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Sample records for 2-microglobulin beta 2-m

  1. [Serum beta 2 microglobulin (beta 2M) following renal transplantation].

    PubMed

    Pacheco-Silva, A; Nishida, S K; Silva, M S; Ramos, O L; Azjen, H; Pereira, A B

    1994-01-01

    Although there was an important improvement in graft and patient survival the last 10 years, graft rejection continues to be a major barrier to the success of renal transplantation. Identification of a laboratory test that could help to diagnose graft rejection would facilitate the management of renal transplanted patients. PURPOSE--To evaluate the utility of monitoring serum beta 2M in recently transplanted patients. METHODS--We daily determined serum beta 2M levels in 20 receptors of renal grafts (10 from living related and 10 from cadaveric donors) and compared them to their clinical and laboratory evolution. RESULTS--Eight patients who presented immediate good renal function following grafting and did not have rejection had a mean serum beta 2M of 3.7 mg/L on the 4th day post transplant. The sensitivity of the test for the diagnosis of acute rejection was 87.5%, but the specificity was only 46%. Patients who presented acute tubular necrosis (ATN) without rejection had a progressive decrease in their serum levels of beta 2M, while their serum creatinine changed as they were dialyzed. In contrast, patients with ATN and concomitance of acute rejection or CSA nephrotoxicity presented elevated beta 2M and creatinine serum levels. CONCLUSION--Daily monitoring of serum beta 2M does not improve the ability to diagnose acute rejection in patients with good renal function. However, serum beta 2M levels seemed to be useful in diagnosing acute rejection or CSA nephrotoxicity in patients with ATN. PMID:7787867

  2. Beta-2 Microglobulin Tumor Marker

    MedlinePlus

    ... limited. Home Visit Global Sites Search Help? Beta-2 Microglobulin Tumor Marker Share this page: Was this page helpful? Also known as: B2M; B 2 M; β2-Microglobulin; Thymotaxin Formal name: Beta 2 ...

  3. The ESAT-6 protein of Mycobacterium tuberculosis interacts with beta-2-microglobulin2M) affecting antigen presentation function of macrophage.

    PubMed

    Sreejit, Gopalkrishna; Ahmed, Asma; Parveen, Nazia; Jha, Vishwanath; Valluri, Vijaya Lakshmi; Ghosh, Sudip; Mukhopadhyay, Sangita

    2014-10-01

    ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90-95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis. PMID:25356553

  4. The ESAT-6 Protein of Mycobacterium tuberculosis Interacts with Beta-2-Microglobulin2M) Affecting Antigen Presentation Function of Macrophage

    PubMed Central

    Parveen, Nazia; Jha, Vishwanath; Valluri, Vijaya Lakshmi; Ghosh, Sudip; Mukhopadhyay, Sangita

    2014-01-01

    ESAT-6, an abundantly secreted protein of Mycobacterium tuberculosis (M. tuberculosis) is an important virulence factor, inactivation of which leads to reduced virulence of M. tuberculosis. ESAT-6 alone, or in complex with its chaperone CFP-10 (ESAT-6:CFP-10), is known to modulate host immune responses; however, the detailed mechanisms are not well understood. The structure of ESAT-6 or ESAT-6:CFP-10 complex does not suggest presence of enzymatic or DNA-binding activities. Therefore, we hypothesized that the crucial role played by ESAT-6 in the virulence of mycobacteria could be due to its interaction with some host cellular factors. Using a yeast two-hybrid screening, we identified that ESAT-6 interacts with the host protein beta-2-microglobulin2M), which was further confirmed by other assays, like GST pull down, co-immunoprecipitation and surface plasmon resonance. The C-terminal six amino acid residues (90–95) of ESAT-6 were found to be essential for this interaction. ESAT-6, in complex with CFP-10, also interacts with β2M. We found that ESAT-6/ESAT-6:CFP-10 can enter into the endoplasmic reticulum where it sequesters β2M to inhibit cell surface expression of MHC-I-β2M complexes, resulting in downregulation of class I-mediated antigen presentation. Interestingly, the ESAT-6:β2M complex could be detected in pleural biopsies of individuals suffering from pleural tuberculosis. Our data highlight a novel mechanism by which M. tuberculosis may undermine the host adaptive immune responses to establish a successful infection. Identification of such novel interactions may help us in designing small molecule inhibitors as well as effective vaccine design against tuberculosis. PMID:25356553

  5. In vitro beta 2-microglobulin (beta 2m) secretion by normal and leukaemic B-cells: effects of recombinant cytokines and evidence for a differential response to the combined stimulus of phorbol ester and calcium ionophore.

    PubMed Central

    Jones, R. A.; Drexler, H. G.; Gignac, S. M.; Child, J. A.; Scott, C. S.

    1990-01-01

    Due to the increasing therapeutic use of immunoregulatory agents and the potential effects on cellular function, we examined the modulation of in vitro beta 2-microglobulin (beta 2m) production rates by 'normal' tonsil and leukaemic B-cells in response to a number of these agents. Tonsil B-cells responded to phorbol ester (TPA) by an increased beta 2m production rate, which was further enhanced by the combined stimuli of TPA plus the calcium ionophore A23187. In marked contrast, however, lymphocytes from a majority (8/11) of B-cell malignancies showed a suppression of the TPA-induced beta 2m production rate in response to the combined TPA/A23187 stimulus. These different responses of 'normal' and malignant B-cells were not apparent when IgM production rates were examined. The recombinant cytokines IL-1, IL-2, IFN-alpha, IFN-gamma and TNF also enhanced beta 2m production rates of both normal and leukaemic B-cells, but to a considerably lesser extent than did TPA. Bryostatin-1 increased beta 2m production to a level intermediate between that obtained by TPA and the cytokines. It is suggested that beta 2m production rates may correspond to the degree of B-cell differentiation, and/or to the degree of cellular 'activation'. The results further indicate that the in vitro measurement of beta 2m production provides a different index of the cellular response than that obtained by the conventional measurement of IgM production. PMID:2110813

  6. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-microglobulin immunological test system....5630 Beta-2-microglobulin immunological test system. (a) Identification. A beta-2-microglobulin... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of...

  7. The effect of surgery on the renal excretion of beta 2-microglobulin.

    PubMed

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  8. Beta-2 Microglobulin Kidney Disease Test

    MedlinePlus

    ... accumulate in joint spaces ( synovitis ) in long-term dialysis patients; this is called dialysis-related amyloidosis (DRA). A B2M test may be ... early kidney dysfunction. People who have been on dialysis for five years or more may develop dialysis- ...

  9. Beta 2-microglobulin amyloidosis presenting as esophageal perforation in a hemodialysis patient.

    PubMed

    Khan, G A; Lewis, F I; Dasgupta, M

    1997-01-01

    A 45-year-old male with hypertensive end-stage renal disease and on maintenance hemodialysis for 13 years is reported. He presented with life-threatening hematemesis, secondary to esophageal rupture. Immunohistological staining and electron microscopy examination of the esophageal perforation showed depositions of beta 2-microglobulin (beta 2-M) amyoloid. The unique aspect presented here is the localized esophageal involvement with beta 2-M amyloidosis. This is the first reported patient with esophageal perforation, due to the deposition and infiltration of the lower esophagus with beta 2-M which predisposed to its rupture. PMID:9426849

  10. Selective elution of HLA antigens and beta 2-microglobulin from human platelets by chloroquine diphosphate

    SciTech Connect

    Kao, K.J.

    1988-01-01

    To determine whether chloroquine can specifically elute HLA antigens and beta 2-microglobulin (beta 2-M) from the platelet surface, quantitative immunofluorescence flow cytometry and monoclonal antibodies were used to show that HLA antigens and beta 2-M were proportionally eluted from the platelet surface without affecting the membrane glycoproteins IIb and IIIa. Second, an autoradiogram of electrophoresed I-125-labeled platelets showed that only beta 2-M but not other I-125-labeled membrane proteins could be eluted. Although HLA antigens were poorly labeled by I-125 and could not be detected on the autoradiogram, the eluted HLA antigens could be detected by anti-HLA monoclonal antibody and immunoblotting techniques. No loss of plasma membrane integrity was observed by transmission electron microscopy after chloroquine treatment of platelets. The results indicate that chloroquine selectively elutes HLA antigens and their noncovalently associated beta 2-M without affecting other integral platelet membrane proteins.

  11. A single disulfide bond differentiates aggregation pathways of beta2-microglobulin.

    PubMed

    Chen, Yiwen; Dokholyan, Nikolay V

    2005-11-25

    Deposition of wild-type beta2-microglobulin (beta2m) into amyloid fibrils is a complication in patients undergoing long-term hemodialysis. The native beta-sandwich fold of beta2m has a highly conserved disulfide bond linking Cys25 and Cys80. Oxidized beta2m forms needle-like amyloid fibrils at pH 2.5 in vitro, whereas reduced beta2m, at acid pH, in which the intra-chain disulfide bond is disrupted, cannot form typical fibrils. Instead, reduced beta2m forms thinner and more flexible filaments. To uncover the difference in molecular mechanisms underlying the aggregation of the oxidized and reduced beta2m, we performed molecular dynamics simulations of beta2m oligomerization under oxidized and reduced conditions. We show that, consistent with experimental observations, the oxidized beta2m forms domain-swapped dimer, in which the two proteins exchange their N-terminal segments complementing each other. In contrast, both dimers and trimers, formed by reduced beta2m, are comprised of parallel beta-sheets between monomers and stabilized by the hydrogen bond network along the backbone. The oligomerized monomers are in extended conformations, capable of further aggregation. We find that both reduced and oxidized dimers are thermodynamically less stable than their corresponding monomers, indicating that beta2m oligomerization is not accompanied by the formation of a thermodynamically stable dimer. Our studies suggest that the different aggregation pathways of oxidized and reduced beta2m are dictated by the formation of distinct precursor oligomeric species that are modulated by Cys25-Cys80 disulfide-bonds. We propose that the propagation of domain swapping is the aggregation mechanism for the oxidized beta2m, while "parallel stacking" of partially unfolded beta2m is the aggregation mechanism for the reduced beta2m. PMID:16242719

  12. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of...

  13. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of...

  14. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of...

  15. 21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Beta-2-microglobulin immunological test system. 866.5630 Section 866.5630 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... beta-2-microglobulin (a protein molecule) in serum, urine, and other body fluids. Measurement of...

  16. Interactions between human serum proteins and oral streptococci reveal occurrence of receptors for aggregated beta 2-microglobulin.

    PubMed Central

    Ericson, D; Bratthall, D; Björck, L; Myhre, E; Kronvall, G

    1979-01-01

    A total of 31 strains of oral streptococci representing Streptococcus mutans, Streptococcus sanguis, Streptococcus mitior, Streptococcus salivarius, and Streptococcus milleri were tested for possible binding of human immunoglobulins G, G1, G2, G3, G4, A1, A2, M1, and M2 and haptoglobin, hemoglobin, fibrinogen, and aggregated beta 2-microglobulin. Radiolabeled beta 2-microglobulin in aggregated form showed affinity for 20 of the 31 strains tested. Binding activity for the protein was found in strains belonging to all five species. The bacterial receptor was resistant to trypsin. Monomeric, unlabeled beta 2-microglobulin did not interfere with the binding of the aggregated form. Of the other proteins tested, only the immunoglobulin A1 protein showed positive binding, and that was only with a single strain of S. milleri. beta 2-Microglobulin is present on all nucleated cell membranes in vivo. The reaction between aggregated beta 2-microglobulin and oral streptococci is a new type of human-bacterium interaction which should be considered in studies of bacterial adherence. PMID:90015

  17. Clearance and synthesis rates of beta 2-microglobulin in patients undergoing hemodialysis and in normal subjects

    SciTech Connect

    Floege, J.; Bartsch, A.; Schulze, M.; Shaldon, S.; Koch, K.M.; Smeby, L.C. )

    1991-08-01

    Retention of {beta} 2-microglobulin in patients undergoing hemodialysis is associated with a {beta} 2-microglobulin-derived amyloidosis. Removal of {beta} 2-microglobulin by renal replacement therapy has been proposed for the prevention of this amyloidosis. Currently, however, data on the {beta} 2-microglobulin synthesis rate in patients undergoing hemodialysis are scarce, and consequently it remains speculative how much removal would be necessary to counterbalance synthesis. The plasma kinetics of iodine 131-labeled {beta} 2-microglobulin were therefore examined in 11 patients with anuria who were undergoing long-term hemodialysis. Five healthy persons served as controls. Kinetic modeling of the plasma curves showed that the data fitted a two-pool model (r2 greater than 0.96) consisting of a rapid 2 to 4 hour distribution phase followed by a less steep curve, described by the plasma (metabolic) clearance (Clp). Synthetic rates were calculated from Clp and the {beta} 2-microglobulin steady state plasma concentration (plus {beta} 2-microglobulin removal during hemodialysis in the case of high flux hemodialysis). The results showed a significantly higher Clp in normal controls as compared with patients undergoing hemodialysis (65.5 {plus minus} 12.8 ml/min (mean {plus minus} SD) versus 3.4 {plus minus} 0.7 ml/min). In contrast, the {beta} 2-microglobulin synthesis rate in the patient group (3.10 {plus minus} 0.79 mg/kg/day) was not significantly different from that of normal controls (2.40 {plus minus} 0.67 mg/kg/day), which was due to markedly elevated {beta} 2-microglobulin plasma concentrations in the patients (37.6 {plus minus} 14.1 mg/L vs 1.92 {plus minus} 0.27 mg/L). These findings suggest that the presence of end-stage renal disease does not have a significant impact on the beta 2-microglobulin generation rate.

  18. A {beta}{sub 2}-microglobulin cleavage variant fibrillates at near-physiological pH

    SciTech Connect

    Corlin, Dorthe B. Johnsen, Christina K.; Nissen, Mogens H.; Heegaard, Niels H.H.

    2009-04-03

    {beta}{sub 2}-microglobulin ({beta}{sub 2}m) deposits as amyloid in dialysis-related amyloidosis (DRA), predominantly in joints. The molecular mechanisms underlying the amyloidogenicity of {beta}{sub 2}m are still largely unknown. In vitro, acidic conditions, pH < 4.5, induce amyloid fibrillation of native {beta}{sub 2}m within several days. Here, we show that amyloid fibrils are generated in less than an hour when a cleavage variant of {beta}{sub 2}m-found in the circulation of many dialysis patients-is exposed to pH levels (pH 6.6) occurring in joints during inflammation. Aggregation and fibrillation, including seeding effects with intact, native {beta}{sub 2}m were studied by Thioflavin T fluorescence spectroscopy, turbidimetry, capillary electrophoresis, and electron microscopy. We conclude that a biologically relevant variant of {beta}{sub 2}m is amyloidogenic at slightly acidic pH. Also, only a very small amount of preformed fibrils of this variant is required to induce fibrillation of native {beta}{sub 2}m. This may explain the apparent lack of detectable amounts of the variant {beta}{sub 2}m in extracts of amyloid from DRA patients.

  19. Beta 2-microglobulin associated amyloidosis: a vanishing complication of long-term hemodialysis?

    PubMed

    Schwalbe, S; Holzhauer, M; Schaeffer, J; Galanski, M; Koch, K M; Floege, J

    1997-10-01

    Beta 2-microglobulin associated amyloidosis (A beta 2m amyloidosis) is considered an inevitable complication of chronic hemodialysis, particularly in hemodialysis with cellulose based membranes. We performed a single center study to assess the prevalence of A beta 2m amyloidosis in 1988 versus 1996. Randomly selected patients, studied in 1988, were matched for time on hemodialysis (mean 71 months, range 3 to 207) and age (mean 51 years, range 22 to 80) with patients of the 1996 population. Compared to 1988 patients, the 1996 patients exhibited a lower prevalence of carpal tunnel syndrome (7 of 43 in 1988 vs. 1 of 43 in 1996; P < 0.001) and radiological evidence of A beta 2m amyloidosis (13 of 34 patients vs. 3 of 34 patients positive; P < 0.001; and 33 of 272 possible sites affected in 1988 vs. 7 of 272 sites in 1996 patients; P < 0.05). Compared to the 1988 population, the 1996 population exhibited significantly lower serum aluminum levels, lower average serum creatinine (but not urea) levels, more frequent therapy with erythropoietin, less home hemodialysis, longer hemodialysis time using high-flux synthetic dialysis membranes (mean of 13% vs. 6% of the total hemodialysis time in the 1988 group), and more frequent usage of reverse osmosis water plus bicarbonate buffer for dialysate preparation. We conclude that the prevalence and severity of A beta 2m amyloidosis unexpectedly decreased by about 80% in our center between 1988 and 1996. Given the relatively short times spent on high flux hemodialysis in both groups, increased beta 2-microglobulin removal is unlikely to account for this phenomenon. Rather, other factors, for example, dialysate composition and purity, may be involved. PMID:9328948

  20. Mass spectrometric characterization of conformational preludes to [beta]2-microglobulin aggregation

    NASA Astrophysics Data System (ADS)

    Jørgensen, Thomas J. D.; Cheng, Lei; Heegaard, Niels H. H.

    2007-12-01

    Characterization of protein folding and unfolding is an important issue for basic biological science, for understanding the devastating amyloid diseases, and for the manufacture and use of biological therapeutics. Unlike nuclear magnetic resonance spectroscopy, the use of mass spectrometry to monitor amide hydrogen (1H/2H) exchange kinetics (HX-MS) allows characterization of structural dynamics even when only limited amounts of protein is available. As an adjunct technique, requiring even less material and very well suited for serial monitoring of folding phenomena in a single solution under native conditions capillary electrophoresis may also be very informative. These approaches are here used to examine the small (99 amino acid residues) protein [beta]2-microglobulin ([beta]2m) which is prone to amyloidogenic unfolding especially after cleavage at its lysine-58 residue. The propensity for unfolding of native, non-cleaved [beta]2m and lysine-58 cleaved [beta]2m variants as well as the effect of acetonitrile on the conformational equilibria could be addressed by these approaches. At physiological conditions, intact [beta]2m and the lysine-58 cleaved variants undergo a transient unfolding that exhibit an EX1 type hydrogen exchange behaviour. We have measured the unfolding rate constants for the cleaved variant where Lys-58 is removed ([Delta]K58-[beta]2m) and the cleaved variant where this residue is preserved (cK58-[beta]2m) at various temperatures. Below 37 °C, the variant devoid of Lys-58 ([Delta]K58-[beta]2m) has a higher unfolding rate than cK58-[beta]2m and this correlates with the observation that [Delta]K58-[beta]2m has a higher propensity to aggregate. The results of our studies provide valuable insight into the early conformational perturbations involved in rendering this protein insoluble and amyloidogenic. The approaches used in this study should be useful also for the characterization of other conformationally unstable proteins.

  1. Polymerization of intact beta 2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis.

    PubMed Central

    Gorevic, P D; Munoz, P C; Casey, T T; DiRaimondo, C R; Stone, W J; Prelli, F C; Rodrigues, M M; Poulik, M D; Frangione, B

    1986-01-01

    Systemic amyloidosis with a predilection for bone and synovium may complicate the course of patients on long-term hemodialysis. This form of amyloidosis can be typed as distinct from other amyloid diseases by using small tissue samples obtained by bone biopsy and at postmortem. Immunoblot analysis of two-dimensional gels of partially solubilized amyloid fibrils established that tissue deposits are composed of monomers, dimers, and higher polymers of beta 2-microglobulin (beta 2m) and that amyloid P component was also present. Anti-beta 2m antiserum recognized fibrils, as shown by immunoelectron microscopy. Purified monomer isolated from dissociated fibrils yielded peptides corresponding to the entire known sequence of beta 2m. Virtually all serum beta 2m, as well as that present in tissue fluid bathing amyloid fibrils, was monomeric. Hemodialysis-related amyloidosis is an example of a deposition disease occurring in hemodialysis patients. We have shown conclusively that, in this amyloid disease, polymerization of an intact normal serum protein to a fibrillar configuration may occur without proteolysis. We propose the designation A beta 2m for this form of amyloid fibril subunit protein. Images PMID:3532124

  2. [beta subsccript 2]-microglobulin forms three-dimensional domain-swapped amyloid fibrils with disulfide linkages

    SciTech Connect

    Liu, Cong; Sawaya, Michael R.; Eisenberg, David

    2011-08-09

    {beta}{sub 2}-microglobulin ({beta}{sub 2}-m) is the light chain of the type I major histocompatibility complex. It deposits as amyloid fibrils within joints during long-term hemodialysis treatment. Despite the devastating effects of dialysis-related amyloidosis, full understanding of how fibrils form from soluble {beta}{sub 2}-m remains elusive. Here we show that {beta}{sub 2}-m can oligomerize and fibrillize via three-dimensional domain swapping. Isolating a covalently bound, domain-swapped dimer from {beta}{sub 2}-m oligomers on the pathway to fibrils, we were able to determine its crystal structure. The hinge loop that connects the swapped domain to the core domain includes the fibrillizing segment LSFSKD, whose atomic structure we also determined. The LSFSKD structure reveals a class 5 steric zipper, akin to other amyloid spines. The structures of the dimer and the zipper spine fit well into an atomic model for this fibrillar form of {beta}{sub 2}-m, which assembles slowly under physiological conditions.

  3. The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator

    PubMed Central

    Li, Ling; Dong, Mei; Wang, Xiao-Guang

    2016-01-01

    Objective: This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin2M), a conservative immune molecule in vertebrate. Data Sources: The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search. Study Selections: Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules. Results: β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis. Conclusions: Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications. PMID:26879019

  4. Structural modifications of human beta 2 microglobulin treated with oxygen-derived radicals.

    PubMed Central

    Capeillere-Blandin, C; Delaveau, T; Descamps-Latscha, B

    1991-01-01

    Treatment of human beta 2 microglobulin (beta 2m) with defined oxygen-derived species generated by treatment with gamma-radiation was studied. As assessed by SDS/PAGE, the hydroxyl radicals (.OH) caused the disappearance of the protein band at 12 kDa that represents beta 2m, and cross-linked the protein into protein bands stable to both SDS and reducing conditions. However, when .OH was generated under oxygen in equimolar combination with the superoxide anion radical (O2.-), the high-molecular-mass protein products were less represented, and fragmented derivatives were not obviously detectable. Exposure to .OH alone, or to .OH + O2.- in the presence of O2, induced the formation of beta 2m protein derivatives with a more acidic net electrical charge than the parent molecule. In contrast, O2.- alone had virtually no effect on molecular mass or pI. Changes in u.v. fluorescence during .OH attack indicated changes in conformation, as confirmed by c.d. spectrometry. A high concentration of radicals caused the disappearance of the beta-pleated sheet structure and the formation of a random coil structure. Loss of tryptophan and significant production of dityrosine (2,2'-biphenol type) were noted, exhibiting a clear dose-dependence with .OH alone or with .OH + O2.-. The combination of .OH + O2.- induced a pattern of changes similar to that with .OH alone, but more extensive for c.d. and tryptophan oxidation (2 Trp/beta 2m molecule), and more limited for dityrosine formation. Lower levels of these oxidative agents caused the reproducible formation of species at 18 and 25 kDa which were recognized by antibodies against native beta 2m. These findings provide a model for the protein pattern observed in beta 2m amyloidosis described in the literature. Images Fig. 4. Fig. 5. PMID:1649598

  5. Electron microscopic localization of receptors for aggregated beta 2-microglobulin on the surface of beta-hemolytic streptococci.

    PubMed Central

    Wagner, M; Wagner, B; Kronvall, G; Björck, L

    1983-01-01

    The presence and location of receptors for aggregated human beta 2-microglobulin (beta 2m) on the surface of group A, C, and G streptococci were studied by electron microscopic techniques. Ferritin-conjugated aggregates of human beta 2m were used in direct binding experiments. Ferritin-conjugated antibodies against beta 2m were employed in a two-step indirect binding assay where the streptococci were incubated with unlabeled beta 2m aggregates before the addition of antibodies. Similar results were obtained with these two methods. Among tested group C and G strains, some showed binding of beta 2m, whereas others were negative. In group A streptococci, beta 2m binding was localized to filamentous structures typical of M protein. In two M protein-negative group A strains, the reactivity was heterogeneous, revealing a majority of unlabeled, but also some heavily labeled streptococci. Morphologically, these beta 2m-binding bacteria exhibited M protein-like projections in contrast to the smooth surfaces of unlabeled cells. Images PMID:6352498

  6. Interaction between the renal excretion rates of beta 2-microglobulin and tobramycin in man.

    PubMed

    Vree, T B; Zweens, K; Huige, P J; Guelen, P J; Jongman-Nix, B

    1984-03-27

    The renal excretion rate of beta 2-microglobulin in man is 127 +/- 98 ng/min at alkaline urine pH (pH 7). Tobramycin, up to intravenous doses of 160 mg (2 mg/kg) does not increase the renal excretion rate of beta 2-microglobulin. Tobramycin must have less affinity than gentamicin for the tubular system for active reabsorption of amino groups containing organic compounds. Due to this reduced affinity tobramycin will be absorbed less by the proximal tubular cells, which may be one of the reasons for tobramycin being less toxic than gentamicin. beta 2-Microglobulin excretion can be used as a parameter for the relative binding affinity of aminoglycosides. PMID:6370509

  7. Beta2-microglobuline plasma level and painful shoulder in haemodialysed patients.

    PubMed

    Barisić, Igor; Ljutić, Dragan; Vlak, Tonko; Bekavac, Josip; Perić, Irena; Mise, Kornelija; Klancnik, Marisa; Janković, Stipan

    2010-03-01

    Painful shoulder in patients on chronic haemodialyis is most often associated with dialysis arthropathy or accumulation of deposits containing modified fibrils of beta2- microglobuline especially in bones and joints due to insufficient elimination during the therapy. The aim of this study is to investigate whether there is connection between painful shoulder and plasma level of beta2-microglobuline and to corroborate that with morphologic parameters found in proved amyloidosis. It has to be emphasized that even other causes may contribute the development of painful shoulder. Real time sonography and conventional plain radiographs of the 108 shoulders were performed in 54 patients receiving chronic haemodialysis as a treatment of terminal renal failure (without previous history of rheumatoid arthritis), 27 symptomatic with persistent pain and stiffness in both shoulders and lasting for more than 6 weeks and restriction of movements in various degree and 27 asymptomatic. Plasma level of beta2-microglobuline, CRP and uric acid were taken periodically as routine procedure during a one year prospective trial, as well as plasma level of calcium, phosphor and alkaline phosphatase. Plasmatic level of beta2-microglobuline is strongly connected with painful shoulder in dialyzed patients, as well as CRP as sign of acute inflammation. That is proved by morphologic parameters associated with histological proved amyloidosis in patients on long term dialysis, more then 10 years. PMID:20402341

  8. Pseudotumoral amyloidosis of beta 2-microglobulin origin in the buttock of a patient receiving long term haemodialysis.

    PubMed Central

    Fernández-Alonso, J; Rios-Camacho, C; Valenzuela-Castaño, A; Rocha-Castilla, J L

    1993-01-01

    A 52 year old man who had been receiving haemodialysis for 13 years, with a history of renal tuberculosis, right ischial tuberculous osteomyelitis, and dialysis arthropathy, developed a soft tissue tumour in his left buttock. Histological analysis, immunohistological staining, and electron microscopic examination of the surgically removed tumour showed massive deposits of beta 2-microglobulin (beta 2-M) amyloid. This case shows the expanding clinical spectrum of this type of amyloidosis, and it is suggested that amyloid infiltration should be considered in the differential diagnosis of gluteal tumours in these patients. Images PMID:8408708

  9. Serum beta-2 microglobulin as a prognostic biomarker in patients with mantle cell lymphoma.

    PubMed

    Yoo, Changhoon; Yoon, Dok Hyun; Kim, Shin; Huh, Jooryung; Park, Chan-Sik; Park, Chan-Jeong; Lee, Sang-Wook; Suh, Cheolwon

    2016-03-01

    Although serum beta-2 microglobulin (B2M) has been suggested as a prognostic factor for mantle cell lymphoma (MCL), additional data are necessary to confirm its role. Between November 2005 and July 2014, a total of 52 patients with MCL were identified from the database of Asan Medical Center, Seoul, Korea. Pretreatment serum B2M information was available in 50 patients (96%). Overall survival (OS) was compared according to the serum B2M level with a cut-off value of 2.5 mg/L. The median MCL international prognostic index (MIPI) score was 5.84 (range 4.72-7.80), and the median biologic MIPI (MIPI-b) score was 6.27 (4.93-8.47). Pretreatment serum B2M was elevated in 30 patients (60%) and was significantly related to advanced stage (p = 0.02) and high MIPI (p = 0.03) and MIPI-b (p = 0.03) scores. With median follow-up duration of 29.8 months (range 0.8-87.0 months), the median OS was 56.2 months [95% confidence interval (CI) 36.6-75.9 months] in all patients, and serum B2M was significantly associated with OS (p = 0.001). In multivariate analyses adjusted for MIPI or MIPI-b scores and rituximab, elevated serum B2M was significantly associated with poor OS (when adjusting MIPI, hazard ratio = 26.4, 95% CI 2.9-241.3, p = 0.004; when adjusting MIPI-b, hazard ratio = 20.1, 95% CI 2.4-170.1, p = 0.006). Thus, pretreatment serum B2M may be an independent and significant prognostic factor in patients with MCL. PMID:25689467

  10. [INTERACTION OF THE DYE CONGO RED WITH FIBRILS OF LYSOZYME, BETA2-MICROGLOBULIN AND TRANSTHYRETIN].

    PubMed

    Antimonova, O I; Grudinina, N A; Egorov, V V; Polyakov, D S; Iljin, V V; Shavlovsky, M M

    2016-01-01

    By means of spectrophotometric assay we investigated interaction of the dye Congo red (CR) with fibrils of model proteins--hen egg white lysozyme, recombinant human beta2-microglobulin (b2M) and recombinant human transthyretin (TTR). The commercial dye sample was found to contain a significant amount of impurities. Methods for the dye purification are disclosed and CR molar extinction coefficient at 490 nm (ε490) was determined to be 3.3 x 10(4) M(-1) x cm(-1) at pH above 6.0. Formation of the CR-fibril complex results in changes in the dye visible absorption spectrum. According to the data on titration of fibril solutions with excess of the dye, CR binds to lysozyme fibrils at a ratio of about 5 molecules per protein monomer within fibril structure, to b2M fibrils--about 4 molecules per monomer, to TTR fibrils--about 4 molecules per subunit of the protein. PMID:27228663

  11. 'Dialysis related arthropathy': a survey of 95 patients receiving chronic haemodialysis with special reference to beta 2 microglobulin related amyloidosis.

    PubMed Central

    Hurst, N P; van den Berg, R; Disney, A; Alcock, M; Albertyn, L; Green, M; Pascoe, V

    1989-01-01

    Ninety five patients receiving chronic haemodialysis (CHD) were surveyed to determine the prevalence of rheumatic disease and, where possible, its aetiology. At least three distinct rheumatic syndromes were identified--a group of patients with a syndrome consisting of large and medium joint synovial swelling, restricted hips and shoulders, tenosynovitis, carpal tunnel syndrome, and bone cysts due to deposition of beta 2 microglobulin related amyloid (AM beta 2m); a second group with erosive azotaemic osteoarthropathy; and a third group with age related degenerative disease of small, large, and axial joints. The data presented suggest that in patients receiving CHD (a) the prevalence of AM beta 2m deposition and the associated syndrome increases with duration of dialysis, but in patients who have been dialysed for more than 10 years the risk of developing AM beta 2m is related to age; (b) AM beta 2m deposition in subchondral cysts, but not synovium, causes joint destruction; also, AM beta 2m may be more prone to deposition in synovium of joints already damaged by other processes; (c) in the absence of synovial iron deposition synovial AM beta 2m is not associated with an inflammatory infiltrate; (d) hyperparathyroidism and perhaps other factors such as synovial iron deposition are probably more important than AM beta 2m as causes of peripheral joint degeneration and destructive spondyloarthropathy in patients receiving CHD. Images PMID:2658876

  12. Differential inhibition of mitogenic responsiveness by monoclonal antibodies to beta 2-microglobulin.

    PubMed

    Tam, P E; Messner, R P

    1991-03-01

    A panel of 10 monoclonal antibodies (MoAbs) to human beta 2-microglobulin (beta 2m) was used to evaluate the modulation of lymphocyte activation induced by different mitogenic stimuli. All 10 MoAbs inhibited proliferative responses of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and allogeneic cells in mixed lymphocyte culture (MLC), although some MoAbs were inhibitory at much lower concentrations than others. No enhancement or direct mitogenicity was observed, but at low MoAb concentrations a delayed peak response sometimes occurred. Differentiation of B cells in PWM-stimulated PBMC cultures was also inhibited as measured by reduced accumulation of supernatant IgM and IgG. Anti-beta 2m MoAb did not interfere with the binding of PHA or PWM to PBMC, and membrane mobility as judged by subsequent capping of these lectins also appeared to be normal. Furthermore, anti-beta 2m was inhibitory when added 24 hr prior to peak responsiveness, and proliferative responses to the phorbol ester PMA in combination with ionomycin were also inhibited by MoAb, indicating that membrane-mediated events were not the target of inhibition. A comparison of the inhibitory effects of anti-beta 2m MoAb on activation by different stimuli revealed that PWM and MLC responses were much more sensitive to inhibition followed by, in order of decreasing inhibition, Con A, PHA, ionomycin alone, and PMA/ionomycin. A MoAb to a monomorphic determinant of HLA-A, B, C exhibited the same inhibitory trend, suggesting that the mechanism of inhibition was the same as for anti-beta 2m MoAbs. No inhibition was observed when PBMC were stimulated by PMA alone, suggesting that the MoAbs have little effect on activation mediated by protein kinase C but may preferentially affect the calcium-dependent pathway of activation. Thus, this differential inhibition observed with different stimuli may reflect the relative contribution of class I

  13. Receptors for fibrinogen and aggregated beta 2-microglobulin detected in strains of group B streptococci.

    PubMed Central

    Schönbeck, C; Björck, L; Kronvall, G

    1981-01-01

    Binding of radiolabeled human fibrinogen and aggregated beta-microglobulin was measured in 60 strains of beta-hemolytic group B streptococci. Positive fibrinogen binding was detected in seven of the strains. Six of the group B strains showed an uptake of aggregated beta 2-microglobulin. Four individual strains carried both receptors, indicating a positive correlation between their occurrence. Inhibition studies showed that fibrinogen competed sterically with beta 2-microglobulin binding. Receptors for both proteins were trypsin sensitive. The presence of receptors did not correlate with the serological type of the 49 group B strains tested. However, all seven type II strains were negative. No uptake of fibrinogen was noted in any of 40 group D strains tested. Binding structures for fibrinogen and aggregated beta 2-microglobulin detected in group B streptococci were similar to receptors for the same proteins in group A, C, and G streptococci in terms of mutual correlation and steric interference of binding. The occasional occurrence of these receptors also in group B strains might reflect a common origin of some types of surface proteins in gram-positive cocci. PMID:6164650

  14. Seeding-dependent maturation of beta2-microglobulin amyloid fibrils at neutral pH.

    PubMed

    Kihara, Miho; Chatani, Eri; Sakai, Miyo; Hasegawa, Kazuhiro; Naiki, Hironobu; Goto, Yuji

    2005-03-25

    Beta2-microglobulin (beta2-m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Recent studies have focused on the mechanism by which amyloid fibrils are formed under physiological conditions, which had been difficult to reproduce quantitatively. Yamamoto et al. (Yamamoto, S., Hasegawa, K., Yamaguchi, I., Tsutsumi, S., Kardos, J., Goto, Y., Gejyo, F. & Naiki, H. (2004) Biochemistry 43, 11075-11082) showed that a combination of seed fibrils prepared under acidic conditions and a low concentration of sodium dodecyl sulfate below its critical micelle concentration enabled extensive fibril formation at pH 7.0. Here, we found that repeated self-seeding at pH 7.0 with fibrils formed at the same pH causes a marked acceleration of growth, indicating the maturation of fibrils. The observed maturation can be simulated by assuming the existence of two types of fibrils with different growth rates. Importantly, some mutations of beta2-m or the addition of a low concentration of urea, both destabilizing the native conformation, were not enough to extend the fibrils at pH 7.0, and a low concentration of sodium dodecyl sulfate (i.e. 0.5 mM) was essential. Thus, even though the first stage fibrils in patients are unstable and require stabilizing factors to remain at neutral pH, they can adapt to a neutral pH with repeated self-seeding, implying a mechanism of development of amyloid deposition after a long latent period in patients. PMID:15659393

  15. Soluble histocompatibility class I antigens and beta 2-microglobulin in pregnant females and cord blood samples.

    PubMed

    Inostroza, J; Ferrada, J; Navarrete, C; Sorensen, R U

    1997-04-15

    Pregnancy can be considered a successful transplantation of allogeneic paternal tissue to the mother. Soluble HLA class I serum levels have been found to increase during solid organ rejection episodes and during graft-versus-host disease after bone marrow transplantation. We wished to determine whether significant changes in sHLA class I and beta 2-microglobulin light chain levels occurred during pregnancy, because these may reflect adaptive changes permitting the acceptance of the fetal graft. Serum samples were obtained from women at different stages of pregnancy and in the postpartum period. Cord blood samples and serum samples from nonpregnant female and male controls living in the same geographic area in Southern Chile were also studied. The levels of sHLA class I heterodimers were determined by an ELISA sandwich technique; beta 2-microglobulin levels were measured by MEIA IMX-Abbott. There was a significant elevation of sHLA class I levels in the first 2 trimesters of pregnancy, followed by a significant drop below normal levels at the end of pregnancy, with normalization in the post-partum period. beta 2-microglobulin levels did not change significantly during pregnancy and did not correlate with sHLA class I levels. In cord blood samples, sHLA class I levels were lower and beta 2-microglobulin levels higher than those of adult controls and of mothers at the time of delivery. The variations in sHLA class I levels during pregnancy may reflect or contribute to immunoregulatory events related to the acceptance of the fetal graft. PMID:9154459

  16. Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children

    PubMed Central

    Herrero-Morín, José David; Málaga, Serafín; Fernández, Nuria; Rey, Corsino; Diéguez, María Ángeles; Solís, Gonzalo; Concha, Andrés; Medina, Alberto

    2007-01-01

    Introduction Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children. Methods This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m2 was evaluated using receiver operating characteristic (ROC) curve analysis. Results Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m2 in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m2 in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m2 was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine). Conclusion Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children. PMID:17519026

  17. The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

    PubMed

    Vree, T B; Guelen, P J; Jongman-Nix, B; Walenkamp, G H

    1981-07-18

    The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin. PMID:6166414

  18. Beta 2-microglobulin-dependent T cells are dispensable for allergen-induced T helper 2 responses.

    PubMed

    Zhang, Y; Rogers, K H; Lewis, D B

    1996-10-01

    CD4+ and CD8+ alpha/beta+ T cells of the T helper cell (Th)2 phenotype produce the cytokines IL-4, IL-5, and IL-13 that promote IgE production and eosinophilic inflammation. IL-4 may play an important role in mediating the differentiation of antigenically naive alpha/beta+ T cells into Th2 cells. Murine NK1.1+ (CD4+ or CD4-CD8-) alpha/beta+ T cells comprise a beta 2-microglobulin (beta 2m)-dependent cell population that rapidly produces IL-4 after cell activation in vitro and in vivo and has been proposed as a source of IL-4 for Th2 cell differentiation. alpha/beta+ CD8+ T cells, most of which require beta 2m for their development, have also been proposed as positive regulators of allergen-induced Th2 responses. We tested whether beta 2m-dependent T cells were essential for Th2 cell-mediated allergic reactions by treating wild-type, beta 2m-deficient (beta 2m -/-), and IL-4-deficient (IL-4 -/-) mice of the C57BL/6 genetic background with ovalbumin (OVA), using a protocol that induces robust allergic pulmonary disease in wild-type mice. OVA-treated beta 2m -/- mice had circulating levels of total and OVA-specific IgE, pulmonary eosinophilia, and expression of IL-4, IL-5, and IL-13 mRNA in bronchial lymph node tissue similar to that of OVA-treated wild-type mice. In contrast, these responses in OVA-treated IL-4 -/- mice were all either undetectable or markedly reduced compared with wild-type mice, confirming that IL-4 was required in this allergic model. These results indicate that the NK1.1+ alpha/beta+ T cell population, as well as other beta 2m-dependent populations, such as most peripheral alpha/beta+ CD8+ T cells, are dispensable for the Th2 pulmonary response to protein allergens. PMID:8879221

  19. Urinary cadmium and beta2-microglobulin: correlation with nutrition and smoking history (journal version)

    SciTech Connect

    Kowal, N.E.

    1988-01-01

    Urinary cadmium and beta2-microglobulin concentrations from approximately 1000 samples from the general adult U.S. population, collected as part of the National Health and Nutritional Examination Survey II (NHANES II), were related to nutritional and smoking history of the individuals. Urinary cadmium concentration was negatively correlated with dietary iron (significance level of 0.0065), negatively correlated with dietary calcium (significance level of less than 0.0001), and significantly (level of less than 0.001) higher in past or present smokers than in those who had never smoked. The results suggest increased cadmium absorption in the presence of low dietary intake of iron, low dietary intake of calcium, and cigarette smoking in the general population of the United States.

  20. The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis.

    PubMed

    Ugan, Yunus; Korkmaz, Hakan; Dogru, Atalay; Koca, Yavuz Savas; Balkarlı, Ayse; Aylak, Firdevs; Tunc, Sevket Ercan

    2016-07-01

    The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-β2M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1-1.5 mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-β2M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-β2M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p < 0.001, p < 0.001, and p < 0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p < 0.001, p = 0.016, p = 0.004, microalbuminuria p < 0.001, p < 0.001, p < 0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p = 0.004). Determination of U-β2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies. PMID:26873102

  1. Imaging of dialysis-related amyloid (AB-amyloid) deposits with sup 131 I-beta 2-microglobulin

    SciTech Connect

    Floege, J.; Burchert, W.; Brandis, A.; Gielow, P.; Nonnast-Daniel, B.; Spindler, E.; Hundeshagen, H.; Shaldon, S.; Koch, K.M. )

    1990-12-01

    The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

  2. Measurement of glomerular filtration rate in homozygous sickle cell disease: a comparison of 51Cr-EDTA clearance, creatinine clearance, serum creatinine and beta 2 microglobulin.

    PubMed Central

    Aparicio, S A; Mojiminiyi, S; Kay, J D; Shepstone, B J; de Ceulaer, K; Serjeant, G R

    1990-01-01

    Glomerular filtration rates (GFR) were measured with 51Cr-EDTA in 38 patients (aged 40-75 years) with homozygous sickle cell disease and compared with serum beta 2 microglobulin concentrations in 38 patients and with creatinine clearance in 21 patients. GFR estimated with 51Cr-EDTA was closely correlated with single serum creatinine measurements and the inverse of serum beta 2 microglobulin. Creatinine clearance was also found to be correlated, but values were, on average, 32% below those obtained by the 51Cr-EDTA method, and this difference was significant. It is concluded that measurements of beta 2 microglobulin, single serum creatinine, and creatinine clearance are valuable indicators of GFR in homozygous sickle cell disease. Measurement of beta 2 microglobulin was a useful and reliable method of estimating GFR from single plasma measurements and is therefore a useful means of screening the population. PMID:2115049

  3. Beta-2 microglobulin and lactate dehydrogenase levels are useful prognostic markers in early stage primary gastric lymphoma.

    PubMed

    Avilés, A; Narváez, B R

    1998-10-01

    The optimal management of primary gastric lymphoma (PGL) remains undecided because a definitive classification for therapeutic decision is not available. The International Index Project has proved to be useful in patients with nodal disease, but in extranodal presentation it has not been tested. We reviewed 297 patients with early stage PGL. They were initially classified according to the prognostic features of the International Index Project. No influence on duration of time to treatment failure (TTF) or overall survival was observed. For this reason we developed a logistical model to identify prognostic factors in patients with early stage PGL. Levels of beta-2 microglobulin and lactic dehydrogenase were observed to have prognostic significance in both univariate and multivariate analysis. With these parameters we constructed a logistical model to identify patients at low risk (TTF = 76%; at 7 years overall survival was 96%), statistically different to patients at high risk (TTF = 34% and overall survival = 22%). The number of patients at intermediate risk were too small to compare with the other groups. Because pathological or other clinical or laboratory prognostic features cannot help in the identification of a prognostic model, we propose that the use beta-2 microglobulin and lactic dehydrogenase can define different groups at risk and develop a prognostic system to define the best therapeutic approach in this patients. PMID:9807677

  4. Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses.

    PubMed Central

    Spriggs, M K; Koller, B H; Sato, T; Morrissey, P J; Fanslow, W C; Smithies, O; Voice, R F; Widmer, M B; Maliszewski, C R

    1992-01-01

    Transgenic mice lacking an intact beta 2-microglobulin (beta 2m) gene fail to express major histocompatibility complex (MHC) class I proteins on the cell surface and, as a result, are virtually devoid of CD4- CD8+ lymphocytes. These animals provide a unique model system for directly assessing the role of CD8+ lymphocytes in the modulation of viral infection in vivo. beta 2m- CD8- mice and their normal littermates were inoculated at the base of the tail with the WR strain of vaccinia virus and monitored for serum antibody and lesion formation. Both groups developed similar lesions in response to a broad virus dose range, and all animals had completely recovered by day 28 after inoculation. Isotype-specific immunoglobulin levels were determined for each animal on day 7 and day 14 after primary inoculation, and again 7 days after a virus challenge. The virus-specific IgG1, IgG2a, and IgG2b levels were significantly different in the beta 2m-/- group (20-, 9-, and 30-fold lower, respectively, on day 7 after challenge) compared with the beta 2m+/- group. Virus-specific serum IgM levels for both groups remained similar throughout the experiment. In a separate experiment, beta 2m-/- mice were immunized with a nonviral antigen, 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin, and both total and antigen-specific isotype-specific immunoglobulin titers were determined. Total IgG1, IgG2a, IgG2b, and IgG3 tended to be lower overall in the beta 2m-/- mice compared with beta 2m+/- littermates. In contrast, total and antigen-specific IgE titers were similar in the two groups. These data indicate that CD8+ lymphocytes are not required to clear high doses of vaccinia virus, and they suggest that beta 2m-/- mice are less efficient at antigen-specific IgG production than their beta 2m+/- littermates. PMID:1631092

  5. Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA.

    PubMed Central

    Wang, Z; Cao, Y; Albino, A P; Zeff, R A; Houghton, A; Ferrone, S

    1993-01-01

    The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2-mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression. Images PMID:8432869

  6. A Study on the Relationship between Serum Beta 2-Microglobulin Levels, Underlying Chronic Kidney Disease, and Peripheral Arterial Disease in High-Vascular-Risk Patients

    PubMed Central

    Real de Asúa, Diego; Puchades, Ramón; García-Polo, Iluminada; Suárez, Carmen

    2012-01-01

    Background Serum beta 2-microglobulin (B2M) levels have been found to be increased in patients with peripheral arterial disease (PAD), yet it is still unknown whether B2M correlates with PAD intensity. Objectives We aim to evaluate the correlation between B2M and the ankle-brachial index (ABI) values in high-vascular-risk patients. Methods This is a cross-sectional study of 63 high-vascular-risk patients admitted to the Cardiology Department or evaluated as outpatients in the Internal Medicine Department of our institution. Patients were classified into two groups according to their ABI: patients without PAD (n = 44, ABI values between 0.9 and 1.4) and patients with PAD (n = 19, ABI values lower than 0.9 or higher than 1.4). We performed univariate and multivariate analysis based on a multiple linear regression model. Results Serum B2M levels were higher in patients with pathological ABI values than in those without PAD (2.36 ± 1.13 vs. 1.80 ± 0.65 mg/L; P<0.05). We found no correlation between B2M and ABI in our total population (r = –0.12) or in patients with PAD (r = –0.09; NS for both comparisons). Age, gender, arterial hypertension, estimated glomerular filtration rate (eGFR), uric acid, total cholesterol, and LDL-cholesterol correlated with B2M in the univariate analysis. In the final linear regression model, eGFR, uric acid and total cholesterol correlated independently with B2M (P<0.01). Conclusion We found no correlation between B2M levels and ABI values in high-vascular-risk patients that could usefully help in the subsequent diagnosis of PAD. However, we observed a significant correlation between B2M and eGFR, even when renal function was only slightly impaired. PMID:24757603

  7. Revisiting the Middle Molecule Hypothesis of Uremic Toxicity: A Systematic Review of Beta 2 Microglobulin Population Kinetics and Large Scale Modeling of Hemodialysis Trials In Silico

    PubMed Central

    Roumelioti, Maria Eleni; Nolin, Thomas; Unruh, Mark L.; Argyropoulos, Christos

    2016-01-01

    Background Beta-2 Microglobulin2M) is a prototypical “middle molecule” uremic toxin that has been associated with a higher risk of death in hemodialysis patients. A quantitative description of the relative importance of factors determining β2M concentrations among patients with impaired kidney function is currently lacking. Methods Herein we undertook a systematic review of existing studies reporting patient level data concerning generation, elimination and distribution of β2M in order to develop a population model of β2M kinetics. We used this model and previously determined relationships between predialysis β2M concentration and survival, to simulate the population distribution of predialysis β2M and the associated relative risk (RR) of death in patients receiving conventional thrice-weekly hemodialysis with low flux (LF) and high flux (HF) dialyzers, short (SD) and long daily (LD) HF hemodialysis sessions and on-line hemodiafiltration at different levels of residual renal function (RRF). Results We identified 9 studies of 106 individuals and 156 evaluations of or more compartmental kinetic parameters of β2M. These studies used a variety of experimental methods to determine β2M kinetics ranging from isotopic dilution to profiling of intra/inter dialytic concentration changes. Most of the patients (74/106) were on dialysis with minimal RRF, thus facilitating the estimation of non-renal elimination kinetics of β2M. In large scale (N = 10000) simulations of individuals drawn from the population of β2M kinetic parameters, we found that, higher dialytic removal materially affects β2M exposures only when RRF (renal clearance of β2M) was below 2 ml/min. In patients initiating conventional HF hemodialysis, total loss of RRF was predicted to be associated with a RR of death of more than 20%. Hemodiafiltration and daily dialysis may decrease the high risk of death of anuric patients by 10% relative to conventional, thrice weekly HF dialysis. Only daily

  8. beta-2 Microglobulin values among human immunodeficiency virus (HIV)-negative, HIV-positive asymptomatic, and HIV-positive symptomatic Ugandans.

    PubMed Central

    Piwowar, E M; Tugume, S B; Grant, R M; Lutalo, T; Pattishall, K; Katongole-Mbidde, E

    1995-01-01

    Mean serum beta-2 microglobulin levels among healthy human immunodeficiency virus-seronegative and asymptomatic and symptomatic human immunodeficiency virus-seropositive Ugandans were found to be 2.35, 3.75, and 5.06 mg/liter, respectively (P < 0.001). The upper limit of the normal range (3.5 mg/liter) is higher in this African population than that reported elsewhere. PMID:7697536

  9. Structural Analysis of H2-Db Class I Molecules Containing Two Different Allelic Forms of the type 1 Diabetes Susceptibility Factor beta-2 Microglobulin: Implications for the Mechanism Underlying Viriations in Antigen Presentation

    SciTech Connect

    Roden,M.; Brims, D.; Fedorov, A.; DiLorenzo, T.; Almo, S.; Nathenson, s.; Anovitz, L.; Wesolowski, D.

    2006-01-01

    Beta-2 microglobulin ({beta}2m) is a member of the immunoglobulin-like domain superfamily that is an essential structural subunit of the MHC class I (MHC-I) molecule. {beta}2m was previously identified as a susceptibility factor for the development of type 1 diabetes (T1D) in NOD mice, whereby transgenic expression of the {beta}2m{sup a} variant, but not the {beta}2mb variant, restored diabetes susceptibility to normally resistant NOD.{beta}2m{sup null} mice. Here we report the crystal structures and thermodynamic stabilities of the NOD MHC-I molecule H2-D{sup b} containing these two variants. Our results reveal subtle differences in the structures of the {beta}2m variants, namely in minor loop shifts and in variations in the hydrogen bonding networks at the interfaces between the components of the ternary complex. We also demonstrate that the thermodynamic stabilities of the {beta}2m variants in isolation differ. However, the conformation of the peptide in the MHC cleft is unchanged in {beta}2m allelic Db complexes, as are the TCR recognition surfaces. Thus, despite modest structural differences between allelic complexes, the evidence indicates that D{sup b} peptide presentation of the representative peptide is unchanged in the context of either {beta}2m allelic variant. These data suggest that other mechanisms, such as differential association of MHC-I in multiprotein complexes, are likely responsible for the effect of {beta}2m on T1D development.

  10. The relationship between concentrations of magnesium and oxidized low-density lipoprotein and Beta2-microglobulin in the serum of patients on the end-stage of renal disease.

    PubMed

    Raikou, Vaia D; Kyriaki, Despina

    2016-05-01

    The end-stage of renal disease is associated with increased oxidative stress and oxidative modification of low-density lipoproteins (LDLs). Beta2 microglobulin (beta2M) is accumulated in the serum of dialysis patients. Magnesium (Mg) plays a protective role in the development of oxidative stress in healthy subjects. We studied the relationship between concentrations of magnesium and oxidized LDL (ox-LDL) and beta2M in the serum of patients on the end stage of renal disease. In 96 patients on on-line- predilution hemodiafiltration, beta2M and intact parathormone were measured by radioimmunoassays. High-sensitivity C-reactive protein (hsCRP) and ox-LDL were measured using ΕLISA. Serum bicarbonate levels were measured in the blood gas analyser gas machine. We performed logistic regression analysis models to investigate Mg as an important independent predictor of elevated ox-LDL and high beta2M serum concentrations, after adjustment to traditional and specific for dialysis patients' factors. We observed a positive correlation of Mg with ox-LDL (r = 0.383, P = 0.001), but the association of Mg with beta2M, hsCRP, and serum bicarbonate levels was significantly inverse (r = -0.252, P = 0.01, r = -0.292, P = 0.004, and r = -0.282, P = 0.04 respectively). The built logistic-regression analysis showed that Mg act as a significant independent factor for the elevated ox-LDL and beta2M serum concentrations adjusting to traditional and specific factors for these patients. We observed a positive relationship between magnesium and acidosis status- related ox-LDL concentrations, but the inverse association between magnesium and beta2M serum concentrations in hemodialysis patients. PMID:27215248

  11. Calcium Binding to Beta-2-Microglobulin at Physiological Ph Drives the Occurrence of Conformational Changes Which Cause the Protein to Precipitate into Amorphous Forms That Subsequently Transform into Amyloid Aggregates

    PubMed Central

    Kumar, Sukhdeep; Sharma, Prerna; Arora, Kanika; Raje, Manoj; Guptasarma, Purnananda

    2014-01-01

    Using spectroscopic, calorimetric and microscopic methods, we demonstrate that calcium binds to beta-2-microglobulin2m) under physiological conditions of pH and ionic strength, in biological buffers, causing a conformational change associated with the binding of up to four calcium atoms per β2m molecule, with a marked transformation of some random coil structure into beta sheet structure, and culminating in the aggregation of the protein at physiological (serum) concentrations of calcium and β2m. We draw attention to the fact that the sequence of β2m contains several potential calcium-binding motifs of the DXD and DXDXD (or DXEXD) varieties. We establish (a) that the microscopic aggregation seen at physiological concentrations of β2m and calcium turns into actual turbidity and visible precipitation at higher concentrations of protein and β2m, (b) that this initial aggregation/precipitation leads to the formation of amorphous aggregates, (c) that the formation of the amorphous aggregates can be partially reversed through the addition of the divalent ion chelating agent, EDTA, and (d) that upon incubation for a few weeks, the amorphous aggregates appear to support the formation of amyloid aggregates that bind to the dye, thioflavin T (ThT), resulting in increase in the dye's fluorescence. We speculate that β2m exists in the form of microscopic aggregates in vivo and that these don't progress to form larger amyloid aggregates because protein concentrations remain low under normal conditions of kidney function and β2m degradation. However, when kidney function is compromised and especially when dialysis is performed, β2m concentrations probably transiently rise to yield large aggregates that deposit in bone joints and transform into amyloids during dialysis related amyloidosis. PMID:24755626

  12. Excretion of urinary cadmium, copper, and zinc in cadmium-exposed and nonexposed subjects, with special reference to urinary excretion of beta2-microglobulin and metallothionein.

    PubMed

    Nakajima, Maki; Kobayashi, Etsuko; Suwazono, Yasushi; Uetani, Mirei; Oishi, Mitsuhiro; Inaba, Takeya; Kido, Teruhiko; Shaikh, Zahir A; Nogawa, Koji

    2005-01-01

    The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd), copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of beta2-microglobulin [U-beta2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-beta2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls. Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-beta2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-beta2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-beta2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT). PMID:16327056

  13. [The dynamic level of beta 2-microglobulin, the basic lipid peroxidation indices and middle molecules in the blood and urine in patients with acute calculous pyelonephritis against a background of endovascular helium-neon laser therapy].

    PubMed

    Safafov, R M; Ianenko, E K; Nikitinskaia, L P; Golovanov, S A; Drozhzheva, V V; Kon'kova, T A; Danilkov, A P

    1997-01-01

    The authors present the effect of intravenous He-Ne laser therapy on the changes in beta 2-microglobulin, lipid peroxidation, middle-size molecules in the blood and urine of patients with acute calculous pyelonephritis. Endovascular He-Ne laser therapy was found an effective treatment of acute calculous pyelonephritis. The authors propose to combine hemosorption with endovascular He-Ne laser radiation. PMID:9123656

  14. Serum Levels of Beta2-Microglobulin and Free Light Chains of Immunoglobulins Are Associated with Systemic Disease Activity in Primary Sjögren’s Syndrome. Data at Enrollment in the Prospective ASSESS Cohort

    PubMed Central

    Gottenberg, Jacques-Eric; Seror, Raphaèle; Miceli-Richard, Corinne; Benessiano, Joelle; Devauchelle-Pensec, Valerie; Dieude, Philippe; Dubost, Jean-Jacques; Fauchais, Anne-Laure; Goeb, Vincent; Hachulla, Eric; Hatron, Pierre Yves; Larroche, Claire; Le Guern, Véronique; Morel, Jacques; Perdriger, Aleth; Puéchal, Xavier; Rist, Stephanie; Saraux, Alain; Sene, Damien; Sibilia, Jean; Vittecoq, Olivier; Nocturne, Gaétane; Ravaud, Philippe; Mariette, Xavier

    2013-01-01

    Objectives To analyze the clinical and immunological characteristics at enrollment in a large prospective cohort of patients with primary Sjögren's syndrome (pSS) and to investigate the association between serum BAFF, beta2-microglobulin and free light chains of immunoglobulins and systemic disease activity at enrollment. Methods Three hundred and ninety five patients with pSS according to American-European Consensus Criteria were included from fifteen centers of Rheumatology and Internal Medicine in the “Assessment of Systemic Signs and Evolution of Sjögren's Syndrome” (ASSESS) 5-year prospective cohort. At enrollment, serum markers were assessed as well as activity of the disease measured with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results Patient median age was 58 (25th–75th: 51–67) and median disease duration was 5 (2–9) years. Median ESSDAI at enrollment was 2 (0–7) with 30.9% of patients having features of systemic involvement. Patients with elevated BAFF, beta2-microglobulin and kappa, lambda FLCS had higher ESSDAI scores at enrollment (4 [2]–[11] vs 2 [0–7], P = 0.03; 4 [1]–[11] vs 2 [0–7], P< 0.0001); 4 [2]–[10] vs 2 [0–6.6], P< 0.0001 and 4 [2–8.2] vs 2 [0–7.0], P = 0.02, respectively). In multivariate analysis, increased beta2-microglobulin, kappa and lambda FLCs were associated with a higher ESSDAI score. Median BAFF and beta2-microglobulin were higher in the 16 patients with history of lymphoma (1173.3(873.1–3665.5) vs 898.9 (715.9–1187.2) pg/ml, P = 0.01 and 2.6 (2.2–2.9) vs 2.1 (1.8–2.6) mg/l, P = 0.04, respectively). Conclusion In pSS, higher levels of beta2-microglobulin and free light chains of immunoglobulins are associated with increased systemic disease activity. PMID:23717383

  15. Estimation of benchmark dose as the threshold levels of urinary cadmium, based on excretion of total protein, {beta} {sub 2}-microglobulin, and N-acetyl-{beta}-D-glucosaminidase in cadmium nonpolluted regions in Japan

    SciTech Connect

    Kobayashi, Etsuko . E-mail: ekoba@faculty.chiba-u.jp; Suwazono, Yasushi; Uetani, Mirei; Inaba, Takeya; Oishi, Mitsuhiro; Kido, Teruhiko; Nishijo, Muneko; Nakagawa, Hideaki; Nogawa, Koji

    2006-07-15

    Previously, we investigated the association between urinary cadmium (Cd) concentration and indicators of renal dysfunction, including total protein, {beta} {sub 2}-microglobulin ({beta} {sub 2}-MG), and N-acetyl-{beta}-D-glucosaminidase (NAG). In 2778 inhabitants {>=}50 years of age (1114 men, 1664 women) in three different Cd nonpolluted areas in Japan, we showed that a dose-response relationship existed between renal effects and Cd exposure in the general environment without any known Cd pollution. However, we could not estimate the threshold levels of urinary Cd at that time. In the present study, we estimated the threshold levels of urinary Cd as the benchmark dose low (BMDL) using the benchmark dose (BMD) approach. Urinary Cd excretion was divided into 10 categories, and an abnormality rate was calculated for each. Cut-off values for urinary substances were defined as corresponding to the 84% and 95% upper limit values of the target population who have not smoked. Then we calculated the BMD and BMDL using a log-logistic model. The values of BMD and BMDL for all urinary substances could be calculated. The BMDL for the 84% cut-off value of {beta} {sub 2}-MG, setting an abnormal value at 5%, was 2.4 {mu}g/g creatinine (cr) in men and 3.3 {mu}g/g cr in women. In conclusion, the present study demonstrated that the threshold level of urinary Cd could be estimated in people living in the general environment without any known Cd-pollution in Japan, and the value was inferred to be almost the same as that in Belgium, Sweden, and China.

  16. Urinary beta-2 microglobulin and alpha-1 microglobulin are useful screening markers for tenofovir-induced kidney tubulopathy in patients with HIV-1 infection: a diagnostic accuracy study.

    PubMed

    Nishijima, Takeshi; Shimbo, Takuro; Komatsu, Hirokazu; Takano, Misao; Tanuma, Junko; Tsukada, Kunihisa; Teruya, Katsuji; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Oka, Shinichi

    2013-10-01

    Kidney tubulopathy is a well-known adverse event of antiretroviral agent tenofovir. A cross-sectional study was conducted to compare the diagnostic accuracy of five tubular markers, with a collection of abnormalities in these markers as the reference standard. The study subjects were patients with HIV-1 infection on ritonavir-boosted darunavir plus tenofovir/emtricitabine with suppressed viral load. Kidney tubular dysfunction (KTD) was predefined as the presence of at least three abnormalities in the following five parameters: β2-microglobulinuria (β2M), α1-microglobulinuria (α1M), high urinary N-acetyl-β-D-glucosaminidase (NAG), fractional excretion of phosphate (FEIP), and fractional excretion of uric acid (FEUA). Receiver operating characteristic curves and areas under the curves (AUC) were estimated, and the differences between the largest AUC and each of the other AUCs were tested using a nonparametric method. The cutoff value of each tubular marker was determined using raw data of 100% sensitivity with maximal specificity. KTD was diagnosed in 19 of the 190 (10%) patients. The AUCs (95% CIs) of each tubular marker were β2M, 0.970 (0.947-0.992); α1M, 0.968 (0.944-0.992); NAG, 0.901 (0.828-0.974); FEIP, 0.757 (0.607-0.907), and FEUA, 0.762 (0.653-0.872). The AUCs of β2M and α1M were not significantly different, whereas those of the other three markers were smaller. The optimal cutoff values with 100% sensitivity were 1,123 μg/gCr (β2M, specificity 89%), 15.4 mg/gCr (α1M, specificity 87%), 3.58 U/gCr (NAG, specificity 46%), 1.02% (FEIP, specificity 0%), and 3.92% (FEUA, specificity 12%). Urinary β2M and α1M are potentially suitable screening tools for tenofovir-induced KTD. Monitoring either urinary β2M or α1M should be useful in early detection of tenofovir nephrotoxicity. PMID:23467792

  17. Systemic Amyloidosis: Lessons from β2-Microglobulin*

    PubMed Central

    Stoppini, Monica; Bellotti, Vittorio

    2015-01-01

    β2-Microglobulin is responsible for systemic amyloidosis affecting patients undergoing long-term hemodialysis. Its genetic variant D76N causes a very rare form of familial systemic amyloidosis. These two types of amyloidoses differ significantly in terms of the tissue localization of deposits and for major pathological features. Considering how the amyloidogenesis of the β2-microglobulin mechanism has been scrutinized in depth for the last three decades, the comparative analysis of molecular and pathological properties of wild type β2-microglobulin and of the D76N variant offers a unique opportunity to critically reconsider the current understanding of the relation between the protein's structural properties and its pathologic behavior. PMID:25750126

  18. Selective development of T helper (Th)2 cells induced by continuous administration of low dose soluble proteins to normal and beta(2)-microglobulin-deficient BALB/c mice.

    PubMed

    Guery, J C; Galbiati, F; Smiroldo, S; Adorini, L

    1996-02-01

    Continuous administration of soluble proteins, delivered over a 10-d period by a mini-osmotic pump implanted subcutaneously, induces a long-lasting inhibition of antigen-specific T cell proliferation in lymph node cells from BALB/c mice subsequently primed with antigen in adjuvant. The decreased T cell proliferative response is associated with a down-regulation of the T helper cell (Th)1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma and with a strong increase in the secretion of the Th2 cytokines IL-4 and IL-5 by antigen specific CD4+ T cells. This is accompanied by predominant inhibition of antigen-specific antibody production of IgG2a and IgG2b, rather than IgG1 isotype. Interestingly, inhibition of Th1 and priming of Th2 cells is also induced in beta(2) microglobulin-deficient BALB/c mice, indicating that neither CD8+ nor CD4+ NK1.1+ T cells, respectively, are required. The polarization in Th2 cells is stably maintained by T cell lines, all composed of CD4+/CD8- cells expressing T cell receptor for antigen (TCR) alpha/beta chains, derived from BALB/c mice treated with continuous antigen administration, indicating that they originate from Th2 cells fully differentiated in vivo. This polarization is induced in BALB/c mice by continuous administration of any protein antigen tested, including soluble extracts from pathogenic microorganisms. Priming of Th2 cells is dose dependent and it is optimal for low rather than high doses of protein. Blocking endogenous IL-4 in vivo inhibits expansion of antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen-specific Th2 cells, but does not restore IFN-gamma production by T cells from mice treated with soluble antigen, indicating the involvement of two independent mechanisms. Consistent with this, Th2 cell development, but not inhibition of Th1 cells, depends on non-major histocompatibility complex genetic predisposition, since the Th2 response is

  19. Targeted Disruption of the β2-Microglobulin Gene Minimizes the Immunogenicity of Human Embryonic Stem Cells

    PubMed Central

    Quan, Yuan; Yan, Qing; Morales, John E.

    2015-01-01

    Human embryonic stem cells (hESCs) are a promising source of cells for tissue regeneration, yet histoincompatibility remains a major challenge to their clinical application. Because the human leukocyte antigen class I (HLA-I) molecules are the primary mediators of immune rejection, we hypothesized that cells derived from a hESC line lacking HLA-I expression could be transplanted without evoking a robust immune response from allogeneic recipients. In the present study, we used the replacement targeting strategy to delete exons 2 and 3 of β2-microglobulin on both gene alleles in hESCs. Because β2-microglobulin serves as the HLA-I light chain, disruption of the β2-microglobulin gene led to complete HLA-I deficiency on the cell surface of hESCs and their derivatives. Therefore, these cells were resistant to CD8+ T-cell-mediated destruction. Although interferon-γ (IFN-γ) treatment significantly induced β2-microglobulin expression, promoting CD8+ T cell-mediated killing of control hESCs and their derivatives, CD8+ T-cell-mediated cytotoxicity was barely observed with β2-microglobulin-null hESCs and their derivatives treated with IFN-γ. This genetic manipulation to disrupt HLA-I expression did not affect the self-renewal capacity, genomic stability, or pluripotency of hESCs. Despite being relatively sensitive to natural killer (NK) cell-mediated killing due to the lack of HLA-I expression, when transplanted into NK cell-depleted immunocompetent mice, β2-microglobulin-null hESCs developed into tumors resembling those derived from control hESCs in severe combined immunodeficiency mice. These results demonstrate that β2-microglobulin-null hESCs significantly reduce immunogenicity to CD8+ T cells and might provide a renewable source of cells for tissue regeneration without the need for HLA matching in the future. Significance This study reports the generation of a novel β2-microglobulin (B2M)−/− human embryonic stem cell (hESC) line. Differentiated mature cells

  20. A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells

    PubMed Central

    Chiou, Shean-Jaw; Wang, Chan-Chi; Tseng, Yan-Shen; Lee, Yen-Jung; Chen, Shih-Chieh; Chou, Chi-Hsien; Chuang, Lea-Yea; Hong, Yi-Ren; Lu, Chi-Yu; Chiu, Chien-Chih; Chignard, Michel

    2016-01-01

    We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration. PMID:27503241

  1. A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells.

    PubMed

    Chiou, Shean-Jaw; Wang, Chan-Chi; Tseng, Yan-Shen; Lee, Yen-Jung; Chen, Shih-Chieh; Chou, Chi-Hsien; Chuang, Lea-Yea; Hong, Yi-Ren; Lu, Chi-Yu; Chiu, Chien-Chih; Chignard, Michel

    2016-01-01

    We analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration. PMID:27503241

  2. Construction of bioactive chimeric MHC class I tetramer by expression and purification of human-murine chimeric MHC heavy chain and beta(2)m as a fusion protein in Escherichia coli.

    PubMed

    Ren, Ding; Wang, Fang; He, Xiaowen; Jiang, Lei; Li, Dean; Ying, He; Sun, Shuhan

    2006-12-01

    Major histocompatibility (MHC) class I tetramers are used in the quantitative analysis of epitope peptide-specific CD8+ T-cells. An MHC class I tetramer was composed of 4 MHC class I complexes and a fluorescently labeled streptavidin (SA) molecule. Each MHC class I complex consists of an MHC heavy chain, a beta(2)-microglobulin (beta(2)m) molecule and a synthetic epitope peptide. In most previous studies, an MHC class I complex was formed in the refolding buffer with an expressed MHC heavy chain molecule and beta(2)m, respectively. This procedure inevitably resulted in the disadvantages of forming unwanted multimers and self-refolding products, and the purification of each kind of monomer was time-consuming. In the present study, the genes of a human/murine chimeric MHC heavy chain (HLA-A2 alpha1, HLA-A2 alpha2 and MHC-H2D alpha3) and beta(2)m were tandem-cloned into plasmid pET17b and expressed as a fusion protein. The recombinant fusion protein was refolded with each of the three HLA-A2 restricted peptides (HBc18-27 FLPSDFFPSI, HBx52-60 HLSLRGLPV, and HBx92-100 VLHKRTLGL) and thus three chimeric MHC class I complexes were obtained. Biotinylation was performed, and its level of efficiency was observed via a band-shift assay in non-reducing polyacrylamide gel electrophoresis (PAGE). Such chimeric MHC class I tetramers showed a sensitive binding activity in monitoring HLA/A2 restrictive cytotoxic T lymphocytes (CTLs) in immunized HLA/A*0201 transgenic mice. PMID:17046278

  3. Can small hydrophobic gold nanoparticles inhibit β2-microglobulin fibrillation?

    NASA Astrophysics Data System (ADS)

    Brancolini, Giorgia; Toroz, Dimitrios; Corni, Stefano

    2014-06-01

    Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or suppress the natural propensity of proteins to form fibrils. Functionalization facilitates targeted delivery of the nanoparticles to various cell types, bioimaging, drug delivery and other therapeutic and diagnostic applications. In this study, we provide a computational model of the effect of a prototypical thiol-protected gold nanoparticle, Au25L18- (L = S(CH2)2Ph) on the β2-microglobulin natural fibrillation propensity. To reveal the molecular basis of the protein-nanoparticle association process, we performed various simulations at multiple levels (Classical Molecular Dynamics and Brownian Dynamics) that cover multiple length- and timescales. The results provide a model of the ensemble of structures constituting the protein-gold nanoparticle complexes, and insights into the driving forces for the binding of β2-microglobulin to hydrophobic small size gold nanoparticles. We have found that the small nanoparticles can bind the protein to form persistent complexes. This binding of nanoparticles is able to block the active sites of domains from binding to another protein, thus leading to potential inhibition of the fibrillation activity. A comparison with the binding patches identified for the interaction of the protein with a known inhibitor of fibrillation, supports our conclusion.Inorganic nanoparticles stabilized by a shell of organic ligands can enhance or suppress the natural propensity of proteins to form fibrils. Functionalization facilitates targeted delivery of the nanoparticles to various cell types, bioimaging, drug delivery and other therapeutic and diagnostic applications. In this study, we provide a computational model of the effect of a prototypical thiol-protected gold nanoparticle, Au25L18- (L = S(CH2)2Ph) on the β2-microglobulin natural fibrillation propensity. To reveal the molecular basis of the protein-nanoparticle association process, we performed various

  4. Characterization of Salt-Induced Oligomerization of Human β2-Microglobulin at Low pH.

    PubMed

    Narang, Dominic; Singh, Anubhuti; Swasthi, Hema M; Mukhopadhyay, Samrat

    2016-08-18

    Misfolding and amyloid aggregation of human β2-microglobulin2m) have been linked to dialysis-related amyloidosis. Previous studies have shown that in the presence of different salt concentrations and at pH 2.5, β2m assembles into aggregates with distinct morphologies. However, the structural and mechanistic details of the aggregation of β2m, giving rise to different morphologies, are poorly understood. In this work, we have extensively characterized the salt-induced oligomers of the acid-unfolded state of β2m using an array of biophysical tools including steady-state and time-resolved fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy imaging. Fluorescence studies using the oligomer-sensitive molecular rotor, 4-(dicyanovinyl)-julolidine, in conjunction with the light scattering and cross-linking assay indicated that at low salt (NaCl) concentrations β2m exists as a disordered monomer, capable of transforming into ordered amyloid. In the presence of higher concentrations of salt, β2m aggregates into a larger oligomeric species that does not appear to transform into amyloid fibrils. Site-specific fluorescence experiments using single Trp variants of β2m revealed that the middle region of the protein is incorporated into these oligomers, whereas the C-terminal segment is highly exposed to bulk water. Additionally, stopped-flow kinetic experiments indicated that the formation of hydrophobic core and oligomerization occur concomitantly. Our results revealed the distinct pathways by which β2m assembles into oligomers and fibrils. PMID:27467899

  5. Molecular insights into cell toxicity of a novel familial amyloidogenic variant of β2-microglobulin.

    PubMed

    Leri, Manuela; Bemporad, Francesco; Oropesa-Nuñez, Reinier; Canale, Claudio; Calamai, Martino; Nosi, Daniele; Ramazzotti, Matteo; Giorgetti, Sofia; Pavone, Francesco S; Bellotti, Vittorio; Stefani, Massimo; Bucciantini, Monica

    2016-08-01

    The first genetic variant of β2 -microglobulin (b2M) associated with a familial form of systemic amyloidosis has been recently described. The mutated protein, carrying a substitution of Asp at position 76 with an Asn (D76N b2M), exhibits a strongly enhanced amyloidogenic tendency to aggregate with respect to the wild-type protein. In this study, we characterized the D76N b2M aggregation path and performed an unprecedented analysis of the biochemical mechanisms underlying aggregate cytotoxicity. We showed that, contrarily to what expected from other amyloid studies, early aggregates of the mutant are not the most toxic species, despite their higher surface hydrophobicity. By modulating ganglioside GM1 content in cell membrane or synthetic lipid bilayers, we confirmed the pivotal role of this lipid as aggregate recruiter favouring their cytotoxicity. We finally observed that the aggregates bind to the cell membrane inducing an alteration of its elasticity (with possible functional unbalance and cytotoxicity) in GM1-enriched domains only, thus establishing a link between aggregate-membrane contact and cell damage. PMID:26990223

  6. Structure, Folding Dynamics, and Amyloidogenesis of D76N β2-Microglobulin

    PubMed Central

    Mangione, P. Patrizia; Esposito, Gennaro; Relini, Annalisa; Raimondi, Sara; Porcari, Riccardo; Giorgetti, Sofia; Corazza, Alessandra; Fogolari, Federico; Penco, Amanda; Goto, Yuji; Lee, Young-Ho; Yagi, Hisashi; Cecconi, Ciro; Naqvi, Mohsin M.; Gillmore, Julian D.; Hawkins, Philip N.; Chiti, Fabrizio; Rolandi, Ranieri; Taylor, Graham W.; Pepys, Mark B.; Stoppini, Monica; Bellotti, Vittorio

    2013-01-01

    Systemic amyloidosis is a fatal disease caused by misfolding of native globular proteins, which then aggregate extracellularly as insoluble fibrils, damaging the structure and function of affected organs. The formation of amyloid fibrils in vivo is poorly understood. We recently identified the first naturally occurring structural variant, D76N, of human β2-microglobulin2m), the ubiquitous light chain of class I major histocompatibility antigens, as the amyloid fibril protein in a family with a new phenotype of late onset fatal hereditary systemic amyloidosis. Here we show that, uniquely, D76N β2m readily forms amyloid fibrils in vitro under physiological extracellular conditions. The globular native fold transition to the fibrillar state is primed by exposure to a hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild type β2m is recruited by the variant into amyloid fibrils in vitro but is absent from amyloid deposited in vivo. This may be because, as we show here, such recruitment is inhibited by chaperone activity. Our results suggest general mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a previously obscure process. Elucidation of this crucial causative event in clinical amyloidosis should also help to explain the hitherto mysterious timing and location of amyloid deposition. PMID:24014031

  7. Co-fibrillogenesis of Wild-type and D76N β2-Microglobulin

    PubMed Central

    Natalello, Antonino; Mangione, P. Patrizia; Giorgetti, Sofia; Porcari, Riccardo; Marchese, Loredana; Zorzoli, Irene; Relini, Annalisa; Ami, Diletta; Faravelli, Giulia; Valli, Maurizia; Stoppini, Monica; Doglia, Silvia M.; Bellotti, Vittorio; Raimondi, Sara

    2016-01-01

    The amyloidogenic variant of β2-microglobulin, D76N, can readily convert into genuine fibrils under physiological conditions and primes in vitro the fibrillogenesis of the wild-type β2-microglobulin. By Fourier transformed infrared spectroscopy, we have demonstrated that the amyloid transformation of wild-type β2-microglobulin can be induced by the variant only after its complete fibrillar conversion. Our current findings are consistent with preliminary data in which we have shown a seeding effect of fibrils formed from D76N or the natural truncated form of β2-microglobulin lacking the first six N-terminal residues. Interestingly, the hybrid wild-type/variant fibrillar material acquired a thermodynamic stability similar to that of homogenous D76N β2-microglobulin fibrils and significantly higher than the wild-type homogeneous fibrils prepared at neutral pH in the presence of 20% trifluoroethanol. These results suggest that the surface of D76N β2-microglobulin fibrils can favor the transition of the wild-type protein into an amyloid conformation leading to a rapid integration into fibrils. The chaperone crystallin, which is a mild modulator of the lag phase of the variant fibrillogenesis, potently inhibits fibril elongation of the wild-type even once it is absorbed on D76N β2-microglobulin fibrils. PMID:26921323

  8. Uncovering the Early Assembly Mechanism for Amyloidogenic β2-Microglobulin Using Cross-linking and Native Mass Spectrometry*

    PubMed Central

    Hall, Zoe; Schmidt, Carla; Politis, Argyris

    2016-01-01

    β2-Microglobulin2m), a key component of the major histocompatibility class I complex, can aggregate into fibrils with severe clinical consequences. As such, investigating the structural aspects of the formation of oligomeric intermediates of β2m and their subsequent progression toward fibrillar aggregates is of great importance. However, β2m aggregates are challenging targets in structural biology, primarily due to their inherent transient and heterogeneous nature. Here we study the oligomeric distributions and structures of the early intermediates of amyloidogenic β2m and its truncated variant ΔN6-β2m. We established compact oligomers for both variants by integrating advanced mass spectrometric techniques with available electron microscopy maps and atomic level structures from NMR spectroscopy and x-ray crystallography. Our results revealed a stepwise assembly mechanism by monomer addition and domain swapping for the oligomeric species of ΔN6-β2m. The observed structural similarity and common oligomerization pathway between the two variants is likely to enable ΔN6-β2m to cross-seed β2m fibrillation and allow the formation of mixed fibrils. We further determined the key subunit interactions in ΔN6-β2m tetramer, revealing the importance of a domain-swapped hinge region for formation of higher order oligomers. Overall, we deliver new mechanistic insights into β2m aggregation, paving the way for future studies on the mechanisms and cause of amyloid fibrillation. PMID:26655720

  9. Copper Binding to β-2-Microglobulin and its Pre-Amyloid Oligomers†

    PubMed Central

    Srikanth, Rapole; Mendoza, Vanessa Leah; Bridgewater, Juma D.; Zhang, Guanshi; Vachet, Richard W.

    2009-01-01

    β-2-microglobulin2m) deposits as amyloid fibrils in the musculoskeletal system of patients undergoing long-term dialysis treatment as a result of kidney failure. Previous work has shown that Cu(II) binding causes β2m to organize into native-like dimers and tetramers that precede amyloid formation. Cu(II) is then released from higher order oligomers before mature Cu(II)-free amyloid fibrils are formed. While some of the Cu(II)-induced structural changes that enable β2m self assembly are starting to be revealed, the details of how the Cu(II) binding site evolves from the monomer to the dimers and tetramers are not known. Here, we report results from three mass spectrometry (MS) based methods that provide insight into the changing Cu-β2m interactions. We find that monomeric β2m binds Cu(II) via the N-terminal amine, the amide of Gln2, His31, and Asp59. In the dimer and tetramer, Asp59 is no longer bound to Cu(II), but the other residues still comprise a well-defined albeit weaker binding site that is better able to release Cu(II). Consistent with this is the observation that a fraction of the tetrameric species no longer binds Cu(II) at this weakened binding site, which agrees with a previous report that suggested the tetramer as the first Cu(II)-free oligomer. Our results also provide some insight into structural changes caused by Cu(II) binding that facilitate oligomer formation. Specifically, binding by Asp59 in the monomer requires significant movement of this residue, and we propose that this repositioning is important for establishing a pair of dimer-stabilizing salt bridges between this residue and Lys19. We also find evidence that Cu(II) binding in the N-terminal region of the monomer repels Arg3, which likely allows this residue to form a pair of dimer-stabilizing salt bridges with Glu16. Overall, our measurements suggest that the previously proposed conformational switch caused by Cu(II) binding includes not only a cis-trans isomerization at Pro32

  10. Comparison of the aggregation of homologous β2-microglobulin variants reveals protein solubility as a key determinant of amyloid formation

    PubMed Central

    Pashley, Clare L.; Hewitt, Eric W.; Radford, Sheena E.

    2016-01-01

    The mouse and human β2-microglobulin protein orthologs are 70 % identical in sequence and share 88 % sequence similarity. These proteins are predicted by various algorithms to have similar aggregation and amyloid propensities. However, whilst human β2m (hβ2m) forms amyloid-like fibrils in denaturing conditions (e.g. pH 2.5) in the absence of NaCl, mouse β2m (mβ2m) requires the addition of 0.3 M NaCl to cause fibrillation. Here, the factors which give rise to this difference in amyloid propensity are investigated. We utilise structural and mutational analyses, fibril growth kinetics and solubility measurements under a range of pH and salt conditions, to determine why these two proteins have different amyloid propensities. The results show that, although other factors influence the fibril growth kinetics, a striking difference in the solubility of the proteins is a key determinant of the different amyloidogenicity of hβ2m and mβ2m. The relationship between protein solubility and lag time of amyloid formation is not captured by current aggregation or amyloid prediction algorithms, indicating a need to better understand the role of solubility on the lag time of amyloid formation. The results demonstrate the key contribution of protein solubility in determining amyloid propensity and lag time of amyloid formation, highlighting how small differences in protein sequence can have dramatic effects on amyloid formation. PMID:26780548

  11. Comparison of the aggregation of homologous β2-microglobulin variants reveals protein solubility as a key determinant of amyloid formation.

    PubMed

    Pashley, Clare L; Hewitt, Eric W; Radford, Sheena E

    2016-02-13

    The mouse and human β2-microglobulin protein orthologs are 70% identical in sequence and share 88% sequence similarity. These proteins are predicted by various algorithms to have similar aggregation and amyloid propensities. However, whilst human β2m (hβ2m) forms amyloid-like fibrils in denaturing conditions (e.g. pH2.5) in the absence of NaCl, mouse β2m (mβ2m) requires the addition of 0.3M NaCl to cause fibrillation. Here, the factors which give rise to this difference in amyloid propensity are investigated. We utilise structural and mutational analyses, fibril growth kinetics and solubility measurements under a range of pH and salt conditions, to determine why these two proteins have different amyloid propensities. The results show that, although other factors influence the fibril growth kinetics, a striking difference in the solubility of the proteins is a key determinant of the different amyloidogenicity of hβ2m and mβ2m. The relationship between protein solubility and lag time of amyloid formation is not captured by current aggregation or amyloid prediction algorithms, indicating a need to better understand the role of solubility on the lag time of amyloid formation. The results demonstrate the key contribution of protein solubility in determining amyloid propensity and lag time of amyloid formation, highlighting how small differences in protein sequence can have dramatic effects on amyloid formation. PMID:26780548

  12. β2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

    PubMed Central

    Goodchild, Sophia C.; Sheynis, Tania; Thompson, Rebecca; Tipping, Kevin W.; Xue, Wei-Feng; Ranson, Neil A.; Beales, Paul A.; Hewitt, Eric W.; Radford, Sheena E.

    2014-01-01

    Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of β2-microglobulin2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which β2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of β2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that β2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between β2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of β2m amyloid-associated osteoarticular tissue destruction in DRA. PMID:25100247

  13. High Beta Steady State Research and Future Directions on JT-60U and JFT-2M

    NASA Astrophysics Data System (ADS)

    Ishida, Shinichi

    2003-10-01

    JT-60U and JFT-2M research is focused on high beta steady state operation towards economically and environmentally attractive reactors. In JT-60U, a high-βp H-mode plasma was sustained with βN 2.7 for 7.4 s in which neoclassical tearing modes (NTMs) limited the attainable β_N. Real-time tracking NTM stabilization system using ECCD demonstrated complete suppression of NTM leading to recovery of βN before onset of NTM. Performance in a fully non-inductive H-mode plasma was improved up to n_i(0) τE T_i(0) = 3.1 x 10^20 keV s m-3 using N-NBCD with βN 2.4, HH_y,2=1.2 and bootstrap fraction f_BS 0.5. ECH experiments extended the confinement enhancement for dominantly electron heated reversed shear plasmas up to HH_y,2 2 at T_e/Ti 1.25. A world record ECCD efficiency, 4.2 x 10^18 A/W/m^2, was achieved at Te 23 keV with a highly localized central current density. Innovative initiation and current build-up without center solenoid currents were established by LHCD/ECH and bootstrap current up to f_BS 0.9. In JFT-2M, the inside of the vacuum vessel wall was fully covered with low-activation ferritic steel plates to investigate their use in plasmas near fusion conditions. High βN plasmas were produced up to βN = 3.3 with an internal transport barrier (ITB) and a steady H-mode edge. A new H-mode regime with steady high recycling (HRS) and an ITB was exploited leading to βN H_89P 6.2 at n_e/nG 0.7. In 2003, JT-60U will be able to operate for the duration up to 65 s at 1 MA/2.7 T and the heating/current-drive duration up to 30 s at 17 MW to prolong high-βN and/or high-f_BS discharges with feedback controls. JFT-2M is planning to implement wall stabilization experiments in 2004 to pursue plasmas above the ideal no-wall limit using a ferritic wall. The modification of JT-60 to a fully superconducting tokamak is under discussion to explore high-β steady state operation in collision-less plasmas well above no-wall limit with ferritic wall in a steady state.

  14. Macromolecular crowding favors the fibrillization of β2-microglobulin by accelerating the nucleation step and inhibiting fibril disassembly.

    PubMed

    Luo, Xu-Dong; Kong, Fan-Lou; Dang, Hai-Bin; Chen, Jie; Liang, Yi

    2016-11-01

    Hemodialysis-associated amyloidosis (HAA) involves the fibrillization of β2-microglobulin2M) and occurs in crowded physiological environments. However, how macromolecular crowding affects amyloid formation of β2M remains elusive. Here we study the effects of macromolecular crowding on amyloid formation and fibril disassembly of wild-type human β2M and its pathogenic mutant ΔN6. At strongly acidic pH2.5, the presence of a strong crowding agent (Ficoll 70 or dextran 70) not only dramatically accelerates the fibrillization of both wild-type β2M and its ΔN6 variant by reducing the lag time to a large extent, indicating the acceleration of the nucleation phase, but also remarkably increases the amount of β2M fibrils. At weakly acidic pH6.2, such an enhancing effect of macromolecular crowding on fibril formation is only observed for pathogenic mutant ΔN6, but not for wild-type β2M which does not form amyloid fibrils in the absence and presence of a crowding agent. Thus, we propose that the monomers of β2M form the nuclei, which is enhanced by macromolecular crowding, followed by the step of fibril elongation. Furthermore, at physiological pH, macromolecular crowding remarkably inhibits β2M fibril disassembly by decreasing rate constants corresponding to fast and slow stages of fibril disaggregation. Our data demonstrate that macromolecular crowding favors the fibrillization of β2M by accelerating the nucleation step and inhibiting fibril disassembly. Our findings provide clear evidence for the pathology of HAA that macromolecular crowding should be taken into account. PMID:27481166

  15. Structural Insights into the Pre-amyloid Tetramer of β-2-microglobulin from Covalent Labeling and Mass Spectrometry‡

    PubMed Central

    Mendoza, Vanessa Leah; Barón-Rodríguez, Mario A.; Blanco, Cristian; Vachet, Richard W.

    2011-01-01

    The main pathogenic process underlying dialysis-related amyloidosis (DRA) is the accumulation of β-2-microglobulin2m) as amyloid fibrils in the musculoskeletal system, and some evidence suggests that Cu(II) may play a role in β2m amyloid formation. Cu(II)-induced β2m fibril formation is preceded by the formation of discrete, oligomeric intermediates, including dimers, tetramers, and hexamers. In this work, we use selective covalent labeling reactions combined with mass spectrometry to investigate the amino acids responsible for mediating tetramer formation in wild-type β2m. By comparing the labeling patterns of the monomer, dimer, and tetramer, we find evidence that the tetramer interface is formed by the interaction of D strands from one dimer unit and G strands from another dimer unit. This covalent labeling data along with molecular dynamics calculations enable the construction of a tetramer model that indicates how the protein might proceed to form even higher order oligomers. PMID:21718071

  16. Dissociation of β2-microglobulin determines the surface quality control of major histocompatibility complex class I molecules.

    PubMed

    Montealegre, Sebastián; Venugopalan, Vaishnavi; Fritzsche, Susanne; Kulicke, Corinna; Hein, Zeynep; Springer, Sebastian

    2015-07-01

    Major histocompatibility complex class I proteins, which present antigenic peptides to cytotoxic T lymphocytes at the surface of all nucleated cells, are endocytosed and destroyed rapidly once their peptide ligand has dissociated. The molecular mechanism of this cellular quality control process, which prevents rebinding of exogenous peptides and thus erroneous immune responses, is unknown. To identify the nature of the decisive step in endocytic sorting of class I molecules and its location, we have followed the removal of optimally and suboptimally peptide-loaded murine H-2K(b) class I proteins from the cell surface. We find that the binding of their light chain, β2-microglobulin2m), protects them from endocytic destruction. Thus, the extended survival of suboptimally loaded K(b) molecules at 25°C is attributed to decreased dissociation of β2m. Because all forms of K(b) are constantly internalized but little β2m-receptive heavy chain is present at the cell surface, it is likely that β2m dissociation and recognition of the heavy chain for lysosomal degradation take place in an endocytic compartment. PMID:25782992

  17. β2-Microglobulin Amyloid Fibrils Are Nanoparticles That Disrupt Lysosomal Membrane Protein Trafficking and Inhibit Protein Degradation by Lysosomes*

    PubMed Central

    Jakhria, Toral; Hellewell, Andrew L.; Porter, Morwenna Y.; Jackson, Matthew P.; Tipping, Kevin W.; Xue, Wei-Feng; Radford, Sheena E.; Hewitt, Eric W.

    2014-01-01

    Fragmentation of amyloid fibrils produces fibrils that are reduced in length but have an otherwise unchanged molecular architecture. The resultant nanoscale fibril particles inhibit the cellular reduction of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), a substrate commonly used to measure cell viability, to a greater extent than unfragmented fibrils. Here we show that the internalization of β2-microglobulin2m) amyloid fibrils is dependent on fibril length, with fragmented fibrils being more efficiently internalized by cells. Correspondingly, inhibiting the internalization of fragmented β2m fibrils rescued cellular MTT reduction. Incubation of cells with fragmented β2m fibrils did not, however, cause cell death. Instead, fragmented β2m fibrils accumulate in lysosomes, alter the trafficking of lysosomal membrane proteins, and inhibit the degradation of a model protein substrate by lysosomes. These findings suggest that nanoscale fibrils formed early during amyloid assembly reactions or by the fragmentation of longer fibrils could play a role in amyloid disease by disrupting protein degradation by lysosomes and trafficking in the endolysosomal pathway. PMID:25378395

  18. Many de novo donor-specific antibodies recognize β2 -microglobulin-free, but not intact HLA heterodimers.

    PubMed

    Michel, K; Santella, R; Steers, J; Sahajpal, A; Downey, F X; Thohan, V; Oaks, M

    2016-05-01

    Solid-phase single antigen bead (SAB) assays are standard of care for detection and identification of donor-specific antibody (DSA) in patients who receive solid organ transplantation (SOT). While several studies have documented the reproducibility and sensitivity of SAB testing for DSA, there are little data available concerning its specificity. This study describes the identification of antibodies to β2 -microglobulin-free human leukocyte antigen (β2 -m-fHLA) heavy chains on SAB arrays and provides a reassessment of the clinical relevance of DSA testing by this platform. Post-transplant sera from 55 patients who were positive for de novo donor-specific antibodies on a SAB solid-phase immunoassay were tested under denaturing conditions in order to identify antibodies reactive with β2 -m-fHLA or native HLA (nHLA). Antibodies to β2 -m-fHLA were present in nearly half of patients being monitored in the post-transplant period. The frequency of antibodies to β2 -m-fHLA was similar among DSA and HLA antigens that were irrelevant to the transplant (non-DSA). Among the seven patients with clinical or pathologic antibody-mediated rejection (AMR), none had antibodies to β2 -m-fHLA exclusively; thus, the clinical relevance of β2 -m-fHLA is unclear. Our data suggests that SAB testing produces false positive reactions due to the presence of β2 -m-fHLA and these can lead to inappropriate assignment of unacceptable antigens during transplant listing and possibly inaccurate identification of DSA in the post-transplant period. PMID:27060279

  19. Adenovirus expressing β2-microglobulin recovers HLA class I expression and antitumor immunity by increasing T-cell recognition.

    PubMed

    Del Campo, A B; Carretero, J; Muñoz, J A; Zinchenko, S; Ruiz-Cabello, F; González-Aseguinolaza, G; Garrido, F; Aptsiauri, N

    2014-08-01

    Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, β2-microglobulin2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the β2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human β2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in β2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with β2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy. PMID:24971583

  20. The molten globule of β(2)-microglobulin accumulated at pH 4 and its role in protein folding.

    PubMed

    Mukaiyama, Atsushi; Nakamura, Takashi; Makabe, Koki; Maki, Kosuke; Goto, Yuji; Kuwajima, Kunihiro

    2013-01-23

    The acid transition of β(2)-microglobulin2m) was studied by tryptophan fluorescence, peptide circular dichroism, and NMR spectroscopy. The protein exhibits a three-state transition with an equilibrium intermediate accumulated at pH4 (25°C). The pH4 intermediate has typical characteristics of the molten globule (MG) state; it showed a native-like secondary structure without specific side-chain tertiary structure, and the hydrodynamic radius determined by pulse field gradient NMR was only 20% larger than that of the native state. The accumulation of the pH4 intermediate is very analogous to the behavior of apomyoglobin, for which the pH4 MG has been well characterized, although β2m, a β-protein, is structurally very different from α-helical apomyoglobin. NMR pH titration of histidine residues of β2m has also indicated that His84 has an abnormally low pK(a) value in the native state. From the pH dependence of the unfolding transition, the protonations of this histidine and 10 weakly abnormal carboxylates triggered the transition from the native to the MG state. This behavior is again analogous to that of apomyoglobin, suggesting a common mechanism of production of the pH4 MG. In contrast to the folding of apomyoglobin, in which the MG was equivalent to the burst-phase kinetic folding intermediate, the burst-phase refolding intermediate of β2m, detected by stopped-flow circular dichroism, was significantly more structured than the pH4 intermediate. It is proposed that the folding of β2m from its acid-denatured state takes place in the following order: denatured state→MG→burst-phase intermediate→native state. PMID:23154171

  1. Urinary β2 microglobulin in workers exposed to arc welding fumes.

    PubMed

    Aminian, Omid; Eftekhari, Saeid; Mazaheri, Maria; Sharifian, Seyed Akbar; Sadeghniiat-Haghighi, Khosro

    2011-01-01

    Welding is a process in which two or more metals are attached by the use of heat and, in some cases, pressure. Direct exposure and inhalation of welding fumes causes acute and chronic side effects in humans. Kidney damage is one of these important side effects. β(2) microglobulin is an 11.8 kilodalton protein and levels increase in the case of some inflammatory and viral diseases, or kidney malfunction and autoimmune diseases. In this study measurements of β(2) microglobulin were used as a criterion for assessing effects on the kidneys of workers exposed to welding fumes. The study population were electric arc welders in an industrial plant in Tehran, Iran. For control we selected workers who did not have any exposure to welding fumes. Both groups were selected on the basis of a questionnaire and the consideration of criteria for inclusion and exclusion. In the end 50 cases and 50 controls were chosen. A urine sample was collected from all participants and urinary pH was set to between 6-8 using NaOH (1M). Sample transportation to the laboratory complied with the related standards. The samples were assessed using the ORG 5BM kit. For quantitative assessment of β(2) microglobulin we used the Enzyme-linked Immunosorbent Assay (ELISA) method. The ages of the welders ranged from 21 to 48 years (mean=30.5 ± 5.9 yrs) and of controls from 23 to 56 years (mean=31.8 ± 5.9 yrs). Mean employment duration was 7.86 ± 5.01 years (range 2 to 27 years) for welders. Mean β(2) microglobulin level was 0.10 ± 0.096 μg/ml in welders and 0.11 ± 0.06 in controls. This difference was not statistically significant (P=0.381). In conclusion we don't find that exposure to electric arc welding fumes cause a significant change in urinary β(2) microglobulin compared to the control group. PMID:22131246

  2. Decoding the Structural Bases of D76N ß2-Microglobulin High Amyloidogenicity through Crystallography and Asn-Scan Mutagenesis.

    PubMed

    de Rosa, Matteo; Barbiroli, Alberto; Giorgetti, Sofia; Mangione, Patrizia P; Bolognesi, Martino; Ricagno, Stefano

    2015-01-01

    D76N is the first natural variant of human β-2 microglobulin2m) so far identified. Contrary to the wt protein, this mutant readily forms amyloid fibres in physiological conditions, leading to a systemic and severe amyloidosis. Although the Asp76Asn mutant has been extensively characterized, the molecular bases of its instability and aggregation propensity remain elusive. In this work all Asp residues of human β2m were individually substituted to Asn; D-to-N mutants (D34N, D38N, D53N, D59N, D96N and D98N) were characterised in terms of thermodynamic stability and aggregation propensity. Moreover, crystal structures of the D38N, D53N, D59N and D98N variants were solved at high-resolution (1.24-1.70 Å). Despite showing some significant variations in their thermal stabilities, none showed the dramatic drop in melting temperature (relative to the wt protein) as observed for the pathogenic mutant. Consistently, none of the variants here described displayed any increase in aggregation propensity under the experimental conditions tested. The crystal structures confirmed that D-to-N mutations are generally well tolerated, and lead only to minor reorganization of the side chains in close proximity of the mutated residue. D38N is the only exception, where backbone readjustments and a redistribution of the surface electrostatic charges are observed. Overall, our results suggest that neither removing negative charges at sites 34, 38, 53, 59, 96 and 98, nor the difference in β2m pI, are the cause of the aggressive phenotype observed in D76N. We propose that the dramatic effects of the D76N natural mutation must be linked to effects related to the crucial location of this residue within the β2m fold. PMID:26625273

  3. Decoding the Structural Bases of D76N ß2-Microglobulin High Amyloidogenicity through Crystallography and Asn-Scan Mutagenesis

    PubMed Central

    de Rosa, Matteo; Barbiroli, Alberto; Giorgetti, Sofia; Mangione, Patrizia P.; Bolognesi, Martino; Ricagno, Stefano

    2015-01-01

    D76N is the first natural variant of human β-2 microglobulin2m) so far identified. Contrary to the wt protein, this mutant readily forms amyloid fibres in physiological conditions, leading to a systemic and severe amyloidosis. Although the Asp76Asn mutant has been extensively characterized, the molecular bases of its instability and aggregation propensity remain elusive. In this work all Asp residues of human β2m were individually substituted to Asn; D-to-N mutants (D34N, D38N, D53N, D59N, D96N and D98N) were characterised in terms of thermodynamic stability and aggregation propensity. Moreover, crystal structures of the D38N, D53N, D59N and D98N variants were solved at high-resolution (1.24–1.70 Å). Despite showing some significant variations in their thermal stabilities, none showed the dramatic drop in melting temperature (relative to the wt protein) as observed for the pathogenic mutant. Consistently, none of the variants here described displayed any increase in aggregation propensity under the experimental conditions tested. The crystal structures confirmed that D-to-N mutations are generally well tolerated, and lead only to minor reorganization of the side chains in close proximity of the mutated residue. D38N is the only exception, where backbone readjustments and a redistribution of the surface electrostatic charges are observed. Overall, our results suggest that neither removing negative charges at sites 34, 38, 53, 59, 96 and 98, nor the difference in β2m pI, are the cause of the aggressive phenotype observed in D76N. We propose that the dramatic effects of the D76N natural mutation must be linked to effects related to the crucial location of this residue within the β2m fold. PMID:26625273

  4. Assessing the effect of loop mutations in the folding space of β2-microglobulin with molecular dynamics simulations.

    PubMed

    Estácio, Sílvia G; Shakhnovich, Eugene I; Faísca, Patrícia F N

    2013-01-01

    We use molecular dynamics simulations of a full atomistic Gō model to explore the impact of selected DE-loop mutations (D59P and W60C) on the folding space of protein human β2-microglobulin (Hβ2m), the causing agent of dialysis-related amyloidosis, a conformational disorder characterized by the deposition of insoluble amyloid fibrils in the osteoarticular system. Our simulations replicate the effect of mutations on the thermal stability that is observed in experiments in vitro. Furthermore, they predict the population of a partially folded state, with 60% of native internal free energy, which is akin to a molten globule. In the intermediate state, the solvent accessible surface area increases up to 40 times relative to the native state in 38% of the hydrophobic core residues, indicating that the identified species has aggregation potential. The intermediate state preserves the disulfide bond established between residue Cys25 and residue Cys80, which helps maintain the integrity of the core region, and is characterized by having two unstructured termini. The movements of the termini dominate the essential modes of the intermediate state, and exhibit the largest displacements in the D59P mutant, which is the most aggregation prone variant. PROPKA predictions of pKa suggest that the population of the intermediate state may be enhanced at acidic pH explaining the larger amyloidogenic potential observed in vitro at low pH for the WT protein and mutant forms. PMID:23975166

  5. Pretransplant β2-Microglobulin Is Associated with the Risk of Acute Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplant.

    PubMed

    Costa-Lima, Carolina; Miranda, Eliana Cristina Martins; Colella, Marcos Paulo; Aranha, Francisco Jose Penteado; de Souza, Carmino Antonio; Vigorito, Afonso Celso; De Paula, Erich Vinicius

    2016-07-01

    The risk of acute graft-versus-host disease (aGVHD) can be reliably estimated by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), which can be further refined by the incorporation of pre-hematopoietic cell transplantation (HCT) serum levels of inflammatory biomarkers such as ferritin and albumin. β2-Microglobulin2-m) is a key component of the MHC class I complex, which is independently associated with mortality and frailty in the general population. We took advantage of our institutional protocol that includes measurement of pre-HCT β2-m serum levels in the most patients to investigate whether pre-transplant β2-m levels were associated with the risk of aGVHD. One hundred three consecutive patients submitted to allogeneic HCT, of which 26 developed grades II to IV aGVHD, were included in the analysis. β2-m was significantly associated with age and HCT-CI. Higher levels of β2-m were observed in patients who developed aGVHD (P = .008). In the multivariate Cox regression model, β2-m and HCT-CI remained independently associated with the risk of developing aGVHD. In conclusion, the association between β2-m and the occurrence of aGVHD suggests that the measurement of this protein before HCT might represent an additional element for risk stratification of aGVHD. PMID:27044906

  6. Expression, refolding and crystallization of murine MHC class I H-2D{sup b} in complex with human β{sub 2}-microglobulin

    SciTech Connect

    Sandalova, Tatyana; Michaëlsson, Jakob; Harris, Robert A.; Ljunggren, Hans-Gustaf; Kärre, Klas; Schneider, Gunter; Achour, Adnane

    2005-12-01

    Mouse MHC class I H-2Db in complex with human β2m and the LCMV-derived peptide gp33 has been produced and crystallized. Resolution of the structure of this complex combined with the structural comparison with the previously solved crystal structure of H-2Db/mβ2m/gp33 should lead to a better understanding of how the β2m subunit affects the overall conformation of MHC complexes as well as the stability of the presented peptides. β{sub 2}-Microglobulin (β{sub 2}m) is non-covalently linked to the major histocompatibility (MHC) class I heavy chain and interacts with CD8 and Ly49 receptors. Murine MHC class I can bind human β{sub 2}m (hβ{sub 2}m) and such hybrid molecules are often used in structural and functional studies. The replacement of mouse β{sub 2}m (mβ{sub 2}m) by hβ{sub 2}m has important functional consequences for MHC class I complex stability and specificity, but the structural basis for this is unknown. To investigate the impact of species-specific β{sub 2}m subunits on MHC class I conformation, murine MHC class I H-2D{sup b} in complex with hβ{sub 2}m and the peptide gp33 derived from lymphocytic choriomeningitis virus (LCMV) has been expressed, refolded in vitro and crystallized. Crystals containing two complexes per asymmetric unit and belonging to the space group P2{sub 1}, with unit-cell parameters a = 68.1, b = 65.2, c = 101.9 Å, β = 102.4°, were obtained.

  7. Host Susceptibility to Brucella abortus Infection Is More Pronounced in IFN-γ knockout than IL-12/β2-Microglobulin Double-Deficient Mice

    PubMed Central

    Brandão, Ana Paula M. S.; Oliveira, Fernanda S.; Carvalho, Natalia B.; Vieira, Leda Q.; Azevedo, Vasco; Macedo, Gilson C.; Oliveira, Sergio C.

    2012-01-01

    Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. IFN-γ, IL-12, and CD8+ T lymphocytes are important components of host immune responses against B. abortus. Herein, IFN-γ and IL-12/β2-microglobulin2-m) knockout mice were used to determine whether CD8+ T cells and IL-12-dependent IFN-γ deficiency would be more critical to control B. abortus infection compared to the lack of endogenous IFN-γ. At 1 week after infection, IFN-γ KO and IL-12/β2-m KO mice showed increased numbers of bacterial load in spleens; however, at 3 weeks postinfection (p.i.), only IFN-γ KO succumbed to Brucella. All IFN-γ KO had died at 16 days p.i. whereas death within the IL-12/β2-m KO group was delayed and occurred at 32 days until 47 days postinfection. Susceptibility of IL-12/β2-m KO animals to Brucella was associated to undetectable levels of IFN-γ in mouse splenocytes and inability of these cells to lyse Brucella-infected macrophages. However, the lack of endogenous IFN-γ was found to be more important to control brucellosis than CD8+ T cells and IL-12-dependent IFN-γ deficiencies. PMID:22194770

  8. Molecular Basis for the Cu2+ Binding-Induced Destabilization of β2-Microglobulin Revealed by Molecular Dynamics Simulation

    PubMed Central

    Deng, Nan-Jie; Yan, Lisa; Singh, Deepak; Cieplak, Piotr

    2006-01-01

    According to experimental data, binding of the Cu2+ ions destabilizes the native state of β2-microglobulin2m). The partial unfolding of the protein was generally considered an early step toward fibril formation in dialysis-related amyloidosis. Recent NMR studies have suggested that the destabilization of the protein might be achieved through increased flexibility upon Cu2+ binding. However, the molecular mechanism of destabilization due to Cu2+, its role in amyloid formation, and the relative contributions of different potential copper-binding sites remain unclear. To elucidate the effect of ion ligation at atomic detail, a series of molecular dynamics simulations were carried out on apo- and Cu2+-β2m systems in explicit aqueous solutions, with varying numbers of bound ions. Simulations at elevated temperatures (360 K) provide detailed pictures for the process of Cu2+-binding-induced destabilization of the native structure at the nanosecond timescale, which are in agreement with experiments. Conformational transitions toward partially unfolded states were observed in protein solutions containing bound copper ions at His-31 and His-51, which is marked by an increase in the protein vibrational entropy, with TΔS(vibr) ranging from 30 to 69 kcal/mol. The binding of Cu2+ perturbs the secondary structure and the hydrogen bonding pattern disrupts the native hydrophobic contacts in the neighboring segments, which include the β-strand D2 and part of the β-strand E, B, and C and results in greater exposure of the D-E loop and the B-C loop to the water environment. Analysis of the MD trajectories suggests that the changes in the hydrophobic environment near the copper-binding sites lower the barrier of conformational transition and stabilize the more disordered conformation. The results also indicate that the binding of Cu2+ at His-13 has little effect on the conformational stability, whereas the copper-binding site His-31, and to a lesser extent His-51, are

  9. Characterization of intermolecular structure of β(2)-microglobulin core fragments in amyloid fibrils by vacuum-ultraviolet circular dichroism spectroscopy and circular dichroism theory.

    PubMed

    Matsuo, Koichi; Hiramatsu, Hirotsugu; Gekko, Kunihiko; Namatame, Hirofumi; Taniguchi, Masaki; Woody, Robert W

    2014-03-20

    Intermolecular structures are important factors for understanding the conformational properties of amyloid fibrils. In this study, vacuum-ultraviolet circular dichroism (VUVCD) spectroscopy and circular dichroism (CD) theory were used for characterizing the intermolecular structures of β2-microglobulin2m) core fragments in the amyloid fibrils. The VUVCD spectra of β2m20-41, β2m21-31, and β2m21-29 fragments in the amyloid fibrils exhibited characteristic features, but they were affected not only by the backbone conformations but also by the aromatic side-chain conformations. To estimate the contributions of aromatic side-chains to the spectra, the theoretical spectra were calculated from the simulated structures of β2m21-29 amyloid fibrils with various types of β-sheet stacking (parallel or antiparallel) using CD theory. We found that the experimental spectrum of β2m21-29 fibrils is largely affected by aromatic-backbone couplings, which are induced by the interaction between transitions within the aromatic and backbone chromophores, and these couplings are sensitive to the type of stacking among the β-sheets of the fibrils. Further theoretical analyses of simulated structures incorporating mutated aromatic residues suggested that the β2m21-29 fibrils are composed of amyloid accumulations in which the parallel β-sheets stack in an antiparallel manner and that the characteristic Phe-Tyr interactions among the β-sheet stacks affect the aromatic-backbone coupling. These findings indicate that the coupling components, which depend on the characteristic intermolecular structures, induce the spectral differences among three fragments in the amyloid fibrils. These advanced spectral analyses using CD theory provide a useful method for characterizing the intermolecular structures of protein and peptide fragment complexes. PMID:24512563

  10. Marked elevation of urinary β2-microglobulin in patients with reversible splenial lesions: A small case series.

    PubMed

    Azuma, Junji; Nabatame, Shin; Katsura, Toshiya; Yamamoto, Kyoko; Kaneno, Hiroshi; Kijima, Eri; Mizoguchi, Yoshimi; Shimotsuji, Tunesuke; Yamamoto, Takehisa; Ozono, Keiichi

    2016-09-15

    The magnetic resonance imaging findings of reversible isolated lesions with transiently reduced diffusion in the splenium of corpus callosum of patients with a wide spectrum of pathological conditions are referred to as reversible splenial lesion syndrome (RESLES). Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is probably included within the spectrum of RESLES; however, its exact pathophysiology is not known. Here, we describe three patients with MERS and one patient with RESLES, all of whom showed elevated urinary β2-microglobulin regardless of diagnosis and presence of pathogens. Elevated urinary β2-microglobulin suggested that an excessive immune response might play a role in the pathophysiology of reversible splenial lesions. PMID:27538611

  11. Activation of Nonclassical CD1d-Restricted NK T Cells Induces Airway Hyperreactivity in β2-Microglobulin-Deficient Mice1

    PubMed Central

    Meyer, Everett H.; Pichavant, Muriel; Akbari, Omid; Yasumi, Takahiro; Savage, Paul B.; DeKruyff, Rosemarie H.; Umetsu, Dale T.

    2016-01-01

    Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in β2-microglobulin2m)−/− mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1+ noninvariant TCR NKT cell population is present in β2m−/− mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of β2m−/− mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to α-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a β2m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR. PMID:18802058

  12. High Serum Level of β2-Microglobulin in Late Posttransplant Period Predicts Subsequent Decline in Kidney Allograft Function: A Preliminary Study

    PubMed Central

    Trailin, Andriy V.; Pleten, Marina V.; Ostapenko, Tatiana I.; Iefimenko, Nadiia F.; Nikonenko, Olexander S.

    2015-01-01

    Background. Identification of patients at risk for kidney allograft (KAG) failure beyond the first posttransplant year is an unmet need. We aimed to determine whether serum beta-2-microglobulin (β2MG) in the late posttransplant period could predict a decline in KAG function. Methods. We assessed a value of single measurement of serum β2MG at one to seventeen years after transplantation in predicting the estimated glomerular filtration rate (eGFR) and the decline in eGFR over a period of two years in 79 recipients of KAG. Results. At baseline serum β2MG concentration was higher (P = 0.011) in patients with allograft dysfunction: 8.67 ± 2.48 µg/mL versus those with satisfactory graft function: 6.67 ± 2.13 µg/mL. Higher β2MG independently predicted the lower eGFR, the drop in eGFR by ≥25% after one and two years, and the value of negative eGFR slope. When combined with proteinuria and acute rejection, serum β2MG had excellent power in predicting certain drop in eGFR after one year (AUC = 0.910). In conjunction with posttransplant time serum β2MG had good accuracy in predicting certain eGFR drop after two years (AUC = 0.821). Conclusions. Elevated serum β2MG in the late posttransplant period is useful in identifying patients at risk for rapid loss of graft function. PMID:26633915

  13. Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids with a Significant Elevation of β-2 Microglobulin Levels

    PubMed Central

    Fujisawa, Naoaki; Mori, Harushi; Matsui, Toru

    2015-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a relapsing-remitting disorder for which steroid administration is a key to control the progression. CLIPPERS can exhibit radiological features similar to malignant lymphoma, whose diagnosis is confounded by prior steroid administration. We report a case of CLIPPERS accompanied by abnormal elevation of β-2 microglobulin in the cerebrospinal fluid (CSF). A 62-year-old man started to experience numbness in all fingers of his left hand one year ago, which gradually extended to his body trunk and legs on both sides. Magnetic resonance imaging demonstrated numerous small enhancing spots scattered in his brain and spinal cord. CSF levels of β-2 microglobulin were elevated; although this often indicates central nervous system involvement in leukemia and lymphoma, the lesions were diagnosed as CLIPPERS based on the pathological findings from a biopsy specimen. We emphasize the importance of biopsy to differentiate between CLIPPERS and malignant lymphoma because the temporary radiological response to steroid might be the same in both diseases but the treatment strategies regarding the use of steroid are quite different. PMID:26713153

  14. A Simulated Intermediate State for Folding and Aggregation Provides Insights into ΔN6 β2-Microglobulin Amyloidogenic Behavior

    PubMed Central

    Estácio, Sílvia G.; Krobath, Heinrich; Vila-Viçosa, Diogo; Machuqueiro, Miguel; Shakhnovich, Eugene I.; Faísca, Patrícia F. N.

    2014-01-01

    A major component of ex vivo amyloid plaques of patients with dialysis-related amyloidosis (DRA) is a cleaved variant of β2-microglobulin (ΔN6) lacking the first six N-terminal residues. Here we perform a computational study on ΔN6, which provides clues to understand the amyloidogenicity of the full-length β2-microglobulin. Contrary to the wild-type form, ΔN6 is able to efficiently nucleate fibrillogenesis in vitro at physiological pH. This behavior is enhanced by a mild acidification of the medium such as that occurring in the synovial fluid of DRA patients. Results reported in this work, based on molecular simulations, indicate that deletion of the N-terminal hexapeptide triggers the formation of an intermediate state for folding and aggregation with an unstructured strand A and a native-like core. Strand A plays a pivotal role in aggregation by acting as a sticky hook in dimer assembly. This study further predicts that the detachment of strand A from the core is maximized at pH 6.2 resulting into higher aggregation efficiency. The structural mapping of the dimerization interface suggests that Tyr10, His13, Phe30 and His84 are hot-spot residues in ΔN6 amyloidogenesis. PMID:24809460

  15. GABA-induced intersubunit conformational movement in the GABAA receptor alpha 1M1-beta 2M3 transmembrane subunit interface: experimental basis for homology modeling of an intravenous anesthetic binding site.

    PubMed

    Bali, Moez; Jansen, Michaela; Akabas, Myles H

    2009-03-11

    The molecular basis of general anesthetic interactions with GABA(A) receptors is uncertain. An accurate homology model would facilitate studies of anesthetic action. Construction of a GABA(A) model based on the 4 A resolution acetylcholine receptor structure is complicated by alignment uncertainty between the acetylcholine and GABA(A) receptor M3 and M4 transmembrane segments. Using disulfide crosslinking we previously established the orientation of M2 and M3 within a single GABA(A) subunit. The resultant model predicts that the betaM3 residue beta2M286, implicated in anesthetic binding, faces the adjacent alpha1-M1 segment and not into the beta2 subunit interior as some models have suggested. To assess the proximity of beta2M286 to the alpha1-M1 segment we expressed beta2M286C and gamma2 with 10 consecutive alpha1-M1 cysteine (Cys) mutants, alpha1I223C to alpha1L232C, in and flanking the extracellular end of alpha1-M1. In activated states, beta2M286C formed disulfide bonds with alpha1Y225C and alpha1Q229C based on electrophysiological assays and dimers on Western blots, but not with other alpha1-M1 mutants. beta2F289, one helical turn below beta2M286, formed disulfide bonds with alpha1I228C, alpha1Q229C and alpha1L232C in activated states. The intervening residues, beta2G287C and beta2C288, did not form disulfide bonds with alpha1-M1 Cys mutants. We conclude that the beta2-M3 residues beta2M286 and beta2F289 face the intersubunit interface in close proximity to alpha1-M1 and that channel gating induces a structural rearrangement in the transmembrane subunit interface that reduces the betaM3 to alphaM1 separation by approximately 7 A. This supports the hypothesis that some intravenous anesthetics bind in the betaM3-alphaM1 subunit interface consistent with azi-etomidate photoaffinity labeling. PMID:19279245

  16. [Circadian variations of urinary excretions of microproteins and N-acetyl-beta-D-glucosaminidase (NAG) during the ordinary activity day].

    PubMed

    Suzuki, M; Ikawa, S

    1990-06-01

    The present investigation was performed to confirm the relationship between the circadian variation of microproteinuria and physical activity. Urine samples from 10 normal male volunteers, collected during six consecutive 4-h periods, were examined for albumin, alpha 1-, beta 2-microglobulin, NAG, electrolytes and hormones. The fluctuations in heart rate (HR) and blood pressure (BP) over 24-h were measured at 30-min and 1-h intervals, respectively. Energy expenditure (EE) was calculated using the equation of regression between HR and oxygen uptake measured on another day. The variations of HR (delta HR) and EE (delta EE) based on a 24-h average (bpm and kcal/kg/h) were used as indices of change in physical activity during an ordinary day. The correlation coefficients between delta HR and the variations of albumin (delta Alb) and beta 2-microglobulin (delta beta 2M) from the 24-h average (micrograms/h.cr 1 mg) were 0.619 and 0.670 (p less than 0.001), respectively. Increased excretions of both glomerular and tubular proteins were correlated with the increase in HR and/or EE during daytime activity. During rest time at night, the variations in alpha 1M, beta 2M and NAG excretion were different from the variations in albumin. A temporary inhibition of tubular protein excretion was observed only in the early morning (04:00-08:00), although albumin excretion was inhibited throughout the nighttime. These findings suggested that physical activity may influence the diurnal variations in protein excretions, that albuminuria may be more sensitive to daytime activity, and that fluctuation of tubular protein excretion may be preferably controlled by an endogenous mechanism. Timed overnight or first-morning urine may be recommendable as a sample for determination of microalbuminuria for screening of clinical diabetic nephropathy. PMID:1699014

  17. Is the staple diet eaten in Medawachchiya, Sri Lanka, a predisposing factor in the development of chronic kidney disease of unknown etiology? - A comparison based on urinary β2-microglobulin measurements

    PubMed Central

    2014-01-01

    Background Exact mechanism of causation of chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is not described to date, despite the identification of possible multiple risk factors. Questions have been raised as to why only some are affected while others remain intact, though they are inhabitants of the same locality. Methods Comparative studies were carried out, assessing urinary β2 microglobulin2m) and the dietary patterns of CKDu patients and age sex matched non-CKDu subjects. Urinary β2m levels of spot urine samples were analyzed using the Enzyme-linked Immunosorbent assay (ELISA) and dietary patterns were studied using twenty four hour dietary recalls and frequency consumption of foods of animal origin performed on three occasions at six months intervals within a period of one and half years. Results The mean urinary β2m level of CKDu patients from Medawachchiya was significantly (p < 0.05) higher when compared with that of the non-CKDu subjects. The mean urinary β2m level of the non-CKDu subjects was within the reference limits for spot urine samples (0 – 0.3 μg/mL). White raw rice was the staple diet of both CKDu patients and non-CKDu subjects and the level of consumption was almost the same. The consumption of fresh water fish products of CKDu patients under high (14, 14%), moderate (36, 36%), low (26, 26%) and less (20, 20%) categories did not show significant variations (p > 0.05) compared to non-CKDu subjects. Conclusions Staple food in diet and the consumption pattern of CKDu patients from Medawachchiya were similar to that of non-CKDu subjects from the same area despite their urinary β2m concentration being significantly higher. PMID:24988874

  18. H2-M3 Major Histocompatibility Complex Class Ib-Restricted CD8 T Cells Induced by Salmonella enterica Serovar Typhimurium Infection Recognize Proteins Released by Salmonella Serovar Typhimurium

    PubMed Central

    Ugrinovic, S.; Brooks, C. G.; Robson, J.; Blacklaws, B. A.; Hormaeche, C. E.; Robinson, J. H.

    2005-01-01

    Salmonella enterica serovar Typhimurium causes a typhoid-like disease in mice which has been studied extensively as a model for typhoid fever in humans. CD8 T cells contribute to protection against S. enterica serovar Typhimurium in mice, but little is known about the specificity and major histocompatibility complex (MHC) restriction of the response. We report here that CD8 T-cell lines derived from S. enterica serovar Typhimurium-infected BALB/c mice lysed bone marrow macrophages infected with S. enterica serovar Typhimurium or pulsed with proteins from S. enterica serovar Typhimurium culture supernatants. Cytoxicity was beta-2-microglobulin dependent and largely TAP dependent, although not MHC class Ia restricted, as target cells of several different MHC haplotypes were lysed. The data suggested the participation of class Ib MHC molecules although no evidence for the presence of Qa1-restricted T cells could be found, unlike in previous reports. Instead, the T-cell lines lysed H2-M3-transfected fibroblasts infected with S. enterica serovar Typhimurium SL3261 or treated with Salmonella culture supernatants. Thus, this report increases the number of MHC class Ib antigen-presenting molecules known for Salmonella antigens to three: Qa-1, HLA-E, and now H2-M3. It also expands the range of pathogens that induce H2-M3-restricted CD8 T cells to include an example of gram-negative bacteria. PMID:16299293

  19. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice.

    PubMed

    Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W; Corao, Diana; Barwe, Sonali P

    2016-01-01

    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80-90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

  20. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice

    PubMed Central

    Gopalakrishnapillai, Anilkumar; Kolb, E. Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W.; Corao, Diana; Barwe, Sonali P.

    2016-01-01

    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80–90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

  1. Defining a novel cis element in the 3'-untranslated region of mammalian ribonucleotide reductase component R2 mRNA: role in transforming growth factor-beta 1 induced mRNA stabilization.

    PubMed Central

    Amara, F M; Chen, F Y; Wright, J A

    1995-01-01

    Ribonucleotide reductase R2 gene expression is elevated in BALB/c 3T3 fibroblasts treated with transforming growth factor beta 1. We investigated the possibility that the 3'-UTR of ribonucleotide reductase R2 mRNA contains regulatory information for TGF-beta 1 induced message stability. Using end-labeled RNA fragments in gel shift assays and UV cross-linking analyses, we detected in the 3'-UTR a novel 9 nucleotide (nt) cis element, 5'-GAGUUUGAG-3' site, which interacted specifically with a cytosolic protease sensitive factor to form a 75 kDa complex. The cis element protein binding activity was inducible and markedly up-regulated cross-link 4 h after TGF-beta 1 treatment of mouse BALB/c 3T3 cells. Other 3'-UTRs [IRE, GM-CSF, c-myc and homopolymer (U)] were poor competitors to the cis element with regard to forming the TGF-beta 1 dependent RNA-protein complex. However, the cis element effectively competed out the formation of the R2 3'-UTR protein complex. Cytosolic extracts from a variety of mammalian cell lines (monkey Cos7, several mouse fibrosarcomas and human HeLa S3) demonstrated similar TGF-beta 1 dependent RNA-protein band shifts as cell extract from BALB/c 3T3 mouse fibroblasts. Binding was completely prevented by several different mutations within the cis element, and by substitution mutagenesis, we were able to predict the consensus sequences, 5'-GAGUUUNNN-3' and 5'-NNNUUUGAG-3' for optimal protein binding. These results support a model in which the 9 nt region functions in cis to destabilize R2 mRNA in cells; and upon activation, a TGF-beta 1 responsive protein is induced and interacts with the 9 nt cis element in a mechanism that leads to stabilization of the mRNA. This appears to be the first example of a mRNA binding site that is involved in TGF-beta 1-mediated effects. Images PMID:7784197

  2. Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection.

    PubMed

    Takagi, Junko; Morita, Hiroyuki; Ito, Kiyoaki; Ohashi, Tomohiko; Hirase, Sho; Ito, Tatsuo; Morishima, Takkan; Otake, Kazuo; Yoneda, Masashi

    2016-01-01

    Adefovir dipivoxil (ADV) is effective for hepatitis B virus (HBV) infection; however, ADV may provoke renal injury resulting in osteomalacia, and this side effect is seldom recognized until bone fractures emerge. We herein present a 66-year-old woman with HBV infection who received ADV for 6 years. Although she exhibited no sign of bone fractures, her urinary β-2 microglobulin (β2MG) level increased to 83,837 μg/L and scintigraphy revealed minimal fractures of the third rib. ADV was subsequently reduced and her urinary β2MG rapidly fell to 3,637 μg/L. Conversely, her urinary N-acetyl-β-D-glucosaminidase, and serum phosphate, alkaline phosphatase levels did not respond. PMID:27301512

  3. Preliminary study on the role of virtual touch tissue quantification combined with a urinary β2-microglobulin test on the early diagnosis of gouty kidney damage.

    PubMed

    Tian, Fei; Wang, Zheng-Bin; Meng, Dong-Mei; Liu, Rong-Gui; Zhang, Hai-Yan; Li, Hui-Ying; Lv, Fei-Fei

    2014-07-01

    The goal of the work described here was to evaluate the role of virtual touch tissue quantification (VTQ) combined with urinary β2-microglobulin (β2-MG) measurement in the early diagnosis of gouty kidney damage. Two hundred fifty-nine patients with gouty kidney damage and 200 healthy control subjects were tested. The shear wave velocity (SWV) of the renal parenchyma and sinus as determined with VTQ and the urinary β2-MG level of the two groups were analyzed. Although there were no significant differences in age, body mass index, creatinine level and blood urea nitrogen between the two groups (all p's > 0.05), the aforementioned parameters were higher in the group with gouty kidney damage than in the control group. Urinary β2-MG levels of the patients with kidney damage were significantly higher than those of the control subjects (t = 6.38, p < 0.01). The SWV of the renal parenchyma was higher than that of the sinus in both groups. Compared with controls, patients with kidney damage had significantly increased renal parenchyma and sinus SWVs (all p-values < 0.05). Urinary β2-MG level was positively linearly correlated with the SWV of renal parenchyma in patients with kidney damage (r = 0.442, p < 0.0001). However, there was no correlation between urinary β2-MG level and the SWV of the sinus in patients with kidney damage (r = 0). In the control group, there was no correlation between urinary β2-MG level and the SWV of the renal parenchyma or sinus. The elasticity of the kidney as determined with VTQ, combined with the urinary β2-MG level, may be helpful in the early diagnosis of gouty kidney damage. PMID:24642221

  4. Effect of Membrane Permeability on Cardiovascular Risk Factors and β2m Plasma Levels in Patients on Long-Term Haemodialysis: A Randomised Crossover Trial.

    PubMed

    Chazot, Charles; Kirchgessner, Judith; Pham, Jenny; Vo-Van, Cyril; Lorriaux, Christie; Hurot, Jean-Marc; Zaoui, Eric; Grassmann, Aileen; Jean, Guillaume; Marcelli, Daniele

    2015-01-01

    Survival of haemodialysis (HD) patients is influenced by many factors. Mortality is mainly of cardiovascular (CV) origin and related to both traditional and nontraditional CV risk factors. Low plasma Beta2-microglobulin2m) levels are associated with improved HD patient survival. HD session times that are longer than the conventional 4 h (i.e., extended dialysis) provide better middle molecule clearance and are also associated with a survival advantage. In this crossover randomised trial, we investigated the effect of membrane flux on CV risk factors and on β2m plasma levels in patients treated with extended dialysis. Dialysis session duration was between 5 and 8 h for all patients. Patients were randomly assigned to the treatment sequences low-flux/high-flux dialysis versus high-flux/low-flux dialysis in a crossover design after a 3-month run-in period, with each phase lasting 9 months. Of the initially enrolled 168 patients, 155 patients started the study after the run-in period, 117 patients completed Phase 1, and 83 patients completed the whole study. Lp(a), homocystein, LDL cholesterol, HDL cholesterol and serum albumin were comparable in the low-flux and high-flux treatments. The average β2m level was 43.3 ± 11.1 mg/l at the end of the low-flux phase. Independent of sequence assignation, average β2m was significantly lower at the end of the high-flux phase (27.5 ± 76.0 mg/l, p < 0.0001 versus end of low-flux phase). Both phosphate and nPNA were significantly lower at the end of the high-flux phase compared to the low-flux phase (p = 0.045 and p = 0.002, respectively). Inclusion of those patients who completed Phase 1 and who dropped out of the study during Phase 2 did not significantly change the results. In conclusion, this study did not find an influence of high-flux filters on several traditional CV risk factors in a population of HD patients treated with extended dialysis. However, high-flux filters are necessary to optimise middle molecule

  5. HLA-E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression.

    PubMed

    Bossard, Céline; Bézieau, Stéphane; Matysiak-Budnik, Tamara; Volteau, Christelle; Laboisse, Christian L; Jotereau, Francine; Mosnier, Jean-François

    2012-08-15

    The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)-E/β2m on tumor cells. The inhibitory effect of HLA-E/β2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA-E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ, in a series of 80 CRC (i) the HLA-E and β2m coexpression by tumor cells, (ii) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial tumor-infiltrating lymphocyte (IEL-TIL) and (iii) the expression of CD94/NKG2 receptor on IEL-TIL. These data were then correlated to patient survival. We provided (i) the in situ demonstration of HLA-E/β2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant association between HLA-E/β2m overexpression by tumor cells and increased density of CD8+ cytotoxic, CD244+ and CD94+ IEL-TIL and (iii) finally, the unfavorable prognosis associated with HLA-E/β2m overexpression by tumor cells. Our findings show that HLA-E/β2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL-TIL. PMID:21953582

  6. Evaluation of serum markers in the LRF CLL4 trial: β2-microglobulin but not serum free light chains, is an independent marker of overall survival.

    PubMed

    Pratt, Guy; Thomas, Peter; Marden, Nicola; Alexander, Denis; Davis, Zadie; Hussey, David; Parry, Helen; Harding, Stephen; Catovsky, Daniel; Begley, Joe; Oscier, David

    2016-10-01

    Chronic lymphocytic leukemia (CLL) is characterized by heterogeneous clinical behavior and there is a need for improved biomarkers. The current study evaluated the prognostic significance of serum free light chains (sFLC, kappa, and lambda) and other serum markers (bar, serum thymidine kinase (sTK), soluble CD23, and LDH) together with established biomarkers in 289 patients enrolled into the LRF CLL4 trial. In a multivariable analysis of serum markers alone, higher big and kappa light chains were statistically significant in predicting disease progression and higher blg, and sTK in predicting mortality. In multivariable analysis for overall survival the following were independently significant: β2M levels, immunoglobulin gene (IGHV) mutational status (>98% homology), age, 17p13 deletions (>10%), and CD38 expression. β2M is the only serum marker that retained clear independent value as a biomarker in the LRF CLL4 trial and remains powerfully prognostic requiring evaluation in any future method of risk stratifying patients. PMID:26732125

  7. Synthesis and characterization of HC[C(Me)N(C(6)H(3)-2,6-i-Pr(2))](2)MX(2) (M = Al, X = Cl, I; M = Ga, In, X = Me, Cl, I): sterically encumbered beta-diketiminate group 13 metal derivatives.

    PubMed

    Stender, M; Eichler, B E; Hardman, N J; Power, P P; Prust, J; Noltemeyer, M; Roesky, H W

    2001-06-01

    A series of group 13 metal complexes featuring the beta-diketiminate ligand [[(C(6)H(3)-2,6-i-Pr(2))NC(Me)](2)CH](-) (i.e., [Dipp(2)nacnac](-), Dipp = C(6)H(3)-2,6-i-Pr(2)) have been prepared and spectroscopically and structurally characterized. The chloride derivatives Dipp(2)nacnacMCl(2) (M = Al (3), Ga (5), In (8)) were isolated in good yield by the reaction of 1 equiv of Dipp(2)nacnacLi.Et(2)O (2) and the respective metal halides. The iodide derivatives Dipp(2)nacnacMI(2) (M = Al (4), Ga (6), In (9)), which are useful for reduction to afford M(I) species, were made by a variety of routes. Thus, 4 was obtained by treatment of the previously reported Dipp(2)nacnacAlMe(2) with I(2), whereas the gallium analogue 6 was obtained as a product of the reaction of "GaI" with Dipp(2)nacnacLi.Et(2)O, and 9 was obtained by direct reaction of InI(3) and the lithium salt. The methyl derivatives Dipp(2)nacnacMMe(2) (M = Ga (7), In (10)), which are analogous to the previously reported Dipp(2)nacnacAlMe(2), were synthesized by the reaction of GaMe(3) with Dipp(2)nacnacH (1) or by reaction of the indium chloride derivative 8 with 2 equiv of MeMgBr in diethyl ether. The compounds 3-10 exist as colorless, air- and moisture-sensitive crystalline solids. Their X-ray crystal structures feature nearly planar C(3)N(2) arrays in the Dipp(2)nacnac ligand backbone with short C-C and C-N distances that are consistent with a delocalized structure. However, there are large dihedral angles between the C(3)N(2) plane and the N(2)M metal coordination plane which have been attributed mainly to steric effects. The relatively short M-N distances are consistent with the coordination numbers of the metals and the normal/dative character of the nitrogen ligands. The compounds were also characterized by (1)H and (13)C NMR spectroscopy. (1)H NMR data for 7 revealed equivalent methyl groups whereas the spectrum of 10 displayed two In-Me signals which indicated that ring wagging was slow on the (1)H NMR

  8. Monoclonal antibodies to HLA-E bind epitopes carried by unfolded β2 m-free heavy chains.

    PubMed

    Tremante, Elisa; Lo Monaco, Elisa; Ingegnere, Tiziano; Sampaoli, Camilla; Fraioli, Rocco; Giacomini, Patrizio

    2015-08-01

    Since HLA-E heavy chains accumulate free of their light β2 -microglobulin2 m) subunit, raising mAbs to folded HLA-E heterodimers has been difficult, and mAb characterization has been controversial. Herein, mAb W6/32 and 5 HLA-E-restricted mAbs (MEM-E/02, MEM-E/07, MEM-E/08, DT9, and 3D12) were tested on denatured, acid-treated, and natively folded (both β2 m-associated and β2 m-free) HLA-E molecules. Four distinct conformations were detected, including unusual, partially folded (and yet β2 m-free) heavy chains reactive with mAb DT9. In contrast with previous studies, epitope mapping and substitution scan on thousands of overlapping peptides printed on microchips revealed that mAbs MEM-E/02, MEM-E/07, and MEM-E/08 bind three distinct α1 and α2 domain epitopes. All three epitopes are linear since they span just 4-6 residues and are "hidden" in folded HLA-E heterodimers. They contain at least one HLA-E-specific residue that cannot be replaced by single substitutions with polymorphic HLA-A, HLA-B, HLA-C, HLA-F, and HLA-G residues. Finally, also the MEM-E/02 and 3D12 epitopes are spatially distinct. In summary, HLA-E-specific residues are dominantly immunogenic, but only when heavy chains are locally unfolded. Consequently, the available mAbs fail to selectively bind conformed HLA-E heterodimers, and HLA-E expression may have been inaccurately assessed in some previous oncology, reproductive immunology, virology, and transplantation studies. PMID:25982269

  9. 2m class telescope project at Lijiang

    NASA Astrophysics Data System (ADS)

    Chen, Dong; Wang, Jian-Cheng; Xu, Jun; Zhang, Bai-Rong; Luo, Guo-Quan; Liu, Zhong; Tan, Hui-Song

    Supported by the ministry of science and technology, government of Yunnan Province and Chinese Academy of Sciences, a 2m class telescope project was granted. In this paper, we will first review the site, Gaomeigu, briefly, then give the details of 2m class telescope project, and finally discuss the future plans of this new telescope.

  10. Present and Future of M2M

    NASA Astrophysics Data System (ADS)

    Ono, Satoru; Watanabe, Takashi

    In recent years, the rapid progress in the development of hardware and software technologies enables tiny and low cost information devices hereinafter referred to as Machine to be widely available. M2M (Machine to Machine) has been of much attention where many tiny machines are connected to each other through networks with minimal human intervention to provide smooth and intelligent management. M2M is a promising core technology providing timely, flexible, efficient and comprehensive service at low cost. M2M has wide variety of applications including energy management system, environmental monitoring system, intelligent transport system, industrial automation system and other applications. M2M consists of terminals and networks that connect them. In this paper, we mainly focus on M2M networking and mention the future direction of the technology.

  11. Secondary Structure in the Core of Amyloid Fibrils Formed from Human β2m and its Truncated Variant ΔN6

    PubMed Central

    2014-01-01

    Amyloid fibrils formed from initially soluble proteins with diverse sequences are associated with an array of human diseases. In the human disorder, dialysis-related amyloidosis (DRA), fibrils contain two major constituents, full-length human β2-microglobulin (hβ2m) and a truncation variant, ΔN6 which lacks the N-terminal six amino acids. These fibrils are assembled from initially natively folded proteins with an all antiparallel β-stranded structure. Here, backbone conformations of wild-type hβ2m and ΔN6 in their amyloid forms have been determined using a combination of dilute isotopic labeling strategies and multidimensional magic angle spinning (MAS) NMR techniques at high magnetic fields, providing valuable structural information at the atomic-level about the fibril architecture. The secondary structures of both fibril types, determined by the assignment of ∼80% of the backbone resonances of these 100- and 94-residue proteins, respectively, reveal substantial backbone rearrangement compared with the location of β-strands in their native immunoglobulin folds. The identification of seven β-strands in hβ2m fibrils indicates that approximately 70 residues are in a β-strand conformation in the fibril core. By contrast, nine β-strands comprise the fibrils formed from ΔN6, indicating a more extensive core. The precise location and length of β-strands in the two fibril forms also differ. The results indicate fibrils of ΔN6 and hβ2m have an extensive core architecture involving the majority of residues in the polypeptide sequence. The common elements of the backbone structure of the two proteins likely facilitates their ability to copolymerize during amyloid fibril assembly. PMID:24679070

  12. Structural Basis of the CD8[alpha beta]/MHC Class I Interaction: Focused Recognition Orients CD8[beta] to a T Cell Proximal Position[superscript 1,2

    SciTech Connect

    Wang, Rui; Natarajan, Kannan; Margulies, David H.

    2009-09-18

    In the immune system, B cells, dendritic cells, NK cells, and T lymphocytes all respond to signals received via ligand binding to receptors and coreceptors. Although the specificity of T cell recognition is determined by the interaction of T cell receptors with MHC/peptide complexes, the development of T cells in the thymus and their sensitivity to Ag are also dependent on coreceptor molecules CD8 (for MHC class I (MHCI)) and CD4 (for MHCII). The CD8{alpha}{beta} heterodimer is a potent coreceptor for T cell activation, but efforts to understand its function fully have been hampered by ignorance of the structural details of its interactions with MHCI. In this study we describe the structure of CD8{alpha}{beta} in complex with the murine MHCI molecule H-2D{sup d} at 2.6 {angstrom} resolution. The focus of the CD8{alpha}{beta} interaction is the acidic loop (residues 222-228) of the {alpha}3 domain of H-2D{sup d}. The {beta} subunit occupies a T cell membrane proximal position, defining the relative positions of the CD8{alpha} and CD8{beta} subunits. Unlike the CD8{alpha}{alpha} homodimer, CD8{alpha}{beta} does not contact the MHCI {alpha}{sub 2}- or {beta}{sub 2}-microglobulin domains. Movements of the CD8{alpha} CDR2 and CD8{beta} CDR1 and CDR2 loops as well as the flexibility of the H-2D{sup d} CD loop facilitate the monovalent interaction. The structure resolves inconclusive data on the topology of the CD8{alpha}{beta}/MHCI interaction, indicates that CD8{beta} is crucial in orienting the CD8{alpha}{beta} heterodimer, provides a framework for understanding the mechanistic role of CD8{alpha}{beta} in lymphoid cell signaling, and offers a tangible context for design of structurally altered coreceptors for tumor and viral immunotherapy.

  13. Renal tubular dysfunction in a patient with beta-thalassemia minor.

    PubMed

    Oktenli, Cagatay; Bulucu, Fatih

    2002-09-01

    Beta-thalassemia minor is a hemoglobinopathy which has been known as a symptomless carrier state. Although there are many causes leading to renal tubular dysfunction, beta-thalassemia minor has not been reported among them in reviewing the literature. In a 20-year-old male patient referred to us because of glucosuria detected with dipstick, there was also anemia (hemoglobin, 11.5 g/dl; mean cell volume, 60 fl; and mean cell hemoglobin concentration, 19.5 pg). The 24-hour urinary glucose excretion rate was 5 g and, additionally, he had tubular proteinuria (albumin/beta(2)-microglobulin ratio in urine was 17.32). Based upon the detailed evaluation for both asymptomatic urinary abnormality and anemia, he was diagnosed as having renal tubular dysfunction and beta-thalassemia minor (hemoglobin A(1)was 91%, and hemoglobin A(2)was 9%). In conclusion, further reports are needed to reveal whether there is an association between these two distinct disorders. PMID:12187108

  14. Development of 2 m×2 m size glass RPCs for INO

    NASA Astrophysics Data System (ADS)

    Bhuyan, M.; Datar, V. M.; Kalmani, S. D.; Lahamge, S. M.; Mohammed, S.; Mondal, N. K.; Nagaraj, P.; Redij, A.; Samuel, D.; Saraf, M. N.; Satyanarayana, B.; Shinde, R. R.; Verma, P.

    2012-01-01

    The India-based Neutrino Observatory (INO) collaboration is planning to build a massive 50 kt magnetised iron calorimeter (ICAL) detector to study atmospheric neutrinos and to precisely determine the neutrino oscillation parameters. About 30,000 2 m×2 m size glass Resistive Plate Chambers (RPCs) will be used as active detector elements in ICAL. Starting with a small 30 cm ×30 cm size RPCs, we have now succeeded in developing full size 2 m ×2 m RPCs. The fabrication procedures used for these large size RPCs as well as their performance will be discussed in this paper. We will also present some preliminary results from our studies on SF6 based gas mixtures on the RPC operation and characteristics.

  15. Kinetics of the reaction HO2 + NO2 + M yields HO2NO2 + M

    NASA Technical Reports Server (NTRS)

    Sander, S. P.; Peterson, M. E.

    1984-01-01

    The flash photolysis/ultraviolet absorption technique was used to measure the rate constants for the reaction HO2 + NO2 + M yields HO2NO2 + M over the pressure range 50-700 torr and temperature range 229-362 K using He, O2, and N2 as diluent gases. The data were fit to the expression derived by Troe (1979) and co-workers for describing the pressure and temperature dependence of reactions in the falloff region. By combining these data with recent measurements of the rate constant for HO2NO2 thermal decomposition values of 73.8 + or - 2 eu for the standard entropy and -12.6 + or - kcal/mol for the standard enthalpy of formation of HO2NO2 were obtained. A significant enhancement in the rate constant was observed when water vapor was added to the system.

  16. Beta experiment

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser doppler velocimeter (LDV) system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. A Doppler signal generator was used in mapping the coherent sensitive focal volume of a focused LDV system. System calibration data was analyzed during the flight test activity scheduled for the Beta system. These analyses were performed to determine the acceptability of the Beta measurement system's performance.

  17. A polymorphism in metallothionein 1A (MT1A) is associated with cadmium-related excretion of urinary beta 2‐microglobulin

    SciTech Connect

    Lei, Lijian; Chang, Xiuli; Rentschler, Gerda; Tian, Liting; Zhu, Guoying; Chen, Xiao; Jin, Taiyi; Broberg, Karin

    2012-12-15

    Objectives: Cadmium (Cd) toxicity of the kidney varies between individuals despite similar exposure levels. In humans Cd is mainly bound to metallothioneins (MT), which scavenge its toxic effects. Here we analyzed whether polymorphisms in MT genes MT1A and MT2A influence Cd-related kidney damage. Methods: In a cross-sectional study N = 512 volunteers were selected from three areas in South-Eastern China, which to varying degree were Cd-polluted from a smelter (control area [median Cd in urine U-Cd = 2.67 μg/L], moderately [U-Cd = 4.23 μg/L] and highly [U-Cd = 9.13 μg/L] polluted areas). U-Cd and blood Cd (B-Cd) concentrations were measured by graphite-furnace atomic absorption spectrometry. MT1A rs11076161 (G/A), MT2A rs10636 (G/C) and MT2A rs28366003 (A/G) were determined by Taqman assays; urinary N-Acetyl-beta-(D)-Glucosaminidase (UNAG) by spectrometry, and urinary β2-microglobulin (UB2M) by ELISA. Results: Higher B-Cd (natural log-transformed) with increasing number of MT1A rs11076161 A-alleles was found in the highly polluted group (p-value trend = 0.033; all p-values adjusted for age, sex, and smoking). In a linear model a significant interaction between rs11076161 genotype and B-Cd was found for UNAG (p = 0.001) and UB2M concentrations (p = 0.001). Carriers of the rs11076161 AA genotype showed steeper slopes for the associations between Cd in blood and natural log-transformed UB2M (β = 1.2, 95% CI 0.72–1.6) compared to GG carriers (β = 0.30, 95% CI 0.15–0.45). Also for UNAG (natural log-transformed) carriers of the AA genotype had steeper slopes (β = 0.55, 95% CI 0.27–0.84) compared to GG carriers (β = 0.018, 95% CI − 0.79–0.11). Conclusions: MT1A rs11076161 was associated with B-Cd concentrations and Cd-induced kidney toxicity at high exposure levels. -- Highlights: ► Cadmium is toxic to the kidney but the susceptibility differs between individuals. ► The toxic effect of cadmium is scavenged by metallothioneins. ► A common variant of

  18. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    SciTech Connect

    Dalgaard, Louise T.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiency improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.

  19. Ultrasound assisted ambient temperature synthesis of ternary oxide AgMO{sub 2} (M=Fe, Ga)

    SciTech Connect

    Nagarajan, R.; Tomar, Nobel

    2009-06-15

    The application of ultrasound for the synthesis of ternary oxide AgMO{sub 2} (M=Fe, Ga) was investigated. Crystalline alpha-AgFeO{sub 2} was obtained from the alkaline solutions of silver and iron hydroxides by sonication for 40 minutes. alpha-AgFeO{sub 2} was found to absorb optical radiation in the 300-600 nm range as shown by diffuse reflectance spectroscopy. The Raman spectrum of alpha-AgFeO{sub 2} exhibited two bands at 345 and 638 cm{sup -1}. When beta-NaFeO{sub 2} was sonicated with aqueous silver nitrate solution for 60 minutes, beta-AgFeO{sub 2} possessing orthorhombic structure was obtained as the ion-exchanged product. The Raman spectrum of beta-AgFeO{sub 2} showed four strong bands at 295, 432, 630 and 690 cm{sup -1}. Sonication of beta-NaGaO{sub 2} with aqueous silver nitrate solution for 60 minutes resulted in olive green colored, alpha-AgGaO{sub 2}. The diffuse reflectance spectrum and the EDX analysis confirmed that the ion-exchange through sonication was complete. The Raman spectrum of alpha-AgGaO{sub 2} had weak bands at 471 and 650 cm{sup -1}. - Graphical abstract: The application of ultrasound in the formation of alpha and beta-forms of AgMO{sub 2} (M=Fe, Ga) has been demonstrated.

  20. Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

    SciTech Connect

    Gamo, Masashi . E-mail: masashi-gamo@aist.go.jp; Ono, Kyoko; Nakanishi, Junko

    2006-05-15

    A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature and those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.

  1. Perforin facilitates beta cell killing and regulates autoreactive CD8+ T-cell responses to antigen in mouse models of type 1 diabetes.

    PubMed

    Trivedi, Prerak; Graham, Kate L; Krishnamurthy, Balasubramaninan; Fynch, Stacey; Slattery, Robyn M; Kay, Thomas W H; Thomas, Helen E

    2016-04-01

    In type 1 diabetes, cytotoxic CD8(+) T lymphocytes (CTLs) directly interact with pancreatic beta cells through major histocompatibility complex class I. An immune synapse facilitates delivery of cytotoxic granules, comprised mainly of granzymes and perforin. Perforin deficiency protects the majority of non-obese diabetic (NOD) mice from autoimmune diabetes. Intriguingly perforin deficiency does not prevent diabetes in CD8(+) T-cell receptor transgenic NOD8.3 mice. We therefore investigated the importance of perforin-dependent killing via CTL-beta cell contact in autoimmune diabetes. Perforin-deficient CTL from NOD mice or from NOD8.3 mice were significantly less efficient at adoptive transfer of autoimmune diabetes into NODRag1(-/-) mice, confirming that perforin is essential to facilitate beta cell destruction. However, increasing the number of transferred in vitro-activated perforin-deficient 8.3 T cells reversed the phenotype and resulted in diabetes. Perforin-deficient NOD8.3 T cells were present in increased proportion in islets, and proliferated more in response to antigen in vivo indicating that perforin may regulate the activation of CTLs, possibly by controlling cytokine production. This was confirmed when we examined the requirement for direct interaction between beta cells and CD8(+) T cells in NOD8.3 mice, in which beta cells specifically lack major histocompatibility complex (MHC) class I through conditional deletion of β2-microglobulin. Although diabetes was significantly reduced, 40% of these mice developed diabetes, indicating that NOD8.3 T cells can kill beta cells in the absence of direct interaction. Our data indicate that although perforin delivery is the main mechanism that CTL use to destroy beta cells, they can employ alternative mechanisms to induce diabetes in a perforin-independent manner. PMID:26446877

  2. Rate coefficient for H + O2 + M = HO2 + M evaluated from shock tube measurements of induction times

    NASA Technical Reports Server (NTRS)

    Slack, M. W.

    1977-01-01

    Shock tube experiments measured hydrogen-air induction times near the second explosion limit. By matching these experimental results with numerically predicted induction times, the rate coefficient for the reaction H + O2 + M = HO2 + M was evaluated as k-sub 4,N2 = 3.3 (plus or minus .6) x 10 to the 15 cm to the 6th/sq mole/s.

  3. Increased interleukin-1beta mRNA expression in skin biopsies of horses with Culicoides hypersensitivity following challenge with Culicoides nubeculosus extract.

    PubMed

    Kolm, Gabriela; Knapp, Elzbieta; Wagner, Regina; Klein, Dieter

    2006-09-15

    Interleukin-1beta (IL-1beta) is a primary cytokine of the skin that has a pivotal role in keratinocyte differentiation, epidermal wound healing and host defense. Pathological increase of cutaneous IL-1beta is associated with edema formation, epidermal hyperproliferation and atopic dermatitis in humans. However, in horses the role of cutaneous IL-1beta in edema formation and allergic skin disease has not been characterised so far. Particularly in Culicoides hypersensitivity (CHS), intradermal injection of Culicoides extract may be associated with enhanced transcription of local IL-1beta. To examine the mRNA expression of IL-1beta and its receptor antagonist IL-1RA in the skin of horses, biopsy specimens of horses affected and non-affected by CHS prior and following intradermal challenge with a commercial C. nubeculosus extract were examined. Our hypothesis was that cutaneous IL-1beta mRNA was significantly upregulated in horses with CHS in response to Culicoides allergen. Biopsies were taken from sites prior to and 4 h following intradermal challenge with C. nubeculosus extract. In order to obtain reliable data, real time PCR was performed and genes of interest were normalized using three different housekeeping genes, beta-actin, GAPDH, beta-2-microglobulin. No significant difference was detected in non-challenged cutaneous IL-1beta mRNA and IL-1RA mRNA levels between CHS affected and non-affected horses. Intradermal injection of C. nubeculosus extract resulted in local upregulation of IL-1beta mRNA both in horses with typical history, characteristic clinical signs for CHS and a positive intradermal skin test (IDT), and non-affected horses with a negative IDT. However, the difference in prior and post challenged site IL-1beta mRNA levels only reached statistical significance in the affected horses (p=0.01 versus 0.7). In contrast, IL-1RA mRNA levels did not demonstrate any modification following intradermal injection with C. nubeculosus in either group. In contrast

  4. CH2M Hill cleared in tunnel explosion case

    SciTech Connect

    Krizan, W.G.; Bradford, H.; Schriener, J.

    1993-09-06

    One of the most critical issues in industry is whether architects and engineers should be held responsible for construction safety on jobsites. The Occupational Safety and Health Administration says yes under certain conditions. But the Occupational Safety and Health Review Commission has overturned one application of that view on appeal in a controversial case. It involves a unit of Denver-based CH2M Hill Cos.'s role as program manager for the Milwaukee Metropolitan Sewerage District (MMSD) on its $2.2-billion water pollution abatement program. On May 5, 1989, OSHA cited CH2M Hill Central Inc. for 46 willful safety violations in connection with a 1988 methane tunnel explosion that killed three supervisors of contractor S.A. Healy Co., Chicago, Healy was charged with 68 violations. Healy encountered methane while boring CT-7, a two-mile crosstown tunnel. It evacuated the site, but didn't follow the evacuation plan. It failed to shut down all nonessential equipment and the supervisors returned after waiting only 17 minutes instead of the one hour minimum. CH2M Hill's citations and proposed $460,000 fine for violating OSHA's construction standards were for having 45 pieces of unapproved electrical equipment in the tunnel and improper ventilation equipment. CH2M Hill claimed the standards did not apply to it because the firm did not engage in construction work, exercise substantial supervision over the construction work performed by the contractor or create or control the hazardous condition.

  5. Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis.

    PubMed Central

    Coker, R. K.; Laurent, G. J.; Shahzeidi, S.; Lympany, P. A.; du Bois, R. M.; Jeffery, P. K.; McAnulty, R. J.

    1997-01-01

    Transforming growth factor (TGF)-beta 1 may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear. We examined their effects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three isoforms stimulated fibroblast procollagen production. TGF-beta 3 was the most potent and also reduced procollagen degradation. In normal mouse lung, TGF-beta 1 and TGF-beta 3 mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta 1 gene expression was maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endothelial, and mesothelial cells. After 35 days, the pattern of TGF-beta 1 gene expression returned to that of control lung. TGF-beta 3 gene expression remained unchanged throughout compared with controls. TGF-beta 2 mRNA was not detected with the antisense probe, but signal obtained with the sense probe suggests the presence of a naturally occurring antisense. This study demonstrates that TGF-beta 1, -beta 2, and -beta 3 all exert profibrotic effects in vitro. However, TGF-beta isoform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta 1 the predominant isoform expressed during pathogenesis. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9060836

  6. Recent activities on the compatibility of the ferritic steel wall with the plasma in the JFT-2M tokamak

    NASA Astrophysics Data System (ADS)

    Tsuzuki, K.; Sato, M.; Kawashima, H.; Isei, N.; Kimura, H.; Ogawa, H.; Miyachi, K.; Yamamoto, M.; Shibata, T.

    2002-12-01

    The compatibility of the low activation ferritic steel with a fusion plasma has been investigated in the JFT-2M tokamak. The program consists of three stages. In the first stage, the reduction of fast ion losses was well demonstrated by ferritic steel plates (FPs) outside the vacuum vessel (VV). In the second stage, 20% of the inner surface of the VV was covered by the FPs. The plasma control, stability, and impurity release were preliminary investigated. No deteriorative effect on the plasma was observed at least in the following conditions: partial covering of 20% and the normalized beta value less than 2.8. First boronization was applied to JFT-2M leading to a remarkable decrease of the oxygen impurity. After the boronization, plasmas with the highest normalized beta in JFT-2M were obtained. Thus encouraging results were gained for this stage. In the third stage, the VV was fully covered by FPs, where the ripple reduction and the plasma stability will be investigated as a full scale testing.

  7. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

    PubMed Central

    Flynn, F. V.; Lapsley, M.; Sansom, P. A.; Cohen, S. L.

    1992-01-01

    AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive

  8. Contact aiming system of 2m laser automatic interferometric comparator

    NASA Astrophysics Data System (ADS)

    Sun, Shuanghua; Ye, Xiaoyou; Zou, Lingding; Gao, Hongtang; Gan, Xiaochuan; Shen, Xueping

    2013-01-01

    Composition and principle of 2m laser automatic interferometric comparator were introduced. A novel contact aiming system based on high precision inductance sensor was designed. The zero-cross trigger signal of inductance sensor output voltage was treated as the aiming signal. A rotating mechanism was designed and a segmental shifting motion control model was established. Two key problems, avoiding probe crash and aiming repeatability, were solved. The one dimension end standards such as gauge block, step gauge could be measured directly by this means. The data of test revealed that aiming repeatability was less than 0.2μm.

  9. Automation of Pic du Midi 2-m Telescope Bernard Lyot

    NASA Astrophysics Data System (ADS)

    Lavie-Cambot, Jean-Marie; Lacassagne, F.; Ambert, P.; Arrotis, J.-M.; Argentin, Y.; Arberet, M.-P.; Chereau, E.; Decha, C.; Delaigue, C.; Guesdon, L.; Laurent-Burguiere, D.; Malbreil, G.

    2011-03-01

    Since 2007, Pic du Midi 2-m Telescope Bernard Lyot is dedicated to spectropolarimetry with a scientific niche in stella magnetism. In parallel, TBL is progressively evolving from an analogic human-controlled telescope, to a fully automated computer controlled digital telescope. This evolution required TBL team to replace all electronics and motors with digital system (parvex, brushless motors, buscan) components, and to integrate the dataflow system from proposal to archiving into a fully coordinates, remote-access software suite. A trained technician can already control remotely the telescope, instrument and science programs from anywhere. Further robotisation will require a high-level expert system to be defined.

  10. A Native to Amyloidogenic Transition Regulated by a Backbone Trigger

    SciTech Connect

    Eakin,C.; Berman, A.; Miranker, A.

    2006-01-01

    Many polypeptides can self-associate into linear, aggregated assemblies termed amyloid fibers. High-resolution structural insights into the mechanism of fibrillogenesis are elusive owing to the transient and mixed oligomeric nature of assembly intermediates. Here, we report the conformational changes that initiate fiber formation by beta-2-microglobulin (beta2m) in dialysis-related amyloidosis. Access of beta2m to amyloidogenic conformations is catalyzed by selective binding of divalent cations. The chemical basis of this process was determined to be backbone isomerization of a conserved proline. On the basis of this finding, we designed a beta2m variant that closely adopts this intermediate state. The variant has kinetic, thermodynamic and catalytic properties consistent with its being a fibrillogenic intermediate of wild-type beta2m. Furthermore, it is stable and folded, enabling us to unambiguously determine the initiating conformational changes for amyloid assembly at atomic resolution.

  11. Fatigue crack propagation in carburized X-2M steel

    NASA Astrophysics Data System (ADS)

    Averbach, B. L.; Lou, Bingzhe; Pearson, P. K.; Fairchild, R. E.; Bamberger, E. N.

    1985-07-01

    The growth rates of fatigue cracks propagating through the case and into the core have been studied for carburized X-2M steel (0.14 C, 4.91 Cr, 1.31 Mo, 1.34 W, 0.42 V). Fatigue cracks were propagated at constant stress intensities, ΔK, and also at a constant cyclic peak load, and the crack growth rates were observed to pass through a minimum value as the crack traversed the carburized case. The reduction in the crack propagation rates is ascribed to the compressive stresses which were developed in the case, and a pinched clothespin model is used to make an approximate calculation of the effects of internal stress on the crack propagation rates. We define an effective stress intensity, Ke = Ka + Ki, where Ka is the applied stress intensity, Ki = σid{i/1/2}, σi is the internal stress, and di is a characteristic distance associated with the depth of the internal stress field. In our work, a value of di = 11 mm (0.43 inch) fits the data quite well. A good combination of resistance to fatigue crack propagation in the case and fracture toughness in the core can be achieved in carburized X-2M steel, suggesting that this material will be useful in heavy duty gears and in aircraft gas turbine mainshaft bearings operating under high hoop stresses.

  12. 2-m LAMOST-type telescope for the Antarctic

    NASA Astrophysics Data System (ADS)

    Cui, Xiangqun; Zhao, Yongheng; Wang, Yanan; Li, Guoping

    2006-06-01

    The Large-Sky-Area Multi-object Fiber Spectroscopic Telescope (LAMOST) put forward by Shou-guan Wang and Ding-qiang Su is a special reflecting Schmidt telescope with the spherical mirror fixed and the correcting plate acts as both correcting plate and tractor. The correcting plate is installed on an alt-azimuth mounting and its aspherical figure is variable to meet the requirement for eliminate the spherical aberration of the spherical primary mirror when it is at variant orientations during the observation course and for different sky area. With LAMOST, both large aperture and large field of view can been obtained. Benefited from the LAMOST design and practice, a LAMOST-type telescope for full-sky survey is conceived for the Antarctic. Because of the favorable seeing condition and all-winter continuous observation, a telescope with aperture of the 2-m could be equivalent to the 4-m LAMOST. We preliminarily considered a 2-m telescope with a primary focus and a Cassegrain focus. The f-ratio of 5 and FOV 3-degree for the primary focus, and f-ratio of 15 and 8 minutes FOV with the diffraction limited image for the Cassegrain focus. In this paper, the scientific goals, the optical system of the telescope, particular material and technique which are applicable under the extreme low temperature condition at the Antarctic are described.

  13. Cereal beta-glucans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereal beta-glucans occur predominantly in oats and barley, but can be found in other cereals. Beta-glucan structure is a mixture of single beta-1,3-linkages and consecutive beta-1,4-linkages, and cellotriosyl and cellotetraosyl units typically make up 90-95% of entire molecule. Lichenase can hydr...

  14. Kinetics of the reaction Cl + NO2 + M

    NASA Technical Reports Server (NTRS)

    Leu, M.-T.

    1984-01-01

    Using atomic chlorine resonance fluorescence at 140 nm to detect the decay of atomic chlorine in the presence of an excess of NO2, the rate constant for the reaction Cl + NO2 + M, where M is the total gas concentration, is measured over the temperature range 264 to 417 K and at a pressure 1 to 7 torr in a discharge flow system. The rate constants for M= He and M= N2 are measured and the results are summarized in a table. The systematic error of the rate constants is estimated to be about 15 percent. A static photolysis system coupled with an FTIR spectrophotometer is used to determine the branching ratio for the formation of two possible isomers. The ratio is concluded to be ClONO (greater than or equal 75 percent) and ClNO2 (less than or equal 25 percent) which is in agreement with the results of Niki et al. (1978).

  15. Direct drive targets for the megajoule facility UFL-2M

    NASA Astrophysics Data System (ADS)

    Rozanov, V. B.; Gus'kov, S. Yu; Vergunova, G. A.; Demchenko, N. N.; Stepanov, R. V.; Doskoch, I. Ya; Yakhin, R. A.; Zmitrenko, N. V.

    2016-03-01

    Development of direct drive target schemes for the megajoule facility is a topical problem of up-to-date inertial fusion physics. The choice of possible schemes and solutions depends essentially on the irradiation conditions. The installations both running (NIF) and under construction (LMJ) are destined to the 3ω irradiation in PDD (polar direct drive) configuration. The UFL-2M installation that is under construction is based on 2ω irradiation and a symmetrical scheme of direct drive target irradiation. Under these conditions possible schemes for direct drive targets demonstrating the ignition and the achievement of gain G=10÷20 are considered in this report. At the same time, the possibilities are analyzed for the target compression and ignition with a reliability reserve at the conditions that can deviate from the standard ones, and if our understanding of the physics of the processes is not completely adequate to the physics of the real processes.

  16. Global magnetohydrodynamic instabilities in the L-2M stellarator

    SciTech Connect

    Mikhailov, M. I.; Shchepetov, S. V.; Nührenberg, C.; Nührenberg, J.

    2015-12-15

    Analysis of global magnetohydrodynamic (MHD) instabilities in the L-2M stellarator (Prokhorov General Physics Institute, Russian Academy of Sciences) is presented. The properties of free-boundary equilibria states are outlined, the stability conditions for small-scale modes are briefly discussed, and the number of trapped particles is estimated. All the magnetic configurations under study are stable against ballooning modes. It is shown that global ideal internal MHD modes can be found reliably only in Mercier unstable plasmas. In plasma that is stable with respect to the Mercier criterion, global unstable modes that are localized in the vicinity of the free plasma boundary and are not associated with any rational magnetic surface inside the plasma (the so-called peeling modes) can be found. The radial structure of all perturbations under study is almost entirely determined by the poloidal coupling of harmonics. The results of calculations are compared with the available experimental data.

  17. Experimental study of hot electrons in LECR2M plasma

    SciTech Connect

    Zhao, H. Y.; Zhao, H. W.; Ma, X. W.; Wang, H.; Zhang, X. Z.; Sun, L. T.; Ma, B. H.; Li, X. X.; Sha, S.; Zhu, Y. H.; Lu, W.; Shang, Y.

    2008-02-15

    In order to investigate the hot electron component in electron cyclotron resonance (ECR) plasmas, the volume bremsstrahlung spectra in the x-ray photon energy range were measured with a high-purity germanium detector on Lanzhou ECR Ion Source No. 2 Modified (LECR2M). A collimation system similar to Bernhardi's was used to focus at the central part of the plasma. The ion source was operated under various source conditions with argon; sometimes oxygen was added to enhance high charge state ion beam intensities. The spectral temperature of hot electrons T{sub spe} was derived from the measured bremsstrahlung spectra. The evolution of the deduced temperature of hot electrons T{sub spe} with the ion source parameters, such as the rf frequency, power, and the magnetic confinement configuration, was investigated.

  18. Kinetics of the ClO + NO2 + M reaction

    NASA Technical Reports Server (NTRS)

    Molina, M. J.; Molina, L. T.; Ishiwata, T.

    1980-01-01

    The ClO + NO2 + M reaction has been studied with two techniques: Fourier transform infrared spectroscopy of the products, and flash photolysis-ultraviolet absorption to monitor the decay of ClO in excess NO2. The measured third-order rate constant is 1.5 x 10 to the -31st cm to the 6th/molecule-squared per sec at 298 K with M = N2, in good agreement with previous literature values, but the rate constant appears to decrease by up to a factor of three in the presence of increasing amounts of OClO. For the infrared studies a stoichiometric mixture of ClO and NO2 was prepared in a flow system by mixing NO with OClO; at least as much NO2 as ClONO2 was produced under a variety of experimental conditions. These two sets of results are incompatible with the assumption made in previous kinetic studies that ClONO2 is the only recombination product; other isomers such as OClONO or ClOONO are likely to be formed three to four times faster. These results imply that potential stratospheric ozone depletion due to chlorofluoromethanes may be even larger than previously thought.

  19. Particle Shape and Composition of NU-LHT-2M

    NASA Technical Reports Server (NTRS)

    Rickman, D. L.; Lowers, H.

    2012-01-01

    Particle shapes of the lunar regolith simulant NU-LHT-2M were analyzed by scanning electron microscope of polished sections. These data provide shape, size, and composition information on a particle by particle basis. 5,193 particles were measured, divided into four sized fractions: less than 200 mesh, 200-100 mesh, 100-35 mesh, and greater than 35 mesh. 99.2% of all particles were monominerallic. Minor size versus composition effects were noted in minor and trace mineralogy. The two metrics used are aspect ratio and Heywood factor, plotted as normalized frequency distributions. Shape versus composition effects were noted for glass and possibly chlorite. To aid in analysis, the measured shape distributions are compared to data for ellipses and rectangles. Several other simple geometric shapes are also investigated as to how they plot in aspect ratio versus Heywood factor space. The bulk of the data previously reported, which were acquired in a plane of projection, are between the ellipse and rectangle lines. In contrast, these data, which were acquired in a plane of section, clearly show that a significant number of particles have concave hulls in this view. Appendices cover details of measurement error, use of geometric shapes for comparative analysis, and a logic for comparing data from plane of projection and plane of section measurements.

  20. A Regulatable Switch Mediates Self Association in an Immunoglobulin Fold

    SciTech Connect

    Calabrese,M.; Eakin, C.; Wang, J.; Miranker, A.

    2008-01-01

    beta-2 microglobulin (beta2m) is a globular protein that self-associates into fibrillar amyloid deposits in patients undergoing hemodialysis therapy. Formation of these beta-sheet-rich assemblies is a fundamental property of polypeptides that can be triggered by diverse conditions. For beta2m, oligomerization into pre-amyloidogenic states occurs in specific response to coordination by Cu2+. Here we report the basis for this self-association at atomic resolution. Metal is not a direct participant in the molecular interface. Rather, binding results in distal alterations enabling the formation of two new surfaces. These interact to form a closed hexameric species. The origins of this include isomerization of a buried and conserved cis-proline previously implicated in the beta2m aggregation pathway. The consequences of this isomerization are evident and reveal a molecular basis for the conversion of this robust monomeric protein into an amyloid-competent state.

  1. Lack of interaction between LRP1 and A2M polymorphisms for the risk of Alzheimer disease.

    PubMed

    Bruno, Elisa; Quattrocchi, Graziella; Nicoletti, Alessandra; Le Pira, Francesco; Maci, Tiziana; Mostile, Giovanni; Andreoli, Virginia; Quattrone, Aldo; Zappia, Mario

    2010-09-27

    Alzheimer disease (AD) has a heterogeneous aetiology, involving genetic and environmental factors. Low-density lipoprotein receptor-related protein 1 (LRP1), alpha-2-macroglobulin (A2M) and apolipoprotein E (APOE) are involved in molecular pathways leading to beta-amyloid deposition. Three polymorphic sites in these genes (APOE-epsilon 2/epsilon 3/epsilon 4, A2M-Ile/Val and LRP1-C/T) have been associated with AD, but the results were not univocal. We carried out a case-control study to investigate the association between these polymorphisms and the risk of developing AD and their possible interaction. We recruited 125 AD patients who fulfilled the diagnostic criteria proposed by NINCDS-ADRDA for probable or possible AD and 310 controls subjects. PCR was used to detect the polymorphisms. ORs and 95% CIs were estimated using logistic regression analysis. The OR for subjects carrying at least one allele Val (A2M-Val+) in their genotypes was 1.52 (95% CI 1.00-2.31; p=0.05); for subjects carrying at least one allele C (LRP1-C+), 1.58 (95% CI 1.00-2.50; p=0.05); for subjects carrying at least one allele epsilon 4 (APOE-epsilon 4+), 3.1 (95%CI 1.87-5.00; p<0.001). The coexistence of at least one allele Val (A2M-Val+) and one allele C (LRP1-C+) increased up two times the risk of AD (OR 2.32; 95% CI 1.23-4.35; p<0.009). No evidence of significant interaction has been found between the studied polymorphisms (p>0.05). In conclusion our study suggests that LRP1-C/T, A2M-Ile/Val and APOE-epsilon 2/epsilon 3/epsilon 4 polymorphisms are associated with AD. PMID:20637261

  2. beta-Hexachlorocyclohexane (beta-HCH)

    Integrated Risk Information System (IRIS)

    beta - Hexachlorocyclohexane ( beta - HCH ) ; CASRN 319 - 85 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Asses

  3. Human Fucci Pancreatic Beta Cell Lines: New Tools to Study Beta Cell Cycle and Terminal Differentiation

    PubMed Central

    Carlier, Géraldine; Maugein, Alicia; Cordier, Corinne; Pechberty, Séverine; Garfa-Traoré, Meriem; Martin, Patrick; Scharfmann, Raphaël; Albagli, Olivier

    2014-01-01

    Regulation of cell cycle in beta cells is poorly understood, especially in humans. We exploited here the recently described human pancreatic beta cell line EndoC-βH2 to set up experimental systems for cell cycle studies. We derived 2 populations from EndoC-βH2 cells that stably harbor the 2 genes encoding the Fucci fluorescent indicators of cell cycle, either from two vectors, or from a unique bicistronic vector. In proliferating non-synchronized cells, the 2 Fucci indicators revealed cells in the expected phases of cell cycle, with orange and green cells being in G1 and S/G2/M cells, respectively, and allowed the sorting of cells in different substeps of G1. The Fucci indicators also faithfully red out alterations in human beta cell proliferative activity since a mitogen-rich medium decreased the proportion of orange cells and inflated the green population, while reciprocal changes were observed when cells were induced to cease proliferation and increased expression of some beta cell genes. In the last situation, acquisition of a more differentiated beta cell phenotype correlates with an increased intensity in orange fluorescence. Hence Fucci beta cell lines provide new tools to address important questions regarding human beta cell cycle and differentiation. PMID:25259951

  4. Gadd45 proteins induce G2/M arrest and modulate apoptosis in kidney cells exposed to hyperosmotic stress.

    PubMed

    Mak, Sally K; Kültz, Dietmar

    2004-09-10

    Gadd45 proteins are induced by hyperosmolality in renal inner medullary (IM) cells, but their role for cell adaptation to osmotic stress is not known. We show that a cell line derived from murine renal IM cells responds to moderate hyperosmotic stress (540 mosmol/kg) by activation of G(2)/M arrest without significant apoptosis. If the severity of hyperosmotic stress exceeds the tolerance limit of this cell line (620 mosmol/kg) apoptosis is strongly induced. Using transient overexpression of ectopic Gadd45 proteins and simultaneous analysis of transfected versus non-transfected cells by laser-scanning cytometry, we were able to measure the effects of Gadd45 super-induction during hyperosmolality on G(2)/M arrest and apoptosis. Our results demonstrate that induction of all three Gadd45 isoforms inhibits mitosis and promotes G(2)/M arrest during moderate hyperosmotic stress but not in isosmotic controls. Furthermore, all three Gadd45 proteins are also involved in control of apoptosis during severe hyperosmotic stress. Under these conditions Gadd45gamma induction strongly potentiates apoptosis. In contrast, Gadd45alpha/beta induction transiently increases caspase 3/7 and annexin V binding before 12 h but inhibits later stages of apoptosis during severe hyperosmolality. These results show that Gadd45 isoforms function in common but also in distinct pathways during hyperosmolality and that their increased abundance contributes to the low mitotic index and protection of genomic integrity in cells of the mammalian renal inner medulla. PMID:15262964

  5. Two VLT 8.2-m Unit Telescopes in Action

    NASA Astrophysics Data System (ADS)

    1999-04-01

    Visitors at ANTU - Astronomical Images from KUEYEN The VLT Control Room at the Paranal Observatory is becoming a busy place indeed. From here, two specialist teams of ESO astronomers and engineers now operate two VLT 8.2-m Unit Telescopes in parallel, ANTU and KUEYEN (formerly UT1 and UT2, for more information about the naming and the pronunciation, see ESO Press Release 06/99 ). Regular science observations have just started with the first of these giant telescopes, while impressive astronomical images are being obtained with the second. The work is hard, but the mood in the control room is good. Insiders claim that there have even been occasions on which the groups have had a friendly "competition" about which telescope makes the "best" images! The ANTU-team has worked with the FORS multi-mode instrument , their colleagues at KUEYEN use the VLT Test Camera for the ongoing tests of this new telescope. While the first is a highly developed astronomical instrument with a large-field CCD imager (6.8 x 6.8 arcmin 2 in the normal mode; 3.4 x 3.4 arcmin 2 in the high-resolution mode), the other is a less complex CCD camera with a smaller field (1.5 x 1.5 arcmin 2 ), suited to verify the optical performance of the telescope. As these images demonstrate, the performance of the second VLT Unit Telescope is steadily improving and it may not be too long before its optical quality will approach that of the first. First KUEYEN photos of stars and galaxies We present here some of the first astronomical images, taken with the second telescope, KUEYEN, in late March and early April 1999. They reflect the current status of the optical, electronic and mechanical systems, still in the process of being tuned. As expected, the experience gained from ANTU last year has turned out to be invaluable and has allowed good progress during this extremely delicate process. ESO PR Photo 19a/99 ESO PR Photo 19a/99 [Preview - JPEG: 400 x 433 pix - 160k] [Normal - JPEG: 800 x 866 pix - 457k] [High

  6. Interaction of transforming growth factor-beta-1 with alpha-2-macroglobulin from normal and inflamed equine joints.

    PubMed Central

    Coté, N; Trout, D R; Hayes, M A

    1998-01-01

    Binding between equine plasma alpha-2-macroglobulin (alpha 2M) and several cytokines known to participate in inflammatory reactions in other species was initially examined. Plasma was obtained from 5 horses with various abnormalities. Samples, both untreated and after reaction with methylamine, were incubated with exogenous, radiolabeled, porcine-derived transforming growth factor-beta-1 (125I-TGF-beta 1), recombinant human interleukin-1-beta (125I-IL-1 beta), and recombinant human tumor necrosis factor-alpha (125I-rhTNF-alpha). They were then subjected to nondenaturing polyacrylamide gel electrophoresis (PAGE). Binding of the native (slow) and activated (fast) forms of alpha 2M to each cytokine was subjectively evaluated with autoradiography. Equine alpha 2M bound 125I-TGF-beta 1. However, poor or no binding was observed between alpha 2M and either of 125I-rhTNF-alpha or 125I-IL-1 beta. Synovial fluid was then obtained from 6 normal horses, 6 horses with septic arthritis, and 6 horses with degenerative joint disease. Untreated and methylamine-reacted samples were quantitatively examined for binding with 125I-TGF-beta 1, using the autoradiographic techniques described above and densitometry. Native and activated alpha 2M were also quantified by densitometry of PAGE gels. Native alpha 2M was significantly elevated in septic arthritis (6.4% to 29.5% of total protein detected) and degenerative joint disease (2.8% to 12.3%), compared to normal joints (0.9% to 4.2%). Activated alpha 2M, however, was not detected in untreated synovial fluid samples. In all plasma and joint fluid samples, whether untreated or reacted with methylamine, 125I-TGF-beta 1 bound predominantly to alpha 2M, and preferentially to the activated form of alpha 2M. In synovial fluid, the amount of 125I-TGF-beta 1 binding was proportional to the quantity of alpha 2M present. These results indicate that: 1) equine alpha 2M binds TGF-beta 1; 2) the native form of alpha 2M is present in both equine plasma

  7. Gross alpha and beta activities in tap waters in Eastern Black Sea region of Turkey.

    PubMed

    Damla, N; Cevik, U; Karahan, G; Kobya, A I

    2006-02-01

    Gross alpha and gross beta activities were determined for 27 different tap water samples collected from Eastern Black Sea region of Turkey. The instrumentation used to count the gross alpha and gross beta activities was a alpha/beta counter of the low background multiple detector type with 10 sample detectors (Berthold LB770). The obtained results showed that natural activity concentrations of alpha- and beta-emitting radionuclides in tap water samples did not exceed WHO and ITS recommended levels. Concentrations ranging from 0.2 mBq/l to 15 mBq/l and from 25.2 mBq/l to 264.4 mBq/l were observed for the gross alpha and gross beta activities, respectively. For all samples the gross beta activities were higher than the corresponding gross alpha activities. PMID:16084570

  8. Two VLT 8.2-m Unit Telescopes in Action

    NASA Astrophysics Data System (ADS)

    1999-04-01

    Visitors at ANTU - Astronomical Images from KUEYEN The VLT Control Room at the Paranal Observatory is becoming a busy place indeed. From here, two specialist teams of ESO astronomers and engineers now operate two VLT 8.2-m Unit Telescopes in parallel, ANTU and KUEYEN (formerly UT1 and UT2, for more information about the naming and the pronunciation, see ESO Press Release 06/99 ). Regular science observations have just started with the first of these giant telescopes, while impressive astronomical images are being obtained with the second. The work is hard, but the mood in the control room is good. Insiders claim that there have even been occasions on which the groups have had a friendly "competition" about which telescope makes the "best" images! The ANTU-team has worked with the FORS multi-mode instrument , their colleagues at KUEYEN use the VLT Test Camera for the ongoing tests of this new telescope. While the first is a highly developed astronomical instrument with a large-field CCD imager (6.8 x 6.8 arcmin 2 in the normal mode; 3.4 x 3.4 arcmin 2 in the high-resolution mode), the other is a less complex CCD camera with a smaller field (1.5 x 1.5 arcmin 2 ), suited to verify the optical performance of the telescope. As these images demonstrate, the performance of the second VLT Unit Telescope is steadily improving and it may not be too long before its optical quality will approach that of the first. First KUEYEN photos of stars and galaxies We present here some of the first astronomical images, taken with the second telescope, KUEYEN, in late March and early April 1999. They reflect the current status of the optical, electronic and mechanical systems, still in the process of being tuned. As expected, the experience gained from ANTU last year has turned out to be invaluable and has allowed good progress during this extremely delicate process. ESO PR Photo 19a/99 ESO PR Photo 19a/99 [Preview - JPEG: 400 x 433 pix - 160k] [Normal - JPEG: 800 x 866 pix - 457k] [High

  9. 40 CFR 180.325 - 2-(m-Chlorophenoxy) propionic acid; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false 2-(m-Chlorophenoxy) propionic acid... Tolerances § 180.325 2-(m-Chlorophenoxy) propionic acid; tolerances for residues. (a) General. A tolerance is established for negligible residues of the plant regulator 2-(m-chlorophenoxy) propionic acid from...

  10. The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors.

    PubMed

    Baker, Jillian G

    2005-02-01

    Beta-adrenoceptor antagonists ("beta-blockers") are one of the most widely used classes of drugs in cardiovascular medicine (hypertension, ischaemic heart disease and increasingly in heart failure) as well as in the management of anxiety, migraine and glaucoma. Where known, the mode of action in cardiovascular disease is from antagonism of endogenous catecholamine responses in the heart (mainly at beta1-adrenoceptors), while the worrisome side effects of bronchospasm result from airway beta2-adrenoceptor blockade. The aim of this study was to determine the selectivity of beta-antagonists for the human beta-adrenoceptor subtypes. (3)H-CGP 12177 whole cell-binding studies were undertaken in CHO cell lines stably expressing either the human beta1-, beta2- or the beta3-adrenoceptor in order to determine the affinity of ligands for each receptor subtype in the same cell background. In this study, the selectivity of well-known subtype-selective ligands was clearly demonstrated: thus, the selective beta1 antagonist CGP 20712A was 501-fold selective over beta2 and 4169-fold selective over beta3; the beta2-selective antagonist ICI 118551 was 550- and 661-fold selective over beta1 and beta3, respectively, and the selective beta3 compound CL 316243 was 10-fold selective over beta2 and more than 129-fold selective over beta1. Those beta2-adrenoceptor agonists used clinically for the treatment of asthma and COPD were beta2 selective: 29-, 61- and 2818-fold for salbutamol, terbutaline and salmeterol over beta1, respectively. There was little difference in the affinity of these ligands between beta1 and beta3 adrenoceptors. The clinically used beta-antagonists studied ranged from bisoprolol (14-fold beta1-selective) to timolol (26-fold beta2-selective). However, the majority showed little selectivity for the beta1- over the beta2-adrenoceptor, with many actually being more beta2-selective. This study shows that the beta1/beta2 selectivity of most clinically used beta-blockers is

  11. Protection of transforming growth factor-beta 1 activity by heparin and fucoidan.

    PubMed

    McCaffrey, T A; Falcone, D J; Vicente, D; Du, B; Consigli, S; Borth, W

    1994-04-01

    The transforming growth factor-beta (TGF-beta) family of proteins exert diverse and potent effects on proliferation, differentiation, and extracellular matrix synthesis. However, relatively little is known about the stability or processing of endogenous TGF-beta activity in vitro or in vivo. Our previous work indicated that 1) TGF-beta 1 has strong heparin-binding properties that were not previously recognized because of neutralization by iodination, and 2) heparin, and certain other polyanions, could block the binding of TGF-beta 1 to alpha 2-macroglobulin (alpha 2-M). The present studies investigated the influence of heparin-like molecules on the stability of the TGF-beta 1 signal in the pericellular environment. The results indicate that heparin and fucoidan, a naturally occurring sulfated L-fucose polymer, suppress the formation of an initial non-covalent interaction between 125I-TGF-beta 1 and activated alpha 2-M. Electrophoresis of 125I-TGF-beta 1 showed that fucoidan protects TGF-beta 1 from proteolytic degradation by plasmin and trypsin. While plasmin caused little, if any, activation of latent TGF-beta derived from vascular smooth muscle cells (SMC), plasmin degraded acid-activated TGF-beta, and purified TGF-beta 1, and this degradation was inhibited by fucoidan. In vitro, heparin and fucoidan tripled the half-life of 125I-TGF-beta 1 and doubled the amount of cell-associated 125I-TGF-beta 1. Consistent with this protective effect, heparin- and fucoidan-treated SMC demonstrated elevated levels of active, but not latent, TGF-beta activity. PMID:7511146

  12. High Beta Tokamaks

    SciTech Connect

    Cowley, S.

    1998-11-14

    Perhaps the ideal tokamak would have high {beta} ({beta} {approx}> 1) and classical confinement. Such a tokamak has not been found, and we do not know if one does exist. We have searched for such a possibility, so far without success. In 1990, we obtained analytic equilibrium solutions for large aspect ratio tokamaks at {beta} {approx} {Omicron}(1) [1]. These solutions and the extension at high {beta} poloidal to finite aspect ratio [2] provided a basis for the study of high {beta} tokamaks. We have shown that these configurations can be stable to short scale MHD modes [3], and that they have reduced neoclassical transport [4]. Microinstabilities (such as the {del}T{sub i} mode) seem to be stabilized at high {beta} [5] - this is due to the large local shear [3] and the magnetic well. We have some concerns about modes associated with the compressional branch which may appear at high {beta}. Bill Dorland and Mike Kotschenreuther have studied this issue and our concerns may be unfounded. It is certainly tantalizing, especially given the lowered neoclassical transport values, that these configurations could have no microinstabilities and, one could assume, no anomalous transport. Unfortunately, while this work is encouraging, the key question for high {beta} tokamaks is the stability to large scale kink modes. The MHD {beta} limit (Troyon limit) for kink modes at large aspect ratio is problematically low. There is ample evidence from computations that the limit exists. However, it is not known if stable equilibria exist at much higher {beta}--none have been found. We have explored this question in the asymptotic high {beta} poloidal limit. Unfortunately, we are unable to find stable equilibrium and also unable to show that they don't exist. The results of these calculations will be published when a more definitive answer is found.

  13. Beta-Carotene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beta-carotene is a pigment that occurs naturally in many photosynthetic plants and organisms and one of the most abundant carotenoids found in human blood. The richest dietary sources of beta-carotene are yellow, orange, and leafy green fruits and vegetables, such as carrots, spinach, sweet potatoes...

  14. BETA GAUGE OPERATION MANUAL

    EPA Science Inventory

    This manual provides description and operating instructions for a redesigned Beta Gauge for measuring particles from vehicle exhaust. The improvements and a new control system including a control unit which is radically different from the prior unit, are described. Complete Beta ...

  15. An explanation of the preferential formation of less stable isomers in three-body reactions - Cl + NO2 + M; ClO + NO2 + M

    NASA Technical Reports Server (NTRS)

    Chang, J. S.; Baldwin, A. C.; Golden, D. M.

    1979-01-01

    A realistic assessment of the potential depletion of stratospheric ozone due to manmade emissions requires a knowledge of the sources and sinks of the potential threat. The reactions ClO + NO2 + M yield products and Cl + NO2 + M yield products are of interest because they represent possible sink mechanism for both odd chlorine and odd nitrogen species. In this paper, the Troe method (1977) is used to calculate the low-pressure limit rate constants of the above three-body reactions. The result for the Cl + NO2 + M reaction is found to be in excellent agreement with the experimental finding of Niki et al. (1978), where both nitryl chloride and chlorine nitrate are products of the cited reaction. An explanation is proposed to account for apparent discrepancy between the measured rate constants for ClO + NO2 + M in the forward and reverse directions. Stratospheric implications are also discussed.

  16. Rapid synthesis of beta zeolites

    SciTech Connect

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  17. Role of cyclooxygenase 2 in protein kinase C beta II-mediated colon carcinogenesis.

    PubMed

    Yu, Wangsheng; Murray, Nicole R; Weems, Capella; Chen, Lu; Guo, Huiping; Ethridge, Richard; Ceci, Jeffrey D; Evers, B Mark; Thompson, E Aubrey; Fields, Alan P

    2003-03-28

    Elevated expression of protein kinase C beta II (PKC beta II) is an early promotive event in colon carcinogenesis (Gokmen-Polar, Y., Murray, N. R., Velasco, M. A., Gatalica, Z., and Fields, A. P. (2001) Cancer Res. 61, 1375-1381). Expression of PKC beta II in the colon of transgenic mice leads to hyperproliferation and increased susceptibility to colon carcinogenesis due, at least in part, to repression of transforming growth factor beta type II receptor (TGF-beta RII) expression (Murray, N. R., Davidson, L. A., Chapkin, R. S., Gustafson, W. C., Schattenberg, D. G., and Fields, A. P. (1999) J. Cell Biol., 145, 699-711). Here we report that PKC beta II induces the expression of cyclooxygenase type 2 (Cox-2) in rat intestinal epithelial (RIE) cells in vitro and in transgenic PKC beta II mice in vivo. Cox-2 mRNA increases more than 10-fold with corresponding increases in Cox-2 protein and PGE2 production in RIE/PKC beta II cells. PKC beta II activates the Cox-2 promoter by 2- to 3-fold and stabilizes Cox-2 mRNA by at least 4-fold. The selective Cox-2 inhibitor Celecoxib restores expression of TGF-beta RII both in vitro and in vivo and restores TGF beta-mediated transcription in RIE/PKC beta II cells. Likewise, the omega-3 fatty acid eicosapentaenoic acid (EPA), which inhibits PKC beta II activity and colon carcinogenesis, causes inhibition of Cox-2 protein expression, re-expression of TGF-beta RII, and restoration of TGF-beta1-mediated transcription in RIE/PKC beta II cells. Our data demonstrate that PKC beta II promotes colon cancer, at least in part, through induction of Cox-2, suppression of TGF-beta signaling, and establishment of a TGF-beta-resistant, hyperproliferative state in the colonic epithelium. Our data define a procarcinogenic PKC beta II --> Cox-2 --> TGF-beta signaling axis within the colonic epithelium, and provide a molecular mechanism by which dietary omega-3 fatty acids and nonsteroidal antiinflammatory agents such as Celecoxib suppress colon

  18. On resolving 2M - 1 narrow-band signals with an M sensor uniform linear array

    NASA Technical Reports Server (NTRS)

    Williams, Douglas B.; Johnson, Don H.

    1992-01-01

    Length 2M real signal vectors are used to address the problem of determining the maximum number of narrow-band signals whose parameters can be estimated with a linear array of M equally spaced sensors. It is shown that 2M of these real vectors are linearly independent with probability one, and, thus in the presence of additive white noise, the parameters of 2M - 1 signals can be estimated. An algorithm for determining directions and amplitudes is presented.

  19. Beta experiment flight report

    NASA Technical Reports Server (NTRS)

    1982-01-01

    A focused laser Doppler velocimeter system was developed for the measurement of atmospheric backscatter (beta) from aerosols at infrared wavelengths. The system was flight tested at several different locations and the results of these tests are summarized.

  20. Beta-carotene

    MedlinePlus

    ... brain in people who drink alcohol. Preventing abdominal aortic aneurysm, or the enlargement of a large vessel running ... years does not reduce the occurrence of abdominal aortic aneurysm in male smokers. Cancer. Beta-carotene does not ...

  1. Beta-carotene

    MedlinePlus

    ... blindness during pregnancy, as well as diarrhea and fever after giving birth. Some people who sunburn easily, ... seems to reduce the incidence of diarrhea and fever post-childbirth. Pregnancy-related complications. Taking beta-carotene ...

  2. High beta multipoles

    SciTech Connect

    Prager, S C

    1982-05-01

    Multipoles are being employed as devices to study fusion issues and plasma phenomena at high values of beta (plasma pressure/magnetic pressure) in a controlled manner. Due to their large volume, low magnetic field (low synchrotron radiation) region, they are also under consideration as potential steady state advanced fuel (low neutron yield) reactors. Present experiments are investigating neoclassical (bootstrap and Pfirsch-Schlueter) currents and plasma stability at extremely high beta.

  3. Engineering lower inhibitor affinities in beta-D-xylosidase by site-directed mutagenesis of Trp 145

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Beta- D-xylosidase catalyzes hydrolysis of xylooligosaccharides to D-xylose monosaccharides. beta-Xylosidase from Selenomonas ruminantium, SXA, is the most active catalyst known for the reaction; however, its activity is inhibited by D-xylose and D-glucose (Ki values of ~10-2 M). Higher Ki’s could...

  4. [Identification of C(2)M interacting proteins by yeast two-hybrid screening].

    PubMed

    Shanshan, Yue; Laixin, Xia

    2015-11-01

    The synaptonemal complex (SC) is a huge structure which assembles between the homologous chromosomes during meiotic prophase I. Drosophila germ cell-specific nucleoprotein C(2)M clustering at chromosomes can induce SC formation. To further study the molecular function and mechanism of C(2)M in meiosis, we constructed a bait vector for C(2)M and used the yeast two-hybrid system to identify C(2)M interacting proteins. Forty interacting proteins were obtained, including many DNA and histone binding proteins, ATP synthases and transcription factors. Gene silencing assays in Drosophila showed that two genes, wech and Psf1, may delay the disappearance of SC. These results indicate that Wech and Psf1 may form a complex with C(2)M to participate in the formation or stabilization of the SC complex. PMID:26582530

  5. Cigarette Smoking and Tryptophan Hydroxylase 2 mRNA in the Dorsal Raphe Nucleus in Suicides

    PubMed Central

    Bach, Helene; Arango, Victoria; Kassir, Suham A.; Dwork, Andrew J.; Mann, J. John; Underwood, Mark D.

    2016-01-01

    Cigarette smoking is associated with suicide and mood disorders and stimulates serotonin release. Tryptophan hydroxylase (TPH2) synthesizes serotonin and is over-expressed in suicides. We determined whether smoking is associated with TPH2 mRNA in suicides and controls. TPH2 mRNA was measured postmortem in the dorsal raphe nucleus (DRN) of controls (N=26, 17 nonsmokers and nine smokers) and suicides (N=23, 5 nonsmokers and 18 smokers). Psychiatric history was obtained by psychological autopsy. TPH2 mRNA was greater in suicide nonsmokers than suicide smokers, control smokers and control nonsmokers (p=0.006). There was more TPH2 mRNA throughout the DRN. Smoking interferes with the TPH2 mRNA increase observed in suicide nonsmokers. The absence of altered TPH2 expression in non-suicide smokers suggests no pharmacological effect of smoking. PMID:26954509

  6. Inhaled beta agonists.

    PubMed

    Op't Holt, Timothy B

    2007-07-01

    The beta(2) adrenoreceptor is a large molecule of some 413 amino acids. The duration of stimulation of this receptor depends on where and for how long a beta(2) adrenergic drug attaches itself to the beta(2) adrenoreceptor. beta(2) adrenergic drugs have been used for over 5,000 years, but only recently have we had the advantage of adrenergic drugs specific to the beta(2) adrenoreceptor. The short-acting beta(2) adrenergic drugs most frequently used include albuterol, pirbuterol, and levalbuterol. Levalbuterol, the R enantiomer of albuterol, has been described by some as a more effective bronchodilator than racemic albuterol, because it contains none of the S enantiomer. Some contend that the S isomer has pro-inflammatory properties. The 2 long-acting beta(2) adrenergic drugs are salmeterol and formoterol. These drugs have a duration of 12 h and reportedly improve forced expiratory volume in the first second, quality of life, and symptoms. Some recent reports indicate that these drugs are associated with higher mortality, but several authors have registered the opinion that it is not the bronchodilator that should be questioned, but instead that the fault lies in the patient recruitment in those studies. Regardless, if these long-acting drugs are effective for a given patient, it would seem inadvisable to withdraw them, given the current state of evidence. Arformoterol tartrate, the R enantiomer of formoterol, was approved by the U.S. Food and Drug Administration in October 2006; it is available as a nebulizer solution, to be administered every 12 h. Several other long-acting R isomers and RR isomers are in the approval pipeline. PMID:17594727

  7. A Single-Nucleotide Polymorphism in ABCC4 Is Associated with Tenofovir-Related Beta2-Microglobulinuria in Thai Patients with HIV-1 Infection

    PubMed Central

    Likanonsakul, Sirirat; Suntisuklappon, Bussakorn; Nitiyanontakij, Ravee; Prasithsirikul, Wisit; Nakayama, Emi E.; Shioda, Tatsuo; Sangsajja, Chariya

    2016-01-01

    Background In Thailand, the combined generic anti-retroviral drug stavudine/lamivudine/nevirapine (d4T/3TC/NVP) has been used to treat human immunodeficiency virus (HIV)-infected individuals since 2001. Due to relatively frequent adverse effects, d4T gradually has been replaced with tenofovir disoproxil fumarate (TDF). Although the frequency of adverse drug effects with TDF is lower than that with d4T, TDF is known to induce kidney dysfunction, especially in the proximal tubules. It has been reported that renal tubular transporters, including members of the multi-drug resistant (MDR) protein family, are implicated in tenofovir extrusion and may, therefore, confer susceptibility to TDF-induced kidney tubular dysfunction (KTD). We have explored the association between KTD and polymorphisms in genes that encode adenosine triphosphate-binding cassette (ABC)-type MDRs. Methods HIV-infected patients receiving TDF-containing antiretroviral regimens for at least one year were enrolled in the study. The levels of beta2-microglobulin in urine and creatinine (Cr) were measured. Three single-nucleotide polymorphisms, ABCC2 C-24T (rs717620), ABCC2 G1429A (rs2273697), and ABCC4 T4976C (rs1059751), were analyzed using TaqMan SNP genotyping assays. Results A total of 273 HIV-infected patients were recruited. The median number of years of TDF treatment was 5.04 with interquartile range (IQR) of 3.9–6.7. Despite the length of treatment with TDF, 98.5% patients maintained an estimated glomerular filtration rate (eGFR) of >60 mL/min as calculated by the CKD-EPI formula. Fifty-four patients (19.8%) showed beta2-microglobulinuria (median 2636 μg/g Cr with IQR of 1519–13197 μg/g Cr). The allele frequency of ABCC4 T4976C among those 54 patients was 0.602, compared to 0.475 among the 219 remaining patients (p = 0.018). Conclusions Approximately 20% of HIV-infected patients receiving TDF showed beta2-microglobulinuria. The C allele at position 4976 of the ABCC4 gene was associated

  8. Boosted Beta Regression

    PubMed Central

    Schmid, Matthias; Wickler, Florian; Maloney, Kelly O.; Mitchell, Richard; Fenske, Nora; Mayr, Andreas

    2013-01-01

    Regression analysis with a bounded outcome is a common problem in applied statistics. Typical examples include regression models for percentage outcomes and the analysis of ratings that are measured on a bounded scale. In this paper, we consider beta regression, which is a generalization of logit models to situations where the response is continuous on the interval (0,1). Consequently, beta regression is a convenient tool for analyzing percentage responses. The classical approach to fit a beta regression model is to use maximum likelihood estimation with subsequent AIC-based variable selection. As an alternative to this established - yet unstable - approach, we propose a new estimation technique called boosted beta regression. With boosted beta regression estimation and variable selection can be carried out simultaneously in a highly efficient way. Additionally, both the mean and the variance of a percentage response can be modeled using flexible nonlinear covariate effects. As a consequence, the new method accounts for common problems such as overdispersion and non-binomial variance structures. PMID:23626706

  9. IO SUBSYSTEM 1 BETA

    SciTech Connect

    Sjaardema, Greg

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/output library for finite element analysis, preprocessing, post processing, and translation programs.

  10. IO SUBSYSTEM 1 BETA

    2002-08-21

    "IO Subsystem Ver. 1.0 Beta" uses standard object-oriented principles to minimize dependencies between the underlying input or output database format and the client code (i.e., Sierra) using the io subsystem. The interface and priciples are simolar to the Facade pattern described in the "Design Patterns" book by Gamma, et.al. The software uses data authentication algorithms to ensure data input/output is consistent with model being defined. "IO Subsystem Ver. 1.0 Beta" is a database independent input/outputmore » library for finite element analysis, preprocessing, post processing, and translation programs.« less

  11. Structural chemistry of M2Si5N8:Eu2+ (M = Ca, Sr, Ba) phosphor via structural refinement.

    PubMed

    Kim, Yong-Il; Kim, Kwang Bok; Lee, Yun-Hee; Kim, Ki-Bok

    2012-04-01

    Structural refinement using X-ray powder diffraction data and geometry energy calculations using quantum mechanics were used to investigate the preferential substitution sites and the amount of Eu2+ ions in the host lattice of alkaline earth elements co-doped M2Si5N8:Eu2+ (M = Ca, Sr, and Ba), which is a red color-emitting nitride phosphor prepared via a carbothermal reaction method. Of the possible preferential sites, the preferential site proposed by the structural refinement results, in which the Eu2+ ions might preferentially occupy nine coordinated sites with nitrogen in M2Si5N8:Eu2+, was confirmed via geometry energy calculations using a first-principle based on the density-functional theory. The final converged weighted R factor (R(wp)) and the goodness-of-fit indicator [S(= R(wp)/R(e))] were 9.51% and 1.77, respectively. Each occupancy of Eu2+ ions for the two non-equivalent M sites, M(1) and M(2), was 0.10(2) and 0.04(2), respectively. The final refined model described the crystal structure in a space group Pmn2, (No. 31) with Z = 2, a = 5.7424(1) angstroms, b = 6.8837(1) angstroms, c = 9.3586(1) angstroms, and alpha(= beta= gamma)= 90 degrees. PMID:22849142

  12. 113. JOB NO. 1347K, SHEET 2M, 1929, FORD MOTOR COMPANY; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    113. JOB NO. 1347-K, SHEET 2M, 1929, FORD MOTOR COMPANY; BOILER HOUSE ASSEMBLY PLANT; SECTIONS - Ford Motor Company Long Beach Assembly Plant, Assembly Building, 700 Henry Ford Avenue, Long Beach, Los Angeles County, CA

  13. CH2M Hill Hanford Group Inc (CHG) Information Resource Management (IRM) Strategic Plan

    SciTech Connect

    NELSON, R.L.

    2000-05-08

    The CH2M Hill Hanford Group, Inc., Information Resource Management Strategic Plan is the top-level planning document for applying information and information resource management to achieve the CHG mission for the management of the River Protection Project

  14. Idaho National Laboratory Technology to Market (T2M) Final Report

    SciTech Connect

    Wright, Christopher Todd; Bush, Jason William; Gentle, Jake Paul; Hill, Porter Jack; Myers, Kurt Steven; Williams, Christopher Luke

    2016-01-01

    The objective of this project is to establish a tiered Technology to Market (T2M) curriculum for basic researchers to project leads to measure the effect of technology transfer skills on project success and impact. The plan will train five researchers in basic technology transfer principles where success will be measured by assessing improvements in T2M skills and knowledge after the training is complete, likely using before and after surveys.

  15. Dynamics model of the IBR-2M pulsed reactor for analysis of fast transition processes

    NASA Astrophysics Data System (ADS)

    Pepelyshev, Yu. N.; Popov, A. K.; Sumkhuu, D.; Sangaa, D.

    2015-05-01

    A nonlinear model of the IBR-2M pulsed reactor dynamics relating values of variables at discreet instants of time (when power pulses appear) is developed on the basis of the MATLAB program system. The tests of the model by simulating calculated processes in the IBR-2M reactor proved the correctness of the model. A tentative estimate of the transfer coefficient for the linear part of the automatic regulator is obtained.

  16. Elevated TREM2 mRNA expression in leukocytes in schizophrenia but not major depressive disorder.

    PubMed

    Yoshino, Yuta; Kawabe, Kentaro; Yamazaki, Kiyohiro; Watanabe, Shinya; Numata, Shusuke; Mori, Yoko; Yoshida, Taku; Iga, Junichi; Ohmori, Tetsuro; Ueno, Shu-Ichi

    2016-06-01

    The pathological mechanisms of schizophrenia (SCZ) have not been clarified, but the microglia hypothesis has recently been discussed. We previously reported that the mRNA for a protein related to activation of microglia, triggering receptor expressed on myeloid cell 2 (TREM2), is expressed higher in peripheral leukocytes in SCZ than controls. In this study, we analyzed TREM2 mRNA expression in leukocytes from both SCZ and major depressive disorder (MDD) patients. We compared 50 SCZ patients and 42 MDD patients with age-matched controls. Levels of TREM2 mRNA in leukocytes were analyzed with quantitative real-time PCR method using TaqMan probe. TREM2 mRNA expression was significantly higher in leukocytes of SCZ subjects than controls, but the expression level was non-significantly different in MDD subjects. We observed a decrease in TREM2 mRNA expression in leukocytes from one SCZ patient after clozapine treatment. The expression did not change following ECT, but the expression level in this patient was still significantly higher than that in controls. We conclude that the high amount of TREM2 mRNA expression in leukocytes is specific to SCZ but not MDD and that changes in TREM2 mRNA expression may be a trait biomarker for SCZ. PMID:27130565

  17. Regulation of. beta. -cell glucose transporter gene expression

    SciTech Connect

    Chen, Ling; Alam, Tausif; Johnson, J.H.; Unger, R.H. Department of Veterans Affairs Medical Center, Dallas, TX ); Hughes, S.; Newgard, C.B. )

    1990-06-01

    It has been postulated that a glucose transporter of {beta} cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, the authors subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated {beta}-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia, GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days, GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively. After 12 days of hypoglycemia, the K{sub m} for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high K{sub m} glucose transporter in {beta} cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, they also infused animals with 50% (wt/vol) glucose for 5 days. Hyperglycemic clamping increased GLUT-2 mRNA by 46% whereas proinsulin mRNA doubled. They conclude that GLUT-2 expression in {beta} cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis.

  18. Applied Beta Dosimetry

    SciTech Connect

    Rich, B.L.

    1986-01-01

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  19. beta-Chloronaphthalene

    Integrated Risk Information System (IRIS)

    beta - Chloronaphthalene ; CASRN 91 - 58 - 7 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcin

  20. beta-Propiolactone

    Integrated Risk Information System (IRIS)

    beta - Propiolactone ; CASRN 57 - 57 - 8 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogen

  1. Pharmacogenetic Study on the Impact of Rivastigmine Concerning Genetic Variants of A2M and IL-6 Genes on Iranian Alzheimer's Patients.

    PubMed

    Zamani, Mahdi; Mohammadi, Masomeh; Zamani, Hamid; Tavasoli, Alireza

    2016-09-01

    Alzheimer's disease (AD) is a polygenic and multifactorial disease with a complex inheritance caused by the formation of amyloid plaques and neurofibrillary tangles in the brain. Increasing evidence indicates that many genes including interleukin-6 (IL-6) and alpha 2-macroglobulin (A2M) may contribute to the pathogenesis of AD. The A2M gene encodes α2-macroglobulin which specifically binds with the beta-amyloid peptides and prevents fibril formation. Protein of the IL-6 gene linked to beta-amyloid (βA) aggregation was detected in βA plaques in the brain of AD patients. The aim of the present study is to investigate the relationship of the IL-6 and A2M gene polymorphisms with AD and also the impact of rivastigmine on AD patients regarding their genotypes on IL-6 and A2M genes in 150 Iranian AD patients under rivastigmine therapy and 150 matched healthy controls. The results indicated that IL-6 G and C alleles had significant positive and negative association with AD, respectively, (P = 0.0001, relative risks (RR) = 1.39) and frequency of AD patients carrying IL-6 GG genotype was significantly in higher proportion in familial Alzheimer's disease (FAD) patients compared to controls (P = 0.02, RR = 2.25), and the IL-6 CC genotype was significantly protective against AD (P = 0.0003, RR = 0.65). Genotype analysis of A2M gene showed a significant positive correlation between A2M AA genotype and the AD patients (sporadic Alzheimer's disease (SAD) and FAD) (P = 0.001, RR = 1.56), proposing it as a possible risk factor for AD. Drug response from pharmacogenetic viewpoint after 3-year follow-up of AD patients and Clinical Dementia Rating (CDR) analysis demonstrated that AD patients carrying bigenic genotype IL-6 CC-A2M AG (ΔCDR = 4.5) and male patients with IL-6 CC genotype (ΔCDR = 3.83) provided the best response and the A2M GG genotype (ΔCDR = 7.97) and bigenic genotype IL-6 GG-A2M GG (ΔCDR = 8.5) conferred the worst

  2. M{sup II}Ge(PO{sub 4}){sub 2} (M=Ca, Sr, Ba): Crystal structure, phase transitions and thermal expansion

    SciTech Connect

    Popa, Karin; Wallez, Gilles; Bregiroux, Damien; Loiseau, Pascal

    2011-10-15

    Three earth alkali-germanium monophosphates M{sup II}Ge(PO{sub 4}){sub 2} (M=Ca, Sr, Ba) were prepared by solid state reaction and their structures, previously unknown, studied by Rietveld analysis. BaGe(PO{sub 4}){sub 2} and high-temperature {beta}-SrGe(PO{sub 4}){sub 2} (space group C2/m, Z=2) are fully isotypic with yavapaiite, whereas CaGe(PO{sub 4}){sub 2} and low-temperature {alpha}-SrGe(PO{sub 4}){sub 2} (C2/c, Z=4) are distorted derivatives. The phase transition between the two forms is observed for the first time. The thermal expansion, resulting from several structural mechanisms, is very anisotropic. - Graphical abstract: The superstructure of SrGe(PO{sub 4}){sub 2} at room temperature ({alpha}) results from the off-centering of cation Sr{sup II}. Highlights: > Crystal structures of yavapaiite-type M{sup II}Ge(PO{sub 4}){sub 2} (M=Ca, Sr, Ba) have been solved. > Distortion and superstructure result from Ca and Sr off-centering. > A global scheme for the polymorphism of yavapaiites is proposed.

  3. Crystal structure of beta-cyclodextrin-benzoic acid inclusion complex.

    PubMed

    Aree, Thammarat; Chaichit, Narongsak

    2003-02-14

    The inclusion complex of beta-cyclodextrin (beta-CD) with benzoic acid (BA) has been characterized crystallographically. Two beta-CDs cocrystallize with two BAs, 0.7 ethanol and 20.65 water molecules [2(C(6)H(10)O(5))(7).2(C(7)H(6)O(2)).0.7(C(2)H(6)O).20.65H(2)O] in the triclinic space group P1 with unit cell constants: a=15.210(1), b=15.678(1), c=15.687(1) A, alpha=89.13(1), beta=74.64(1), gamma=76.40(1) degrees. The anisotropic refinement of 1840 atomic parameters against 16,201 X-ray diffraction data converged at R=0.078. In the crystal lattice, beta-CD forms dimers stabilized by direct O-2(m)_1/O-3(m)_1...O-2(n)_2/O-3(n)_2 hydrogen bonds (intradimer) and by indirect O-6(m)_1...,O-6(n)_2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These dimers are stacked like coins in a roll constructing endless channels where the guest molecules are included. The BA molecules protrude with their COOH groups at the beta-CD O-6-sides and are maintained in positions by hydrogen bonding to the surrounding O-6-H groups and water molecules. Water molecules (20.65) are distributed over 30 positions in the interstices between beta-CD molecules, except the water sites W-1, W-2 that are located in the channel of the beta-CD dimer. Water site W-2 is hydrogen bonded to the disordered ethanol molecule (occupancy 0.7). PMID:12559746

  4. Misleading Betas: An Educational Example

    ERIC Educational Resources Information Center

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  5. Beta Pictoris planet finally imaged?

    NASA Astrophysics Data System (ADS)

    2008-11-01

    A team of French astronomers using ESO's Very Large Telescope have discovered an object located very close to the star Beta Pictoris, and which apparently lies inside its disc. With a projected distance from the star of only 8 times the Earth-Sun distance, this object is most likely the giant planet suspected from the peculiar shape of the disc and the previously observed infall of comets onto the star. It would then be the first image of a planet that is as close to its host star as Saturn is to the Sun. Sharpening Up Jupiter ESO PR Photo 42a/08 Beta Pictoris as seen in infrared light The hot star Beta Pictoris is one of the best-known examples of stars surrounded by a dusty 'debris' disc. Debris discs are composed of dust resulting from collisions among larger bodies like planetary embryos or asteroids. They are a bigger version of the zodiacal dust in our Solar System. Its disc was the first to be imaged -- as early as 1984 -- and remains the best-studied system. Earlier observations showed a warp of the disc, a secondary inclined disc and infalling comets onto the star. "These are indirect, but tell-tale signs that strongly suggest the presence of a massive planet lying between 5 and 10 times the mean Earth-Sun distance from its host star," says team leader Anne-Marie Lagrange. "However, probing the very inner region of the disc, so close to the glowing star, is a most challenging task." In 2003, the French team used the NAOS-CONICA instrument (or NACO [1]), mounted on one of the 8.2 m Unit Telescopes of ESO's Very Large Telescope (VLT), to benefit from both the high image quality provided by the Adaptive Optics system at infrared wavelengths and the good dynamics offered by the detector, in order to study the immediate surroundings of Beta Pictoris. Recently, a member of the team re-analysed the data in a different way to seek the trace of a companion to the star. Infrared wavelengths are indeed very well suited for such searches. "For this, the real challenge

  6. Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation.

    PubMed

    Kim, Eun-A; Kim, Ji Eon; Sung, Ki Sa; Choi, Dong Wook; Lee, Byeong Jae; Choi, Cheol Yong

    2010-04-16

    The regulation of intracellular beta-catenin levels is central in the Wnt/beta-catenin signaling cascade and the activation of the Wnt target genes. Here, we show that homeodomain-interacting protein kinase 2 (HIPK2) acts as a negative regulator of the Wnt/beta-catenin pathway. Knock-down of endogenous HIPK2 increases the stability of beta-catenin and results in the accumulation of beta-catenin in the nucleus, consequently enhancing the expression of Wnt target genes and cell proliferation both in vivo and in cultured cells. HIPK2 inhibits TCF/LEF-mediated target gene activation via degradation of beta-catenin. HIPK2 phosphorylates beta-catenin at its Ser33 and Ser37 residues without the aid of a priming kinase. Substitutions of Ser33 and Ser37 for alanines abolished the degradation of beta-catenin associated with HIPK2. In ex vivo mouse model, HIPK2 knock-down resulted in accumulation of beta-catenin, thereby potentiated beta-catenin-mediated cell proliferation and tumor formation. Furthermore, the axis duplication induced by the ectopic expression of beta-catenin was blocked by co-injection of HIPK2 mRNAs into Xenopus embryos. Taken together, HIPK2 appears to function as a novel negative regulator of beta-catenin through its phosphorylation and proteasomal degradation. PMID:20307497

  7. Homeodomain-interacting protein kinase 2 (HIPK2) targets {beta}-catenin for phosphorylation and proteasomal degradation

    SciTech Connect

    Kim, Eun-A; Kim, Ji Eon; Sung, Ki Sa; Choi, Dong Wook; Lee, Byeong Jae; Choi, Cheol Yong

    2010-04-16

    The regulation of intracellular {beta}-catenin levels is central in the Wnt/{beta}-catenin signaling cascade and the activation of the Wnt target genes. Here, we show that homeodomain-interacting protein kinase 2 (HIPK2) acts as a negative regulator of the Wnt/{beta}-catenin pathway. Knock-down of endogenous HIPK2 increases the stability of {beta}-catenin and results in the accumulation of {beta}-catenin in the nucleus, consequently enhancing the expression of Wnt target genes and cell proliferation both in vivo and in cultured cells. HIPK2 inhibits TCF/LEF-mediated target gene activation via degradation of {beta}-catenin. HIPK2 phosphorylates {beta}-catenin at its Ser33 and Ser37 residues without the aid of a priming kinase. Substitutions of Ser33 and Ser37 for alanines abolished the degradation of {beta}-catenin associated with HIPK2. In ex vivo mouse model, HIPK2 knock-down resulted in accumulation of {beta}-catenin, thereby potentiated {beta}-catenin-mediated cell proliferation and tumor formation. Furthermore, the axis duplication induced by the ectopic expression of {beta}-catenin was blocked by co-injection of HIPK2 mRNAs into Xenopus embryos. Taken together, HIPK2 appears to function as a novel negative regulator of {beta}-catenin through its phosphorylation and proteasomal degradation.

  8. Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy

    PubMed Central

    Wang, Yingmei; Ji, Ping; Liu, Jinsong; Broaddus, Russell R; Xue, Fengxia; Zhang, Wei

    2009-01-01

    In eukaryotic cells, control mechanisms have developed that restrain cell-cycle transitions in response to stress. These regulatory pathways are termed cell-cycle checkpoints. The G2/M checkpoint prevents cells from entering mitosis when DNA is damaged in order to afford these cells an opportunity to repair the damaged DNA before propagating genetic defects to the daughter cells. If the damage is irreparable, checkpoint signaling might activate pathways that lead to apoptosis. Since alteration of cell-cycle control is a hallmark of tumorigenesis, cell-cycle regulators represent potential targets for therapy. The centrosome has recently come into focus as a critical cellular organelle that integrates G2/M checkpoint control and repairs signals in response to DNA damage. A growing number of G2/M checkpoint regulators have been found in the centrosome, suggesting that centrosome has an important role in G2/M checkpoint function. In this review, we discuss centrosome-associated regulators of the G2/M checkpoint, the dysregulation of this checkpoint in cancer, and potential candidate targets for cancer therapy. PMID:19216791

  9. Viscum album-Mediated COX-2 Inhibition Implicates Destabilization of COX-2 mRNA

    PubMed Central

    Saha, Chaitrali; Hegde, Pushpa; Friboulet, Alain; Bayry, Jagadeesh; Kaveri, Srinivas V.

    2015-01-01

    Extensive use of Viscum album (VA) preparations in the complementary therapy of cancer and in several other human pathologies has led to an increasing number of cellular and molecular approaches to explore the mechanisms of action of VA. We have recently demonstrated that, VA preparations exert a potent anti-inflammatory effect by selectively down-regulating the COX-2-mediated cytokine-induced secretion of prostaglandin E2 (PGE2), one of the important molecular signatures of inflammatory reactions. In this study, we observed a significant down-regulation of COX-2 protein expression in VA-treated A549 cells however COX-2 mRNA levels were unaltered. Therefore, we hypothesized that VA induces destabilisation of COX-2 mRNA, thereby depleting the available functional COX-2 mRNA for the protein synthesis and for the subsequent secretion of PGE2. To address this question, we analyzed the molecular degradation of COX-2 protein and its corresponding mRNA in A549 cell line. Using cyclohexamide pulse chase experiment, we demonstrate that, COX-2 protein degradation is not affected by the treatment with VA whereas experiments on transcriptional blockade with actinomycin D, revealed a marked reduction in the half life of COX-2 mRNA due to its rapid degradation in the cells treated with VA compared to that in IL-1β-stimulated cells. These results thus demonstrate that VA-mediated inhibition of PGE2 implicates destabilization of COX-2 mRNA. PMID:25664986

  10. Beta-thalassemia.

    PubMed

    Galanello, Renzo; Origa, Raffaella

    2010-01-01

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  11. Beta-thalassemia

    PubMed Central

    2010-01-01

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  12. Triiodothyronine receptor beta-2 messenger ribonucleic acid expression by somatotropes and thyrotropes: effect of propylthiouracil-induced hypothyroidism in rats.

    PubMed

    Childs, G V; Taub, K; Jones, K E; Chin, W W

    1991-11-01

    mRNA for a thyroid hormone receptor isoform that is unique to the pituitary gland (TR beta-2) is down-regulated by T3. Increases in the expression of this mRNA are seen in rats rendered hypothyroid by treatment with propylthiouracil (PTU). This study used dual labeling to determine which pituitary cells expressed TR beta-2 mRNA in normal and PTU-treated rats. In situ hybridization protocols localized the mRNA (with biotinylated complementary oligonucleotide probes detected by avidin-biotin-peroxidase), and immunoperoxidase protocols identified the pituitary hormone proteins. In dispersed pituitary cells, 20 +/- 2% (average +/- SD) of cells from normal rats and 30 +/- 3% of cells from PTU-treated rats were labeled for TR beta-2 mRNA. PTU caused increases in the area of the labeled cells (from 114 +/- 11 to 225 +/- 7 microns 2), the area of the label per cell (from 27 +/- 3 to 71 +/- 11 microns 2), and label density. PTU produced increases in the percentage of TSH cells from 8 +/- 1% to 19 +/- 2%, decreases in the percentage of GH cells from 27 +/- 3% to 11 +/- 2%, and no change in other cell types. After dual labeling, 73% of cells that expressed TR beta-2 mRNA stored either TSH (35 +/- 8) or GH (38 +/- 6). Less than 10% stored other hormones. When each cell type was analyzed, 56 +/- 3% of TSH cells and 43 +/- 4% of GH cells expressed TR beta-2 mRNA. When these percentages were multiplied by the percentages of each cell type in the overall population, TSH and GH cells with TR beta-2 mRNA represented 6.8 +/- 1% and 11.6 +/- 1% of the pituitary cells, respectively. Less than 1% of all pituitary cells expressed TR beta-2 and ACTH (0.9 +/- 0.06), LH (0.8 +/- 0.1), FSH (0.8 +/- 0.1), and PRL (0.9 +/- 0.04). PTU treatment increased the percentage of TSH cells with TR beta-2 mRNA to 72 +/- 4% and decreased the percentage of GH cells with TR beta-2 mRNA to 30 +/- 3%. However, some enlarged putative TSH cells could not be identified by immunolabel because the storage levels

  13. Measurement of $\\beta_s$ at CDF

    SciTech Connect

    Oakes, Louise; /Oxford U.

    2011-02-01

    The latest results for the measurement of the CP violating phase {beta}{sub s} in B{sub s}{sup 0} {yields} J/{Psi}{phi} decays, from 5.2 fb{sup -1} integrated luminosity of CDF data are presented. For the first time, this measurement includes the contribution of B{sub s}{sup 0} {yields} J/{Psi}K{sup +}K{sup -} or B{sub s}{sup 0} {yields} J/{Psi}f{sub 0} events to the signal sample, where the f{sub 0} and non-resonant K{sup +}K{sup -} are S-wave states. Additional improvements to the analysis include more than doubling the signal sample, improved selection and particle ID, and fully calibrated flavour tagging for the full dataset. Additionally, the world's most precise single measurements of the B{sub s}{sup 0} lifetime, {tau}{sub s}, and width difference, {Delta}{Gamma}{sub s} are given.

  14. Thermophilic Beta-Glycosidase

    NASA Technical Reports Server (NTRS)

    Grogan, Dennis W.

    1992-01-01

    Report describes identification of thermophilic Beta-glycosidase enzyme from isolate of Sulfolobus solfataricus, sulfur-metabolizing archaebacteria growing aerobically and heterotrophically to relatively high cell yields. Enzyme useful in enzymatic conversion of cellulose to D-glucose and important in recycling of biomass. Used for removal of lactose from milk products. Offers promise as model substance for elucidation of basic principles of structural stabilization of proteins.

  15. Dietary NiCl2 causes G2/M cell cycle arrest in the broiler's kidney

    PubMed Central

    Guo, Hongrui; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan; Chen, Kejie; Deng, Jie

    2015-01-01

    Here we showed that dietary NiCl2 in excess of 300 mg/kg caused the G2/M cell cycle arrest and the reduction of cell proportion at S phase. The G2/M cell cycle arrest was accompanied by up-regulation of phosphorylated ataxia telangiectasia mutated (p-ATM), p53, p-Chk1, p-Chk2, p21 protein expression and ATM, p53, p21, Chk1, Chk2 mRNA expression, and down-regulation of p-cdc25C, cdc2, cyclinB and proliferating cell nuclear antigen (PCNA) protein expression and the cdc25, cdc2, cyclinB, PCNA mRNA expression. PMID:26440151

  16. Current status of advanced pelletized cold moderators development for IBR-2M research reactor

    NASA Astrophysics Data System (ADS)

    Kulikov, S.; Belyakov, A.; Bulavin, M.; Mukhin, K.; Shabalin, E.; Verhoglyadov, A.

    2013-03-01

    The world's first advanced pelletized cold neutron moderator is prepared to be put into operation at the IBR-2M pulsed research reactor. It provides long-wavelength neutrons to the most of neutron spectrometers at the beams of the IBR-2M reactor. Aromatic hydrocarbons are used as a material for cold moderators. It is a very attractive material because of its high radiation resistance, good moderating properties, incombustibility, etc. It is shown that the idea of beads transport by a helium flow at cryogenic temperatures is successful. The recent progress and plans for moderator development at the IBR-2M reactor as well as the experimental results of beads transport are discussed in the paper.

  17. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest

    PubMed Central

    Ujiki, Michael B; Ding, Xian-Zhong; Salabat, M Reza; Bentrem, David J; Golkar, Laleh; Milam, Ben; Talamonti, Mark S; Bell, Richard H; Iwamura, Takeshi; Adrian, Thomas E

    2006-01-01

    Background Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. Results Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. Conclusion Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer. PMID:17196098

  18. Weak-value thermostat with 0.2 mK precision.

    PubMed

    Egan, Patrick; Stone, Jack A

    2012-12-01

    A new laser-based thermostat sensitive to 0.2 mK at room temperature is reported. The method utilizes a fluid-filled prism and interferometric weak-value amplification to sense nanoradian deviations of a laser beam: due to the high thermo-optic coefficient of the fluid (colorless fluorocarbon), the deviation angle through the prism is sensitive to temperature. We estimate the daily stability of our device to be 0.2 mK, which is limited by drifts in the apparatus, and the narrow 20 mK capture range is the price paid for the weak measurement. PMID:23202114

  19. Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: a proteomic study

    PubMed Central

    2014-01-01

    Background Cordyceps cicadae is a medicinal fungus that is often used for treating cancer. However, the anticancer mechanisms of C. cicadae are largely unknown. This study aims to investigate the anticancer mechanisms of C. cicadae against hepatocellular carcinoma cells in vitro using a proteomic approach. Methods Human hepatocellular carcinoma MHCC97H cells were treated with a water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) for 48 h and harvested for cell viability assays. The significant differences in protein expression between control and C. cicadae-treated cells were analyzed by two-dimensional gel-based proteomics coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry. Flow cytometry analysis was employed to investigate the cell cycle and cell death. The anticancer molecular mechanism was analyzed by whole proteome mapping. Results The water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) inhibited the growth of MHCC97H cells in a dose-dependent manner via G2/M phase cell cycle arrest with no evidence of apoptosis. Among the identified proteins with upregulated expression were dynactin subunit 2, N-myc downstream-regulated gene 1, heat shock protein beta-1, alpha-enolase isoform 1, phosphatidylinositol transfer protein, and WD repeat-containing protein 1. Meanwhile, the proteins with downregulated expression were 14-3-3 gamma, BUB3, microtubule-associated protein RP/EB family member 1, thioredoxin-like protein, chloride intracellular channel protein 1, ectonucleoside triphosphate diphosphohydrolase 5, xaa-Pro dipeptidase, enoyl-CoA delta isomerase 1, protein-disulfide isomerase-related chaperone Erp29, hnRNP 2H9B, peroxiredoxin 1, WD-40 repeat protein, and serine/threonine kinase receptor-associated protein. Conclusion The water extract of C. cicadae reduced the growth of human hepatocellular carcinoma MHCC97H cells via G2/M cell cycle arrest. PMID:24872842

  20. Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas.

    PubMed Central

    Eder, I. E.; Stenzl, A.; Hobisch, A.; Cronauer, M. V.; Bartsch, G.; Klocker, H.

    1997-01-01

    We previously detected elevated transforming growth factor beta-1 (TGF-beta1) serum levels in patients with invasive bladder carcinomas. In this study, we therefore investigated whether elevated serum levels correlate with enhanced TGF-beta expression in human bladder tumours. mRNA levels of TGF-beta1, -beta2 and -beta3 were reduced in bladder tumour tissue to 86%, 68% and 56%, respectively, of the levels in normal urothelium. On the other hand, TGF-beta1 protein levels were found to be higher in superficial tumours (Ta-T1) (mean level of 0.153 ng mg(-1)) and in invasive T2/T3 tumours (mean level of 0.104 ng mg(-1)) compared with normal urothelium (mean level of 0.065 ng mg(-1)). Invasive T4 tumours, however, contained only low amounts of TGF-beta1 (mean level of 0.02 ng mg(-1)). Neither in mean nor in individual patients were serum and tissue TGF-beta levels correlated with each other. Cell culture experiments on primary bladder cells revealed a 57% decrease in TGF-beta1 mRNA levels in tumour compared with normal epithelial cells. Tumour epithelial cells contained about two times higher levels of TGF-beta2 and TGF-beta3 mRNA than normal epithelial cells. Fibroblasts expressed about the same amount of TGF-beta1 or TGF-beta2 as epithelial cells. Yet, fibroblasts released only 19% and 13% of the amount secreted by tumour epithelial cells into the supernatant. TGF-beta3, on the other hand, was expressed by fibroblasts with higher levels than by epithelial cells. TGF-beta1 was the predominent isoform in bladder tissue and cells at protein as well as on mRNA levels indicating that TGFs-beta2 and -beta3 are of minor importance in bladder cancer. In summary, there is a lack of correlation between TGF-beta serum levels and TGF-beta expression in tumour tissue in bladder cancer. Images Figure 1 PMID:9192977

  1. Tubulin-targeted drug action: functional significance of class ii and class IVb beta-tubulin in vinca alkaloid sensitivity.

    PubMed

    Gan, Pei Pei; Kavallaris, Maria

    2008-12-01

    Aberrant expression of beta-tubulin isotypes is frequently described in tumor tissues and tubulin-binding agent (TBA)-resistant cell lines. There is limited understanding of the role of specific beta-tubulin isotypes in cellular sensitivity to TBAs, and to gain insights into the functional role of betaII- and betaIVb-tubulin, we examined these isotypes in lung cancer cell lines NCI-H460 (H460) and Calu-6. Drug-treated clonogenic assays revealed that small interfering RNA-mediated knockdown of either betaII- or betaIVb-tubulin hypersensitized the lung cancer cell lines to Vinca alkaloids, with the effects more pronounced following betaIVb-tubulin knockdown. In contrast, there was no change in paclitaxel sensitivity following knockdown of either isotype. Cell cycle analysis revealed a greater propensity for the betaII- and betaIVb-tubulin knockdown cells to undergo G2-M cell cycle block following 5 nmol/L vincristine treatment, with the betaIVb knockdown cells being more sensitive than the betaII-tubulin knockdown cells compared with control. In contrast to betaII-tubulin knockdown, betaIVb-tubulin knockdown cells showed a significant increase in the sub-G1 population (cell death) following treatment with both 5 and 40 nmol/L of vincristine compared with controls. Importantly, betaIVb-tubulin knockdown in H460 cells caused a significant dose-dependent increase in Annexin V staining in response to vincristine but not paclitaxel. Therefore, increased sensitivity to induction of apoptosis is one mechanism underlying the Vinca alkaloid hypersensitivity. This study provides direct evidence that betaII- or betaIVb-tubulins have functionally distinct roles and expression of these isotypes may serve as strong predictors of Vinca alkaloid response and resistance. PMID:19047161

  2. Beta* and beta-waist measurement and control at RHIC

    SciTech Connect

    Ptitsyn,V.; Della Penna, A.; Litvinenko, V.N.; Malitsky, N.; Satogata, T.

    2009-05-04

    During the course of last RHIC runs the beta-functions at the collision points ({beta}*) have been reduced gradually to 0.7m. In order to maximize the collision luminosity and ensure the agreement of the actual machine optics with the design one, more precise measurements and control of {beta}* value and {beta}-waist location became necessary. The paper presents the results of the implementation of the technique applied in last two RHIC runs. The technique is based on well-known relation between the tune shift and the beta function and involves precise betatron tune measurements using BBQ system as well as specially developed knobs for {beta}-waist location control.

  3. Syntheses and structural characterization of non-centrosymmetric Na2M2M'S6 (M, M‧=Ga, In, Si, Ge, Sn, Zn, Cd) sulfides

    NASA Astrophysics Data System (ADS)

    Yohannan, Jinu P.; Vidyasagar, Kanamaluru

    2016-06-01

    Seven new non-centrosymmetric Na2M2M'S6 sulfides, namely, Na2Sn2ZnS6(1), Na2Ga2GeS6(2), Na2Ga2SnS6(3-α), Na2Ga2SnS6(3-β), Na2Ge2ZnS6(4), Na2Ge2CdS6(5), Na2In2SiS6(6) and Na2In2GeS6(7), were synthesized by high temperature solid state reactions and structurally characterized by single crystal X-ray diffraction. They crystallize in non-centrosymmetric Fdd2 and Cc space groups and their three-dimensional [M2M‧S6]2-framework structures consist of MS4 and M‧S4 tetrahedra corner-connected to one another in either orderly or disordered fashion. Sodium ions reside in the tunnels of the anionic framework. Compounds 1, 2 and 3-α have the structure of known Li2Ga2GeS6, whereas compounds 6 and 7 are isostructural with known Li2In2GeS6 compound. Isostructural compounds 4 and 5 represent a new structural variant. Compounds 3-α and its new monoclinic structural variant 3-β have disordered structural framework. All of them are wide band gap semiconductors. Na2Ga2GeS6(2), Na2Ga2SnS6(3), Na2Ge2ZnS6(4) and Na2In2GeS6(7) compounds are found to be second-harmonic generation (SHG) active. Compounds 1, 2 and 3-α melt congruently.

  4. A survey on M2M systems for mHealth: a wireless communications perspective.

    PubMed

    Kartsakli, Elli; Lalos, Aris S; Antonopoulos, Angelos; Tennina, Stefano; Renzo, Marco Di; Alonso, Luis; Verikoukis, Christos

    2014-01-01

    In the new era of connectivity, marked by the explosive number of wireless electronic devices and the need for smart and pervasive applications, Machine-to-Machine (M2M) communications are an emerging technology that enables the seamless device interconnection without the need of human interaction. The use of M2M technology can bring to life a wide range of mHealth applications, with considerable benefits for both patients and healthcare providers. Many technological challenges have to be met, however, to ensure the widespread adoption of mHealth solutions in the future. In this context, we aim to provide a comprehensive survey on M2M systems for mHealth applications from a wireless communication perspective. An end-to-end holistic approach is adopted, focusing on different communication aspects of the M2M architecture. Hence, we first provide a systematic review ofWireless Body Area Networks (WBANs), which constitute the enabling technology at the patient's side, and then discuss end-to-end solutions that involve the design and implementation of practical mHealth applications. We close the survey by identifying challenges and open research issues, thus paving the way for future research opportunities. PMID:25264958

  5. CH2M Hill Hanford Group Inc (CHG) Information Resource Management (IRM) Strategic Plan

    SciTech Connect

    NELSON, R.L.

    2000-06-06

    The CH2M HILL Hanford Group, Inc. (CHG), Information Resource Management Strategic Plan is the top-level planning document for applying information and information resource management to achieve the CHG mission for the management of the River Protection Project waste tank farm.

  6. LTE-advanced random access mechanism for M2M communication: A review

    NASA Astrophysics Data System (ADS)

    Mustafa, Rashid; Sarowa, Sandeep; Jaglan, Reena Rathee; Khan, Mohammad Junaid; Agrawal, Sunil

    2016-03-01

    Machine Type Communications (MTC) enables one or more self-sufficient machines to communicate directly with one another without human interference. MTC applications include smart grid, security, e-Health and intelligent automation system. To support huge numbers of MTC devices, one of the challenging issues is to provide a competent way for numerous access in the network and to minimize network overload. In this article, the different control mechanisms for overload random access are reviewed to avoid congestion caused by random access channel (RACH) of MTC devices. However, past and present wireless technologies have been engineered for Human-to-Human (H2H) communications, in particular, for transmission of voice. Consequently the Long Term Evolution (LTE) -Advanced is expected to play a central role in communicating Machine to Machine (M2M) and are very optimistic about H2H communications. Distinct and unique characteristics of M2M communications create new challenges from those in H2H communications. In this article, we investigate the impact of massive M2M terminals attempting random access to LTE-Advanced all at once. We discuss and review the solutions to alleviate the overload problem by Third Generation Partnership Project (3GPP). As a result, we evaluate and compare these solutions that can effectively eliminate the congestion on the random access channel for M2M communications without affecting H2H communications.

  7. NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

    SciTech Connect

    Bu, Youquan; Suenaga, Yusuke; Okoshi, Rintaro; Sang, Meixiang; Kubo, Natsumi; Song, Fangzhou; Nakagawara, Akira; Ozaki, Toshinori

    2010-06-25

    NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of {gamma}H2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.

  8. The Discharge Design of HL-2M with the Tokamak Simulation Code (TSC)

    SciTech Connect

    Yudong Pan, S.C. Jardin, and C. Kes

    2007-10-10

    We present results on the discharge design of the HL-2M tokamak, which is to be an upgrade to the existing HL-2A tokamak. We present simulation results for complete 5-sec. discharges, both double null and lower single null, for both ohmic and auxiliary heated discharges. We also discuss the vertical stability properties of the device. __________________________________________________

  9. Performance of V-4Cr-4Ti Alloy Exposed to the JFT-2M Tokamak Environment

    SciTech Connect

    Johnson, W.R.; Trester, P.W.; Sengoku, S.; Ishiyama, S.; Fukaya, K.; Eto, M.; Oda, T.; Hirohata, Y.; Hino, T.; Tsai, H.

    1999-10-01

    A long-term test has been conducted in the JFT-2M tokamak fusion device to determine the effects of environmental exposure on the mechanical and chemical behavior of a V-4Cr-4Ti alloy. Test specimens of the alloy were exposed in the outward lower divertor chamber of JFT-2M in a region away from direct contact with the plasma and were preheated to 300 C just prior to and during selected plasma discharges. During their nine-month residence time in JFT-2M, the specimens experienced approximately 200 lower single-null divertor shots at 300 C, during which high energy particle fluxes to the preheated test specimens were significant, and approximately 2,010 upper single-null divertor shots and non-diverter shots at room temperature, for which high energy particle fluxes to and expected particle retention in the test specimens were very low. Data from post-exposure tests have indicated that the performance of the V-4Cr-4Ti alloy would not be significantly affected by environmental exposure to gaseous species at partial pressures typical for tokamak operation. Deuterium retention in the exposed alloy was also low (<2 ppm). Absorption of interstitial by the alloy was limited to the very near surface, and neither the strength nor the Charpy impact properties of the alloy appeared to be significantly changed from the exposure to the JFT-2M tokamak environment.

  10. A Survey on M2M Systems for mHealth: A Wireless Communications Perspective

    PubMed Central

    Kartsakli, Elli; Lalos, Aris S.; Antonopoulos, Angelos; Tennina, Stefano; Di Renzo, Marco; Alonso, Luis; Verikoukis, Christos

    2014-01-01

    In the new era of connectivity, marked by the explosive number of wireless electronic devices and the need for smart and pervasive applications, Machine-to-Machine (M2M) communications are an emerging technology that enables the seamless device interconnection without the need of human interaction. The use of M2M technology can bring to life a wide range of mHealth applications, with considerable benefits for both patients and healthcare providers. Many technological challenges have to be met, however, to ensure the widespread adoption of mHealth solutions in the future. In this context, we aim to provide a comprehensive survey on M2M systems for mHealth applications from a wireless communication perspective. An end-to-end holistic approach is adopted, focusing on different communication aspects of the M2M architecture. Hence, we first provide a systematic review of Wireless Body Area Networks (WBANs), which constitute the enabling technology at the patient's side, and then discuss end-to-end solutions that involve the design and implementation of practical mHealth applications. We close the survey by identifying challenges and open research issues, thus paving the way for future research opportunities. PMID:25264958

  11. Cell Cycle Arrest in G2/M Promotes Early Steps of Infection by Human Immunodeficiency Virus

    PubMed Central

    Groschel, Bettina; Bushman, Frederic

    2005-01-01

    We have identified four small molecules that boost transduction of cells by human immunodeficiency virus (HIV) and investigated their mechanism of action. These molecules include etoposide and camptothecin, which induce DNA damage by inhibiting religation of cleaved topoisomerase-DNA complexes, taxol, which interferes with the function of microtubules, and aphidicolin, which inhibits DNA polymerases. All four compounds arrest the cell cycle at G2/M, though in addition high concentrations of aphidicolin arrest in G1. We find that early events of HIV replication, including synthesis of late reverse transcription products, two-long terminal repeat circles, and integrated proviruses, were increased after treatment of cells with concentrations of each compound that arrested in G2/M. Stimulation was seen for both transformed cell lines (293T and HeLa cells) and primary cells (IMR90 lung fibroblasts). Arrest in G1 with high concentrations of aphidicolin boosted transduction, though not much as with lower concentrations that arrested in G2/M. Arrest of IMR90 cells in G1 by serum starvation and contact inhibition reduced transduction. Previously, the proteasome inhibitor MG132 was reported to increase HIV infection—here we investigated the effects of combinations of the cell cycle inhibitors with MG132 and obtained data suggesting that MG132 may also boost transduction by causing G2/M cell cycle arrest. These data document that cell cycle arrest in G2/M boosts the early steps of HIV infection and suggests methods for increasing transduction with HIV-based vectors. PMID:15827184

  12. [Beta blockers in migraine prophylaxis].

    PubMed

    Shimizu, Toshihiko

    2009-10-01

    Beta blockers (beta-adrenoceptor blockers) are known to be used for the prophylactic treatment of migraine. The improvement of migraine in the patients who recieved propranolol for angina pectoris revealed the effectiveness of propranolol in migraine prophylaxis. Many clinical trials have confirmed that propranolol is effective in the prophylactic treatment of migraine. Other beta-blocking drugs, namely nadolol, metoprolol, atenolol, timolol and bisoprolol, have also been demonstrated to be effective in the prophylaxis of migraine. In contrast, several beta blockers with intrinsic sympathetic activity (ISA), such as alprenolol, oxprenolol, pindolol and acebutolol, have not been demonstrated to be effective in migraine prophylaxis. In this review, we have descrived the pharmacologic background and pharmacokinetics of the beta blockers that demonstrated a prophylactic effect for migraine will be described. We have also reviewed the results of clinical trials of beta-blocking drugs for migraine. PMID:19882938

  13. Solergy (Beta Version 1)

    2009-03-30

    SOLERGY simulates the operation and power output of a user-defined solar central receiver power plant for a time period of up to one year. SOLERGY utilizes recorded or simulated weather data and plant component performance models to calculate the power flowing through each part of the solar plant. A plant control subroutine monitors these powers and determines when to operate the various plant subsystems. The original version of the code was released in May 1987,more » within SAND86-8060 and was widely distributed. The Beta Version 1 to be released in 2009, includes some relatively small modifications to the original code.« less

  14. The Octahedral Sheet of Metamorphic 2M 1-Phengites: a Combined EMPA And AXANES Study

    SciTech Connect

    Cibin, G.; Cinque, G.; Marcelli, A.; Mottana, A.; Sassi, R.

    2009-05-12

    Two types of metamorphic phengites are known: one is linked to high pressure and is 3T; the other is 2M{sub 1}, and its composition is linked to rock-compositional constraints. This work investigates the octahedral sheet crystal-chemical differences between the two phengite types. Seven dioctahedral micas were studied: (1) one 3T phengite from an ultrahigh-pressure metagranitoid in the Dora Maira massif, Italy (P {approx} 4.3 GPa, T {approx} 730 C); (2) five 2M{sub 1} phengites from medium-P orthogneisses in the Eastern Alps metamorphic basement, Italy (P {le} 0.7 GPa, T {approx} 500-600 C); and (3) one 2M{sub 1} ferroan muscovite from pegmatite in Antarctica (P {le} 0.2 GPa, T {approx}500 C). All micas display significant extents of celadonite substitution. In particular, the 2M{sub 1}-phengite formulae (calculated on the basis of 11 O) have 0.68 < {sup IV}Al < 0.82 atoms per formula unit (apfu); octahedral atoms are dominated by Al (1.6-1.8 apfu), with minor and variable Fe (0.20-0.35 apfu) and Mg (0.05-0.17 apfu), and very minor Ti, Mn, and Cr. Total octahedral occupancies are slightly above 2.00 apfu, i.e., there seems to be partial occupancy of the third M site. For all micas, we recorded XAFS spectra on mosaics of carefully separated flakes oriented flat on a plastic support that could be rotated so as to account for the polarization of the synchrotron radiation beam, and we processed them on the basis of the AXANES theory. Spectra show angle-dependent absorption variations for Al and Fe, which can be deconvoluted and fitted by dichroic effects. Pre-edges consistently show most Fe to be Fe{sup 3+} and little angle-dependent intensity variations. The 2M{sub 1}-ferroan muscovite from Antarctica displays the same AXANES behavior as 2M{sub 1}-phengites. By contrast, the ultrahigh-pressure 3T-phengite from Dora Maira (having {sup IV}Al = 0.42 apfu, and Al and Mg as the dominant octahedral constituents) has XAFS spectra that differ significantly. Not only is the

  15. Simultaneous beta and gamma spectroscopy

    DOEpatents

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  16. LiMO{sub 2} (M=Mn, Fe, and Co): Energetics, polymorphism and phase transformation

    SciTech Connect

    Wang Miaojun; Navrotsky, Alexandra . E-mail: anavrotsky@ucdavis.edu

    2005-04-15

    LiMO{sub 2} materials (M=Mn, Fe, and Co) with different structures were synthesized and their enthalpies of formation from oxides (Li{sub 2}O and M{sub 2}O{sub 3}, M=Mn and Fe), or from oxides (Li{sub 2}O and CoO) plus oxygen at 25{sup o}C were determined by high-temperature oxide melt solution calorimetry. The relative stability of the polymorphs of the compound LiMO{sub 2} was established based on their enthalpies of formation. Phase transformations in LiFeO{sub 2} were investigated by differential scanning calorimetry and high-temperature oxide melt solution calorimetry. The phase transition enthalpies at 25{sup o}C for {beta}->{alpha}, {gamma}->{beta}, and {gamma}->{alpha} are 4.9+/-0.7, 4.3+/-0.8 and 9.2+/-0.9kJ/mol, respectively. Thus the {gamma} phase (ordered cations) is the stable form of LiFeO{sub 2} at room temperature, the {alpha} phase (disordered cations) is stable at high temperature and the {beta} phase may have a stability field at intermediate temperatures.

  17. The Construction of M2M System with Sensor Networks Using Digital Plethysmograph Sensor

    NASA Astrophysics Data System (ADS)

    Segawa, Norihisa; Asakawa, Kazuhisa; Takahashi, Yoshitsugu; Yamada, Tomoko; Togashi, Atsushi; Sawamoto, Jun

    In recent years, the research of sensor networks advances and it is expected to be used in a wide variety of fields such as traceability system of products, environmental monitoring, health care, etc. We develop a M2M system with the sensor network technology for collection and analysis of the state of health and feedback of advices for better physical activity without human intervention. The system detects abnormality from pulse wave data from pulse wave sensor attached to the user. In this paper, we construct M2M sensor network system with continuous monitoring of arterial pulse wave and an advice generation function based on pr-installed rules, then we evaluate the usefulness of the system through experiment.

  18. VLSI architectures for computing multiplications and inverses in GF(2m).

    PubMed

    Wang, C C; Truong, T K; Shao, H M; Deutsch, L J; Omura, J K; Reed, I S

    1985-08-01

    Finite field arithmetic logic is central in the implementation of Reed-Solomon coders and in some cryptographic algorithms. There is a need for good multiplication and inversion algorithms that can be easily realized on VLSI chips. Massey and Omura recently developed a new multiplication algorithm for Galois fields based on a normal basis representation. In this paper, a pipeline structure is developed to realize the Massey-Omura multiplier in the finite field GF(2m). With the simple squaring property of the normal basis representation used together with this multiplier, a pipeline architecture is developed for computing inverse elements in GF(2m). The designs developed for the Massey-Omura multiplier and the computation of inverse elements are regular, simple, expandable, and therefore, naturally suitable for VLSI implementation. PMID:11539660

  19. VLSI architectures for computing multiplications and inverses in GF(2-m)

    NASA Technical Reports Server (NTRS)

    Wang, C. C.; Truong, T. K.; Shao, H. M.; Deutsch, L. J.; Omura, J. K.; Reed, I. S.

    1983-01-01

    Finite field arithmetic logic is central in the implementation of Reed-Solomon coders and in some cryptographic algorithms. There is a need for good multiplication and inversion algorithms that are easily realized on VLSI chips. Massey and Omura recently developed a new multiplication algorithm for Galois fields based on a normal basis representation. A pipeline structure is developed to realize the Massey-Omura multiplier in the finite field GF(2m). With the simple squaring property of the normal-basis representation used together with this multiplier, a pipeline architecture is also developed for computing inverse elements in GF(2m). The designs developed for the Massey-Omura multiplier and the computation of inverse elements are regular, simple, expandable and, therefore, naturally suitable for VLSI implementation.

  20. VLSI architectures for computing multiplications and inverses in GF(2m)

    NASA Technical Reports Server (NTRS)

    Wang, C. C.; Truong, T. K.; Shao, H. M.; Deutsch, L. J.; Omura, J. K.

    1985-01-01

    Finite field arithmetic logic is central in the implementation of Reed-Solomon coders and in some cryptographic algorithms. There is a need for good multiplication and inversion algorithms that are easily realized on VLSI chips. Massey and Omura recently developed a new multiplication algorithm for Galois fields based on a normal basis representation. A pipeline structure is developed to realize the Massey-Omura multiplier in the finite field GF(2m). With the simple squaring property of the normal-basis representation used together with this multiplier, a pipeline architecture is also developed for computing inverse elements in GF(2m). The designs developed for the Massey-Omura multiplier and the computation of inverse elements are regular, simple, expandable and, therefore, naturally suitable for VLSI implementation.

  1. THE WHITE DWARF COMPANION OF A 2 M{sub sun} NEUTRON STAR

    SciTech Connect

    Bhalerao, Varun B.; Kulkarni, S. R.

    2011-08-10

    We report the optical discovery of the companion to the 2 M{sub sun} millisecond pulsar PSR J1614-2230. The optical colors show that the 0.5 M{sub sun} companion is a 2.2 Gyr old He-CO white dwarf. We infer that M-dot during the accretion phase is <10{sup -2} M-dot{sub edd}. We show that the pulsar was born with a spin close to its current value, well below the rebirth line. The spin-down parameters, the mass of the pulsar, and the age of the system challenge the simple recycling model for the formation of millisecond pulsars.

  2. Rate constant for formation of chlorine nitrate by the reaction ClO + NO2 + M

    NASA Technical Reports Server (NTRS)

    Leu, M. T.; Lin, C. L.; Demore, W. B.

    1977-01-01

    The pseudo-first-order decay of ClO in a large excess of NO2 was monitored in a discharge flow/mass-spectrometer apparatus in order to measure the rate constant of the reaction ClO + NO2 + M yields ClONO2 + M for M = He, Ar, and N2 over the temperature range from 248 to 417 K. Numerical results are given for He at 248, 299, 360, and 417 K (1 to 9 torr); for Ar at 298 K (1 to 4 torr); and for N2 at 299, 360, and 417 K (1 to 6 torr). Systematic errors are estimated, and identification of the reaction product is discussed. The results obtained are shown to be in excellent agreement with other recent measurements of the same rate constant.

  3. On the Diophantine equation x^2+q^2m=2y^p

    NASA Astrophysics Data System (ADS)

    Tengely, Sz

    In this paper we consider the Diophantine equation $x^2+q^{2m}=2y^p$ where $m,p,q,x,y$ are integer unknowns with $m>0,$ $p$ and $q$ are odd primes and $\\gcd(x,y)=1.$ We prove that there are only finitely many solutions $(m,p,q,x,y)$ for which $y$ is not a sum of two consecutive squares. We also study the above equation with fixed $y$ and with fixed $q.$

  4. E2/M1 ratio of the N to Delta transition in a modified Skyrme model

    NASA Astrophysics Data System (ADS)

    Back, Anthony Randolph

    1997-08-01

    I use a chiral effective Lagrangian to find the E2/M1 ratio. This ratio is a measure of the deformation of the nucleon. The Lagrangian is a modified Skyrme model (1). Its construction is guided by chiral symmetry and the symmetries of QCD, which dictates the addition of the Wess-Zumino term. The current is quantized using collective coordinates (2). I find the ratio to be - .118%, which is smaller than most other models.

  5. Industry 4.0, M2m, Iot&S - All Equal?

    NASA Astrophysics Data System (ADS)

    Dobrin, Carmen

    2014-11-01

    Similarity between Industry 4.0, M2M, IOT&S. Advantages and disadvantages obtained using this three important methods. Decreasing costs while components are getting smaller and smaller in a world with better networking. Influence of business management applications integrated in smart factory logistic. The most important impacts in merging virtual and real production world, with the improvement of best processes having the same goal: creating value by open innovation

  6. Operation of the University of Hawaii 2.2M Telescope on Mauna Kea

    NASA Technical Reports Server (NTRS)

    McLaren, Robert A.

    1999-01-01

    This paper presents a final report from March 1, 1997-February 28, 1999 on the Operation of the University of Hawaii 2.2M Telescope on Mauna Kea. The topics include: 1) Telescope and Instrumentation (Newsletter and Documentation, Scheduling Periods); and 2) Scientific Highlights (The Outer Solar System-Trans-Neptunian Objects and the Kuiper Belt, Comet Hale-Bopp, Near-Earth Asteroids, Asteroid Families, and Galileo Mission Support).

  7. Differential distribution of ELMO1 and ELMO2 mRNAs in the developing mouse brain.

    PubMed

    Katoh, Hironori; Fujimoto, Satoshi; Ishida, Chisaki; Ishikawa, Yukio; Negishi, Manabu

    2006-02-16

    ELMO is an upstream regulator of the Rho family small GTPase Rac. We investigated the distributions of mRNAs of two subtypes of ELMO, ELMO1 and ELMO2, in the developing mouse brain. Both ELMO1 and ELMO2 mRNAs are widely distributed in the developing mouse brain, but they were expressed in different neuronal populations in the cerebral cortex, thalamus, and cerebellum. Thus, ELMO1 and ELMO2 may play different roles during brain development. PMID:16443196

  8. 25. Perimeter acquisition radar building room #2M4, (mezzanine), power supply ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. Perimeter acquisition radar building room #2M4, (mezzanine), power supply room; computer power supply on left and water flow on right. This room is directly below data processing area (room #318). Sign on right reads: High purity water digital rack - Stanley R. Mickelsen Safeguard Complex, Perimeter Acquisition Radar Building, Limited Access Area, between Limited Access Patrol Road & Service Road A, Nekoma, Cavalier County, ND

  9. The Irradiation Facility at the IBR-2M Reactor in Dubna

    NASA Astrophysics Data System (ADS)

    Bulavin, M.; Cheplakov, A.; Kulikov, S.; Kukhtin, V.; Shabalin, E.; Verhoglyadov, A.

    2014-06-01

    After renovation neutron pulsed reactor was successfully put into operation. In view of HL-LHC development, the irradiation facility at the IBR-2m, previously used for the ATLAS Liquid Argon calorimeters electronics and materials certification, has been upgraded to permit accumulation in the warm temperature conditions of the fast neutrons fluences up to k*1017 n/cm2 per one standard reactor operation cycle - 11 days. The first test of materials for ATLAS was conducted.

  10. Development of Lunar Highland REgolith Simulants, NU-LHT-1M,-2M

    NASA Technical Reports Server (NTRS)

    Stoeser, D. B.; Wilson, S. A.; Fikes, J.; McLemore, C.; Rickman, Douglas

    2008-01-01

    As part of a collaborative agreement between the U.S, Geological Survey (USGS) and NASA's Marshall Space Flight Center (MSFC) lunar highland simulants are being produced to support engineers and scientists in developing the technologies required to put a base on the moon by 2024. Two simulants have been produced to date: NU-LHT-1M and -2M (NASA/USGS-Lunar Highlands Type-l & 2 Medium-grained). Using starting material chiefly collected from the Stillwater Mine, Nye, MT, blending protocols were developed based on normative mineralogy calculated from average chemistry, for the Apollo 16 regolith. New technologies using a high temperature remotely coupled plasma melter were developed to generate both high quality and agglutinitic glasses that simulate the glassy components of the regolith. Detailed chemical, mineralogical and physical properties analysis of NU-LHT-1M indicate that it is overall a good surrogate for highlands lunar regolith (our new simulant LHT-2M has not be analyzed yet). The primary difference between 1M and 2M was the inclusion of trace mineralogy (phosphates and sulfide). Plans will also be presented on the future direction of the simulant project.

  11. RESTful M2M Gateway for Remote Wireless Monitoring for District Central Heating Networks

    PubMed Central

    Cheng, Bo; Wei, Zesan

    2014-01-01

    In recent years, the increased interest in energy conservation and environmental protection, combined with the development of modern communication and computer technology, has resulted in the replacement of distributed heating by central heating in urban areas. This paper proposes a Representational State Transfer (REST) Machine-to-Machine (M2M) gateway for wireless remote monitoring for a district central heating network. In particular, we focus on the resource-oriented RESTful M2M gateway architecture, and present an uniform devices abstraction approach based on Open Service Gateway Initiative (OSGi) technology, and implement the resource mapping mechanism between resource address mapping mechanism between RESTful resources and the physical sensor devices, and present the buffer queue combined with polling method to implement the data scheduling and Quality of Service (QoS) guarantee, and also give the RESTful M2M gateway open service Application Programming Interface (API) set. The performance has been measured and analyzed. Finally, the conclusions and future work are presented. PMID:25436650

  12. On the age of the TW Hydrae association and 2M1207334-393254

    NASA Astrophysics Data System (ADS)

    Barrado Y Navascués, D.

    2006-11-01

    Aims.We have estimated the age of the young moving group TW Hydrae Association, a cohort of a few dozen stars and brown dwarfs located near the Sun which share the same kinematic properties and, presumably, the same origin and age. Methods: .The chronology has been determined by analyzing different properties (magnitudes, colors, activity, lithium) of its members and comparing them with several well-known star forming regions and open clusters, as well as theoretical models. In addition, by using medium-resolution optical spectra of two M8 members of the association (2M1139 and 2M1207 - an accreting brown dwarf with a planetary mass companion), we have derived spectral types and measured Hα and lithium equivalent widths. We have also estimated their effective temperature and gravity, which were used to produce an independent age estimation for these two brown dwarfs. We have also collected spectra of 2M1315, a candidate member with a L5 spectral type and measured its Hα equivalent width. Results: .Our age estimate for the association, 10+10-7 Myr, agrees with previous values cited in the literature. In the case of the two brown dwarfs, we have derived an age of 15+15-10 Myr, which also agree with our estimate for the whole group. Conclusions: .We compared our results with recent articles published on the same subject using other techniques, and discuss the limits of the age-dating techniques.

  13. S2M: A Stochastic Simulation Model of Poliovirus Genetic State Transition

    PubMed Central

    Ecale Zhou, Carol L.

    2016-01-01

    Modeling the molecular mechanisms that govern genetic variation can be useful in understanding the dynamics that drive genetic state transition in quasispecies viruses. For example, there is considerable interest in understanding how the relatively benign vaccine strains of poliovirus eventually revert to forms that confer neurovirulence and cause disease (ie, vaccine-derived poliovirus). This report describes a stochastic simulation model, S2M, which can be used to generate hypothetical outcomes based on known mechanisms of genetic diversity. S2M begins with predefined genotypes based on the Sabin-1 and Mahoney wild-type sequences, constructs a set of independent cell-based populations, and performs in-cell replication and cell-to-cell infection cycles while quantifying genetic changes that track the transition from Sabin-1 toward Mahoney. Realism is incorporated into the model by assigning defaults for variables that constrain mechanisms of genetic variability based roughly on metrics reported in the literature, yet these values can be modified at the command line in order to generate hypothetical outcomes driven by these parameters. To demonstrate the utility of S2M, simulations were performed to examine the effects of the rates of replication error and recombination and the presence or absence of defective interfering particles, upon reaching the end states of Mahoney resemblance (semblance of a vaccine-derived state), neurovirulence, genome fitness, and cloud diversity. Simulations provide insight into how modeled biological features may drive hypothetical outcomes, independently or in combination, in ways that are not always intuitively obvious. PMID:27385911

  14. Product analysis of the OH + NO/sub 2/ + M reaction

    SciTech Connect

    Burkholder, J.B.; Hammer, P.D.; Howard, C.J.

    1987-04-09

    A high-resolution Fourier transform spectrometer optically coupled to a fast flow multipass absorption cell was used to spectroscopically study the products of OH + NO/sub 2/ + M ..-->.. HONO/sub 2/ + M (1a) and OH + NO/sub 2/ + M ..-->.. HOONO + M (1b). Infrared absorption spectra of the products of reaction 1 were recorded over the range 1850-3850 cm/sup -1/ for the following conditions: pressure 3 to 850 Torr, temperature 248 to 298 K, and (OH)/sub 0/ = (5 to 100) x 10/sup 11/ molecules cm/sup -3/. The infrared absorption spectrum of HOONO was not observed under these conditions. If the OH stretch band strength of HOONO is equal to that of HONO/sub 2/ this indicates <5% HOONO formation in reaction 1. Quantitative measurements of the conversion of OH to HONO/sub 2/ show that 75/sup +25//sub -10/% of reaction 1 forms HONO/sub 2/. These results are compared with predictions of the branching ratio of reaction 1 obtained from statistical theory.

  15. Dynamic RACH Partition for Massive Access of Differentiated M2M Services

    PubMed Central

    Du, Qinghe; Li, Wanyu; Liu, Lingjia; Ren, Pinyi; Wang, Yichen; Sun, Li

    2016-01-01

    In machine-to-machine (M2M) networks, a key challenge is to overcome the overload problem caused by random access requests from massive machine-type communication (MTC) devices. When differentiated services coexist, such as delay-sensitive and delay-tolerant services, the problem becomes more complicated and challenging. This is because delay-sensitive services often use more aggressive policies, and thus, delay-tolerant services get much fewer chances to access the network. To conquer the problem, we propose an efficient mechanism for massive access control over differentiated M2M services, including delay-sensitive and delay-tolerant services. Specifically, based on the traffic loads of the two types of services, the proposed scheme dynamically partitions and allocates the random access channel (RACH) resource to each type of services. The RACH partition strategy is thoroughly optimized to increase the access performances of M2M networks. Analyses and simulation demonstrate the effectiveness of our design. The proposed scheme can outperform the baseline access class barring (ACB) scheme, which ignores service types in access control, in terms of access success probability and the average access delay. PMID:27043568

  16. CyclinB1/Cdk1 Coordinates Mitochondrial Respiration for Cell Cycle G2/M Progression

    PubMed Central

    Wang, Zhaoqing; Fan, Ming; Candas, Demet; Zhang, Tie-Qiao; Eldridge, Angela; Wachsmann-Hogiu, Sebastian; Ahmed, Kazi M.; Chromy, Brett A.; Nantajit, Danupon; Duru, Nadire; He, Fuchu; Chen, Min; Finkel, Toren; Weinstein, Lee S.; Li, Jian Jian

    2014-01-01

    SUMMARY A substantial amount of mitochondrial energy is required for cell cycle progression. However, the mechanisms coordinating the mitochondrial respiration with G2/M transition, a critical step in cell division, remains to be elucidated. Here we show that a fraction of cell cycle CyclinB1/Cdk1 proteins localizes into the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins including the complex I (CI) subunits in the respiratory chain. The CyclinB1/Cdk1-mediated CI subunit phosphorylation enhances CI activity, whereas deficiency of such phosphorylation in each of the relevant CI subunits results in impairment of CI function. Mitochondria-targeted CyclinB1/Cdk1 increases mitochondrial respiration with enhanced oxygen consumption and ATP generation, which provides cells with efficient bioenergy for G2/M transition and shortens overall cycling time. Thus, CyclinB1/Cdk1-mediated phosphorylation of mitochondrial substrates allows cells to sense and respond to an increased energy demand for G2/M transition, and subsequently to up-regulate mitochondrial respiration for a successful cell cycle progression. PMID:24746669

  17. RESTful M2M gateway for remote wireless monitoring for district central heating networks.

    PubMed

    Cheng, Bo; Wei, Zesan

    2014-01-01

    In recent years, the increased interest in energy conservation and environmental protection, combined with the development of modern communication and computer technology, has resulted in the replacement of distributed heating by central heating in urban areas. This paper proposes a Representational State Transfer (REST) Machine-to-Machine (M2M) gateway for wireless remote monitoring for a district central heating network. In particular, we focus on the resource-oriented RESTful M2M gateway architecture, and present an uniform devices abstraction approach based on Open Service Gateway Initiative (OSGi) technology, and implement the resource mapping mechanism between resource address mapping mechanism between RESTful resources and the physical sensor devices, and present the buffer queue combined with polling method to implement the data scheduling and Quality of Service (QoS) guarantee, and also give the RESTful M2M gateway open service Application Programming Interface (API) set. The performance has been measured and analyzed. Finally, the conclusions and future work are presented. PMID:25436650

  18. Dynamic RACH Partition for Massive Access of Differentiated M2M Services.

    PubMed

    Du, Qinghe; Li, Wanyu; Liu, Lingjia; Ren, Pinyi; Wang, Yichen; Sun, Li

    2016-01-01

    In machine-to-machine (M2M) networks, a key challenge is to overcome the overload problem caused by random access requests from massive machine-type communication (MTC) devices. When differentiated services coexist, such as delay-sensitive and delay-tolerant services, the problem becomes more complicated and challenging. This is because delay-sensitive services often use more aggressive policies, and thus, delay-tolerant services get much fewer chances to access the network. To conquer the problem, we propose an efficient mechanism for massive access control over differentiated M2M services, including delay-sensitive and delay-tolerant services. Specifically, based on the traffic loads of the two types of services, the proposed scheme dynamically partitions and allocates the random access channel (RACH) resource to each type of services. The RACH partition strategy is thoroughly optimized to increase the access performances of M2M networks. Analyses and simulation demonstrate the effectiveness of our design. The proposed scheme can outperform the baseline access class barring (ACB) scheme, which ignores service types in access control, in terms of access success probability and the average access delay. PMID:27043568

  19. The ASTRI SST-2M prototype for the Cherenkov Telescope Array: primary mirror characterization by deflectometry

    NASA Astrophysics Data System (ADS)

    Sironi, Giorgia; Canestrari, Rodolfo

    2015-09-01

    In 2014 the ASTRI Collaboration, led by the Italian National Institute for Astrophysics, has constructed an end-to-end prototype of a dual-mirror imaging air Cherenkov telescope, proposed for the small size class of telescopes for the Cherenkov Telescope Array. The prototype, named ASTRI SST-2M, has been installed at the observing station located at Serra La Nave (Italy). In this project the Brera Astronomical Observatory was responsible for the production and the testing of the primary mirror. The ASTRI SST-2M telescope's primary mirror has an aperture of ~ 4 m, a polynomial design, and consists of 18 individual hexagonal facets. These characteristics require the production and testing of panels with a typical size of ~1 m vertex-to-vertex and with an aspheric component of up to several millimetres. The mirror segments were produced assembling a sandwich of thin glass foils bent at room temperature to reach the desired shape. For the characterization of the mirrors we developed an ad-hoc deflectometry facility that works as an inverse Ronchi test in combination with a ray-tracing code. In this contribution we report the results of the deflectometric measurements performed on the primary mirror segments of the ASTRI SST-2M dual mirror telescope. The expected point spread function and the contributions to the degradation of the image quality are studied.

  20. Signature of the Superatom to Superhalogen Behavior of Aun(BO2)m clusters

    NASA Astrophysics Data System (ADS)

    Kandalam, Anil; Gotz, Matthias; Willis, Mary; Gantefor, Gerd; Jena, Puru

    2010-03-01

    We report the discovery of a new class of clusters consisting of Aun(BO2)m which formed during the oxygenation of gold clusters when boron nitride was used as insulation in the pulsed arc cluster ion source (PACIS). Using DFT based calculations, we trace the origin of these species to be due to the unusual stability of the BO2 moiety as well as shed light on their formation process. PES measurements and the corresponding DFT calculations further reveal some rather remarkable properties of Aun(BO2)m clusters such as large HOMO-LUMO gaps in the range of 3.00 eV -- 3.95 eV and electron affinities substantially larger than that of F, the most electronegative element in the periodic table. In addition, some of the most predominant features of the electronic structure of the bare Au clusters, namely odd-even alternation in the electron affinity, are preserved in the Aun(BO2) species. The synergy between theory and experiment illustrates that Aun(BO2)m clusters, behave as superatoms and superhalogens, opening the door for the synthesis of a new class of cluster-assembled materials.

  1. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  2. Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Cremonesi, Oliviero

    2016-05-01

    After more than 3/4 of century from its proposal, Neutrinoless Double Beta Decay (NLDBD) is still missing observation and continues to represent the only practical method for investigating the Dirac/Majorana nature of neutrinos. In case neutrinos would be Majorana particles, NLDBD would provide unique informations on their properties (absolute mass scale and Majorana phases). Boosted by the discovery of neutrino oscillations, a number of experiments with improved sensitivity have been proposed in the past decade. Some of them have recently started operation and others are ready to start. They will push the experimental sensitivity on the decay halflife beyond 1026 year, starting to analyze the region of the inverted mass hierarchy. The status and perspectives of the ongoing experimental effort are reviewed. Uncertainties coming from the calculation othe decay nuclear matrix elements (NME) as well as the recently suggested possibility of a relevant quenching of the axial coupling constant are also discussed.

  3. Beta systems error analysis

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The atmospheric backscatter coefficient, beta, measured with an airborne CO Laser Doppler Velocimeter (LDV) system operating in a continuous wave, focussed model is discussed. The Single Particle Mode (SPM) algorithm, was developed from concept through analysis of an extensive amount of data obtained with the system on board a NASA aircraft. The SPM algorithm is intended to be employed in situations where one particle at a time appears in the sensitive volume of the LDV. In addition to giving the backscatter coefficient, the SPM algorithm also produces as intermediate results the aerosol density and the aerosol backscatter cross section distribution. A second method, which measures only the atmospheric backscatter coefficient, is called the Volume Mode (VM) and was simultaneously employed. The results of these two methods differed by slightly less than an order of magnitude. The measurement uncertainties or other errors in the results of the two methods are examined.

  4. Predicting neutrinoless double beta decay

    SciTech Connect

    Hirsch, M.; Villanova del Moral, A.; Valle, J.W.F.

    2005-11-01

    We give predictions for the neutrinoless double beta decay rate in a simple variant of the A{sub 4} family symmetry model. We show that there is a lower bound for the {beta}{beta}{sub 0{nu}} amplitude even in the case of normal hierarchical neutrino masses, corresponding to an effective mass parameter vertical bar m{sub ee} vertical bar {>=}0.17{radical}({delta}m{sub ATM}{sup 2}). This result holds both for the CP conserving and CP violating cases. In the latter case we show explicitly that the lower bound on vertical bar m{sub ee} vertical bar is sensitive to the value of the Majorana phase. We conclude therefore that in our scheme, {beta}{beta}{sub 0{nu}} may be accessible to the next generation of high sensitivity experiments.

  5. Possible role of TIEG1 as a feedback regulator of myostatin and TGF-{beta} in myoblasts

    SciTech Connect

    Miyake, Masato; Hayashi, Shinichiro; Iwasaki, Shunsuke; Chao, Guozheng; Takahashi, Hideyuki; Watanabe, Kouichi; Ohwada, Shyuichi; Aso, Hisashi; Yamaguchi, Takahiro

    2010-03-19

    Myostatin and TGF-{beta} negatively regulate skeletal muscle development and growth. Both factors signal through the Smad2/3 pathway. However, the regulatory mechanism of myostatin and TGF-{beta} signaling remains unclear. TGF-{beta} inducible early gene (TIEG) 1 is highly expressed in skeletal muscle and has been implicated in the modulation of TGF-{beta} signaling. These findings prompted us to investigate the effect of TIEG1 on myostatin and TGF-{beta} signaling using C2C12 myoblasts. Myostatin and TGF-{beta} induced the expression of TIEG1 and Smad7 mRNAs, but not TIEG2 mRNA, in proliferating C2C12 cells. When differentiating C2C12 myoblasts were stimulated by myostatin, TIEG1 mRNA was up-regulated at a late stage of differentiation. In contrast, TGF-{beta} enhanced TIEG1 expression at an early stage. Overexpression of TIEG1 prevented the transcriptional activation of Smad by myostatin and TGF-{beta} in both proliferating or differentiating C2C12 cells, but the expression of Smad2 and Smad7 mRNAs was not affected. Forced expression of TIEG1 inhibited myogenic differentiation but did not cause more inhibition than the empty vector in the presence of myostatin or TGF-{beta}. These results demonstrate that TIEG1 is one possible feedback regulator of myostatin and TGF-{beta} that prevents excess action in myoblasts.

  6. Solution structure of oxidized rat microsomal cytochrome b5 in the presence of 2 M guanidinium chloride: monitoring the early steps in protein unfolding.

    PubMed

    Arnesano, F; Banci, L; Bertini, I; Koulougliotis, D

    1998-12-01

    " supporting the heme, whose plane is also rotated by approximately 10 degrees around an axis connecting the C2 and C8 carbon atoms. The initial steps of the unfolding process involve breaking of a few hydrogen bonds that stabilize local structural conformations. The hydrogen bond between Ser 64 and propionate 7, which stabilizes the heme binding to the protein frame, is broken in the presence of 2 M GdmCl. The same occurs for two hydrogen bonds between two beta-strands (beta2 and beta3), thus inducing the disruption of one of the antiparallel beta-sheets forming one side of the heme cavity. Our results are critically discussed in connection with the native-state protein local backbone mobility characteristics and point to the backbone carbons of Glu 37 and Ser 64 being the first "breaking points" of the protein frame once the global unfolding reaction is initiated at a somewhat higher concentration of denaturant. PMID:9836603

  7. High Temperature Stability of Potassium Beta Alumina

    NASA Technical Reports Server (NTRS)

    Williams, R. M.; Kisor, A.; Ryan, M. A.

    1996-01-01

    None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

  8. CNP2 mRNA directs synthesis of both CNP1 and CNP2 polypeptides.

    PubMed

    O'Neill, R C; Minuk, J; Cox, M E; Braun, P E; Gravel, M

    1997-10-15

    The ribosome scanning model for translational initiation predicts that eukaryotic mRNAs should, as a rule, be monocistronic. However, cases have recently been described of eukaryotic mRNAs producing more than one protein through alternative translational initiation at several different AUG codons. The present work reports the occurrence of two translational start sites on the mRNA encoding isoform 2 of the myelin marker enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in rat and mouse. We show that the CNP2 mRNA is able to direct synthesis of not only CNP2, but also CNP1 polypeptide. Immunoprecipitation experiments using a polyclonal antibody directed against CNP detect both CNP isoforms in tissues or cell lines expressing only the CNP2 transcript. Thus, the synthesis of CNP1 and CNP2 polypeptides must be encoded by the CNP2 transcript. In vitro translation of synthetic CNP2 mRNA demonstrates that both CNP isoforms are synthesized by initiation at different AUG codons. Furthermore, by introducing mutations to "switch off" translation from the second in-frame AUG codon in the CNP2 cDNA, and transfecting 293T cells with those constructs, we are able to correlate the production of CNP1 and CNP2 with different translational start sites. These results lead us to conclude that the CNP2 mRNA is able to produce both CNP1 and CNP2 polypeptides. This investigation has altered our understanding of the temporal expression of the CNP protein isoforms during development of the central nervous system (CNS). PMID:9373034

  9. The mini-array of ASTRI SST-2M telescopes, precursors for the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Pareschi, Giovanni; Bonnoli, Giacomo; Vercellone, Stefano; ASTRI Collaboration; CTA Consortium

    2016-05-01

    In the framework of the Cherenkov Telescope Array (CTA) Observatory, the Italian National Institute of Astrophysics (INAF) has recently inaugurated in Sicily (Italy), at the Serra La Nave astronomical site on the slopes of Mount Etna, a large field of view (FoV, ~ 9.6°) dual-mirror prototype (ASTRI SST-2M) of the CTA small size class of telescopes (SST). The CTA plans to install about 70 SST in the southern site to allow the study of the gamma rays from a few TeV up to hundreds of TeV. The ASTRI SST-2M telescope prototype has been developed following an end-to-end approach, since it includes the entire system of structure, mirrors optics (primary and secondary mirrors), camera, and control/acquisition software. A remarkable performance improvement could come from the operation of the ASTRI mini-array, led by INAF in synergy with the Universidade de Sao Paulo (Brazil) and the North-West University (South Africa). The ASTRI mini-array will be composed of nine ASTRI SST-2M units and it is proposed as a precursor and initial seed of the CTA to be installed at the final CTA southern site. Apart from the assessment of a number of technological aspects related to the CTA, the ASTRI mini-array will, if compared for instance to H.E.S.S., extend the point source sensitivity up to ~ 100 TeV, also improving it above 5-10 TeV. Moreover, the unprecedented width of the FoV, with its homogeneous acceptance and angular resolution, will significantly contribute to the achievement of original results during the early CTA science phase.

  10. Towards Efficient Mobile M2M Communications: Survey and Open Challenges

    PubMed Central

    Pereira, Carlos; Aguiar, Ana

    2014-01-01

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways. PMID:25333291

  11. Towards efficient mobile M2M communications: survey and open challenges.

    PubMed

    Pereira, Carlos; Aguiar, Ana

    2014-01-01

    Machine-to-Machine (M2M) communications enable networked devices and services to exchange information and perform actions seamlessly without the need for human intervention. They are viewed as a key enabler of the Internet of Things (IoT) and ubiquitous applications, like mobile healthcare, telemetry, or intelligent transport systems. We survey existing work on mobile M2M communications, we identify open challenges that have a direct impact on performance and resource usage efficiency, especially the impact on energy efficiency, and we review techniques to improve communications. We review the ETSI standard and application protocols, and draw considerations on the impact of their use in constrained mobile devices. Nowadays, smartphones are equipped with a wide range of embedded sensors, with varied local and wide area connectivity capabilities, and thus they offer a unique opportunity to serve as mobile gateways for other more constrained devices with local connectivity. At the same time, they can gather context data about users and environment from the embedded sensors. These capabilities may be crucial for mobile M2M applications. Finally, in this paper, we consider a scenario where smartphones are used as gateways that collect and aggregate data from sensors in a cellular network. We conclude that, in order for their use to the feasible in terms of a normal depletion time of a smartphone's battery, it is a good advice to maximize the collection of data necessary to be transmitted from nearby sensors, and maximize the intervals between transmissions. More research is required to devise energy efficient transmission methods that enable the use of smartphones as mobile gateways. PMID:25333291

  12. Results on E+ E- to Hadrons Cross Sections from VEPP-2M and BaBar

    SciTech Connect

    Solodov, E.; /Novosibirsk, IYF

    2011-11-22

    In 1992-2000, data on e{sup +}e{sup -} annihilation into hadrons were collected in the energy range 0.36 < {radical}s < 1.4 GeV with the CMD-2 and SND detectors at the VEPP-2M collider in Novosibirsk. The results of the R(s) measurements in these experiments are presented. The radiative return program at BaBar also allows to study low energy e{sup +}e{sup -} annihilation and overview of the results are presented in this paper.

  13. A 2 m inelastic x-ray scattering spectrometer at CMC-XOR, Advanced Photon Source.

    SciTech Connect

    Hill, J. P.; Coburn, D. S.; Kim, Y. J.; Gog, T.; Casa, D. M.; Kodituwakku, C. N.; Sinn, H.; X-Ray Science Division; BNL; Univ. of Toronto

    2007-07-01

    The design and commissioning of an inelastic X-ray scattering instrument at CMC-XOR at the Advanced Photon Source is reported. The instrument features a 2 m vertical-scattering arm with a novel counterweight design to reduce the twisting moment as the arm is moved in the scattering plane. A Ge(733) spherical analyzer was fabricated and an overall resolution of 118 meV (FWHM) was obtained with a Si(444) monochromator and a Si(111) pre-monochromator. Early results from a representative cuprate, La{sub 2}CuO{sub 4}, are reported.

  14. The r-step Fibonacci-Hurwitz sequences in the binary polyhedral group <2, m, 2>

    NASA Astrophysics Data System (ADS)

    Deveci, Ömür; Ćiçekci, Deniz

    2016-04-01

    In [1], Deveci et al. defined the r-step Fibonacci-Hurwitz sequences from the Hurwitz matrices obtained from the characteristic polynomial of the k-step Fibonacci sequence. Also, they extended the r-step Fibonacci-Hurwitz sequences to groups. In this work, we obtain the periods of the r-step Fibonacci-Hurwitz sequences in the binary polyhedral group <2, m, 2> for generating triple {x, y, z} and generating pair {y, z} by the aid of the periods of the r-step Fibonacci-Hurwitz sequences according to modulo m.

  15. Robotic operation of the DAO 1.2-m telescope and McKellar spectrograph

    NASA Astrophysics Data System (ADS)

    Monin, D.; Saddlemyer, L.; Bohlender, D.

    2014-12-01

    The DAO 1.2-m telescope has been successfully used to obtain astronomical spectra in unattended robotic mode for a decade and approximately 2/3 of the nights scheduled on the telescope are now used in this fashion. The availability of such robotic operation has boosted the telescope's subscription rate by approximately 50% since telescope users no longer have to travel to the DAO in order to conduct their observing programs. An overview of the robotic system and some details of its operation are presented.

  16. The New 2-M RCC Telescope in the Northern Caucasus for Modern Astronomical Research

    NASA Astrophysics Data System (ADS)

    Tarady, V. K.; Yatskiv, Ya. S.

    A new 2-m Ritchey-Chretien-Coude (RCC) telescope in the Northern Caucasus (the Kabardin-Balkar Republic, Russian Federation) is nearing being put into operation. It has been developed by the National Academy of Sciences of the Ukraine on the Terskol peak (near Elbrus) which seems to be one of the best sites for astronomical ground observations in terms of its astroclimate. This paper describes the present status of the telescope, its instrumentation and outlines the scientific problems that can be solved using the telescope.

  17. Observation of Surface Composition during ECR Discharge Cleaning in JFT-2M

    NASA Astrophysics Data System (ADS)

    Matsuzaki, Yoshimi; Ohtsuka, Hideo

    1986-03-01

    Surface composition on a molybdenum sample has been observed during ECR discharge cleaning (ECR-DC) by Auger electron spectroscopy in JFT-2M. ECR-DC reduces oxygen levels to one-thrid of those before exposure within thirty minutes, and the molybdenum concentration increases up to a factor of three during ECR-DC. Carbon levels decrease once, then increase gradually. In the later phase Auger line shapes are similar to pure carbon. Sulfur, which appears under 120°C baking, surfaces from the stainless steel of the chamber as a result of the baking, and is sputtered by plasmas and deposited on the sample.

  18. Temperature and Pressure Dependence of the Reaction S + CS (+M) → CS2 (+M).

    PubMed

    Glarborg, Peter; Marshall, Paul; Troe, Jürgen

    2015-07-16

    Experimental data for the unimolecular decomposition of CS2 from the literature are analyzed by unimolecular rate theory with the goal of obtaining rate constants for the reverse reaction S + CS (+M) → CS2 (+M) over wide temperature and pressure ranges. The results constitute an important input for the kinetic modeling of CS2 oxidation. CS2 dissociation proceeds as a spin-forbidden process whose detailed properties are still not well understood. The role of the singlet-triplet transition involved is discussed. PMID:25669352

  19. Ion heat pulse after sawtooth crash in the JFT-2M tokamak

    NASA Astrophysics Data System (ADS)

    Miura, Y.; Okano, F.; Suzuki, N.; Mori, M.; Hoshino, K.; Maeda, H.; Takizuka, T.; Itoh, K.; Itoh, S.

    1993-08-01

    The ion heat pulse after sawtooth crash is studied with the time-of-flight neutral measurement on the JFT-2M tokamak. The rapid change of the bulk ion energy distribution near the edge is observed after sawtooth crash. The delay time is measured and the effective measuring position is estimated by a neutral transport code, then the thermal conductivity, chi(sub i)(exp HP), of about 15 +/- 10 sq m/sec is evaluated for the L-mode plasma. The simple diffusive model with constant chi(sub i)(exp HP), however, does not explain the amplitude of the pulse in the ion energy distribution.

  20. Chlorine nitrate - The sole product of the ClO + NO2 + M recombination

    NASA Technical Reports Server (NTRS)

    Margitan, J. J.

    1983-01-01

    A laser operating at 266 nm is used to photolyze the product of the ClO + NO2 + M reaction, and the yield of Cl atoms, measured by resonance fluorescence, is found to be identical with that from equivalent concentrations of ClONO2. This is interpreted as a strong indication that no other isomers are formed in the recombination reaction. Evidence for isomers is surveyed, and the apparent forward-and-reverse-rate constant discrepancy is explained as a probable uncertainty in the thermochemistry.

  1. Credit WCT. Original 2A" x 2M" color negative is housed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Credit WCT. Original 2-A" x 2-M" color negative is housed in the JPL Photography Laboratory, Pasadena, California. Photo shows John Morrow in charge of milling operations on coupons ("dogbones") of propellant on an Index milling machine. Coupons were milled to precise dimensions for tensile tests. Note that two sprinkler heads have been placed in very close proximity to the milling table for fire suppression purposes (JPL negative no. JPL-10283AC, 27 January 1989) - Jet Propulsion Laboratory Edwards Facility, Preparation Building, Edwards Air Force Base, Boron, Kern County, CA

  2. Adenosine induces G2/M cell-cycle arrest by inhibiting cell mitosis progression.

    PubMed

    Jia, Kun-Zhi; Tang, Bo; Yu, Lu; Cheng, Wei; Zhang, Rong; Zhang, Jian-Fa; Hua, Zi-Chun

    2010-01-01

    Cellular adenosine accumulates under stress conditions. Few papers on adenosine are concerned with its function in the cell cycle. The cell cycle is the essential mechanism by which all living things reproduce and the target machinery when cells encounter stresses, so it is necessary to examine the relationship between adenosine and the cell cycle. In the present study, adenosine was found to induce G-2/M cell-cycle arrest. Furthermore, adenosine was found to modulate the expression of some important proteins in the cell cycle, such as cyclin B and p21, and to inhibit the transition of metaphase to anaphase in mitosis. PMID:19947935

  3. Mammalian mitochondrial beta-oxidation.

    PubMed Central

    Eaton, S; Bartlett, K; Pourfarzam, M

    1996-01-01

    The enzymic stages of mammalian mitochondrial beta-oxidation were elucidated some 30-40 years ago. However, the discovery of a membrane-associated multifunctional enzyme of beta-oxidation, a membrane-associated acyl-CoA dehydrogenase and characterization of the carnitine palmitoyl transferase system at the protein and at the genetic level has demonstrated that the enzymes of the system itself are incompletely understood. Deficiencies of many of the enzymes have been recognized as important causes of disease. In addition, the study of these disorders has led to a greater understanding of the molecular mechanism of beta-oxidation and the import, processing and assembly of the beta-oxidation enzymes within the mitochondrion. The tissue-specific regulation, intramitochondrial control and supramolecular organization of the pathway is becoming better understood as sensitive analytical and molecular techniques are applied. This review aims to cover enzymological and organizational aspects of mitochondrial beta-oxidation together with the biochemical aspects of inherited disorders of beta-oxidation and the intrinsic control of beta-oxidation. PMID:8973539

  4. Effect of beta blockade and beta stimulation on stage fright.

    PubMed

    Brantigan, C O; Brantigan, T A; Joseph, N

    1982-01-01

    Stage fright, physiologically the "fight or flight" reaction, is a disabling condition to the professional musician. Because it is mediated by the sympathetic nervous system, we have investigated the effects of beta blockade on musical performance with propranolol in a double blind fashion and the effects of beta stimulation using terbutaline. Stage fright symptoms were evaluated in two trials, which included a total of 29 subjects, by questionnaire and by the State Trai Anxiety Inventory. Quality of musical performance was evaluated by experienced music critics. Beta blockade eliminates the physical impediments to performance caused by stage fright and even eliminates the dry mouth so frequently encountered. The quality of musical performance as judged by experienced music critics is significantly improved. This effect is achieved without tranquilization. Beta stimulating drugs increase stage fright problems, and should be used in performing musicians only after consideration of the detrimental effects which they may have on musical performance. PMID:6120650

  5. Variants of beta-glucosidase

    SciTech Connect

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian

    2015-07-14

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  6. Variants of beta-glucosidases

    SciTech Connect

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian

    2014-10-07

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  7. Variants of beta-glucosidases

    DOEpatents

    Fidantsef, Ana; Lamsa, Michael; Clancy, Brian Gorre

    2008-08-19

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  8. Variants of beta-glucosidase

    DOEpatents

    Fidantsef, Ana; Lamsa, Michael; Gorre-Clancy, Brian

    2009-12-29

    The present invention relates to variants of a parent beta-glucosidase, comprising a substitution at one or more positions corresponding to positions 142, 183, 266, and 703 of amino acids 1 to 842 of SEQ ID NO: 2 or corresponding to positions 142, 183, 266, and 705 of amino acids 1 to 844 of SEQ ID NO: 70, wherein the variant has beta-glucosidase activity. The present invention also relates to nucleotide sequences encoding the variant beta-glucosidases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  9. Machine to machine (M2M) technology in demand responsive commercial buildings

    SciTech Connect

    Watson, David S.; Piette, Mary Ann; Sezgen, Osman; Motegi, Naoya; ten Hope, Laurie

    2004-08-01

    Machine to Machine (M2M) is a term used to describe the technologies that enable computers, embedded processors, smart sensors, actuators and mobile devices to communicate with one another, take measurements and make decisions--often without human intervention. M2M technology was applied to five commercial buildings in a test. The goal was to reduce electric demand when a remote price signal rose above a predetermine price. In this system, a variable price signal was generated from a single source on the Internet and distributed using the meta-language, XML (Extensible Markup Language). Each of five commercial building sites monitored the common price signal and automatically shed site-specific electric loads when the price increased above predetermined thresholds. Other than price signal scheduling, which was set up in advance by the project researchers, the system was designed to operate without human intervention during the two-week test period. Although the buildings responded to the same price signal, the communication infrastructures used at each building were substantially different. This study provides an overview of the technologies used at each building site, the price generator/server, and each link in between. Network architecture, security, data visualization and site-specific system features are characterized. The results of the test are discussed, including: functionality at each site, measurement and verification techniques, and feedback from energy managers and building operators. Lessons learned from the test and potential implications for widespread rollout are provided.

  10. Role of reactive oxygen species and MAPKs in vanadate-induced G(2)/M phase arrest.

    PubMed

    Zhang, Zhuo; Leonard, Stephen S; Huang, Chuanshu; Vallyathan, Val; Castranova, Vince; Shi, Xianglin

    2003-05-15

    Cell growth arrest is an important mechanism in maintaining genomic stability and integrity in response to environmental stress. Using the human lung alveolar epithelial cancer cell line A549, we investigated the role of reactive oxygen species (ROS), extracellular signal-regulated protein kinase (ERK), and p38 protein kinase in vanadate-induced cell growth arrest. Exposure of cells to vanadate led to cell growth arrest at the G(2)/M phase and caused upregulation of p21 and phospho-cdc2 and degradation of cdc25C in a time- and dose-dependent manner. Vanadate stimulated mitogen-activated protein kinases (MAPKs) family members, as determined by the phosphorylation of ERK and p38. PD98059, an inhibitor of ERK, and SB202190, an inhibitor of p38, inhibited vanadate-induced cell growth arrest, upregulation of p21 and cdc2, and degradation of cdc25C. In addition to hydroxyl radical ((*)OH) formation, cellular reduction of vanadate generated superoxide radical (O(2)(*)(-)) and hydrogen peroxide (H(2)O(2)), as determined by confocal microscopy using specific dyes. Generation of O(2)(*)(-) and H(2)O(2) was inhibited by specific antioxidant enzymes, superoxide dismutase (SOD) and catalase, respectively. ROS activate ERK and p38, which in turn upregulate p21 and cdc2 and cause degradation of cdc25C, leading to cell growth arrest at the G(2)/M phase. Specific ROS affect different MAPK family members and cell growth regulatory proteins with different potencies. PMID:12726921

  11. The ASTRI SST-2M prototype for the Cherenkov Telescope Array: opto-mechanical test results

    NASA Astrophysics Data System (ADS)

    Canestrari, Rodolfo; Giro, Enrico; Antolini, Elisa; Bonnoli, Giacomo; Cascone, Enrico; La Palombara, Nicola; Leto, Giuseppe; Pareschi, Giovanni; Scuderi, Salvo; Stringhetti, Luca; Tanci, Claudio; Tosti, Gino

    2015-09-01

    The Cherenkov Telescope Array (CTA) observatory, with a combination of large-, medium-, and small-size telescopes (LST, MST and SST, respectively), will represent the next generation of imaging atmospheric Cherenkov telescopes. It will explore the very high-energy domain from a few tens of GeV up to few hundreds of TeV with unprecedented sensitivity, angular resolution and imaging resolution. In this framework, the Italian ASTRI program, led by the Italian National Institute of Astrophysics (INAF), is currently developing a scientific and technological SST dual-mirror end-to-end prototype named ASTRI SST-2M. It is a 4-meter class telescope; it adopts an aplanatic, wide-field, double-reflection optical layout in a Schwarzschild-Couder configuration. The ASTRI SST-2M telescope structure and mirrors have been already installed at the INAF observing station at Serra La Nave, on Mt. Etna (Sicily, Italy). In this contribution we report about the on-site deployment and the latest results on the opto-mechanical performance test conducted soon after the telescope installation

  12. HERSCHEL/HIFI OBSERVATIONS OF HYDROGEN FLUORIDE TOWARD SAGITTARIUS B2(M)

    SciTech Connect

    Monje, R. R.; Emprechtinger, M.; Phillips, T. G.; Lis, D. C.; Goldsmith, P. F.; Bergin, E. A.; Bell, T. A.; Neufeld, D. A.; Sonnentrucker, P.

    2011-06-10

    Herschel/HIFI observations have revealed the presence of widespread absorption by hydrogen fluoride (HF) J = 1-0 rotational transition, toward a number of Galactic sources. We present observations of HF J = 1-0 toward the high-mass star-forming region Sagittarius B2(M). The spectrum obtained shows a complex pattern of absorption, with numerous features covering a wide range of local standard of rest velocities (-130 to 100 km {sup -1}). An analysis of this absorption yields HF abundances relative to H{sub 2} of {approx}1.3 x 10{sup -8}, in most velocity intervals. This result is in good agreement with estimates from chemical models, which predict that HF should be the main reservoir of gas-phase fluorine under a wide variety of interstellar conditions. Interestingly, we also find velocity intervals in which the HF spectrum shows strong absorption features that are not present, or are very weak, in spectra of other molecules, such as {sup 13}CO (1-0) and CS (2-1). HF absorption reveals components of diffuse clouds with small extinction that can be studied for the first time. Another interesting observation is that water is significantly more abundant than hydrogen fluoride over a wide range of velocities toward Sagittarius B2(M), in contrast to the remarkably constant H{sub 2}O/HF abundance ratio with average value close to unity measured toward other Galactic sources.

  13. Utilizing G2/M retention effect to enhance tumor accumulation of active targeting nanoparticles

    PubMed Central

    Hu, Guanlian; Cun, Xingli; Ruan, Shaobo; Shi, Kairong; Wang, Yang; Kuang, Qifang; Hu, Chuan; Xiao, Wei; He, Qin; Gao, Huile

    2016-01-01

    In recent years, active targeting strategies by ligand modification have emerged to enhance tumor accumulation of NP, but their clinical application was strictly restricted due to the complex preparation procedures, poor stability and serious toxicity. An effective and clinical translational strategy is required to satisfy the current problems. Interestingly, the internalization of NP is intimately related with cell cycle and the expression of receptors is not only related with cancer types but also cell cycle progression. So the cellular uptake of ligand modified NP may be related with cell cycle. However, few investigations were reported about the relationship between cell cycle and the internalization of ligand modified NP. Herein, cellular uptake of folic acid (FA) modified NP after utilizing chemotherapeutic to retain the tumor cells in G2/M phase was studied and a novel strategy was designed to enhance the active targeting effect. In our study, docetaxel (DTX) notably synchronized cells in G2/M phase and pretreatment with DTX highly improved in vitro and in vivo tumor cell targeting effect of FA decorated NP (FANP). Since FA was a most common used tumor active targeting ligand, we believe that this strategy possesses broader prospects in clinical application for its simplicity and effectiveness. PMID:27273770

  14. Study of the Polarization Strategy for Electron Cyclotron Heating Systems on HL-2M

    NASA Astrophysics Data System (ADS)

    Zhang, F.; Huang, M.; Xia, D. H.; Song, S. D.; Wang, J. Q.; Huang, B.; Wang, H.

    2016-06-01

    As important components integrated in transmission lines of electron cyclotron heating systems, polarizers are mainly used to obtain the desired polarization for highly efficient coupling between electron cyclotron waves and plasma. The polarization strategy for 105-GHz electron cyclotron heating systems of HL-2M tokamak is studied in this paper. Considering the polarizers need high efficiency, stability, and low loss to realize any polarization states, two sinusoidal-grooved polarizers, which include a linear polarizer and an elliptical polarizer, are designed with the coordinate transformation method. The parameters, the period p and the depth d, of two sinusoidal-grooved polarizers are optimized by a phase difference analysis method to achieve an almost arbitrary polarization. Finally, the optimized polarizers are manufactured and their polarization characteristics are tested with a low-power test platform. The experimental results agree well with the numerical calculations, indicating that the designed polarizers can meet the polarization requirements of the electron cyclotron heating systems of HL-2M tokamak.

  15. IEEE802.15.6 NB portable BAN clinic and M2M international standardization.

    PubMed

    Kuroda, Masahiro; Nohara, Yasunobu

    2013-01-01

    The increase of non communicable diseases (NCDs) will change the direction of health services to emphasize the role of preventive medicine in healthcare services. The first short-range medical body are network (BAN) standard IEEE802.15.6 is expected to be used for secure and user-friendly sensor devices for portable medical equipment. A BAN is an enabler for uploading medical data to a backend system for remote diagnoses and treatment. Machine-to-Machine (M2M) infrastructure is also a key technology for providing flexible and affordable services extending electronic health record (EHR) systems. This paper proposes a BAN-based portable clinic that collects health-check data from user-friendly medical devices and sensors and sends the data to a local backend server, and it evaluates the clinic in fields of actual usage. We discuss issues experienced from actual deployment of the system and focus on integrating it into upcoming healthcare M2M infrastructure to achieve affordable and dependable clinic services. We explain the components and workflow of the clinic and the system model. The system is set up at a temporary health center and has a network link to a remote medical help center. The paper concludes with our plan to introduce our system to contribute to internationally standardized preventive medicine. PMID:24110023

  16. Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing.

    PubMed

    Trochet, Delphine; Prudhon, Bernard; Jollet, Arnaud; Lorain, Stéphanie; Bitoun, Marc

    2016-01-01

    Dynamin 2 (DNM2) is a large GTPase, ubiquitously expressed, involved in membrane trafficking and regulation of actin and microtubule cytoskeletons. DNM2 mutations cause autosomal dominant centronuclear myopathy which is a rare congenital myopathy characterized by skeletal muscle weakness and histopathological features including nuclear centralization in absence of regeneration. No curative treatment is currently available for the DNM2-related autosomal dominant centronuclear myopathy. In order to develop therapeutic strategy, we evaluated here the potential of Spliceosome-Mediated RNA Trans-splicing technology to reprogram the Dnm2-mRNA in vitro and in vivo in mice. We show that classical 3'-trans-splicing strategy cannot be considered as accurate therapeutic strategy regarding toxicity of the pre-trans-splicing molecules leading to low rate of trans-splicing in vivo. Thus, we tested alternative strategies devoted to prevent this toxicity and enhance frequency of trans-splicing events. We succeeded to overcome the toxicity through a 5'-trans-splicing strategy which also allows detection of trans-splicing events at mRNA and protein levels in vitro and in vivo. These results suggest that the Spliceosome-Mediated RNA Trans-splicing strategy may be used to reprogram mutated Dnm2-mRNA but highlight the potential toxicity linked to the molecular tools which have to be carefully investigated during preclinical development. PMID:27623444

  17. Interferon Beta-1b Injection

    MedlinePlus

    ... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... interferon beta-1b injection at around the same time of day each time you inject it. Follow ...

  18. Peginterferon Beta-1a Injection

    MedlinePlus

    ... course of disease where symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which ... peginterferon beta-1a injection at around the same time of day each time you inject it. Follow ...

  19. Genetics Home Reference: beta thalassemia

    MedlinePlus

    ... a blood disorder that reduces the production of hemoglobin . Hemoglobin is the iron-containing protein in red blood ... In people with beta thalassemia , low levels of hemoglobin lead to a lack of oxygen in many ...

  20. Questions Students Ask: Beta Decay.

    ERIC Educational Resources Information Center

    Koss, Jordan; Hartt, Kenneth

    1988-01-01

    Answers a student's question about the emission of a positron from a nucleus. Discusses the problem from the aspects of the uncertainty principle, beta decay, the Fermi Theory, and modern physics. (YP)

  1. Physics with Beta-Beam

    SciTech Connect

    Agarwalla, Sanjib Kumar; Choubey, Sandhya; Raychaudhuri, Amitava

    2008-02-21

    A Beta-beam would be a high intensity source of pure {nu}{sub e} and/or {nu}-bar{sub e} flux with known spectrum, ideal for precision measurements. Myriad of possible set-ups with suitable choices of baselines, detectors and the beta-beam neutrino source with desired energies have been put forth in the literature. In this talk we present a comparitive discussion of the physics reach of a few such experimental set-ups.

  2. Medium Beta Superconducting Accelerating Structures

    SciTech Connect

    Jean Delayen

    2001-09-01

    While, originally, the development of superconducting structures was cleanly divided between low-beta resonators for heavy ions and beta=1 resonators for electrons, recent interest in protons accelerators (high and low current, pulsed and cw) has necessitated the development of structures that bridge the gap between the two. These activities have resulted both in new geometries and in the adaptation of well-known geometries optimized to this intermediate velocity range. Their characteristics and properties are reviewed.

  3. Beta function and anomalous dimensions

    SciTech Connect

    Pica, Claudio; Sannino, Francesco

    2011-06-01

    We demonstrate that it is possible to determine the coefficients of an all-orders beta-function linear in the anomalous dimensions using as data the 2-loop coefficients together with the first one of the anomalous dimensions which are universal. The beta function allows us to determine the anomalous dimension of the fermion masses at the infrared fixed point, and the resulting values compare well with the lattice determinations.

  4. Crystal Structure of Staphylococcal Enterotoxin G (SEG) in Complex with a Mouse T-cell Receptor Beta Chain

    SciTech Connect

    Fernandez, M.M.; Robinson, H.; Cho, S.; De Marzi, M. C.; Kerzic, M. C.; Mariuzza, R. A.; Malchiodi, E. L.

    2011-01-14

    Superantigens (SAgs) are bacterial or viral toxins that bind MHC class II (MHC-II) molecules and T-cell receptor (TCR) in a nonconventional manner, inducing T-cell activation that leads to inflammatory cytokine production, which may result in acute toxic shock. In addition, the emerging threat of purpura fulminans and community-associated meticillin-resistant Staphylococcus aureus emphasizes the importance of a better characterization of SAg binding to their natural ligands that may allow the development of reagents to neutralize their action. The three-dimensional structure of the complex between a mouse TCR {beta} chain (mV{beta}8.2) and staphylococcal enterotoxin G (SEG) at 2.0 {angstrom} resolution revealed a binding site that does not conserve the 'hot spots' present in mV{beta}8.2-SEC2, mV{beta}8.2-SEC3, mV{beta}8.2-SEB, and mV{beta}8.2-SPEA complexes. Analysis of the mV{beta}8.2-SEG interface allowed us to explain the higher affinity of this complex compared with the others, which may account for the early activation of T-cells bearing mV{beta}8.2 by SEG. This mode of interaction between SEG and mV{beta}8.2 could be an adaptive advantage to bestow on the pathogen a faster rate of colonization of the host.

  5. Apollo applications of beta fiber glass

    NASA Technical Reports Server (NTRS)

    Naimer, J.

    1971-01-01

    The physical characteristics of Beta fiber glass are discussed. The application of Beta fiber glass for fireproofing the interior of spacecraft compartments is described. Tests to determine the flammability of Beta fiber glass are presented. The application of Beta fiber glass for commercial purposes is examined.

  6. Model and Mockup of DEMO Ceramic Breeding Zone for Testing in the IVV-2M Reactor

    SciTech Connect

    Kapychev, V.; Gorokhov, V.; Davydov, D.

    2001-01-15

    A model of a ceramic breeding zone has been designed and manufactured for testing in the IVV-2M fission reactor. The model contains both lithium orthosilicate and beryllium spheroid particles 1 to 2 mm in diameter. The structural material is ferritic-martensitic stainless steel. In addition, a mockup of the model for verification of neutronics calculation methods has been designed and manufactured. A special facility (Functional In-Reactor Investigations of Tritium-Breeding Models) has been designed, fabricated, and assembled at the reactor for studying the kinetics of tritium extraction from the ceramic material under irradiation. Neutronic and thermo-hydraulic calculations and an initial measurement of tritium release from the model under reactor irradiation have been performed.

  7. Unmasking the masked Universe: the 2M++ catalogue through Bayesian eyes

    NASA Astrophysics Data System (ADS)

    Lavaux, Guilhem; Jasche, Jens

    2016-01-01

    This work describes a full Bayesian analysis of the Nearby Universe as traced by galaxies of the 2M++ survey. The analysis is run in two sequential steps. The first step self-consistently derives the luminosity-dependent galaxy biases, the power spectrum of matter fluctuations and matter density fields within a Gaussian statistic approximation. The second step makes a detailed analysis of the three-dimensional large-scale structures, assuming a fixed bias model and a fixed cosmology. This second step allows for the reconstruction of both the final density field and the initial conditions at z = 1000 assuming a fixed bias model. From these, we derive fields that self-consistently extrapolate the observed large-scale structures. We give two examples of these extrapolation and their utility for the detection of structures: the visibility of the Sloan Great Wall, and the detection and characterization of the Local Void using DIVA, a Lagrangian based technique to classify structures.

  8. Two color satellite laser ranging upgrades at Goddard's 1.2m telescope facility

    NASA Technical Reports Server (NTRS)

    Zagwodzki, Thomas W.; Mcgarry, Jan F.; Degnan, John J.; Varghese, Thomas K.

    1993-01-01

    The ranging laboratory at Goddard's 1.2 m telescope tracking facility has recently been upgraded to include a single photoelectron sensitive Hamamatsu streak camera-based range receiver which uses doubled and tripled Nd:YAG frequencies for satellite laser ranging. Other ranging system upgrades include a new continuum laser, which will deliver up to 30 millijoules (mJ) at both 532 and 355 nm at a pulsewidth of 30 picoseconds (FWHM), and replacement of both ranging and tracking computers with COMPAQ 386 based systems. Preliminary results using a photomultiplier-tube based receiver and waveform digitizer indicate agreement within the accuracy of the measurement with the theoretical Marini and Murray model for atmospheric refraction. Two color streak camera measurements are used to further analyze the accuracy of these and other atmospheric refraction models.

  9. Wavelet analysis of the parameters of edge plasma fluctuations in the L-2M stellarator

    NASA Astrophysics Data System (ADS)

    Maslov, S. A.; Vasilkov, D. G.; Kholnov, Yu V.; Skvortsova, N. N.

    2016-01-01

    Wavelet analysis results are presented for evolution of the spectral fluctuation characteristics of the edge plasma density and potential in the L-2M stellarator for fast and slow transport transitions. The fast transition comes out as a sharp increase of the energy and electron density within ∼0.1ms and the slow one as a weak parameter change during a 0.5 to 1 ms time interval. It is shown that the use of the “Mexican hat” and Morlet wavelets allows one to detect the moment of the fast transition, whereas applying the Haar wavelet adds to this also an estimate of its duration, conforming to the analytical calculations, and reveals the temporal structure of the slow transition.

  10. WARM DUSTY DEBRIS DISKS AND DISTANT COMPANION STARS: V488 PER AND 2M1337

    SciTech Connect

    Zuckerman, B.

    2015-01-10

    A possible connection between the presence of large quantities of warm (T ≥ 200 K) circumstellar dust at youthful stars and the existence of wide-separation companion stars has been noted in the literature. Here we point out the existence of a distant companion star to V488 Per, a K-type member of the α Persei cluster with the largest known fractional excess infrared luminosity (∼16%) of any main sequence star. We also report the presence of a distant companion to the previously recognized warm dust star 2M1337. With these discoveries the existence of a cause and effect relationship between a distant companion and large quantities of warm dust in orbit around youthful stars now seems compelling.

  11. Active optics system of the ASTRI SST-2M prototype for the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Gardiol, Daniele; Capobianco, Gerardo; Fantinel, Daniela; Giro, Enrico; Lessio, Luigi; Loreggia, Davide; Rodeghiero, Gabriele; Russo, Federico; Volpicelli, Antonio C.

    2014-07-01

    ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) SST-2M is an end-to-end prototype of Small Size class of Telescope for the Cherenkov Telescope Array. It will apply a dual mirror configuration to Imaging Atmospheric Cherenkov Telescopes. The 18 segments composing the primary mirror (diameter 4.3 m) are equipped with an active optics system enabling optical re-alignment during telescope slew. The secondary mirror (diameter 1.8 m) can be moved along three degrees of freedom to perform focus and tilt corrections. We describe the kinematic model used to predict the system performance as well as the hardware and software design solution that will be implemented for optics control.

  12. Holographic cosmology from a system of M2-M5 branes

    NASA Astrophysics Data System (ADS)

    Sepehri, Alireza; Faizal, Mir; Setare, Mohammad Reza; Ali, Ahmed Farag

    2016-05-01

    In this paper, we analyze the holographic cosmology using a M2-M5 brane configuration. In this configuration, a M2-brane will be placed in between a M5-brane and an anti-M5-brane. The M2-brane will act as a channel for energy to flow from an anti-M5-brane to a M5-brane, and this will increase the degrees of freedom on the M5-brane causing inflation. The inflation will end when the M5-brane and anti-M5-brane get separated. However, at a later stage the distance between the M5-brane and the anti-M5-bran can reduce and this will cause the formation of tachyonic states. These tachyonic states will again open a bridge between the M5-branes and the anti-M5-branes, which will cause further acceleration of the universe.

  13. Change in Edge Fluctuations Synchronized with Heat Pulse in the JFT-2M Tokamak

    NASA Astrophysics Data System (ADS)

    Nagashima, Yoshihiko; Itoh, Kimitaka; Itoh, Sanae-I.; Fujisawa, Akihide; Hoshino, Katsumichi

    2016-06-01

    The change in edge fluctuations synchronized with a heat pulse during Sawtooth oscillation has been investigated in the JFT-2M tokamak using a reciprocating Langmuir probe. Data window of a heat pulse is segmented into a number of time frames, and time traces of auto-power spectra at each frame are calculated. Conditional averaging over a number of heat pulse events in a single discharge is performed in order to reduce the variance of the fluctuation spectra. At each heat pulse event, a reduction in the geodesic acoustic mode fluctuation power and an increase in the turbulence fluctuation power are observed. The change in the fluctuation powers suggests that the edge heat pulse during Sawtooth instability could affect the edge turbulence structure.

  14. Two color satellite laser ranging upgrades at Goddard's 1.2m telescope facility

    NASA Astrophysics Data System (ADS)

    Zagwodzki, Thomas W.; McGarry, Jan F.; Degnan, John J.; Varghese, Thomas K.

    1993-06-01

    The ranging laboratory at Goddard's 1.2 m telescope tracking facility has recently been upgraded to include a single photoelectron sensitive Hamamatsu streak camera-based range receiver which uses doubled and tripled Nd:YAG frequencies for satellite laser ranging. Other ranging system upgrades include a new continuum laser, which will deliver up to 30 millijoules (mJ) at both 532 and 355 nm at a pulsewidth of 30 picoseconds (FWHM), and replacement of both ranging and tracking computers with COMPAQ 386 based systems. Preliminary results using a photomultiplier-tube based receiver and waveform digitizer indicate agreement within the accuracy of the measurement with the theoretical Marini and Murray model for atmospheric refraction. Two color streak camera measurements are used to further analyze the accuracy of these and other atmospheric refraction models.

  15. The design and analysis of 2m telescope's K Mirror system

    NASA Astrophysics Data System (ADS)

    Guo, Peng; Zhang, Jingxu; Yang, Fei; Zhang, Yan

    2014-09-01

    During the alt-azimuth telescope tracking, due to the frame structure of tracking support and relative movement of each mirror in Coude optical path, image plane is rotating. To eliminate the effects of image rotation for imaging and subsequent image processing, dove prism or K mirror are generally used. A set of K mirror system designed for 2m telescope. Affected by various errors in the alignment process, the rotating axis K, the optical axis of the K mirror, and the optical axis of the telescope's optical system can't be fully coincide. This causes the track optical axis drawn on the image is not a point, but a Pascal's limacon. The impact caused by the various sources of error were analyzed in this paper and simulation results have important guiding significance for the alignment error distribution.

  16. Ortho/para ratio of H2O+ toward Sagittarius B2(M) revisited.

    PubMed

    Schilke, Peter; Lis, Dariusz C; Bergin, Edwin A; Higgins, Ronan; Comito, Claudia

    2013-10-01

    The HIFI instrument aboard the Herschel satellite has allowed the observation and characterization of light hydrides, the building blocks of interstellar chemistry. In this article, we revisit the ortho/para ratio for H2O(+) toward the Sgr B2(M) cloud core. The line of sight toward this star forming region passes through several spiral arms and the gas in the Bar potential in the inner Galaxy. In contrast to earlier findings, which used fewer lines to constrain the ratio, we find a ratio of 3, which is uniformly consistent with high-temperature formation of the species. In view of the reactivity of this ion, this matches the expectations. PMID:23713712

  17. Proposed structures for poorly characterized phases in C2M carbonaceous chondrite meteorites

    NASA Technical Reports Server (NTRS)

    Mackinnon, I. D. R.; Zolensky, M. E.

    1984-01-01

    A recent investigation of C2M carbonaceous chondrite meteorite matrices using electron microscopy and High-Resolution Transmission Electron Microscopy (HRTEM) has provided data on the structure and chemistry of Poorly Characterized Phases (PCP). It is suggested that a dominant matrix variety (10 A PCP) has a structure equivalent to iron-rich tochinilite (6Fe0.9S5/Fe, Mg//OHO2/), which consists of coherently intrastratified mackinawite and brucite sheets. In addition, it is proposed that 17 A PCP is a commensurate intergrowth of serpentine and tochinilite layers. Various forms of PCP observed in carbonaceous chondrites appear to be intergrowths of tochinilite, serpentine, and tochinilite-serpentine minerals.

  18. Type 2M and Type 2A von Willebrand Disease: Similar but Different.

    PubMed

    Favaloro, Emmanuel J; Pasalic, Leonardo; Curnow, Jennifer

    2016-07-01

    Analogous to the differentiation between hemophilia A and B, respectively, reflecting deficiency in factor VIII (FVIII) and FIX, and increasing being recognized as reflecting clinically different disorders, types 2A and 2M von Willebrand disease (VWD) can also be shown to express both similarities and differences in their prevalence, genetic defects, laboratory test results, clinical features, and treatment responses. In this narrative review, we explore these two "subtypes" of type 2 VWD, identifying parallels and dissimilarities in various aspects of their presentation to clinicians and to scientists/laboratories. This differential will become increasingly important as we strive to provide personalized approaches to future management of patients with VWD, particularly in the emerging landscape of recombinant von Willebrand factor. PMID:27148841

  19. A cost-effective and serviceable ATLAST 9.2m telescope architecture

    NASA Astrophysics Data System (ADS)

    Feinberg, Lee D.; Jones, Andrew; Mosier, Gary; Rioux, Norman; Redding, Dave; Kienlen, Mike

    2014-08-01

    The ATLAST 9.2m architecture has evolved to be more cost effective while also meeting a more thorough understanding of the driving science requirements. The new approach can fit in an existing Delta IV Heavy rocket and makes extensive use of heritage and selective use of technology in order to minimize development time and cost. We have performed a more thorough look at how to meet the stability requirements for both thermal and dynamics and have an approach consistent with an initial error budget. In addition, we have developed concepts to support robotic or human servicing in a cost effective manner through a modular approach that relies on simple, external access and metrology. These refinements to the architecture enable a cost-effective, long-lifecycle, and relatively low risk approach to development.

  20. Spectrofluorimetric determination of cysteine by 5-maleimidyl-2-( m-methylphenyl)benzoxazole

    NASA Astrophysics Data System (ADS)

    Liang, Shu-Cai; Wang, Hong; Zhang, Zhi-Min; Zhang, Xian; Zhang, Hua-Shan

    2002-10-01

    A new thiol weak-fluorescence probe, 5-maleimidyl-2-( m-methylphenyl)benzoxazole (MMPB), gives a highly fluorescence product in the presence of Cys. In this paper, MMPB has been developed for the fluorimetric determination of cysteine (Cys). At λex/ λem=305.6/425.6 nm, the linear range is from 0 to 3.3×10 -7 mol l -1 and the detection limit ( σ=3) of 6.2×10 -10 mol l -1. The main advantage of this method lies in the relative high selectivity compared with the methods using other N-substituted maleimide type of thiol reagents, in which 0.15-fold (molar ratio) of GSH is allowed and most of other amino acids at 100-fold (molar ratio) level had no obvious effect on the results. The proposed method has been applied to the determination of Cys in real samples.

  1. Nanodopant-Induced Band Modulation in AgPbmSbTe2+m-Type Nanocomposites

    SciTech Connect

    Zhang, Yi; Ke, Xuezhi; Chen, Changfeng; Yang, Jihui; Kent, Paul R

    2011-01-01

    We elucidate the fundamental physics of nanoscale dopants in narrow band-gap thermoelectric nanocomposites XPbmYTe2+m (X=Ag,Na; Y=Sb,Bi) using first-principles calculations. Our re- sults unveil distinct band-structure modulations, most notably a sizable band-gap widening driven by nanodopant-induced lattice strain and a band split-off at the conduction band minimum caused by the spin-orbit interaction of the dopant Sb or Bi atoms. Boltzmann transport calculations demon- strate that these band modulations have significant but competing effects on high-temperature elec- tron transport behavior. These results offer insights for understanding recent experimental findings and suggest principles for optimizing thermoelectric properties of narrow band-gap semiconductors.

  2. A concept for the modernization of a SANS instrument at the IBR-2M pulsed reactor

    NASA Astrophysics Data System (ADS)

    Erhan, R. V.; Manoshin, S.; Pepy, G.; Kuklin, A. I.; Belushkin, A. V.; Zamfir, N. V.

    2011-04-01

    We consider a new configuration for a neutron small angle scattering instrument at the pulsed IBR-2M reactor with a mixed (cold and thermal) moderator system. This system provides added-up spectra from the cold and thermal parts of the moderator. We have installed the spectrometer using a special collimation system formed by two parts: primary with neutron optics element (divergent neutron guide) and secondary (installed after the divergent neutron guide) with a multiple pinhole collimation system. Our efforts have the goal to obtain smaller Qmin values (as well as higher resolution) with the possibilities to take advantage of an increased neutron flux compared with the present SANS spectrometer in the limited beam hall size. The Monte Carlo simulations will be used to choose and optimize the spectrometer and extraction system using VITESS software package.

  3. Measurement of cold neutron spectra using a model cryogenic moderator of the IBR-2M reactor

    NASA Astrophysics Data System (ADS)

    Kulikov, S. A.; Kalinin, I. V.; Morozov, V. M.; Novikov, A. G.; Puchkov, A. V.; Chernikov, A. N.; Shabalin, E. P.

    2010-01-01

    The method and results of an experiment to determine the cold neutron spectrum from solid mesitylene at moderator temperatures of 10-50 K are presented. This study was performed at the DIN-2PI spectrometer of the IBR-2 reactor. The objective of the study was to verify the system of constants used in the Monte Carlo simulation of cryogenic neutron moderators of the IBR-2M reactor and to obtain the cold neutron yield as a function of the moderator temperature. Satisfactory agreement between the experimental and calculated neutron spectra at a mesitylene temperature of 20 K has been obtained; the ratio of cold neutron intensities at 10 and 50 K is ˜1.8.

  4. Ripple reduction and surface coating tests with ferritic steel on JFT-2M

    NASA Astrophysics Data System (ADS)

    Tsuzuki, K.; Sato, M.; Kawashima, H.; Miura, Y.; Kimura, H.; Abe, T.; Uehara, K.; Ogawa, T.; Akiyama, T.; Shibata, T.; Yamamoto, M.; Koike, T.

    2000-12-01

    Applicability of the low-activation ferritic steel (F82H), which is one of the candidate materials for next generation fusion devices, has been tested in JFT-2M. Ferritic steel boards (FB) were installed between toroidal field coils (TFC) and the vacuum vessel at all toroidal sections. The experiment and the calculation show that the ripple amplitude decreases from 2.2% to 1.1% by the FB installation at R=1.6 m. The ripple reduction results in the reduction of fast ion loss and in the shift of the ripple loss to the outer region. No undesirable effect to the energy confinement and the plasma control was observed. The FB will be installed inside the vacuum vessel in the near future. In preparation, surface coating tests, mainly concerning with an in situ boron coating, are carried out.

  5. IPLA2 mRNA expression by human neutrophils in type 2 diabetes and chronic periodontitis.

    PubMed

    Ayilavarapu, Srinivas; Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

    2014-10-01

    Type 2 diabetes mellitus (T2D) is becoming increasingly prevalent worldwide and complications of T2D cause significant systemic and dental morbidity in the susceptible individual. Although T2D has been linked as a significant risk factor for chronic periodontitis (CP), molecular mechanisms explaining the pathogenesis and inflammatory impact of CP in T2D are lacking. iPLA2 is the calcium-independent form of phospholipase A2. In previous studies, we demonstrated that iPLA2 enzyme activity is altered in T2D. The purpose of this study was to elucidate the level of the iPLA2 abnormality in T2D by measuring messenger RNA levels in T2D-associated CP. A total of 53 healthy and T2D subjects with CP were recruited for this study. The clinical periodontal exam included probing pocket depth, clinical attachment levels and bleeding on probing. Peripheral venous blood was collected and neutrophils were isolated. Real time polymerase chain reaction was used to quantify iPLA2 mRNA in neutrophils from healthy controls and people with diabetes. Results revealed that the prevalence of moderate to severe CP was increased in people with T2D. The iPLA, mRNA levels in diabetics with different severity of CP were not significantly different compared to healthy controls; 1.07 vs 0.97 (mild CP), 1.07 vs 0.85 (moderate CP) and 1.07 vs 1.05 (severe CP). Collectively, the data suggest that levels of iPLA2 mRNA in T2D are not different than in health and are not directly influenced by periodontal disease status. The impact of inflammation on iPLA2 regulation is at the level of activation of the enzyme rather than expression at the mRNA level. PMID:25654966

  6. hnRNP L binds to CA repeats in the 3'UTR of bcl-2 mRNA

    SciTech Connect

    Lee, Dong-Hyoung; Lim, Mi-Hyun; Youn, Dong-Ye; Jung, Seung Eun; Ahn, Young Soo; Tsujimoto, Yoshihide; Lee, Jeong-Hwa

    2009-05-08

    We previously reported that the CA-repeat sequence in the 3'-untranslated region (3'UTR) of bcl-2 mRNA is involved in the decay of bcl-2 mRNA. However, the trans-acting factor for the CA element in bcl-2 mRNA remains unidentified. The heterogeneous nuclear ribonucleoprotein L (hnRNP L), an intron splicing factor, has been reported to bind to CA repeats and CA clusters in the 3'UTR of several genes. We reported herein that the CA repeats of bcl-2 mRNA have the potential to form a distinct ribonuclear protein complex in cytoplasmic extracts of MCF-7 cells, as evidenced by RNA electrophoretic mobility shift assays (REMSA). A super-shift assay using the hnRNP L antibody completely shifted the complex. Immunoprecipitation with the hnRNP L antibody and MCF-7 cells followed by RT-PCR revealed that hnRNP L interacts with endogenous bcl-2 mRNA in vivo. Furthermore, the suppression of hnRNP L in MCF-7 cells by the transfection of siRNA for hnRNP L resulted in a delay in the degradation of RNA transcripts including CA repeats of bcl-2 mRNA in vitro, suggesting that the interaction between hnRNPL and CA repeats of bcl-2 mRNA participates in destabilizing bcl-2 mRNA.

  7. High beta plasmas in the PBX tokamak

    SciTech Connect

    Bol, K.; Buchenauer, D.; Chance, M.; Couture, P.; Fishman, H.; Fonck, R.; Gammel, G.; Grek, B.; Ida, K.; Itami, K.

    1986-04-01

    Bean-shaped configurations favorable for high ..beta.. discharges have been investigated in the Princeton Beta Experiment (PBX) tokamak. Strongly indented bean-shaped plasmas have been successfully formed, and beta values of over 5% have been obtained with 5 MW of injected neutral beam power. These high beta discharges still lie in the first stability regime for ballooning modes, and MHD stability analysis implicates the external kink as responsible for the present ..beta.. limit.

  8. A recombinant, soluble, single-chain class I major histocompatibility complex molecule with biological activity.

    PubMed Central

    Mage, M G; Lee, L; Ribaudo, R K; Corr, M; Kozlowski, S; McHugh, L; Margulies, D H

    1992-01-01

    Heterodimeric class I major histocompatibility complex molecules, which consist of a 45-kDa heavy-chain and a 12-kDa beta 2-microglobulin (beta 2m) light chain, bind endogenously synthesized peptides for presentation to antigen-specific T cells. We have synthesized a gene encoding a single-chain, soluble class I molecule derived from mouse H-2Dd, in which the carboxyl terminus of beta 2m is linked via a peptide spacer to the amino terminus of the heavy chain. The chimeric protein is secreted efficiently from transfected L cells, is thermostable, and when loaded with an appropriate antigenic peptide, stimulates an H-2Dd-restricted antigen-specific T-cell hybridoma. Thus, functional binding of peptide does not require the complete dissociation of beta 2m, implying that a heavy chain/peptide complex is not an obligate intermediate in the assembly of the heavy-chain/beta 2m/peptide heterotrimer. Single-chain major histocompatibility complex molecules uniformly loaded with peptide have potential uses for structural studies, toxin or fluor conjugates, and vaccines. Images PMID:1438262

  9. Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients.

    PubMed

    Everaus, H; Lehtmaa, J; Luik, E; Kŏdar, H

    1992-11-01

    Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy. PMID:1457579

  10. Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells.

    PubMed

    Kuo, Po-Lin; Hsu, Ya-Ling; Cho, Chien-Yu

    2006-12-01

    This study is the first to investigate the anticancer effect of plumbagin in human breast cancer cells. Plumbagin exhibited cell proliferation inhibition by inducing cells to undergo G2-M arrest and autophagic cell death. Blockade of the cell cycle was associated with increased p21/WAF1 expression and Chk2 activation, and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C. Plumbagin also reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and the levels of inactivated phospho-Cdc2 and phospho-Cdc25C by Chk2 activation. Plumbagin triggered autophagic cell death but not predominantly apoptosis. Pretreatment of cells with autophagy inhibitor bafilomycin suppressed plumbagin-mediated cell death. We also found that plumbagin inhibited survival signaling through the phosphatidylinositol 3-kinase/AKT signaling pathway by blocking the activation of AKT and downstream targets, including the mammalian target of rapamycin, forkhead transcription factors, and glycogen synthase kinase 3beta. Phosphorylation of both of mammalian target of rapamycin downstream targets, p70 ribosomal protein S6 kinase and 4E-BP1, was also diminished. Overexpression of AKT by AKT cDNA transfection decreased plumbagin-mediated autophagic cell death, whereas reduction of AKT expression by small interfering RNA potentiated the effect of plumbagin, supporting the inhibition of AKT being beneficial to autophagy. Furthermore, suppression of AKT by plumbagin enhanced the activation of Chk2, resulting in increased inactive phosphorylation of Cdc25C and Cdc2. Further investigation revealed that plumbagin inhibition of cell growth was also evident in a nude mouse model. Taken together, these results imply a critical role for AKT inhibition in plumbagin-induced G2-M arrest and autophagy of human breast cancer cells. PMID:17172425

  11. Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11{beta}-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells

    SciTech Connect

    Hong, Dun; Li, Xing-Wang; Lian, Qing-Quan; Lamba, Pankaj; Bernard, Daniel J.; Hardy, Dianne O.; Chen, Hai-Xiao; Ge, Ren-Shan

    2009-11-13

    Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11{beta}-hydroxysteroid dehydrogenase type 2 (11{beta}-HSD2), not 11{beta}-HSD1, is strongly expressed in murine gonadotrope L{beta}T2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11{beta}-HSD2 enzyme activity in L{beta}T2 cells at as low as 10{sup -7} M. Corticosterone (CORT) at a concentration of 10{sup -6} M significantly inhibited L{beta}T2 cell proliferation after 2-day culture, and 10{sup -6} M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10{sup -5} or 10{sup -4} M MEHP, the minimal concentration of CORT to inhibit the proliferation of L{beta}T2 cells was lowered to 10{sup -7} M, and 10{sup -6} M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11{beta}-HSD2 may have a key role in glucocorticoid metabolism in L{beta}T2 cells. MEHP may participate in the glucocorticoid metabolism in L{beta}T2 cells through inhibition of 11{beta}-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure.

  12. Reflective and antireflective coatings for the optical chain of the ASTRI SST-2M prototype

    NASA Astrophysics Data System (ADS)

    Bonnoli, Giacomo; Canestrari, Rodolfo; Catalano, Osvaldo; Pareschi, Giovanni; Perri, Luca; Stringhetti, Luca

    2013-09-01

    ASTRI is a Flagship Project of the Italian Ministry of Education, University and Research, led by the Italian National Institute of Astrophysics, INAF. One of the main aims of the ASTRI Project is the design, construction and on-field verification of a dual mirror (2M) end-to-end prototype for the Small Size Telescope (SST) envisaged to become part of the Cherenkov Telescope Array. The ASTRI SST-2M prototype is designed according to the Schwarzschild-Couder optical scheme, and adopts a camera based on Silicon Photo Multipliers (SiPM); it will be assembled at the INAF astronomical site of Serra La Nave on mount Etna (Catania, Italy) in the second half of 2014, and will start scientific validation phase soon after. With its 4m wide primary dish, the telescope will be sensitive to multi-TeV Very High Energy (VHE) gamma rays up to 100 TeV and above, with a point spread function of ~2 arcminutes and a wide (semiaperture 4.8°) corrected field of view. The peculiarities of the optical design and of the SiPM bandpass pushed towards specifically optimized choices in terms of reflective coatings for both the primary and the secondary mirror. Fully dielectric multi-layer coatings have been developed and tested as an option for the primary mirror, aiming to filter out the large Night Sky Background contamination at wavelengths λ>~700 nm. On the other hand, for the large monolithic secondary mirror a simpler design with quartz-overcoated aluminium has been optimized for incidences far from normality. The conformation of the ASTRI camera in turn pushed towards the design of a reimaging system based on thin pyramidal light guides, that could be optionally integrated in the focal surface, aiming to increase the fill factor. An anti-reflective coating optimized for a wide range of incident angles faraway from normality was specifically developed to enhance the UV-optical transparency of these elements. The issues, strategy, simulations and experimental results are thoroughly

  13. Disorder of G2-M Checkpoint Control in Aniline-Induced Cell Proliferation in Rat Spleen

    PubMed Central

    Wang, Jianling; Wang, Gangduo; Khan, M. Firoze

    2015-01-01

    Aniline, a toxic aromatic amine, is known to cause hemopoietic toxicity both in humans and animals. Aniline exposure also leads to toxic response in spleen which is characterized by splenomegaly, hyperplasia, fibrosis and the eventual formation of tumors on chronic in vivo exposure. Previously, we have shown that aniline exposure leads to iron overload, oxidative DNA damage, and increased cell proliferation, which could eventually contribute to a tumorigenic response in the spleen. Despite our demonstration that cell proliferation was associated with deregulation of G1 phase cyclins and increased expression of G1 phase cyclin-dependent kinases (CDKs), molecular mechanisms, especially the regulation of G2 phase and contribution of epigenetic mechanisms in aniline-induced splenic cellular proliferation remain largely unclear. This study therefore, mainly focused on the regulation of G2 phase in an animal model preceding a tumorigenic response. Male Sprague-Dawley rats were given aniline (0.5 mmol/kg/day) in drinking water or drinking water only (controls) for 30 days, and expression of G2 phase cyclins, CDK1, CDK inhibitors and miRNAs were measured in the spleen. Aniline treatment resulted in significant increases in cell cycle regulatory proteins, including cyclins A, B and CDK1, particularly phosphor-CDK1, and decreases in CDK inhibitors p21 and p27, which could promote the splenocytes to go through G2/M transition. Our data also showed upregulation of tumor markers Trx-1 and Ref-1 in rats treated with aniline. More importantly, we observed lower expression of miRNAs including Let-7a, miR-15b, miR24, miR-100 and miR-125, and greater expression of CDK inhibitor regulatory miRNAs such as miR-181a, miR-221 and miR-222 in the spleens of aniline-treated animals. Our findings suggest that significant increases in the expression of cyclins, CDK1 and aberrant regulation of miRNAs could lead to an accelerated G2/M transition of the splenocytes, and potentially to a

  14. Preparation and crystal structure of new potassium niobium oxides: K{sub 2}M{sub 2}Nb{sub 4}O{sub 13} (M = Mg,Fe)

    SciTech Connect

    Kumada, N.; Kinomura, N.

    1997-05-01

    Single crystals of new niobium oxides, K{sub 2}M{sub 2}Nb{sub 4}O{sub 13} (M = Mg,Fe) were prepared at 1,200 C. These niobium oxides crystallize in the K{sub 2}Ti{sub 6}O{sub 13}-type structure and have the monoclinic space group C2/m and Z = 2. The lattice parameters were a = 16.028(6), b = 3.885(3), c = 9.473(3){angstrom} and {beta} = 99.26(3){degree} for M = Mg, and a = 16.095(2), b = 3.886(2), c = 9.474(1){angstrom} and {beta} = 99.62(1){degree} for M = Fe. The final R-factors were R = 0.046 and Rw = 0.044 for 2,142 unique reflections for M = Mg, and R = 0.026 and Rw = 0.029 for 2,144 unique reflections for M = Fe. These niobium oxides are the first example of niobium oxides with the K{sub 2}Ti{sub 6}O{sub 13}-type structure. The niobium and magnesium atoms are statistically distributed in triple octahedra sharing edges in K{sub 2}Mg{sub 2}Nb{sub 4}O{sub 13}, and in contrast the iron atom is located in one of triple octahedra sharing edges in K{sub 2}Fe{sub 2}Nb{sub 4}O{sub 13}.

  15. Diosgenin induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells.

    PubMed

    Li, Yongjian; Wang, Xiaorong; Cheng, Silu; Du, Juan; Deng, Zhengting; Zhang, Yani; Liu, Qun; Gao, Jingdong; Cheng, Binbin; Ling, Changquan

    2015-02-01

    Diosgenin is a major compound of Dioscoreaceae plants such as yam, which is used as a drug in Traditional Chinese Medicine, and a common vegetable worldwide. The anticancer effect of diosgenin has been reported in various tumor cells, including leukemia, gastric, colorectal, and breast cancer. However, the activity of diosgenin on hepatocellular carcinoma (HCC) and the underlying mechanism have not been completely investigated. Therefore, we investigated the efficacy and associated mechanisms of diosgenin in HCC cells. Flow cytometric analysis was performed to determine the presence of cell cycle arrest and apopotic cells. Diosgenin significantly inhibited the growth of Bel-7402, SMMC-7721 and HepG2 HCC cells in a concentration-dependent manner. Diosgenin treatment for 24 h induced G2/M cell cycle arrest and apoptosis of hepatoma cells. Diosgenin inhibited Akt phosphorylation and upregulated p21 and p27 expression, but did not alter the expression of p53, suggesting diosgenin-induced upregulation of p21 and p57 is p53-independent in HCC cells. Diosgenin induced HCC cell apoptosis by activating caspase cascades -3, -8 and -9. However, diosgenin did not affect Bcl-2 and Bax levels. In conclusion, results of the present study suggest that diosgenin may be an active anti-HCC agent obtained from natural plants and provide new insights in understanding the mechanisms of diosgenin. PMID:25434486

  16. Distributed net-centric architecture of m2m acquisition units with optical GVA

    NASA Astrophysics Data System (ADS)

    Guha, Dipnarayan; Choi, Jun; Hassan, Mashfique

    2005-05-01

    This paper describes the architecture of a low-latency symmetric multiprocessing optical soft memory system to cluster computing inside the core of an adaptive optical signal processor with the aid of soft decision algebraic polynomial algorithms. The optical system hardware is shown to evolve along with the iterator instantiations of the soft algorithm that forms the core of the memory map. The system enables efficient cache coherence protocols used in unit multiprocessors to be run across a homogeneous cluster in optical soft memory systems. We define a structure called the Optical Generalized Viterbi Algorithm Data Structure (Optical GVA DS) that makes up the system map for adaptive optical signal processing. The system executes transforms where algorithms for handling the entire data vector is processed, shortening the computational complexity effectively. Thus the optical soft memory system as described by the evolving Optical GVA DS iterator instantiates enables the design of parallel processors to handle modulated data in the optical domain. This is of importance in the realization of distributed netcentric architectures and forms the basis of large-scale real-time data processing and acquisition in m2m units.

  17. Phosphorylation-dependent degradation of MEF2C contributes to regulate G2/M transition.

    PubMed

    Badodi, Sara; Baruffaldi, Fiorenza; Ganassi, Massimo; Battini, Renata; Molinari, Susanna

    2015-01-01

    The Myocyte Enhancer Factor 2C (MEF2C) transcription factor plays a critical role in skeletal muscle differentiation, promoting muscle-specific gene transcription. Here we report that in proliferating cells MEF2C is degraded in mitosis by the Anaphase Promoting Complex/Cyclosome (APC/C) and that this downregulation is necessary for an efficient progression of the cell cycle. We show that this mechanism of degradation requires the presence on MEF2C of a D-box (R-X-X-L) and 2 phospho-motifs, pSer98 and pSer110. Both the D-box and pSer110 motifs are encoded by the ubiquitous alternate α1 exon. These two domains mediate the interaction between MEF2C and CDC20, a co-activator of APC/C. We further report that in myoblasts, MEF2C regulates the expression of G2/M checkpoint genes (14-3-3γ, Gadd45b and p21) and the sub-cellular localization of CYCLIN B1. The importance of controlling MEF2C levels during the cell cycle is reinforced by the observation that modulation of its expression affects the proliferation rate of colon cancer cells. Our findings show that beside the well-established role as pro-myogenic transcription factor, MEF2C can also function as a regulator of cell proliferation. PMID:25789873

  18. The New Instrument Suite of the TSU/Fairborn 2m Automatic Spectroscopic Telescope

    NASA Astrophysics Data System (ADS)

    Muterspaugh, Matthew W.; Maxwell, T.; Williamson, M. W.; Fekel, F. C.; Ge, J.; Kelly, J.; Ghasempour, A.; Powell, S.; Zhao, B.; Varosi, F.; Schofield, S.; Liu, J.; Warner, C.; Jakeman, H.; Avner, L.; Swihart, S.; Harrison, C.; Fishler, D.

    2014-01-01

    Tied with the Liverpool Telescope as the world's largest fully robotic optical research telescope, Tennessee State University's (TSU) 2m Automatic Spectroscopic Telescope (AST) has recently been upgraded to improve performance and increase versatility by supporting multiple instruments. Its second-generation instrument head enables us to rapidly switch between any of up to twelve fibers optics, each of which can supply light to a different instrument. In 2013 construction was completed on a new temperature-controlled guest instrument building, and two new high resolution spectrographs were commissioned. The current set of instrumentation includes (1) the telescope's original R=30,000 echelle spectrograph (0.38--0.83 microns simultaneous), (2) a single order R=7,000 spectrograph centered at Ca H&K features, (3) a single-mode-fiber fed miniature echelle spectrograph (R=100,000; 0.48--0.62 microns simultaneous), (4) the University of Florida's EXPERT-3 spectrograph (R=100,000; 0.38--0.9 microns simultaneous; vacuum and temperature controlled) and (5) the University of Florida's FIRST spectrograph (R=70,000$; 0.8--1.35 or 1.4--1.8 microns simultaneous; vacuum and temperature controlled). Future instruments include the Externally Dispersed Interferometry (EDI) Testbed, a combination low resolution dispersed spectrograph and Fourier Transform Spectrograph. We welcome inquiries from the community in regards to observing access and/or proposals for future guest instruments.

  19. Numerical investigation of disruption characteristics for the snowflake divertor configuration in HL-2M

    NASA Astrophysics Data System (ADS)

    Xue, L.; Duan, X. R.; Zheng, G. Y.; Liu, Y. Q.; Pan, Y. D.; Yan, S. L.; Dokuka, V. N.; Lukash, V. E.; Khayrutdinov, R. R.

    2016-05-01

    Cold and hot vertical displacement events (VDEs) are frequently related to the disruption of vertically-elongated tokamaks. The weak poloidal magnetic field around the null-points of a snowflake divertor configuration may influence the vertical displacement process. In this paper, the major disruption with a cold VDE and the vertical disruption in the HL-2M tokamak are investigated by the DINA code. In order to better illustrate the effect from the weak poloidal field, a double-null snowflake configuration is compared with the standard divertor (SD) configuration under the same plasma parameters. Computational results show that the weak poloidal magnetic field can be partly beneficial for mitigating the vertical instability of the plasma under small perturbations. For major disruption, the peak poloidal halo current fraction is almost the same between the snowflake and the SD configurations. However, this fraction becomes much larger for the snowflake in the event of a hot VDE. Furthermore, during the disruption for a snowflake configuration, the distribution of electromagnetic force on a vacuum vessel gets more non-uniform during the current quench.

  20. The 64 Mpixel wide field imager for the Wendelstein 2m telescope: design and calibration

    NASA Astrophysics Data System (ADS)

    Kosyra, Ralf; Gössl, Claus; Hopp, Ulrich; Lang-Bardl, Florian; Riffeser, Arno; Bender, Ralf; Seitz, Stella

    2014-11-01

    The Wendelstein Observatory of Ludwig Maximilians University of Munich has recently been upgraded with a modern 2m robotic telescope. One Nasmyth port of the telescope has been equipped with a wide-field corrector which preserves the excellent image quality (<0.8 " median seeing) of the site (Hopp et al. 2008) over a field of view of 0.7 degrees diameter. The available field is imaged by an optical imager (WWFI, the Wendelstein Wide Field Imager) built around a customized 2×2 mosaic of 4 k×4 k 15 μm e2v CCDs from Spectral Instruments. This paper provides an overview of the design and the WWFI's performance. We summarize the system mechanics (including a structural analysis), the electronics (and its electromagnetic interference (EMI) protection) and the control software. We discuss in detail detector system parameters, i.e. gain and readout noise, quantum efficiency as well as charge transfer efficiency (CTE) and persistent charges. First on sky tests yield overall good predictability of system throughput based on lab measurements.

  1. HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS.

    PubMed

    Zhang, C; Liu, K; Yao, K; Reddy, K; Zhang, Y; Fu, Y; Yang, G; Zykova, T A; Shin, S H; Li, H; Ryu, J; Jiang, Y-N; Yin, X; Ma, W; Bode, A M; Dong, Z; Dong, Z

    2015-01-01

    Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth. PMID:26469961

  2. Probe measurements of hydrogen fluxes during discharge cleaning in JFT-2M

    NASA Astrophysics Data System (ADS)

    JFT-2M Team; Maeda, H.; Susuki, K.; Hasegawa, K.; Honda, A.; Ishibori, I.; Kashiwa, Y.; Kazawa, M.; Kikuchi, K.; Ohuchi, K.; Okano, F.; Sato, E.; Shibata, T.; Tani, T.; Uno, S.; Hoshino, K.; Kasai, S.; Kawakami, T.; Kawashima, K.; Matsuda, T.; Matsumoto, H.; Miura, Y.; Mori, M.; Nakazawa, I.; Odajima, K.; Ogawa, H.; Ogawa, T.; Ohasa, K.; Ohtsuka, H.; Sengoku, S.; Shoji, T.; Suzuki, N.; Tamai, H.; Uesugi, Y.; Yamamoto, T.; Yamauchi, T.; Matsuzaki, Y.

    1989-04-01

    Thermal desorption spectroscopy (TDS) has been applied during discharge cleaning in the JFT-2M tokamak to measure hydrogen fluxes. The TDS carbon sample, thickness 0.13 mm, was heated to 1000°C by direct current and the temperature distribution of the sample surface measured by infrared thermography. The probe was exposed to three types of plasma: Taylor-type discharge cleaning (TDC), ECR discharge cleaning (ECR-DC), and glow discharge cleaning (GDC). The TDS spectra show peak desorption at around 800°C. The hydrogen flux, obtained by integration of the TDS spectrum, decreases exponentially in the radial direction with decay length 7.4 cm and 5.8 cm in TDC and ECR-DC, respectively. The relation between hydrogen fluxes and water vapour production was investigated. In TDC, the amount of water vapour depends more strongly on the electron temperature of the plasma than on the hydrogen flux. In ECR-DC, the production of water vapour increases approximately linearly with the hydrogen-flux. In GDC, hydrogen fluxes were measured by TDS but no water vapour could be detected in the residual gases during the discharge.

  3. 1.2 m Shielded Cassegrain Antenna for Close-Packed Radio Interferometer

    NASA Astrophysics Data System (ADS)

    Koch, Patrick M.; Raffin, Philippe; Huang, Yau-De; Chen, Ming-Tang; Han, Chih-Chiang; Lin, Kai-Yang; Altamirano, Pablo; Granet, Christophe; Ho, Paul T. P.; Huang, Chih-Wei L.; Kesteven, Michael; Li, Chao-Te; Liao, Yu-Wei; Liu, Guo-Chin; Nishioka, Hiroaki; Ong, Ching-Long; Oshiro, Peter; Umetsu, Keiichi; Wang, Fu-Cheng; Proty Wu, Jiun-Huei

    2011-02-01

    Interferometric millimeter observations of the cosmic microwave background and clusters of galaxies with arcminute resolutions require antenna arrays with short spacings. Having all antennas co-mounted on a single steerable platform sets limits to the overall weight. A 25 kg lightweight novel carbon-fiber design for a 1.2 m diameter Cassegrain antenna is presented. The finite element analysis predicts excellent structural behavior under gravity, wind, and thermal load. The primary- and secondary-mirror surfaces are aluminum-coated with a thin TiO2 top layer for protection. A low beam sidelobe level is achieved with a Gaussian feed-illumination pattern with edge taper, designed based on feed-horn antenna simulations and verified in a far-field beam-pattern measurement. A shielding baffle reduces interantenna coupling to below ~-135 dB. The overall antenna efficiency, including a series of efficiency factors, is estimated to be around 60%, with major losses coming from the feed spillover and secondary blocking. With this new antenna, a detection rate of about 50 clusters yr-1 is anticipated in a 13-element array operation.

  4. Rates of E1, E2, M1, and M2 transitions in Ni II

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  5. Edge plasma dynamics during L-H transition in the JFT-2M tokamak

    NASA Astrophysics Data System (ADS)

    Kobayashi, T.; Itoh, K.; Ido, T.; Kamiya, K.; Itoh, S.-I.; Miura, Y.; Nagashima, Y.; Fujisawa, A.; Inagaki, S.; Ida, K.; Hoshino, K.

    2015-06-01

    This article presents a radial electric field measurement by a heavy ion beam probe in the JFT-2M tokamak, during the L-H transition. An abrupt increase (time scale of O(100 µs)) of the strong edge radial electric field (localized in the radius with FWHM ∼7 mm) results in the increase of density gradient and turbulence reduction. Rapid inward propagation of the turbulence suppression front is observed at the transition. After the transition, the electric field structure in the tiny edge localized modes (ELMs) is analyzed. Transport self-regulation events observed in the vicinity of the L-H transition, i.e. the limit cycle oscillation (LCO) in the L-mode, the tiny ELM in the H-mode, as well as the L-H transition itself, are summarized in a single Lissajous diagram in the electric field-density gradient space, which provides a comprehensive explanation of the transition dynamics. This article is dedicated to the memory of Professor Tihiro Ohkawa.

  6. McGee Mountain Shallow (2m) Temperature Survey, Humboldt County, Nevada 2009

    DOE Data Explorer

    Richard Zehner

    2009-01-01

    This shapefile contains location and attribute data for a shallow (2 meter) temperature survey conducted by Geothermal Technical Partners, Inc. during late 2008 and early 2009. Temperatures at 2m depth were measured at 192 separate points as outlined by Coolbaugh et al., 2007. The purpose of the survey was to try and detect a shallow thermal anomaly associated with the McGee Mountain geothermal area as discovered by Phillips Petroleum and Earth Power Resources in the late 1970’s. Drilling identified ~120oC temperatures at ~100m depth. This 2-meter survey delineated what was interpreted as a steam-heated fault zone centered along a range front fault in the vicinity of the drilled holes and fumaroles. Coolbaugh, M.F., Sladek, C., Faulds, J.E., Zehner, R.E., and Oppliger, G.L., 2007, Use of rapid temperature measurements at a 2-meter depth to augment deeper temperature gradient drilling: Proceedings, 32nd Workshop on Geothermal Reservoir Engineering, Stanford University, Stanford, CA, Jan. 22-24, 2007, p. 109-116. Zehner, R., Tullar, K., and Rutledge, E., 2012, Effectiveness of 2-Meter and geoprobe shallow temperature surveys in early stage geothermal exploration: Geothermal Resources Council Transactions, v. 36, in press.

  7. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma.

    PubMed

    Kroesen, Michiel; Büll, Christian; Gielen, Paul R; Brok, Ingrid C; Armandari, Inna; Wassink, Melissa; Looman, Maaike W G; Boon, Louis; den Brok, Martijn H; Hoogerbrugge, Peter M; Adema, Gosse J

    2016-06-01

    Neuroblastoma (NBL) is a childhood malignancy of the sympathetic nervous system. For high-risk NBL patients, the mortality rate is still over 50%, despite intensive multimodal treatment. Anti-GD2 monoclonal antibody (mAB) in combination with systemic cytokine immunotherapy has shown clinical efficacy in high-risk NBL patients. Targeted therapy using histone deacetylase inhibitors (HDACi) is currently being explored in cancer treatment and already shows promising results. Using our recently developed transplantable TH-MYCN NBL model, we here report that the HDAC inhibitor Vorinostat synergizes with anti-GD2 mAb therapy in reducing NBL tumor growth. Further mechanistic studies uncovered multiple mechanisms for the observed synergy, including Vorinostat-induced specific NBL cell death and upregulation of the tumor antigen GD2 on the cell surface of surviving NBL cells. Moreover, Vorinostat created a permissive tumor microenvironment (TME) for tumor-directed mAb therapy by increasing macrophage effector cells expressing high levels of Fc-receptors (FcR) and decreasing the number and function of myeloid-derived suppressor cells (MDSC). Collectively, these data imply further testing of other epigenetic modulators with immunotherapy and provide a strong basis for clinical testing of anti-GD2 plus Vorinostat combination therapy in NBL patients. PMID:27471639

  8. Ultrasound assisted ambient temperature synthesis of ternary oxide Ag MO 2 ( M=Fe, Ga)

    NASA Astrophysics Data System (ADS)

    Nagarajan, R.; Tomar, Nobel

    2009-06-01

    The application of ultrasound for the synthesis of ternary oxide Ag MO 2 ( M=Fe, Ga) was investigated. Crystalline α-AgFeO 2 was obtained from the alkaline solutions of silver and iron hydroxides by sonication for 40 minutes. α-AgFeO 2 was found to absorb optical radiation in the 300-600 nm range as shown by diffuse reflectance spectroscopy. The Raman spectrum of α-AgFeO 2 exhibited two bands at 345 and 638 cm -1. When β-NaFeO 2 was sonicated with aqueous silver nitrate solution for 60 minutes, β-AgFeO 2 possessing orthorhombic structure was obtained as the ion-exchanged product. The Raman spectrum of β-AgFeO 2 showed four strong bands at 295, 432, 630 and 690 cm -1. Sonication of β-NaGaO 2 with aqueous silver nitrate solution for 60 minutes resulted in olive green colored, α-AgGaO 2. The diffuse reflectance spectrum and the EDX analysis confirmed that the ion-exchange through sonication was complete. The Raman spectrum of α-AgGaO 2 had weak bands at 471 and 650 cm -1.

  9. Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts

    PubMed Central

    Benavides Damm, Tatiana; Franco-Obregón, Alfredo; Egli, Marcel

    2013-01-01

    Prolonged spaceflight gives rise to muscle loss and reduced strength, a condition commonly referred to as space atrophy. During exposure to microgravity, skeletal muscle myoblasts are mechanically unloaded and respond with attenuated cell proliferation, slowed cell cycle progression, and modified protein expression. To elucidate the underlying mechanisms by which muscle mass declines in response to prolonged microgravity exposure, we grew C2C12 mouse muscle cells under conditions of simulated microgravity (SM) and analyzed their proliferative capacity, cell cycle progression, and cyclin B and D expression. We demonstrated that the retarded cell growth observed in SM was correlated with an approximate 16 h delay in G2/M phase progression, where cells accumulated specifically between the G2 checkpoint and the onset of anaphase, concomitantly with a positive expression for cyclin B. The effect was specific for gravitational mechanical unloading as cells grown under conditions of hypergravity (HG, 4 g) for similar durations of time exhibited normal proliferation and normal cell cycle progression. Our results show that SM and HG exert phenomenological distinct responses over cell cycle progression. The deficits of SM can be restored by terrestrial gravitational force, whereas the effects of HG are indistinguishable from the 1 g control. This suggests that the mechanotransduction apparatus of cells responds differently to mechanical unloading and loading. PMID:23974110

  10. Results from recent hydrogen pellet acceleration studies with a 2-m railgun

    SciTech Connect

    Kim, K.; Zhang, D.J.; King, T.; Haywood, R.; Manns, W.; Venneri, F.

    1989-12-01

    A new 3.2-mm-diameter, two-stage, fuseless, plasma-arc-driven electromagnetic railgun has been designed, constructed, and successfully operated to achieve a record velocity of 2.67 km/s({sup b}) for 3.2 mmD {times} 4 mmL solid hydrogen pellet. The first stage of this hydrogen pellet injector is a combination of a hydrogen pellet generator and a gas fun. The second stage is a 2-m-long railgun which serves as a booster accelerator. The gas fun accelerates a frozen hydrogen pellet to a medium velocity and injects it into the railgun through a perforated coupling piece, which also serves a pressure-relieving mechanism. An electrical breakdown of the propellant gas, which has followed the pellet from the gas fun into the railgun, forms a conducting plasma-arc armature immediately behind the pellet allowing for fuseless operation of the railgun. Study of the pressure profile and the behavior of the plasma-arc armature inside the railgun bore led to elimination of spurious arcing, which prevents operation of the railgun at high voltages (and, therefore, at high currents). A timing circuit that can automatically measure the pellet input velocity and allows for accurate control of arc initiation behind the pellet helps prevent pellet disintegration and mistriggering of the arc initiation circuit. Results from the recent cryogenic operation of the two-stage pellet acceleration system are reported. 11 refs., 2 figs., 1 tab.

  11. Cummingtonite: A reversible, nonquenchable transition from P21/m to C2/m symmetry

    USGS Publications Warehouse

    Prewitt, C.T.; Papike, J.J.; Ross, M.

    1970-01-01

    Cummingtonite from the Gouverneur, New York, talc district (Sample No. U.S.N.M. 115046) with the composition, (Ca0.36Na0.06Mn0.96Mg0.57) Mg5Si8O22 (OH)2, unit cell parameters a = 9.550 ?? 0.001, b = 18.007 ?? 0.003, c = 5.298 ?? 0.001 A ??, ?? = 102??39??? ?? 1???, and space group P21/m, has been used in a high-temperature, single-crystal, X-ray diffraction study. When diffraction patterns are taken of the crystals heated in a sealed silica capillary to 45??C or higher, these reflections disappear, indicating a transition to C2/m symmetry. The transition appears to be analogous to the P21/c to C2/c transition between 700?? and 800??C discovered recently in (Mg0.30Fe0.70) SiO3 clinopyroxene. In addition to the cummingtonite transition, we have also found a transition in pigeonite at higher temperatures. The transition occurs in this pigeonite (Gunflint Iron Formation, Minnesota, (Ca0.04Fe0.78Mg0.18)SiO3) at about 670??C. This is a significantly lower temperature than was found for the Ca-poor clinopyroxene. ?? 1970.

  12. Aerodynamic performance of a new LM 17.2 m rotor

    NASA Astrophysics Data System (ADS)

    Rasmussen, F.

    1985-03-01

    The aerodynamic properties of a 17.2 m diameter rotor mounted on a 55 kW windmill were measured. Power curves were measured for a range of blade tip angles to find the best angle in relation to energy production and stalling characteristics. With this optimum blade setting the flapwise blade root bending moment was measured as a function of wind speed. The drag coefficient at 90 deg angle of attack was calculated from measurements of the integrated value, i.e., the flapwise blade root bending moment as a function of wind speed during stand still. Profile properties are estimated from aerodynamic calculations, and the results compared to profile data from three dimensional wind tunnel measurements. The flapwise blade root bending moment versus blade angular position during one revolution was measured in skew wind and compared with calculations. The influence of surface roughnes introduced at a certain percentage of the section chord and the dependency on the Reynolds number is investigated, and discussed from observed discrepancies in the measured power curves.

  13. HOI-02 induces apoptosis and G2-M arrest in esophageal cancer mediated by ROS

    PubMed Central

    Zhang, C; Liu, K; Yao, K; Reddy, K; Zhang, Y; Fu, Y; Yang, G; Zykova, T A; Shin, S H; Li, H; Ryu, J; Jiang, Y-n; Yin, X; Ma, W; Bode, A M; Dong, Z; Dong, Z

    2015-01-01

    Reactive oxygen species (ROS) are chemically reactive molecules that perform essential functions in living organisms. Accumulating evidence suggests that many types of cancer cells exhibit elevated levels of ROS. Conversely, generation of ROS has become an effective method to kill cancer cells. (E)-3-hydroxy-3-(4-(4-nitrophenyl)-2-oxobut-3-en-1-yl) indolin-2-one, which is an NO2 group-containing compound designated herein as HOI-02, generated ROS and, in a dose-dependent manner, decreased esophageal cancer cell viability and inhibited anchorage-independent growth, followed by apoptosis and G2-M arrest. Moreover, results of an in vivo study using a patient-derived xenograft mouse model showed that HOI-02 treatment suppressed the growth of esophageal tumors, without affecting the body weight of mice. The expression of Ki-67 was significantly decreased with HOI-02 treatment. In addition, the phosphorylation of c-Jun, and expression of p21, cleaved caspase 3, and DCFH-DA were increased in the HOI-02-treated group compared with the untreated control group. In contrast, treatment of cells with (E)-3-(4-(4-aminophenyl)-2-oxobut-3-en-1-yl)-3-hydroxyindolin-2-one, which is an NH2 group-containing compound designated herein as HOI-11, had no effect. Overall, we identified HOI-02 as an effective NO2 group-containing compound that was an effective therapeutic or preventive agent against esophageal cancer cell growth. PMID:26469961

  14. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  15. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    SciTech Connect

    Faraci, W.S.; Walsh, C.T.

    1989-01-24

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of (1-/sup 14/C)trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and /sup 14/CO/sub 2/ release. At this point, reduction by NaB/sub 3/H/sub 4/ and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes.

  16. Interplanetary Lyman-beta emissions

    NASA Technical Reports Server (NTRS)

    Paresce, F.

    1973-01-01

    Derivation of the intensity of the diffuse hydrogen Lyman-beta glow at 1025 A which is due to resonance scattering of the solar H I 1025 A line by interstellar and interplanetary hydrogen. Two sources of neutral hydrogen are considered: the local interstellar medium interacting with the solar system, and the dust deionization of the H(+) component of the solar wind. It is shown that if the dust geometrical factor is less than or equal to five quintillionths per cm, observations of backscattered Lyman-beta radiation will provide a unique determination of the density and temperature of the local interstellar medium.

  17. Beta Adrenergic Receptors in Keratinocytes

    PubMed Central

    Sivamani, Raja K.; Lam, Susanne T.; Isseroff, R. Rivkah

    2007-01-01

    Synopsis Beta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated in the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound re-epithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease. PMID:17903623

  18. BETA-GAMMA PERSONNEL DOSIMETER

    DOEpatents

    Davis, D.M.; Gupton, E.D.; Hart, J.C.; Hull, A.P.

    1961-01-17

    A personnel dosimeter is offered which is sensitive to both gamma and soft beta radiations from all directions within a hemisphere. The device is in the shape of a small pill box which is worn on a worker-s wrist. The top and sides of the device are provided with 50 per cent void areas to give 50 per cent response to the beta rays and complete response to the gamma rays. The device is so constructed as to have a response which will approximate the dose received by the basal layer of the human epidermis.

  19. Determination of formation constants of hydroxo and carbonate complexes of Pr(3+) in 2 M NaCl at 303 K.

    PubMed

    López-González, H; Jiménez-Reyes, M; Rojas-Hernández, A; Solache-Ríos, M

    1997-10-01

    The hydrolysis of praseodymium III in 2 M sodium chloride at 303 K was studied. Two methods were used: pH titration followed by a computational refinement and solvent extraction in the presence of a competitive ligand. The hydrolysis constants obtained by pH titration were: logbeta(1,H)=-7.68+/-0.07, logbeta(1,2H)=-15.10+/-0.03, and beta(1,3H)=-23.80+/-0.04. The stability constants of praseodymium carbonate complexes were determined by pH titration as well and were: logbeta(1,CO(2-)(3))=5.94+/-0.08 and logbeta(1,2CO(2-)(3))=11.15+/-0.15. Praseodymium carbonate species were taken into consideration for calculating the first hydrolysis constants by the solvent extraction method and the value obtained was: logbeta(1,H)=-7.69+/-0.27. The values for logbeta(1,H) attained by both methods are the same. The species-distribution diagram was obtained from the stability constants of praseodymium carbonate complexes and hydrolysis products in the conditions of the present work. PMID:18966931

  20. Existence of stable solutions to (- Δ) m u =eu in RN with m ≥ 3 and N > 2m

    NASA Astrophysics Data System (ADS)

    Huang, Xia; Ye, Dong

    2016-04-01

    We consider the polyharmonic equation (- Δ) m u =eu in RN with m ≥ 3 and N > 2 m. We prove the existence of many entire stable solutions. This answers some questions raised by Farina and Ferrero in [7].

  1. Genetic Control of the Trigger for the G2/M Checkpoint

    SciTech Connect

    Hall, Eric J.; Smilenov, Lubomir B.; Young, Erik F.

    2013-10-01

    system, the engagement of the G2/M checkpoint only occurs at doses where most of the cells are bound for mitotic catastrophe. Further, compound haploinsufficiency of various radiosensitizing genes does not impact the threshold of activation. The experiments confirm a threshold of activation for the G2/M checkpoint, hinting at two separate radiation response programs acting below and above this threshold. Small RNA transfer in bystander effect biology: Small regulatory RNA molecules have now risen in prominence and utility. Specific examples are small interfering RNAs (siRNA) which are employed in cell level expression ablation projects and micro-RNAs (miRNA) which are a pool of short transcription products which serve to modulate the expression of other transcripts emerging from the genome in a meta-regulatory fine tuning of gene expression. The existing tenets of bystander effect radiation biology involve the communication of inflammatory mediators or direct intercellular communication of reactive oxygen/nitrogen species in cell-to-cell communicative organelles called gap junctions. By ablating gap junctions, reducing the ROS/inflammatory cytokine expression one can attenuate bystander effect signaling in cell culture systems. We hypothesized that miRNAs are a competent intercellular communication molecule and therefore a possible component of the bystander response. This view is supported by the observation that miRNA are secreted from cells in exosomes found in the circulation. This circulating pool reports disease type and severity in humans. We proposed use of microbeam irradiation technology at our facilities and enhancement of this capability with a new sorting technology which would allow us to sort irradiated and non-irradiated cells with absolute fidelity. Pursuing direct quantitative transfer assessment, we succeeded in designing and constructing a new add-on sorting appliance which harmonized with our existing instruments. The sorter allowed us to gently sort

  2. The ASTRI SST-2M telescope prototype for the Cherenkov Telescope Array: camera DAQ software architecture

    NASA Astrophysics Data System (ADS)

    Conforti, Vito; Trifoglio, Massimo; Bulgarelli, Andrea; Gianotti, Fulvio; Fioretti, Valentina; Tacchini, Alessandro; Zoli, Andrea; Malaguti, Giuseppe; Capalbi, Milvia; Catalano, Osvaldo

    2014-07-01

    ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is a Flagship Project financed by the Italian Ministry of Education, University and Research, and led by INAF, the Italian National Institute of Astrophysics. Within this framework, INAF is currently developing an end-to-end prototype of a Small Size dual-mirror Telescope. In a second phase the ASTRI project foresees the installation of the first elements of the array at CTA southern site, a mini-array of 7 telescopes. The ASTRI Camera DAQ Software is aimed at the Camera data acquisition, storage and display during Camera development as well as during commissioning and operations on the ASTRI SST-2M telescope prototype that will operate at the INAF observing station located at Serra La Nave on the Mount Etna (Sicily). The Camera DAQ configuration and operations will be sequenced either through local operator commands or through remote commands received from the Instrument Controller System that commands and controls the Camera. The Camera DAQ software will acquire data packets through a direct one-way socket connection with the Camera Back End Electronics. In near real time, the data will be stored in both raw and FITS format. The DAQ Quick Look component will allow the operator to display in near real time the Camera data packets. We are developing the DAQ software adopting the iterative and incremental model in order to maximize the software reuse and to implement a system which is easily adaptable to changes. This contribution presents the Camera DAQ Software architecture with particular emphasis on its potential reuse for the ASTRI/CTA mini-array.

  3. Uncoupling protein-2 mRNA expression in mice subjected to intermittent hypoxia*

    PubMed Central

    Vieira, Luciana Rodrigues; Martinez, Denis; Forgiarini, Luiz Felipe; da Rosa, Darlan Pase; de Muñoz, Gustavo Alfredo Ochs; Fagundes, Micheli; Martins, Emerson Ferreira; Montanari, Carolina Caruccio; Fiori, Cintia Zappe

    2015-01-01

    Objective: To investigate the effect of intermittent hypoxia-a model of obstructive sleep apnea (OSA)-on pancreatic expression of uncoupling protein-2 (UCP2), as well as on glycemic and lipid profiles, in C57BL mice. Methods: For 8 h/day over a 35-day period, male C57BL mice were exposed to intermittent hypoxia (hypoxia group) or to a sham procedure (normoxia group). The intermittent hypoxia condition involved exposing mice to an atmosphere of 92% N and 8% CO2 for 30 s, progressively reducing the fraction of inspired oxygen to 8 ± 1%, after which they were exposed to room air for 30 s and the cycle was repeated (480 cycles over the 8-h experimental period). Pancreases were dissected to isolate the islets. Real-time PCR was performed with TaqMan assays. Results: Expression of UCP2 mRNA in pancreatic islets was 20% higher in the normoxia group than in the hypoxia group (p = 0.11). Fasting serum insulin was higher in the hypoxia group than in the normoxia group (p = 0.01). The homeostasis model assessment of insulin resistance indicated that, in comparison with the control mice, the mice exposed to intermittent hypoxia showed 15% lower insulin resistance (p = 0.09) and 21% higher pancreatic β-cell function (p = 0.01). Immunohistochemical staining of the islets showed no significant differences between the two groups in terms of the area or intensity of α- and β-cell staining for insulin and glucagon. Conclusions: To our knowledge, this is the first report of the effect of intermittent hypoxia on UCP2 expression. Our findings suggest that UCP2 regulates insulin production in OSA. Further study of the role that UCP2 plays in the glycemic control of OSA patients is warranted. PMID:25909153

  4. On the behavior of plasma with a negative current in the L-2M stellarator

    SciTech Connect

    Shchepetov, S. V. Khol’nov, Yu. V.; Vasil’kov, D. G.

    2015-09-15

    The behavior of plasma with a negative current in the range of 5 kA ≤ vertical bar J vertical bar ≤ 16 kA in the L-2M stellarator is studied. Plasma is created and heated by means of electron cyclotron resonance heating (ECRH). Here, the definition “negative” stands for a toroidal current directed in such a way that it reduces the initial rotational transform µ in absolute value. It is shown that, only at relatively small values of the negative current ( vertical bar J vertical bar ∼ 6 kA), the increase in the shear leads to a reduction in electromagnetic turbulence. As vertical bar J vertical bar rises, the average level of magnetic fluctuations in the stationary phase of the discharge gradually increases. After ECRH is switched off (i.e., when plasma cools down), there is a time interval in which the amplitude of magnetic field fluctuations increases. No coherent three-dimensional modes (e.g., double tearing modes) that could accompany the penetration of the current into the plasma were observed. As for axisymmetric perturbations with m ≠ 0, analysis of the experimental data shows that they are absent at vertical bar J vertical bar ≤ 8 kA, appear in some discharges at vertical bar J vertical bar = 9 kA, and are observed in each discharge at vertical bar J vertical bar ≥ 10 kA. The frequency of these oscillations is on the order of 10 kHz, the poloidal mode number is m = 2, and the duration is 4–6 ms. The absence of oscillations with m = 1 and the small value of the external magnetic field for the m = 2 perturbation indicate that the radial size of the magnetic island is less than 1 cm. This, in turn, suggests that the radial profile of the plasma current changes with increasing vertical bar J vertical bar.

  5. The Protein Kinase Cδ Catalytic Fragment Is Critical for Maintenance of the G2/M DNA Damage Checkpoint*

    PubMed Central

    LaGory, Edward L.; Sitailo, Leonid A.; Denning, Mitchell F.

    2010-01-01

    Protein kinase Cδ (PKCδ) is an essential component of the intrinsic apoptotic program. Following DNA damage, such as exposure to UV radiation, PKCδ is cleaved in a caspase-dependent manner, generating a constitutively active catalytic fragment (PKCδ-cat), which is necessary and sufficient for keratinocyte apoptosis. We found that in addition to inducing apoptosis, expression of PKCδ-cat caused a pronounced G2/M cell cycle arrest in both primary human keratinocytes and immortalized HaCaT cells. Consistent with a G2/M arrest, PKCδ-cat induced phosphorylation of Cdk1 (Tyr15), a critical event in the G2/M checkpoint. Treatment with the ATM/ATR inhibitor caffeine was unable to prevent PKCδ-cat-induced G2/M arrest, suggesting that PKCδ-cat is functioning downstream of ATM/ATR in the G2/M checkpoint. To better understand the role of PKCδ and PKCδ-cat in the cell cycle response to DNA damage, we exposed wild-type and PKCδ null mouse embryonic fibroblasts (MEFs) to UV radiation. Wild-type MEFs underwent a pronounced G2/M arrest, Cdk1 phosphorylation, and induction of apoptosis following UV exposure, whereas PKCδ null MEFs were resistant to these effects. Expression of PKCδ-green fluorescent protein, but not caspase-resistant or kinase-inactive PKCδ, was able to restore G2/M checkpoint integrity in PKCδ null MEFs. The function of PKCδ in the DNA damage-induced G2/M cell cycle checkpoint may be a critical component of its tumor suppressor function. PMID:19917613

  6. Expression, purification and characterization of a recombinant beta-glucosidase from Volvariella Volvacea.

    PubMed

    Li, Xun; Pei, Jianjun; Wu, Guogan; Shao, Weilan

    2005-09-01

    For the first time, a beta-glucosidase gene from the edible straw mushroom, Volvariella volvacea V1-1, has been over-expressed in E. coli. The gene product was purified by chromatography showing a single band on SDS-PAGE. The recombinant enzyme had a molecular mass of 380 kDa with subunits of 97 kDa. The maximum activity was at pH 6.4 and 50 degrees C over a 5 min assay. The purified enzyme was stable from pH 5.6-8.0, had a half life of 1 h at 45 degrees C. The beta-glucosidase had a K(m) of 0.2 mM: for p-nitrophenyl-beta-D: -glucopyranoside. PMID:16215851

  7. Hyperthermia induces expression of transforming growth factor-beta s in rat cardiac cells in vitro and in vivo.

    PubMed Central

    Flanders, K C; Winokur, T S; Holder, M G; Sporn, M B

    1993-01-01

    Hyperthermia causes changes in expression of TGF-beta mRNA and protein in cultured cardiac cells, as well as in the heart in vivo. 12 h after hyperthermia, primary cultures of neonatal rat cardiomyocytes show a two- to threefold decreased expression of TGF-beta mRNAs which returns to control levels by 48 h after heat shock. In cultures of cardiac fibroblasts, expression of TGF-beta mRNAs increases 5-25-fold, 12-48 h after heat shock, while fetal bovine heart endothelial cells show little change in TGF-beta expression after hyperthermia. In each case, mRNAs for TGF-beta s 1, 2, and 3 are regulated similarly. Hearts isolated from rats exposed to hyperthermia show an initial 20-fold decrease in TGF-beta 1 and 3 mRNA levels which return to control levels by 24 h and subsequently are elevated two- to threefold above normal 48-72 h after heat shock; there is little change in TGF-beta 2 mRNA. Expression of immunoreactive TGF-beta 1 and 3 protein, localized intracellularly in myocytes, follows the same pattern as the mRNA expression. By 72 h, some myocytes show hyperstaining for TGF-beta 1. Staining for extracellular TGF-beta 1/3 exhibits the opposite time course, being most intense 3-6 h after heat shock and returning to control levels by 48 h. The increase in TGF-beta s after hyperthermia could play a role in mediating the reported cardioprotective effects of heat shock. Images PMID:8326008

  8. Caliber Schools. Caliber: Beta Academy

    ERIC Educational Resources Information Center

    EDUCAUSE, 2015

    2015-01-01

    Caliber: Beta Academy is reimagining education as we know it, with the belief that the innovations in its model will allow 100% of its students to graduate ready to attend and succeed in a competitive four-year college and beyond. The academic model of the school features personalized learning plans, blended learning for English and math,…

  9. Spectrometers for Beta Decay Electrons

    NASA Astrophysics Data System (ADS)

    Jiang, Yong; Hirshfield, Jay

    2015-04-01

    Inspired by the neutrino mass direct measurement experiment Project 8, precision spectrometers are proposed to simultaneously measure energy and momentum of beta-decay electrons produced in rare nuclear events with improved energy resolution. For detecting single beta decay electrons near the end-point from a gaseous source such as tritium, one type of spectrometer is proposed to utilize stimulated cyclotron resonance interaction of microwaves with electrons in a waveguide immersed in a magnetic mirror. In the external RF fields, on-resonance electrons will satisfy both the cyclotron resonance condition and waveguide dispersion relationship. By correlating the resonances at two waveguide modes, one can associate the frequencies with both the energy and longitudinal momentum of an on-resonance electron to account for the Doppler shifts. For detecting neutrino-less double-beta decay, another spectrometer is proposed with thin foil of double-beta-allowed material immersed in a magnetic field, and RF antenna array for detection of synchrotron radiation from electrons. It utilizes the correlation between the antenna signals including higher harmonics of radiation to reconstruct the total energy distribution.

  10. Neutron Beta Decay Studies with Nab

    SciTech Connect

    Baessler, S.; Alarcon, R.; Alonzi, L. P.; Balascuta, S.; Barron-Palos, L.; Bowman, James David; Bychkov, M. A.; Byrne, J.; Calarco, J; Chupp, T.; Cianciolo, T. V.; Crawford, C.; Frlez, E.; Gericke, M. T.; Glück, F.; Greene, G. L.; Grzywacz, R. K.; Gudkov, V.; Harrison, D.; Hersman, F. W.; Ito, T.; Makela, M.; Martin, J.; McGaughey, P. L.; McGovern, S.; Page, S.; Penttila, Seppo I; Pocanic, Dinko; Salas-Bacci, A.; Tompkins, Z.; Wagner, D.; Wilburn, W. S.; Young, A. R.

    2013-01-01

    Precision measurements in neutron beta decay serve to determine the coupling constants of beta decay and allow for several stringent tests of the standard model. This paper discusses the design and the expected performance of the Nab spectrometer.

  11. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  12. Characterizing Rocky and Gaseous Exoplanets with 2 m Class Space-based Coronagraphs

    NASA Astrophysics Data System (ADS)

    Robinson, Tyler D.; Stapelfeldt, Karl R.; Marley, Mark S.

    2016-02-01

    Several concepts now exist for small, space-based missions to directly characterize exoplanets in reflected light. While studies have been performed that investigate the potential detection yields of such missions, little work has been done to understand how instrumental and astrophysical parameters will affect the ability of these missions to obtain spectra that are useful for characterizing their planetary targets. Here, we develop an instrument noise model suitable for studying the spectral characterization potential of a coronagraph-equipped, space-based telescope. We adopt a baseline set of telescope and instrument parameters appropriate for near-future planned missions like WFIRST-AFTA, including a 2 m diameter primary aperture, an operational wavelength range of 0.4-1.0 μm, and an instrument spectral resolution of λ/Δλ = 70, and apply our baseline model to a variety of spectral models of different planet types, including Earth twins, Jupiter twins, and warm and cool Jupiters and Neptunes. With our exoplanet spectral models, we explore wavelength-dependent planet-star flux ratios for main-sequence stars of various effective temperatures and discuss how coronagraph inner and outer working angle constraints will influence the potential to study different types of planets. For planets most favorable to spectroscopic characterization—cool Jupiters and Neptunes as well as nearby super-Earths—we study the integration times required to achieve moderate signal-to-noise ratio spectra. We also explore the sensitivity of the integration times required to either detect the bottom or presence of key absorption bands (for methane, water vapor, and molecular oxygen) to coronagraph raw contrast performance, exozodiacal light levels, and the distance to the planetary system. Decreasing detector quantum efficiency at longer visible wavelengths makes the detection of water vapor in the atmospheres of Earth-like planets extremely challenging, and also hinders detections

  13. Recent results from the CMD-2 detector at the VEPP-2M collider

    SciTech Connect

    Solodov, E.P.

    1997-01-01

    The general-purpose detector CMD-2 is taking data at the Novosibirsk VEPP-2M e{sup -}e{sup -} collider in the energy range 360-1400 MeV, with luminosity of {approx} 5.0 x 10{sup 30} cm{sup -2} s{sup -1} for the {phi} resonance region. Data from {approx} 1500 nb{sup -1} of integrated luminosity around 1.02 GeV and {approx}500 nb{sup -1} in the 600-1000 MeV range have been collected and preliminary analyses performed. We present progress in studies of the {phi} meson and K{sub S}K{sub L} systems: (a) measurement of the {phi} meson parameters; (b) searches for {phi} rare decays. The new upper limits B({phi}{yields}{eta}{prime} {gamma}) < 2.4 x 10{sup -4}, B({phi} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup +}{pi}{sup -}) < 1.0 x 10{sup -4}, and B({phi} {yields} f{sub 0}{gamma}) < 8 x 10{sup -4} have been obtained; (c) the study of the K{sub L} interactions in the CsI calorimeter; (d) with the help of 32,340 tagged K{sub S}, the semi-rare decay of K{sub S} {yields} {pi}{sup +}{pi}{sup -}{gamma} has been observed with a branching ratio of (1.82 {+-} 0.49)x10{sup -3}; and (e) selection of events with K{sub S}K{sub L} coupled decays and interactions. The regeneration cross section of the low moments K{sub L} was found to be {sigma}{sub reg}{sup Be} = 63 {+-} 19 mb. Data from the 600-1000 MeV energy range are used for high-accuracy measurement of the e{sup +}e{sup -} annihilation cross section, and the preliminary analysis is presented in this paper.

  14. Neoclassical transport in high [beta] tokamaks

    SciTech Connect

    Cowley, S.C.

    1992-12-01

    Neoclassical, transport in high [beta] large aspect ratio tokamaks is calculated. The variational method introduced by Rosenbluth, et al., is used to calculate the full Onsager matrix in the banana regime. These results are part of a continuing study of the high [beta] large aspect ratio equilibria introduced in Cowley, et al. All the neoclassical coefficients are reduced from their nominal low [beta] values by a factor ([var epsilon]/q[sup 2][beta])[sup [1/2

  15. Tryptophan mutations at azi-etomidate photo-incorporation sites on alpha1 or beta2 subunits enhance GABAA receptor gating and reduce etomidate modulation.

    PubMed

    Stewart, Deirdre; Desai, Rooma; Cheng, Qi; Liu, Aiping; Forman, Stuart A

    2008-12-01

    The potent general anesthetic etomidate produces its effects by enhancing GABA(A) receptor activation. Its photolabel analog [(3)H]azi-etomidate labels residues within transmembrane domains on alpha and beta subunits: alphaMet236 and betaMet286. We hypothesized that these methionines contribute to etomidate sites formed at alpha-beta subunit interfaces and that increasing side-chain bulk and hydrophobicity at either locus would mimic etomidate binding and block etomidate effects. Channel activity was electrophysiologically quantified in alpha(1)beta(2)gamma(2L) receptors with alpha(1)M236W or beta(2)M286W mutations, in both the absence and the presence of etomidate. Measurements included spontaneous activation, GABA EC(50), etomidate agonist potentiation, etomidate direct activation, and rapid macrocurrent kinetics. Both alpha(1)M236W and beta(2)M286W mutations induced spontaneous channel opening, lowered GABA EC(50), increased maximal GABA efficacy, and slowed current deactivation, mimicking effects of etomidate on alpha(1)beta(2)gamma(2L) channels. These changes were larger with alpha(1)M236W than with beta(2)M286W. Etomidate (3.2 muM) reduced GABA EC(50) much less in alpha(1)M236Wbeta(2)gamma(2L) receptors (2-fold) than in wild type (23-fold). However, etomidate was more potent and efficacious in directly activating alpha(1)M236Wbeta(2)gamma(2L) compared with wild type. In alpha(1)beta(2)M286Wgamma(2L) receptors, etomidate induced neither agonist-potentiation nor direct channel activation. These results support the hypothesis that alpha(1)Met236 and beta(2)Met286 are within etomidate sites that allosterically link to channel gating. Although alpha(1)M236W produced the larger impact on channel gating, beta(2)M286W produced more profound changes in etomidate sensitivity, suggesting a dominant role in drug binding. Furthermore, quantitative mechanistic analysis demonstrated that wild-type and mutant results are consistent with the presence of only one class of

  16. Auxiliary instruments for the absolute calibration of the ASTRI SST-2M prototype for the Cherenkov Telescope Array

    NASA Astrophysics Data System (ADS)

    Maccarone, Maria C.; Segreto, Alberto; Catalano, Osvaldo; La Rosa, Giovanni; Russo, Francesco; Sottile, Giuseppe; Gargano, Carmelo; Biondo, Benedetto; Fiorini, Mauro; Incorvaia, Salvatore; Toso, Giorgio

    2014-08-01

    ASTRI SST-2M is the end-to-end prototype telescope under development by the Italian National Institute of Astrophysics, INAF, proposed for the investigation of the highest-energy gamma-ray band in the framework of the Cherenkov Telescope Array, CTA. The ASTRI SST-2M prototype will be installed in Italy at the INAF station located at Serra La Nave on Mount Etna during Fall 2014. The calibration and scientific validation phase will start soon after. The calibration of a Cherenkov telescope includes several items and tools. The ASTRI SST- 2M camera is equipped with an internal fiber illumination system that allows to perform the relative calibration through monitoring of gain and efficiency variations of each pixel. The absolute calibration of the overall system, including optics, will take advantage from auxiliary instrumentation, namely UVscope and UVSiPM, two small-aperture multi-pixels photon detectors NIST calibrated in lab. During commissioning phase, to measure the main features of ASTRI SST-2M, as its overall spectral response, the main telescope and the auxiliary UVscope-UVSiPM will be illuminated simultaneously by a spatially uniform flux generated by a ground-based light source, named Illuminator, placed at a distance of few hundreds meters. Periodically, during clear nights, the flux profiles of a reference star tracked simultaneously by ASTRI SST-2M and UVscope-UVSiPM will allow to evaluate the total atmospheric attenuation and the absolute calibration constant of the ASTRI SST-2M prototype. In this contribution we describe the auxiliary UVscope-UVSiPM and Illuminator sub-system together with an overview of the end-to-end calibration procedure foreseen for the ASTRI SST-2M telescope prototype.

  17. Polypeptides having beta-glucosidase activity and beta-xylosidase activity and polynucleotides encoding same

    SciTech Connect

    Morant, Marc Dominique

    2014-04-29

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  18. Polypeptides having beta-glucosidase activity and beta-xylosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  19. Polypeptides having beta-glucosidase and beta-xylosidase activity and polynucleotides encoding same

    DOEpatents

    Morant, Marc Dominique

    2014-05-06

    The present invention relates to isolated polypeptides having beta-glucosidase activity, beta-xylosidase activity, or beta-glucosidase and beta-xylosidase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  20. Genetics Home Reference: beta-ureidopropionase deficiency

    MedlinePlus

    ... eliminate beta-ureidopropionase enzyme activity. Loss of this enzyme function reduces the production of beta-aminoisobutyric acid and ... aminoisobutyric acid and beta-alanine may impair the function of these molecules in the ... in enzyme activity caused by a particular UPB1 gene mutation, ...

  1. Anionic ring-opening polymerization of beta-alkoxymethyl-substituted beta-lactones.

    PubMed

    Adamus, Grazyna; Kowalczuk, Marek

    2008-02-01

    We report on anionic ring-opening polymerization (ROP) of racemic beta-(methoxymethyl)-beta-propiolactone (MOMPL) and beta-(ethoxymethyl)-beta-propiolactone (EOMPL) initiated by supramolecular complex of potassium acetate and tetrabutylammonium acetate (Bu4N+ Ac) as well as by tetrabutylammonium hydroxide, respectively. Structure of the resulting polymers has been established at the molecular level by electrospray ionization multistage mass spectrometry (ESI-MS(n)) and has been confirmed by FT-IR, NMR, and GPC analyses. Similar behavior of MOMPL and EOMPL with respect to already-studied beta-alkyl-substituted beta-lactones, e.g., beta-butyrolactone (MPL), has been observed under the conditions of anionic ROP (including observed side reactions leading to unsaturated end groups) and the already-established mechanisms of anionic polymerization of beta-alkyl-substituted beta-lactones are extended on beta-alkoxymethyl-substituted ones. PMID:18179174

  2. Modulation of radiation-induced apoptosis and G{sub 2}/M block in murine T-lymphoma cells

    SciTech Connect

    Palayoor, S.T.; Macklis, R.M.; Bump, E.A.; Coleman, C.N.

    1995-03-01

    Radiation-induced apoptosis in lymphocyte-derived cell lines is characterized by endonucleolytic cleavage of cellular DNA within hours after radiation exposure. We have studied this phenomenon qualitatively (DNA gel electrophoresis) and quantitatively (diphenylamine reagent assay) in murine EL4 T-lymphoma cells exposed to {sup 137}Cs {gamma} irradiation. Fragmentation was discernible within 18-24 h after exposure. It increased with time and dose and reached a plateau after 8 Gy of {gamma} radiation. We studied the effect of several pharmacological agents on the radiation-induced G{sub 2}/M block and DNA fragmentation. The agents which reduced the radiation-induced G{sub 2}/M-phase arrest (caffeine, theobromine, theophylline and 2-aminopurine) enhanced the degree of DNA fragmentation at 24 h. In contrast, the agents which sustained the radiation-induced G{sub 2}/M-phase arrest (TPA, DBcAMP, IBMX and 3-aminobenzamide) inhibited the DNA fragmentation at 24 h. These studies on EL4 lymphoma cells are consistent with the hypothesis that cells with radiation-induced genetic damage are eliminated by apoptosis subsequent to a G{sub 2}/M block. Furthermore, it may be possible to modulate the process of radiation-induced apoptosis in lymphoma cells with pharmacological agents that modify the radiation-induced G{sub 2}/M block, and to use this effect in the treatment of patients with malignant disease. 59 refs., 7 figs.

  3. The telescope control of the ASTRI SST-2M prototype for the Cherenkov telescope Array: hardware and software design architecture

    NASA Astrophysics Data System (ADS)

    Antolini, Elisa; Cascone, Enrico; Schwarz, Joseph; Stringhetti, Luca; Tanci, Claudio; Tosti, Gino; Aisa, Damiano; Aisa, Simone; Bagaglia, Marco; Busatta, Andrea; Campeggi, Carlo; Cefala, Marco; Farnesini, Lucio; Giacomel, Stefano; Marchiori, Gianpiero; Marcuzzi, Enrico; Nucciarelli, Giuliano; Piluso, Antonfranco

    2014-07-01

    ASTRI (Astrofisica con Specchi a Tecnologia Replicante Italiana) is a flagship project of the Italian Ministry of Research and led by the Italian National Institute of Astrophysics (INAF). One of its aims is to develop, within the Cherenkov Telescope Array (CTA) framework, an end-to-end small-sized telescope prototype in a dual-mirror configuration (SST-2M) in order to investigate the energy range E ~ 1-100 TeV. A long-term goal of the ASTRI program is the production of an ASTRI/CTA mini-array composed of seven SST-2M telescopes. The prototype, named ASTRI SST-2M, is seen as a standalone system that needs only network and power connections to work. The software system that is being developed to control the prototype is the base for the Mini-Array Software System (MASS), which has the task to make possible the operation of both the ASTRI SST-2M prototype and the ASTRI/CTA mini-array. The scope of this contribution is to give an overview of the hardware and software architecture adopted for the ASTRI SST- 2M prototype, showing how to apply state of the art industrial technologies to telescope control and monitoring systems.

  4. THE YOUNG PLANET-MASS OBJECT 2M1207b: A COOL, CLOUDY, AND METHANE-POOR ATMOSPHERE

    SciTech Connect

    Barman, Travis S.; Macintosh, Bruce; Konopacky, Quinn M.; Marois, Christian

    2011-07-10

    The properties of 2M1207b, a young ({approx}8 Myr) planet-mass companion, have lacked a satisfactory explanation for some time. The combination of low luminosity, red near-IR colors, and L-type near-IR spectrum (previously consistent with T{sub eff} {approx} 1600 K) implies an abnormally small radius. Early explanations for the apparent underluminosity of 2M1207b invoked an edge-on disk or the remnant of a recent protoplanetary collision. The discovery of a second planet-mass object (HR8799b) with similar luminosity and colors as 2M1207b indicates that a third explanation, one of a purely atmospheric nature, is more likely. By including clouds, non-equilibrium chemistry, and low gravity, an atmosphere with effective temperature consistent with evolution cooling-track predictions is revealed. Consequently, 2M1207b, and others like it, requires no new physics to explain nor do they belong to a new class of objects. Instead they most likely represent the natural extension of cloudy substellar atmospheres down to low T{sub eff} and log (g). If this atmosphere only explanation for 2M1207b is correct, then very young planet-mass objects with near-IR spectra similar to field T dwarfs may be rare.

  5. Sterile neutrinos in neutrinoless double beta decay

    SciTech Connect

    Benes, P.; Faessler, Amand; Simkovic, F.; Kovalenko, S.

    2005-04-01

    We study possible contribution of the Majorana neutrino mass eigenstate {nu}{sub h}, dominated by a sterile neutrino component, to neutrinoless double beta (0{nu}{beta}{beta}) decay. A special emphasis is made on accurate calculation of the corresponding nuclear matrix elements. From the current experimental lower bound on the 0{nu}{beta}{beta}-decay half-life of 76 Ge we derive stringent constraints on the {nu}{sub h}-{nu}{sub e} mixing in a wide region of the values of {nu}{sub h} mass. We discuss cosmological and astrophysical status of {nu}{sub h} in this mass region.

  6. Beta Genus Papillomaviruses and Skin Cancer

    PubMed Central

    Howley, Peter M.; Pfister, Herbert J.

    2015-01-01

    A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. PMID:25724416

  7. Dialysis-related amyloidosis: visceral involvement and protein constituents.

    PubMed

    Campistol, J M; Argilés, A

    1996-01-01

    beta 2-M amyloidosis mainly concerns dialysis patients and typically presents with osteoarticular symptoms. In order to precise the incidence and gravity of visceral involvement, subcutaneous abdominal fat aspirates, skin and rectal biopsies, as well as echocardiograms were performed in 26 patients with severe beta 2-M amyloidosis. Visceral amyloidosis was confirmed in 58% and the numbers were even higher when including heart abnormalities suggestive of amyloidosis (81%). Clinical manifestations of visceral involvement were usually not severe and include odynophagia, gastrointestinal haemorrhage, intestinal obstruction, kidney stones, myocardial dysfunction and subcutaneous tumours. The removal and synthesis rates of beta 2-M were assessed during dialysis. Serum 131I-beta 2-M levels decreased by 5-10% with cuprophane and by 40-45% with polysulfone and polyacrylonitrile membranes. These reduction rates were higher than those found with unlabelled beta 2-M suggesting an increased synthesis or release during dialysis. The protein constituents of amyloid deposits were studied. Two different preparative methods to extract the proteins from amyloid deposits were used. TCA precipitation showed the presence of several proteins which were not observed with PBS homogenizing and resuspending in guanidine. The protein constituents of amyloid fibrils were studied by both, two dimensional gel electrophoresis (2D-gel) as well as protein sequencing after gel filtration. Similarly, the technical approach used for protein analysis greatly influenced the results. It was observed that 2D-gel displayed the presence of proteins which were missed by the gel filtration technique. Some of the proteins contained in amyloid deposits in addition to beta 2-M, were identified as globin chains, kappa and lambda light chains of immunoglobulins, and alpha 2 macroglobulin. A putative participation of these other protein constituents on the pathogenesis of beta 2-microglobulin amyloidosis is

  8. Bioavailability of beta-carotene (betaC) from purple carrots is the same as typical orange carrots while high-betaC carrots increase betaC stores in Mongolian gerbils (Meriones unguiculatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin A (VA) deficiency is a worldwide public health problem. Biofortifying existing sources of beta-carotene (betaC) and increasing dietary betaC could help combat the issue. Two studies were performed to investigate the relative betaC bioavailability of a betaC supplement to purple, high-betaC o...

  9. Quantitative autoradiography of. beta. /sub 1/- and. beta. /sub 2/-adrenergic receptors in rat brain

    SciTech Connect

    Rainbow, T.C.; Parsons, B.; Wolfe, B.B.

    1984-03-01

    The authors used quantitative autoradiography to localize in rat brain ..beta../sub 1/- and ..beta../sub 2/-adrenergic receptors. These receptors were labeled in vitro with /sup 125/I-labeled pindolol, an antagonist of ..beta..-adrenergic receptors that binds nonselectively to both ..beta../sub 1/ and ..beta../sub 2/ subtypes. The selective inhibition of /sup 125/I-labeled pindolol binding with specific antagonists of ..beta../sub 1/ and ..beta../sub 2/ receptors allowed the visualization of ..beta..-adrenergic receptor subtypes. High levels of ..beta../sub 1/ receptors were observed in the cingulate cortex, layers I and II of the cerebral cortex, the hippocampus, the Islands of Calleja, and the gelatinosus, mediodorsal, and ventral nuclei of the thalamus. High levels of ..beta../sub 2/ receptors were found in the molecular layer of the cerebellum, over pia mater, and in the central, paraventricular, and caudal lateral posterior thalamic nuclei. Approximately equal levels of ..beta../sub 1/ and ..beta../sub 2/ receptors occurred in the substantia nigra, the olfactory tubercle, layer IV of the cerebral cortex, the medial preoptic nucleus, and all nuclei of the medulla. The pronounced differences in the ratio of ..beta../sub 1/ to ..beta../sub 2/ receptors among brain regions suggests that the subtypes of ..beta..-adrenergic receptors may play different roles in neuronal function. 38 references, 3 figures, 1 table.

  10. Ofloxacin/beta-cyclodextrin complexation.

    PubMed

    Koester, L S; Guterres, S S; Le Roch, M; Eifler-Lima, V L; Zuanazzi, J A; Bassani, V L

    2001-07-01

    Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with beta-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and 1H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and beta-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling. PMID:11548860

  11. Beta-catenin expression in human cancers.

    PubMed Central

    Takayama, T.; Shiozaki, H.; Shibamoto, S.; Oka, H.; Kimura, Y.; Tamura, S.; Inoue, M.; Monden, T.; Ito, F.; Monden, M.

    1996-01-01

    Cell-cell adhesion in tissue is mainly regulated by homotypic interaction of cadherin molecules, which are anchored to the cytoskeleton via cytoplasmic proteins, including alpha- and beta-catenin. Although we previously demonstrated that alpha-catenin is crucial for cadherin function in vivo, little is known about the role of beta-catenin. We examined the expression of beta-catenin in human carcinoma samples along with normal tissue (esophagus, stomach, and colon) by immunostaining using our antibody for beta-catenin. Normal epithelium strongly expressed beta-catenin. However, beta-catenin expression was frequently reduced in primary tumors of the esophagus (10 of 15, 67%), stomach (9 of 19, 47%), and colon (11 of 22, 50%). From an immunoprecipitation study, we found that beta-catenin forms a complex with E-cadherin not only in the normal epithelium but also in cancerous tissues. In coexpression patterns of E-cadherin and beta-catenin, 43 (77%) of the 56 tumors showed a similar expression of both molecules, whereas the other 13 tumors (23%) showed positive staining for E-cadherin and reduced expression of beta-catenin. These findings suggest that beta-catenin forms a complex with E-cadherin in vivo and down-regulation of beta-catenin expression is associated with malignant transformation. Images Figure 1 Figure 2 Figure 3 PMID:8546224

  12. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  13. [Beta-adrenergic receptor blocker poisoning].

    PubMed

    Reingardiene, Dagmara

    2007-01-01

    Beta-adrenergic receptor blocking drugs are used in the treatment of hypertension, angina, myocardial infarction, cardiac dysrhythmia, cardiomyopathy, migraine headache, thyrotoxicosis, and glaucoma. beta-adrenergic receptor blocking agents are competitive antagonist at beta(1), beta(2), or both types of adrenergic receptors. Overdoses of beta-adrenergic receptor blockers are uncommon, but are associated with significant morbidity and mortality. This review article discusses the properties of beta-adrenergic receptor blockers, presents the doses of these drugs causing toxicity and doses, after ingestion of which, referral to an emergency department is recommended. Clinical presentation of overdose (the cardiovascular, neurologic manifestations, pulmonary and other complications), diagnosis, and treatment (gastrointestinal decontamination; the usage of atropine, phosphodiesterase inhibitors, glucagon, insulin; indications for cardiac pacing, extracorporeal procedures of drug removal, etc.) are analyzed. In addition, this article focuses on clinical course and prognosis of beta-blocker overdose. PMID:17768375

  14. Estimating beta-mixing coefficients

    PubMed Central

    McDonald, Daniel J.; Shalizi, Cosma Rohilla; Schervish, Mark

    2015-01-01

    The literature on statistical learning for time series assumes the asymptotic independence or “mixing” of the data-generating process. These mixing assumptions are never tested, and there are no methods for estimating mixing rates from data. We give an estimator for the beta-mixing rate based on a single stationary sample path and show it is L1-risk consistent. PMID:26279742

  15. [The beta-adrenergic receptor].

    PubMed

    Bicho, M P; Manso, C F

    1992-12-01

    The Authors review the constitution and mechanism of action of the beta adrenergic receptor. It is part of a large family which includes visual pigments, muscarinic, serotonergic, olfactive and substance K receptors. Catecholamines given an electron to the receptor. It goes then successively to the alpha submit of Gs protein ant to adenylyl cyclase. The process of activation consists in a successive transfer of one electron. PMID:1337834

  16. DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization

    NASA Astrophysics Data System (ADS)

    Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.

    2016-06-01

    Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

  17. The expression of transforming growth factor-beta by cultured chick growth plate chondrocytes: differential regulation by 1,25-dihydroxyvitamin D3.

    PubMed

    Farquharson, C; Law, A S; Seawright, E; Burt, D W; Whitehead, C C

    1996-05-01

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and transforming growth factor-beta (TGF-beta) are both important regulators of chondrocyte growth and differentiation. We report here that 1,25(OH)2D3 differentially regulates the expression of the genes for TGF-beta 1 to -beta 3 and the secretion of the corresponding proteins in cultured chick chondrocytes. Confluent growth plate chondrocytes were serum-deprived and cultured in varying concentrations of 1,25(OH)2D3. Cells were assayed for TGF-beta mRNA and conditioned medium was assayed for TGF-beta activity and isoform composition. Active TGF-beta was only detected in 10(-8) M 1,25(OH)2D3-treated cultures (8.37 ng active TGF-beta/mg protein). There was a significant decrease in total (latent-active) TGF-beta activity in conditioned medium of 10(-12) M (23.4%; P < 0.05) and 10(-10) M (20.7%; P < 0.05) 1,25(OH)2D3-treated cultures but 10(-8) M 1,25(OH)2D3 significantly increased (30.9%; P < 0.01) TGF-beta activity. The amounts of TGF-beta 1, -beta 2 and -beta 3 isoforms produced were similar in control, 10(-10) or 10(-12) M 1,25(OH)2D3-treated cultures but the conditioned medium of 10(-8) M 1,25(OH)2D3-treated cultures contained significantly higher amounts of all three isoforms. Quantification of TGF-beta mRNA demonstrated differential control of TGF-beta gene expression with TGF-beta 1 and -beta 3 mRNA levels reduced by all concentrations of 1,25(OH)2D3 examined (10(-8), 10(-10) and 10(-12) M) whilst TGF-beta 2 mRNA concentrations were elevated. Our results indicated that 1,25(OH)2D3 regulates chick growth plate chondrocyte TGF-beta secretion and mRNA expression in a concentration-dependent and isoform-specific manner. This interaction may be important in the regulation of chondrocyte metabolism and endochondral bone growth. PMID:8708539

  18. Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids

    SciTech Connect

    Freneaux, E.; Fromenty, B.; Berson, A.; Labbe, G.; Degott, C.; Letteron, P.; Larrey, D.; Pessayre, D. , Hopital Beaujon, Clichy )

    1990-11-01

    The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of (1-{sup 14}C)palmitic acid but not that of (1-{sup 14}C)palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of (1-{sup 14}C)palmitic acid and markedly inhibited the beta oxidation of (1-{sup 14}C)octanoic acid and (1-{sup 14}C)butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of ({sup 14}C)CO{sub 2} from (1-{sup 14}C)fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids.

  19. TGF-{beta} modulates {beta}-Catenin stability and signaling in mesenchymal proliferations

    SciTech Connect

    Amini Nik, Saeid; Ebrahim, Rasoul Pour; Dam, Kim van; Cassiman, Jean-Jacques; Tejpar, Sabine . E-mail: sabine.tejpar@med.kuleuven.be

    2007-08-01

    Here for the first time we showed, despite the oncogenic mutations in {beta}-Catenin, that TGF-{beta} is a modulator of {beta}-Catenin levels in tumoral fibroblasts as well as non-tumoral fibroblasts. The results show that the TGF-{beta} pathway is active in desmoids cells and in in situ tumors. A dose dependent increase in {beta}-Catenin protein levels was observed after TGF-{beta} treatment in combination with an increased repression of GSK-3{beta} both in normal and tumoral fibroblasts. TGF-{beta} stimulation also led to an altered - up to 5 fold - transcriptional activity of {beta}-Catenin responsive promoters, such as IGFBP6 as well as increase of TOPflash activity. TGF-{beta} stimulation increased cell proliferation and BrdU incorporation 2.5 times. Taken together, we propose that TGF-{beta} is a modulator of {beta}-Catenin levels in tumoral fibroblasts and non-tumoral fibroblasts, despite the oncogenic mutations already present in this gene in tumoral fibroblasts of desmoid tumors. This modulation of {beta}-Catenin levels by TGF-{beta} may be involved in determining the tumoral phenotype of the cells.

  20. Some aspects of lunar photography with an 8-inch (0.2m) Schmidt-Cassegrain telescope

    NASA Astrophysics Data System (ADS)

    Marsh, J. C. D.

    1992-04-01

    A brief review of telescope properties and basic data on the Moon leads to some pragmatic conclusions on how to take a high resolution photograph of the lunar surface through an 8-inch (0.2m) Schmidt-Cassegrain telescope using a single lens reflex camera body as the film holder.

  1. A polyphenol mixture from cinnamon targets p38 MAP kinase-regulated signaling pathways to produce G2/M arrest

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We recently demonstrated that treatment of three leukemic cell lines with an aqueous extract of cinnamon (CE) for 24 h produced dose-dependent arrests in the G2/M phase of the cell cycle. To accomplish the goal of understanding underlying mechanisms, we selected the cell line most responsive to the...

  2. Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani

    PubMed Central

    Yadav, Aarti; Chandra, Udita; Saha, Swati

    2016-01-01

    Histone acetyltransferases impact multiple processes. This study investigates the role of histone acetyltransferase HAT4 in Leishmania donovani. Though HAT4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with HAT4-nulls experiencing an unusually long G2/M. Survival of HAT4-nulls in macrophages was also substantially compromised. DNA microarray analysis revealed that HAT4 modestly regulated the expression of only a select number of genes, thus not being a major modulator of global gene expression. Significantly, cdc20 was among the downregulated genes. To ascertain if decreased expression of cdc20 was responsible for HAT4-null growth and cell cycle defects we expressed LdCdc20 ectopically in HAT4-nulls. We found this to alleviate the aberrant growth and cell cycle progression patterns displayed by HAT4-nulls, with cells navigating G2/M phase and re-entering G1 phase smoothly. HAT4-nulls expressing LdCdc20 ectopically showed survival rates comparable to wild type within macrophages, suggesting that G2/M defects were responsible for poor survival of HAT4-nulls within host cells also. These are the first data analyzing the in vivo functional role of HAT4 in any trypanosomatid. Our results directly demonstrate for the first time a role for Cdc20 in regulating trypanosomatid G2/M events, opening avenues for further research in this area. PMID:27272906

  3. Grazing-incidence monochromator for the 15--800 A wavelength range at the storage ring VEPP-2M

    SciTech Connect

    Gluskin, E. S.; Kuzminykh, V. S.; Trakhtenberg, E. M.; Koscheev, S. V.; Devyatov, V. G.; Cherkashin, A. E.; Blau, W.; Meisel, A.; Ehrhardt, H.

    1989-07-01

    A new Rowland monochromator with a fixed output slit, which operates according to the grazing-incidence scheme, is described. The device is notable for the capability to change the Rowland radius within 1--3 m. The monochromator was tested using synchrotron radiation from the storage ring VEPP-2M.

  4. Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani.

    PubMed

    Yadav, Aarti; Chandra, Udita; Saha, Swati

    2016-01-01

    Histone acetyltransferases impact multiple processes. This study investigates the role of histone acetyltransferase HAT4 in Leishmania donovani. Though HAT4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with HAT4-nulls experiencing an unusually long G2/M. Survival of HAT4-nulls in macrophages was also substantially compromised. DNA microarray analysis revealed that HAT4 modestly regulated the expression of only a select number of genes, thus not being a major modulator of global gene expression. Significantly, cdc20 was among the downregulated genes. To ascertain if decreased expression of cdc20 was responsible for HAT4-null growth and cell cycle defects we expressed LdCdc20 ectopically in HAT4-nulls. We found this to alleviate the aberrant growth and cell cycle progression patterns displayed by HAT4-nulls, with cells navigating G2/M phase and re-entering G1 phase smoothly. HAT4-nulls expressing LdCdc20 ectopically showed survival rates comparable to wild type within macrophages, suggesting that G2/M defects were responsible for poor survival of HAT4-nulls within host cells also. These are the first data analyzing the in vivo functional role of HAT4 in any trypanosomatid. Our results directly demonstrate for the first time a role for Cdc20 in regulating trypanosomatid G2/M events, opening avenues for further research in this area. PMID:27272906

  5. Zinc Induced G2/M Blockage is p53 and p21 Dependent in Normal Human Bronchial Epithelial Cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The involvement of the p53 and p21 signal pathway in the G2/M cell cycle progression of zinc supplemented normal human bronchial epithelial (NHBE) cells was examined using the siRNA approach. Cells were cultured for one passage in different concentrations of zinc: <0.4 microM (ZD) as zinc-deficient;...

  6. Phenol-soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells.

    PubMed

    Deplanche, Martine; Filho, Rachid Aref El-Aouar; Alekseeva, Ludmila; Ladier, Emilie; Jardin, Julien; Henry, Gwénaële; Azevedo, Vasco; Miyoshi, Anderson; Beraud, Laetitia; Laurent, Frederic; Lina, Gerard; Vandenesch, François; Steghens, Jean-Paul; Le Loir, Yves; Otto, Michael; Götz, Friedrich; Berkova, Nadia

    2015-05-01

    Staphylococcus aureus is a gram-positive bacterium responsible for a wide range of infections. Host cell cycle alteration is a sophisticated mechanism used by pathogens to hijack the defense functions of host cells. We previously demonstrated that S. aureus MW2 (USA400) bacteria induced a G2/M phase transition delay in HeLa cells. We demonstrate here that this activity is triggered by culture supernatant compounds. Using size exclusion chromatography of the MW2 supernatant, followed by mass spectroscopy analysis of corresponding peaks, we identified phenol-soluble modulin α (PSMα) peptides as the likely candidates for this effect. Indeed, synthetic PSMα1 and PSMα3 caused a G2/M phase transition delay. The implication of PSMα in cell cycle alteration was confirmed by comparison of S. aureus Los Angeles County clone (LAC) wild-type with the isogenic mutant LAC∆psmα, which lacks the psmα operon encoding PSMα1-4. PSMα-induced G2/M transition delay correlated with a decrease in the defensin genes expression suggesting a diminution of antibacterial functions of epithelial cells. By testing the supernatant of S. aureus human clinical isolates, we found that the degree of G2/M phase transition delay correlated with PSMα1 production. We show that PSMs secreted by S. aureus alter the host cell cycle, revealing a newly identified mechanism for fostering an infection. PMID:25648996

  7. Insulin delays the progression of Drosophila cells through G2/M by activating the dTOR/dRaptor complex

    PubMed Central

    Wu, Mary Y W; Cully, Megan; Andersen, Ditte; Leevers, Sally J

    2007-01-01

    In Drosophila and mammals, insulin signalling can increase growth, progression through G1/S, cell size and tissue size. Here, we analyse the way insulin affects cell size and cell-cycle progression in two haemocyte-derived Drosophila cell lines. Surprisingly, we find that although insulin increases cell size, it slows the rate at which these cells increase in number. By using BrdU pulse-chase to label S-phase cells and follow their progression through the cell cycle, we show that insulin delays progression through G2/M, thereby slowing cell division. The ability of insulin to slow progression through G2/M is independent of its ability to stimulate progression through G1/S, so is not a consequence of feedback by the cell-cycle machinery to maintain cell-cycle length. Insulin's effects on progression through G2/M are mediated by dTOR/dRaptor signalling. Partially inhibiting dTOR/dRaptor signalling by dsRNAi or mild rapamycin treatment can increase cell number in cultured haemocytes and the Drosophila wing, respectively. Thus, insulin signalling can influence cell number depending on a balance between its ability to accelerate progression through G1/S and delay progression through G2/M. PMID:17183368

  8. Environmental Solutions: A Summary of Contributions for FY05: PNNL Contributions to CH2M HILL Hanford Group, Inc.

    SciTech Connect

    Brouns, Thomas M.; Manke, Kristin L.

    2006-03-01

    This booklet describes Pacific Northwest National Laboratory's scientific and technical contributions in fiscal year 2005 to the CH2M HILL Hanford Group, Inc., the U.S. Department of Energy Office of River Protection's primte contractor for the Hanford Site radioactive waste tanks.

  9. Environmental Solutions, A Summary of Contributions for FY04: PNNL Contributions to CH2M HILL Hanford Group, Inc.

    SciTech Connect

    Brouns, Thomas M.

    2005-03-08

    In 2004, Pacific Northwest National Laboratory provided analyses, reviews, testing, and new tools to assist CH2M HILL Hanford Group, Inc. in accomplishing their River Protection Project objectives. These objectives are safe storage, retrieval, and treatment of radioactive waste from Hanford's tanks, closure of tanks, and disposal of treated wastes.

  10. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) overexpression in pancreatic ductal adenocarcinoma correlates with poor survival

    PubMed Central

    2010-01-01

    Background Pancreatic ductal adenocarcinoma is a lethal disease with a 5-year survival rate of 4% and typically presents in an advanced stage. In this setting, prognostic markers identifying the more agrressive tumors could aid in managment decisions. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3, also known as IMP3 or KOC) is an oncofetal RNA-binding protein that regulates targets such as insulin-like growth factor-2 (IGF-2) and ACTB (beta-actin). Methods We evaluated the expression of IGF2BP3 by immunohistochemistry using a tissue microarray of 127 pancreatic ductal adenocarcinomas with tumor grade 1, 2 and 3 according to WHO criteria, and the prognostic value of IGF2BP3 expression. Results IGF2BP3 was found to be selectively overexpressed in pancreatic ductal adenocarcinoma tissues but not in benign pancreatic tissues. Nine (38%) patient samples of tumor grade 1 (n = 24) and 27 (44%) of tumor grade 2 (n = 61) showed expression of IGF2BP3. The highest rate of expression was seen in poorly differentiated specimen (grade 3, n = 42) with 26 (62%) positive samples. Overall survival was found to be significantly shorter in patients with IGF2BP3 expressing tumors (P = 0.024; RR 2.3, 95% CI 1.2-4.8). Conclusions Our data suggest that IGF2BP3 overexpression identifies a subset of pancreatic ductal adenocarcinomas with an extremely poor outcome and supports the rationale for developing therapies to target the IGF pathway in this cancer. PMID:20178612

  11. HLA antigen expression in enteropathy associated T cell lymphoma.

    PubMed Central

    Ashton-Key, M; Singh, N; Pan, L X; Smith, M E

    1996-01-01

    AIMS: To investigate the occurrence of abnormal patterns of HLA-ABC and HLA-DR expression in enteropathy associated T cell lymphoma and to relate such abnormalities to the Epstein Barr virus (EBV) status of the tumours. METHODS: Eleven enteropathy associated T cell lymphomas were immunostained with HC10 (HLA-ABC heavy chain) and TAL 1B5 (HLA-DR alpha chain) monoclonal antibodies and polyclonal anti-beta 2 microglobulin (beta 2m, the HLA-ABC light chain) antibodies. In situ hybridisation for EBV using EBER probes was performed on all cases. RESULTS: Tumour cells of two of 11 patients were EBER positive. One of these showed partial, and the other, complete loss of beta 2m. HLA-DR expression was undetectable in both patients. Of the remaining nine EBER negative tumours, two were HLA-ABC heavy chain negative or showed only occasional positive cells and five of nine showed partial or complete loss of the HLA-ABC light chain, beta 2m. Seven of the nine cases were either negative for HLA-DR or showed weak expression in a proportion of tumour cells. CONCLUSIONS: These data show that low or absent HLA-ABC and HLA-DR antigen expression occurs commonly in enteropathy associated T cell lymphoma. These abnormal patterns of HLA expression may be associated with escape from immune attack which, in a minority of patients, could be directed against EBV antigens. Images PMID:8813950

  12. Soluble HL-A antigens in serum. I. Isolation and purification.

    PubMed

    Oh, S K; Pellegrino, M A; Ferrone, S; Sevier, E D; Reisfeld, R A

    1975-03-01

    A new method was developed which utilizes fractional salting out, gel filtration, ion exchange chromatography and polyacrylamide gel electrophoresis for the isolation and purification of soluble HL-A antigens from serum. The method produced purified antigens possessing HL-A 5,9 specificities with yield up to 60% of that detected in the original serum. Up to 150-fold increase in specific HL-A antigenic activity above that in the starting material could be achieved as measured by the ability of the purified antigens to specifically inhibit the cytotoxic activity of HL-A alloantisera against selected target cells. Electrophoretically purified HL-A antigens with different specificities appear to have a similar molecular size, i.e. 33 000, but differ in their electric charge properties, beta2-microglobulin (beta2m) seems to be noncovalently associated with HL-A antigens present in serum, but during purification beta2m in progressively lost until at the final purification by polyacrylamide gel electrophoresis, the material is completely devoid of beta2m. PMID:789087

  13. Bud-Localization of CLB2 mRNA Can Constitute a Growth Rate Dependent Daughter Sizer.

    PubMed

    Spiesser, Thomas W; Kühn, Clemens; Krantz, Marcus; Klipp, Edda

    2015-04-01

    Maintenance of cellular size is a fundamental systems level process that requires balancing of cell growth with proliferation. This is achieved via the cell division cycle, which is driven by the sequential accumulation and destruction of cyclins. The regulatory network around these cyclins, particularly in G1, has been interpreted as a size control network in budding yeast, and cell size as being decisive for the START transition. However, it is not clear why disruptions in the G1 network may lead to altered size rather than loss of size control, or why the S-G2-M duration also depends on nutrients. With a mathematical population model comprised of individually growing cells, we show that cyclin translation would suffice to explain the observed growth rate dependence of cell volume at START. Moreover, we assess the impact of the observed bud-localisation of the G2 cyclin CLB2 mRNA, and find that localised cyclin translation could provide an efficient mechanism for measuring the biosynthetic capacity in specific compartments: The mother in G1, and the growing bud in G2. Hence, iteration of the same principle can ensure that the mother cell is strong enough to grow a bud, and that the bud is strong enough for independent life. Cell sizes emerge in the model, which predicts that a single CDK-cyclin pair per growth phase suffices for size control in budding yeast, despite the necessity of the cell cycle network around the cyclins to integrate other cues. Size control seems to be exerted twice, where the G2/M control affects bud size through bud-localized translation of CLB2 mRNA, explaining the dependence of the S-G2-M duration on nutrients. Taken together, our findings suggest that cell size is an emergent rather than a regulatory property of the network linking growth and proliferation. PMID:25910075

  14. Phenol-soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells

    PubMed Central

    Deplanche, Martine; Filho, Rachid Aref El-Aouar; Alekseeva, Ludmila; Ladier, Emilie; Jardin, Julien; Henry, Gwénaële; Azevedo, Vasco; Miyoshi, Anderson; Beraud, Laetitia; Laurent, Frederic; Lina, Gerard; Vandenesch, François; Steghens, Jean-Paul; Le Loir, Yves; Otto, Michael; Götz, Friedrich; Berkova, Nadia

    2015-01-01

    Staphylococcus aureus is a gram-positive bacterium responsible for a wide range of infections. Host cell cycle alteration is a sophisticated mechanism used by pathogens to hijack the defense functions of host cells. We previously demonstrated that S. aureus MW2 (USA400) bacteria induced a G2/M phase transition delay in HeLa cells. We demonstrate here that this activity is triggered by culture supernatant compounds. Using size exclusion chromatography of the MW2 supernatant, followed by mass spectroscopy analysis of corresponding peaks, we identified phenol-soluble modulin α (PSMα) peptides as the likely candidates for this effect. Indeed, synthetic PSMα1 and PSMα3 caused a G2/M phase transition delay. The implication of PSMα in cell cycle alteration was confirmed by comparison of S. aureus Los Angeles County clone (LAC) wild-type with the isogenic mutant LAC∆psmα, which lacks the psmα operon encoding PSMα1–4. PSMα-induced G2/M transition delay correlated with a decrease in the defensin genes expression suggesting a diminution of antibacterial functions of epithelial cells. By testing the supernatant of S. aureus human clinical isolates, we found that the degree of G2/M phase transition delay correlated with PSMα1 production. We show that PSMs secreted by S. aureus alter the host cell cycle, revealing a newly identified mechanism for fostering an infection.—Deplanche, M., Filho. R. A. E.–A., Alekseeva, L., Ladier, E., Jardin, J., Henry, G., Azevedo, V., Miyoshi, A., Beraud, L., Laurent, F., Lina, G., Vandenesch, F., Steghens, J.-P., Le Loir, Y., Otto, M., Götz, F., Berkova, N. Phenol-soluble modulin α induces G2/M phase transition delay in eukaryotic HeLa cells. PMID:25648996

  15. Beta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter covers the use of wild beets in sugar beet improvement, including the basic botany of the species, its distribution; geographical locations of genetic diversity; morphology; cytology and karyotype; genome size; taxonomic position; agricultural status (model plant/weeds/invasive species/...

  16. beta-Galactosidase enzyme fragment complementation for the measurement of Wnt/beta-catenin signaling.

    PubMed

    Verkaar, Folkert; Blankesteijn, W Matthijs; Smits, Jos F M; Zaman, Guido J R

    2010-04-01

    Wnt/beta-catenin signaling is an important regulator of cell polarity, proliferation, and stem cell maintenance during development and adulthood. Wnt proteins induce the nuclear accumulation of beta-catenin, which regulates the expression of Wnt-responsive genes through association with TCF/LEF transcription factors. Aberrant Wnt/beta-catenin signaling has been implicated in a plethora of pathologies and, most notably, underlies initiation and expansion of several cancers. Here, we apply enzyme fragment complementation to measure the nuclear accumulation of beta-catenin. beta-Catenin was tagged with a peptide fragment of beta-galactosidase and transfected into cells expressing a corresponding deletion mutant of the enzyme exclusively in the nucleus. Stimulation of the cells with recombinant Wnt-3a restored beta-galactosidase activity in a dose-dependent manner with nanomolar potency. Using the assay, we confirmed that Wnt-5a represses beta-catenin-driven reporter gene activity downstream of nuclear entry of beta-catenin. In addition, we tested a library of >2000 synthetic chemical compounds for their ability to induce beta-catenin nuclear accumulation. The immunosuppressive protein kinase C inhibitor sotrastaurin (AEB-071) was identified as an activator of Wnt/beta-catenin signaling at micromolar concentrations. It was confirmed that the compound stabilizes endogenous beta-catenin protein and can induce TCF/LEF-dependent gene transcription. Subsequent biochemical profiling of >200 kinases revealed both isoforms of glycogen synthase kinase 3, as previously unappreciated targets of sotrastaurin. We show that the beta-catenin nuclear accumulation assay contributes to our knowledge of molecular interactions within the Wnt/beta-catenin pathway and can be used to find new therapeutics targeting Wnt/beta-catenin signaling.-Verkaar, F., Blankesteijn, W. M., Smits, J. F. M., Zaman, G. J. R. beta-Galactosidase enzyme fragment complementation for the measurement of Wnt/beta

  17. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    PubMed

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  18. Neutrino Factories and Beta Beams

    SciTech Connect

    Zisman, Michael S.

    2006-06-21

    In this paper we briefly review the concepts of Neutrino Factories and Beta Beam facilities, and indicate the main challenges in terms of beam performance and technological developments. We also describe the worldwide organizations that have embarked on defining and carrying out the necessary R&D on component design, beam simulations of facility performance, and benchmarking of key subsystems via actual beam tests. Currently approved subsystem tests include the Muon Ionization Cooling Experiment (MICE), under construction at Rutherford Appleton Laboratory, and the Mercury Intense Target (MERIT) experiment, to be carried out at CERN. These experiments are briefly described, and their schedules are indicated.

  19. Heterometallic alumo- and gallodisilicates with M(O-Si-O)2M' and [M(O-Si-O)2]2M' cores (M = Al, Ga; M' = Ti, Zr, Hf).

    PubMed

    Huerta-Lavorie, Raúl; Solis-Ibarra, Diego; Báez-Rodríguez, Dana Victoria; Reyes-Lezama, Marisol; de las Nieves Zavala-Segovia, M; Jancik, Vojtech

    2013-06-17

    The synthesis and stabilization of alumo- and gallodisilicates [HC{C(Me)N(2,6-iPr2C6H3)}2]M[(μ-O)Si(OH)(OtBu)2]2 [M = Al (1), Ga (2)] containing two silicate subunits have been achieved through reactions between 2 equiv of the silanediol (tBuO)2Si(OH)2 and the aluminum hydride [HC{C(Me)N(2,6-iPr2C6H3)}2]AlH2 or the gallium amide [HC{C(Me)N(2,6-iPr2C6H3)}2]Ga(NHEt)2, respectively. Compounds 1 and 2 exhibit M(O-SiO2-OH)2 moiety and represent the first molecular metallosilicate-based analogues of neighboring silanol groups found in silicate surfaces. The substitution of both SiOH groups led to the formation of bimetallic compounds with 4R topologies, which are regularly found in zeolitic materials. Thus, reactions between group 4 metal amides M'(NEt2)4 (M' = Ti, Zr, Hf) and 1 and 2 resulted in the formation of nine heterometallic silicates (3-11) containing inorganic M(O-Si-O)2M' and [M(O-Si-O)2]2M' cores with 4R and spiro-4R topologies, respectively. The latter have M···M distances of 0.81 nm. NMR studies of the heterometallic derivatives showed a fluxional behavior at room temperature due to a high flexibility of the eight-membered ring. PMID:23718324

  20. 2-methoxycinnamaldehyde reduces IL-1beta-induced prostaglandin production in rat cerebral endothelial cells.

    PubMed

    Guo, Jian-You; Huo, Hai-Ru; Yang, Yuan-Xiao; Li, Cang-Hai; Liu, Hong-Bin; Zhao, Bao-Sheng; Li, Lan-Fang; Ma, Yue-Ying; Guo, Shu-Ying; Jiang, Ting-Liang

    2006-11-01

    Prostaglandin E2 (PGE2) works as a common final mediator of the febrile. Guizhi-Tang, one of the most famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions, was previously reported to reduce the production of PGE 2 in rats. 2-Methoxycinnamaldehyde is a principle compound isolated from Guizhi-Tang. The aim of the present study was to investigate the effects of 2-methoxycinnamaldehyde on PGE2 production of rat cerebral endothelial cells (CECs). 2-Methoxycinnamaldehyde dose-dependently inhibited interleukin (IL)-1beta-induced PGE2 production in CECs with IC50 values of 174 microM. IL-1beta stimulation increased the protein, activity and mRNA expression of cyclooxygenase (COX)-2 but not COX-1. 2-Methoxycinnamaldehyde reduced IL-1beta-induced protein and activity of COX-2, but did not influence the COX-2 mRNA expression. Our results show that prostaglandin production in CECs during stimulated conditions is sensitive to inhibition by 2-methoxycinnamaldehyde and suggest that 2-methoxycinnamaldehyde may reduce COX-2 protein level and activity but not COX-2 mRNA. PMID:17077517

  1. Method for preparing Pb-. beta. ''-alumina ceramic

    DOEpatents

    Hellstrom, E.E.

    1984-08-30

    A process is disclosed for preparing impermeable, polycrystalline samples of Pb-..beta..''-alumina ceramic from Na-..beta..''-alumina ceramic by ion exchange. The process comprises two steps. The first step is a high-temperature vapor phase exchange of Na by K, followed by substitution of Pb for K by immersing the sample in a molten Pb salt bath. The result is a polycrystalline Pb-..beta..''-alumina ceramic that is substantially crack-free.

  2. C3 polymorphism in beta-thalassemia.

    PubMed

    Germenis, A; Kalantzi, M; Karamerou, A; Politi, C; Fertakis, A

    1984-01-01

    The distribution of phenotypes and gene frequencies of the third component of complement (C3) were studied in 106 beta-thalassemic patients and in 112 carriers of the beta-thalassemia trait. A statistically significant association was found between the C3F gene and homozygous beta-thalassemia. It can be suggested that this association may be related with the high incidence of infections encountered in these patients. PMID:6419525

  3. [Retrospective analysis of prognostic factors in patients with primary lymphoma of the intestine].

    PubMed

    Avilés, A; Guzmán, R; Huerta, J; Díaz-Maqueo, J C

    1991-01-01

    Forty-six patients with stage IE and IIE malignant lymphoma of the intestine were analyzed to assess the efficacy of prognostic factors to predict the course and therapeutic approach in these patients. Because the lesion was considered unresectable in all cases, chemotherapy was given after surgery. Using Cox's univariate regression analysis, survival was found to correlate with stage (IE vs IIE) and high levels of lactic dehidrogenase, nevertheless in the multivariate analysis only beta 2 microglobulin levels were associated with a shorter survival. We believe that treatment of extranodal lymphomas, like nodal presentations, as those of the intestine, could be based in the determinations of prognostic factors and that beta 2 microglobulin would be considered the most powerful prognostic factor. Most studies on patients with malignant lymphoma of the intestine are necessary to define the role of beta 2 microglobulin as therapeutic prognostic index. PMID:1810010

  4. Laboratory and sonographic findings in dialyzed patients with bilateral chronic knee pain versus dialyzed asymptomatic patients.

    PubMed

    Barisić, Igor; Ljutić, Dragan; Vlak, Tonko; Bekavac, Josip; Janković, Stipan

    2007-06-01

    The aim of this study is to evaluate connection of plasma level of beta2-microglobulin, C-reactive protein and uric acid as well as sonographic parameters like thickness of synovial membrane, thickness of femoral condylar cartilage and presence of joint effusion and Baker's cysts with bilateral knee pain in dialyzed patients, comparing them with parameters in asymptomatic dialyzed patients. Plasma levels of beta2-microglobulin and C-reactive protein were significantly higher in symptomatic patients while uric acid level showed no difference among the groups. In symptomatic patients synovial membrane was thicker and in those patients there were more knee effusions and Baker's cysts. Thickness of femoral condylar cartilage showed no difference between groups. That suggests that inflammatory mechanisms developing from beta2-microglobulin accumulation could be important factor in bilateral knee pain in dialyzed patients even in shorter duration dialysis. PMID:17847928

  5. Milk Intolerance, Beta-Casein and Lactose

    PubMed Central

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-01-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  6. Gyrokinetic turbulence simulations at high plasma beta

    SciTech Connect

    Pueschel, M. J.; Kammerer, M.; Jenko, F.

    2008-10-15

    Electromagnetic gyrokinetic turbulence simulations employing Cyclone Base Case parameters are presented for {beta} values up to and beyond the kinetic ballooning threshold. The {beta} scaling of the turbulent transport is found to be linked to a complex interplay of linear and nonlinear effects. Linear investigation of the kinetic ballooning mode is performed in detail, while nonlinearly, it is found to dominate the turbulence only in a fairly narrow range of {beta} values just below the respective ideal limit. The magnetic transport scales like {beta}{sup 2} and is well described by a Rechester-Rosenbluth-type ansatz.

  7. Milk Intolerance, Beta-Casein and Lactose.

    PubMed

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-09-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  8. Regulation of pancreatic beta-cell mass.

    PubMed

    Bouwens, Luc; Rooman, Ilse

    2005-10-01

    Beta-cell mass regulation represents a critical issue for understanding diabetes, a disease characterized by a near-absolute (type 1) or relative (type 2) deficiency in the number of pancreatic beta cells. The number of islet beta cells present at birth is mainly generated by the proliferation and differentiation of pancreatic progenitor cells, a process called neogenesis. Shortly after birth, beta-cell neogenesis stops and a small proportion of cycling beta cells can still expand the cell number to compensate for increased insulin demands, albeit at a slow rate. The low capacity for self-replication in the adult is too limited to result in a significant regeneration following extensive tissue injury. Likewise, chronically increased metabolic demands can lead to beta-cell failure to compensate. Neogenesis from progenitor cells inside or outside islets represents a more potent mechanism leading to robust expansion of the beta-cell mass, but it may require external stimuli. For therapeutic purposes, advantage could be taken from the surprising differentiation plasticity of adult pancreatic cells and possibly also from stem cells. Recent studies have demonstrated that it is feasible to regenerate and expand the beta-cell mass by the application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others. Treatment with these external stimuli can restore a functional beta-cell mass in diabetic animals, but further studies are required before it can be applied to humans. PMID:16183912

  9. A covalent homodimer probing early oligomers along amyloid aggregation.

    PubMed

    Halabelian, Levon; Relini, Annalisa; Barbiroli, Alberto; Penco, Amanda; Bolognesi, Martino; Ricagno, Stefano

    2015-01-01

    Early oligomers are crucial in amyloid aggregation; however, due to their transient nature they are among the least structurally characterized species. We focused on the amyloidogenic protein beta2-microglobulin2m) whose early oligomers are still a matter of debate. An intermolecular interaction between D strands of facing β2m molecules was repeatedly observed, suggesting that such interface may be relevant for β2m dimerization. In this study, by mutating Ser33 to Cys, and assembling the disulphide-stabilized β2m homodimer (DimC33), such DD strand interface was locked. Although the isolated DimC33 display a stability similar to wt β2m under native conditions, it shows enhanced amyloid aggregation propensity. Three distinct crystal structures of DimC33 suggest that dimerization through the DD interface is instrumental for enhancing DimC33 aggregation propensity. Furthermore, the crystal structure of DimC33 in complex with the amyloid-specific dye Thioflavin-T pinpoints a second interface, which likely participates in the first steps of β2m aggregation. The present data provide new insight into β2m early steps of amyloid aggregation. PMID:26420657

  10. A covalent homodimer probing early oligomers along amyloid aggregation

    PubMed Central

    Halabelian, Levon; Relini, Annalisa; Barbiroli, Alberto; Penco, Amanda; Bolognesi, Martino; Ricagno, Stefano

    2015-01-01

    Early oligomers are crucial in amyloid aggregation; however, due to their transient nature they are among the least structurally characterized species. We focused on the amyloidogenic protein beta2-microglobulin2m) whose early oligomers are still a matter of debate. An intermolecular interaction between D strands of facing β2m molecules was repeatedly observed, suggesting that such interface may be relevant for β2m dimerization. In this study, by mutating Ser33 to Cys, and assembling the disulphide-stabilized β2m homodimer (DimC33), such DD strand interface was locked. Although the isolated DimC33 display a stability similar to wt β2m under native conditions, it shows enhanced amyloid aggregation propensity. Three distinct crystal structures of DimC33 suggest that dimerization through the DD interface is instrumental for enhancing DimC33 aggregation propensity. Furthermore, the crystal structure of DimC33 in complex with the amyloid-specific dye Thioflavin-T pinpoints a second interface, which likely participates in the first steps of β2m aggregation. The present data provide new insight into β2m early steps of amyloid aggregation. PMID:26420657

  11. The C.elegans MAPK phosphatase LIP-1 is required for the G2/M meiotic arrest of developing oocytes

    PubMed Central

    Hajnal, Alex; Berset, Thomas

    2002-01-01

    In the Caenorhabditis elegans hermaphrodite germline, spatially restricted mitogen-activated protein kinase (MAPK) signalling controls the meiotic cell cycle. First, the MAPK signal is necessary for the germ cells to progress through pachytene of meiotic prophase I. As the germ cells exit pachytene and enter diplotene/diakinesis, MAPK is inactivated and the developing oocytes arrest in diakinesis (G2/M arrest). During oocyte maturation, a signal from the sperm reactivates MAPK to promote M phase entry. Here, we show that the MAPK phosphatase LIP-1 dephosphorylates MAPK as germ cells exit pachytene in order to maintain MAPK in an inactive state during oocyte development. Germ cells lacking LIP-1 fail to arrest the cell cycle at the G2/M boundary, and they enter a mitotic cell cycle without fertilization. LIP-1 thus coordinates oocyte cell cycle progression and maturation with ovulation and fertilization. PMID:12169634

  12. Ideals generated by traces in the algebra of symplectic reflections {H_{1,{v_{1,}}{v_2}}}( {{I_2}( {2m} )} )

    NASA Astrophysics Data System (ADS)

    Konstein, S. E.; Tyutin, I. V.

    2016-05-01

    The associative algebra of symplectic reflections H: = {H_{1,{v_{1,}}{v_2}}}( {{I_2}( {2m} )} ) based on the group generated by the root system I 2(2m) depends on two parameters, ν 1 and ν 2. For each value of these parameters, the algebra admits an m-dimensional space of traces. A trace tr is said to be degenerate if the corresponding symmetric bilinear form B tr( x, y) = tr( xy) is degenerate. We find all values of the parameters ν 1 and ν 2 for which the space of traces contains degenerate traces and the algebra H consequently has a two-sided ideal. It turns out that a linear combination of degenerate traces is also a degenerate trace. For the ν 1 and ν 2 values corresponding to degenerate traces, we find the dimensions of the space of degenerate traces.

  13. Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things

    PubMed Central

    Hernández-Ramos, José L.; Bernabe, Jorge Bernal; Moreno, M. Victoria; Skarmeta, Antonio F.

    2015-01-01

    As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M) nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things. PMID:26140349

  14. Preserving Smart Objects Privacy through Anonymous and Accountable Access Control for a M2M-Enabled Internet of Things.

    PubMed

    Hernández-Ramos, José L; Bernabe, Jorge Bernal; Moreno, M Victoria; Skarmeta, Antonio F

    2015-01-01

    As we get into the Internet of Things era, security and privacy concerns remain as the main obstacles in the development of innovative and valuable services to be exploited by society. Given the Machine-to-Machine (M2M) nature of these emerging scenarios, the application of current privacy-friendly technologies needs to be reconsidered and adapted to be deployed in such global ecosystem. This work proposes different privacy-preserving mechanisms through the application of anonymous credential systems and certificateless public key cryptography. The resulting alternatives are intended to enable an anonymous and accountable access control approach to be deployed on large-scale scenarios, such as Smart Cities. Furthermore, the proposed mechanisms have been deployed on constrained devices, in order to assess their suitability for a secure and privacy-preserving M2M-enabled Internet of Things. PMID:26140349

  15. [A case of limb-girdle muscular dystrophy 2M diagnosed by the occurence of dilated cardiomyopathy].

    PubMed

    Matsui, Misa; Endo, Takuyuki; Matsumura, Tsuyoshi; Saito, Toshio; Fujimura, Harutoshi

    2015-01-01

    We report a 24-year-old Japanese man initially suspected to have Becker's muscular dystrophy at the age of 6 years, because of a high level of creatine kinase in serum, though he discontinued visiting the hospital. At the age of 23, he was admitted to the hospital for severe dilated cardiomyopathy, and subsequently diagnosed with limb-girdle muscular dystrophy2M (LGMD2M) based on muscle biopsy and gene analysis. It was recently reported that some patients with fukutinopathy develop LGMD. Most of the cases reported in Japan showed mild skeletal muscle involvement despite serious cardiomyopathy, which may sometimes the initial symptom of the disease. Since muscular dystrophy patients can develop severe cardiac failure, irrespective of the severity of skeletal muscle involvement, regular examinations of cardiopulmonary function are necessary. PMID:26050665

  16. The impact of heterogeneous surface temperatures on the 2-m air temperature over the Arctic Ocean in spring

    NASA Astrophysics Data System (ADS)

    Tetzlaff, A.; Kaleschke, L.; Lüpkes, C.; Ament, F.; Vihma, T.

    2012-07-01

    The influence of spatial surface temperature changes over the Arctic Ocean on the 2-m air temperature variability is estimated using backward trajectories based on ERA-Interim and the JRA25 wind fields. They are initiated at Alert, Barrow and at the Tara drifting station. Three different methods are used. The first one compares mean ice surface temperatures along the trajectories to the observed 2-m air temperatures at the stations. The second one correlates the observed temperatures to air temperatures obtained using a simple Lagrangian box model which only includes the effect of sensible heat fluxes. For the third method, mean sensible heat fluxes from the model are correlated with the difference of the air temperatures at the model starting point and the observed temperatures at the stations. The calculations are based on MODIS ice surface temperatures and four different sets of ice concentration derived from SSM/I and AMSR-E data. Under nearly cloud free conditions, up to 90% of the 2-m air temperature variance can be explained for Alert, and 60% for Barrow using these methods. The differences are attributed to the different ice conditions, which are characterized by high ice concentration around Alert and lower ice concentration near Barrow. These results are robust for the different sets of reanalyses and ice concentration data. Near-surface winds of both reanalyses show a large inconsistency in the Central Arctic, which leads to a large difference in the correlations between modeled and observed 2-m air temperatures at Tara. Explained variances amount to 70% using JRA and only 45% using ERA. The results also suggest that near-surface temperatures at a given site are influenced by the variability of surface temperatures in a domain of about 150 to 350 km radius around the site.

  17. FOXA2 mRNA expression is associated with relapse in patients with Triple-Negative/Basal-like breast carcinoma.

    PubMed

    Perez-Balaguer, Ariadna; Ortiz-Martínez, Fernando; García-Martínez, Araceli; Pomares-Navarro, Critina; Lerma, Enrique; Peiró, Gloria

    2015-09-01

    The FOXA family of transcription factors regulates chromatin structure and gene expression especially during embryonic development. In normal breast tissue FOXA1 acts throughout mammary development; whereas in breast carcinoma its expression promotes luminal phenotype and correlates with good prognosis. However, the role of FOXA2 has not been previously studied in breast cancer. Our purpose was to analyze the expression of FOXA2 in breast cancer cells, to explore its role in breast cancer stem cells, and to correlate its mRNA expression with clinicopathological features and outcome in a series of patients diagnosed with breast carcinoma. We analyzed FOXA2 mRNA expression in a retrospective cohort of 230 breast cancer patients and in cell lines. We also knocked down FOXA2 mRNA expression by siRNA to determine the impact on cell proliferation and mammospheres formation using a cancer stem cells culture assay. In vitro studies demonstrated higher FOXA2 mRNA expression in Triple-Negative/Basal-like cells. Further, when it was knocked down, cells decreased proliferation and its capability of forming mammospheres. Similarly, FOXA2 mRNA expression was detected in 10% (23/230) of the tumors, especially in Triple-Negative/Basal-like phenotype (p < 0.001, Fisher's test). Patients whose tumors expressed FOXA2 had increased relapses (59 vs. 79%, p = 0.024, log-rank test) that revealed an independent prognostic value (HR = 3.29, C.I.95% = 1.45-7.45, p = 0.004, Cox regression). Our results suggest that FOXA2 promotes cell proliferation, maintains cancer stem cells, favors the development of Triple-Negative/Basal-like tumors, and is associated with increase relapses. PMID:26298189

  18. Security Aspects of Smart Cards vs. Embedded Security in Machine-to-Machine (M2M) Advanced Mobile Network Applications

    NASA Astrophysics Data System (ADS)

    Meyerstein, Mike; Cha, Inhyok; Shah, Yogendra

    The Third Generation Partnership Project (3GPP) standardisation group currently discusses advanced applications of mobile networks such as Machine-to-Machine (M2M) communication. Several security issues arise in these contexts which warrant a fresh look at mobile networks’ security foundations, resting on smart cards. This paper contributes a security/efficiency analysis to this discussion and highlights the role of trusted platform technology to approach these issues.

  19. Prediction of Liquid Sodium Flow Rate through the Core of the IBR-2M Reactor Using Nonlinear Autoregressive Neural Networks

    NASA Astrophysics Data System (ADS)

    Ososkov, G.; Pepelyshev, Yu.; Tsogtsaikhan, Ts.

    2016-02-01

    This paper presents an artificial neural network method for long-term prediction of liquid sodium flow rate through the core of the IBR-2M reactor. The nonlinear autoregressive neural network (NAR) with local feedback connection has been considered as the most appropriate tool for such a prediction. The predicted results were compared with experimental values. NAR model predicts slow changes of liquid sodium flow rate up to two days with an error less than 5%.

  20. Human Antigen R Binding and Regulation of SOX2 mRNA in Human Mesenchymal Stem Cells.

    PubMed

    Latorre, Elisa; Carelli, Stephana; Caremoli, Filippo; Giallongo, Toniella; Colli, Mattia; Canazza, Alessandra; Provenzani, Alessandro; Di Giulio, Anna Maria; Gorio, Alfredo

    2016-02-01

    Since 2005, sex determining region y-box 2 (SOX2) has drawn the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in regenerative medicine. Mitoxantrone is a drug that acts on nucleic acids primarily used to treat certain types of cancer and was recently shown to ameliorate the outcome of autoimmune diseases such as multiple sclerosis. In addition, mitoxantrone has been shown to inhibit the binding of human antigen R (HuR) RNA-binding protein to tumor necrosis factor-α mRNA. Our results show that HuR binds to the 3'-untranslated region of SOX2 mRNA together with the RNA-induced silencing complex miR145. The HuR binding works by stabilizing the interaction between the 3'-untranslated region and the RNA-induced silencing complex. Cell exposure to mitoxantrone leads to HuR detachment and the subsequent prolongation of the SOX2 mRNA half-life. The prolonged SOX2 half-life allows improvement of the spheroid-forming capability of the adipose-derived stem cells. The silencing of HuR confirmed the above observations and illustrates how the RNA-binding protein HuR may be a required molecule for regulation of SOX2 mRNA decay. PMID:26677051

  1. Pin1 promotes production of Alzheimer's amyloid {beta} from {beta}-cleaved amyloid precursor protein

    SciTech Connect

    Akiyama, Hirotada; Shin, Ryong-Woon; Uchida, Chiyoko; Kitamoto, Tetsuyuki; Uchida, Takafumi . E-mail: uchidat@cir.tohoku.ac.jp

    2005-10-21

    Here we show that prolyl isomerase Pin1 is involved in the A{beta} production central to the pathogenesis of Alzheimer's disease. Enzyme immunoassay of brains of the Pin1-deficient mice revealed that production of A{beta}40 and A{beta}42 was lower than that of the wild-type mice, indicating that Pin1 promotes A{beta} production in the brain. GST-Pin1 pull-down and immunoprecipitation assay revealed that Pin1 binds phosphorylated Thr668-Pro of C99. In the Pin1 {sup -/-} MEF transfected with C99, Pin1 co-transfection enhanced the levels of A{beta}40 and A{beta}42 compared to that without Pin1 co-transfection. In COS7 cells transfected with C99, Pin1 co-transfection enhanced the generation of A{beta}40 and A{beta}42, and reduced the expression level of C99, facilitating the C99 turnover. Thus, Pin1 interacts with C99 and promotes its {gamma}-cleavage, generating A{beta}40 and A{beta}42. Further, GSK3 inhibitor lithium blocked Pin1 binding to C99 by decreasing Thr668 phosphorylation and attenuated A{beta} generation, explaining the inhibitory effect of lithium on A{beta} generation.

  2. Antibodies to beta 1 and beta 2 adrenoreceptors in Chagas' disease.

    PubMed Central

    Sterin-Borda, L; Perez Leiros, C; Wald, M; Cremaschi, G; Borda, E

    1988-01-01

    Evidence accumulated over the last decade concerning human and experimental models suggests that an immunopathological mechanism may be involved in the pathogenesis of chronic Chagas' disease. In this paper we demonstrate the existence of two different circulating IgG in chagasic patients which bind with myocardial beta 1 and spleen cell beta 2 adrenoceptors, acting as non-competitive inhibitors. Both chagasic IgG against beta 1 and beta 2 adrenoceptor increased intracellular levels of cAMP that could be blocked by specific beta 1 and beta 2 adrenoceptor antagonists. The specificity for beta 1 and beta 2 adrenoceptors and the independence of other tissue reactive antibodies was demonstrated by IgG absorption with turkey red blood cell (TRBC), human lymphocytes (HL) or guinea pig red blood cells (GPRBC). The F(ab')2 fraction acted similarly. This supports the specificity of beta 1 and beta 2 adrenoceptors to the chagasic IgG and the independence of the other tissue reactive antibodies, such as EVI system. The probable pathogenic role of both beta 1 and beta 2 adrenergic chagasic antibody is discussed. PMID:2853016

  3. H2-M polymorphism in mice susceptible to collagen-induced arthritis involves the peptide binding groove

    SciTech Connect

    Walter, W.; Loos, M.; Maeurer, M.J.

    1996-12-31

    The ability to develop type II collagen (CII)-induced arthritis (CIA) in mice is associated with the major histocompatibility I-A gene and with as yet poorly defined regulatory molecules of the major histocompatibility complex (MHC) class II antigen processing and presentation pathway. H2-M molecules are thought to be involved in the loading of antigenic peptides into the MHC class II binding cleft. We sequenced H2-Ma, H2-Mb1, and H2-Mb2 genes from CIA-susceptible and -resistant mouse strains and identified four different Ma and Mb2 alleles, and three different Mb1 alleles defined by polymorphic residues within the predicted peptide binding groove. Most CIA-resistant mouse strains share common Ma, Mb1, and Mb2 alleles. In contrast, H2-M alleles designated Ma-III, Ma-IV, Mb1-III, and Mb2-IV could be exclusively identified in the CIA-susceptible H2{sup r} and H2{sup q} haplotypes, suggesting that allelic H2-M molecules may modulate the composition of different CII peptides loaded onto MHC class II molecules, presumably presenting {open_quotes}arthritogenic{close_quotes} epitopes to T lymphocytes. 42 refs., 4 figs., 3 tabs.

  4. Myb controls G2/M progression by inducing cyclin B expression in the Drosophila eye imaginal disc

    PubMed Central

    Okada, Masahiro; Akimaru, Hiroshi; Hou, De-Xing; Takahashi, Tomomi; Ishii, Shunsuke

    2002-01-01

    The c-myb proto-oncogene product (c-Myb) is a transcriptional activator. Vertebrate c-Myb is a key regulator of the G1/S transition in cell cycle, while Drosophila Myb (dMyb) is important for the G2/M transition. Here we report that dMyb induces expression of cyclin B, a critical regulator of the G2/M transition, in Drosophila eye imaginal disc. In the wild-type eye disc, dmyb mRNA was expressed in the stripes both anterior and posterior to the morphogenetic furrow. Ectopic expression of C-terminal-truncated dMyb in the eye disc caused ectopic expression of cyclin B and the rough eye phenotype. This rough eye phenotype correlated with prolonged M phase, caused by overexpression of cyclin B. Cyclin B expression was lost in dmyb-deficient clones. In Schneider cells, the activity of the cyclin B promoter was dramatically reduced by loss of dMyb using the RNA interference method. Mutations of the multiple AACNG sequences in the cyclin B promoter also abolished the promoter activity. These results indicate that dMyb regulates the G2/M transition by inducing cyclin B expression via binding to its promoter. PMID:11847115

  5. Dissecting the influence of Neolithic demic diffusion on Indian Y-chromosome pool through J2-M172 haplogroup.

    PubMed

    Singh, Sakshi; Singh, Ashish; Rajkumar, Raja; Sampath Kumar, Katakam; Kadarkarai Samy, Subburaj; Nizamuddin, Sheikh; Singh, Amita; Ahmed Sheikh, Shahnawaz; Peddada, Vidya; Khanna, Vinee; Veeraiah, Pandichelvam; Pandit, Aridaman; Chaubey, Gyaneshwer; Singh, Lalji; Thangaraj, Kumarasamy

    2016-01-01

    The global distribution of J2-M172 sub-haplogroups has been associated with Neolithic demic diffusion. Two branches of J2-M172, J2a-M410 and J2b-M102 make a considerable part of Y chromosome gene pool of the Indian subcontinent. We investigated the Neolithic contribution of demic dispersal from West to Indian paternal lineages, which majorly consists of haplogroups of Late Pleistocene ancestry. To accomplish this, we have analysed 3023 Y-chromosomes from different ethnic populations, of which 355 belonged to J2-M172. Comparison of our data with worldwide data, including Y-STRs of 1157 individuals and haplogroup frequencies of 6966 individuals, suggested a complex scenario that cannot be explained by a single wave of agricultural expansion from Near East to South Asia. Contrary to the widely accepted elite dominance model, we found a substantial presence of J2a-M410 and J2b-M102 haplogroups in both caste and tribal populations of India. Unlike demic spread in Eurasia, our results advocate a unique, complex and ancient arrival of J2a-M410 and J2b-M102 haplogroups into Indian subcontinent. PMID:26754573

  6. In Candida albicans hyphae, Sec2p is physically associated with SEC2 mRNA on secretory vesicles

    PubMed Central

    Caballero-Lima, David; Hautbergue, Guillaume M; Wilson, Stuart A; Sudbery, Peter E

    2014-01-01

    Candida albicans hyphae grow in a highly polarized fashion from their tips. This polarized growth requires the continuous delivery of secretory vesicles to the tip region. Vesicle delivery depends on Sec2p, the Guanine Exchange Factor (GEF) for the Rab GTPase Sec4p. GTP bound Sec4p is required for the transit of secretory vesicles from the trans-Golgi to sites of polarized growth. We previously showed that phosphorylation of Sec2p at residue S584 was necessary for Sec2p to support hyphal, but not yeast growth. Here we show that on secretory vesicles SEC2 mRNA is physically associated with Sec2p. Moreover, we show that the phosphorylation of S584 allows SEC2 mRNA to dissociate from Sec2p and we speculate that this is necessary for Sec2p function and/or translation. During hyphal extension, the growing tip may be separated from the nucleus by up to 15 μm. Transport of SEC2 mRNA on secretory vesicles to the tip localizes SEC2 translation to tip allowing a sufficient accumulation of this key protein at the site of polarized growth. PMID:25231350

  7. Dissecting the influence of Neolithic demic diffusion on Indian Y-chromosome pool through J2-M172 haplogroup

    PubMed Central

    Singh, Sakshi; Singh, Ashish; Rajkumar, Raja; Sampath Kumar, Katakam; Kadarkarai Samy, Subburaj; Nizamuddin, Sheikh; Singh, Amita; Ahmed Sheikh, Shahnawaz; Peddada, Vidya; Khanna, Vinee; Veeraiah, Pandichelvam; Pandit, Aridaman; Chaubey, Gyaneshwer; Singh, Lalji; Thangaraj, Kumarasamy

    2016-01-01

    The global distribution of J2-M172 sub-haplogroups has been associated with Neolithic demic diffusion. Two branches of J2-M172, J2a-M410 and J2b-M102 make a considerable part of Y chromosome gene pool of the Indian subcontinent. We investigated the Neolithic contribution of demic dispersal from West to Indian paternal lineages, which majorly consists of haplogroups of Late Pleistocene ancestry. To accomplish this, we have analysed 3023 Y-chromosomes from different ethnic populations, of which 355 belonged to J2-M172. Comparison of our data with worldwide data, including Y-STRs of 1157 individuals and haplogroup frequencies of 6966 individuals, suggested a complex scenario that cannot be explained by a single wave of agricultural expansion from Near East to South Asia. Contrary to the widely accepted elite dominance model, we found a substantial presence of J2a-M410 and J2b-M102 haplogroups in both caste and tribal populations of India. Unlike demic spread in Eurasia, our results advocate a unique, complex and ancient arrival of J2a-M410 and J2b-M102 haplogroups into Indian subcontinent. PMID:26754573

  8. RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast.

    PubMed Central

    Gardner, R; Putnam, C W; Weinert, T

    1999-01-01

    Eukaryotic checkpoint genes regulate multiple cellular responses to DNA damage. In this report, we examine the roles of budding yeast genes involved in G2/M arrest and tolerance to UV exposure. A current model posits three gene classes: those encoding proteins acting on damaged DNA (e.g. RAD9 and RAD24), those transducing a signal (MEC1, RAD53 and DUN1) or those participating more directly in arrest (PDS1). Here, we define important features of the pathways subserved by those genes. MEC1, which we find is required for both establishment and maintenance of G2/M arrest, mediates this arrest through two parallel pathways. One pathway requires RAD53 and DUN1 (the 'RAD53 pathway'); the other pathway requires PDS1. Each pathway independently contributes approximately 50% to G2/M arrest, effects demonstrable after cdc13-induced damage or a double-stranded break inflicted by the HO endonuclease. Similarly, both pathways contribute independently to tolerance of UV irradiation. How the parallel pathways might interact ultimately to achieve arrest is not yet understood, but we do provide evidence that neither the RAD53 nor the PDS1 pathway appears to maintain arrest by inhibiting adaptation. Instead, we think it likely that both pathways contribute to establishing and maintaining arrest. PMID:10357828

  9. Project of the new multifunctional reflectometer GRAINS with horizontal sample plane at the IBR-2M pulsed reactor in Dubna

    NASA Astrophysics Data System (ADS)

    Avdeev, M. V.; Bodnarchuk, V. I.; Lauter-Pasyuk, V. V.; Lauter, H.; Aksenov, V. L.; Yaradaikin, S. P.; Ulyanov, V. A.; Trounov, V. A.; Kalinin, S. I.

    2010-11-01

    The new multifunctional reflectometer GRAINS is under construction at the modernized high flux IBR-2 pulsed reactor (IBR-2M) of the FLNP JINR (Dubna, Russia). The principal feature of this reflectometer, the horizontal sample plane (or vertical scattering plane), enables the study of liquid-containing interfaces. The reflectometer will operate in the time-of-flight regime with constant sample illumination during measurements. The important advantage is the constant angular resolution with unvaried background. The additional modes of the GRAINS reflectometer comprise (1) off-specular scattering and GISANS, which are measured simultaneously in the TOF regime at a 2D position-sensitive detector; (2) angular encoding in the horizontal plane, which is provided by a Larmor precession region limited by current sheets in front of the sample; (3) 3D polarimetry in reflection, which is provided by a Larmor precession region around the sample position. The design of the reflectometer is optimised to take better advantage of an exceptionally broad wavelength band of the new cold moderator at the IBR-2M. The set-up will open up principally new possibilities for investigations in the field of interface nano-science at the IBR-2M reactor.

  10. Transforming growth factor-beta in the chicken fundal layers: an immunohistochemical study.

    PubMed

    Mathis, Ute; Schaeffel, Frank

    2010-06-01

    choroid or sclera, or on the number of TGF-beta2 (active and latent form) expressing amacrine cells. This result did not change when the two identified populations of TGF-beta2 expressing amacrine cells (one calbindin-positive and the other CRABP-positive) were separately considered. Also no modulation was seen in choroid, although an earlier study had found changes in TGF-beta2 mRNA after lens treatment. The lack of any visually-induced changes in retina or choroid suggests that TGF-beta may not represent a key molecule in the retino-choroidal signalling cascade although it has previously been shown to have a primary role in scleral remodelling. PMID:20350541

  11. Imperfect World of beta beta-decay Nuclear Data Sets

    SciTech Connect

    Pritychenko, B.

    2015-01-03

    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  12. Pleiotropic effects of the beta-adrenoceptor blocker carvedilol on calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes.

    PubMed

    Wang, Ruijuan; Miura, Toshiro; Harada, Nozomu; Kametani, Ryosuke; Shibuya, Masaki; Fukagawa, Yasuhiro; Kawamura, Shuji; Ikeda, Yasuhiro; Hara, Masayuki; Matsuzaki, Masunori

    2006-07-01

    Carvedilol is a nonselective beta-adrenoceptor blocker with multiple pleiotropic actions. A recent clinical study suggested that carvedilol may be superior to other beta-adrenoceptor blockers in the treatment of heart failure. Despite numerous investigations, the underlying mechanisms of carvedilol on improving heart failure are yet to be fully established. The purpose of this study is to clarify the pleiotropic effect of carvedilol on cytosolic and mitochondrial calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes. Carvedilol (10 microM), but not metoprolol (10 microM), reduced H2O2 (100 microM)-induced apoptosis in neonatal rat cardiomyocytes. During the process, changes in cytosolic calcium concentration ([Ca2+]i) and mitochondrial calcium concentration ([Ca2+]m) and mitochondrial membrane potential (DeltaPsim) were measured by fluorescent probes [Fluo-3/acetoxymethyl ester (AM), Rhod-2/AM, and tetramethylrhodamine ethyl ester, respectively] and imaged by laser confocal microscopy. The results showed that H2O2 caused [Ca2]m overload first, followed by [Ca2+]i overload, leading to DeltaPsim dissipation and the induction of apoptosis. Carvedilol (10 microM) significantly delayed these processes and reduced apoptosis. These effects were not observed with other beta-adrenoceptor blockers (metoprolol, atenolol, and propranolol) or with a combination of the alpha (phentolamine)- and the beta-adrenoceptor blocker. The antioxidant N-acetyl-L-cysteine (NAC, 5 mM) and the combination of NAC and propranolol (10 microM) showed an effect similar to that of carvedilol. Therefore, the effect of carvedilol on H2O2-induced changes in [Ca2+]m, [Ca2+]i, and DeltaPsi(m) is independent of alpha- and beta-adrenoceptors but is probably dependent on the antioxidant effect. PMID:16611853

  13. TinyECCK: Efficient Elliptic Curve Cryptography Implementation over GF(2m) on 8-Bit Micaz Mote

    NASA Astrophysics Data System (ADS)

    Seo, Seog Chung; Han, Dong-Guk; Kim, Hyung Chan; Hong, Seokhie

    In this paper, we revisit a generally accepted opinion: implementing Elliptic Curve Cryptosystem (ECC) over GF(2m) on sensor motes using small word size is not appropriate because XOR multiplication over GF(2m) is not efficiently supported by current low-powered microprocessors. Although there are some implementations over GF(2m) on sensor motes, their performances are not satisfactory enough to be used for wireless sensor networks (WSNs). We have found that a field multiplication over GF(2m) are involved in a number of redundant memory accesses and its inefficiency is originated from this problem. Moreover, the field reduction process also requires many redundant memory accesses. Therefore, we propose some techniques for reducing unnecessary memory accesses. With the proposed strategies, the running time of field multiplication and reduction over GF(2163) can be decreased by 21.1% and 24.7%, respectively. These savings noticeably decrease execution times spent in Elliptic Curve Digital Signature Algorithm (ECDSA) operations (signing and verification) by around 15-19%. We present TinyECCK (Tiny Elliptic Curve Cryptosystem with Koblitz curve-a kind of TinyOS package supporting elliptic curve operations) which is the first implementation of Koblitz curve on sensor motes as far as we know. Through comparisons with existing software implementations of ECC built in C or hybrid of C and inline assembly on sensor motes, we show that TinyECCK outperforms them in terms of running time, code size and supporting services. Furthermore, we show that a field multiplication over GF(2m) can be faster than that over GF(p) on 8-bit Atmegal28 processor by comparing TinyECCK with TinyECC, a well-known ECC implementation over GF(p). TinyECCK with sect163kl can generate a signature and verify it in 1.37 and 2.32 secs on a Micaz mote with 13,748-byte of ROM and 1,004-byte of RAM.

  14. [Hemoglobin C -- beta-thalassemia disease and homozygous beta-thalassemia in a black African family (author's transl)].

    PubMed

    Basset, P; Fall, M; Oudart, J L

    1975-01-01

    The study of a Malian family has allowed to prove existence of two types of beta-thalassemia genes: the beta0 gene which suppresses the synthesis of the beta chain into cis position and the beta+ gene which slows down only partially this synthesis. The difference between this two genes has been possible owing to the hemoglobin C found in this family and induced by the betaC mutated gene. The segregation of the four genes betaA, betaC, beta0 thal, and beta+ thal. has allowed to compare all the possible phenotypes deriving from the combinations by two of these allelic genes. PMID:128735

  15. The flux control coefficient of carnitine palmitoyltransferase I on palmitate beta-oxidation in rat hepatocyte cultures.

    PubMed Central

    Spurway, T D; Sherratt, H A; Pogson, C I; Agius, L

    1997-01-01

    Two important factors that determine the flux of hepatic beta-oxidation of long-chain fatty acids are the availability of fatty acid and the activity of carnitine palmitoyltransferase I (CPT I). Using Metabolic Control Analysis, the flux control coefficient of CPT I in rat hepatocyte monolayers was determined by titration with 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir), which is converted to Etomoxir-CoA, an irreversible inhibitor of CPT I. We measured CPT I activity and flux through beta-oxidation at 0.2 mM and 1.0 mM palmitate to simulate substrate concentrations in fed and fasted states. Rates of beta-oxidation were 4.5-fold higher at 1. 0 mM palmitate compared with 0.2 mM palmitate. Flux control coefficients of CPT I, estimated by two independent methods, were similar: 0.67 and 0.79 for 0.2 mM palmitate, and 0.68 and 0.77 for 1 mM palmitate. It is concluded that the regulatory potential of CPT I is similar at low and high physiological concentrations of palmitate. PMID:9173869

  16. PI-3 kinase pathway can mediate the effect of TGF-beta1 in inducing the expression of SHARP-2 in LLC-PK1 cells.

    PubMed

    Shou, Zhang-fei; Zhou, Qin; Cai, Jie-ru; Chen, Jiang-hua; Yamada, Kazuya; Miyamoto, Kaoru

    2009-09-01

    We aim to investigate the effect of transforming growth factor (TGF)-beta1 on the expression of enhancer of split- and hairy-related protein-2 (SHARP-2) messenger RNA (mRNA) and its signaling pathway. In this study, several cell lines including LLC-PK1 (a porcine kidney tubular epithelial cell line), MDCK (Madin-Darby canine kidney) and CTLL-2 (cytotoxic T-lymphocyte line) were treated with recombinant human TGF-beta1, and a series of experiments were carried out, involving Northern blot analysis of total RNA from these cells. Further, several specific chemical inhibitors were applied before TGF-beta1 treatment to probe the signaling pathway. The results showed that TGF-beta1 can significantly up-regulate SHARP-2 mRNA expression in the LLC-PK1 cell line. The peak level of induction was found 2 h after TGF-beta1 stimulation. While one phosphoinositide 3-kinases (PI-3) kinase inhibitor, LY294002, completely blocked the effect of TGF-beta1 on SHARP-2 mRNA expression in LLC-PK1 cells at a low concentration, other inhibitors, including PD98059, staurosporine, AG490, wortmannin, okadaic acid and rapamycin, had no effect. The effect of LY294002 was dose-dependent. We conclude that, in LLC-PK1 cells at least, TGF-beta1 can effectively induce the SHARP-2 mRNA expression and that the PI-3 kinase pathway can mediate this effect. PMID:19735104

  17. Influences of the substituents on the M-M bonding in Cp4Al4 and Cp2M2X2 (M = B, Al, Ga; Cp = C5H5, X = halogen).

    PubMed

    Lu, Feifei; Li, Xiaoyan; Sun, Zheng; Zeng, Yanli; Meng, Lingpeng

    2015-08-21

    Although the geometries of CpAl4 (Cp* = C5Me5) and Cp4Al4 (Cp = C5H5) are similar, CpAl4 is more stable than Cp4Al4. CpAl2I2 is the first complex involving an Al(ii)-Al(ii) bond to be supported by Cp-type ligands. In this work, the stability of CpAl4 and Cp4Al4 (Cp = C5H5), the nature of M-M bonding in Cp2M2X2 (M = B, Al, and Ga), and the influences of the X atom on the M-M bonds have been analyzed and compared within the framework of the atoms in molecules (AIM) theory, electron localization function (ELF), energy decomposition analysis (EDA), and natural bond orbital (NBO) analysis. The calculated results show that CpAl4 is more stable than Cp4Al4 because of HH interactions between the methyl groups on the same and different Cp rings and not because of the Al-Al bonds. In Cp2M2X2, the B-B bond is stronger than the Al-Al and Ga-Ga bonds. The B-B bond is most consistent with covalent bonding, whereas the Al-Al and Ga-Ga bonds are more consistent with metallic bonding. The strengths of the B-B bond increase in the sequence X = F, Cl, Br, and I, whereas the Al-Al and Ga-Ga bonds decrease in the sequence X = F, Cl, Br, and I. The different change tendencies arise from the different M-M bonds and the orbital interactions between atoms X and M. PMID:26171664

  18. The COBRA Double Beta Decay Search Experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.

    2006-11-01

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  19. The COBRA double-beta decay experiment

    NASA Astrophysics Data System (ADS)

    Stewart, D. Y.; COBRA Collaboration

    2007-09-01

    The COBRA experiment aims to use a large quantity of Cadmium-Zinc-Telluride (CdZnTe) semiconductor detectors to search for neutrinoless double-beta decay (0 υββ). The current status of the experiment is discussed, and new limits on several double-beta modes are presented. Future plans for a large-scale experiment are also described.

  20. Beta-agonists and animal welfare

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  1. Resistance to beta-lactams--the permutations.

    PubMed

    Amyes, S G B

    2003-12-01

    The beta-lactam family of antimicrobials, in particular penicillins and cephalosporins, is the mainstay of treatment for community-acquired infections. However, the emergence of resistant isolates to these agents has raised concerns regarding the continued efficacy of existing therapies. Resistance to beta-lactams is most commonly expressed by the microbial production of beta-lactamases that hydrolyze the beta-lactam ring. Three further resistance mechanisms include conformational changes in penicillin-binding proteins (PBPs); permeability changes in the outer membrane; and active efflux of the antimicrobial. In addition to the pre-requisite efficacy and tolerability profiles, new beta-lactams should address these four resistance mechanisms. Overcoming resistance may be a serendipitous event or arrived at by design. A unique synthetic beta-lactam class, which demonstrates promise in terms of its activity against the range of bacteria responsible for community-acquired infections and its inherent stability to hydrolysis by beta-lactamases, is the penems. This discrete class of hybrid molecules combines properties from the penicillin (penam) and cephalosporin (cephem) beta-lactam classes. Faropenem is an example of a penem with a broad spectrum of activity designed to address these resistance issues. PMID:14998075

  2. Interferon Beta-1a Intramuscular Injection

    MedlinePlus

    ... symptoms flare up from time to time) of multiple sclerosis (MS, a disease in which the nerves do not ... known how interferon beta-1a works to treat MS. ... doctor.Interferon beta-1a controls the symptoms of MS but does not cure it. Continue to use ...

  3. Beta maritima: the Origin of Beets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Along the undisturbed shores, especially of the Mediterranean Sea and the European North Atlantic Ocean, is a widespread plant called Beta maritima (Beta vulgaris subspecies maritima) by the botanists, or more commonly sea beet. Nothing for the inexperienced observer's eye distinguishes it from surr...

  4. The COBRA Double Beta Decay Search Experiment

    SciTech Connect

    Stewart, D. Y.

    2006-11-17

    The COBRA experiment aims to use a large quantity of CdZnTe semiconductor detectors to search for neutrinoless double beta decay. The current status of the experiment is discussed, and new limits on several double beta modes are presented. Future plans for a large scale experiment are also described.

  5. PBX: the Princeton beta experiment

    SciTech Connect

    Bol, K.; Chance, M.; Dewar, R.

    1983-09-01

    A rearrangement of the divertor coils in PDX will enable a test in 1984 of the MHD stability properties of deeply indented bean-shaped plasmas. The goal is a beta of 10%. Indentation is expected to counter the deterioration of MHD stability against pressure driven modes that is occasioned by the larger aspect ratios typical of anticipated reactor oriented devices. Indeed, as shown by M. Chance et al., indentation may offer direct access to the second region of stability for ballooning modes, and numerical analyses with PEST show the internal kink to be stabilized completely with even relatively modest indentation. The internal kink is implicated in the loss of beam ions in PDX. In this report the theoretical basis for the forthcoming experiment, and the design considerations underlying the modification from PDX to PBX, are described in detail. Additional theoretical material, including an analysis of particle orbits in an indented tokamak plasma, is appended.

  6. DREAM: Research to Operations Beta

    NASA Astrophysics Data System (ADS)

    Friedel, Reiner; Reeves, Geoffrey; Zaharia, Sorin; Koller, Josef; Chen, Yue; Henderson, Mike; Thomsen, Davis

    The Dynamic Radiation Environment Assimilation Model (DREAM) is a dataassimilative model of the Earth's radiation belts that has, until recently, been used primarily as a re-search tool to understand radiation belt dynamics and to develop Kalman filter techniques for application to magnetospheric modeling. More recently, the emphasis of the DREAM program has shifted toward implementation of an operational prototype for testing and validation at the Air Force Research Laboratory's (AFRL) Space Weather Forecast Laboratory (SWFL) and NASA's Community Coordinated Modeling Center (CCMC). The transition has required significant effort, funding, and shifting of priorities that serve as a recent example of the oppor-tunities and challenges of transitioning a model from research to operations (R2O). DREAM is still in the early stages of transition to operations but we do not see any significant obstacles to success. We present here the BETA version of this model, operating in real-time, using GOES energetic particle data as input.

  7. The chromosphere of Beta Cassiopeiae

    NASA Technical Reports Server (NTRS)

    Teays, Terry J.; Schmidt, Edward G.; Pasinetti Fracassini, Laura E.; Fracassini, Massimo

    1989-01-01

    High-resolution, long-wavelength IUE observations and ground-based photometry of the Delta Scuti star Beta Cas is reported. The ground-based observations were used together with previous results of Antonello et al. (1986) to ensure that the IUE observations were correctly phased relative to the photometric variation. Fluxes for the emission core of the Mg II k 2796-A line were obtained from the UV spectra over several cycles in 1986 and 1987. It is found that there is an increase in the emission during part of the cycle, but it occurs near minimum light in contrast to another Delta Scuti star, Rho Pup, and the classical Cepheids (where it occurs near maximum light). The mean level of chromospheric activity is comparable to other early F dwarfs.

  8. Beta-peptide bundles with fluorous cores.

    PubMed

    Molski, Matthew A; Goodman, Jessica L; Craig, Cody J; Meng, He; Kumar, Krishna; Schepartz, Alanna

    2010-03-24

    We reported recently that certain beta-peptides self-assemble spontaneously into cooperatively folded bundles whose kinetic and thermodynamic metrics mirror those of natural helix bundle proteins. The structures of four such beta-peptide bundles are known in atomic detail. These structures reveal a solvent-sequestered, hydrophobic core stabilized by a unique arrangement of leucine side chains and backbone methylene groups. Here we report that this hydrophobic core can be re-engineered to contain a fluorous subdomain while maintaining the characteristic beta-peptide bundle fold. Like alpha-helical bundles possessing fluorous cores, fluorous beta-peptide bundles are stabilized relative to hydrocarbon analogues and undergo cold denaturation. Beta-peptide bundles with fluorous cores represent the essential first step in the synthesis of orthogonal protein assemblies that can sequester selectively in an interstitial membrane environment. PMID:20196598

  9. Effect of finite. beta. on stellarator transport

    SciTech Connect

    Mynick, H.E.

    1984-04-01

    A theory of the modification of stellarator transport due to the presence of finite plasma pressure is developed, and applied to a range of stellarator configurations. For many configurations of interest, plasma transport can change by more than an order of magnitude in the progression from zero pressure to the equilibrium ..beta.. limit of the device. Thus, a stellarator with transport-optimized vacuum fields can have poor confinement at the desired operating ..beta... Without an external compensating field, increasing ..beta.. tends to degrade confinement, unless the initial field structure is very carefully chosen. The theory permits one to correctly determine this vacuum structure, in terms of the desired structure of the field at a prescribed operating ..beta... With a compensating external field, the deleterious effect of finite ..beta.. on transport can be partially eliminated.

  10. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-10-07

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  11. beta -Lactamases: which ones are clinically important?

    PubMed

    Rice, Louis B.; Bonomo, Robert A.

    2000-06-01

    The introduction of a large array of beta-lactam antibiotics has spawned the emergence of an even larger variety of beta-lactamases designed to confer resistance to these agents. beta-lactamases are produced by both gram-positive and gram-negative bacteria, but their clinical importance is far greater among the gram-negatives. The virtual explosion in our knowledge about the variety of these enzymes can often create confusion and frustration among those not well versed in the field. In this paper, we attempt to focus the discussion of beta-lactamases on those enzymes that are of the greatest clinical importance, the Ambler Class A and C enzymes. We also discuss the growing importance of the Ambler Class B metallo beta-lactamases, which hydrolyze carbapenems and are increasing in prevalence in areas of significant carbapenem usage. Copyright 2000 Harcourt Publishers Ltd. PMID:11498383

  12. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, G.G.; Kato, T.R.; Schonegg, E.

    1985-04-11

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed. 5 tabs.

  13. Simultaneous beta/gamma digital spectroscopy

    NASA Astrophysics Data System (ADS)

    Farsoni, Abdollah T.

    A state-of-the-art radiation detection system for simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) built in our laboratory. The DPP board was designed to digitally capture the analog signal pulses and, following several digital preprocessing steps, transfer valid pulses to the host computer for further digital processing. A MATLAB algorithm was developed to digitally discriminate beta and gamma events and reconstruct separate beta and gamma-ray energy spectra with minimum crosstalk. The spectrometer proved to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  14. Process for reducing beta activity in uranium

    DOEpatents

    Briggs, Gifford G.; Kato, Takeo R.; Schonegg, Edward

    1986-01-01

    This invention is a method for lowering the beta radiation hazards associated with the casting of uranium. The method reduces the beta radiation emitted from the as-cast surfaces of uranium ingots. The method also reduces the amount of beta radiation emitters retained on the interiors of the crucibles that have been used to melt the uranium charges and which have undergone cleaning in a remote handling facility. The lowering of the radioactivity is done by scavenging the beta emitters from the molten uranium with a molten mixture containing the fluorides of magnesium and calcium. The method provides a means of collection and disposal of the beta emitters in a manner that reduces radiation exposure to operating personnel in the work area where the ingots are cast and processed.

  15. Gamma-ray blind beta particle probe

    DOEpatents

    Weisenberger, Andrew G.

    2001-01-01

    An intra-operative beta particle probe is provided by placing a suitable photomultiplier tube (PMT), micro channel plate (MCP) or other electron multiplier device within a vacuum housing equipped with: 1) an appropriate beta particle permeable window; and 2) electron detection circuitry. Beta particles emitted in the immediate vicinity of the probe window will be received by the electron multiplier device and amplified to produce a detectable signal. Such a device is useful as a gamma insensitive, intra-operative, beta particle probe in surgeries where the patient has been injected with a beta emitting radiopharmaceutical. The method of use of such a device is also described, as is a position sensitive such device.

  16. Genetics Home Reference: mucolipidosis III alpha/beta

    MedlinePlus

    ... Health Conditions mucolipidosis III alpha/beta mucolipidosis III alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis III alpha/beta is a slowly progressive disorder that affects ...

  17. Genetics Home Reference: mucolipidosis II alpha/beta

    MedlinePlus

    ... Health Conditions mucolipidosis II alpha/beta mucolipidosis II alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis II alpha/beta (also known as I-cell disease) is ...

  18. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin {beta}E subunit

    SciTech Connect

    Hashimoto, Osamu . E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-03-10

    Activins, TGF-{beta} superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin {beta} subunit genes, {beta}C and {beta}E, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin {beta}E subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells.

  19. An update on newer beta-lactamases.

    PubMed

    Gupta, Varsha

    2007-11-01

    The resistance to beta-lactam antibiotics is an increasing problem worldwide and beta lactamases production is the most common mechanism of drug resistance. Both global and Indian figures showed a marked increase in the number of beta-lactamases producing organisms. These enzymes extended spectrum beta-lactamases (ESBLs) are numerous and continuous mutation has led to the development of enzymes having expanded substrate profile. To date, there are more than 130 TEM type and more than 50 sulphydryl variable (SHV) type beta-lactamases found in Gram negative bacilli. ESBL producing Enterobacteriaceae are, as a rule, resistant to all cephalosporins and extended spectrum penicillins including the monobactam, aztreonam, while resistance to trimethoprim - sulphamethaxazole and aminoglycosides is frequently co-transferred on the same plasmid. Many ESBL producing organisms also express Amp C beta-lactamases. Amp C- beta-lactamases are clinically significant, as these confer resistance to cephalosporins in the oxyimino group, 7 alpha-methoxy cephalosporins, and are poorly inhibited by clavulanic acid. Carbepenems are the drugs of choice for the treatment of infections caused by ESBL producing organisms but carbapenemases (MBLs) have emerged and have spread from Pseudomonas aeruginosa to Enterobacteriaceae. The routine clinical microbiology laboratories should employ simple methods to recognize these enzymes using various substrates and inhibitors. These organisms may lead to therapeutic dead ends. Presently, the therapy relies on beta-lactam/ beta-lactamases inhibitor combinations, carbepenems and piperacillin - tazobactam plus aminoglycoside combination. Proper infection control practices and barrier precautions are essential to contain the organisms producing beta-lactamases. PMID:18160745

  20. Beta-dosimetry studies at LLNL

    SciTech Connect

    Hankins, D.E.

    1983-01-01

    This paper summarizes three beta-dosimetry studies made recently at the Lawrence Livermore National Laboratory. The first study was to determine the beta-gamma exposure rates at the Los Alamos Godiva IV Critical Assembly. The beta spectra from the assembly were evaluated using absorption curves and the beta-gamma dose-rate ratios were determined at various distances from the assembly. A comparison was made of the doses determined using two types of TLD personnel dosimeters and a film badge. The readings of an Eberline RO-7 instrument and the dose rates determined by TLDs were compared. Shielding provided by various metals, gloves, and clothing were measured. The second study was to determine the beta energy response of the Eberline RO-7 instrument based on measurements made with the PTB beta sources. This study required additional calibration points for the PTB sources which were made using extrapolation chamber measurements. The third study resulted in two techniques to determine the beta energy (E/sub max/) from the readings of this-window portable survey instruments. Both techniques are based on the readings obtained using aluminium filters. One technique is for field application, requires one filter, and provides a quick estimate of the beta energy in three energy groups: < 0.5 MeV, 0.5 MeV to 1.5 MeV and > 1.5 MeV. The second technique is more complex requiring measurements with two or three filters, but gives the beta energy and the approximate shape of the beta spectrum. 9 references, 6 figures.

  1. The angiotensin II receptor antagonist, losartan, enhances regulator of G protein signaling 2 mRNA expression in vascular smooth muscle cells of Wistar rats.

    PubMed

    Wu, Yaqiong; Nakagawa, Suguru; Takahashi, Hidenori; Kawabata, Yukari; Suzuki, Etsu; Uehara, Yoshio

    2016-05-01

    Angiotensin II (Ang II) reportedly enhances regulator of G-protein signaling 2 (RGS2), thus making a negative feedback loop for Ang II signal transduction. However, few studies have reported whether Ang II receptor (ATR) antagonists influence RGS2 mRNA expression. We investigated RGS2 mRNA expression when Ang II binding to ATR was blocked with Ang II subtype-1 receptor (AT1R) blockers using vascular smooth muscle cells from the thoracic aorta of male Wistar rats. RGS2 mRNA expression significantly increased with Ang II stimulation, and this increase was almost completely abolished by olmesartan, a potent AT1R-specific blocker. Ang II subtype-2 receptor (AT2R) was not involved in Ang II-mediated RGS expression. In contrast, the AT1R blocker, losartan, partially decreased Ang II-mediated RGS2 mRNA expression because this antagonist directly stimulated RGS2 mRNA expression in Ang II-free medium. EXP3174, which is an active metabolite of losartan, almost completely blunted Ang II-mediated RGS2 mRNA expression without direct stimulation of RGS2 mRNA expression. Moreover, pretreatment with olmesartan abolished Ang II-mediated RGS2 mRNA expression. Treatment with a protein kinase C inhibitor partially decreased losartan-mediated RGS2 mRNA expression. These results suggest that AT1R blockers inhibit RGS2 mRNA expression in response to Ang II via an AT1R-mediated mechanism. However, the AT1R blocker, losartan, behaves as a direct agonist for RGS2 mRNA expression via AT1R through protein kinase C-dependent and -independent pathways. In conclusion, losartan exhibits dual effects on RGS2 mRNA expression, and the direct upregulation of RGS2 mRNA expression may provide a new strategy for the treatment of hypertension. PMID:26763849

  2. [Effect of anabolic steroid on immune response].

    PubMed

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin. PMID:6367663

  3. Beta-aminopeptidase-catalyzed biotransformations of beta(2)-dipeptides: kinetic resolution and enzymatic coupling.

    PubMed

    Heck, Tobias; Reimer, Artur; Seebach, Dieter; Gardiner, James; Deniau, Gildas; Lukaszuk, Aneta; Kohler, Hans-Peter E; Geueke, Birgit

    2010-05-17

    We have previously shown that the beta-aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non-natural beta(3)-peptides and beta(3)-amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N-terminal beta(2)-amino acid residues as substrates under aqueous conditions. The suitability of a beta(2)-peptide as a substrate for BapA or DmpA was strongly dependent on the size of the C(alpha) substituent of the N-terminal beta(2)-amino acid. BapA was shown to convert a diastereomeric mixture of the beta(2)-peptide H-beta(2)hPhe-beta(2)hAla-OH, but did not act on diastereomerically pure beta(2),beta(3)-dipeptides containing an N-terminal beta(2)-homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA-catalyzed transformation of the diastereomeric mixture of H-beta(2)hPhe-beta(2)hAla-OH proceeded along two highly S-enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis-to-hydrolysis ratio (v(S)/v(H)) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N-terminal beta-amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of beta(2)-homophenylalanine was detected (ee>99 % for H-(S)-beta(2)-hPhe-OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure beta(2)-amino acids and the enantioselective coupling of N-terminal beta(2)-amino acids to peptides. PMID:20340152

  4. Synthesis of novel heterobranched beta-cyclodextrins having beta-D-N-acetylglucosaminyl-maltotriose on the side chain.

    PubMed

    Tanimoto, Toshiko; Omatsu, Mizue; Ikuta, Akiko; Nishi, Yuki; Murakami, Hiromi; Nakano, Hirofumi; Kitahata, Sumio

    2005-04-01

    From a mixture of N-acetylglucosaminyl-beta-cyclodextrin (GlcNAc-betaCD) and lactose, beta-D-galactosyl-GlcNAc-betaCD (Gal-GlcNAc-betaCD) was synthesized by the transfer action of beta-galactosidase. GlcNAc-maltotriose (Glc3) and Gal-GlcNAc-Glc3 were produced with hydrolysis of GlcNAc-betaCD by cyclodextrin glycosyltransferase, and Gal-GlcNAc-betaCD by bacterial saccharifying alpha-amylase respectively. Finally, GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were synthesized in 5.2% and 3.5% yield when Klebsiella pneumoniae pullulanase was incubated with the mixture of GlcNAc-Glc(3) and betaCD, or Gal-GlcNAc-Glc3 and betaCD respectively. The structures of GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were analyzed by FAB-MS and NMR spectroscopy and identified as 6-O-alpha-(6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD, and 6-O-alpha-(4-O-beta-D-galactopyranosyl-6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD respectively. PMID:15849411

  5. Cross-sectional survey of kidney function in refinery employees

    SciTech Connect

    Viau, C.; Bernard, A.; Lauwerys, R.; Buchet, J.P.; Quaeghebeur, L.; Cornu, M.E.; Phillips, S.C.; Mutti, A.; Lucertini, S.; Franchini, I.

    1987-01-01

    We examined sensitive biochemical and immunological markers of kidney function and damage in 53 male oil refinery workers exposed to hydrocarbons and compared their results with those of a control group of 61 age-matched nonexposed males. The mean duration of employment of exposed males was 11 years. The current levels of exposure to a variety of aliphatic and aromatic hydrocarbons, as determined by personal monitoring, were well below the current threshold limit values. No difference was found in the urinary tubular parameters beta-N-acetyl-D-glucosaminidase, beta 2-microglobulin (beta 2-m) and retinol-binding protein. Similar serum beta 2-m levels indicated no impairment of the glomerular filtration rate in the exposed workers. The levels of circulating immune complexes were also identical in both groups. The mean albuminuria was slightly higher (p less than .005) in the exposed group in a quantitative assay but was not dipstick-detectable. The mean urinary excretion of a renal antigen was also higher (p less than .05) in the exposed group and correlated with the excretion of albumin. Finally, slightly higher titers of anti-laminin antibodies were found in five exposed employees, but this was not accompanied by an increased albuminuria. We conclude that chronic low-level hydrocarbon exposure in these refinery workers does not lead to clinically significant renal abnormalities. Nevertheless, some findings are consistent with the possible role of hydrocarbon exposure in the induction of renal disturbances.

  6. Morphological and functional differentiation in BE(2)-M17 human neuroblastoma cells by treatment with Trans-retinoic acid

    PubMed Central

    2013-01-01

    Background Immortalized neuronal cell lines can be induced to differentiate into more mature neurons by adding specific compounds or growth factors to the culture medium. This property makes neuronal cell lines attractive as in vitro cell models to study neuronal functions and neurotoxicity. The clonal human neuroblastoma BE(2)-M17 cell line is known to differentiate into a more prominent neuronal cell type by treatment with trans-retinoic acid. However, there is a lack of information on the morphological and functional aspects of these differentiated cells. Results We studied the effects of trans-retinoic acid treatment on (a) some differentiation marker proteins, (b) types of voltage-gated calcium (Ca2+) channels and (c) Ca2+-dependent neurotransmitter ([3H] glycine) release in cultured BE(2)-M17 cells. Cells treated with 10 μM trans-retinoic acid (RA) for 72 hrs exhibited marked changes in morphology to include neurite extensions; presence of P/Q, N and T-type voltage-gated Ca2+ channels; and expression of neuron specific enolase (NSE), synaptosomal-associated protein 25 (SNAP-25), nicotinic acetylcholine receptor α7 (nAChR-α7) and other neuronal markers. Moreover, retinoic acid treated cells had a significant increase in evoked Ca2+-dependent neurotransmitter release capacity. In toxicity studies of the toxic gas, phosgene (CG), that differentiation of M17 cells with RA was required to see the changes in intracellular free Ca2+ concentrations following exposure to CG. Conclusion Taken together, retinoic acid treated cells had improved morphological features as well as neuronal characteristics and functions; thus, these retinoic acid differentiated BE(2)-M17 cells may serve as a better neuronal model to study neurobiology and/or neurotoxicity. PMID:23597229

  7. Hydrothermal alteration in the Bosumtwi impact structure: Evidence from 2M1-muscovite, alteration veins, and fracture fillings

    NASA Astrophysics Data System (ADS)

    Petersen, Michael T.; Newsom, Horton E.; Nelson, Melissa J.; Moore, Duane M.

    Drill-core samples from the Bosumtwi impact structure (1.07 Myr old and 10.5 km in diameter) in Ghana exhibit mineralogical evidence for post-impact hydrothermal alteration. Nine samples of drill core obtained through the 2004 International Continental Scientific Drilling Project (ICDP) were studied, including an uppermost fallback layer overlying impactite breccias, and partly deformed massive meta-graywacke bedrock. The petrographic study revealed alteration veins containing secondary sericitic muscovite (comparable to 2M1-muscovite) crosscutting original bedding in meta-graywacke and forming a matrix between clasts in impactite breccias. X-ray diffraction (XRD) shows that these impactite samples are rich in 2M1-muscovite, consistent with post-impact fluid deposition and alteration. Optical analysis indicates the presence of a pre-impact stratiform chlorite in meta-graywacke samples and a secondary alteration chlorite occurring in all samples. Secondary illite was detected in upper impactites of drill core LB-08A and samples containing accretionary lapilli. The lower temperature constraint for the hydrothermal event is given by 2M1-muscovite, secondary chlorite, and illite, all of which form at temperatures greater than 280 °C. An absence of recrystallization of quartz and feldspar indicates an upper temperature constraint below 900 °C. The presence of alteration materials associated with fractures and veins in the uppermost impactites of drill cores LB-07A and LB-08A indicates that a post-impact hydrothermal system was present in and adjacent to the central uplift portion of the Bosumtwi impact structure. A sample containing accretionary lapilli obtained from drill core LB-05A exhibits limited evidence that hydrothermal processes were more widespread within the impactites on the crater floor.

  8. Effect of microwave reflection from the region of electron cyclotron resonance heating in the L-2M stellarator

    SciTech Connect

    Batanov, G. M.; Borzosekov, V. D.; Kolik, L. V.; Konchekov, E. M.; Malakhov, D. V.; Petrov, A. E.; Sarksyan, K. A.; Sakharov, A. S. Skvortsova, N. N.; Stepakhin, V. D.; Kharchev, N. K.

    2013-11-15

    In experiments on electron cyclotron resonance (ECR) heating of plasma at the second harmonic of the electron gyrofrequency in the L-2M stellarator, the effect of partial reflection of high-power gyrotron radiation from the ECR heating region located in the center of the plasma column was revealed. The reflection coefficient is found to be on the order of 10{sup −3}. The coefficient of reflection of an extraordinary wave from the second-harmonic ECR region is calculated in the one-dimensional full-wave model. The calculated and measured values of the reflection coefficient are found to coincide in order of magnitude.

  9. Alkynyl bridged cyclometalated Ir2M2 clusters: impact of the heterometal in the photo- and electro-luminescence properties.

    PubMed

    Fernández-Cestau, Julio; Giménez, Nora; Lalinde, Elena; Montaño, Patricia; Moreno, M Teresa; Sánchez, Sergio; Weber, Michael D; Costa, Rubén D

    2016-02-28

    We report two unprecedent alkynyl bridging cyclometalated clusters [Ir2M2(ppy)4(μ-C[triple bond, length as m-dash]CC6H4-OMe3)4] where M is Ag (2) and Cu (3), which display distinctive luminescence properties. While 2 features a green phosphorescence/electroluminescence nature located at the ppy ligands ((3)LC), 3 shows an orange emission confined to the metals and alkynyl groups having a mixed (3)L'C/(3)L'MCT/(3)MMCT (L' = alkynyl) nature. PMID:26827753

  10. TGF-beta inhibitors for the treatment of cancer.

    PubMed

    Lahn, Michael; Kloeker, Susanne; Berry, Brandi S

    2005-06-01

    Advances in understanding the role of transforming growth factor (TGF)-beta in tumorigenesis have led to the development of TGF-beta inhibitors for cancer treatment. Three platforms of TGF-beta inhibitors have evolved: antisense oligonucleotides, monoclonal antibodies and small molecules. In this review, the current stage of development of each known TGF-beta inhibitor will be discussed. As part of the risk/benefit assessment of TGF-beta inhibitors, the known effects of TGF-beta deficiency in mice, non-clinical toxicology studies with TGF-beta inhibitors in rats, and the clinical studies with monoclonal antibodies against TGF-beta will be summarised. PMID:16004592

  11. Determinants of RNA polymerase alpha subunit for interaction with beta, beta', and sigma subunits: hydroxyl-radical protein footprinting.

    PubMed Central

    Heyduk, T; Heyduk, E; Severinov, K; Tang, H; Ebright, R H

    1996-01-01

    Escherichia coli RNA polymerase (RNAP) alpha subunit serves as the initiator for RNAP assembly, which proceeds according to the pathway 2 alpha-->alpha 2-->alpha 2 beta-->alpha 2 beta beta'-->alpha 2 beta beta' sigma. In this work, we have used hydroxyl-radical protein footprinting to define determinants of alpha for interaction with beta, beta', and sigma. Our results indicate that amino acids 30-75 of alpha are protected from hydroxyl-radical-mediated proteolysis upon interaction with beta (i.e., in alpha 2 beta, alpha 2 beta beta', and alpha 2 beta beta' sigma), and amino acids 175-210 of alpha are protected from hydroxyl-radical-mediated proteolysis upon interaction with beta' (i.e., in alpha 2 beta beta' and alpha 2 beta beta' sigma). The protected regions are conserved in the alpha homologs of prokaryotic, eukaryotic, archaeal, and chloroplast RNAPs and contain sites of substitutions that affect RNAP assembly. We conclude that the protected regions define determinants of alpha for direct functional interaction with beta and beta'. The observed maximal magnitude of protection upon interaction with beta and the observed maximal magnitude of protection upon interaction with beta' both correspond to the expected value for complete protection of one of the two alpha protomers of RNAP (i.e., 50% protection). We propose that only one of the two alpha protomers of RNAP interacts with beta and that only one of the two alpha protomers of RNAP interacts with beta'. Images Fig. 1 Fig. 4 PMID:8816769

  12. Latent TGF-[beta] structure and activation

    SciTech Connect

    Shi, Minlong; Zhu, Jianghai; Wang, Rui; Chen, Xing; Mi, Lizhi; Walz, Thomas; Springer, Timothy A.

    2011-09-16

    Transforming growth factor (TGF)-{beta} is stored in the extracellular matrix as a latent complex with its prodomain. Activation of TGF-{beta}1 requires the binding of {alpha}v integrin to an RGD sequence in the prodomain and exertion of force on this domain, which is held in the extracellular matrix by latent TGF-{beta} binding proteins. Crystals of dimeric porcine proTGF-{beta}1 reveal a ring-shaped complex, a novel fold for the prodomain, and show how the prodomain shields the growth factor from recognition by receptors and alters its conformation. Complex formation between {alpha}v{beta}6 integrin and the prodomain is insufficient for TGF-{beta}1 release. Force-dependent activation requires unfastening of a 'straitjacket' that encircles each growth-factor monomer at a position that can be locked by a disulphide bond. Sequences of all 33 TGF-{beta} family members indicate a similar prodomain fold. The structure provides insights into the regulation of a family of growth and differentiation factors of fundamental importance in morphogenesis and homeostasis.

  13. Study of high-beta ballooning modes

    SciTech Connect

    Price, H.D.; Benjamin, N.M.P.; Kang, B.K.; Lichtenberg, A.J.; Lieberman, M.A.

    1985-01-01

    Ballooning instabilities are studied in the Berkeley multiple mirror experiment. Counterstreaming theta pinch and Marshall gun source hydrogen plasmas are used to achieve a high beta ( ..beta..>25%), where ..beta.. is the ratio of plasma to magnetic pressure at temperatures T/sub e/ = T/sub i/roughly-equal15 eV. Four magnetic field configurations are investigated, each at varying mirror ratios, to explore a range of drive and connection length parameters. In two of these the magnetic field is pulsed from a stable to a locally unstable configuration for initiation of ballooning activity. The other two (static) configurations are a weakly unstable local field region, and the standard linked quadrupole multiple-mirror configuration. Depending on the configuration, critical ..beta..'s are found for the onset of ballooning that vary from 5% for the most unstable configuration to greater than 25% for the standard multiple-mirror configuration. The m = 1 azimuthal mode is predominant, with some admixture of m = 2. The experimental results are compared with predictions from a magnetohydrodynamic theory. In the model the pressure is taken to be isotropic and constant along the axis, except in the diverging field regions at the device ends where the pressure falls to maintain beta constant, consistent with experimental observations. The theoretical results generally predict somewhat higher critical betas for the m = 1 mode than those observed. Estimates of the effect of finite Larmor radii, nearby conducting walls, axially nonuniform pressure profiles and resistivity, are also given.

  14. beta-Endorphin enhances lymphocyte proliferative responses.

    PubMed Central

    Gilman, S C; Schwartz, J M; Milner, R J; Bloom, F E; Feldman, J D

    1982-01-01

    The opioid peptides alpha- and beta-endorphin and [D-Ala2, Met5]enkephalin were investigated for their effect on the proliferation of resting and activated rat splenic lymphocytes in vitro. beta-Endorphin enhanced the proliferative response of spleen cells to the T cell mitogens concanavalin A and phytohemagglutinin. The effect of beta-endorphin was dose dependent and occurred at peptide concentrations similar to those found in rat plasma. alpha-Endorphin and [D-Ala2, Met5]enkephalin did not affect the proliferative responses to any mitogen tested. Furthermore, the potentiating effect of beta-endorphin was not reversed by treatment with 10 microM naloxone. None of the peptides had any effect on resting, unstimulated spleen cells or on the response to a mixture of lipopolysaccharide and dextran sulfate, which is specifically mitogenic for B lymphocytes. The pharmacological properties of the beta-endorphin potentiation indicate that the effect may be mediated by a nonopiate but beta-endorphin-specific mechanism. These results suggest a possible role for peripheral beta-endorphin and may provide a link between stress and disease susceptibility. PMID:6287475

  15. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    SciTech Connect

    Feng, Ying; Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min; Sun, Gui-yuan; Liu, Rui-tian

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  16. Methylation-induced G2/M arrest requires a full complement of the mismatch repair protein hMLH1

    PubMed Central

    Cejka, Petr; Stojic, Lovorka; Mojas, Nina; Russell, Anna Marie; Heinimann, Karl; Cannavó, Elda; di Pietro, Massimiliano; Marra, Giancarlo; Jiricny, Josef

    2003-01-01

    The mismatch repair (MMR) gene hMLH1 is mutated in ∼50% of hereditary non-polyposis colon cancers and transcriptionally silenced in ∼25% of sporadic tumours of the right colon. Cells lacking hMLH1 display microsatellite instability and resistance to killing by methylating agents. In an attempt to study the phenotypic effects of hMLH1 downregulation in greater detail, we designed an isogenic system, in which hMLH1 expression is regulated by doxycycline. We now report that human embryonic kidney 293T cells expressing high amounts of hMLH1 were MMR-proficient and arrested at the G2/M cell cycle checkpoint following treatment with the DNA methylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), while cells not expressing hMLH1 displayed a MMR defect and failed to arrest upon MNNG treatment. Interestingly, MMR proficiency was restored even at low hMLH1 concentrations, while checkpoint activation required a full complement of hMLH1. In the MMR-proficient cells, activation of the MNNG-induced G2/M checkpoint was accompanied by phosphorylation of p53, but the cell death pathway was p53 independent, as the latter polypeptide is functionally inactivated in these cells by SV40 large T antigen. PMID:12727890

  17. Cordycepin induces apoptosis and autophagy in human neuroblastoma SK-N-SH and BE(2)-M17 cells

    PubMed Central

    LI, YIFAN; LI, RONG; ZHU, SHENGLANG; ZHOU, RUYUN; WANG, LEI; DU, JIHUI; WANG, YONG; ZHOU, BEI; MAI, LIWEN

    2015-01-01

    Cordycepin, also termed 3′-deoxyadenosine, is a derivative of the nucleoside adenosine that represents a potential novel class of anticancer drugs targeting the 3′ untranslated region of RNAs. Cordycepin has been reported to induce apoptosis in certain cancer cell lines, but the effects of cordycepin on human neuroblastoma cells have not been studied. In the present study, an MTT assay revealed that cordycepin inhibits the viability of neuroblastoma SK-N-SH and BE(2)-M17 cells in a dose-dependent manner. In addition, cordycepin increases the early-apoptotic cell population of SK-N-SH cells, as determined by fluorescence-activated cell sorting analysis. The induction of apoptosis in neuroblastoma cells by cordycepin was further confirmed by western blotting, which revealed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase 1 in the SK-N-SH and BE(2)-M17 cells. Cordycepin also induced the formation of a punctate pattern of light-chain 3 (LC3)-associated green fluorescence in the SK-N-SH cells transfected with a pEGFP-LC3 vector. Furthermore, western blotting revealed cleavage of LC3 A/B in cordycepin-treated neuroblastoma SK-N-SH cells. Taken together, the results indicate that cordycepin significantly increases apoptosis and autophagy in neuroblastoma cells, and may therefore be a drug candidate for neuroblastoma therapy, but requires additional evaluation. PMID:26137103

  18. COX-2, mPGES-1 and EP2 receptor immunohistochemical expression in canine and feline malignant mammary tumours.

    PubMed

    Millanta, F; Asproni, P; Canale, A; Citi, S; Poli, A

    2016-09-01

    Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E2 (PGE2 ) tumour-promoting activity has been confirmed and its production is controlled by Cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Evidence suggests that mPGES-1 and COX-2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX-2, mPGES-1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non-neoplastic tissues. COX-2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES-1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX-2, EP2 receptor and mPGES-1 expression was significantly higher in carcinomas than in non-neoplastic tissues and adenomas. COX-2, mPGES-1 and EP2 receptor expression was strongly associated. These findings support a role of the COX-2/PGE2 pathway in the pathogenesis of these tumours. PMID:24824420

  19. Cucurbitacin B Causes Increased Radiation Sensitivity of Human Breast Cancer Cells via G2/M Cell Cycle Arrest

    PubMed Central

    Duangmano, Suwit; Sae-lim, Phorntip; Suksamrarn, Apichart; Patmasiriwat, Pimpicha; Domann, Frederick E.

    2012-01-01

    Purpose. To explore the effects of cucurbitacin B on the radiation survival of human breast cancer cells and to elucidate the cellular mechanism of radiosensitization if any. Materials and Methods. Human breast carcinoma cell lines were treated with cucurbitacin B before irradiation with 0–10 Gy of 137Cs gamma rays. The effect of cucurbitacin B on cell-survival following irradiation was evaluated by colony-forming assay. Cell cycle distributions were investigated using flow cytometry. Real-time PCR and western blots were performed to investigate the expression of cell cycle checkpoints. Results. Cucurbitacin B inhibited breast cancer cell proliferation in a dose-dependent manner. Only MDA-MB-231 and MCF7:5C cells but not SKBR-3 cells were radiosensitized by cucurbitacin B. Flow cytometric analysis for DNA content indicated that cucurbitacin B resulted in G2/M arrest in MDA-MB-231 and MCF7:5C but not SKBR-3 cells. Moreover, Real-time PCR and western blot analysis demonstrated upregulated p21 expression before irradiation, a likely cause of the cell cycle arrest. Conclusion. Taken together, these findings suggest that cucurbitacin B causes radiosensitization of some breast cancer cells, and that cucurbitacin B induced G2/M arrest is an important mechanism. Therefore, combinations of cucurbitacin B with radiotherapy may be appropriate for experimental breast cancer treatment. PMID:22690217

  20. GADD45γ induces G2/M arrest in human pharynx and nasopharyngeal carcinoma cells by cucurbitacin E

    PubMed Central

    Hung, Chao-Ming; Chang, Chi-Chang; Lin, Chen-Wei; Chen, Chih-Chen; Hsu, Yi-Chiang

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound-based drug which from the climbing stem of Cucumic melo L (Guadi). Previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study, investigated anti-proliferation and cell cycle G2/M arrest induced by CuE in Detroit 562 cells (pharynx carcinoma) and HONE-1 (nasopharyngeal carcinoma) cells. Results indicate that the cytotoxicity is associated with accumulation in G2/M cell-cycle phases. CuE produced cell cycle arrest as well as the downregulation of cyclin B1 and CDC2 expression. In addition, treated cells with CuE and GADD45γ SiRNA that also coincided with GADD45γ gene activation in cell cycle arrest. Both effects increased proportionally with the dose of CuE; however, proliferation inhibition and mitosis delay was dependant on the amount of CuE treatment in the cancer cells. PMID:25245461

  1. The Drosophila splicing regulator sex-lethal directly inhibits translation of male-specific-lethal 2 mRNA.

    PubMed Central

    Gebauer, F; Merendino, L; Hentze, M W; Valcárcel, J

    1998-01-01

    Male-specific expression of the protein male-specific-lethal 2 (MSL-2) controls dosage compensation in Drosophila. msl-2 gene expression is inhibited in females by Sex-lethal (SXL), an RNA binding protein known to regulate pre-mRNA splicing. An intron present at the 5' untranslated region (UTR) of msl-2 mRNA contains putative SXL binding sites and is retained in female flies. Here we show that SXL plays a dual role in the inhibition of msl-2 expression. Cotransfection of Drosophila Schneider cells with an SXL expression vector and a reporter containing the 5' UTR of msl-2 mRNA resulted in retention of the 5' UTR intron and efficient accumulation of the unspliced mRNA in the cytoplasm, where its translation was blocked by SXL, but not by the intron per se. Both splicing and translation inhibition by SXL were recapitulated in vitro and found to be dependent upon SXL binding to high-affinity sites within the intron, showing that SXL directly regulates these events. Our data reveal a coordinated mechanism for the regulation of msl-2 expression by the same regulatory factor: SXL enforces intron retention in the nucleus and subsequent translation inhibition in the cytoplasm. PMID:9570314

  2. An inhibitor of p34cdc2/cyclin B that regulates the G2/M transition in Xenopus extracts.

    PubMed Central

    Lee, T H; Kirschner, M W

    1996-01-01

    The activity of maturation-promoting factor (MPF), a protein kinase complex composed of p34cdc2 and cyclin B, is undetectable during interphase but rises abruptly at the G2/M transition to induce mitosis. After the synthesis of cyclin B, the suppression of MPF activity before mitosis has been attributed to the phosphorylation of p34cdc2 on sites (threonine-14 and tyrosine-15) that inhibit its catalytic activity. We previously showed that the activity of the mitotic p34cdc2/cyclin B complex is rapidly suppressed when added to interphase Xenopus extracts that lack endogenous cyclin B. Here we show that a mutant of p34cdc2 that cannot be inhibited by phosphorylation (threonine-14-->alanine, tyrosine-15-->phenylalanine) is also susceptible to inactivation, demonstrating that inhibitory mechanisms independent of threonine-14 and tyrosine-15 phosphorylation must exist. We have partially characterized this inhibitory pathway as one involving a reversible binding inhibitor of p34cdc2/cyclin B that is tightly associated with cell membranes. Kinetic analysis suggests that this inhibitor, in conjunction with the kinases that mediate the inhibitory phosphorylations on p34cdc2, maintains the interphase state in Xenopus; it may play an important role in the exact timing of the G2/M transition. Images Fig. 1 Fig. 3 Fig. 4 PMID:8552637

  3. Canthin-6-one displays antiproliferative activity and causes accumulation of cancer cells in the G2/M phase.

    PubMed

    Dejos, Camille; Voisin, Pierre; Bernard, Marianne; Régnacq, Matthieu; Bergès, Thierry

    2014-11-26

    Canthinones are natural substances with a wide range of biological activities, including antipyretic, antiparasitic, and antimicrobial. Antiproliferative and/or cytotoxic effects of canthinones on cancer cells have also been described, although their mechanism of action remains ill defined. To gain better insight into this mechanism, the antiproliferative effect of a commercially available canthin-6-one (1) was examined dose-dependently on six cancer cell lines (human prostate, PC-3; human colon, HT-29; human lymphocyte, Jurkat; human cervix, HeLa; rat glioma, C6; and mouse embryonic fibroblasts, NIH-3T3). Cytotoxic effects of 1 were investigated on the same cancer cell lines by procaspase-3 cleavage and on normal human skin fibroblasts. Strong antiproliferative effects of the compound were observed in all cell lines, whereas cytotoxic effects were very dependent on cell type. A better definition of the mechanism of action of 1 was obtained on PC-3 cells, by showing that it decreases BrdU incorporation into DNA by 60% to 80% and mitotic spindle formation by 70% and that it causes a 2-fold accumulation of cells in the G2/M phase of the cell cycle. Together, the data suggest that the primary effect of canthin-6-one (1) is antiproliferative, possibly by interfering with the G2/M transition. Proapoptotic effects might result from this disturbance of the cell cycle. PMID:25379743

  4. All Sky Camera, LIDAR and Electric Field Meter: Auxiliary instruments for the ASTRI SST-2M prototype

    NASA Astrophysics Data System (ADS)

    Leto, Giuseppe; Zanmar Sanchez, Ricardo; Bellassai, Giancarlo; Bruno, Pietro; Maccarone, Maria Concetta; Martinetti, Eugenio

    2015-03-01

    ASTRI SST-2M is the end-to-end prototype telescope of the Italian National Institute of Astrophysics, INAF, designed to investigate the 10-100 TeV band in the framework of the Cherenkov Telescope Array, CTA. The ASTRI SST-2M telescope has been installed in Italy in September 2014, at the INAF observing station located at Serra La Nave on Mount Etna. The telescope is foreseen to be completed and fully operative in spring 2015 including auxiliary instrumentation needed to support both operations and data analysis. In this contribution we present the current status of a sub-set of the auxiliary instruments that are being used at the Serra La Nave site, namely an All Sky Camera, an Electric Field Meter and a Raman Lidar devoted, together with further instrumentation, to the monitoring of the atmospheric and environmental conditions. The data analysis techniques under development for these instruments could be applied at the CTA sites, where similar auxiliary instrumentation will be installed.

  5. Genotoxic Stress Prevents Ndd1-Dependent Transcriptional Activation of G2/M-Specific Genes in Saccharomyces cerevisiae

    PubMed Central

    Yelamanchi, Syam Kumar; Veis, Jiri; Anrather, Dorothea; Klug, Helene

    2014-01-01

    Downregulation of specific transcripts is one of the mechanisms utilized by eukaryotic checkpoint systems to prevent cell cycle progression. Here we identified and explored such a mechanism in the yeast Saccharomyces cerevisiae. It involves the Mec1-Rad53 kinase cascade, which attenuates G2/M-specific gene transcription upon genotoxic stress. This inhibition is achieved via multiple Rad53-dependent inhibitory phosphorylations on the transcriptional activator Ndd1 that prevent its chromatin recruitment via interactions with the forkhead factor Fkh2. Relevant modification sites on Ndd1 were identified by mass spectrometry, and corresponding alanine substitutions were able to suppress a methyl methanesulfonate-induced block in Ndd1 chromatin recruitment. Whereas effective suppression by these Ndd1 mutants is achieved for DNA damage, this is not the case under replication stress conditions, suggesting that additional mechanisms must operate under such conditions. We propose that budding yeast cells prevent the normal transcription of G2/M-specific genes upon genotoxic stress to precisely coordinate the timing of mitotic and postmitotic events with respect to S phase. PMID:24324010

  6. The long noncoding RNA ASNR regulates degradation of Bcl-2 mRNA through its interaction with AUF1.

    PubMed

    Chen, Jiahui; Liu, Lihui; Wei, Guifeng; Wu, Wei; Luo, Huaxia; Yuan, Jiao; Luo, Jianjun; Chen, Runsheng

    2016-01-01

    The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited. Here, we found a nuclear-retained lncRNA, termed Lnc_ASNR (apoptosis suppressing-noncoding RNA), which serves as a repressor of apoptosis. Lnc_ASNR was discovered in a set of microarray data derived from four kinds of tumor and adjacent normal tissue samples, and displayed significant up-regulation in the tumor tissues. Using an RNA-pull down assay, we found that Lnc_ASNR interacted with the protein ARE/poly (U)-binding/degradation factor 1(AUF1), which is reported to promote rapid degradation of the Bcl-2 mRNA, an inhibitor of apoptosis. Lnc_ASNR binds to AUFI in nucleus, decreasing the cytoplasmic proportion of AUF1 which targets the B-cell lymphoma-2 (Bcl-2) mRNA. Taken together, the overall effect of Lnc_ASNR expression is thus a decrease in cell apoptosis indicating that Lnc_ASNR may play a vital role in tumorigenesis and carcinogenesis. PMID:27578251

  7. Tetrahydrocurcumin induces G2/M cell cycle arrest and apoptosis involving p38 MAPK activation in human breast cancer cells.

    PubMed

    Kang, Ning; Wang, Miao-Miao; Wang, Ying-Hui; Zhang, Zhe-Nan; Cao, Hong-Rui; Lv, Yuan-Hao; Yang, Yang; Fan, Peng-Hui; Qiu, Feng; Gao, Xiu-Mei

    2014-05-01

    Curcumin (CUR) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. In recent years, it has been reported that CUR exhibits significant anti-tumor activity in vivo. However, the pharmacokinetic features of CUR have indicated poor oral bioavailability, which may be related to its extensive metabolism. The CUR metabolites might be responsible for the antitumor pharmacological effects in vivo. Tetrahydrocurcumin (THC) is one of the major metabolites of CUR. In the present study, we examined the efficacy and associated mechanism of action of THC in human breast cancer MCF-7 cells for the first time. Here, THC exhibited significant cell growth inhibition by inducing MCF-7 cells to undergo mitochondrial apoptosis and G2/M arrest. Moreover, co-treatment of MCF-7 cells with THC and p38 MAPK inhibitor, SB203580, effectively reversed the dissipation in mitochondrial membrane potential (Δψm), and blocked THC-mediated Bax up-regulation, Bcl-2 down-regulation, caspase-3 activation as well as p21 up-regulation, suggesting p38 MAPK might mediate THC-induced apoptosis and G2/M arrest. Taken together, these results indicate THC might be an active antitumor form of CUR in vivo, and it might be selected as a potentially effective agent for treatment of human breast cancer. PMID:24593988

  8. PCNA Retention on DNA into G2/M Phase Causes Genome Instability in Cells Lacking Elg1.

    PubMed

    Johnson, Catherine; Gali, Vamsi K; Takahashi, Tatsuro S; Kubota, Takashi

    2016-07-19

    Loss of the genome maintenance factor Elg1 causes serious genome instability that leads to cancer, but the underlying mechanism is unknown. Elg1 forms the major subunit of a replication factor C-like complex, Elg1-RLC, which unloads the ring-shaped polymerase clamp PCNA from DNA during replication. Here, we show that prolonged retention of PCNA on DNA into G2/M phase is the major cause of genome instability in elg1Δ yeast. Overexpression-induced accumulation of PCNA on DNA causes genome instability. Conversely, disassembly-prone PCNA mutants that relieve PCNA accumulation rescue the genome instability of elg1Δ cells. Covalent modifications to the retained PCNA make only a minor contribution to elg1Δ genome instability. By engineering cell-cycle-regulated ELG1 alleles, we show that abnormal accumulation of PCNA on DNA during S phase causes moderate genome instability and its retention through G2/M phase exacerbates genome instability. Our results reveal that PCNA unloading by Elg1-RLC is critical for genome maintenance. PMID:27373149

  9. Xanthatin induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma MKN-45 cells.

    PubMed

    Zhang, Lei; Tao, Li; Ruan, Junshan; Li, Weidong; Wu, Yu; Yan, Linggeng; Zhang, Feng; Fan, Fangtian; Zheng, Shizhong; Wang, Aiyun; Lu, Yin

    2012-06-01

    Xanthatin, a natural bioactive compound of sesquiterpene lactones, was isolated and purified from air-dried aerial part of Xanthium sibiricum Patrin ex Widder. In the present study, we demonstrated the significant antiproliferative and proapoptotic effects of xanthatin on human gastric carcinoma MKN-45 cells. MTS assay showed that xanthatin produced obvious cytotoxicity in MKN-45 cells with IC50 values of 18.6, 9.3, and 3.9 µM for 12, 24, and 48 h, respectively. Results of flow cytometry analysis indicated that the antiproliferative activity induced by xanthatin might be executed via G2/M cell cycle arrest and proapoptosis in MKN-45 cells. Western blot analysis elucidated that: a) xanthatin downregulated expression of Chk1 and Chk2 and phosphorylation of CDC2, which are known as key G2/M transition regulators; b) xanthatin increased p53 activation, decreased the bcl-2/bax ratio and the levels of downstream procaspase-9 and procaspase-3, which are key regulators in the intrinsic apoptosis pathway; c) xanthatin blocked phosphorylation of NF-κB (p65 subunit) and of IκBα, which might contribute to its proapoptotic effects on MKN-45 cells. In conclusion, our results suggest that xanthatin may have therapeutic potential against human gastric carcinoma. PMID:22532019

  10. Investigation of the physical properties of the tetragonal CeMAl4Si2 (M = Rh, Ir, Pt) compounds

    DOE PAGESBeta

    Ghimire, N. J.; Ronning, F.; Williams, D. J.; Scott, B. L.; Luo, Yongkang; Thompson, J. D.; Bauer, E. D.

    2014-12-15

    The synthesis, crystal structure and physical properties studied by means of x-ray diffraction, magnetic, thermal and transport measurements of CeMAl4Si2 (M = Rh, Ir, Pt) are reported, along with the electronic structure calculations for LaMAl4Si2 (M = Rh, Ir, Pt). These materials adopt a tetragonal crystal structure (space group P4/mmm) comprised of BaAl4 blocks, separated by MAl2 units, stacked along the c-axis. Both CeRhAl4Si2 and CeIrAl4Si2 order antiferromagnetically below TN1 = 14 and 16 K, respectively, and undergo a second antiferromagnetic transitition at lower temperature (TN2 = 9 and 14 K, respectively). CePtAl4Si2 orders ferromagnetically below TC = 3 Kmore » with an ordered moment of μsat = 0.8 μB for a magnetic field applied perpendicular to the c-axis. Electronic structure calculations reveal quasi-2D character of the Fermi surface.« less

  11. Correlation Between Pancreatic Islet Uncoupling Protein-2 (UCP2) mRNA Concentration And Insulin Status in Rats

    PubMed Central

    Kassis, Nadim; Bernard, Catherine; Pusterla, Aristide; Casteilla, Louis; Pétnicaud, Luc; Richard, Denis; Ricquier, Daniel

    2000-01-01

    Hypothesizing that UCP2 may influence insulin secretion by modifying the ATP/ADP ratio within pancreatic islets, we have investigated the expression of intraislet UCP2 gene in rats showing insulin oversecretion (non-diabetic Zucker fa/fa obese rats, glucose-infused Wistar rats) or insulin undersecretion (fasting and mildly diabetic rats). We found that in Zucker fa/fa obese rats, hyperinsulinemia (1222 ± 98 pmol/1 vs. 128 ± 22 pmol/1 in lean Zucker rats) was accompanied by a significant increase in UCP2 mRNA levels. In rat submitted to a 5 day infusion with glucose, hyperinsulinemia (1126 ± 101 pmol/l vs. 215 ± 25 pmol/1 in Wistar control rats), coincided with an enhanced intraislet UCP2 gene expression, whereas a 8h or a 2 day-infusion did not induce significant changes in UCP2 mRNA expression. In rats made hypoinsulinemic and mildly diabetic by the injection of a low dose of streptozotocin, and in 4-day-fasting rats (plasma insulin 28 ± 5 pmol/1) UCP2 gene expression was sharply decreased. A 3-day-fast was ineffective. The data show the existence of a time-dependent correlation between islet mRNA UCP2 and insulin that may be interpreted as an adaptative response to prolonged insulin excess. PMID:11467409

  12. The long noncoding RNA ASNR regulates degradation of Bcl-2 mRNA through its interaction with AUF1

    PubMed Central

    Chen, Jiahui; Liu, Lihui; Wei, Guifeng; Wu, Wei; Luo, Huaxia; Yuan, Jiao; Luo, Jianjun; Chen, Runsheng

    2016-01-01

    The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited. Here, we found a nuclear-retained lncRNA, termed Lnc_ASNR (apoptosis suppressing-noncoding RNA), which serves as a repressor of apoptosis. Lnc_ASNR was discovered in a set of microarray data derived from four kinds of tumor and adjacent normal tissue samples, and displayed significant up-regulation in the tumor tissues. Using an RNA-pull down assay, we found that Lnc_ASNR interacted with the protein ARE/poly (U)-binding/degradation factor 1(AUF1), which is reported to promote rapid degradation of the Bcl-2 mRNA, an inhibitor of apoptosis. Lnc_ASNR binds to AUFI in nucleus, decreasing the cytoplasmic proportion of AUF1 which targets the B-cell lymphoma-2 (Bcl-2) mRNA. Taken together, the overall effect of Lnc_ASNR expression is thus a decrease in cell apoptosis indicating that Lnc_ASNR may play a vital role in tumorigenesis and carcinogenesis. PMID:27578251

  13. Study on Matching a 300 MVA Motor Generator with an Ohmic Heating Power Supply in HL-2M

    NASA Astrophysics Data System (ADS)

    Peng, Jianfei; Xuan, Weimin; Wang, Haibing; Li, Huajun; Wang, Yingqiao; Wang, Shujin

    2013-03-01

    A new 300 MVA/1350 MJ motor generator (MG) will be built to feed all of the poloidal field power supplies (PFPS) and auxiliary heating power supplies of the HL-2M tokamak. The MG has a vertical-shaft salient pole 6-phase synchronous generator and a coaxial 8500 kW induction motor. The Ohmic heating power supply (OHPS) consisting of 4-quadrant DC pulsed convertor is the one with the highest parameters among the PFPS. Therefore, the match between the generator and the OHPS is very important. The matching study with Matlab/Simulink is described in this paper. The simulation results show that the subtransient reactance of the generator is closely related to the inversion operation of the OHPS. By setting various subtransient reactance in the simulation generator model and considering the cost reduction, the optimized parameters are obtained as x″d = 0.405 p.u. at 100 Hz for the generator. The models built in the simulation can be used as an important tool for studying the dynamic characteristics and the control strategy of other HL-2M PFPSes.

  14. Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    SciTech Connect

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-06-10

    Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  15. Evidence for Novel [beta]-Sheet Structures in Iowa Mutant [beta]-Amyloid Fibrils

    SciTech Connect

    Tycko, Robert; Sciarretta, Kimberly L.; Orgel, Joseph P.R.O.; Meredith, Stephen C.

    2009-07-24

    Asp23-to-Asn mutation within the coding sequence of {beta}-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A{beta}40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A{beta}40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10{sup -3} min{sup -1} and 1.07 x 10{sup -4} min{sup -1} for D23N-A{beta}40 and the wild-type peptide WT-A{beta}40, respectively) and without a lag phase. Electron microscopy shows that D23N-A{beta}40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-{beta} pattern, with a sharp reflection at 4.7 {angstrom} and a broad reflection at 9.4 {angstrom}, which is notably smaller than the value for WT-A{beta}40 fibrils (10.4 {angstrom}). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A{beta}40 fibrils containing the in-register, parallel {beta}-sheet structure commonly found in WT-A{beta}40 fibrils and most other amyloid fibrils. Antiparallel {beta}-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through 13C-13C and 15N-13C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A{beta}40 fibrils and the unusual vasculotropic clinical picture in these patients.

  16. EURONEAR—Recovery, follow-up and discovery of NEAs and MBAs using large field 1-2 m telescopes

    NASA Astrophysics Data System (ADS)

    Vaduvescu, O.; Birlan, M.; Tudorica, A.; Sonka, A.; Pozo, F. N.; Barr, A. D.; Asher, D. J.; Licandro, J.; Ortiz, J. L.; Unda-Sanzana, E.; Popescu, M.; Nedelcu, A.; Dumitru, D.; Toma, R.; Comsa, I.; Vancea, C.; Vidican, D.; Opriseanu, C.; Badescu, T.; Badea, M.; Constantinescu, M.

    2011-10-01

    We report on the follow-up and recovery of 100 program NEAs, PHAs and VIs using the ESO/MPG 2.2 m, Swope 1 m and INT 2.5 m telescopes equipped with large field cameras. The 127 fields observed during 11 nights covered 29 square degrees. Using these data, we present the incidental survey work which includes 558 known MBAs and 628 unknown moving objects mostly consistent with MBAs from which 58 objects became official discoveries. We planned the runs using six criteria and four servers which focus mostly on faint and poorly observed objects in need of confirmation, follow-up and recovery. We followed 62 faint NEAs within one month after discovery and we recovered 10 faint NEAs having big uncertainties at their second or later opposition. Using the INT we eliminated four PHA candidates and VIs. We observed in total 1286 moving objects and we reported more than 10,000 positions. All data were reduced by the members of our network in a team effort, and reported promptly to the MPC. The positions of the program NEAs were published in 27 MPC and MPEC references and used to improve their orbits. The O-C residuals for known MBAs and program NEAs are smallest for the ESO/MPG and Swope and about four times larger for the INT whose field is more distorted. For the astrometric reduction, the UCAC-2 catalog is recommended instead of USNO-B1. The incidental survey allowed us to study statistics of the MBA and NEA populations observable today with 1-2 m facilities. We calculate preliminary orbits for all unknown objects, classifying them as official discoveries, later identifications and unknown outstanding objects. The orbital elements a, e, i calculated by FIND_ORB software for the official discoveries and later identified objects are very similar with the published elements which take into account longer observational arcs; thus preliminary orbits were used in statistics for the whole unknown dataset. We present a basic model which can be used to distinguish between MBAs and

  17. Fabrication of thin layer beta alumina

    NASA Technical Reports Server (NTRS)

    Tennenhouse, G. J.

    1977-01-01

    Beta alumina tubes having walls 700 microns, 300 microns, and 140 microns were processed by extrusion and sintering utilizing Ford proprietary binder and fabrication systems. Tubes prepared by this method have properties similar to tubes prepared by isostatic pressing and sintering, i.e. density greater than 98% of theoretical and a helium leak rate less than 3 x 10 to the -9th power cc/sq cm/sec. Ford ultrasonic bonding techniques were used for bonding beta alumina end caps to open ended beta -alumina tubes prior to sintering. After sintering, the bond was hermetic, and the integrity of the bonded area was comparable to the body of the tube.

  18. Transport properties of finite-beta microturbulence

    SciTech Connect

    Pueschel, M. J.; Jenko, F.

    2010-06-15

    Via nonlinear gyrokinetic simulations, microturbulent transport is investigated for electromagnetic trapped electron mode (TEM) and ion temperature gradient (ITG) tokamak core turbulence with beta up to and beyond the kinetic ballooning mode threshold. Deviations from linear expectations are explained by zonal flow activity in the TEM case. For the ITG scenario, beta-induced changes are observed in the nonlinear critical gradient upshift--from a certain beta, a strong increase is observed in the Dimits shift. Additionally, a Rechester-Rosenbluth-type model for magnetic transport is applied, and the amplitudes of magnetic field fluctuations are quantified for different types of turbulence.

  19. Syntheses of stable isotope-labeled 6 beta-hydroxycortisol, 6 beta-hydroxycortisone, and 6 beta-hydroxytestosterone.

    PubMed

    Furuta, Takashi; Suzuki, Atsushi; Matsuzawa, Mitsuhiro; Shibasaki, Hiromi; Kasuya, Yasuji

    2003-09-01

    A method is described for the preparation of two types of multi-labeled 6 beta-hydroxycortisol containing either five deuterium atoms at C-19 methyl and C-1 methylene or four 13C atoms at C-1, C-2, C-4, and C-19 in addition to the five deuterium atoms for use as analytical internal standards for gas chromatography-mass spectrometry (GC-MS). BMD derivatives of [1,1,19,19,19-2H(5)]cortisone and [1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone (cortisone-2H(5)-BMD and cortisone-13C(4),2H(5)-BMD) were first synthesized via indan synthon method starting from optical active 11-oxoindanylpropionic acid and labeled isopropenyl anion ([1,1,3,3,3-2H(5)]- or [1,3-13C(2),1,1,3,3,3-2H(5)]isopropenyl anion). The labeled isopropenyl anion was prepared from commercially available [1,1,1,3,3,3-2H(6)]- or [1,3-13C(2),1,1,1,3,3,3-2H(6)]acetone. Ultraviolet (UV) irradiated autoxidation at C-6 position of 3-ethyl-3,5-dienol ether derivatives of the labeled cortisone-BMDs gave 6 beta-hydroxy-[1,1,19,19,19-2H(5)]cortisone-BMD and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisone-BMD, respectively, as a mixture of 6 beta- and 6 alpha-epimers in a ratio of 4:1. Separation of 6 beta- and 6 alpha-epimers by thin-layer chromatography (TLC) and subsequent hydrolysis of the BMD group at C-17 gave pure labeled 6 beta-hydroxycortisone. After protecting the keto group at C-3 of the labeled 6 beta-hydroxycortisone-BMD as semicarbazone, reduction of 11-keto group with NaBH(4) and subsequent removal of the C-3 and C-17 protecting groups gave 6beta-hydroxy-[1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-2H(5)) and 6 beta-hydroxy-[1,2,4,19-13C(4),1,1,19,19,19-2H(5)]cortisol (6 beta-hydroxycortisol-13C(4),2H(5)), respectively, as a mixture of 6 beta- and 6 alpha-epimers (6 beta:6 alpha=4.4:1). The isotopic compositions of 6 beta-hydroxycortisol-2H(5) and 6 beta-hydroxycortisol-13C(4),2H(5) were 90.9 and 92.1 at.%, respectively. Furthermore, 6 beta-hydroxy-[1 alpha,16,16,17 alpha-2H(4

  20. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    SciTech Connect

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K.

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly