin (PRL) titers. The objective of this study was to determine whether seasonal differences in the amount of time male meadow voles self-groom in response to odors of conspecifics are mediated by seasonal rhythms in their circulating T and PRL titers. We tested the hypothesis that high titers of both T and PRL are necessary for ...
Because every cell within the body has the same genetic information, a significant problem in biology is to understand how cells within a tissue express genes selectively. A sophisticated network of physical and biochemical signals converge in a highly orchestrated manner to bring about the exquisite regulation that governs gene expression in diverse tissues. Thus, the ultimate decision of a cell to proliferate, express tissue-specific genes, or apoptose must be a coordinated response to its adhesive, growth factor, and hormonal milieu. The unifying hypothesis examined in this overview is that the unit of function in higher organisms is neither the genome nor the cell alone but the complex, three-dimensional tissue. This is because there are bidirectional connections between the components of the cellular microenvironment (growth factors, hormones, and extracellular matrix) and the ...
Short synthetic single-stranded oligodeoxyribonucleotides (ssODNs) can be used to introduce subtle modifications into the genome of mouse embryonic stem cells (ESCs). We have previously shown that effective application of ssODN-mediated gene targeting in ESC requires (transient) suppression of DNA mismatch repair (MMR). However, whereas transient down-regulation of the mismatch recognition protein MSH2 allowed substitution of 3 or 4 nucleotides, 1 or 2 nucleotide substitutions were still suppressed. We now demonstrate that single- or dinucleotide substitution can effectively be achieved by transient down-regulation of the downstream MMR protein MLH1. By exploiting highly specific real-time PCR, we demonstrate the feasibility of substituting a single basepair in a non-selectable gene. Howev...
The recent acceleration of effort to elucidate and explore the coordination chemistry of technetium has been prompted mainly by the need for a new generation of radiotracers in nuclear medicine, preferentially for tomograhic studies. Current approaches and their limitations in designing "9"9"mTc complexes capable of penetrating cell membranes of the target organs, and remaining there sufficiently long, are reviewed. With the predominance of Tc(V) oxo compounds, especially for brain imaging agents, new N4 and N2S2 coordinate complexes have been developed by shifting from bidentate to tetradentate ligands with a variable side chain or other adjustable reactivity. The search for myocardial imaging agents has focused on a variety of mixed ligand complexes of Tc(III) and most promising [Tc(CNR)_6]"+ complexes of Tc(I). 64 refs. (author).
Positron emission tomography (PET) is the gold standard for non-invasive assessment of myocardial viability and allows accurate detection of coronary artery disease by assessment of myocardial perfusion. Magnetic resonance imaging (MRI) provides high resolution anatomical images that allow accurate evaluation of ventricular structure and function together with detection of myocardial infarction. Potential hybrid PET/MR tomography may potentially facilitate the combination of information from these imaging modalities in cardiology. Furthermore, the combination of anatomical MRI images with the high sensitivity of PET for detecting molecular targets may extent the application of these modalities to the characterization of atherosclerotic plaques and to the evaluation of angiogenetic or stem cell therapies, for example. This article reviews studies using MRI and PET in parallel to compare their performance in cardiac applications together with the ...
Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ?50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyd...
Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracel...
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
Two candidate small interfering RNAs (siRNAs) corresponding to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike gene were designed and in vitro transcribed to explore the possibility of silencing SARS-CoV S gene. The plasmid pEGFP-optS, which contains the codon-optimized SARS-CoV S gene and expresses spike-EGFP fusion protein (S-EGFP) as silencing target and expressing reporter, was transfected with siRNAs into HEK 293T cells. At various time points of posttransfection, the levels of S-EGFP expression and amounts of spike mRNA transcript were detected by fluorescence microscopy, flow cytometry, Western blot, and real-time quantitative PCR, respectively. The results showed that the cells transfected with pEGFP-optS expressed S-EGFP fusion protein at a higher level compared with those transfected with pEGFP-S, which contains wildtype SARS-CoV spike gene sequence. The green fluorescence, mean ...
The patients studied were referred for routine abscess localization with indium-111 labelled autologous leukocytes. One series (n=15) was studied at 1 day after reinjection of labelled cells and a second series (n=9) was studied between 4 hours and 4 days after reinjection of labelled cells. The leukocytes were isolated by a gravity sedimentation method and labelled with In-111 oxinate according to Roevekamp and co-workers. The labelled cell suspension administered to the patient contained between 11 and 15 MegaBq (300-400 microCi). The indium-111 concentration in the liver and spleen was quantitated using a scintillation camera and an on-line computer system. Phantom studies were carried out to obtain conversion factors from geometric mean counts to MegaBq of activity for both liver and spleen. Once determined, the amount of activity in liver and spleen was corrected for physical decay of In-111 and expressed as a ...
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 ...
In situ assembly states of rat adipocyte glucose transport protein in plasma membrane (PM) and in microsomal pool (MM) were assessed by measuring target size (TS) of D glucose-sensitive, cytochalasin B binding activity. High energy radiation inactivated the binding in both PM and MM by reducing the total capacity of the binding (B/sub T/) without affecting the dissociation constant (K/sub D/). The reduction in B/sub T/ as a function of radiation dose was analyzed based on classical target theory, from which TS was calculated. TS in the PM of insulin-treated adipocytes was 58 KDa. TS in the MM of noninsulin-treated and insulin-treated adipocytes were 112 and 109 KDa, respectively. With MM, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses showing a shoulder in the semilog plots, which may be due to an interaction with a radiation sensitive inhibitor. With these results, they propose the following ...
Radioactive ion beams (RIBs) of short-lived isotopes of fluorine are in demand for investigating astrophysical phenomena related to the hot CNO cycle and rp processes responsible for stellar nucleosynthesis. Since negative ion beams are required for injection into tandem electrostatic accelerators, such as the 25 MV tandem accelerator used for post acceleration of RIBs for the Holifield Radioactive Ion Beam Facility (HRIBF) research program at the Oak Ridge National Laboratory (ORNL), efficient, direct-formation F{sup -} ion sources are highly desirable for RIB applications involving this type of post-accelerator. We have conceived and evaluated a direct extraction F{sup -} source for potential RIB applications which is predicated on the reverse polarity operation of a positive electron-beam-plasma target/ion source (EBPTIS) while simultaneously feeding fluorine rich compounds and Cs vapor into the source. The source is found to operate in two ...
Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. We demonstrated that the up-regulation of Redd1 transcription by hypoxia and high cell density (HCD) depends on cooperation between Sp1 and HIF-1#alpha# downstream of the PI3K/Akt pathway.
Macroautophagy is a multistep, vacuolar, degradation pathway terminating in the lysosomal compartment, and it is of fundamental importance in tissue homeostasis. In this review, we consider macroautophagy in the light of recent advances in our understanding of the formation of autophagosomes, which are double-membrane-bound vacuoles that sequester cytoplasmic cargos and deliver them to lysosomes. In most cases, this final step is preceded by a maturation step during which autophagosomes interact with the endocytic pathway. The discovery of AuTophaGy-related genes has greatly increased our knowledge about the mechanism responsible for autophagosome formation, and there has also been progress in the understanding of molecular aspects of autophagosome maturation. Finally, the regulation of au...
Two hypotheses are in the centre of this investigation, on the one hand the question, whether microwaves as exogenous fields alone are able to stimulate human muscle cells above-threshold, and on the other hand, whether microwaves as conditioning to cathodical electrical pulses can modify the excitation threshold and form. No excitation through the application of microwaves alone can be introduced at any subject. The conditioning of above-threshold cathodical electrical pulses with UMTS-microwaves leads not to a transgression of the threshold or the electrical muscle response (EMG) depending on the amplitude, the duration or the dose rate. (orig.)
The autoradiographic appearance of the gastric mucosa, 5 hours after administration of indomethacin, was investigated in 29 adult rats. Indomethacin induced superficial gastric erosions. Autoradiography demonstrated the presence of viable gastric cells (as deduced by their ability to incorporate 3H-cytidin, an RNA precursor) not only in the mucosa without erosions, but also in the mucosa underneath the superficial erosions. The results indicate that indomethacin induced gastric erosions are not the superficial expression of a necrotic process taking place in the full thickness of the gastric mucosa at a particular site. A lumen-borne mechanism appears to be responsible for the formation of erosive areas in the mucosa.
In this paper we describe a Ni-Sn intermetallic material obtained via template electroplating synthesis. The structure and the morphology of this material are investigated by X ray diffraction (XRD) and Scanning Electron Microscopy (SEM) analyses. We demonstrate that Ni-Sn behaves as a sub-micrometric electrode showing a favourable response when cycled in a lithium cell. The results here reported suggest that the template electroplating is a promising synthetic approach that can lead to an optimized structure and morphology of the Ni-Sn electrode, such as to confer it a role of a high capacity anode in advanced lithium ion batteries.
Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low ...
Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the ...
The aim of the present study was to test a mathematical model of the biochemical processes in the parathyroid glands responsible for the secretion of parathyroid hormone resulting from extracellular calcium reduction. A double exponential curve described the parathyroid hormone secretion induced by rapid lowering of blood-ionized calcium in humans with normal as well as abnormal parathyroid tissue. Our data show that it was possible to establish a simple mathematical model of the parathyroid hormone response to blood-ionized calcium lowering, sufficient to fit experimental data obtained from patients with abnormal and normal parathyroid tissue. The fitted parameters showed no significant differences between patients with insulin-dependent diabetes mellitus and controls. In primary hyperparathyroidism, the parathyroid hormone production and steady-state transport across the cell membrane were increased, probably due to the ...
The IRG protein Irgm3 preserves cell survival during coxsackievirus B3 (CVB3) infection. However, the molecular mechanisms are not clear. Here, we examined the effect of Irgm3 expression on ER stress triggered by pharmacological agents or CVB3 infection. In Tet-On/Irgm3 HeLa cells, Irgm3 expression suppressed either chemical- or CVB3-induced upregulation of glucose-regulated protein78. Further, Irgm3 strongly inhibited the activation of both the PERK and ATF6 pathways of ER stress responses, which further led to the diminished phosphorylation of eIF2?, reduced cleavage/activation of transcription factor SREBP1 and attenuated induction of proapoptotic genes CHOP and GADD34. These data were further supported by experiments using Irgm3 knockout mouse embryonic fibroblasts, in which the ER stress induced by CVB3 was not relieved due to the lack of Irgm3 expression. In addition, the tunicamycin-triggered ER stress promoted the ...
We carried out a feeding study in rats aimed at extending our aboservations of contaminant-induced immunosuppression in harbour seals. Two herring batches were freeze-dried, supplemented and fed to female adult PVG rats for a period of 4 1/2 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD{sub 4}{sup +}/CD{sub 8}{sup +} cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD{sub 4}{sup +}/CD{sub 8}{sup +} ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cellresponse to rat ...
Triphenylmethylphosphonium (TPMP+) partitions into the mitochondrial and cytosolic compartments in the rat white adipocyte in a potential-dependent fashion. The relationship between (/sup 3/H)TPMP+ distribution, intracellular cAMP generation and lipolysis in response to hormones and cAMP-mimetic compounds was examined. Half-maximal (/sup 3/H)TPMP+ efflux and glycerol release were produced by 15 and 9 nM adrenocorticotropin, 170 and 110 nM 1-epinephrine, 70 and 27 microM isobutylmethylxanthine and 800 and 750 microM dibutyryl cAMP, respectively. Hormone-stimulated cAMP generation was also correlated with (/sup 3/H)TPMP+ efflux and lipolysis in terms of concentration dependency. In kinetic experiments, glycerol release and (/sup 3/H)TPMP+ efflux in response to adrenocorticotropin or cholera toxin proceeded over a similar time course, whereas an earlier rise in cAMP generation was detected. The depolarizing effect of lipolytic compounds was ...
To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39-89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0-64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. The median follow--up time was 62 months (2-202 months).The 5-year overall survival, locoregional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, ...
The uncoupling protein (UCP) is a proton/anion transporter found in the inner mitochondrial membrane of brown adipocyte. Although UCP has nor been detected in mitochondria from any other tissue, it shares structural and catalytic properties with several other mitochondrial carrier proteins. Although UCP was discovered only recently it is one of the most extensively studied mitochondrial carrier proteins.More recently, the mouse, rat, and human genes encoding for UCP have been isolated and sequenced. The availability of these various tools has led to several significant observations. UCP gene expression is strongly controlled at the level of transcription by signals that are activated after the stimulation of brown adipocytes by norepinephrine. The comparison of UCP gene with the genes encoding the adenine nucleotide translocator revealed the existence of structural and evolutionary homologies. Moreover, in humans the UCP gene and one form of adenine nucleotide translocator gene are ...
Electron beam therapy of lesions such as cutaneous metastatic carcinoma and reticulum cell sarcoma is performed via multiple portals for a wide irradiation field. However, the dose distribution in border areas is generally uneven, resulting in hot and cold dose areas depending on the intervals of the portals. We performed electron irradiation by the pendulum technique, especially on curved areas, and evaluated the technique in various respects. Pendulum electron beam irradiation is indicated when the length of the cone must be reduced in order to deliver the target volume near the skin surface as well as to avoid the occurrence of hot spots deep in the body. We prepared a 15cm rotating cone by cutting a 30cm fixed irradiation cone. The modification posed no disadvantages in terms of extent and flatness of the beam, or stability during rotation. After determining the relationship between the rotation speed and the dose, the technique was ...
The expanding plasma produced when an intense pulse of laser radiation is focused in vacuum onto a solid target has been used as a source of highly stripped ions for collision cross-section measurements. Usable fluxes of carbon nuclei at energies of a few hundred eV/charge have been obtained by irradiation of graphite with pulses of CO"2 laser radiation at a focused power density of 3 x 10_1_0 W/cm_2. Bombardment of aluminum and iron targets at comparable power levels have yielded ions of maximum charges of 9 and 16 respectively. A time-of-flight apparatus has been constructed to utilize the laser source for measurement of electron capture cross sections for highly stripped ions in gases at energies in the few hundred eV/charge range. Apertures collimate an ion beam from the plasma blowoff, and an electrostatic analyzer selects ions from the expanding plasma which have the same energy per charge. The beam is directed through a gas ...
The stunning, intricate interaction between the visual, vestibular and optomotor systems--each a miracle on its own--ensures maintenance of orientation in space as well as visual recognition and target selection despite a host of sensory conflicts and adversary disturbances. Their main goals are to keep a target of interest on the fovea by either maintaining or shifting the direction of gaze in order to produce an accurate internal representation of the visual surroundings, in particular the selected target, and to continuously mirror the spatial relationship between these various visual elements and the self. Not surprising, the implementation of this host of elaborate neural networks encompasses almost every part of the brain, including the brainstem, cerebellum, extrapyramidal system and many areas of the cerebral cortex. Thus far, these systems are among the best investigated in brain research; and enormous knowledge ...
Expression of IGF-2 and changes in its expression in response to systemic endocrine alterations have not been demonstrated for adipocytes. Adipocytes were induced to develop within cultures of 3T3-L1 cells using a medium containing 0.5mM isobutylmethylxanthine, 1uM insulin and 100ng hydrocortisone/ml for 48 hours of exposure. Cultures containing developing adipocytes were incubated with 10% pig serum and 1 uM insulin for several days. The resultant adipocyte cultures were then treated with either 10% pig serum, diabetic pig serum or hypophysectomized pig serum in DMEM for 48 hours. Adipocytes within the cultures were separated from undifferentiated cells using percoll density gradient centrifugation. Total RNA was isolated from adipocytes and dot blotted. Blots were probed with a {sup 32}P-cDNA probe for rat IGF-2. IGF-2 was expressed by the adipocytes and the pattern of expression showed specific differences between serum ...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to ...
We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and ...
Full text: The general population is daily exposed to chronic, low doses of ionizing radiation (IR) from both natural and artificial sources. The biological consequences of acute, high dose IR exposure can be readily determined; however, the nature and significance of low dose, low dose-rate IR effects are still the subject of debate. Confounding the issue, are the phenomena collectively referred to as the Radiation-induced Bystander Effect (RIBE). The RIBE describes a collection of in vitro observations that suggest the presence of a soluble, transmissible factor(s) released from irradiated cells that can induce a biological response in un-irradiated cells. The induction, nature and magnitude of the RIBE varies between cell culture systems, radiation sources and end-points measured. Efforts to confirm the presence of the RIBE in vivo have been confined to in vivo-like culture systems and limited work ...
The cytotoxicity of 15-nm and 46-nm silica nanoparticles was investigated by using crystalline silica (Min-U-Sil 5) as a positive control in cultured human bronchoalveolar carcinoma-derived cells. Exposure to 15-nm or 46-nm SiO_2 nanoparticles for 48 h at dosage levels between 10 and 100 #mu#g/ml decreased cell viability in a dose-dependent manner. Both SiO_2 nanoparticles were more cytotoxic than Min-U-Sil 5; however, the cytotoxicities of 15-nm and 46-nm silica nanoparticles were not significantly different. The 15-nm SiO_2 nanoparticles were used to determine time-dependent cytotoxicity and oxidative stress responses. Cell viability decreased significantly as a function of both nanoparticle dosage (10-100 #mu#g/ml) and exposure time (24 h, 48 h, and 72 h). Indicators of oxidative stress and cytotoxicity, including total reactive oxygen species (ROS), glutathione, malondialdehyde, and lactate ...
Early effects of 100 Kilorads of X-rays on muscle cell membrane properties have been measured in sartorius muscles from Leptodactylus ocellatus. Threshold strength for rectangular current pulses increased 10% after irradiation, and action potential propagation velocity decreased 10%. Passive membrane parameters were calculated from potential responses to sub-threshold current pulses, assuming conventional cable theory. Specific membrane conductance increased to 18% after irradiation, membrane capacitance increased 14%, and length constant decreased 10% but membrane time constant was unchanged. Cell diameter decreased 5%, and resting membrane potential decreased 8%. Membrane parameters during an action potential were also evaluated by the phase-plane and current-voltage plot techniques. Irradiation significantly decreased the action potential amplitude, the excitation potential, and the maximum rates of rise and fall of ...
Active oxygens produced by low-dose irradiation can induce the synthesis of proteins involved in the active oxygen reduction path and can activate the chemical self-defense mechanisms in vivo, which can alleviate the injuries caused by active oxygens themselves. The following findings suggests that it is not only by low-dose irradiation that can induce the responses described above but also by any physical and/or chemical stresses which can produce small amount of active oxygens in vivo. 1. X-irradiation with 0.5 Gy and/or water immersion and restraint induced heat shock protein (HSP)70 in rat stomach cells. HSP70 was also induced in adrenal cells by paraquat administration. 2. The SOD activity in pancreas of rat significantly increased by #gamma#-irradiation with 0.5 Gy. 0.5 Gy irradiation preceeding the alloxan administration significantly suppressed the increase in pancreatic lipid peroxides and in blood glucose levels, ...
Lectin is a generic name of sugar binding protein in living organisms. With an objective to clarify physiological functions of lectin in marine invertebrates and utilize it as a useful material in the bio-chemical industry, studies were carried out on the chemical structure, distribution in living organisms and structural changes of lectin. Lectin is involved with such physiological actions as immunity reactions, generation and differentiation, Ca fixation and symbiosis. Lectin is one of the main components of lymph fluid in shellfish and crustacean, and is a multi-functional polymer that is related with foreign substance recognition, Ca transport, and shell formation. Lectin of a certain kind shows strong actions to accelerate cell division. Organs and cells were cultivated for lectin producing organs and lectin producing cells to verify the production thereof. Elucidation was attempted in a molecular level on such ...
An axisymmetric unit cell model based on a regular array of second-phase particles arranged on a BCC lattice is used to study deformation mechanisms of ferrite-pearlite structural steels. Microstructural characteristics of the steels were parameterized by the pearlite volume fraction, the aspect ratio of the pearlite particles, and the neighboring factor, which represents the ratio of interparticle spacing in the longitudinal direction to that in the transverse direction. FE analyses were carried out to investigate the macroscopic and microscopic response of unit cells with morphological features based on idealizations of the microstructures of the actual steels. Tensile properties of each constituent phase were obtained experimentally and used in the analyses. As compared to traditional axisymmetric models, the BCC tell model appears to be able to capture more realistically the behavior of the materials, and it accurately ...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...
The composite of doped lanthanum gallate (La_0_._9Sr_0_._1Ga_0_._8Mg_0_._2O_2_._8_5, LSGM) and doped ceria (Ce_0_._8Sm_0_._2O_1_._9, CSO) was investigated as an electrolyte for solid oxide fuel cell (SOFC). The LSGM-CSO composite was examined by X-ray diffraction (XRD) and impedance spectroscopy. It was found that the sintered LSGM-CSO composite contains mainly fluorite CeO_2 phase and a minority impurity phase, Sm_3Ga_5O_1_2. The LSGM-CSO composite electrolyte shows a small grain boundary response in the impedance spectroscopy as compared to LSGM and CSO pellets. The composite electrolyte exhibits the highest conductivity in the temperature range of 250-600 "oC, compared to LSGM and CSO. The LSGM-CSO composite can be expected to be an attractive intermediate temperature electrolyte material for solid oxide fuel cells.
The photobiology of mouse melanocyte lines with different pigment genotypes was studied by measuring colony-forming ability after irradiation. The cell lines were wild-type black (melan-a) and the mutants brown (melan-b) and albino (melan-c). Four lamps emitting various UV wavelengths were used. These were germicidal (UVC, 200-280 nm), 82.3% output at 254 nm, TL01 (UVB, 280-320 nm), 64.2% at 310-311 nm, FS20, broadband with peak output at 312 nm and Alisun-S (UVA, 320-400 nm), broadband with peak output at 350-354 nm. Appropriate filtration reduced the contaminating UVC to nonlethal levels for the longer waverange lamps. It is clear from these studies that, in pigment cells, monochromatic results cannot predict polychromatic responses and that cell death from solar irradiations is a complex phenomenon that depends on more than DNA damage. (author).
Boron Neutron Capture Therapy (BNCT) is a promising binary treatment modality for high-grade primary brain tumors (glioblastoma multiforme, GM) and other cancers. BNCT employs a boron-10 containing compound that preferentially accumulates in the cancer cells in the brain. Upon neutron capture by {sup 10}B energetic alpha particles and triton released at the absorption site kill the cancer cell. In order to gain penetration depth in the brain Fairchild proposed, for this purpose, the use of energetic epithermal neutrons at about 10 keV. Phase I/II clinical trials of BNCT for GM are underway at the Brookhaven Medical Research Reactor (BMRR) and at the MIT Reactor, using these nuclear reactors as the source for epithermal neutrons. In light of the limitations of new reactor installations, e.g. cost, safety and licensing, and limited capability for modulating the reactor based neutron beam energy spectra alternative neutron sources are being ...
Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was ...
High quality "3"1P MR spectra (signal to noise ratio (S/N) approximately 18, 15 min acquisition for each spectrum) were consistently obtained with surface coils over a period of 6-week RT. Both transient and steady state alterations in metabolites in response to RT were found in this case. The transient changes occurred during the first 3 hr immediately after the 3rd fractionated RT, these changes include the transient elevation of the PCr resonance, a decrease in PDE and an increase in intracellular pH. The monitoring showed that the metabolites approached steady state approximately 2 hr after the fractionated radiation intervention, suggesting that in vivo MRS can be useful for studying the dynamics of tumor response to RT such as repair of potential lethal damage, growth delay, and reoxygenation etc. The steady-state MR spectra showed the net response to each intervention and can clinically be useful for predicting and ...
Based on the practical condition of the plant and in reference to advanced management experiences worldwide, Daya Bay Nuclear Power Plant has established its own peculiar management system for radiation protection management and ALARA implementation. The characteristics of the system are: radiation protection training to all workers, active involvement of all managers and staffs, and whole process safety control to maintenance activities. The management philosophy of 'workers are responsible for their own radiation safety' is adopted in the plant. A strict, formalized and systematic whole staff radiation protection training, evaluation, authorization and periodically refreshing mechanism had been established and executed in the plant. In the organizational point of view, the responsibilities of line managers were specified in plant procedures, ALARA coordination organization on plant level and for specific activities were established. ...
Combinations of exposure concentrations, durations and frequencies were tested in four-week inhalation exposures followed by two weeks of recovery to define the interactive effects of these variables on biologic responses and to select the most-sensitive biologic response parameters for the subsequent subchronic studies. Response surface modeling was used for the experimental design and statistical analysis of the data. Results of preliminary testing suggested that exposure duration and frequency did not have major effects. Subsequently, male and female Sprague-Dawley rats were exposed in separate studies to RP/BR aerosols ranging from 0.40 to 1.20 mg/1 or to filtered air for 2.25 hr/day on four days/week for four weeks. Test-atmosphere monitoring data demonstrated that aerosol concentrations were consistently within 4% of the target values and mean particle size ranged from 0.44-0.64 ..mu..m with mean ...
Lithium metal-polymer electrolyte batteries with improved utilisation of the active material at a moderate-low temperature (65degC) were realised. Low molecular weight poly(ethylene glycol) (PEG, MW=2000) was used as the lithium-ion conductive matrix in the composite cathode. The cathode active material was crystalline V{sub 2}O{sub 5}. A blend of poly(ethylene oxide) (PEO, MW=4x10{sup 6}) and PEG was used as a solid polymer electrolyte (SPE). The transport properties of the SPE were evaluated at various temperatures. A specific conductivity as high as 1.0x10{sup -4} S cm{sup -1} was calculated at 45degC. The temperature dependence of the interfacial resistances between lithium/SPE and cathode material/PEG was evaluated. The lithium/SPE interfacial resistance decreases linearly with the temperature. The charge transfer resistance between cathode material and PEG reaches a minimum at 60degC and it does not decrease with a further temperature increase. The data clearly show that the ...
We have observed significant differences in the response to ionizing radiation of two closely related human cell lines, and now compare the effects on these lines of both low and intermediate LET radiation. Compared to TK6, WTK1 has an enhanced X-ray survival, and is also more resistant to cell killing by {alpha}-particles. The hprt locus is more mutable in WTK1 than in TK6 by both X-rays and {alpha}-particles. WTK1 is also more mutable by {alpha}-particles than by X-rays at the hprt locus. X-ray-induced mutation at the heterozygous tk locus in WTK1 is about 25 fold higher than in TK6, while {alpha}-particle-induced mutation is nearly 50 fold higher at this locus. Also, the slowly growing tk- mutants, which comprise the majority of spontaneous and X-ray-induced tk- mutants of TK6, were not induced significantly by {alpha}-particles. Previously, we showed that TK6 has a reduced capacity for recombination compared with WTK1, ...
Callus cultures derived from pith tissue of Nicotiana tobacum were grown on two media either under continuous illumination or in complete darkness. The first medium limited greening ability of callus grown in the light (3 milligrams per liter naphthalene acetic acid, 0.3 milligram per liter 2-isopentenylaminopurine, Murashige and Skoog salts, and 2% sucrose). The second medium encouraged chlorophyll synthesis (greening) though not shoot formation (0.3 milligram per liter naphthalene acetic acid; 0.3 milligrams per liter 2-isopentylaminopurine). To measure intracellular concentrations, calli were grown for 15 days on these standard media containing (U-/sup 14/C)sucrose. The dry weight proportions of the calli (as a fraction of fresh weight) and many metabolite concentrations nearly doubled in light-grown cells compared to dark-grown cells and increase 30 to 40% on low-auxin media relative to high-auxin media. Glutamine concentrations (from 4 to ...
Two window layer materials, Al{sub 0.51}In{sub 0.49}P (E{sub g} = 2.3 eV) and Ga{sub 0.51}In{sub 0.49}P (E{sub g} = 1.88 eV) were compared for gas-source and solid-source MBE grown GaAs and Ga{sub 0.84}In{sub 0.16}As{sub 0.68}P{sub 0.32} (E{sub g} = 1.55 eV) solar cells. Due to the wider band-gap of Al{sub 0.51}In{sub 0.49}P, the increased spectral response was observed for both GaAs and Ga{sub 0.84}In{sub 0.16}As{sub 0.68}P{sub 0.32} material based solar cells. In the case of the GaAs cells, the short-circuit current density was observed to increase from 32.5 mA/cm{sup 2} to 34.4 mA/cm{sup 2} with the Al{sub 0.51}In{sub 0.49}P window layer at AM0. Similar improvement was observed for the Ga{sub 0.84}In{sub 0.16}As{sub 0.68}P{sub 0.32} solar cells.
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA ...
A new type of zinc electrode is matched with new bifunctional air electrodes to produce a zinc-air battery of a novel design. The zinc electrode is a flow-thru type made from copper foam-metal. The air electrode uses corrosion resistant carbon black as a high area support for a highly dispersed spinel oxide electrocatalyst. The battery design employs flowing electrolyte, 12 M KOH saturated or supersaturated with zincate. Single cells as large as 200 cm{sup 2} (1/5 EV design scale) having a capacity of 20 AH have been tested with C/4--C/16 constant current cycling. More extensive and realistic life cycle testing was done with 2 Ah cells, including the Simplified Federal Urban Driving Schedule (SFUDS) cycle. This testing has confirmed that these cells can provide the necessary transient power response required for urban EV applications. The cells achieved an average of 72 SFUDS ...
We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to ...
The present study was undertaken to determine the involvement of calcium-protein kinase C pathway in the mechanism of action of Escherichia coli heat stable enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human colonic carcinoma cell line COLO-205, which was used as a model cultured cell line to study the mechanism of action of E. coli STa. In response to E. coli STa, protein kinase C (PKC) activity was increased in a time-dependent manner with its physical translocation from cytosol to membrane. Inhibition of the PKC activity in membrane fraction and inhibition of its physical translocation in response to IP_3-mediated calcium release inhibitor dantrolene suggested the involvement of intracellular store depletion in the regulation of PKC activity. Among different PKC isoforms, predominant involvement of calcium-dependent protein kinase C (PKC#alpha#) was specified using ...
Thin film solar cells and solar cell testing - photovoltaic cells, radiation damage to cadmium sulfide solar cells, and airplane testing of solar cells
There is a lot of interest in the studies that would help to understand whether there is a casual association between cancer and various types of molecular or cytogenetic damage detected in human cells. One major oncogenesis process is activation of proto-oncogenes by point mutations or chromosomal translocation. There are substantial evidence that indicates that the loss of heterozygosity of certain chromosomes is involved in human cancerogenesis. Our study aimed to elicit the possible association between cancer and DNA and cytogenetic abnormalities induced in lymphocytes of people bearing various categories of skin cancer cells. Fresh blood was collected by venipuncture from 25 individuals (including nine prior to cancer treatment). All patients were nonsmoking males, however 42.3 % of them were former smokers. Blood samples were divided into two parts and in the first part of samples cytogenetic studies were performed immediately, while from ...
The quasi-static normal indentation of sandwich panels with quasi-isotropic laminated composite skins and honeycomb or foam cores, by spherical indentors, has been investigated using experiments and finite element analysis. The experimental program emphasized the effects of indentor size on the resulting load indentation responses, failure mechanisms in the skin and the core, and the measurement of contact areas between indentor and the target. The sandwich panels were indented up to the initiation of skin fracture and the resulting contact data was used to characterize contact power laws. A non-linear finite element model was developed based on the experimental observations to systematically explore the indentation behavior of diverse sandwich configurations and to investigate the contact pressure distributions. The finite element model was used as an experimental tool in the development of a simple non-dimensional semi-empirical model that ...
The Thai natural rubber economy is described in the context of the world rubber market. An econometric model is estimated for 15 structural equations; it includes the Thai, US, and rest-of-the-world rubber economies. Several simulation experiments are analyzed for the period from 1984 to 1995. Impact and dynamic multipliers are reported for major endogenous variables in response to changes in US GDP, world crude oil price, Thai replanting cess tax and Thai natural rubber production. A 1%, one-time increase in the US GDP has a positive effect on the Singapore natural rubber price. A world crude oil price decline shock has a negative effect in both the short-run and the long-run. The INRO buffer stock stabilization policy as well as alternative domestic Thai policies of market intervention are analyzed. The simulation results show that buffer stock management which allows a price band of +/-20% around the price target has the most stabilized ...
The purpose of this program was to characterize Time Of Arrival Detectors (TOAD) pins response to shock loading with respect to risetime, amplitude, repeatability and consistency. TOAD pins were subjected to impacts of 35 to 420 kilobars amplitude and approximately 1 ms pulse width to investigate the timing spread of four pins and the voltage output profile of the individual pins. Sets of pins were also aged at 45{degrees}, 60{degrees}, and 80{degrees}C for approximately nine weeks before shock testing at 315 kilobars impact stress. Four sets of pins were heated to 50.2{degrees}C (125{degrees}F) for approximately two hours and then impacted at either 50 or 315 kilobars. Also, four sets of pins were aged at 60{degrees}C for nine weeks and then heated to 50.2{degrees}C before shock testing at 50 and 315 kilobars impact stress, respectively. Particle velocity measurements at the contact point between the stainless steel targets and TOAD pins were ...
The existence, in real-time, of transmission constraints, demand forecasting errors, generator failures, and other factors impose additional costs through the need to run more expensive generation. These costs can appear as a significant component of the wholesale price to demand served by electricity markets operated over transmission networks. In the England & Wales Pool these costs are passed through directly to supply companies. The Transmission System Operator ({open_quotes}TSO{close_quotes}) can exert significant influence on these costs through improved availability of transmission circuits and through appropriate investment, but has no incentive to do so. Since the inception of the Pool, these costs have increased in level and volatility, and have proved difficult to hedge. In response, St Clements Services were instrumental in assisting Pool members to develop an {open_quotes}Uplift Incentive Management Scheme{close_quotes} which has seen controllable ...
Sputter-deposited tantalum (Ta) and reactively sputter-deposited Ta-nitride films were studied with respect to the passivation capability against copper (Cu) oxidation in thermal O{sub 2} ambient. A 200 {angstrom} Ta or Ta-nitride film was sputter-deposited on a 2,000 {angstrom} Cu film using a Ta target in an Ar/N{sub 2} gas mixture. With Ta passivation, Cu was not oxidized at temperatures up to 400 C, which can be further improved by using passivation of an amorphous Ta-nitride film deposited in an appropriate condition. The absence of long-range defects in the Ta-nitride film was presumably responsible for this improvement. However, sputtering-induced surface damage by excess N{sub 2} in the sputter gas mixture may reduce the passivation capability of Ta-nitride films. When the passivated Cu was oxidized, the Cu oxides always resided in the top surface region. That is, in the oxidation process, Cu diffused through the defects of the ...
The goal of this project is to improve energy efficiency of industrial crushing and grinding operations (comminution). Mathematical models of the comminution process are being used to study methods for optimizing the product size distribution, so that the amount of excessively fine material produced can be minimized. The goal is to save energy by reducing the amount of material that is ground below the target size, while simultaneously reducing the quantity of materials wasted as ''slimes'' that are too fine to be useful. This is being accomplished by mathematical modeling of the grinding circuits to determine how to correct this problem. The approaches taken included (1) Modeling of the circuit to determine process bottlenecks that restrict flowrates in one area while forcing other parts of the circuit to overgrind the material; (2) Modeling of hydrocyclones to determine the mechanisms responsible for ...
MicroRNAs (miRNAs) are small non-coding RNAs that play vital roles in plant abiotic stress responses via cleavage or translational inhibition of their target mRNAs. Populus euphratica is a typical stress-resistant sessile organism that grows in desert areas. Here, we identified sequences of 12 miRNA precursors from 11 families and 13 mature miRNAs from 12 families by PCR amplification in P. euphratica. To detect expression differences in mature miRNAs and their precursors under dehydration and high salinity shock in P. euphratica, we examined 14 miRNA precursors from 13 miRNA families and 17 mature miRNAs from 17 miRNA families using the SYBR Green RT?PCR assay. This is the first report of expression profiles for both precursor and mature miRNAs in P. euphratica. By profiling both the matu...
The GTPases comprise a protein superfamily of highly conserved molecular switches adapted to many diverse functions. These proteins are found in all domains of life and often perform essential roles in fundamental cellular processes. Analysis of data from genome sequencing projects demonstrates that bacteria possess a core of 11 universally conserved GTPases (elongation factor G and Tu, initiation factor 2, LepA, Era, Obg, ThdF/TrmE, Ffh, FtsY, EngA and YchF). Investigations aimed at understanding the function of GTPases indicate that a second conserved feature of these proteins is that they elicit their function through interaction with RNA and/or ribosomes. An emerging concept suggests that the 11 universal GTPases are either necessary for ribosome function or transmitting information from the ribosome to downstream targets for the purpose of generating specific cellular responses. Furthermore, it is suggested that progenitor GTPases were ...
The peak flux relationship between hard X-rays and microwaves from solar flares is studied using about 400 events simultaneously recorded with the hard X-ray burst spectrometer on the SMM satellite and the Nobeyama 17 GHz radiometer. The data indicate that the hard X-ray and microwave peak fluxes correlate best for X-ray energies of less than about 80 keV for impulsive flares and greater than about 360 keV for extended flares. By postulating that electrons responsible for microwave emission at 17 GHz are those emitting hard X-rays at these photon energies, it is concluded that: (1) in impulsive flares, microwaves at about 20 GHz are emitted mainly by electrons of less than about 200 keV from a layer through which the electrons stream down into the thick-target hard X-ray source; and (2) in extended flares, microwaves are emitted mainly by MeV electrons trapped in a coronal loop or loops. 59 references.
The survival time of golden hamsters (Mesocricetus auratus) after whole-body "6"0Co-#gamma#-irradiation in the range of 600 to 200 000 rad was investigated. The two plateaus of the dose-survival curve which correspond to bone marrow and gastrointestinal death are similar to those of other species such as mice, rats and mongolian gerbils. A new plateau occurring 40-57 hours after doses of 30 000-60 000 rad, where there is a little reduction in survival time, has been found. It is in addition to the well recognized central nervous system (CNS) syndrome. This plateau is observed only in golden hamsters, presumably because of their relatively high resistance to CNS syndrome. Experiments involving partial body irradiation of the animals indicate that the target is in the cephalic one-third of abdomen. The new segment may well indicate a new type of acute somatic radiation injury different from the well known bone marrow, gastrointestinal and CNS syndromes. (author).
Abstract The term -stem cell- most commonly refers to embryonic stem cells, particularly in the lay media; however, it also describes other cell types. A stem cell represents a cell of multi-lineage potential with the ability for self-renewal. It is now clear that the plasticity and immortality of a given stem cell will depend on what type of stem cell it is, whether an embryonic stem cell, a fetal-placental stem cell or an adult stem cell. Stem cells offer great promise as cell-based therapies for the future. With evolving technology, much of the socio-political debate regarding stem cells can now be avoided.
Characteristics of basal and insulin-stimulated glucose utilization by perifused adipocytes have been investigated by measuring the formation of "3HOH from D-(5-"3H) glucose. At a glucose concentration of 0.55 mmol/L, basal glucose utilization ranged from 0.5 to 1.0 nmol/min/10(6) cells. Perifused adipocytes showed a maximal response to insulin of a threefold to fourfold increase in the conversion of (5-"3H) glucose to "3HOH with a half-maximal response at an insulin concentration of 20 microU/mL. The response to insulin was blocked by phlorizin and cytochalasin B, competitive inhibitors of glucose transport, consistent with an effect of insulin on glucose transport. Insulin increased the Vmax for glucose metabolism but had no effect on the apparent affinity for glucose utilization. The characteristics of glucose utilization and the stimulation of glucose metabolism by insulin in the perifused adipocyte ...
The performance of a convolution/superposition based treatment planning system depends on the ability of the dose calculation algorithm to accurately account for physical interactions taking place in the tissue, key components of the linac head and on the accuracy of the photon beam model. Generally the user has little or no control over the performance of the dose calculation algorithm but is responsible for the accuracy of the beam model within the constraints imposed by the system. This study explores the dosimetric impact of limitations in photon beam modeling accuracy on complex 3D clinical treatment plans. A total of 70 photon beam models was created in the Pinnacle(TM) treatment planning system. Two of the models served as references for 6 MV and 15 MV beams, while the rest were created by perturbing the reference models in order to produce specific deviations in specific regions of the calculated dose profiles (central axis and transverse). The beam models ...
The present publication is based on facts, data, knowledge and projects, which have been incorporated in the development of an energy concept for the district Schmalkalden-Meiningen. The energy concept of a district is a concept oriented at action on and realisation of mid-term and long term decisions in the fields of energy policy, economy and ecology, which must be taken by municipal and economic decision-making bodies. The energy concept accords with the targets of the Agenda 21, the environmental targets of the Federal Republic of Germany and of the Land Thuringia. Accepting this energy concept the district Schmalkalden-Meiningen shows its willingness to contribute to a lasting development in all fields of economy and ecology and thus does justice to its increasing responsibility. (orig.) [German] Die vorliegende Veroeffentlichung baut auf Fakten, Daten, Erkenntnissen und Projekten auf, die in die Erarbeitung des ...
This paper reported on a study in which designs for Chinese and Indian fixed-dome anaerobic digesters were modified in an effort to produce smaller and more affordable digesters. While these types of systems are common in tropical regions of developing countries, they have not been used in colder climates because of the low biogas yield during the winter months. Although there is evidence that sufficient biogas production can be maintained in colder temperatures through design and operational changes, there is a lack of knowledge about the seasonal changes in the composition of the microbial communities in ambient temperature digesters. More knowledge is needed to design and operate systems for maximum biogas yield in temperate climates. The purpose of this study was to cultivate a microbial community that maximizes biogas production at psychrophilic temperatures. The study was conducted on a 300 gallon experimental anaerobic digester on the campus of Ohio State University. ...
Frictional pressure drop and heat transfer performance in a very narrow rectangular channel having one-sided constant heat flux and repeated-ribs for turbulent flow have been investigated experimentally, and their experimental correlations were obtained using the least square method. The rib pitch-to-height ratios(p/k) were 10 and 20 while holding the rib height constant at 0.2mm, the Reynolds number(Re) from 2,414 to 98,458 under different channel heights of 1.2mm, 2.97mm, and 3.24mm, the rib height-to-channel equivalent diameter(k/De) of 0.03, 0.04, and 0.09 respectively. The results show that the rib-roughened surface augments heat transfer 2-3 times higher than that of the smooth surface with the expense of 2.8-4 times higher frictional pressure drop under Re=5000-10{sup 5}, p/k=10, and H=1.2mm. Experimental results obtained by channel height, H=1.2mm shows a little bit higher heat transfer and friction factor performance than the higher channel height, H=3.24mm. The effect of fin ...
Computational prediction of microRNA targets remains a challenging problem. The existing rule-based, data-driven and expression profiling approaches to target prediction are mostly approached from the...Full Text Available
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
Ewing's sarcoma is a highly malignant neoplasm of the bone whose origin is still uncertain. A strong relationship exists between Ewing's sarcoma and tumors of neural origin (Ewing family of tumors). Ewing's sarcoma must be distinguished from other round-cell tumors like lymphoma and neuroblastoma and also must be differentiated from osteogenic sarcomas. On plain radiographs, Ewing's sarcoma appears as a lytic or mixed lytic-sclerotic, rarely as predominantly sclerotic lesion with margins Lodwick grade III. It is located primarily in the diaphyseal and metadiaphyseal regions of the long bones of the lower extremities. A large soft tissue tumor is usually present. Magnetic resonance imaging is the imaging modality of choice to evaluate the extent of the primary lesion, to monitor the response to neoadjuvant chemotherapy and to follow up non-resected Ewing's sarcomas. Bone scintigraphy is necessary to detect skeletal metastasis, and "2"0"1thallium ...
The alpha emitter plutonium-238 ("2"3"8Pu), which is produced in uranium-fueled, light-water reactors, is used as a thermoelectric power source for space applications. Inhalation of a mixed oxide form of Pu is the most likely mode of exposure of workers and the general public. Occupational exposures to "2"3"8PuO_2 have occurred in association with the fabrication of radioisotope thermoelectric generators. Organs and tissue at risk for deterministic and stochastic effects of "2"3"8Pu-alpha irradiation include the lung, liver, skeleton, and lymphatic tissue. Little has been reported about the effects of inhaled "2"3"8PuO_2 on peripheral blood cell counts in humans. The purpose of this study was to investigate hematological responses after a single inhalation exposure of Beagle dogs to alpha-emitting "2"3"8PuO_2 particles and to extrapolate results to humans.
Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation of these serines eliminated the stimulatory effects of CaMKIIalpha. A mutation of the DAT C terminus impairing CaMKIIalpha binding also impaired amphetamine-induced dopamine efflux. An in vivo role for CaMKII was supported by chronoamperometry measurements showing reduced amphetamine-induced dopamine efflux in response to the CaMKII inhibitor KN93. ...
Three regio-isomers of N-(N-benzylpiperidin-4-yl)-4-iodobenzamide, IBP, were prepared and evaluated for their sigma affinities. All three isomers (2, 3, and 4-substituted) showed high affinities for sigma-1 receptors in guinea pig brain membranes (Ki - 1.64 nM, 3.02 nM, 1.70 nM respectively) against ["3H]-(+)-pentazocine, a sigma-1 selective ligand. 2-IBP and 4-IBP showed modest affinities for sigma-2 sites in rat liver (Ki = 29.6 nM. 25.2 nM respectively) against ["3H]DTG in the presence of dextrallorphan to mask sigma-1 sites. The homologous competition binding studies of 4-["1"2"5I]BP in MCF-7 human breast tumor cells showed high affinity dose-dependent binding. Competition binding studies with haloperidol and DTG also showed a high affinity binding (Ki = 4.6 nM, 60 nM respectively), demonstrating the sigma specificity. The saturation binding (Scatchard analysis) of ["3H]DTG with MCF-7 cell membrane preparations gave Kd of 24.54 nM and a ...
There is very little known about the long-term evolution of the MHC and MHC-like molecules. This is because both the theory (the evolutionary questions and models) and the practice (the animals systems, functional assays and reagents to identify and characterize these molecules) have been difficult to develop. There is no molecular evidence yet to decide whether vertebrate immune systems (and particularly the MHC molecules) are evolutionarily related to invertebrate allorecognition systems, and the functional evidence can be interpreted either way. Even among the vertebrates, there is great heterogeneity in the quality and quantity of the immune response. The functional evidence for T-lymphocyte function in jawless and cartilagenous fish is poor, while the bony fish seem to have many characteristics of a mammalian immune system. The organization and sequence of fish Ig genes also indicate that important events in the evolution of the immune system and the MHC ...
Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.
Recent studies have shown Y chromosome microdeletions associated with male infertility. The factors responsible for Y chromosome microdeletions in spermatozoa remain unresolved. However, the environmental pollutants are known to damage DNA in differentiating and maturing germ cells in the male reproductive tract. Therefore, the aim of this study was to investigate the effects of seminal hexachlorocyclohexane (HCH) and its isomers, an environmental pollutant, in 50 fertile and 50 infertile males in relation to semen quality and the incidence of Y chromosome microdeletion in azoospermic factor (AZF) region. As compared to control, an increased HCH level and significantly decreased semen quality were observed in the infertile males. A positive significant association was found between sperm c...
DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...
Integrative and firing properties are important characteristics of neuronal circuits and these responses are determined in large part by the repertoire of ion channels they express, which can vary considerably between cell types. Recently, a new mode of operation of voltage dependent sodium channels has been described that generates a so-called resurgent Na^+ current. Accumulating evidence suggests resurgent Na current participates in the generation of sub-threshold inward Na^+ current causing membrane depolarization which provides the necessary drive to fire high-frequency action potentials. Recent studies indicate that resurgent Na^+ current could be a more widespread feature than previously thought.
Health risks associated with inhalation of mineral dusts have been identified to a great extent through epidemiology studies, but also have been assessed by conducting subchronic and chronic inhalation studies typically on rodents. However, in vivo studies are softly, time-consuming, requiring complex technologies, and may not yield information on cellular and molecular mechanisms of response. As a result, the use of in vitro cell culture systems has played an important role in studying the toxicology of mineral dusts and providing insight into action mechanisms. This article reviews selected in vitro approaches that are used to investigate the cytotoxic and inflammatory properties of mineral particles and fibers. In addition key findings as they relate to understanding the toxicology of mineral dusts are presented. 165 refs., 1 fig., 5 tab.
Summaries are included of research contracts which expired prior to Dec. 31, 1960. The contracts were concerned with investigations of: electrophysiological responses of biological systems in nerve cells to irradiation with small doses of ionizing radiations; the mode of the protective action of certain sulfhydryl compounds against radiation effects on the synthesis of deoxyribonucleic acid, using tritium-labeled thymidine; development of a bubble chamber method of monitoring and dosimetry for Low fast neutron fluxes; effects of incorporated radioisotopes on the stability of genetic materials; interrelation of root and leaf absorption of radioisotopes in herbaceous plants; uptake of radioactive wastes by lowland rice from soils contaminated by irrigation water, and decontamination of the rice; and comparison between mutation rates induced by acute and chronic gamma irradiations. (B.O.G.)
Data from Monte Carlo transport codes are used to model radiobiological effects. We previously reported the Fourier analysis of ionization data generated by simulating a 500-keV proton traversing water. Here, we extend Fourier analysis to energy transfer data of another radiation type, a 14-MeV #alpha#-particle. A radiobiological model based on this frequency-domain analysis views cell as an information processing system . It lends itself naturally to traditional engineering analyses. One engineering principle-the output response of a linear system to random signal-is applied here to explain the fact that there is measurable difference in the magnitude of the biological effectiveness when a given biological system is irradiated with two different radiation types of the same Linear Energy Transfer (LET).
Upgrading of potato pulp, a byproduct stream from industrial manufacture of potato starch, is important for the continued economic competitiveness of the potato starch industry. The major part of potato pulp consists of the tuber plant cell wall material which is particularly rich in galactan branched rhamnogalacturonan I type pectin. In the work reported here, the release of high-molecular weight pectinaceous dietary fiber polysaccharides from starch free potato pulp was accomplished by use of a multicomponent pectinase preparation from Aspergillus aculeatus (Viscozyme L). The enzyme reaction conditions for the solubilization were optimized via a surface response design to be addition of 0.27% Viscozyme L by weight of potato pulp substrate dry matter, 1h treatment at pH 3.5, 62.5degreeC. ...
Several old and new observations suggest the existence in Crohn's disease of a phagocytic disorder of macrophages related to impaired bactericidal activity of host cells or to the presence of invasive bacteria that have developed strategies to counteract macrophage killing. It was recently reported that disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. Secretion of proinflammatory cytokines by CD macrophages was impaired in response to E. coli or specific Toll-like receptor agonists. In addition, major advances in the etiology of Crohn's disease came from the existence of polymorphism in NOD2 and autophagy-related susceptibility genes (ATG16L1 and IRGM) in patients and from the identification of the presence of adhere...
Purpose: The DBA/2J mice have been used as an animal model for human pigmentary glaucoma. However, these mice develop various degrees of disease symptoms at different ages, making it difficult to detect pathological changes of retinal degeneration at glaucoma onset. The purpose of this study is to develop a non-invasive assay to identify individual mice that develop visual deficits. Materials and Methods: We apply two behavioral tests, a swimming test of visual discrimination and a test of optomotor response, to identify glaucomatous DBA/2J mice. We then examine whether the elevation of intraocular pressure (IOP), the common risk factor for glaucoma, affects visual performances of the DBA/2J mice. We further compare the retinal ganglion cell death, one of the signature glaucoma symptoms, i...
The concept of the 'white-light cavity' has recently generated considerable research interest in the context of gravitational wave detection. Cavity designs are proposed using negative (or anomalous) dispersion in an intracavity medium to make the cavity resonate over a large range of frequencies and still maintain a high cavity build-up. This paper presents the first experimental attempt and demonstration of white-light effect in a meter long ring cavity using an intracavity atomic medium. The medium's negative dispersion is caused by bi-frequency Raman gain in an atomic vapor cell. Although the white light condition was not perfectly achieved and improvements in experimental control are still desirable, significantly broad cavity response over bandwidth greater than 20 MHz has been observed. These devices will have potential applications in new generation laser interferometer gravitational wave detectors.
Researchers at the Laboratory of Nuclear Microanalysis in Besancon (France) are developing and improving radon measurements in order to detect and analyse, more precisely radon emanation anomalies in both fields of Earth Sciences and Radioprotection. In order to characterize radon emanation, two complementary techniques are developed; continuous measurement through a portable proportional counter and passive measurements by nuclear track detectors for both fieldwork and laboratory analysis. A mathematical model is being devised to interpret the nuclear track detector response. This model is performed according to the device characteristics: type of detectors, shape and size of cells and whether a membrane is used or not. In addition to the theoritical study, experimental radon concentration measurements will be reported. (author).
Researchers at the Laboratory of Nuclear Microanalysis in Besancon (France) are developing and improving radon measurements in order to detect and analyse, more precisely radon emanation anomalies in both fields of Earth Sciences and Radioprotection. In order to characterize radon emanation, two complementary techniques are developed; continuous measurement through a portable proportional counter and passive measurements by nuclear track detectors for both fieldwork and laboratory analysis. A mathematical model is being devised to interpret the nuclear track detector response. This model is performed according to the device characteristics: type of detectors, shape and size of cells and whether a membrane is used or not. In addition to the theoritical study, experimental radon concentration measurements will be reported. (author).
Summary Background Sorafenib is an oral multikinase inhibitor that blocks cell proliferation via the ERK pathway and angiogenesis via the VEGF pathway. This phase II trial was conducted to determine the efficacy and tolerability of sorafenib for the treatment of patients with metastatic urothelial cancer (UC) who had not had prior chemotherapy for advanced disease. Patients and Methods Seventeen chemo-na?ve UC patients with adequate performance status and organ function were treated with sorafenib 400?mg twice daily on a continuous basis until progression or unacceptable toxicity. The primary endpoint was objective tumor response rate as measured by RECIST criteria. Secondary endpoints included rate of prolonged stable disease (>3?months), time to progression, median and 1?yr survival and ...
In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available
The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.
... L. Sutton. 2000. Is the aquatic weed hygrophila, Hygrophila polysperma (Polemoniales: Acanthaceae), a suitable target for classical biological ... ...
Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...
By W. Wayne Scott. Langley Research Center. SUMMARY. Thin- and thick-target bremsstrahlung spectra are presented for electron energies up to 7.0 MeV. ...
Sixteen patients with advanced cutaneous T-cell lymphoma (CTCL) with or without lymph node involvement, but without evidence of extranodal manifestations, were treated with a combination of total skin electron beam therapy (TSEB) and total nodal irradiation (TNI). Fourteen (87%) patients achieved a complete response (CR) lasting from 1 to 84+ months (median, 8+ months) from the completion of treatment. The best results occurred in 6 patients with pretumorous intracutaneous CTCL (Stages IB and IIA) where the CR has lasted in all patients from 8 to 84+ months (median about 27+ months). Radiotherapy was well tolerated with the major toxicity being bone marrow suppression. The authors conclude that combined TSEB and TNI is a relatively safe and effective treatment for patients with CTCL prior to the development of lymph node involvement. Long-term follow-up is needed to assess the curative potential of this treatment.
Indoline dye sensitizers were designed and studied theoretically to increase molar extinction coefficients in the visible to near infrared region for solar-cell devices. To gain insight into dye sensitizers' structural, electronic, and optical properties, DFT/TDDFT calculations were performed on a series of dye sensitizers derived from the D149. The good agreement between the experimental and TDDFT calculated absorption spectra of the D149 sensitizer allowed us to provide a detailed assessment of the main spectral features of a series of dye sensitizers. Increase in the conjugation length resulted in a more red-shifted spectral response and less positive oxidation potential than that of the D149. The dye with the dimethylfluorene group showed stronger absorption bands due to a large dipole moment. The calculated dipoles for the dye series correlate well with the observed strong absorption bands of the electronic spectra. These results provided ...
Abstract in english Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are e (more) xpressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's ...
The effects of muscarinic agonists and diisopropylfluorophosphate (DFP) on muscarinic receptor density and muscarinic receptor-mediated responses was assessed in mouse brain and mouse neuroblastoma cells (clone N1E-115). Utilizing the antagonist ({sup 3}H)quinuclidinyl benzilate (({sup 3}H)QNB), there was no difference in the maximal binding capacity (B{sub max}) or equilibrium dissociation constant (K{sub d}) between untreated and 24 hour DFP-treated mice. However, one administration of DFP produced a 24% and 33% decrease in B{sub max} measured by ({sup 3}H)N-methylscopolamine (({sup 3}H)NMS) after 18 and 24 hours which was rapidly reversible within 36 hours after DFP treatment. The loss of ({sup 3}H)NMS binding sites following acute DFP treatment was not accompanied by a change in a particular muscarinic receptor binding conformation. Furthermore, the magnitude of muscarinic receptor-mediated phosphoinositide hydrolysis was unchanged ...
A series of cyclic strain controlled tests have been carried out at 600/sup 0/C on three high temperature austenitic iron-based alloys, AISI type 316 stainless steel, Alloy 800 H and Sandvik 253 MA. The tests were carried out under constant total strain control using a constant strain rate of 0.005 s/sup -1/. By considering the changes in modulus throughout the life of each specimen it was found that damage evolution could be successfully predicted as a function of plastic strain range despite the fact that each alloy had been chosen because of a different stress response at 600/sup 0/C. Although each alloy accumulated fatigue damage in a similar manner the longer lives of Sandvik 253 MA and Alloy 800 H at a given total strain range were due to a smaller plastic strain component and a reduced stage I crack propagation rate. In the 253 MA alloy, slip was predominantly planar with some cells occasionally forming at high strain ranges. Slip was ...
The purpose of this text is to train engineers and technologists not just to understand corrosion but to control it. Materials selection, coatings, chemical inhibitors, cathodic and anodic protection, and equipment design are covered in separate chapters. High-temperature oxidation is discussed in the final two chapters ne on oxidation theory and one on controlling oxidation by alloying and with coatings. This book treats corrosion and high-temperature oxidation separately. Corrosion is divided into three groups: (1) chemical dissolution including uniform attack, (2) electrochemical corrosion from either metallurgical or environmental cells, and (3) stress-assisted corrosion. Corrosion is logically grouped according to mechanisms rather than arbitrarily separated into different types of corrosion as if they were unrelated. For those university students and industry personnel who approach corrosion theory very hesitantly, this text will present the electrochemical ...
The purpose of this text is to train engineers and technologists not just to understand corrosion but to control it. Materials selection, coatings, chemical inhibitors, cathodic and anodic protection, and equipment design are covered in separate chapters. High-temperature oxidation is discussed in the final two chapters ne on oxidation theory and one on controlling oxidation by alloying and with coatings. This book treats corrosion and high-temperature oxidation separately. Corrosion is divided into three groups: (1) chemical dissolution including uniform attack, (2) electrochemical corrosion from either metallurgical or environmental cells, and (3) stress-assisted corrosion. Corrosion is logically grouped according to mechanisms rather than arbitrarily separated into different types of corrosion as if they were unrelated. For those university students and industry personnel who approach corrosion theory very hesitantly, this text will present the electrochemical ...
The TRAC/PFI-MOD2 Version 5.3 code was assessed against six FLECHT-SEASET forced reflood tests (31504, 31203, 31302, 31701, 34209, and 31922) and two cylindrical core test facility (CCTF) tests [C1-19 and C2-6]. The objective of this study was to evaluate the clad thermal response predictive capabilities of the code with the newly added reflood model under large-break loss-of-coolant accident (LOCA) conditions in a pressurized water reactor (PWR). The TRAC model for the FLECHT-SEASET test facility was developed from a RELAP5 model. The test section was modeled using a vessel component with 23 axial levels, 1 radial ring, and 1 azimuthal cell. Test inlet and exit conditions were modeled using fill and break components, respectively. The measured lower and upper plenum test conditions were input to the model. The electrically heated rod was modeled using a rod component with 22 axial mesh points. The axial boundary of each mesh point coincided ...
This chapter provides an overview of the problem of response to a nuclear weapon accident, the fundamentals of response to an accident, and a summary of the NARP Manual. The manual provides a summary of procedural guidance, technical information, and DoD responsibilities, to assist DoD forces in preparing a response to a nuclear weapon accident.
The effect of various window layers for InP solar cells are studied. Window materials that have type 1 and type 2 alignment in the window/emitter interface are compared. All window materials that form a type 2 alignment with InP, such as Al{sub 0.20}In{sub 0.80}P, Ga{sub 0.20}In{sub 0.80}P, Al{sub 0.55}In{sub 0.45}As and Al{sub 0.60}In{sub 0.40}P, cause a high interface recombination velocity, which deteriorates the carrier collection. This recombination takes place due to the spatially indirect quantum well transition between the triangular quantum wells formed in the interface. ZnSe as a window layer material with type 1 alignment does not have this problem, but still decreased response in the short wavelength region is observed due to misfit dislocation induced trap sites. Future prospects for the window layer development for InP are discussed. The discussion is extended also to other III-V semiconductor based solar cell ...
The rapid growth in the use of in vitro methods for nanoparticle toxicity assessment has proceeded with limited consideration of the unique kinetics of these materials in solution. Particles in general and nanoparticles specifically, diffuse, settle and agglomerate in cell culture media as a function of several systemic and particle factors: media density and viscosity, particle size, shape and density. Cellular dose then is also a function of these factors as they determine the rate of transport of nanoparticles to cells in culture. Here we develop and apply the principles of particokinetics and dosimetry in vitro and outline an approach for simulation of nanoparticle particokinetics in cell culture systems. We illustrate that where equal mass concentrations (?g/ml) imply equal doses for dissimilar materials, the corresponding particle number or surface area concentration doses differ by orders of magnitude. When rates of ...
We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with ...
Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke ...
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic ...
Adolescent exposure to anabolic androgenic steroids (AAS) alters the development and activity of the glutamate neural system in the latero-anterior hypothalamus (LAH) in hamsters (Mesocricetus auratus); that is, an important neural component of the adolescent AAS-induced aggressive response. In this article, we used retrograde tracing to investigate glutamate-specific alterations in the connections between the LAH and several other nuclei implicated in adolescent AAS-induced aggression. Briefly, hamsters were treated with AAS or sesame-oil control during adolescence and then microinjected with retrograde tracer into the medial amygdala (MeA), lateral septum (LS), or bed nucleus of the stria terminalis (BNST). Brains were then processed for vesicular glutamate transporter 2 (VGLUT2) and examined for AAS-induced changes in the number VGLUT2 cells containing retrograde tracer (VGLUT2/tracer) within the LAH. It is interesting to note that while ...
Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis ...
A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, "3H-thymidine uptake labeling ...
The hypothesis that intracellular Ca/sup 2 +/ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca/sup 2 +/ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl/sub 2/ and the Ca/sup 2 +/ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl/sub 2/ from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal ...
The hypothesis that intracellular Ca"2"+ is an essential component of the intracellular mechanism of insulin action in the adipocyte was evaluated. Cells were loaded with the Ca"2"+ chelator quin-2, by preincubating them with quin-2 AM, the tetrakis(acetoxymethyl) ester of quin-2. Quin-2 loading inhibited insulin-stimulated glucose transport without affecting basal activity. The ability of insulin to stimulate glucose uptake in quin-2-loaded cells could be partially restored by preincubating cells with buffer supplemented with 1.2 mM CaCl_2 and the Ca"2"+ ionophore A23187. These conditions had no effect on basal activity and omission of CaCl_2 from the buffer prevented the restoration of insulin-stimulated glucose uptake by A23187. Quin-2 loading also inhibited insulin-stimulated glucose oxidation and the ability of insulin to inhibit cAMP-stimulated lipolysis without affecting their basal activities. Incubation of ...
Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ...
beta-Bungarotoxin (beta-Bgt), a presynaptic phospholipase A(2) (PLA(2)) neurotoxin isolated from the venom of Bungarus multicinctus, consists of A chain and B chain. The goal of the present study is to explore the functional contribution of the two subunits to the toxicity of beta-Bgt. beta-Bgt was found to induce apoptotic death of SK-N-SH cells via elevating intracellular Ca(2+) and intracellular ROS production. Moreover, an activation of p38 MAPK was associated with the cytotoxicity of beta-Bgt. SB202190 (p38 MAPK inhibitor), N-acetylcysteine (antioxidant reagent), 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid (BAPTA) (Ca(2+) chelator) and the inhibitors of Ca(2+) release from intracellular depots (ruthenium red and 2-aminoethoxydiphenyl borate) effectively attenuated the cytotoxicity of beta-Bgt. In sharp contrast to the inability of A chain, B chain was able to induce cytotoxic effects on SK-N-SH cells as beta-Bgt did. Abolishment ...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism of rAAV-hTERTC27-mediated antitumor ...
This paper presents an uplink capacity analysis and interference avoidance technique for a femtocell based two-tier DS-CDMA network using shared spectrum. Assuming randomly distributed macrocell users and femtocell base stations (BS), we evaluate a network-wide area spectral efficiency metric called the operating contour (OC) defined as the feasible combinations of the average macrocell users and femtocell BS per cell-site that meet a target outage constraint $\\epsilon$. A contribution of this work is an accurate characterization of the uplink outage probability taking cross-tier power control, path-loss and shadowing effects into account. We show that a time-hopped CDMA physical layer coupled with sectorized receive antennas shows dramatic performance improvements in both light and heavily loaded two-tier networks, relative to a split spectrum two-tier network with omnidirectional femtocell antennas. These results provide insights into design ...
Variations in skin perfusion are easily detected by laser speckle contrast maps, but a robust interpretation of the information has been lacking. We show that multiple-exposure laser speckle methods produce the same spectral information as laser Doppler methods when applied to targets with embedded moving scatterers. This enables laser speckle measurements to be interpreted more quantitatively. We do this by using computer simulation of speckle data, and by experimental measurements on Brownian motion and skin perfusion using a laser Doppler system and a multiple-exposure laser speckle system. The power spectral density measurements of the light fluctuations derived using both techniques are exactly equivalent. Dermal perfusion can therefore be measured by laser Doppler or laser speckle contrast methods. In particular, multiexposure laser speckle can be rapidly processed to generate a full-field map of the perfusion index proportional to the concentration and mean ...
A conjugate of 6-hydrazinopyridine-3-carboxylic acid (HYNIC) with the amino analogue of metronidazole (MN) was synthesized through a multiple-step reaction. HYNIC-MN could be labeled easily and efficiently with 99mTc using N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine -N,N?-diacetic acid (EDDA) as coligands to form the 99mTc?HYNIC?MN complex in high yield (>95%). Its partition coefficient indicated that it was a good hydrophilic complex. The tumor cell experiment showed that the 99mTc?HYNIC?MN complex had a certain hypoxic selectivity. The biodistribution studies of 99mTc?HYNIC?MN in Kunming mice bearing S180 tumor showed a favorable tissue distribution profile with high tumor uptake, and low or negligible accumulation in non-target organs, suggesting 99mTc...
Isotope shift measurements have been performed for the {sup 242{ital f}}Am fission isomer with target production rates of only a few per second. The method is based on resonance ionization spectroscopy (RIS) in a buffer gas cell with radioactive decay detection of the ionization process (RADRIS). A relative isotope shift ratio X{sub {ital exp}}=IS{sup 242{ital f},241}/IS{sup 243,241}=41.7{plus_minus}0.9 has been measured for the 500.02 nm transition corresponding to a nuclear parameter A{sup 242{ital f},241}=(5.4{plus_minus}0.3) fm{sup 2}. A preliminary analysis of the quadrupole moment based on the deformed Fermi model of the nuclear charge distribution results in Q{sub 20}=35.9{plus_minus}1.1({sup +0.3}{sub {minus}0.7}) {sub model} eb. {copyright} 1995 {ital American} {ital Institute} {ital of} {ital Physics}
It is very well known that the CANDU reactor has positive Coolant Void Reactivity (CVR), which is most important criticisms about CANDU. The most recent innovations based on using a thin absorbent Hafnium shell in the central bundle element were successfully been applied to the Advanced CANDU Reactor (ACR) project. The paper's objective is to analyze elementary lattice cell effects in applying such methods to reduce the CVR. Three basic fuel designs in their corresponding geometries were chosen to be compared: the ACR-1000TM, the RU-43 (developed in INR Pitesti) and the standard CANDU fuel. The bundle geometry influence on void effect was also evaluated. The WIMS calculations proved the Hafnium absorber suitability (in the latest 'shell design') to achieve the negative CVR target with great accuracy for the ACR-1000 fuel bundle design than for the other two projects. (authors)
Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional ...
Activation has been used for many kinds of useful applications, such as use of the radioisotopes for diagnosis and treatment of cancer, and wear (or corrosion) investigation for using thin layer activation (TLA) technique, etc. But activation also has severe problems for the post-processing of the samples; such as time-loss, inconvenience of sample handling, personal radiation safety, etc. For in-vitro experiments, we observed death of tumor cells by proton irradiation. The use of large activated container material can cause erroneous results in this case. To solve these problems, we studied why the samples were activated and how the level of the activation could be reduced. In proton beam irradiation experiments, the target materials could be defined as the container and sample itself. We could easily reduce activation of container material comparing to activation of sample itself. Therefore, we tried to find less activated container material ...
The aim of this paper is to analyse the role that the Japanese Government has played in the development of alternatives to conventional vehicles, the effect of government programmes, and the importance of technical flexibility in government support schemes. The focus is on battery-powered electric vehicles (BPEVs), hybrid electric vehicles (HEVs), and fuel cell electric vehicles. The effects of government policy and the process of innovation are analysed from a systems approach drawing on the literature regarding technical change and innovation. The whole chain of government support, including the context in which these different policies have been implemented since the early 1970s, is studied. The Japanese Government has adopted a comprehensive strategy including R and D, demonstration programmes and market support guided by long-term strategic plans. The role of the Government has been that of a conductor in the development process supplying both R and D support ...