Sample records for nas bk020032 american

  1. Decay properties of Bk24397 and Bk24497

    NASA Astrophysics Data System (ADS)

    Ahmad, I.; Kondev, F. G.; Greene, J. P.; Zhu, S.

    2018-01-01

    Electron capture decays of 243Bk and 244Bk have been studied by measuring the γ -ray spectra of mass-separated sources and level structures of 243Cm and 244Cm have been deduced. In 243Cm, the electron capture population to the ground state, 1 /2+[631 ] , and 1 /2+[620 ] Nilsson states have been observed. The octupole Kπ=2- band was identified in 244Cm at 933.6 keV. In addition, spins and parities were deduced for several other states and two-quasiparticle configurations have been tentatively assigned to them.

  2. Modulation of BK channels by ethanol

    PubMed Central

    Dopico, Alex M.; Bukiya, Anna N.; Kuntamallappanavar, Guruprasad; Liu, Jianxi

    2017-01-01

    In alcohol-naïve systems, ethanol (<100 mM) exposure of calcium-gated BK channels perturbs physiology and behavior. Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain. The importance of this region in alcohol-induced intoxication has been addressed in Caenorhabditis elegans slo1 mutants. However, ethanol-induced BK activation is not universal as refractoriness and inhibition have been reported. The final effect depends on many factors, including intracellular calcium levels, slo1 isoform, BK beta subunit composition, post-translational modification of BK proteins, channel lipid microenvironment and type of ethanol administration. Studies in Drosophila melanogaster, Caenorhabditis elegans and rodents show that protracted/repeated ethanol administration leads to tolerance to alcohol-induced modification of BK-driven physiology and behavior. Unveiling the mechanisms underlying tolerance is of major importance, as tolerance to alcohol has been proposed as predictor of risk for alcoholism. PMID:27238266

  3. BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection

    PubMed Central

    Vigil, Darlene; Konstantinov, Nikifor K; Barry, Marc; Harford, Antonia M; Servilla, Karen S; Kim, Young Ho; Sun, Yijuan; Ganta, Kavitha; Tzamaloukas, Antonios H

    2016-01-01

    Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research. PMID:27683628

  4. Decay properties of Bk 97 243 and Bk 97 244

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmad, I.; Kondev, F. G.; Greene, J. P.

    2018-01-01

    Electron capture decays of Bk-243 and Bk-244 have been studied by measuring the gamma-ray spectra of mass-separated sources and level structures of Cm-243 and Cm-244 have been deduced. In Cm-243, the electron capture population to the ground state, 1/2(+)[631], and 1/2(+)[620] Nilsson states have been observed. The octupole K-pi = 2(-) band was identified in Cm-244 at 933.6 keV. In addition, spins and parities were deduced for several other states and two-quasiparticle configurations have been tentatively assigned to them

  5. Molecular mechanism of pharmacological activation of BK channels

    PubMed Central

    Gessner, Guido; Cui, Yong-Mei; Otani, Yuko; Ohwada, Tomohiko; Soom, Malle; Hoshi, Toshinori; Heinemann, Stefan H.

    2012-01-01

    Large-conductance voltage- and Ca2+-activated K+ (Slo1 BK) channels serve numerous cellular functions, and their dysregulation is implicated in various diseases. Drugs activating BK channels therefore bear substantial therapeutic potential, but their deployment has been hindered in part because the mode of action remains obscure. Here we provide mechanistic insight into how the dehydroabietic acid derivative Cym04 activates BK channels. As a representative of NS1619-like BK openers, Cym04 reversibly left-shifts the half-activation voltage of Slo1 BK channels. Using an established allosteric BK gating model, the Cym04 effect can be simulated by a shift of the voltage sensor and the ion conduction gate equilibria toward the activated and open state, respectively. BK activation by Cym04 occurs in a splice variant-specific manner; it does not occur in such Slo1 BK channels using an alternative neuronal exon 9, which codes for the linker connecting the transmembrane segment S6 and the cytosolic RCK1 domain—the S6/RCK linker. In addition, Cym04 does not affect Slo1 BK channels with a two-residue deletion within this linker. Mutagenesis and model-based gating analysis revealed that BK openers, such as Cym04 and NS1619 but not mallotoxin, activate BK channels by functionally interacting with the S6/RCK linker, mimicking site-specific shortening of this purported passive spring, which transmits force from the cytosolic gating ring structure to open the channel's gate. PMID:22331907

  6. Diagnosis of BK viral nephropathy in the renal allograft biopsy: role of fluorescence in situ hybridization.

    PubMed

    Wang, Zhen; Portier, Bryce P; Hu, Bo; Chiesa-Vottero, Andres; Myles, Jonathan; Procop, Gary W; Tubbs, Raymond R

    2012-09-01

    Early recognition of BK viral nephropathy is essential for successful management. Our aim in this study was to evaluate a novel fluorescence in situ hybridization (FISH) assay for detection of BK virus in renal transplant biopsies in the context of standard detection methods. Renal allograft biopsies (n = 108) were analyzed via H&E, immunohistochemistry (IHC) for simian virus 40, and FISH for BK virus. BK virus was detected in 16 (14.8%) cases by H&E, 13 (12%) cases by IHC, 18 (16.6%) cases by FISH, and 19 (17.6%) cases by real-time PCR; 24 of 108 showed a discrepancy in ≥1 testing modalities. Comparison of H&E, IHC, and FISH showed no statistical difference in detection of BK virus. However, performing comparisons between the different tissue-based assays in the context of plasma or urine real-time PCR results showed significant improvement in detection of BK by FISH over H&E (P = 0.02) but not IHC (P = 0.07). This novel FISH-based approach for BK virus identification in renal allograft biopsy tissue mirrored real-time PCR results and showed superior performance to detection of inclusions by H&E. Therefore, use of FISH for BK virus detection in the setting of renal allograft biopsy is a useful and sensitive detection method and could be adopted in any laboratory that currently performs FISH analysis. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  7. Proximal clustering between BK and CaV1.3 channels promotes functional coupling and BK channel activation at low voltage

    PubMed Central

    Vivas, Oscar; Moreno, Claudia M; Santana, Luis F; Hille, Bertil

    2017-01-01

    CaV-channel dependent activation of BK channels is critical for feedback control of both calcium influx and cell excitability. Here we addressed the functional and spatial interaction between BK and CaV1.3 channels, unique CaV1 channels that activate at low voltages. We found that when BK and CaV1.3 channels were co-expressed in the same cell, BK channels started activating near −50 mV, ~30 mV more negative than for activation of co-expressed BK and high-voltage activated CaV2.2 channels. In addition, single-molecule localization microscopy revealed striking clusters of CaV1.3 channels surrounding clusters of BK channels and forming a multi-channel complex both in a heterologous system and in rat hippocampal and sympathetic neurons. We propose that this spatial arrangement allows tight tracking between local BK channel activation and the gating of CaV1.3 channels at quite negative membrane potentials, facilitating the regulation of neuronal excitability at voltages close to the threshold to fire action potentials. DOI: http://dx.doi.org/10.7554/eLife.28029.001 PMID:28665272

  8. Correlation of BK Virus Neutralizing Serostatus With the Incidence of BK Viremia in Kidney Transplant Recipients.

    PubMed

    Abend, Johanna R; Changala, Marguerite; Sathe, Atul; Casey, Fergal; Kistler, Amy; Chandran, Sindhu; Howard, Abigail; Wojciechowski, David

    2017-06-01

    BK virus (BKV)-associated nephropathy is the second leading cause of graft loss in kidney transplant recipients. Due to the high prevalence of persistent infection with BKV in the general population, it is possible that either the transplant recipient or donor may act as the source of virus resulting in viruria and viremia. Although several studies suggest a correlation between donor-recipient serostatus and the development of BK viremia, specific risk factors for BKV-related complications in the transplant setting remain to be established. We retrospectively determined the pretransplant BKV neutralizing serostatus of 116 donors (D)-recipient (R) pairs using infectious BKV neutralization assays with representatives from the 4 major viral serotypes. The neutralizing serostatus of donors and recipients was then correlated with the incidence of BK viremia during the first year posttransplantation. There were no significant differences in baseline demographics or transplant data among the 4 neutralizing serostatus groups, with the exception of calculated panel-reactive antibody which was lowest in the D+/R- group. Recipients of kidneys from donors with significant serum neutralizing activity (D+) had elevated risk for BK viremia, regardless of recipient serostatus (D+ versus D-: odd ratio, 5.0; 95% confidence interval, 1.9-12.7]; P = 0.0008). Furthermore, donor-recipient pairs with D+/R- neutralizing serostatus had the greatest risk for BK viremia (odds ratio, 4.9; 95% confidence interval, 1.7-14.6; P = 0.004). Donor neutralizing serostatus correlates significantly with incidence of posttransplant BK viremia. Determination of donor-recipient neutralizing serostatus may be useful in assessing the risk of BKV infection in kidney transplant recipients.

  9. BK Channels in the Vascular System.

    PubMed

    Krishnamoorthy-Natarajan, G; Koide, M

    2016-01-01

    Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the β1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or β1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators. © 2016 Elsevier Inc. All rights reserved.

  10. Introducing the Big Knowledge to Use (BK2U) challenge.

    PubMed

    Perl, Yehoshua; Geller, James; Halper, Michael; Ochs, Christopher; Zheng, Ling; Kapusnik-Uner, Joan

    2017-01-01

    The purpose of the Big Data to Knowledge initiative is to develop methods for discovering new knowledge from large amounts of data. However, if the resulting knowledge is so large that it resists comprehension, referred to here as Big Knowledge (BK), how can it be used properly and creatively? We call this secondary challenge, Big Knowledge to Use. Without a high-level mental representation of the kinds of knowledge in a BK knowledgebase, effective or innovative use of the knowledge may be limited. We describe summarization and visualization techniques that capture the big picture of a BK knowledgebase, possibly created from Big Data. In this research, we distinguish between assertion BK and rule-based BK (rule BK) and demonstrate the usefulness of summarization and visualization techniques of assertion BK for clinical phenotyping. As an example, we illustrate how a summary of many intracranial bleeding concepts can improve phenotyping, compared to the traditional approach. We also demonstrate the usefulness of summarization and visualization techniques of rule BK for drug-drug interaction discovery. © 2016 New York Academy of Sciences.

  11. Introducing the Big Knowledge to Use (BK2U) challenge

    PubMed Central

    Perl, Yehoshua; Geller, James; Halper, Michael; Ochs, Christopher; Zheng, Ling; Kapusnik-Uner, Joan

    2016-01-01

    The purpose of the Big Data to Knowledge (BD2K) initiative is to develop methods for discovering new knowledge from large amounts of data. However, if the resulting knowledge is so large that it resists comprehension, referred to here as Big Knowledge (BK), how can it be used properly and creatively? We call this secondary challenge, Big Knowledge to Use (BK2U). Without a high-level mental representation of the kinds of knowledge in a BK knowledgebase, effective or innovative use of the knowledge may be limited. We describe summarization and visualization techniques that capture the big picture of a BK knowledgebase, possibly created from Big Data. In this research, we distinguish between assertion BK and rule-based BK and demonstrate the usefulness of summarization and visualization techniques of assertion BK for clinical phenotyping. As an example, we illustrate how a summary of many intracranial bleeding concepts can improve phenotyping, compared to the traditional approach. We also demonstrate the usefulness of summarization and visualization techniques of rule-based BK for drug–drug interaction discovery. PMID:27750400

  12. Blocking the BK Channel Impedes Acquisition of Trace Eyeblink Conditioning

    ERIC Educational Resources Information Center

    Matthews, Elizabeth A.; Disterhoft, John F.

    2009-01-01

    Big-K[superscript +] conductance (BK)-channel mediated fast afterhyperpolarizations (AHPs) following action potentials are reduced after eyeblink conditioning. Blocking BK channels with paxilline increases evoked firing frequency in vitro and spontaneous pyramidal activity in vivo. To examine how increased excitability after BK-channel blockade…

  13. BK virus-associated hemorrhagic cystitis after pediatric stem cell transplantation

    PubMed Central

    Han, Seung Beom; Kang, Jin Han

    2014-01-01

    Hemorrhagic cystitis is a common stem cell transplantation-related complication. The incidence of early-onset hemorrhagic cystitis, which is related to the pretransplant conditioning regimen, has decreased with the concomitant use of mesna and hyperhydration. However, late-onset hemorrhagic cystitis, which is usually caused by the BK virus, continues to develop. Although the BK virus is the most common pathogenic microorganism of poststem cell transplantation late-onset hemorrhagic cystitis, pediatricians outside the hemato-oncology and nephrology specialties tend to be unfamiliar with hemorrhagic cystitis and the BK virus. Moreover, no standard guidelines for the early diagnosis and treatment of BK virus-associated hemorrhagic cystitis after stem cell transplantation have been established. Here, we briefly introduce poststem cell transplantation BK virus-associated hemorrhagic cystitis. PMID:25653684

  14. Polyomavirus BK infection in blood and marrow transplant recipients

    PubMed Central

    Dropulic, LK; Jones, RJ

    2011-01-01

    The association of BK virus infection with hemorrhagic cystitis in blood and marrow transplant (BMT) recipients was first demonstrated two decades ago. During this time, therapeutic interventions focused on supportive measures such as hyperhydration, continuous bladder irrigation and topical administration of agents that alter the mucosal surface of the bladder wall. In recent years, PCR amplification of viral DNA in the urine and plasma has solidified the association of BK virus infection with hemorrhagic cystitis, demonstrating that higher urine and plasma viral loads occur in the setting of disease. The evaluation of virus-specific therapy has lagged behind assessment of the viral load and theories of pathogenesis. Extrapolating from successes in the treatment of BK virus nephropathy in the renal transplant population, cidofovir and leflunomide are identified as potential effective agents for the treatment of BK virus-associated hemorrhagic cystitis. The fluoroquinolone antibiotics may prove to be effective as prophylactic agents. Given the manifestation of BK virus infection in organs outside of the urinary tract in an increasing immunocompromised patient population and the availability of potential antiviral agents, therapeutic trials need to progress beyond the small case series in order to improve the morbidity and mortality caused by BK virus-associated hemorrhagic cystitis in the BMT population. PMID:17952131

  15. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation.

    PubMed

    Gabardi, Steven; Waikar, Sushrut S; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

    2010-07-01

    Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

  16. Coronary arterial BK channel dysfunction exacerbates ischemia/reperfusion-induced myocardial injury in diabetic mice.

    PubMed

    Lu, Tong; Jiang, Bin; Wang, Xiao-Li; Lee, Hon-Chi

    2016-09-01

    The large conductance Ca(2+)-activated K(+) (BK) channels, abundantly expressed in coronary artery smooth muscle cells (SMCs), play a pivotal role in regulating coronary circulation. A large body of evidence indicates that coronary arterial BK channel function is diminished in both type 1 and type 2 diabetes. However, the consequence of coronary BK channel dysfunction in diabetes is not clear. We hypothesized that impaired coronary BK channel function exacerbates myocardial ischemia/reperfusion (I/R) injury in streptozotocin-induced diabetic mice. Combining patch-clamp techniques and cellular biological approaches, we found that diabetes facilitated the colocalization of angiotensin II (Ang II) type 1 receptors and BK channel α-subunits (BK-α), but not BK channel β1-subunits (BK-β1), in the caveolae of coronary SMCs. This caveolar compartmentation in vascular SMCs not only enhanced Ang II-mediated inhibition of BK-α but also produced a physical disassociation between BK-α and BK-β1, leading to increased infarct size in diabetic hearts. Most importantly, genetic ablation of caveolae integrity or pharmacological activation of coronary BK channels protected the cardiac function of diabetic mice from experimental I/R injury in both in vivo and ex vivo preparations. Our results demonstrate a vascular ionic mechanism underlying the poor outcome of myocardial injury in diabetes. Hence, activation of coronary BK channels may serve as a therapeutic target for cardiovascular complications of diabetes.

  17. Evaluation of Fluoroquinolones for the Prevention of BK Viremia after Renal Transplantation

    PubMed Central

    Waikar, Sushrut S.; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K.; Tullius, Stefan G.; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

    2010-01-01

    Background and objectives: Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. Design, setting, participants, & measurements: This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. Results: A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. Conclusions: This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation. PMID:20507960

  18. Modulation of BK channel voltage gating by different auxiliary β subunits

    PubMed Central

    Contreras, Gustavo F.; Neely, Alan; Alvarez, Osvaldo; Gonzalez, Carlos; Latorre, Ramon

    2012-01-01

    Calcium- and voltage-activated potassium channels (BK) are regulated by a multiplicity of signals. The prevailing view is that different BK gating mechanisms converge to determine channel opening and that these gating mechanisms are allosterically coupled. In most instances the pore forming α subunit of BK is associated with one of four alternative β subunits that appear to target specific gating mechanisms to regulate the channel activity. In particular, β1 stabilizes the active configuration of the BK voltage sensor having a large effect on BK Ca2+ sensitivity. To determine the extent to which β subunits regulate the BK voltage sensor, we measured gating currents induced by the pore-forming BK α subunit alone and with the different β subunits expressed in Xenopus oocytes (β1, β2IR, β3b, and β4). We found that β1, β2, and β4 stabilize the BK voltage sensor in the active conformation. β3 has no effect on voltage sensor equilibrium. In addition, β4 decreases the apparent number of charges per voltage sensor. The decrease in the charge associated with the voltage sensor in α β4 channels explains most of their biophysical properties. For channels composed of the α subunit alone, gating charge increases slowly with pulse duration as expected if a significant fraction of this charge develops with a time course comparable to that of K+ current activation. In the presence of β1, β2, and β4 this slow component develops in advance of and much more rapidly than ion current activation, suggesting that BK channel opening proceeds in two steps. PMID:23112204

  19. Biophysics of BK Channel Gating.

    PubMed

    Pantazis, A; Olcese, R

    2016-01-01

    BK channels are universal regulators of cell excitability, given their exceptional unitary conductance selective for K(+), joint activation mechanism by membrane depolarization and intracellular [Ca(2+)] elevation, and broad expression pattern. In this chapter, we discuss the structural basis and operational principles of their activation, or gating, by membrane potential and calcium. We also discuss how the two activation mechanisms interact to culminate in channel opening. As members of the voltage-gated potassium channel superfamily, BK channels are discussed in the context of archetypal family members, in terms of similarities that help us understand their function, but also seminal structural and biophysical differences that confer unique functional properties. © 2016 Elsevier Inc. All rights reserved.

  20. BK channels in innate immune functions of neutrophils and macrophages

    PubMed Central

    Essin, Kirill; Gollasch, Maik; Rolle, Susanne; Weissgerber, Patrick; Sausbier, Matthias; Bohn, Erwin; Autenrieth, Ingo B.; Ruth, Peter; Luft, Friedrich C.; Kettritz, Ralph

    2009-01-01

    Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK−/−) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-α secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK−/− and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-κB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-α release and signal transduction BMDMs. PMID:19074007

  1. BK viruria and viremia in children with systemic lupus erythematosus.

    PubMed

    Gupta, Nirupama; Nguyen, Cuong Q; Modica, Renee F; Elder, Melissa E; Garin, Eduardo H

    2017-04-11

    BK virus (BKV) is a ubiquitous polyoma virus that lies dormant in the genitourinary tract once acquired in early childhood. In states of cellular immunodeficiency, the virus can reactivate to cause hemorrhagic cystitis and nephritis. Children with systemic lupus erythematosus (SLE) have an increased risk of developing infectious complications secondary to their immunocompromised state from the administration of several immuno-modulatory drugs. Currently, there are no data regarding the prevalence of BK viruria or viremia in children with SLE. We conducted a prospective cohort study involving children with SLE of 18 years and younger. We obtained urine and blood samples at baseline and every 3 months up to 1 year for BK virus detection by real-time, quantitative polymerase chain reaction analysis. A comprehensive review of demographic information, clinical characteristics and medication history was also obtained. Thirty-two pediatric patients (26 females and 6 males) with SLE were enrolled. Median age at the time of SLE diagnosis and enrollment into study was 13.6 years and 16.0 years old, respectively. The prevalence at enrollment was 3.1% (1/32) for BK viruria and 6.2% (2/32) for BK viremia. During the study period, 3 patients had viruria, 5 had viremia and 4 had both viruria and viremia. Of the 12 patients with BKV reactivation, only one was positive for microscopic hematuria, all others were asymptomatic. A total of nine of 97(9.2%) urine samples and 10 of 96(10.4%) blood samples were positive for BK virus. The most commonly utilized biologics in this cohort group were Rituximab (90.6%), Abatacept (12.5%), and Belimumab (9.3%). The type of medication exposure and clinical characteristics did not statistically differ between the groups that did or did not have BK viruria and/or viremia. Our study suggests that pediatric patients with SLE have BK viremia and/or viruria at a higher rate than the general healthy population, although the significance of the

  2. A BK (Slo1) channel journey from molecule to physiology

    PubMed Central

    Contreras, Gustavo F; Castillo, Karen; Enrique, Nicolás; Carrasquel-Ursulaez, Willy; Castillo, Juan Pablo; Milesi, Verónica; Neely, Alan; Alvarez, Osvaldo; Ferreira, Gonzalo; González, Carlos; Latorre, Ramón

    2013-01-01

    Calcium and voltage-activated potassium (BK) channels are key actors in cell physiology, both in neuronal and non-neuronal cells and tissues. Through negative feedback between intracellular Ca2+ and membrane voltage, BK channels provide a damping mechanism for excitatory signals. Molecular modulation of these channels by alternative splicing, auxiliary subunits and post-translational modifications showed that these channels are subjected to many mechanisms that add diversity to the BK channel α subunit gene. This complexity of interactions modulates BK channel gating, modifying the energetic barrier of voltage sensor domain activation and channel opening. Regions for voltage as well as Ca2+ sensitivity have been identified, and the crystal structure generated by the 2 RCK domains contained in the C-terminal of the channel has been described. The linkage of these channels to many intracellular metabolites and pathways, as well as their modulation by extracellular natural agents, has been found to be relevant in many physiological processes. This review includes the hallmarks of BK channel biophysics and its physiological impact on specific cells and tissues, highlighting its relationship with auxiliary subunit expression. PMID:24025517

  3. Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations.

    PubMed

    Lee, Yeon Joo; Zheng, Junting; Kolitsopoulos, Yovanna; Chung, Dick; Amigues, Isabelle; Son, Tammy; Choo, Kathleen; Hester, Jeff; Giralt, Sergio A; Glezerman, Ilya G; Jakubowski, Ann A; Papanicolaou, Genovefa A

    2014-08-01

    Hematopoietic stem cell transplant (HSCT) recipients are at significant risk for BK virus (BKV) reactivation, hemorrhagic cystitis (HC), and renal dysfunction. We prospectively monitored 98 patients who had received HSCT by serial BKV PCR in the urine through day (D) +100 to analyze the relationship between BK viruria and HC, serum creatinine (Cr), and creatinine clearance (CrCl) through D +180 or death. Patients, median age 52 years (range, 20 to 73), received T cell-depleted (50%) or cord blood allografts (21%). Median pre-HSCT BKV IgG titers were 1:10,240. Incremental increase in BKV IgG titers correlated with developing BK viruria ≥ 10(7) copies/mL. By D +100, 53 (54%) patients had BK viruria. BKV load in the urine increased at engraftment and persisted throughout D +100. HC developed in 10 patients (10%); 7 of 10 with BK viruria. In competing risk analyses, BK viruria ≥ 10(7) copies/mL, older age, cytomegalovirus reactivation, and foscarnet use were risk factors for HC. Cr and CrCl at 2, 3, and 6 months after HSCT were similar between patients with and without BK viruria. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation.

    PubMed

    Leung, A Y; Suen, C K; Lie, A K; Liang, R H; Yuen, K Y; Kwong, Y L

    2001-09-15

    Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 x 10(12) versus 5.7 x 10(7) genome copies/d, P <.001) and larger total amounts of BKV excreted during BMT (4.9 x 10(13) versus 7.7 x 10(8) genome copies, P <.001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT.

  5. A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping

    PubMed Central

    Morel, Virginie; Martin, Elodie; François, Catherine; Helle, François; Faucher, Justine; Mourez, Thomas; Choukroun, Gabriel; Duverlie, Gilles; Castelain, Sandrine

    2017-01-01

    ABSTRACT BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases. PMID:28151406

  6. The human polyomavirus BK: Potential role in cancer.

    PubMed

    Fioriti, D; Videtta, M; Mischitelli, M; Degener, A M; Russo, G; Giordano, A; Pietropaolo, V

    2005-08-01

    In human cancer, a role has been suggested for the human polyomavirus BK, primarily associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients, and with hemorrhagic cystitis in bone marrow transplant (BMT) recipients. After the initial infection, primarily unapparent and without clinical signs, the virus disseminates and establishes a persistent infection in the urinary tract and lymphocytes. There is correlative evidence regarding potential role of polyomavirus BK in cancer. In fact, the BK virus (BKV) DNA (complete genome and/or subgenomic fragments containing the early region) is able to transform embryonic fibroblasts and cells cultured from kidney and brain of hamster, mouse, rat, rabbit, and monkey. Nevertheless, transformation of human cells by BKV is inefficient and often abortive. Evidence supporting a possible role for BKV in human cancer has accumulated slowly in recent years, after the advent of polymerase chain reaction (PCR). BKV is known to commonly establish persistent infections in people and to be excreted in the urine by individuals who are asymptomatic, complicating the evaluation of its potential role in development of human cancer. Therefore, there is no certain proof that human polyomavirus BK directly causes the cancer in humans or acts as a cofactor in the pathogenesis of some types of human cancer. (c) 2005 Wiley-Liss, Inc.

  7. BK Viremia Precedes Hemorrhagic Cystitis in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Laskin, Benjamin L.; Denburg, Michelle; Furth, Susan; Diorio, Donna; Goebel, Jens; Davies, Stella M.; Jodele, Sonata

    2013-01-01

    BK virus is associated with hemorrhagic cystitis after hematopoietic stem cell transplantation (HSCT), although evidence supporting a causal relationship remains limited. Although BK viruria is common after HSCT, BK viremia may better predict clinically significant cystitis, similar to its predictive value for nephropathy after kidney transplantation. We hypothesized that BK viremia would precede hemorrhagic cystitis in a cohort of 88 consecutive children prospectively enrolled to originally study thrombotic microangiopathy in the first 100 days after allogeneic HSCT. Cox regression models with time-varying covariates assessed the association between different BK viremia cutoffs and the development of hemorrhagic cystitis, defined as at least macroscopic hematuria. Subjects with a peak plasma BK viral load 1 to 9999 copies/mL had an adjusted hazard ratio of 4.2 (95% confidence interval (CI), 1.3 to 13.7) for the development of hemorrhagic cystitis. Those with peak BK viremia >100,000 copies/mL had an adjusted hazard ratio of 116.8 (95% CI, 12 to 1136) for cystitis. Other independent risk factors for hemorrhagic cystitis included age >7 years and HHV-6 viremia. Neither graft-versus-host disease nor achieving engraftment increased the risk for cystitis. If therapeutic strategies are found to be effective, these observations may support screening for BK viremia after HSCT, as currently recommended for other DNA viruses. PMID:23665115

  8. Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock

    PubMed Central

    McNally, Beth A.

    2018-01-01

    Large conductance K+ (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca2+ (Ca2+i). To enable this regulation, BK channels functionally couple to both voltage-gated Ca2+ channels (VGCCs) and channels mediating Ca2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)—the brain’s circadian clock—BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca2+i are reduced. Here, to determine whether diurnal regulation of Ca2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca2+ channels (LTCCs) are the primary daytime Ca2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)–mediated Ca2+i release. The N- and P/Q-type Ca2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. PMID:29237755

  9. Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock.

    PubMed

    Whitt, Joshua P; McNally, Beth A; Meredith, Andrea L

    2018-02-05

    Large conductance K + (BK) channels are expressed widely in neurons, where their activation is regulated by membrane depolarization and intracellular Ca 2+ (Ca 2+ i ). To enable this regulation, BK channels functionally couple to both voltage-gated Ca 2+ channels (VGCCs) and channels mediating Ca 2+ release from intracellular stores. However, the relationship between BK channels and their specific Ca 2+ source for particular patterns of excitability is not well understood. In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca 2+ i are diurnally regulated, but paradoxically, BK current is greatest at night when VGCC current and Ca 2+ i are reduced. Here, to determine whether diurnal regulation of Ca 2+ is relevant for BK channel activation, we combine pharmacology with day and night patch-clamp recordings in acute slices of SCN. We find that activation of BK current depends primarily on three types of channels but that the relative contribution changes between day and night. BK current can be abrogated with nimodipine during the day but not at night, establishing that L-type Ca 2+ channels (LTCCs) are the primary daytime Ca 2+ source for BK activation. In contrast, dantrolene causes a significant decrease in BK current at night, suggesting that nighttime BK activation is driven by ryanodine receptor (RyR)-mediated Ca 2+ i release. The N- and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC causes a smaller reduction of BK current that does not differ between day and night. Finally, inhibition of LTCCs, but not RyRs, eliminates BK inactivation, but the BK β2 subunit was not required for activation of BK current by LTCCs. These data reveal a dynamic coupling strategy between BK channels and their Ca 2+ sources in the SCN, contributing to diurnal regulation of SCN excitability. © 2018 Whitt et al.

  10. Outcomes of renal transplant recipients with BK virus infection and BK virus surveillance in the Auckland region from 2006 to 2012.

    PubMed

    Hsiao, Chun-Yuan; Pilmore, Helen L; Zhou, Lifeng; de Zoysa, Janak R

    2016-11-06

    To evaluate incidence, risk factors and treatment outcome of BK polyomavirus nephropathy (BKVN) in a cohort of renal transplant recipients in the Auckland region without a formal BK polyomavirus (BKV) surveillance programme. A cohort of 226 patients who received their renal transplants from 2006 to 2012 was retrospectively reviewed. Seventy-six recipients (33.6%) had a BK viral load (BKVL) test and 9 patients (3.9%) developed BKVN. Cold ischaemia time (HR = 1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had graft failure from BKVN. BKVN has a negative impact on graft function [median estimated glomerular filtration rate (eGFR) 22.5 (IQR 18.5-53.0) mL/min per 1.73 m 2 , P = 0.015), but no statistically significant difference ( P = 0.374) in renal allograft function was found among negative BK viraemia group [median eGFR 60.0 (IQR 48.5-74.2) mL/min per 1.73 m 2 ), positive BK viraemia without BKVN group [median eGFR 55.0 (IQR 47.0-76.0) mL/min per 1.73 m 2 ] and unknown BKV status group [median eGFR 54.0 (IQR 43.8-71.0) mL/min per 1.73 m 2 ]. The incidence and treatment outcomes of BKVN were similar to some centres with BKV surveillance programmes. Recipients with BVKN have poorer graft function. Although active surveillance for BKV has been shown to be effective in reducing incidence of BKVN, it should be tailored specifically to that transplant centre based on its epidemiology and outcomes of BKVN, particularly in centres with limited resources.

  11. Antibodies to BK virus in children prior to allogeneic hematopoietic cell transplant

    PubMed Central

    Laskin, Benjamin L; Sullivan, Kathleen E; Hester, Jeff; Goebel, Jens; Davies, Stella M; Jodele, Sonata

    2015-01-01

    BK virus (BKV) is associated with kidney and bladder disease after hematopoietic cell transplantation (HCT) but less is known about the seroprevalence of pre-transplant antibodies to BKV in children. We measured BKV IgG antibody titers in 36 children before HCT. BKV IgG antibodies were detected in all 36 patients, with 28/36 (77.8%) developing BK viremia in the first 100 days. Pre-HCT BKV IgG antibody titers >1:40,960 were protective against later BK viremia ≥10,000 copies/mL. The seroprevalence of antibodies to BKV is high in children undergoing HCT and post-transplant BK viremia, which is associated with bladder and kidney injury, is common. PMID:25833296

  12. Knockout of the BK β2 subunit abolishes inactivation of BK currents in mouse adrenal chromaffin cells and results in slow-wave burst activity

    PubMed Central

    Martinez-Espinosa, Pedro L.; Yang, Chengtao; Gonzalez-Perez, Vivian; Xia, Xiao-Ming

    2014-01-01

    Rat and mouse adrenal medullary chromaffin cells (CCs) express an inactivating BK current. This inactivation is thought to arise from the assembly of up to four β2 auxiliary subunits (encoded by the kcnmb2 gene) with a tetramer of pore-forming Slo1 α subunits. Although the physiological consequences of inactivation remain unclear, differences in depolarization-evoked firing among CCs have been proposed to arise from the ability of β2 subunits to shift the range of BK channel activation. To investigate the role of BK channels containing β2 subunits, we generated mice in which the gene encoding β2 was deleted (β2 knockout [KO]). Comparison of proteins from wild-type (WT) and β2 KO mice allowed unambiguous demonstration of the presence of β2 subunit in various tissues and its coassembly with the Slo1 α subunit. We compared current properties and cell firing properties of WT and β2 KO CCs in slices and found that β2 KO abolished inactivation, slowed action potential (AP) repolarization, and, during constant current injection, decreased AP firing. These results support the idea that the β2-mediated shift of the BK channel activation range affects repetitive firing and AP properties. Unexpectedly, CCs from β2 KO mice show an increased tendency toward spontaneous burst firing, suggesting that the particular properties of BK channels in the absence of β2 subunits may predispose to burst firing. PMID:25267913

  13. Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels.

    PubMed

    Tessitore, Nicola; Lapolla, Annunziata; Aricò, Nadia Concetta; Poli, Albino; Gammaro, Linda; Bassi, Antonella; Bedogna, Valeria; Corgnati, Angela; Reitano, Rachele; Fedele, Domenico; Lupo, Antonio

    2004-01-01

    Advanced glycation end-products (AGEs) are now considered to contribute to the middle molecule toxicity of uremia and, because they are not cleared by conventional low-flux hemodialysis, alternative strategies are needed to improve their removal. In a prospective cross-over trial involving 18 adult chronic hemodialysis subjects, we evaluated the intradialytic removal and the long-term effect on predialysis levels of Protein-bound (PBPe) and Free (FPe) pentosidine by high-pore, protein-leaking BK-F Polymethylmethacrylate-based hemodialysis (BK-F-HD), by comparing it to hemodialysis using low-flux dialyzers (LF-HD). A single BK-F-HD session removed more PBPe, but not FPe, than LF-HD. Long-term BK-F-HD was associated with a significant decrease in pre-dialysis PBPe, FPe, and albumin (17.7 +/- 20.8, 25.3 +/- 17.3 and 8.0 +/- 3.3%, p<0.01) and no change in body mass index and protein catabolic rate, compared to LF-HD. Multiple stepwise regression analysis identified C-reactive Protein (CRP) (standardized beta coefficient=-0.629), pre-dialysis levels in LF-HD (beta=0.452) and dialysis vintage (beta=0.428) as significant determinants of BK-F-induced changes in predialysis PBPe, and predialysis FPe and PBPe levels in LF-HD as significant determinants of BK-F-induced changes in predialysis FPe (beta=0.720 and 0.286, respectively). Our study shows that long-term standard diffusive hemodialysis with BK-F membrane reduces predialysis PBPe and FPe levels by comparison with LF-HD, largely due to a greater intradialytic clearance of PBPe. Serum albumin is also reduced without any associated changes in nutritional status markers. The study also suggests that the effect of BK-F-HD in lowering PBPe levels is modulated by the body burden of pentosidine and is blunted or even lost in the presence of elevated CRP levels.

  14. BK Channels Mediate Synaptic Plasticity Underlying Habituation in Rats.

    PubMed

    Zaman, Tariq; De Oliveira, Cleusa; Smoka, Mahabba; Narla, Chakravarthi; Poulter, Michael O; Schmid, Susanne

    2017-04-26

    Habituation is a basic form of implicit learning and represents a sensory filter that is disrupted in autism, schizophrenia, and several other mental disorders. Despite extensive research in the past decades on habituation of startle and other escape responses, the underlying neural mechanisms are still not fully understood. There is evidence from previous studies indicating that BK channels might play a critical role in habituation. We here used a wide array of approaches to test this hypothesis. We show that BK channel activation and subsequent phosphorylation of these channels are essential for synaptic depression presumably underlying startle habituation in rats, using patch-clamp recordings and voltage-sensitive dye imaging in slices. Furthermore, positive modulation of BK channels in vivo can enhance short-term habituation. Although results using different approaches do not always perfectly align, together they provide convincing evidence for a crucial role of BK channel phosphorylation in synaptic depression underlying short-term habituation of startle. We also show that this mechanism can be targeted to enhance short-term habituation and therefore to potentially ameliorate sensory filtering deficits associated with psychiatric disorders. SIGNIFICANCE STATEMENT Short-term habituation is the most fundamental form of implicit learning. Habituation also represents a filter for inundating sensory information, which is disrupted in autism, schizophrenia, and other psychiatric disorders. Habituation has been studied in different organisms and behavioral models and is thought to be caused by synaptic depression in respective pathways. The underlying molecular mechanisms, however, are poorly understood. We here identify, for the first time, a BK channel-dependent molecular synaptic mechanism leading to synaptic depression that is crucial for habituation, and we discuss the significance of our findings for potential treatments enhancing habituation. Copyright © 2017

  15. The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

    PubMed

    Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

    2015-07-01

    The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Downregulation of BK Channel Function and Protein Expression in Coronary Arteriolar Smooth Muscle Cells of Type 2 Diabetic Patients.

    PubMed

    Lu, Tong; Chai, Qiang; Jiao, Guoqing; Wang, Xiao-Li; Sun, Xiaojing; Furuseth, Jonathan D; Stulak, John M; Daly, Richard C; Greason, Kevin L; Cha, Yong-Mei; Lee, Hon-Chi

    2018-05-30

    Type 2 diabetes (T2D) is strongly associated with cardiovascular morbidity and mortality in patients. Vascular large conductance Ca2+-activated potassium (BK) channels, composed of four pore-forming α subunits (BK-α) and four regulatory β1 subunits (BK-β1), are densely expressed in coronary arterial smooth muscle cells (SMCs) and play an important role in regulating vascular tone and myocardial perfusion. However, the role of BK channels in coronary microvascular dysfunction of human subjects with diabetes is unclear. In this study, we examined BK channel function and protein expression, and BK channel-mediated vasodilation in freshly isolated coronary arterioles from T2D patients. Atrial tissues were obtained from 25 patients with T2D and 16 matched non-diabetic subjects during cardiopulmonary bypass procedure. Microvessel videomicroscopy and immunoblot analysis were performed in freshly dissected coronary arterioles and inside-out single BK channel currents was recorded in enzymatically isolated coronary arteriolar SMCs. We found that BK channel sensitivity to physiological Ca2+ concentration and voltage was downregulated in the coronary arteriolar SMCs of diabetic patients, compared with non-diabetic controls. BK channel kinetics analysis revealed that there was significant shortening of the mean open time and prolongation of the mean closed time in diabetic patients, resulting in a remarkable reduction of the channel open probability. Functional studies showed that BK channel activation by dehydrosoyasaponin-1 was diminished and that BK channel-mediated vasodilation in response to shear stress was impaired in diabetic coronary arterioles. Immunoblot experiments confirmed that the protein expressions of BK-α and BK-β1 subunits were significantly downregulated, but the ratio of BK-α/BK-β1 was unchanged in the coronary arterioles of T2D patients. Our results demonstrated for the first time that BK channel function and BK channel-mediated vasodilation were

  17. Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in rice.

    PubMed

    Lee, Sais-Beul; Hur, Yeon-Jae; Cho, Jun-Hyeon; Lee, Jong-Hee; Kim, Tae-Heon; Cho, Soo-Min; Song, You-Chun; Seo, Young-Su; Lee, Jungkwan; Kim, Tae-Sung; Park, Yong-Jin; Oh, Myung-Kyu; Park, Dong-Soo

    2018-01-10

    Bakanae or foot rot disease is a prominent disease of rice caused by Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence stage to the mature stage. In recent years, raising rice seedlings in seed boxes for mechanical transplanting has increased the incidence of many seedling diseases; only a few rice varieties have been reported to exhibit resistance to bakanae disease. In this study, we attempted to identify quantitative trait loci (QTLs) conferring bakanae disease resistance from the highly resistant japonica variety Wonseadaesoo. A primary QTL study using the genotypes/phenotypes of the recombinant inbred lines (RILs) indicated that the locus qBK1 WD conferring resistance to bakanae disease from Wonseadaesoo was located in a 1.59 Mb interval delimited on the physical map between chr01_13542347 (13.54 Mb) and chr01_15132528 (15.13 Mb). The log of odds (LOD) score of qBK1 WD was 8.29, accounting for 20.2% of the total phenotypic variation. We further identified a gene pyramiding effect of two QTLs, qBK WD and previously developed qBK1. The mean proportion of healthy plant for 31 F 4 RILs that had no resistance genes was 35.3%, which was similar to that of the susceptible check variety Ilpum. The proportion of healthy plants for the lines with only qBK WD or qBK1 was 66.1% and 55.5%, respectively, which was significantly higher than that of the lines without resistance genes and that of Ilpum. The mean proportion of the healthy plant for 15 F 4 RILs harboring both qBK WD and qBK1 was 80.2%, which was significantly higher than that of the lines with only qBK WD or qBK1. Introducing qBK WD or pyramiding the QTLs qBK WD and qBK1 could provide effective tools for breeding rice with bakanae disease resistance. To our knowledge, this is the first report on a gene pyramiding effect that provides higher resistance against bakanae disease.

  18. Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy

    PubMed Central

    Ge, Lisheng; Hoa, Neil T.; Wilson, Zechariah; Arismendi-Morillo, Gabriel; Kong, Xia-Tang; Tajhya, Rajeev B.; Beeton, Christine; Jadus, Martin R.

    2017-01-01

    The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, Stretch-activated potassium channels, KCa1.1). Each name reflects a different physical property displayed by this single ion channel. This transmembrane channel is found on nearly every cell type of the body and has its own distinctive roles for that tissue type. The BKα channel contains the pore that releases potassium ions from intracellular stores. This ion channel is found on the cell membrane, endoplasmic reticulum, Golgi and mitochondria. Complex splicing pathways produce different isoforms. The BKα channels can be phosphorylated, palmitoylated and myristylated. BK is composed of a homo-tetramer that interacts with β and γ chains. These accessory proteins provide a further modulating effect on the functions of BKα channels. BK channels play important roles in cell division and migration. In this review, we will focus on the biology of BK channels, especially its role, and that it has in the immune response towards cancer. Recent proteomic studies have linked BK channels with various proteins. Some of these interactions offer further insight into the role that BK channels have with cancers, especially with brain tumors. This review shows that BK channels have a complex interplay with intracellular components of cancer cells and still have plenty of secrets to be discovered. PMID:25027630

  19. BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide.

    PubMed

    Cheerva, Alexandra C; Raj, Ashok; Bertolone, Salvatore J; Bertolone, Kathy; Silverman, Craig L

    2007-09-01

    Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.

  20. Nuclear BK Channels Regulate Gene Expression via the Control of Nuclear Calcium Signaling

    PubMed Central

    Li, Boxing; Jie, Wei; Huang, Lianyan; Wei, Peng; Li, Shuji; Luo, Zhengyi; Friedman, Allyson K.; Meredith, Andrea L.; Han, Ming-Hu; Zhu, Xin-Hong; Gao, Tian-Ming

    2014-01-01

    Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca2+ is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca2+ release, nucleoplasmic Ca2+ elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca2+-sensitive gene expression and promotes dendritic arborization in a nuclear Ca2+-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca2+ to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level. PMID:24952642

  1. Management of BK virus nephropathy in kidney transplant recipients at the Royal Hospital - Clinical Audit - Oman.

    PubMed

    Al-Raisi, Fatma; Mohsin, Nabil; Kamble, Pramod

    2015-04-01

    Nephropathy from BK virus (BKV) infection is a growing challenge in kidney transplant recipients globally. It is the result of contemporary potent immunosuppressives aimed at reducing acute rejection and improving allograft survival. Untreated BK virus infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening for early detection and prevention of symptomatic BK virus nephropathy may improve outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous immunoglobulin have been used. Since the introduction of the new immunosuppressive agents in the transplant regimen at the Royal Hospital, Few cases of BK virus have been detected, and the challenge was to decide upon the best treatment option. The audit was carried out at the Royal Hospital-Oman between January 2010 and December 2012. The nephrology consultant and the clinical pharmacist reviewed all the BK cases and the Royal Hospital. Extensive literature review carried out by the pharmacist to look into the prevalence, prognosis and treatment of BK nephropathy. A treatment protocol was prepared by the clinical pharmacist through guidance of the consultant and was peer reviewed by team of clinical pharmacists and nephrology doctors and approved by the consultant. The audit included 19 patients with positive BK virus ployoma nephropathy. The treatment options were applied stepwise in all the patients with BK virus nephropathy with success rate more than 70%. BK virus nephropathy is emerging at an alarming rate and requires increasing awareness. The uses of current treatment options are still questionable. Our audit confirms that reducing immunosuppression appears to be the criterian standard for the treatment of BK nephropathy.

  2. Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits

    PubMed Central

    Torres, Yolima P.; Granados, Sara T.; Latorre, Ramón

    2014-01-01

    Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca2+ concentration, the large conductance voltage- and Ca2+-activated K+ channel (BK) is unique among the superfamily of K+ channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K+ channels) and a large C terminus composed of two regulators of K+ conductance domains (RCK domains), where the Ca2+-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca2+ sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above. PMID:25346693

  3. Pharmacological consequences of the coexpression of BK channel α and auxiliary β subunits.

    PubMed

    Torres, Yolima P; Granados, Sara T; Latorre, Ramón

    2014-01-01

    Coded by a single gene (Slo1, KCM) and activated by depolarizing potentials and by a rise in intracellular Ca(2+) concentration, the large conductance voltage- and Ca(2+)-activated K(+) channel (BK) is unique among the superfamily of K(+) channels. BK channels are tetramers characterized by a pore-forming α subunit containing seven transmembrane segments (instead of the six found in voltage-dependent K(+) channels) and a large C terminus composed of two regulators of K(+) conductance domains (RCK domains), where the Ca(2+)-binding sites reside. BK channels can be associated with accessory β subunits and, although different BK modulatory mechanisms have been described, greater interest has recently been placed on the role that the β subunits may play in the modulation of BK channel gating due to its physiological importance. Four β subunits have currently been identified (i.e., β1, β2, β3, and β4) and despite the fact that they all share the same topology, it has been shown that every β subunit has a specific tissue distribution and that they modify channel kinetics as well as their pharmacological properties and the apparent Ca(2+) sensitivity of the α subunit in different ways. Additionally, different studies have shown that natural, endogenous, and synthetic compounds can modulate BK channels through β subunits. Considering the importance of these channels in different pathological conditions, such as hypertension and neurological disorders, this review focuses on the mechanisms by which these compounds modulate the biophysical properties of BK channels through the regulation of β subunits, as well as their potential therapeutic uses for diseases such as those mentioned above.

  4. BK channel β1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization.

    PubMed

    Semenov, Iurii; Wang, Bin; Herlihy, Jeremiah T; Brenner, Robert

    2011-04-01

    The large conductance calcium- and voltage-activated potassium channel (BK channel) and its smooth muscle-specific β1 subunit regulate excitation–contraction coupling in many types of smooth muscle cells. However, the relative contribution of BK channels to control of M2- or M3-muscarinic acetylcholine receptor mediated airway smooth muscle contraction is poorly understood. Previously, we showed that knockout of the BK channel β1 subunit enhances cholinergic-evoked trachea contractions. Here, we demonstrate that the enhanced contraction of the BK β1 knockout can be ascribed to a defect in BK channel opposition of M2 receptor-mediated contractions. Indeed, the enhanced contraction of β1 knockout is eliminated by specific M2 receptor antagonism. The role of BK β1 to oppose M2 signalling is evidenced by a greater than fourfold increase in the contribution of L-type voltage-dependent calcium channels to contraction that otherwise does not occur with M2 antagonist or with β1 containing BK channels. The mechanism through which BK channels oppose M2-mediated recruitment of calcium channels is through a negative shift in resting voltage that offsets, rather than directly opposes, M2-mediated depolarization. The negative shift in resting voltage is reduced to similar extents by BK β1 knockout or by paxilline block of BK channels. Normalization of β1 knockout baseline voltage with low external potassium eliminated the enhanced M2-receptor mediated contraction. In summary, these findings indicate that an important function of BK/β1 channels is to oppose cholinergic M2 receptor-mediated depolarization and activation of calcium channels by restricting excitation–contraction coupling to more negative voltage ranges.

  5. Genotyping of polyomavirus BK by Real Time PCR for VP1 gene.

    PubMed

    Gambarino, Stefano; Costa, Cristina; Astegiano, Sara; Piasentin, Elsa Alessio; Segoloni, Giuseppe P; Cavallo, Rossana; Bergallo, Massimiliano

    2011-10-01

    Polyomavirus BK latently persist in different sites, including the renourinary tract, and may reactivate causing nephropathy in renal transplant recipients or hemorrhagic cystitis in bone marrow recipients. Based on the sequence of the VP1 gene, four genotypes have been described, corresponding to the four serologically differentiated subtypes I-IV, with different prevalence and geographic distribution. In this study, the development and clinical validation of four different Real-Time PCR assays for the detection and discrimination of BKV genotypes as a substitute of DNA sequencing are described. 379 BK VP1 sequences, belonging to the main four genotypes, were aligned and "hot spots" of mutation specific for all the strains or isolates were identified. Specific primers and probes for the detection and discrimination of each genotype by four Real-Time PCR assays were designed and technically validated. Subsequently, the four Real-Time PCR assays were used to test 20 BK-positive urine specimens from renal transplant patients, and evidenced a prevalence of BK genotype I, as previously reported in Europe. Results were confirmed by sequencing. The availability of a rapid and simple genotyping method could be useful for the evaluation of BK genotypes prevalence and studies on the impact of the infecting genotype on viral biological behavior, pathogenic role, and immune evasion strategies.

  6. Cadmium-cysteine coordination in the BK inner pore region and its structural and functional implications.

    PubMed

    Zhou, Yu; Xia, Xiao-Ming; Lingle, Christopher J

    2015-04-21

    To probe structure and gating-associated conformational changes in BK-type potassium (BK) channels, we examined consequences of Cd(2+) coordination with cysteines introduced at two positions in the BK inner pore. At V319C, the equivalent of valine in the conserved Kv proline-valine-proline (PVP) motif, Cd(2+) forms intrasubunit coordination with a native glutamate E321, which would place the side chains of V319C and E321 much closer together than observed in voltage-dependent K(+) (Kv) channel structures, requiring that the proline between V319C and E321 introduces a kink in the BK S6 inner helix sharper than that observed in Kv channel structures. At inner pore position A316C, Cd(2+) binds with modest state dependence, suggesting the absence of an ion permeation gate at the cytosolic side of BK channel. These results highlight fundamental structural differences between BK and Kv channels in their inner pore region, which likely underlie differences in voltage-dependent gating between these channels.

  7. BK channel β1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization

    PubMed Central

    Semenov, Iurii; Wang, Bin; Herlihy, Jeremiah T; Brenner, Robert

    2011-01-01

    Abstract The large conductance calcium- and voltage-activated potassium channel (BK channel) and its smooth muscle-specific β1 subunit regulate excitation–contraction coupling in many types of smooth muscle cells. However, the relative contribution of BK channels to control of M2- or M3-muscarinic acetylcholine receptor mediated airway smooth muscle contraction is poorly understood. Previously, we showed that knockout of the BK channel β1 subunit enhances cholinergic-evoked trachea contractions. Here, we demonstrate that the enhanced contraction of the BK β1 knockout can be ascribed to a defect in BK channel opposition of M2 receptor-mediated contractions. Indeed, the enhanced contraction of β1 knockout is eliminated by specific M2 receptor antagonism. The role of BK β1 to oppose M2 signalling is evidenced by a greater than fourfold increase in the contribution of L-type voltage-dependent calcium channels to contraction that otherwise does not occur with M2 antagonist or with β1 containing BK channels. The mechanism through which BK channels oppose M2-mediated recruitment of calcium channels is through a negative shift in resting voltage that offsets, rather than directly opposes, M2-mediated depolarization. The negative shift in resting voltage is reduced to similar extents by BK β1 knockout or by paxilline block of BK channels. Normalization of β1 knockout baseline voltage with low external potassium eliminated the enhanced M2-receptor mediated contraction. In summary, these findings indicate that an important function of BK/β1 channels is to oppose cholinergic M2 receptor-mediated depolarization and activation of calcium channels by restricting excitation–contraction coupling to more negative voltage ranges. PMID:21300746

  8. Review article: BK virus in systemic lupus erythematosus.

    PubMed

    Gupta, Nirupama; Lawrence, Robert M; Nguyen, Cuong; Modica, Renee F

    2015-08-21

    BK virus (BKV) is a human polyomavirus with a seroprevalence of 60-80 % in the general population. In renal transplant patients, it is known to cause renal failure, ureteric stenosis and hemorrhagic cystitis. In bone marrow transplant patients, it is evident that BKV can also cause hemorrhagic cystitis along with BK virus nephropathy (BKVN) in the native kidneys, with subsequent renal failure. However, little is known about BVKN in non-transplanted immune-compromised patients, such as systemic lupus erythematosus (SLE) who may have underlying nephritis and have a compromised immune system due to therapy and/or systemic illness. Thus, this article will focus on the clinical aspects of BKV and its association in patients with SLE.

  9. BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies.

    PubMed

    Ambalathingal, George R; Francis, Ross S; Smyth, Mark J; Smith, Corey; Khanna, Rajiv

    2017-04-01

    BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications. Copyright © 2017 American Society for Microbiology.

  10. Effect of aldosterone on BK channel expression in mammalian cortical collecting duct

    PubMed Central

    Estilo, Genevieve; Liu, Wen; Pastor-Soler, Nuria; Mitchell, Phillip; Carattino, Marcelo D.; Kleyman, Thomas R.; Satlin, Lisa M.

    2008-01-01

    Apical large-conductance Ca2+-activated K+ (BK) channels in the cortical collecting duct (CCD) mediate flow-stimulated K+ secretion. Dietary K+ loading for 10–14 days leads to an increase in BK channel mRNA abundance, enhanced flow-stimulated K+ secretion in microperfused CCDs, and a redistribution of immunodetectable channels from an intracellular pool to the apical membrane (Najjar F, Zhou H, Morimoto T, Bruns JB, Li HS, Liu W, Kleyman TR, Satlin LM. Am J Physiol Renal Physiol 289: F922–F932, 2005). To test whether this adaptation was mediated by a K+-induced increase in aldosterone, New Zealand White rabbits were fed a low-Na+ (LS) or high-Na+ (HS) diet for 7–10 days to alter circulating levels of aldosterone but not serum K+ concentration. Single CCDs were isolated for quantitation of BK channel subunit (total, α-splice variants, β-isoforms) mRNA abundance by real-time PCR and measurement of net transepithelial Na+ (JNa) and K+ (JK) transport by microperfusion; kidneys were processed for immunolocalization of BK α-subunit by immunofluorescence microscopy. At the time of death, LS rabbits excreted no urinary Na+ and had higher circulating levels of aldosterone than HS animals. The relative abundance of BK α-, β2-, and β4-subunit mRNA and localization of immunodetectable α-subunit were similar in CCDs from LS and HS animals. In response to an increase in tubular flow rate from ∼1 to 5 nl·min−1·mm−1, the increase in JNa was greater in LS vs. HS rabbits, yet the flow-stimulated increase in JK was similar in both groups. These data suggest that aldosterone does not contribute to the regulation of BK channel expression/activity in response to dietary K+ loading. PMID:18579708

  11. Vertebrate rod photoreceptors express both BK and IK calcium-activated potassium channels, but only BK channels are involved in receptor potential regulation.

    PubMed

    Pelucchi, Bruna; Grimaldi, Annalisa; Moriondo, Andrea

    2008-01-01

    In salamander rods, Ca(2+)-activated K(+) current (I(KCa)) provides an effective "clamp" of the dark membrane potential to its normal resting level. By a combination of electrophysiological, pharmacological, and immunohistochemical approaches, we show that salamander rods functionally express large-conductance Ca(2+)- and voltage-dependent potassium (BK) channel and intermediate-conductance Ca(2+)-dependent potassium (IK) channel, but not small-conductance Ca(2+)-dependent potassium channel (SK) subtypes. Application of 100 nM iberiotoxin and 100 nM clotrimazole reduced net I(KCa) to 36% and 63%, respectively, whereas the current was unaffected by application of 1 microM apamin. Consistently, anti- SK1, -SK2, and -SK3 antibodies were unable to stain rod photoreceptors, whereas both anti-BK and -SK4/ IK1 antibodies heavily stained the ellipsoid region of the inner segments of the rods. Moreover, by using current-clamp experiments, it was clearly seen that the strong clamping effect of the total I(KCa) was lost when IbTx, but not CLTZ, was applied to the bath. This behavior strongly suggests that of BK and IK channels, only the former are responsible for the clamping effect on the photoreceptor membrane potential.

  12. Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial

    PubMed Central

    Lee, Belinda T.; Gabardi, Steven; Grafals, Monica; Hofmann, R. Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A.; Adey, Deborah B.; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine

    2014-01-01

    Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression. PMID:24482066

  13. Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial.

    PubMed

    Lee, Belinda T; Gabardi, Steven; Grafals, Monica; Hofmann, R Michael; Akalin, Enver; Aljanabi, Aws; Mandelbrot, Didier A; Adey, Deborah B; Heher, Eliot; Fan, Pang-Yen; Conte, Sarah; Dyer-Ward, Christine; Chandraker, Anil

    2014-03-01

    BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively (P=0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P=0.47) and 6 months (82.1% versus 90.5%; P=0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

  14. Long-term hypoxia increases calcium affinity of BK channels in ovine fetal and adult cerebral artery smooth muscle

    PubMed Central

    Tao, Xiaoxiao; Lin, Mike T.; Thorington, Glyne U.; Wilson, Sean M.; Longo, Lawrence D.

    2015-01-01

    Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K+ channel activity. We hypothesized that to maintain oxygenation during LTH, basilar arteries (BA) in the ovine adult and near-term fetus would show increased large-conductance Ca2+ activated potassium (BK) channel activity. We measured BK channel activity, expression, and cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, and confocal microscopy, respectively, in myocytes from normoxic control and LTH adult and near-term fetus BA. Electrophysiological data showed that BK channels in LTH myocytes exhibited 1) lowered Ca2+ set points, 2) left-shifted activation voltages, and 3) longer dwell times. BK channels in LTH myocytes also appeared to be more dephosphorylated. These differences collectively make LTH BK channels more sensitive to activation. Studies using flow cytometry showed that the LTH fetus exhibited increased BK β1 subunit surface expression. In addition, in both fetal groups confocal microscopy revealed increased BK channel clustering and colocalization to myocyte lipid rafts. We conclude that increased BK channel activity in LTH BA occurred in association with increased channel affinity for Ca2+ and left-shifted voltage activation. Increased cerebrovascular BK channel activity may be a mechanism by which LTH adult and near-term fetal sheep can acclimatize to long-term high altitude hypoxia. Our findings suggest that increasing BK channel activity in cerebral myocytes may be a therapeutic target to ameliorate the adverse effects of high altitude in adults or of intrauterine hypoxia in the fetus. PMID:25599571

  15. Low Na, High K Diet and the Role of Aldosterone in BK-Mediated K Excretion

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Li, Huaqing; Yuan, Yang; Wang-France, Jun; Warner, Paige C.; Sansom, Steven C.

    2015-01-01

    A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular (CV) disease in many societies. Part of the benefit of LNaHK relies on its diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not understood. LNaHK mice exhibit an increase in renal K secretion that is dependent on the large, Ca-activated K channel, (BK-α with accessory BK-β4; BK-α/β4). We hypothesized that aldo causes an osmotic diuresis by increasing BK-α/β4-mediated K secretion in LNaHK mice. We found that the plasma aldo concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham), adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate, transtubular K gradient (TTKG), and BK-α and BK-β4 expressions, were decreased in ADX-LA, but not different in ADX-HA. BK-β4 knockout (β4KO) and WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in sham and ADX-HA, the K clearance and TTKG of β4KO were less than WT. In response to amiloride treatment, the osmolar clearance was increased in WT Con, decreased in WT LNaHK, and unchanged in β4KO LNaHK. These data show that the high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-α/β4-mediated K secretion, which creates an osmotic diuresis that may contribute to a reduction in CV disease. PMID:25607984

  16. Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I.

    PubMed

    Texter, Kelly B; Waymach, Rachel; Kavanagh, Pierce V; O'Brien, John E; Talbot, Brian; Brandt, Simon D; Gardner, Elizabeth A

    2018-01-01

    2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) has recently emerged as a new psychoactive substance (NPS). It is most commonly consumed orally, although there are indications that it might also be ingested by inhalation or 'smoking'. Information about the stability of bk-2C-B when exposed to heat is unavailable and the potential for pyrolytic degradation and formation of unknown substances available for inhalation prompted an investigation using a simulated 'meth pipe' scenario. Twelve products following pyrolysis of bk-2C-B were detected and verified by organic synthesis of the corresponding standards. In addition, 2-amino-1-(4-iodo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-I) was characterized for the first time and subjected to pyrolysis as well. Similar products were formed, which indicated that the replacement of the bromo with the iodo substituent did not affect the pyrolysis pattern under the conditions used. Two additional products were detected in the bk-2C-I pyrolates, namely 1-(2,5-dimethoxyphenyl)-ethanone and 1-iodo-4-ethenyl-5-methoxyphenol. The potential ingestion of pyrolysis products with unknown toxicity adds an element of concern. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Time-resolved resonance Raman spectroscopy of intermediates of bacteriorhodopsin: The bK(590) intermediate.

    PubMed

    Terner, J; Hsieh, C L; Burns, A R; El-Sayed, M A

    1979-07-01

    We have combined microbeam and flow techniques with computer subtraction methods to obtain the resonance Raman spectrum of the short lived batho-intermediate (bK(590)) of bacteriorhodopsin. Comparison of the spectra obtained in (1)H(2)O and (2)H(2)O, as well as the fact that the bK(590) intermediate shows large optical red shifts, suggests that the Schiff base linkage of this intermediate is protonated. The fingerprint region of the spectrum of bK(590), sensitive to the isomeric configuration of the retinal chromophore, does not resemble the corresponding region of the parent bR(570) form. The resonance Raman spectrum of bK(590) as well as the spectra of all of the other main intermediates in the photoreaction cycle of bacteriorhodopsin are discussed and compared with resonance Raman spectra of published model compounds.

  18. A New Splice Variant of Large Conductance Ca2+-activated K+ (BK) Channel α Subunit Alters Human Chondrocyte Function.

    PubMed

    Suzuki, Yoshiaki; Ohya, Susumu; Yamamura, Hisao; Giles, Wayne R; Imaizumi, Yuji

    2016-11-11

    Large conductance Ca 2+ -activated K + (BK) channels play essential roles in both excitable and non-excitable cells. For example, in chondrocytes, agonist-induced Ca 2+ release from intracellular store activates BK channels, and this hyperpolarizes these cells, augments Ca 2+ entry, and forms a positive feed-back mechanism for Ca 2+ signaling and stimulation-secretion coupling. In the present study, functional roles of a newly identified splice variant in the BK channel α subunit (BKαΔe2) were examined in a human chondrocyte cell line, OUMS-27, and in a HEK293 expression system. Although BKαΔe2 lacks exon2, which codes the intracellular S0-S1 linker (Glu-127-Leu-180), significant expression was detected in several tissues from humans and mice. Molecular image analyses revealed that BKαΔe2 channels are not expressed on plasma membrane but can traffic to the plasma membrane after forming hetero-tetramer units with wild-type BKα (BKαWT). Single-channel current analyses demonstrated that BKα hetero-tetramers containing one, two, or three BKαΔe2 subunits are functional. These hetero-tetramers have a smaller single channel conductance and exhibit lower trafficking efficiency than BKαWT homo-tetramers in a stoichiometry-dependent manner. Site-directed mutagenesis of residues in exon2 identified Helix2 and the linker to S1 (Trp-158-Leu-180, particularly Arg-178) as an essential segment for channel function including voltage dependence and trafficking. BKαΔe2 knockdown in OUMS-27 chondrocytes increased BK current density and augmented the responsiveness to histamine assayed as cyclooxygenase-2 gene expression. These findings provide significant new evidence that BKαΔe2 can modulate cellular responses to physiological stimuli in human chondrocyte and contribute under pathophysiological conditions, such as osteoarthritis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Conopeptide Vt3.1 preferentially inhibits BK potassium channels containing β4 subunits via electrostatic interactions.

    PubMed

    Li, Min; Chang, Shan; Yang, Longjin; Shi, Jingyi; McFarland, Kelli; Yang, Xiao; Moller, Alyssa; Wang, Chunguang; Zou, Xiaoqin; Chi, Chengwu; Cui, Jianmin

    2014-02-21

    BK channel β subunits (β1-β4) modulate the function of channels formed by slo1 subunits to produce tissue-specific phenotypes. The molecular mechanism of how the homologous β subunits differentially alter BK channel functions and the role of different BK channel functions in various physiologic processes remain unclear. By studying channels expressed in Xenopus laevis oocytes, we show a novel disulfide-cross-linked dimer conopeptide, Vt3.1 that preferentially inhibits BK channels containing the β4 subunit, which is most abundantly expressed in brain and important for neuronal functions. Vt3.1 inhibits the currents by a maximum of 71%, shifts the G-V relation by 45 mV approximately half-saturation concentrations, and alters both open and closed time of single channel activities, indicating that the toxin alters voltage dependence of the channel. Vt3.1 contains basic residues and inhibits voltage-dependent activation by electrostatic interactions with acidic residues in the extracellular loops of the slo1 and β4 subunits. These results suggest a large interaction surface between the slo1 subunit of BK channels and the β4 subunit, providing structural insight into the molecular interactions between slo1 and β4 subunits. The results also suggest that Vt3.1 is an excellent tool for studying β subunit modulation of BK channels and for understanding the physiological roles of BK channels in neurophysiology.

  20. Molecular mechanism underlying β1 regulation in voltage- and calcium-activated potassium (BK) channels

    PubMed Central

    Castillo, Karen; Contreras, Gustavo F.; Pupo, Amaury; Torres, Yolima P.; Neely, Alan; González, Carlos; Latorre, Ramon

    2015-01-01

    Being activated by depolarizing voltages and increases in cytoplasmic Ca2+, voltage- and calcium-activated potassium (BK) channels and their modulatory β-subunits are able to dampen or stop excitatory stimuli in a wide range of cellular types, including both neuronal and nonneuronal tissues. Minimal alterations in BK channel function may contribute to the pathophysiology of several diseases, including hypertension, asthma, cancer, epilepsy, and diabetes. Several gating processes, allosterically coupled to each other, control BK channel activity and are potential targets for regulation by auxiliary β-subunits that are expressed together with the α (BK)-subunit in almost every tissue type where they are found. By measuring gating currents in BK channels coexpressed with chimeras between β1 and β3 or β2 auxiliary subunits, we were able to identify that the cytoplasmic regions of β1 are responsible for the modulation of the voltage sensors. In addition, we narrowed down the structural determinants to the N terminus of β1, which contains two lysine residues (i.e., K3 and K4), which upon substitution virtually abolished the effects of β1 on charge movement. The mechanism by which K3 and K4 stabilize the voltage sensor is not electrostatic but specific, and the α (BK)-residues involved remain to be identified. This is the first report, to our knowledge, where the regulatory effects of the β1-subunit have been clearly assigned to a particular segment, with two pivotal amino acids being responsible for this modulation. PMID:25825713

  1. BK channels are required for multisensory plasticity in the oculomotor system

    PubMed Central

    Nelson, Alexandra; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-01

    SUMMARY Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually-evoked eye movements rapidly restore oculomotor function in wildtype mice but are profoundly impaired in BK channel null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. PMID:27989457

  2. [The BK virus load in urine in association with the development of hemorrhagic cystitis after hematopoietic stem cell transplantation].

    PubMed

    Xie, Ying; Han, Yue; Wu, De-pei; Sun, Ai-ning; Cen, Jian-nong; Yao, Li; Ruan, Chang-geng

    2009-08-01

    To analyze the relationship between BK viruria and the late onset hemorrhagic cystitis (LOHC) after hematopoietic stem cell transplantation (HSCT), and investigate the role of BK virus load in the development of LOHC. From August 2006 to April 2008, urine samples were collected weekly from 113 patients undergoing HSCT. Virus DNA were extracted from the urine samples and amplified by qualitative PCR. Real-time quantitative PCR was used to quantify BKV DNA in the urine samples of all BK viruria patients. LOHC occurred in 22 patients (19.5%), including grade 1 in 7, grade 2 in 11, grade 3 in 3, and grade 4 in one. The median onset time was 44 (13 - 114) days after transplantation. Twenty-one of which (95.5%) were BK virus positive, being significantly higher than that in non-LOHC patients (31.9%) (P = 0.000). No BK virus was detected in the healthy control group at the same time. Quantitative PCR detection showed that the mean BK virus DNA copies in LOHC patients at a week before occurring HC was higher than that at the first positive samples (10(5) copies/microl versus 10(4) copies/microl, P = 0.025), and it was no significant change at the onset and a week after HC. Meanwhile, there was no statistical difference in the mean level of BK virus DNA copies among the LOHC patients with different grades. The mean level of BK virus DNA copies in non-HC patients was 10(3) to 10(4) copies/microl, being lower than that in LOHC patients. BK viruria is an important pathogenic cause of the LOHC after HSCT. The occurrence of BKV viruria in HSCT patients, together with the increasing of BK virus DNA copies in urine, over the level of 10(5) copies/microl may indicate a possible development of LOHC.

  3. Heme Regulates Allosteric Activation of the Slo1 BK Channel

    PubMed Central

    Horrigan, Frank T.; Heinemann, Stefan H.; Hoshi, Toshinori

    2005-01-01

    Large conductance calcium-dependent (Slo1 BK) channels are allosterically activated by membrane depolarization and divalent cations, and possess a rich modulatory repertoire. Recently, intracellular heme has been identified as a potent regulator of Slo1 BK channels (Tang, X.D., R. Xu, M.F. Reynolds, M.L. Garcia, S.H. Heinemann, and T. Hoshi. 2003. Nature. 425:531–535). Here we investigated the mechanism of the regulatory action of heme on heterologously expressed Slo1 BK channels by separating the influences of voltage and divalent cations. In the absence of divalent cations, heme generally decreased ionic currents by shifting the channel's G–V curve toward more depolarized voltages and by rendering the curve less steep. In contrast, gating currents remained largely unaffected by heme. Simulations suggest that a decrease in the strength of allosteric coupling between the voltage sensor and the activation gate and a concomitant stabilization of the open state account for the essential features of the heme action in the absence of divalent ions. At saturating levels of divalent cations, heme remained similarly effective with its influence on the G–V simulated by weakening the coupling of both Ca2+ binding and voltage sensor activation to channel opening. The results thus show that heme dampens the influence of allosteric activators on the activation gate of the Slo1 BK channel. To account for these effects, we consider the possibility that heme binding alters the structure of the RCK gating ring and thereby disrupts both Ca2+- and voltage-dependent gating as well as intrinsic stability of the open state. PMID:15955873

  4. S-acylation dependent post-translational cross-talk regulates large conductance calcium- and voltage- activated potassium (BK) channels

    PubMed Central

    Shipston, Michael J.

    2014-01-01

    Mechanisms that control surface expression and/or activity of large conductance calcium-activated potassium (BK) channels are important determinants of their (patho)physiological function. Indeed, BK channel dysfunction is associated with major human disorders ranging from epilepsy to hypertension and obesity. S-acylation (S-palmitoylation) represents a major reversible, post-translational modification controlling the properties and function of many proteins including ion channels. Recent evidence reveals that both pore-forming and regulatory subunits of BK channels are S-acylated and control channel trafficking and regulation by AGC-family protein kinases. The pore-forming α-subunit is S-acylated at two distinct sites within the N- and C-terminus, each site being regulated by different palmitoyl acyl transferases (zDHHCs) and acyl thioesterases (APTs). S-acylation of the N-terminus controls channel trafficking and surface expression whereas S-acylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. S-acylation of the regulatory β4-subunit controls ER exit and surface expression of BK channels but does not affect ion channel kinetics at the plasma membrane. Furthermore, a significant number of previously identified BK-channel interacting proteins have been shown, or are predicted to be, S-acylated. Thus, the BK channel multi-molecular signaling complex may be dynamically regulated by this fundamental post-translational modification and thus S-acylation likely represents an important determinant of BK channel physiology in health and disease. PMID:25140154

  5. Bicarbonate promotes BK-α/β4-mediated K excretion in the renal distal nephron

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Hatcher, Lori I.

    2012-01-01

    Ca-activated K channels (BK), which are stimulated by high distal nephron flow, are utilized during high-K conditions to remove excess K. Because BK predominantly reside with BK-β4 in acid/base-transporting intercalated cells (IC), we determined whether BK-β4 knockout mice (β4KO) exhibit deficient K excretion when consuming a high-K alkaline diet (HK-alk) vs. high-K chloride diet (HK-Cl). When wild type (WT) were placed on HK-alk, but not HK-Cl, renal BK-β4 expression increased (Western blot). When WT and β4KO were placed on HK-Cl, plasma K concentration ([K]) was elevated compared with control K diets; however, K excretion was not different between WT and β4KO. When HK-alk was consumed, the plasma [K] was lower and K clearance was greater in WT compared with β4KO. The urine was alkaline in mice on HK-alk; however, urinary pH was not different between WT and β4KO. Immunohistochemical analysis of pendrin and V-ATPase revealed the same increases in β-IC, comparing WT and β4KO on HK-alk. We found an amiloride-sensitive reduction in Na excretion in β4KO, compared with WT, on HK-alk, indicating enhanced Na reabsorption as a compensatory mechanism to secrete K. Treating mice with an alkaline, Na-deficient, high-K diet (LNaHK) to minimize Na reabsorption exaggerated the defective K handling of β4KO. When WT on LNaHK were given NH4Cl in the drinking water, K excretion was reduced to the magnitude of β4KO on LNaHK. These results show that WT, but not β4KO, efficiently excretes K on HK-alk but not on HK-Cl and suggest that BK-α/β4-mediated K secretion is promoted by bicarbonaturia. PMID:22993067

  6. Reactive Oxygen Species Signaling Facilitates FOXO-3a/FBXO-Dependent Vascular BK Channel β1 Subunit Degradation in Diabetic Mice

    PubMed Central

    Lu, Tong; Chai, Qiang; Yu, Ling; d’Uscio, Livius V.; Katusic, Zvonimir S.; He, Tongrong; Lee, Hon-Chi

    2012-01-01

    Activity of the vascular large conductance Ca2+-activated K+ (BK) channel is tightly regulated by its accessory β1 subunit (BK-β1). Downregulation of BK-β1 expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)–dependent F-box–only protein (FBXO) expression. However, the upstream signaling regulating this process is unclear. Overproduction of reactive oxygen species (ROS) is a common finding in diabetic vasculopathy. We hypothesized that ROS signaling cascade facilitates the FOXO-3a/FBXO-mediated BK-β1 degradation and leads to diabetic BK channel dysfunction. Using cellular biology, patch clamp, and videomicroscopy techniques, we found that reduced BK-β1 expression in streptozotocin (STZ)-induced diabetic mouse arteries and in human coronary smooth muscle cells (SMCs) cultured with high glucose was attributable to an increase in protein kinase C (PKC)-β and NADPH oxidase expressions and accompanied by attenuation of Akt phosphorylation and augmentation of atrogin-1 expression. Treatment with ruboxistaurin (a PKCβ inhibitor) or with GW501516 (a peroxisome proliferator–activated receptor δ activator) reduced atrogin-1 expression and restored BK channel-mediated coronary vasodilation in diabetic mice. Our results suggested that oxidative stress inhibited Akt signaling and facilitated the FOXO-3a/FBXO-dependent BK-β1 degradation in diabetic vessels. Suppression of the FOXO-3a/FBXO pathway prevented vascular BK-β1 degradation and protected coronary function in diabetes. PMID:22586590

  7. Evaluating the BK 21 Program. Research Brief

    ERIC Educational Resources Information Center

    Seong, Somi; Popper, Steven W.; Goldman, Charles A.; Evans, David K.; Grammich, Clifford A.

    2008-01-01

    The Brain Korea 21 program (BK21), an effort to improve Korean universities and research, has attracted a great deal of attention in Korea, producing the need to understand how well the program is meeting its goals. RAND developed a logic model for identifying program goals and dynamics, suggested quantitative and qualitative evaluation methods,…

  8. Putative calcium-binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation

    PubMed Central

    Davis, S. J.; Scott, L. L.; Ordemann, G.; Philpo, A.; Cohn, J.; Pierce-Shimomura, J. T.

    2016-01-01

    Alcohol modulates the highly conserved, voltage- and calcium-activated potassium (BK) channel, which contributes to alcohol-mediated behaviors in species from worms to humans. Previous studies have shown that the calcium-sensitive domains, RCK1 and the Ca2+ bowl, are required for ethanol activation of the mammalian BK channel in vitro. In the nematode Caenorhabditis elegans, ethanol activates the BK channel in vivo, and deletion of the worm BK channel, SLO-1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel-dependent behaviors in C. elegans, we generated transgenic worms that express mutated SLO-1 channels predicted to have the RCK1, Ca2+ bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO-1 in vivo as neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO-1 had no effect on intoxication in C. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO-1 channel in vitro with or without these domains. By contrast, in agreement with previous in vitro findings, C. elegans harboring a human BK channel with mutated calcium-sensing domains displayed resistance to intoxication. Thus, for the worm SLO-1 channel, the putative calcium-sensitive domains are critical for basal in vivo function but unnecessary for in vivo ethanol action. PMID:26113050

  9. Intermediate-dose cidofovir without probenecid in the treatment of BK virus allograft nephropathy.

    PubMed

    Araya, Carlos E; Lew, Judy F; Fennell, Robert S; Neiberger, Richard E; Dharnidharka, Vikas R

    2006-02-01

    BK virus allograft nephropathy (BKVAN) is a rising complication in kidney transplant recipients. Reducing immunosuppression has been the initial form of therapy in most cases, but is not always associated with improvement in graft function. Anti-viral therapy with low-dose cidofovir (0.25-0.42 mg/kg/dose) has been used successfully in some patients, but dose-related nephrotoxicity has limited its use. We present our experience with 3 kidney transplant recipients diagnosed with BKVAN who received intermediate-dose cidofovir (0.75-1.0 mg/kg/dose) without probenecid, and without concomitant nephrotoxicity. Three female patients, ages 8, 19 and 20 yr, presented with elevated serum creatinine (SCr) values, BK virus stain positive on renal biopsy and high plasma BK viral loads. As a result of viral loads being >2 million copies/ml in two patients and a lack of response to reduction in immunosuppression in the third, we initiated therapy with low-dose cidofovir. Because of persistent positive BK stain and positive plasma viral load, we then administered intermediate-dose cidofovir, without probenecid, for several subsequent doses (seven to 15 infusions till date). All patients tolerated the intermediate-dose cidofovir with no significant rise in SCr during the course of the infusions. The most recent SCr values in all three patients were improved from those at the initial diagnosis of BKVAN. All three patients showed a marked drop in BK viral loads when on intermediate-dose cidofovir, with complete clearing of viremia in two patients. In our experience, intermediate-dose cidofovir without probenecid, used judiciously, is not associated with additional nephrotoxicity and may provide an additional alternative for treatment.

  10. Alcohol modulation of BK channel gating depends on β subunit composition

    PubMed Central

    Kuntamallappanavar, Guruprasad

    2016-01-01

    In most mammalian tissues, Ca2+i/voltage-gated, large conductance K+ (BK) channels consist of channel-forming slo1 and auxiliary (β1–β4) subunits. When Ca2+i (3–20 µM) reaches the vicinity of BK channels and increases their activity at physiological voltages, β1- and β4-containing BK channels are, respectively, inhibited and potentiated by intoxicating levels of ethanol (50 mM). Previous studies using different slo1s, lipid environments, and Ca2+i concentrations—all determinants of the BK response to ethanol—made it impossible to determine the specific contribution of β subunits to ethanol action on BK activity. Furthermore, these studies measured ethanol action on ionic current under a limited range of stimuli, rendering no information on the gating processes targeted by alcohol and their regulation by βs. Here, we used identical experimental conditions to obtain single-channel and macroscopic currents of the same slo1 channel (“cbv1” from rat cerebral artery myocytes) in the presence and absence of 50 mM ethanol. First, we assessed the role five different β subunits (1,2,2-IR, 3-variant d, and 4) in ethanol action on channel function. Thus, two phenotypes were identified: (1) ethanol potentiated cbv1-, cbv1+β3-, and cbv1+β4-mediated currents at low Ca2+i while inhibiting current at high Ca2+i, the potentiation–inhibition crossover occurring at 20 µM Ca2+i; (2) for cbv1+β1, cbv1+wt β2, and cbv1+β2-IR, this crossover was shifted to ∼3 µM Ca2+i. Second, applying Horrigan–Aldrich gating analysis on both phenotypes, we show that ethanol fails to modify intrinsic gating and the voltage-dependent parameters under examination. For cbv1, however, ethanol (a) drastically increases the channel’s apparent Ca2+ affinity (nine-times decrease in Kd) and (b) very mildly decreases allosteric coupling between Ca2+ binding and channel opening (C). The decreased Kd leads to increased channel activity. For cbv1+β1, ethanol (a) also decreases Kd

  11. TRPV1 Channels Are Functionally Coupled with BK(mSlo1) Channels in Rat Dorsal Root Ganglion (DRG) Neurons

    PubMed Central

    Yan, Zonghe; Kong, Wenjuan; Liu, Beiying; Li, Xia; Yao, Jing; Zhang, Yuexuan; Qin, Feng; Ding, Jiuping

    2013-01-01

    The transient receptor potential vanilloid receptor 1 (TRPV1) channel is a nonselective cation channel activated by a variety of exogenous and endogenous physical and chemical stimuli, such as temperature (≥42 °C), capsaicin, a pungent compound in hot chili peppers, and allyl isothiocyanate. Large-conductance calcium- and voltage-activated potassium (BK) channels regulate the electric activities and neurotransmitter releases in excitable cells, responding to changes in membrane potentials and elevation of cytosolic calcium ions (Ca2+). However, it is unknown whether the TRPV1 channels are coupled with the BK channels. Using patch-clamp recording combined with an infrared laser device, we found that BK channels could be activated at 0 mV by a Ca2+ influx through TRPV1 channels not the intracellular calcium stores in submilliseconds. The local calcium concentration around BK is estimated over 10 μM. The crosstalk could be affected by 10 mM BAPTA, whereas 5 mM EGTA was ineffectual. Fluorescence and co-immunoprecipitation experiments also showed that BK and TRPV1 were able to form a TRPV1-BK complex. Furthermore, we demonstrated that the TRPV1-BK coupling also occurs in dosal root ganglion (DRG) cells, which plays a critical physiological role in regulating the “pain” signal transduction pathway in the peripheral nervous system. PMID:24147119

  12. Co-infection with human polyomavirus BK enhances gene expression and replication of human adenovirus.

    PubMed

    Bil-Lula, Iwona; Woźniak, Mieczysław

    2018-03-26

    Immunocompromised patients are susceptible to multiple viral infections. Relevant interactions between co-infecting viruses might result from viral regulatory genes which trans-activate or repress the expression of host cell genes as well as the genes of any co-infecting virus. The aim of the current study was to show that the replication of human adenovirus 5 is enhanced by co-infection with BK polyomavirus and is associated with increased expression of proteins including early region 4 open reading frame 1 and both the large tumor antigen and small tumor antigen. Clinical samples of whole blood and urine from 156 hematopoietic stem cell transplant recipients were tested. We also inoculated adenocarcinomic human alveolar basal epithelial cells with both human adenovirus 5 and BK polyomavirus to evaluate if co-infection of viruses affected their replication. Data showed that adenovirus load was significantly higher in the plasma (mean 7.5 x 10 3  ± 8.5 x 10 2 copies/ml) and urine (mean 1.9 x 10 3  ± 8.0 x 10 2 copies/ml) of samples from patients with co-infections, in comparison to samples from patients with isolated adenovirus infection. In vitro co-infection led to an increased (8.6 times) expression of the adenovirus early region 4 open reading frame gene 48 hours post-inoculation. The expression of the early region 4 open reading frame gene positively correlated with the expression of BK polyomavirus large tumor antigen (r = 0.90, p < 0.0001) and small tumor antigen (r = 0.83, p < 0.001) genes. The enhanced expression of the early region 4 open reading frame gene due to co-infection with BK polyomavirus was associated with enhanced adenovirus, but not BK polyomavirus, replication. The current study provides evidence that co-infection of adenovirus and BK polyomavirus contributes to enhanced adenovirus replication. Data obtained from this study may have significant importance in the clinical setting.

  13. Use of hybridot assay to screen for BK and JC polyomaviruses in non-immunosuppressed patients.

    PubMed Central

    Cobb, J J; Wickenden, C; Snell, M E; Hulme, B; Malcolm, A D; Coleman, D V

    1987-01-01

    Urine samples from 50 patients attending a genitourinary outpatient clinic and from 13 renal allograft recipients were investigated for evidence of infection with human BK and JC polyomaviruses using cytology and a new DNA hybridot assay. Forty four per cent of samples from the renal allograft recipients were positive by cytology and 75% by DNA hybridisation, indicating that hybridot assay is more sensitive than cytological screening. BK and JC viral DNA was found in 20% of the patients attending the genitourinary clinic, showing infection with BK virus and JC virus in a group of patients with clinical conditions not normally associated with immunological deficiency-a finding that has not been reported before. Images Figure PMID:3040812

  14. Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

    PubMed Central

    Zuidema, Mozow Y.; Yang, Yan; Wang, Meifang; Kalogeris, Theodore; Liu, Yajun; Meininger, Cynthia J.; Hill, Michael A.; Davis, Michael J.

    2010-01-01

    The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BKα subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism. PMID:20833953

  15. The BK(Ca) channels deficiency as a possible reason for radiation-induced vascular hypercontractility.

    PubMed

    Kyrychenko, Sergii; Tishkin, Sergey; Dosenko, Victor; Ivanova, Irina; Novokhatska, Tatiana; Soloviev, Anatoly

    2012-01-01

    It is likely that large-conductance Ca²⁺-activated K⁺ (BK(Ca)) channels channelopathy tightly involved in vascular malfunctions and arterial hypertension development. In the present study, we compared the results of siRNAs-induced α-BK(Ca) gene silencing and vascular abnormalities produced by whole-body ionized irradiation in rats. The experimental design comprised RT-PCR and patch clamp technique, thoracic aorta smooth muscle (SM) contractile recordings and arterial blood pressure (BP) measurements on the 30th day after whole body irradiation (6Gy) and following siRNAs KCNMA1 gene silencing in vivo. The expression profile of BK(Ca) mRNA transcripts in SM was significantly decreased in siRNAs-treated rats in a manner similar to irradiated SM. In contrast, the mRNA levels of K(v) and K(ATP) were significantly increased while L-type calcium channels mRNA transcripts demonstrated tendency to increment. The SMCs obtained from irradiated animals and after KCNMA1 gene silencing showed a significant decrease in total K⁺ current density amplitude. Paxilline (500 nM)-sensitive components of outward current were significantly decreased in both irradiated and gene silencing SMCs. KCNMA1 gene silencing increased SM sensitivity to norepinephrine while Ach-induced relaxation had decreased. The silencing of KCNMA1 had no significant effect on BP while radiation produced sustained arterial hypertension. Therefore, radiation alters the form and function of the BK(Ca) channel and this type of channelopathy may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BK(Ca) can operate as a crucial factor for radiation-induced arterial hypertension. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels

    PubMed Central

    Malysz, John; Afeli, Serge A. Y.; Provence, Aaron

    2013-01-01

    Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca2+-activated K+ (BK) channels or L-type voltage-dependent Ca2+ channels (VDCCs), major regulators of DSM excitability and contractility, are targets for EtOH by patch-clamp electrophysiology (conventional and perforated whole cell and excised patch single channel) and isometric tension recordings using guinea pig DSM cells and isolated tissue strips, respectively. EtOH at 0.3% vol/vol (∼50 mM) enhanced whole cell BK currents at +30 mV and above, determined by the selective BK channel blocker paxilline. In excised patches recorded at +40 mV and ∼300 nM intracellular Ca2+ concentration ([Ca2+]), EtOH (0.1–0.3%) affected single BK channels (mean conductance ∼210 pS and blocked by paxilline) by increasing the open channel probability, number of open channel events, and open dwell-time constants. The amplitude of single BK channel currents and unitary conductance were not altered by EtOH. Conversely, at ∼10 μM but not ∼2 μM intracellular [Ca2+], EtOH (0.3%) decreased the single BK channel activity. EtOH (0.3%) affected transient BK currents (TBKCs) by either increasing frequency or decreasing amplitude, depending on the basal level of TBKC frequency. In isolated DSM strips, EtOH (0.1–1%) reduced the amplitude and muscle force of spontaneous phasic contractions. The EtOH-induced DSM relaxation, except at 1%, was attenuated by paxilline. EtOH (1%) inhibited L-type VDCC currents in DSM cells. In summary, we reveal the involvement of BK channels and L-type VDCCs in mediating EtOH-induced urinary bladder relaxation accommodating alcohol-induced diuresis. PMID:24153429

  17. BK Channels Localize to the Paranodal Junction and Regulate Action Potentials in Myelinated Axons of Cerebellar Purkinje Cells.

    PubMed

    Hirono, Moritoshi; Ogawa, Yasuhiro; Misono, Kaori; Zollinger, Daniel R; Trimmer, James S; Rasband, Matthew N; Misonou, Hiroaki

    2015-05-06

    In myelinated axons, K(+) channels are clustered in distinct membrane domains to regulate action potentials (APs). At nodes of Ranvier, Kv7 channels are expressed with Na(+) channels, whereas Kv1 channels flank nodes at juxtaparanodes. Regulation of axonal APs by K(+) channels would be particularly important in fast-spiking projection neurons such as cerebellar Purkinje cells. Here, we show that BK/Slo1 channels are clustered at the paranodal junctions of myelinated Purkinje cell axons of rat and mouse. The paranodal junction is formed by a set of cell-adhesion molecules, including Caspr, between the node and juxtaparanodes in which it separates nodal from internodal membrane domains. Remarkably, only Purkinje cell axons have detectable paranodal BK channels, whose clustering requires the formation of the paranodal junction via Caspr. Thus, BK channels occupy this unique domain in Purkinje cell axons along with the other K(+) channel complexes at nodes and juxtaparanodes. To investigate the physiological role of novel paranodal BK channels, we examined the effect of BK channel blockers on antidromic AP conduction. We found that local application of blockers to the axon resulted in a significant increase in antidromic AP failure at frequencies above 100 Hz. We also found that Ni(2+) elicited a similar effect on APs, indicating the involvement of Ni(2+)-sensitive Ca(2+) channels. Furthermore, axonal application of BK channel blockers decreased the inhibitory synaptic response in the deep cerebellar nuclei. Thus, paranodal BK channels uniquely support high-fidelity firing of APs in myelinated Purkinje cell axons, thereby underpinning the output of the cerebellar cortex. Copyright © 2015 the authors 0270-6474/15/357082-13$15.00/0.

  18. Intracellular segment between transmembrane helices S0 and S1 of BK channel α subunit contains two amphipathic helices connected by a flexible loop

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shi, Pan; High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui, 230031; Li, Dong

    2013-08-02

    Highlights: •The loop between S0 and S1 of BK channel was overexpressed and purified in DPC. •NMR studies indicated BK-IS1 contained two helices connected by a flexible loop. •Mg{sup 2+} titration of BK-IS1 indicated two possible binding sites of divalent ions. -- Abstract: The BK channel, a tetrameric potassium channel with very high conductance, has a central role in numerous physiological functions. The BK channel can be activated by intracellular Ca{sup 2+} and Mg{sup 2+}, as well as by membrane depolarization. Unlike other tetrameric potassium channels, the BK channel has seven transmembrane helices (S0–S6) including an extra helix S0. Themore » intracellular segment between S0 and S1 (BK-IS1) is essential to BK channel functions and Asp99 in BK-IS1 is reported to be responsible for Mg{sup 2+} coordination. In this study, BK-IS1 (44–113) was over-expressed using a bacterial system and purified in the presence of detergent micelles for multidimensional heteronuclear nuclear magnetic resonance (NMR) structural studies. Backbone resonance assignment and secondary structure analysis showed that BK-IS1 contains two amphipathic helices connected by a 36-residue loop. Amide {sup 1}H–{sup 15}N heteronuclear NOE analysis indicated that the loop is very flexible, while the two amphipathic helices are possibly stabilized through interaction with the membrane. A solution NMR-based titration assay of BK-IS1 was performed with various concentrations of Mg{sup 2+}. Two residues (Thr45 and Leu46) with chemical shift changes were observed but no, or very minor, chemical shift difference was observed for Asp99, indicating a possible site for binding divalent ions or other modulation partners.« less

  19. BK polyomavirus-associated hemorrhagic cystitis among pediatric allogeneic bone marrow transplant recipients: treatment response and evidence for nosocomial transmission.

    PubMed

    Koskenvuo, Minna; Dumoulin, Alexis; Lautenschlager, Irmeli; Auvinen, Eeva; Mannonen, Laura; Anttila, Veli-Jukka; Jahnukainen, Kirsi; Saarinen-Pihkala, Ulla M; Hirsch, Hans H

    2013-01-01

    BK polyomavirus-associated hemorrhagic cystitis (BK-PyVHC) is a significant complication of allogenic hematopoietic stem cell transplantation (HSCT), but risk factors and treatment are currently unresolved. BK-PyVHC typically presents with clinical cystitis, macrohematuria, and increasing urine and blood BKV loads. Characterization of children undergoing allogeneic HSCT with BK-PyVHC and their clinical and antibody response to cidofovir treatment. By prospective screening of urine and plasma in 50 pediatric allogenic HSCT performed between 2008 and 2010, we identified 6 (12%) children with BK-PyVHC. Cidofovir was administered intravenously to 5 patients and intravesically to 4 patients (3 double treatments). Decreasing BKV viremia of>2log(10)copies/mL and clinical resolution was seen in 4 patients over 5-12 weeks. Responses occurred only in patients mounting BKV-specific IgM and IgG responses. Epidemic curve plots, BKV genotyping and contact tracing provided evidence of transmission between 2 BKV-seronegative patients, but ruled out transmission among the remaining four patients The data suggest that BK-PyVHC may be the result of nosocomial transmission in children with low/undetectable BKV antibodies and raises urgent questions about appropriate infection control measures and the role of cidofovir. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. BK/TD models for analyzing in vitro impedance data on cytotoxicity.

    PubMed

    Teng, S; Barcellini-Couget, S; Beaudouin, R; Brochot, C; Desousa, G; Rahmani, R; Pery, A R R

    2015-06-01

    The ban of animal testing has enhanced the development of new in vitro technologies for cosmetics safety assessment. Impedance metrics is one such technology which enables monitoring of cell viability in real time. However, analyzing real time data requires moving from static to dynamic toxicity assessment. In the present study, we built mechanistic biokinetic/toxicodynamic (BK/TD) models to analyze the time course of cell viability in cytotoxicity assay using impedance. These models account for the fate of the tested compounds during the assay. BK/TD models were applied to analyze HepaRG cell viability, after single (48 h) and repeated (4 weeks) exposures to three hepatotoxic compounds (coumarin, isoeugenol and benzophenone-2). The BK/TD models properly fit the data used for their calibration that was obtained for single or repeated exposure. Only for one out of the three compounds, the models calibrated with a single exposure were able to predict repeated exposure data. We therefore recommend the use of long-term exposure in vitro data in order to adequately account for chronic hepatotoxic effects. The models we propose here are capable of being coupled with human biokinetic models in order to relate dose exposure and human hepatotoxicity. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  1. The oncogenic potential of BK-polyomavirus is linked to viral integration into the human genome.

    PubMed

    Kenan, Daniel J; Mieczkowski, Piotr A; Burger-Calderon, Raquel; Singh, Harsharan K; Nickeleit, Volker

    2015-11-01

    It has been suggested that BK-polyomavirus is linked to oncogenesis via high expression levels of large T-antigen in some urothelial neoplasms arising following kidney transplantation. However, a causal association between BK-polyomavirus, large T-antigen expression and oncogenesis has never been demonstrated in humans. Here we describe an investigation using high-throughput sequencing of tumour DNA obtained from an urothelial carcinoma arising in a renal allograft. We show that a novel BK-polyomavirus strain, named CH-1, is integrated into exon 26 of the myosin-binding protein C1 gene (MYBPC1) on chromosome 12 in tumour cells but not in normal renal cells. Integration of the BK-polyomavirus results in a number of discrete alterations in viral gene expression, including: (a) disruption of VP1 protein expression and robust expression of large T-antigen; (b) preclusion of viral replication; and (c) deletions in the non-coding control region (NCCR), with presumed alterations in promoter feedback loops. Viral integration disrupts one MYBPC1 gene copy and likely alters its expression. Circular episomal BK-polyomavirus gene sequences are not found, and the renal allograft shows no productive polyomavirus infection or polyomavirus nephropathy. These findings support the hypothesis that integration of polyomaviruses is essential to tumourigenesis. It is likely that dysregulation of large T-antigen, with persistent over-expression in non-lytic cells, promotes cell growth, genetic instability and neoplastic transformation. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  2. Prediction of Early BK Virus Infection in Kidney Transplant Recipients by the Number of Cells With Intranuclear Inclusion Bodies (Decoy Cells)

    PubMed Central

    Yamada, Yoshiteru; Tsuchiya, Tomohiro; Inagaki, Isao; Seishima, Mitsuru; Deguchi, Takashi

    2018-01-01

    Background BK virus (BKV) is the cause of nephropathy. Because BKV nephropathy can progress to graft loss, early diagnosis of BKV infection is very important. In this study, we aimed to investigate the utility of quantifying cells with intranuclear inclusion bodies (decoy cells) in urinary sediment for the screening and monitoring of BKV infection in renal transplant recipients at our hospital. Methods This was a retrospective single-center study. Urine sediment examination was performed at each outpatient visit, and the number of decoy cells was measured in the whole microscopic field. Patients (n = 41) were divided into the BK viremia group (blood positive for BKV DNA by polymerase chain reaction [PCR]) and non-BK viremia group (blood negative for BKV DNA by PCR), and the decoy cell count in urinary sediments was examined. Results The maximum decoy cell count was significantly higher (P = 0.04) in the BK viremia group than in the non-BK viremia group. In the receiver operating characteristic curve for the maximum decoy cells, the cutoff value was 507 cells. The area under the receiver operating characteristic curve was 0.8774 (95% confidence interval, 0.7739-0.9810). The number of decoy cells at the time of appearance in the BK viremia group was not significantly different from that in the non-BK viremia group. However, the BK viremia group showed an increasing trend, whereas the non-BK viremia group showed a decreasing trend, in the number of decoy cells. There was a positive correlation between the number of decoy cells and the data from the urine BKV-DNA PCR quantification (correlation coefficient [r] = 0.74). Conclusions Measurement of decoy cells in urinary sediments may predict early BKV infection, and if performed quickly, it may be useful for screening and continuous monitoring of BKV infection in renal transplant recipients. PMID:29464201

  3. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    PubMed

    Basara, N; Rasche, F-M; Schwalenberg, T; Wickenhauser, C; Maier, M; Ivovic, J; Niederwieser, D; Lindner, T H

    2010-01-01

    We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor.

  4. The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells

    PubMed Central

    Shao, Li-Rong; Halvorsrud, Ragnhild; Borg-Graham, Lyle; Storm, Johan F

    1999-01-01

    The role of large-conductance Ca2+-dependent K+ channels (BK-channels; also known as maxi-K- or slo-channels) in spike broadening during repetitive firing was studied in CA1 pyramidal cells, using sharp electrode intracellular recordings in rat hippocampal slices, and computer modelling. Trains of action potentials elicited by depolarizing current pulses showed a progressive, frequency-dependent spike broadening, reflecting a reduced rate of repolarization. During a 50 ms long 5 spike train, the spike duration increased by 63·6 ± 3·4% from the 1st to the 3rd spike. The amplitude of the fast after-hyperpolarization (fAHP) also rapidly declined during each train. Suppression of BK-channel activity with (a) the selective BK-channel blocker iberiotoxin (IbTX, 60 nM), (b) the non-peptidergic BK-channel blocker paxilline (2–10 μM), or (c) calcium-free medium, broadened the 1st spike to a similar degree (≈60%). BK-channel suppression also caused a similar change in spike waveform as observed during repetitive firing, and eliminated (occluded) most of the spike broadening during repetitive firing. Computer simulations using a reduced compartmental model with transient BK-channel current and 10 other active ionic currents, produced an activity-dependent spike broadening that was strongly reduced when the BK-channel inactivation mechanism was removed. These results, which are supported by recent voltage-clamp data, strongly suggest that in CA1 pyramidal cells, fast inactivation of a transient BK-channel current (ICT), substantially contributes to frequency-dependent spike broadening during repetitive firing. PMID:10562340

  5. Nanofinishing of BK7 glass using a magnetorheological solid rotating core tool.

    PubMed

    Kumar, Sumit; Singh, Anant Kumar

    2018-02-01

    Surface finishing is a promising method to improve the optical characteristics of crown glass. BK7 finds its applications in transmissive optics, i.e., lenses of binoculars, lenses of microscopes, lenses of telescopes, and light-emitting diodes. The magnetorheological (MR) nanofinishing of optical glasses using a solid rotating core tool is found more advantageous than the other advanced finishing processes in aspects such as precision and accuracy. In the present research, the MR nanofinishing with a solid rotating core tool is carried out on the BK7 glass of size 10×10×3  mm. Response surface methodology is conducted in order to find the optimum process parameters. The effects of process parameters on the percentage change in surface roughness are analyzed. The best surface roughness R a and R q values are achieved at 22 nm and 32 nm from the initial of 41 nm and 57 nm in 30 min of the finishing time cycle. To study the surface morphology of nanofinished BK7 glass, scanning electron microscopy is performed with sputter coating of gold on a glass specimen.

  6. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons

    PubMed Central

    Kimm, Tilia; Khaliq, Zayd M.

    2015-01-01

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency–current (f–I) relationship, whereas BK channel inhibition had little effect on the f–I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f–I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. SIGNIFICANCE STATEMENT This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra

  7. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

    PubMed

    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  8. Hydronephrosis Resulting from Bilateral Ureteral Stenosis: A Late Complication of Polyoma BK Virus Cystitis?

    PubMed Central

    Basara, N.; Rasche, F.-M.; Schwalenberg, T.; Wickenhauser, C.; Maier, M.; Ivovic, J.; Niederwieser, D.; Lindner, T. H.

    2010-01-01

    We report here a case of acute lymphoblastic leukemia in remission presenting a late-onset bilateral hydronephrosis probably due to polyoma BK virus-induced proliferation of bladder endothelium on both ostii. The diagnosis was made virologically by BK virus Polymerase Chain Reaction (PCR) detection in the absence of any other bladder disease. Awareness of this late complication is necessary not only in patients after renal transplantation but also in patients after hematopoietic stem cell transplantation from matched unrelated donor. PMID:20936157

  9. Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore–quencher pairing

    PubMed Central

    Pantazis, Antonios

    2012-01-01

    Voltage-activated proteins can sense, and respond to, changes in the electric field pervading the cell membrane by virtue of a transmembrane helix bundle, the voltage-sensing domain (VSD). Canonical VSDs consist of four transmembrane helices (S1–S4) of which S4 is considered a principal component because it possesses charged residues immersed in the electric field. Membrane depolarization compels the charges, and by extension S4, to rearrange with respect to the field. The VSD of large-conductance voltage- and Ca-activated K+ (BK) channels exhibits two salient inconsistencies from the canonical VSD model: (1) the BK channel VSD possesses an additional nonconserved transmembrane helix (S0); and (2) it exhibits a “decentralized” distribution of voltage-sensing charges, in helices S2 and S3, in addition to S4. Considering these unique features, the voltage-dependent rearrangements of the BK VSD could differ significantly from the standard model of VSD operation. To understand the mode of operation of this unique VSD, we have optically tracked the relative motions of the BK VSD transmembrane helices during activation, by manipulating the quenching environment of site-directed fluorescent labels with native and introduced Trp residues. Having previously reported that S0 and S4 diverge during activation, in this work we demonstrate that S4 also diverges from S1 and S2, whereas S2, compelled by its voltage-sensing charged residues, moves closer to S1. This information contributes spatial constraints for understanding the BK channel voltage-sensing process, revealing the structural rearrangements in a non-canonical VSD. PMID:22802360

  10. BK Virus-Associated Nephropathy: Current Situation in a Resource-Limited Country.

    PubMed

    Yooprasert, P; Rotjanapan, P

    Data on BK virus-associated nephropathy (BKVAN) and treatment strategy in a resource-limited country are scarce. This study aimed to evaluate epidemiology of BKVAN and its situation in Thailand. A retrospective analysis was conducted among adult kidney transplant recipients at Ramathibodi Hospital from October 2011 to September 2016. Patients' demographic data, information on kidney transplantation, immunosuppressive therapy, cytomegalovirus and BK virus infections, and allograft outcomes were retrieved and analyzed. This study included 623 kidney transplant recipients. Only 327 patients (52.49%) received BK virus infection screening, and 176 of 327 patients had allograft dysfunction as a trigger for screening. BKVAN was identified in 39 of 327 patients (11.93%). Deceased donor transplantation and cytomegalovirus infection were associated with a higher risk of BKVAN (odds ratio = 2.2, P = .024, 95% confidence intervals [1.1, 4.43], and odds ratio = 2.6, P = .006, 95% confidence intervals [1.29, 5.26], respectively). BKVAN patients were at significantly higher risk for allograft rejection (P < .001) and allograft failure (P = .036). At the end of the study, 4 graft losses were documented (12.12%). BKVAN was associated with high rate of allograft rejection and failure. However, surveillance of its complications has been underperformed at our facility. Implementing a formal practice guideline may improve allograft outcome in resource-limited countries. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Single-channel kinetics of BK (Slo1) channels

    PubMed Central

    Geng, Yanyan; Magleby, Karl L.

    2014-01-01

    Single-channel kinetics has proven a powerful tool to reveal information about the gating mechanisms that control the opening and closing of ion channels. This introductory review focuses on the gating of large conductance Ca2+- and voltage-activated K+ (BK or Slo1) channels at the single-channel level. It starts with single-channel current records and progresses to presentation and analysis of single-channel data and the development of gating mechanisms in terms of discrete state Markov (DSM) models. The DSM models are formulated in terms of the tetrameric modular structure of BK channels, consisting of a central transmembrane pore-gate domain (PGD) attached to four surrounding transmembrane voltage sensing domains (VSD) and a large intracellular cytosolic domain (CTD), also referred to as the gating ring. The modular structure and data analysis shows that the Ca2+ and voltage dependent gating considered separately can each be approximated by 10-state two-tiered models with five closed states on the upper tier and five open states on the lower tier. The modular structure and joint Ca2+ and voltage dependent gating are consistent with a 50 state two-tiered model with 25 closed states on the upper tier and 25 open states on the lower tier. Adding an additional tier of brief closed (flicker states) to the 10-state or 50-state models improved the description of the gating. For fixed experimental conditions a channel would gate in only a subset of the potential number of states. The detected number of states and the correlations between adjacent interval durations are consistent with the tiered models. The examined models can account for the single-channel kinetics and the bursting behavior of gating. Ca2+ and voltage activate BK channels by predominantly increasing the effective opening rate of the channel with a smaller decrease in the effective closing rate. Ca2+ and depolarization thus activate by mainly destabilizing the closed states. PMID:25653620

  12. BK potassium channels facilitate high-frequency firing and cause early spike frequency adaptation in rat CA1 hippocampal pyramidal cells

    PubMed Central

    Gu, Ning; Vervaeke, Koen; Storm, Johan F

    2007-01-01

    Neuronal potassium (K+) channels are usually regarded as largely inhibitory, i.e. reducing excitability. Here we show that BK-type calcium-activated K+ channels enhance high-frequency firing and cause early spike frequency adaptation in neurons. By combining slice electrophysiology and computational modelling, we investigated functions of BK channels in regulation of high-frequency firing in rat CA1 pyramidal cells. Blockade of BK channels by iberiotoxin (IbTX) selectively reduced the initial discharge frequency in response to strong depolarizing current injections, thus reducing the early spike frequency adaptation. IbTX also blocked the fast afterhyperpolarization (fAHP), slowed spike rise and decay, and elevated the spike threshold. Simulations with a computational model of a CA1 pyramidal cell confirmed that the BK channel-mediated rapid spike repolarization and fAHP limits activation of slower K+ channels (in particular the delayed rectifier potassium current (IDR)) and Na+ channel inactivation, whereas M-, sAHP- or SK-channels seem not to be important for the early facilitating effect. Since the BK current rapidly inactivates, its facilitating effect diminishes during the initial discharge, thus producing early spike frequency adaptation by an unconventional mechanism. This mechanism is highly frequency dependent. Thus, IbTX had virtually no effect at spike frequencies < 40 Hz. Furthermore, extracellular field recordings demonstrated (and model simulations supported) that BK channels contribute importantly to high-frequency burst firing in response to excitatory synaptic input to distal dendrites. These results strongly support the idea that BK channels play an important role for early high-frequency, rapidly adapting firing in hippocampal pyramidal neurons, thus promoting the type of bursting that is characteristic of these cells in vivo, during behaviour. PMID:17303637

  13. Tagging of Endogenous BK Channels with a Fluorogen-Activating Peptide Reveals β4-Mediated Control of Channel Clustering in Cerebellum

    PubMed Central

    Pratt, Christopher P.; Kuljis, Dika A.; Homanics, Gregg E.; He, Jianjun; Kolodieznyi, Dmytro; Dudem, Srikanth; Hollywood, Mark A.; Barth, Alison L.; Bruchez, Marcel P.

    2017-01-01

    BK channels are critical regulators of neuronal activity, controlling firing, neurotransmitter release, cerebellar function, and BK channel mutations have been linked to seizure disorders. Modulation of BK channel gating is well characterized, regulated by accessory subunit interactions, intracellular signaling pathways, and membrane potential. In contrast, the role of intracellular trafficking mechanisms in controlling BK channel function, especially in live cells, has been less studied. Fluorogen-activating peptides (FAPs) are well-suited for trafficking and physiological studies due to the binding of malachite green (MG)-based dyes with sub-nanomolar affinity to the FAP, resulting in bright, photostable, far-red fluorescence. Cell-excluded MG dyes enable the selective tagging of surface protein and tracking through endocytic pathways. We used CRISPR to insert the FAP at the extracellular N-terminus of BKα in the first exon of its native locus, enabling regulation by the native promoter elements and tag incorporation into multiple splice isoforms. Motor coordination was found to be normal; however, BK channel expression seems to be reduced in some locations. Alternate start site selection or post-translational proteolytic processing resulted in incomplete FAP tagging of the BKα proteins in brain tissues. In Purkinje cell somata, FAP revealed BK channel clustering previously only observed by electron microscopy. Measurement of these clusters in β4+/- and β4-/- mice showed that puncta number and cluster fluorescence intensity on the soma are reduced in β4-/- knockout animals. This novel mouse line provides a versatile fluorescent platform for studying endogenous BK channels in living and fixed tissues. Future studies could apply this line to ex vivo neuronal cultures to study live-cell channel trafficking. PMID:29163049

  14. Testosterone decreases urinary bladder smooth muscle excitability via novel signaling mechanism involving direct activation of the BK channels

    PubMed Central

    Hristov, Kiril L.; Parajuli, Shankar P.; Provence, Aaron

    2016-01-01

    In addition to improving sexual function, testosterone has been reported to have beneficial effects in ameliorating lower urinary tract symptoms by increasing bladder capacity and compliance, while decreasing bladder pressure. However, the cellular mechanisms by which testosterone regulates detrusor smooth muscle (DSM) excitability have not been elucidated. Here, we used amphotericin-B perforated whole cell patch-clamp and single channel recordings on inside-out excised membrane patches to investigate the regulatory role of testosterone in guinea pig DSM excitability. Testosterone (100 nM) significantly increased the depolarization-induced whole cell outward currents in DSM cells. The selective pharmacological inhibition of the large-conductance voltage- and Ca2+-activated K+ (BK) channels with paxilline (1 μM) completely abolished this stimulatory effect of testosterone, suggesting a mechanism involving BK channels. At a holding potential of −20 mV, DSM cells exhibited transient BK currents (TBKCs). Testosterone (100 nM) significantly increased TBKC activity in DSM cells. In current-clamp mode, testosterone (100 nM) significantly hyperpolarized the DSM cell resting membrane potential and increased spontaneous transient hyperpolarizations. Testosterone (100 nM) rapidly increased the single BK channel open probability in inside-out excised membrane patches from DSM cells, clearly suggesting a direct BK channel activation via a nongenomic mechanism. Live-cell Ca2+ imaging showed that testosterone (100 nM) caused a decrease in global intracellular Ca2+ concentration, consistent with testosterone-induced membrane hyperpolarization. In conclusion, the data provide compelling mechanistic evidence that under physiological conditions, testosterone at nanomolar concentrations directly activates BK channels in DSM cells, independent from genomic testosterone receptors, and thus regulates DSM excitability. PMID:27605581

  15. Polyomavirus-Specific Cellular Immunity: From BK-Virus-Specific Cellular Immunity to BK-Virus-Associated Nephropathy?

    PubMed Central

    Dekeyser, Manon; François, Hélène; Beaudreuil, Séverine; Durrbach, Antoine

    2015-01-01

    In renal transplantation, BK-virus (BKV)-associated nephropathy has emerged as a major complication, with a prevalence of 1–10% and graft loss in >50% of cases. BKV is a member of the polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BKV-specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BKV-associated nephropathy. PMID:26136745

  16. Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis.

    PubMed

    Azzi, A; Fanci, R; Bosi, A; Ciappi, S; Zakrzewska, K; de Santis, R; Laszlo, D; Guidi, S; Saccardi, R; Vannucchi, A M

    1994-08-01

    An association between long-lasting hemorrhagic cystitis (HC) in bone marrow transplantation (BMT) patients and viral infections, mostly with reactivation of the human polyomavirus BK (BKV), is suggested by several previous reports. We have carried out a prospective study in 55 (30 allogeneic, 24 autologous, 1 syngeneic) BMT recipients with the aim of evaluating the role of BKV in this frequent complication after BMT. To overcome the well known difficulties in BK virus isolation in cell cultures, a DNA hybridization assay and the polymerase chain reaction (PCR) were used for the detection and monitoring of viral urinary shedding, respectively. The presence of human polyomavirus JC and adenovirus DNA was also sought in urine specimens. BK viruria was demonstrated in 52.7% of patients (in 53.3% allogeneic and in 54.1% autologous BMT), whereas JCV and adenovirus were seldom present. Seven cases of HC (20% in allogeneic and 4% in autologous BMT) occurred and in all cases the clinical event was associated with BKV urinary shedding. This study suggests that BKV infection alone does not invariably lead to HC in BMT patients; for HC to occur the presence of other, at present unidentified, factors seems to be necessary.

  17. Collinearly-improved BK evolution meets the HERA data

    DOE PAGES

    Iancu, E.; Madrigal, J. D.; Mueller, A. H.; ...

    2015-10-03

    In a previous publication, we have established a collinearly-improved version of the Balitsky–Kovchegov (BK) equation, which resums to all orders the radiative corrections enhanced by large double transverse logarithms. Here, we study the relevance of this equation as a tool for phenomenology, by confronting it to the HERA data. To that aim, we first improve the perturbative accuracy of our resummation, by including two classes of single-logarithmic corrections: those generated by the first non-singular terms in the DGLAP splitting functions and those expressing the one-loop running of the QCD coupling. The equation thus obtained includes all the next-to-leading order correctionsmore » to the BK equation which are enhanced by (single or double) collinear logarithms. Furthermore, we then use numerical solutions to this equation to fit the HERA data for the electron–proton reduced cross-section at small Bjorken x. We obtain good quality fits for physically acceptable initial conditions. Our best fit, which shows a good stability up to virtualities as large as Q 2 = 400 GeV 2 for the exchanged photon, uses as an initial condition the running-coupling version of the McLerran–Venugopalan model, with the QCD coupling running according to the smallest dipole prescription.« less

  18. Intermittent losartan administration triggers cardiac post-conditioning in isolated rat hearts: role of BK2 receptors.

    PubMed

    Sgarra, Luca; Leo, Valentina; Addabbo, Francesco; Iacobazzi, Dominga; Carratù, Maria Rosaria; Montagnani, Monica; Potenza, Maria Assunta

    2014-01-01

    The angiotensin (Ang) and bradykinin (BK) tissue-system plays a pivotal role in post-conditioning, but the efficacy of angiotensin type 1 receptor (AT1R) blockers (ARBs) in post-ischemic strategies is still under investigation. We evaluated functional and morphological outcomes, together with activation of cytosolic RISK pathway kinases, in rat hearts subjected to losartan (LOS) or irbesartan (IRB) post-ischemic administration. Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Post-conditioning was obtained by intermittent (10 s/each) or continuous drug infusion during the first 3 min of reperfusion. Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (dLVP), coronary flow (CF), and left ventricular infarct mass (IM) were measured together with the activation status of RISK kinases Akt, p42/44 MAPK and GSK3β. When compared to hearts subjected to ischemia/reperfusion (iI/R) alone, continuous IRB or LOS administration did not significantly reduce total infarct mass (cIRB or cLOS vs. iI/R, p = 0.2). Similarly, intermittent IRB (iIRB) was not able to enhance cardioprotection. Conversely, intermittent LOS administration (iLOS) significantly ameliorated cardiac recovery (iLOS vs iI/R, p<0.01). Differences between iLOS and iIRB persisted under continuous blockade of AT2R (iLOS+cPD vs. iIRB+cPD, p<0.05). Interestingly, iLOS cardioprotection was lost when BK2R was simultaneously blocked (iLOS+cHOE vs. iI/R, p = 0.6), whereas concurrent administration of iBK and iIRB replicated iLOS effects (iIRB+iBK vs. iLOS, p = 0.7). At the molecular level, iIRB treatment did not significantly activate RISK kinases, whereas both iLOS and iBK treatments were associated with activation of the Akt/GSK3β branch of the RISK pathways (p<0.05 vs. iI/R, for both). Our results suggest that intermittent losartan is effective in mediating post-conditioning cardioprotection, whereas irbesartan is not. The infarct mass reduction by intermittent

  19. Intermittent Losartan Administration Triggers Cardiac Post-Conditioning in Isolated Rat Hearts: Role of BK2 Receptors

    PubMed Central

    Sgarra, Luca; Leo, Valentina; Addabbo, Francesco; Iacobazzi, Dominga; Carratù, Maria Rosaria; Montagnani, Monica; Potenza, Maria Assunta

    2014-01-01

    Introduction The angiotensin (Ang) and bradykinin (BK) tissue-system plays a pivotal role in post-conditioning, but the efficacy of angiotensin type 1 receptor (AT1R) blockers (ARBs) in post-ischemic strategies is still under investigation. We evaluated functional and morphological outcomes, together with activation of cytosolic RISK pathway kinases, in rat hearts subjected to losartan (LOS) or irbesartan (IRB) post-ischemic administration. Methods Isolated rat hearts underwent 30 min ischemia and 120 min reperfusion. Post-conditioning was obtained by intermittent (10 s/each) or continuous drug infusion during the first 3 min of reperfusion. Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (dLVP), coronary flow (CF), and left ventricular infarct mass (IM) were measured together with the activation status of RISK kinases Akt, p42/44 MAPK and GSK3β. Results When compared to hearts subjected to ischemia/reperfusion (iI/R) alone, continuous IRB or LOS administration did not significantly reduce total infarct mass (cIRB or cLOS vs. iI/R, p = 0.2). Similarly, intermittent IRB (iIRB) was not able to enhance cardioprotection. Conversely, intermittent LOS administration (iLOS) significantly ameliorated cardiac recovery (iLOS vs iI/R, p<0.01). Differences between iLOS and iIRB persisted under continuous blockade of AT2R (iLOS+cPD vs. iIRB+cPD, p<0.05). Interestingly, iLOS cardioprotection was lost when BK2R was simultaneously blocked (iLOS+cHOE vs. iI/R, p = 0.6), whereas concurrent administration of iBK and iIRB replicated iLOS effects (iIRB+iBK vs. iLOS, p = 0.7). At the molecular level, iIRB treatment did not significantly activate RISK kinases, whereas both iLOS and iBK treatments were associated with activation of the Akt/GSK3β branch of the RISK pathways (p<0.05 vs. iI/R, for both). Conclusions Our results suggest that intermittent losartan is effective in mediating post-conditioning cardioprotection, whereas irbesartan

  20. Towards saturation of the electron-capture delayed fission probability: The new isotopes 240Es and 236Bk

    NASA Astrophysics Data System (ADS)

    Konki, J.; Khuyagbaatar, J.; Uusitalo, J.; Greenlees, P. T.; Auranen, K.; Badran, H.; Block, M.; Briselet, R.; Cox, D. M.; Dasgupta, M.; Di Nitto, A.; Düllmann, Ch. E.; Grahn, T.; Hauschild, K.; Herzán, A.; Herzberg, R.-D.; Heßberger, F. P.; Hinde, D. J.; Julin, R.; Juutinen, S.; Jäger, E.; Kindler, B.; Krier, J.; Leino, M.; Lommel, B.; Lopez-Martens, A.; Luong, D. H.; Mallaburn, M.; Nishio, K.; Pakarinen, J.; Papadakis, P.; Partanen, J.; Peura, P.; Rahkila, P.; Rezynkina, K.; Ruotsalainen, P.; Sandzelius, M.; Sarén, J.; Scholey, C.; Sorri, J.; Stolze, S.; Sulignano, B.; Theisen, Ch.; Ward, A.; Yakushev, A.; Yakusheva, V.

    2017-01-01

    The new neutron-deficient nuclei 240Es and 236Bk were synthesised at the gas-filled recoil separator RITU. They were identified by their radioactive decay chains starting from 240Es produced in the fusion-evaporation reaction 209Bi(34S,3n)240Es. Half-lives of 6 (2)s and 22-6+13s were obtained for 240Es and 236Bk, respectively. Two groups of α particles with energies Eα = 8.19 (3)MeV and 8.09 (3)MeV were unambiguously assigned to 240Es. Electron-capture delayed fission branches with probabilities of 0.16 (6) and 0.04 (2) were measured for 240Es and 236Bk, respectively. These new data show a continuation of the exponential increase of ECDF probabilities in more neutron-deficient isotopes.

  1. Functional validation of Ca2+-binding residues from the crystal structure of the BK ion channel.

    PubMed

    Kshatri, Aravind S; Gonzalez-Hernandez, Alberto J; Giraldez, Teresa

    2018-04-01

    BK channels are dually regulated by voltage and Ca 2+ , providing a cellular mechanism to couple electrical and chemical signalling. Intracellular Ca 2+ concentration is sensed by a large cytoplasmic region in the channel known as "gating ring", which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. The recent crystal structure of the full-length BK channel from Aplysia californica has provided new information about the residues involved in Ca 2+ coordination at the high-affinity binding sites located in the RCK1 and RCK2 domains, as well as their cooperativity. Some of these residues have not been previously studied in the human BK channel. In this work we have investigated, through site directed mutagenesis and electrophysiology, the effects of these residues on channel activation by voltage and Ca 2+ . Our results demonstrate that the side chains of two non-conserved residues proposed to coordinate Ca 2+ in the A. californica structure (G523 and E591) have no apparent functional role in the human BK Ca 2+ sensing mechanism. Consistent with the crystal structure, our data indicate that in the human channel the conserved residue R514 participates in Ca 2+ coordination in the RCK1 binding site. Additionally, this study provides functional evidence indicating that R514 also interacts with residues E902 and Y904 connected to the Ca 2+ binding site in RCK2. Interestingly, it has been proposed that this interaction may constitute a structural correlate underlying the cooperative interactions between the two high-affinity Ca 2+ binding sites regulating the Ca 2+ dependent gating of the BK channel. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Oshrine, Benjamin; Bunin, Nancy; Li, Yimei; Furth, Susan; Laskin, Benjamin L

    2013-12-01

    BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HSCT) recipients and nephropathy after kidney transplantation. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children's Hospital of Philadelphia from 2005 to 2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N = 68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥ 10,000 copies/mL (high viremia) with severe HC (defined as grade IV-bladder catheterization or surgical intervention); the need for dialysis; serum creatinine-estimated glomerular filtration rate at the time of BKV testing, day 100, and day 365; and death. Children with high viremia more likely developed severe HC compared with those with peak viremia < 10,000 copies/mL (21% versus 2%; P = .02). BKV infection of the blood or urine was not associated with the need for dialysis, change in estimated glomerular filtration rate, or mortality. BKV infection is common after pediatric allogeneic HSCT, and plasma testing in those with HC may predict patients who will develop severe bladder injury. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Calcium-activated potassium (BK) channels are encoded by duplicate slo1 genes in teleost fishes.

    PubMed

    Rohmann, Kevin N; Deitcher, David L; Bass, Andrew H

    2009-07-01

    Calcium-activated, large conductance potassium (BK) channels in tetrapods are encoded by a single slo1 gene, which undergoes extensive alternative splicing. Alternative splicing generates a high level of functional diversity in BK channels that contributes to the wide range of frequencies electrically tuned by the inner ear hair cells of many tetrapods. To date, the role of BK channels in hearing among teleost fishes has not been investigated at the molecular level, although teleosts account for approximately half of all extant vertebrate species. We identified slo1 genes in teleost and nonteleost fishes using polymerase chain reaction and genetic sequence databases. In contrast to tetrapods, all teleosts examined were found to express duplicate slo1 genes in the central nervous system, whereas nonteleosts that diverged prior to the teleost whole-genome duplication event express a single slo1 gene. Phylogenetic analyses further revealed that whereas other slo1 duplicates were the result of a single duplication event, an independent duplication occurred in a basal teleost (Anguilla rostrata) following the slo1 duplication in teleosts. A third, independent slo1 duplication (autotetraploidization) occurred in salmonids. Comparison of teleost slo1 genomic sequences to their tetrapod orthologue revealed a reduced number of alternative splice sites in both slo1 co-orthologues. For the teleost Porichthys notatus, a focal study species that vocalizes with maximal spectral energy in the range electrically tuned by BK channels in the inner ear, peripheral tissues show the expression of either one (e.g., vocal muscle) or both (e.g., inner ear) slo1 paralogues with important implications for both auditory and vocal physiology. Additional loss of expression of one slo1 paralogue in nonneural tissues in P. notatus suggests that slo1 duplicates were retained via subfunctionalization. Together, the results predict that teleost fish achieve a diversity of BK channel subfunction via

  4. Calcium-Activated Potassium (BK) Channels Are Encoded by Duplicate slo1 Genes in Teleost Fishes

    PubMed Central

    Deitcher, David L.; Bass, Andrew H.

    2009-01-01

    Calcium-activated, large conductance potassium (BK) channels in tetrapods are encoded by a single slo1 gene, which undergoes extensive alternative splicing. Alternative splicing generates a high level of functional diversity in BK channels that contributes to the wide range of frequencies electrically tuned by the inner ear hair cells of many tetrapods. To date, the role of BK channels in hearing among teleost fishes has not been investigated at the molecular level, although teleosts account for approximately half of all extant vertebrate species. We identified slo1 genes in teleost and nonteleost fishes using polymerase chain reaction and genetic sequence databases. In contrast to tetrapods, all teleosts examined were found to express duplicate slo1 genes in the central nervous system, whereas nonteleosts that diverged prior to the teleost whole-genome duplication event express a single slo1 gene. Phylogenetic analyses further revealed that whereas other slo1 duplicates were the result of a single duplication event, an independent duplication occurred in a basal teleost (Anguilla rostrata) following the slo1 duplication in teleosts. A third, independent slo1 duplication (autotetraploidization) occurred in salmonids. Comparison of teleost slo1 genomic sequences to their tetrapod orthologue revealed a reduced number of alternative splice sites in both slo1 co-orthologues. For the teleost Porichthys notatus, a focal study species that vocalizes with maximal spectral energy in the range electrically tuned by BK channels in the inner ear, peripheral tissues show the expression of either one (e.g., vocal muscle) or both (e.g., inner ear) slo1 paralogues with important implications for both auditory and vocal physiology. Additional loss of expression of one slo1 paralogue in nonneural tissues in P. notatus suggests that slo1 duplicates were retained via subfunctionalization. Together, the results predict that teleost fish achieve a diversity of BK channel subfunction via

  5. Iberiotoxin-sensitive and -insensitive BK currents in Purkinje neuron somata

    PubMed Central

    Benton, Mark D.; Lewis, Amanda H.; Bant, Jason S.

    2013-01-01

    Purkinje cells have specialized intrinsic ionic conductances that generate high-frequency action potentials. Disruptions of their Ca or Ca-activated K (KCa) currents correlate with altered firing patterns in vitro and impaired motor behavior in vivo. To examine the properties of somatic KCa currents, we recorded voltage-clamped KCa currents in Purkinje cell bodies isolated from postnatal day 17–21 mouse cerebellum. Currents were evoked by endogenous Ca influx with approximately physiological Ca buffering. Purkinje somata expressed voltage-activated, Cd-sensitive KCa currents with iberiotoxin (IBTX)-sensitive (>100 nS) and IBTX-insensitive (>75 nS) components. IBTX-sensitive currents activated and partially inactivated within milliseconds. Rapid, incomplete macroscopic inactivation was also evident during 50- or 100-Hz trains of 1-ms depolarizations. In contrast, IBTX-insensitive currents activated more slowly and did not inactivate. These currents were insensitive to the small- and intermediate-conductance KCa channel blockers apamin, scyllatoxin, UCL1684, bicuculline methiodide, and TRAM-34, but were largely blocked by 1 mM tetraethylammonium. The underlying channels had single-channel conductances of ∼150 pS, suggesting that the currents are carried by IBTX-resistant (β4-containing) large-conductance KCa (BK) channels. IBTX-insensitive currents were nevertheless increased by small-conductance KCa channel agonists EBIO, chlorzoxazone, and CyPPA. During trains of brief depolarizations, IBTX-insensitive currents flowed during interstep intervals, and the accumulation of interstep outward current was enhanced by EBIO. In current clamp, EBIO slowed spiking, especially during depolarizing current injections. The two components of BK current in Purkinje somata likely contribute differently to spike repolarization and firing rate. Moreover, augmentation of BK current may partially underlie the action of EBIO and chlorzoxazone to alleviate disrupted Purkinje cell

  6. Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.

    PubMed

    Nankivell, Brian J; Renthawa, Jasveen; Jeoffreys, Neisha; Kable, Kathy; O'Connell, Philip J; Chapman, Jeremy R; Wong, Germaine; Sharma, Raghwa N

    2015-08-01

    Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.

  7. BK Virus Load Associated with Serum Levels of sCD30 in Renal Transplant Recipients

    PubMed Central

    Malik, Salma N.; Al-Saffer, Jinan M.; Jawad, Rana S.

    2016-01-01

    Background. Rejection is the main drawback facing the renal transplant operations. Complicated and overlapping factors, mainly related to the immune system, are responsible for this rejection. Elevated serum levels of sCD30 were frequently recorded as an indicator for renal allograft rejection, while BV virus is considered as one of the most serious consequences for immunosuppressive treatment of renal transplant recipients (RTRs). Aims. This study aimed to determine the association of BK virus load with serum levels of sCD30 in RTRs suffering from nephropathy. Patients and Methods. A total of 50 RTRs with nephropathy and 30 age-matched apparently healthy individuals were recruited for this study. Serum samples were obtained from each participant. Real-time PCR was used to quantify BK virus load in RTRs serum, while ELISA technique was employed to estimate serum levels of sCD30. Results. Twenty-two percent of RTRs had detectable BKV with mean viral load of 1.094E + 06 ± 2.291E + 06. RTRs showed higher mean serum level of sCD30 (20.669 ± 18.713 U/mL) than that of controls (5.517 ± 5.304 U/mL) with significant difference. BK virus load had significant positive correlation with the serum levels of sCD30 in RTRs group. Conclusion. These results suggest that serum levels of sCD30 could be used as an indicator of BK viremia, and accordingly the immunosuppressive regime should be adjusted. PMID:27051424

  8. BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.

    PubMed

    Nelson, Alexandra B; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-04

    Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mechanisms underlying activation of transient BK current in rabbit urethral smooth muscle cells and its modulation by IP3-generating agonists

    PubMed Central

    Kyle, Barry D.; Bradley, Eamonn; Large, Roddy; Sergeant, Gerard P.; McHale, Noel G.; Thornbury, Keith D.

    2013-01-01

    We used the perforated patch-clamp technique at 37°C to investigate the mechanisms underlying the activation of a transient large-conductance K+ (tBK) current in rabbit urethral smooth muscle cells. The tBK current required an elevation of intracellular Ca2+, resulting from ryanodine receptor (RyR) activation via Ca2+-induced Ca2+ release, triggered by Ca2+ influx through L-type Ca2+ (CaV) channels. Carbachol inhibited tBK current by reducing Ca2+ influx and Ca2+ release and altered the shape of spike complexes recorded under current-clamp conditions. The tBK currents were blocked by iberiotoxin and penitrem A (300 and 100 nM, respectively) and were also inhibited when external Ca2+ was removed or the CaV channel inhibitors nifedipine (10 μM) and Cd2+ (100 μM) were applied. The tBK current was inhibited by caffeine (10 mM), ryanodine (30 μM), and tetracaine (100 μM), suggesting that RyR-mediated Ca2+ release contributed to the activation of the tBK current. When IP3 receptors (IP3Rs) were blocked with 2-aminoethoxydiphenyl borate (2-APB, 100 μM), the amplitude of the tBK current was not reduced. However, when Ca2+ release via IP3Rs was evoked with phenylephrine (1 μM) or carbachol (1 μM), the tBK current was inhibited. The effect of carbachol was abolished when IP3Rs were blocked with 2-APB or by inhibition of muscarinic receptors with the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (1 μM). Under current-clamp conditions, bursts of action potentials could be evoked with depolarizing current injection. Carbachol reduced the number and amplitude of spikes in each burst, and these effects were reduced in the presence of 2-APB. In the presence of ryanodine, the number and amplitude of spikes were also reduced, and carbachol was without further effect. These data suggest that IP3-generating agonists can modulate the electrical activity of rabbit urethral smooth muscle cells and may contribute to the effects of neurotransmitters on

  10. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters.

    PubMed

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-05-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. © 2016 Kumar et al.; Published by Cold Spring Harbor Laboratory Press.

  11. Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters

    PubMed Central

    Kumar, Vibhor; Rayan, Nirmala Arul; Muratani, Masafumi; Lim, Stefan; Elanggovan, Bavani; Xin, Lixia; Lu, Tess; Makhija, Harshyaa; Poschmann, Jeremie; Lufkin, Thomas; Ng, Huck Hui; Prabhakar, Shyam

    2016-01-01

    Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation. PMID:26957309

  12. NAS: The first year

    NASA Technical Reports Server (NTRS)

    Bailey, F. R.; Kutler, Paul

    1988-01-01

    Discussed are the capabilities of NASA's Numerical Aerodynamic Simulation (NAS) Program and its application as an advanced supercomputing system for computational fluid dynamics (CFD) research. First, the paper describes the NAS computational system, called the NAS Processing System Network, and the advanced computational capabilities it offers as a consequence of carrying out the NAS pathfinder objective. Second, it presents examples of pioneering CFD research accomplished during NAS's first operational year. Examples are included which illustrate CFD applications for predicting fluid phenomena, complementing and supplementing experimentation, and aiding in design. Finally, pacing elements and future directions for CFD and NAS are discussed.

  13. Towards industrial ultrafast laser microwelding: SiO2 and BK7 to aluminum alloy.

    PubMed

    Carter, Richard M; Troughton, Michael; Chen, Jianyong; Elder, Ian; Thomson, Robert R; Daniel Esser, M J; Lamb, Robert A; Hand, Duncan P

    2017-06-01

    We report systematic analysis and comparison of ps-laser microwelding of industry relevant Al6082 parts to SiO 2 and BK7. Parameter mapping of pulse energy and focal depth on the weld strength is presented. The welding process was found to be strongly dependent on the focal plane but has a large tolerance to variation in pulse energy. Accelerated lifetime tests by thermal cycling from -50° to +90°C are presented. Welds in Al6082-BK7 parts survive over the full temperature range where the ratio of thermal expansion coefficients is 3.4:1. Welds in Al6082-SiO 2 parts (ratio 47.1:1) survive only a limited temperature range.

  14. Developing a Native American Studies Program.

    ERIC Educational Resources Information Center

    Whiteman, Henrietta V.

    The development of Native American Studies (NAS) is an attempt at self-awareness and an exercise in self-determination. One area of concern in the development of a program for Native Americans is their high attrition rate in college. Specially designed programs for the Native American student could offer (1) Native American student orientation…

  15. Nitric oxide decreases the excitability of interstitial cells of Cajal through activation of the BK channel

    PubMed Central

    Zhu, Yaohui; Huizinga, Jan D

    2008-01-01

    Abstract Nitrergic nerves are structurally and functionally associated with ICC. To further understand mechanisms of communication, the hypothesis was investigated that NO might affect large conductance K channels. To that end, we searched for IbTX-sensitive currents in ICC obtained through explant cultures from the mouse small intestine and studied effects of the NOS inhibitor omega N-nitro-L-arginine (LNNA) and the NO donor sodium nitroprusside (SNP). IbTX-sensitive currents acquired in the whole-cell configuration through nystatin perforated patches exhibited high noise levels but relatively low amplitude, whereas currents obtained in the conventional whole-cell configuration exhibited less noise and higher amplitudes; depolarization from −80 to + 40 mV evoked 357 ± 159 pA current in the nystatin perforated patch configuration and 1075 ± 597 pA using the conventional whole-cell configuration. Immunohistochemistry showed that ICC associated with ganglia and Auerbach's plexus nerve fibers were immunoreactive to BK antibodies. The IbTX-sensitive currents were increased by SNP and inhibited by LNNA. BK blockers suppressed spontaneous transit outward currents in ICC. After block of BK currents, or before these currents became prominent, calcium currents were activated by depolarization in the same cells. Their peak amplitude occurred at −25 mV and the currents were increased with increasing extracellular calcium and inhibited by cobalt. The hypothesis is warranted that nitrergic innervation inhibits ICC excitability in part through activation of BK channels. In addition, NO is an intracellular regulator of ICC excitability. PMID:18194464

  16. Recombined sequences between the non-coding control regions of JC and BK viruses found in the urine of a renal transplantation patient.

    PubMed

    Liaw, Yu-Ching; Chen, Cheng-Hsu; Shu, Kuo-Hsiung; Fang, Chiung-Yao; Ou, Wei-Chih; Chen, Pei-Lain; Shen, Cheng-Huang; Lin, Mien-Chun; Chang, Deching; Wang, Meilin

    2012-12-01

    Kidney cells are the common host for JC virus (JCV) and BK virus (BKV). Reactivation of JCV and/or BKV in patients after organ transplantation, such as renal transplantation, may cause hemorrhagic cystitis and polyomavirus-associated nephropathy. Furthermore, JCV and BKV may be shed in the urine after reactivation in the kidney. Rearranged as well as archetypal non-coding control regions (NCCRs) of JCV and BKV have been frequently identified in human samples. In this study, three JC/BK recombined NCCR sequences were identified in the urine of a patient who had undergone renal transplantation. They were designated as JC-BK hybrids 1, 2, and 3. The three JC/BK recombinant NCCRs contain up-stream JCV as well as down-stream BKV sequences. Deletions of both JCV and BKV sequences were found in these recombined NCCRs. Recombination of DNA sequences between JCV and BKV may occur during co-infection due to the relatively high homology of the two viral genomes.

  17. Broadening roles for FMRP: big news for big potassium (BK) channels.

    PubMed

    Contractor, Anis

    2013-02-20

    FMRP is an RNA-binding protein that negatively regulates translation and which is lost in fragile X syndrome. In this issue of Neuron, Deng et al. (2013) demonstrate a novel translation-independent function for FMRP as a regulator of presynaptic BK channels that modulate the dynamics of neurotransmitter release. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The temperature dependence of the BK channel activity - kinetics, thermodynamics, and long-range correlations.

    PubMed

    Wawrzkiewicz-Jałowiecka, Agata; Dworakowska, Beata; Grzywna, Zbigniew J

    2017-10-01

    Large-conductance, voltage dependent, Ca 2+ -activated potassium channels (BK) are transmembrane proteins that regulate many biological processes by controlling potassium flow across cell membranes. Here, we investigate to what extent temperature (in the range of 17-37°C with ΔT=5°C step) is a regulating parameter of kinetic properties of the channel gating and memory effect in the series of dwell-time series of subsequent channel's states, at membrane depolarization and hyperpolarization. The obtained results indicate that temperature affects strongly the BK channels' gating, but, counterintuitively, it exerts no effect on the long-range correlations, as measured by the Hurst coefficient. Quantitative differences between dependencies of appropriate channel's characteristics on temperature are evident for different regimes of voltage. Examining the characteristics of BK channel activity as a function of temperature allows to estimate the net activation energy (E act ) and changes of thermodynamic parameters (ΔH, ΔS, ΔG) by channel opening. Larger E act corresponds to the channel activity at membrane hyperpolarization. The analysis of entropy and enthalpy changes of closed to open channel's transition suggest the entropy-driven nature of the increase of open state probability during voltage activation and supports the hypothesis about the voltage-dependent geometry of the channel vestibule. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels.

    PubMed

    Zhang, Guohui; Geng, Yanyan; Jin, Yakang; Shi, Jingyi; McFarland, Kelli; Magleby, Karl L; Salkoff, Lawrence; Cui, Jianmin

    2017-03-06

    Large conductance Ca 2+ -activated K + channels (BK channels) gate open in response to both membrane voltage and intracellular Ca 2+ The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca 2+ sensor. How these voltage and Ca 2+ sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca 2+ activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA http://dx.doi.org/10.1073/pnas.1313433110). In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca 2+ sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel's β1 and β2 subunits. © 2017 Zhang et al.

  20. Deletion of cytosolic gating ring decreases gate and voltage sensor coupling in BK channels

    PubMed Central

    Zhang, Guohui; Shi, Jingyi; McFarland, Kelli; Magleby, Karl L.; Salkoff, Lawrence

    2017-01-01

    Large conductance Ca2+-activated K+ channels (BK channels) gate open in response to both membrane voltage and intracellular Ca2+. The channel is formed by a central pore-gate domain (PGD), which spans the membrane, plus transmembrane voltage sensors and a cytoplasmic gating ring that acts as a Ca2+ sensor. How these voltage and Ca2+ sensors influence the common activation gate, and interact with each other, is unclear. A previous study showed that a BK channel core lacking the entire cytoplasmic gating ring (Core-MT) was devoid of Ca2+ activation but retained voltage sensitivity (Budelli et al. 2013. Proc. Natl. Acad. Sci. USA. http://dx.doi.org/10.1073/pnas.1313433110). In this study, we measure voltage sensor activation and pore opening in this Core-MT channel over a wide range of voltages. We record gating currents and find that voltage sensor activation in this truncated channel is similar to WT but that the coupling between voltage sensor activation and gating of the pore is reduced. These results suggest that the gating ring, in addition to being the Ca2+ sensor, enhances the effective coupling between voltage sensors and the PGD. We also find that removal of the gating ring alters modulation of the channels by the BK channel’s β1 and β2 subunits. PMID:28196879

  1. BK virus (BKV) plasma dynamics in patients with BKV-associated hemorrhagic cystitis following allogeneic stem cell transplantation.

    PubMed

    Drew, R J; Walsh, A; Ní Laoi, B; Conneally, E; Crowley, B

    2013-06-01

    The use of real-time polymerase chain reaction testing in the investigation of BK virus (BKV)-associated disease has been widely studied in renal transplant recipients; however, far less research has been done in this area with respect to the plasma BK viral load dynamics of BKV hemorrhagic cystitis (BKV-HC) in hematopoietic stem cell transplant recipients. The aim of this study was to examine the BK viral load dynamics in plasma samples collected from patients post transplant who had laboratory-confirmed BKV-HC. Patients who developed BK viremia were compared with patients who did not develop viremia, and a statistical comparison of risk factors for viremia was performed. Seventeen patients were included in this study. Urine samples from the day of BKV diagnosis were available in 13 of the 17 cases. In total, 154 archived plasma samples from around the time of the BKV-HC event were also included in the study from these 17 patients. The median time from transplantation to the onset of detectable viremia was 68 days. The median viral load in the 13 urine samples was 1.8 × 10(8) copies/mL, which was significantly higher than the median viral load in the 38 positive plasma samples of 6.6 × 10(2) copies/mL (Mann-Whitney test, U = 16, P < 0.001). The lymphocyte count on the day of the positive BKV test was significantly lower in patients with BKV viremia than in patients with no viremia (P = 0.02) and also the white cell and platelet counts were lower on the day of the first positive BKV test. Although there is not inter-patient consistency as regards correlation between urinary BK viral loads and severity of clinical BKV-HC, in individual patients the decline in viral load in plasma did correlate with clinical recovery. © 2013 John Wiley & Sons A/S.

  2. Cysteine residue 911 in C-terminal tail of human BK(Ca)α channel subunit is crucial for its activation by carbon monoxide.

    PubMed

    Telezhkin, Vsevolod; Brazier, Stephen P; Mears, Ruth; Müller, Carsten T; Riccardi, Daniela; Kemp, Paul J

    2011-06-01

    The large conductance, voltage- and calcium-activated potassium channel, BK(Ca), is a known target for the gasotransmitter, carbon monoxide (CO). Activation of BK(Ca) by CO modulates cellular excitability and contributes to the physiology of a diverse array of processes, including vascular tone and oxygen-sensing. Currently, there is no consensus regarding the molecular mechanisms underpinning reception of CO by the BK(Ca). Here, employing voltage-clamped, inside-out patches from HEK293 cells expressing single, double and triple cysteine mutations in the BK(Ca) α-subunit, we test the hypothesis that CO regulation is conferred upon the channel by interactions with cysteine residues within the RCK2 domain. In physiological [Ca(2+)](i), all mutants carrying a cysteine substitution at position 911 (C911G) demonstrated significantly reduced CO sensitivity; the C911G mutant did not express altered Ca(2+)-sensitivity. In contrast, histidine residues in RCK1 domain, previously shown to ablate CO activation in low [Ca(2+)](i), actually increased CO sensitivity when [Ca(2+)](i) was in the physiological range. Importantly, cyanide, employed here as a substituent for CO at potential metal centres, occluded activation by CO; this effect was freely reversible. Taken together, these data suggest that a specific cysteine residue in the C-terminal domain, which is close to the Ca(2+) bowl but which is not involved in Ca(2+) activation, confers significant CO sensitivity to BK(Ca) channels. The rapid reversibility of CO and cyanide binding, coupled to information garnered from other CO-binding proteins, suggests that C911 may be involved in formation of a transition metal cluster which can bind and, thereafter, activate BK(Ca).

  3. Determination of the Stoichiometry between α- and γ1 Subunits of the BK Channel Using LRET.

    PubMed

    Carrasquel-Ursulaez, Willy; Alvarez, Osvaldo; Bezanilla, Francisco; Latorre, Ramon

    2018-06-05

    Two families of accessory proteins, β and γ, modulate BK channel gating and pharmacology. Notably, in the absence of internal Ca 2+ , the γ1 subunit promotes a large shift of the BK conductance-voltage curve to more negative potentials. However, very little is known about how α- and γ1 subunits interact. In particular, the association stoichiometry between both subunits is unknown. Here, we propose a method to answer this question using lanthanide resonance energy transfer. The method assumes that the kinetics of lanthanide resonance energy transfer-sensitized emission of the donor double-labeled α/γ1 complex is the linear combination of the kinetics of the sensitized emission in single-labeled complexes. We used a lanthanide binding tag engineered either into the α- or the γ1 subunits to bind Tb +3 as the donor. The acceptor (BODIPY) was attached to the BK pore-blocker iberiotoxin. We determined that γ1 associates with the α-subunit with a maximal 1:1 stoichiometry. This method could be applied to determine the stoichiometry of association between proteins within heteromultimeric complexes. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  4. Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

    PubMed

    Palacpac, Nirianne Marie Q; Ntege, Edward; Yeka, Adoke; Balikagala, Betty; Suzuki, Nahoko; Shirai, Hiroki; Yagi, Masanori; Ito, Kazuya; Fukushima, Wakaba; Hirota, Yoshio; Nsereko, Christopher; Okada, Takuya; Kanoi, Bernard N; Tetsutani, Kohhei; Arisue, Nobuko; Itagaki, Sawako; Tougan, Takahiro; Ishii, Ken J; Ueda, Shigeharu; Egwang, Thomas G; Horii, Toshihiro

    2013-01-01

    Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36) is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711). A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds) to 1-mL BK-SE36 (BKSE1.0) (n = 36) or saline (n = 20) and in Stage2 (6-20 year-olds) to BKSE1.0 (n = 33), 0.5-mL BK-SE36 (BKSE0.5) (n = 33), or saline (n = 18). Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42) were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96%) as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004) and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002) vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75). In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio for BKSE1.0 was 0.48 (95% CI, 0

  5. Assessing the Progress of New American Schools: A Status Report.

    ERIC Educational Resources Information Center

    Berends, Mark

    This report presents a data-collection plan for addressing these questions: (1) What were the New American Schools (NAS) like before they implemented their restructuring design efforts? (2) How have these evolved over time? (3) Are the critical components of the NAS designs being implemented across a wide array of schools? (4) Do the NAS designs…

  6. Polyomavirus BK non-coding control region rearrangements in health and disease.

    PubMed

    Sharma, Preety M; Gupta, Gaurav; Vats, Abhay; Shapiro, Ron; Randhawa, Parmjeet S

    2007-08-01

    BK virus is an increasingly recognized pathogen in transplanted patients. DNA sequencing of this virus shows considerable genomic variability. To understand the clinical significance of rearrangements in the non-coding control region (NCCR) of BK virus (BKV), we report a meta-analysis of 507 sequences, including 40 sequences generated in our own laboratory, for associations between rearrangements and disease, tissue tropism, geographic origin, and viral genotype. NCCR rearrangements were less frequent in (a) asymptomatic BKV viruria compared to patients viral nephropathy (1.7% vs. 22.5%), and (b) viral genotype 1 compared to other genotypes (2.4% vs. 11.2%). Rearrangements were commoner in malignancy (78.6%), and Norwegians (45.7%), and less common in East Indians (0%), and Japanese (4.3%). A surprising number of rearranged sequences were reported from mononuclear cells of healthy subjects, whereas most plasma sequences were archetypal. This difference could not be related to potential recombinase activity in lymphocytes, as consensus recombination signal sequences could not be found in the NCCR region. NCCR rearrangements are neither required nor a sufficient condition to produce clinical disease. BKV nephropathy and hemorrhagic cystitis are not associated with any unique NCCR configuration or nucleotide sequence.

  7. Type 2 diabetes elicits lower nitric oxide, bradykinin concentration and kallikrein activity together with higher DesArg(9)-BK and reduced post-exercise hypotension compared to non-diabetic condition.

    PubMed

    Simões, Herbert Gustavo; Asano, Ricardo Yukio; Sales, Marcelo Magalhães; Browne, Rodrigo Alberto Vieira; Arsa, Gisela; Motta-Santos, Daisy; Puga, Guilherme Morais; Lima, Laila Cândida de Jesus; Campbell, Carmen Sílvia Grubert; Franco, Octavio Luiz

    2013-01-01

    This study compared the plasma kallikrein activity (PKA), bradykinin concentration (BK), DesArg(9)-BK production, nitric oxide release (NO) and blood pressure (BP) response after moderate-intensity aerobic exercise performed by individuals with and without type 2 diabetes. Ten subjects with type 2 diabetes (T2D) and 10 without type 2 diabetes (ND) underwent three sessions: 1) maximal incremental test on cycle ergometer to determine lactate threshold (LT); 2) 20-min of constant-load exercise on cycle ergometer, at 90% LT and; 3) control session. BP and oxygen uptake were measured at rest and at 15, 30 and 45 min post-exercise. Venous blood samples were collected at 15 and 45 minutes of the recovery period for further analysis of PKA, BK and DesArg(9)-BK. Nitrite plus nitrate (NOx) was analyzed at 15 minutes post exercise. The ND group presented post-exercise hypotension (PEH) of systolic blood pressure and mean arterial pressure on the 90% LT session but T2D group did not. Plasma NOx increased ~24.4% for ND and ~13.8% for T2D group 15 min after the exercise session. Additionally, only ND individuals showed increases in PKA and BK in response to exercise and only T2D group showed increased DesArg(9)-BK production. It was concluded that T2D individuals presented lower PKA, BK and NOx release as well as higher DesArg(9)-BK production and reduced PEH in relation to ND participants after a single exercise session.

  8. Type 2 Diabetes Elicits Lower Nitric Oxide, Bradykinin Concentration and Kallikrein Activity Together with Higher DesArg9-BK and Reduced Post-Exercise Hypotension Compared to Non-Diabetic Condition

    PubMed Central

    Browne, Rodrigo Alberto Vieira; Arsa, Gisela; Motta-Santos, Daisy; Puga, Guilherme Morais; Lima, Laila Cândida de Jesus; Campbell, Carmen Sílvia Grubert; Franco, Octavio Luiz

    2013-01-01

    This study compared the plasma kallikrein activity (PKA), bradykinin concentration (BK), DesArg9-BK production, nitric oxide release (NO) and blood pressure (BP) response after moderate-intensity aerobic exercise performed by individuals with and without type 2 diabetes. Ten subjects with type 2 diabetes (T2D) and 10 without type 2 diabetes (ND) underwent three sessions: 1) maximal incremental test on cycle ergometer to determine lactate threshold (LT); 2) 20-min of constant-load exercise on cycle ergometer, at 90% LT and; 3) control session. BP and oxygen uptake were measured at rest and at 15, 30 and 45 min post-exercise. Venous blood samples were collected at 15 and 45 minutes of the recovery period for further analysis of PKA, BK and DesArg9-BK. Nitrite plus nitrate (NOx) was analyzed at 15 minutes post exercise. The ND group presented post-exercise hypotension (PEH) of systolic blood pressure and mean arterial pressure on the 90% LT session but T2D group did not. Plasma NOx increased ~24.4% for ND and ~13.8% for T2D group 15min after the exercise session. Additionally, only ND individuals showed increases in PKA and BK in response to exercise and only T2D group showed increased DesArg9-BK production. It was concluded that T2D individuals presented lower PKA, BK and NOx release as well as higher DesArg9-BK production and reduced PEH in relation to ND participants after a single exercise session. PMID:24265812

  9. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

    PubMed

    Gilis, L; Morisset, S; Billaud, G; Ducastelle-Leprêtre, S; Labussière-Wallet, H; Nicolini, F-E; Barraco, F; Detrait, M; Thomas, X; Tedone, N; Sobh, M; Chidiac, C; Ferry, T; Salles, G; Michallet, M; Ader, F

    2014-05-01

    BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \\[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

  10. SLO BK Potassium Channels Couple Gap Junctions to Inhibition of Calcium Signaling in Olfactory Neuron Diversification.

    PubMed

    Alqadah, Amel; Hsieh, Yi-Wen; Schumacher, Jennifer A; Wang, Xiaohong; Merrill, Sean A; Millington, Grethel; Bayne, Brittany; Jorgensen, Erik M; Chuang, Chiou-Fen

    2016-01-01

    The C. elegans AWC olfactory neuron pair communicates to specify asymmetric subtypes AWCOFF and AWCON in a stochastic manner. Intercellular communication between AWC and other neurons in a transient NSY-5 gap junction network antagonizes voltage-activated calcium channels, UNC-2 (CaV2) and EGL-19 (CaV1), in the AWCON cell, but how calcium signaling is downregulated by NSY-5 is only partly understood. Here, we show that voltage- and calcium-activated SLO BK potassium channels mediate gap junction signaling to inhibit calcium pathways for asymmetric AWC differentiation. Activation of vertebrate SLO-1 channels causes transient membrane hyperpolarization, which makes it an important negative feedback system for calcium entry through voltage-activated calcium channels. Consistent with the physiological roles of SLO-1, our genetic results suggest that slo-1 BK channels act downstream of NSY-5 gap junctions to inhibit calcium channel-mediated signaling in the specification of AWCON. We also show for the first time that slo-2 BK channels are important for AWC asymmetry and act redundantly with slo-1 to inhibit calcium signaling. In addition, nsy-5-dependent asymmetric expression of slo-1 and slo-2 in the AWCON neuron is necessary and sufficient for AWC asymmetry. SLO-1 and SLO-2 localize close to UNC-2 and EGL-19 in AWC, suggesting a role of possible functional coupling between SLO BK channels and voltage-activated calcium channels in AWC asymmetry. Furthermore, slo-1 and slo-2 regulate the localization of synaptic markers, UNC-2 and RAB-3, in AWC neurons to control AWC asymmetry. We also identify the requirement of bkip-1, which encodes a previously identified auxiliary subunit of SLO-1, for slo-1 and slo-2 function in AWC asymmetry. Together, these results provide an unprecedented molecular link between gap junctions and calcium pathways for terminal differentiation of olfactory neurons.

  11. 76 FR 21702 - Foreign-Trade Subzone 124B; Application for Expansion; North American Shipbuilding, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-18

    ...; Application for Expansion; North American Shipbuilding, LLC (Shipbuilding), Houma, LA An application has been... FTZ 124, on behalf of North American Shipbuilding, LLC (NAS), operator of Subzone 124B at NAS' shipbuilding facilities in Larose, Houma, and Port Fourchon, Louisiana, requesting authority to expand the...

  12. Novel mechanism of hydrogen sulfide-induced guinea pig urinary bladder smooth muscle contraction: role of BK channels and cholinergic neurotransmission

    PubMed Central

    Fernandes, Vítor S.; Xin, Wenkuan

    2015-01-01

    Hydrogen sulfide (H2S) is a key signaling molecule regulating important physiological processes, including smooth muscle function. However, the mechanisms underlying H2S-induced detrusor smooth muscle (DSM) contractions are not well understood. This study investigates the cellular and tissue mechanisms by which H2S regulates DSM contractility, excitatory neurotransmission, and large-conductance voltage- and Ca2+-activated K+ (BK) channels in freshly isolated guinea pig DSM. We used a multidisciplinary experimental approach including isometric DSM tension recordings, colorimetric ACh measurement, Ca2+ imaging, and patch-clamp electrophysiology. In isolated DSM strips, the novel slow release H2S donor, P-(4-methoxyphenyl)-p-4-morpholinylphosphinodithioic acid morpholine salt (GYY4137), significantly increased the spontaneous phasic and nerve-evoked DSM contractions. The blockade of neuronal voltage-gated Na+ channels or muscarinic ACh receptors with tetrodotoxin or atropine, respectively, reduced the stimulatory effect of GYY4137 on DSM contractility. GYY4137 increased ACh release from bladder nerves, which was inhibited upon blockade of L-type voltage-gated Ca2+ channels with nifedipine. Furthermore, GYY4137 increased the amplitude of the Ca2+ transients and basal Ca2+ levels in isolated DSM strips. GYY4137 reduced the DSM relaxation induced by the BK channel opener, NS11021. In freshly isolated DSM cells, GYY4137 decreased the amplitude and frequency of transient BK currents recorded in a perforated whole cell configuration and reduced the single BK channel open probability measured in excised inside-out patches. GYY4137 inhibited spontaneous transient hyperpolarizations and depolarized the DSM cell membrane potential. Our results reveal the novel findings that H2S increases spontaneous phasic and nerve-evoked DSM contractions by activating ACh release from bladder nerves in combination with a direct inhibition of DSM BK channels. PMID:25948731

  13. Vaccine for BK Polyomavirus-associated Infections in Transplant Recipients | NCI Technology Transfer Center | TTC

    Cancer.gov

    NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.

  14. BK virus: opportunity makes a pathogen.

    PubMed

    Hirsch, Hans H

    2005-08-01

    More than 70% of the general population worldwide has serological evidence of exposure to Polyomavirus hominis type 1, better known as BK virus (BKV). BKV infection typically occurs during childhood, without specific symptoms, followed by a state of nonreplicative infection in various tissues, with the urogenital tract as the principal site. Asymptomatic reactivation and low-level replication with viruria is observed in 5% of healthy individuals. Persistent high-level BKV replication is the hallmark of polyomavirus-associated nephropathy in renal transplantation and of hemorrhagic cystitis in bone marrow transplantation. Since these manifestations are rare in other types of immunocompromised patients, the presence of specific cofactors is postulated. The role of BKV in autoimmune disease and cancer is a controversial topic and is difficult to determine, because the pathology no longer depends on BKV replication. This article discusses current views of pathogenesis, diagnosis, and treatment.

  15. Unraveling hominin behavior at another anthropogenic site from Olduvai Gorge (Tanzania): new archaeological and taphonomic research at BK, Upper Bed II.

    PubMed

    Domínguez-Rodrigo, M; Mabulla, A; Bunn, H T; Barba, R; Diez-Martín, F; Egeland, C P; Espílez, E; Egeland, A; Yravedra, J; Sánchez, P

    2009-09-01

    New archaeological excavations and research at BK, Upper Bed II (Olduvai Gorge, Tanzania) have yielded a rich and unbiased collection of fossil bones. These new excavations show that BK is a stratified deposit formed in a riverine setting close to an alluvial plain. The present taphonomic study reveals the second-largest collection of hominin-modified bones from Olduvai, with abundant cut marks found on most of the anatomical areas preserved. Meat and marrow exploitation is reconstructed using the taphonomic signatures left on the bones by hominins. Highly cut-marked long limb shafts, especially those of upper limb bones, suggest that hominins at BK were actively engaged in acquiring small and middle-sized animals using strategies other than passive scavenging. The exploitation of large-sized game (Pelorovis) by Lower Pleistocene hominins, as suggested by previous researchers, is supported by the present study.

  16. Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients.

    PubMed

    Dalianis, Tina; Ljungman, Per

    2011-03-01

    BK virus (BKV)-associated hemorrhagic cystitis (HC), varying from mild hematuria with or without dysuria to life-threating bleeding and clots that may cause urinary obstruction and renal failure, causes significant morbidity and mortality in haematopoetic stem cell transplanted (HSCT) patients. Unfortunately, its development is difficult to predict since BK viruria is very common after HSCT and can be present in patients with and without HC. There is therefore the need to identify risk factors that may increase the risk of developing HC after HSCT. The viral load of BK-viruria, as well as BK viremia, has been monitored for this purpose. Moreover, having full myeoblative conditioning (MC) versus reduced intensity conditioning (RIC) prior to HSCT and an HLA-matched or -mismatched graft from an unrelated donor in contrast to an HLA-matched graft from a related donor have been studied as risk factors for HC. In addition, graft versus host disease has been examined, but has not been defined as a definite risk factor for HC. We conclude that the present evidence suggests that HSCT patients with BK viruria, receiving MC and an unrelated donor graft that is HLA-mismatched have an increased risk for developing HC in comparison to patients receiving RIC and an HLA-matched related donor graft.

  17. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

    PubMed

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  18. Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

    PubMed Central

    Chandran, Sindhu; Vagefi, Parsia A.

    2014-01-01

    Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

  19. BK Polyomavirus-Specific 9mer CD8 T Cell Responses Correlate With Clearance of BK Viremia in Kidney Transplant Recipients: First Report From the Swiss Transplant Cohort Study.

    PubMed

    Leboeuf, C; Wilk, S; Achermann, R; Binet, I; Golshayan, D; Hadaya, K; Hirzel, C; Hoffmann, M; Huynh-Do, U; Koller, M T; Manuel, O; Mueller, N J; Mueller, T F; Schaub, S; van Delden, C; Weissbach, F H; Hirsch, H H

    2017-10-01

    BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Because antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and peripheral blood mononuclear cells at the time of transplantation (T0) and at 6 mo (T6) and 12 mo (T12) after transplant from 28 viremic KT patients and 68 nonviremic controls matched for the transplantation period. BKPyV IgG seroprevalence was comparable between cases (89.3%) and controls (91.2%; p = 0.8635), but cases had lower antibody levels (p = 0.022) at T0. Antibody levels increased at T6 and T12 but were not correlated with viremia clearance. BKPyV-specific T cell responses to pools of overlapping 15mers (15mer peptide pool [15mP]) or immunodominant CD8 9mers (9mer peptide pool [9mP]) from the early viral gene region were not different between cases and controls at T0; however, clearance of viremia was associated with stronger 9mP responses at T6 (p = 0.042) and T12 (p = 0.048), whereas 15mP responses were not informative (T6 p = 0.359; T12 p = 0.856). BKPyV-specific T cells could be expanded in vitro from all patients after transplant, permitting identification of 78 immunodominant 9mer epitopes including 50 new ones across different HLA class I. Thus, 9mP-responses may be a novel marker of reconstituting CD8 T cell function that warrants further study as a complement of plasma BKPyV loads for guiding immunosuppression reduction. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. UAS-NAS Stakeholder Feedback Report

    NASA Technical Reports Server (NTRS)

    Randall, Debra; Murphy, Jim; Grindle, Laurie

    2016-01-01

    The need to fly UAS in the NAS to perform missions of vital importance to national security and defense, emergency management, science, and to enable commercial applications has been continually increasing over the past few years. To address this need, the NASA Aeronautics Research Mission Directorate (ARMD) Integrated Aviation Systems Program (IASP) formulated and funded the Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project (hereafter referred to as UAS-NAS Project) from 2011 to 2016. The UAS-NAS Project identified the following need statement: The UAS community needs routine access to the global airspace for all classes of UAS. The Project identified the following goal: To provide research findings to reduce technical barriers associated with integrating UAS into the NAS utilizing integrated system level tests in a relevant environment. This report provides a summary of the collaborations between the UAS-NAS Project and its primary stakeholders and how the Project applied and incorporated the feedback.

  1. BK virus has tropism for human salivary gland cells in vitro: Implications for transmission

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jeffers, Liesl K.; Madden, Vicki; Webster-Cyriaque, Jennifer, E-mail: jennifer@med.unc.ed

    Background: In this study, it was determined that BKV is shed in saliva and an in vitro model system was developed whereby BKV can productively infect both submandibular (HSG) and parotid (HSY) salivary gland cell lines. Results: BKV was detected in oral fluids using quantitative real-time PCR (QRTPCR). BKV infection was determined using quantitative RT-PCR, immunofluorescence and immunoblotting assays. The infectivity of BKV was inhibited by pre-incubation of the virus with gangliosides that saturated the major capsid protein, VP1, halting receptor mediated BKV entry into salivary gland cells. Examination of infected cultures by transmission electron microscopy revealed 45-50 nm BKmore » virions clearly visible within the cells. Subsequent to infection, encapsidated BK virus was detected in the supernatant. Conclusion: We thus demonstrated that BKV was detected in oral fluids and that BK infection and replication occur in vitro in salivary gland cells. These data collectively suggest the potential for BKV oral route of transmission and oral pathogenesis.« less

  2. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    PubMed

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Structural Determinants for Functional Coupling Between the β and α Subunits in the Ca2+-activated K+ (BK) Channel

    PubMed Central

    Orio, Patricio; Torres, Yolima; Rojas, Patricio; Carvacho, Ingrid; Garcia, Maria L.; Toro, Ligia; Valverde, Miguel A.; Latorre, Ramon

    2006-01-01

    High conductance, calcium- and voltage-activated potassium (BK, MaxiK) channels are widely expressed in mammals. In some tissues, the biophysical properties of BK channels are highly affected by coexpression of regulatory (β) subunits. The most remarkable effects of β1 and β2 subunits are an increase of the calcium sensitivity and the slow down of channel kinetics. However, the detailed characteristics of channels formed by α and β1 or β2 are dissimilar, the most remarkable difference being a reduction of the voltage sensitivity in the presence of β1 but not β2. Here we reveal the molecular regions in these β subunits that determine their differential functional coupling with the pore-forming α-subunit. We made chimeric constructs between β1 and β2 subunits, and BK channels formed by α and chimeric β subunits were expressed in Xenopus laevis oocytes. The electrophysiological characteristics of the resulting channels were determined using the patch clamp technique. Chimeric exchange of the different regions of the β1 and β2 subunits demonstrates that the NH3 and COOH termini are the most relevant regions in defining the behavior of either subunit. This strongly suggests that the intracellular domains are crucial for the fine tuning of the effects of these β subunits. Moreover, the intracellular domains of β1 are responsible for the reduction of the BK channel voltage dependence. This agrees with previous studies that suggested the intracellular regions of the α-subunit to be the target of the modulation by the β1-subunit. PMID:16446507

  4. Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK.

    PubMed

    Randhawa, P; Pastrana, D V; Zeng, G; Huang, Y; Shapiro, R; Sood, P; Puttarajappa, C; Berger, M; Hariharan, S; Buck, C B

    2015-04-01

    Neutralizing antibodies (NAbs) form the basis of immunotherapeutic strategies against many important human viral infections. Accordingly, we studied the prevalence, titer, genotype-specificity, and mechanism of action of anti-polyomavirus BK (BKV) NAbs in commercially available human immune globulin (IG) preparations designed for intravenous (IV) use. Pseudovirions (PsV) of genotypes Ia, Ib2, Ic, II, III, and IV were generated by co-transfecting a reporter plasmid encoding luciferase and expression plasmids containing synthetic codon-modified VP1, VP2, and VP3 capsid protein genes into 293TT cells. NAbs were measured using luminometry. All IG preparations neutralized all BKV genotypes, with mean EC50 titers as high as 254 899 for genotype Ia and 6,666 for genotype IV. Neutralizing titers against genotypes II and III were higher than expected, adding to growing evidence that infections with these genotypes are more common than currently appreciated. Batch to batch variation in different lots of IG was within the limits of experimental error. Antibody mediated virus neutralizing was dose dependent, modestly enhanced by complement, genotype-specific, and achieved without effect on viral aggregation, capsid morphology, elution, or host cell release. IG contains potent NAbs capable of neutralizing all major BKV genotypes. Clinical trials based on sound pharmacokinetic principles are needed to explore prophylactic and therapeutic applications of these anti-viral effects, until effective small molecule inhibitors of BKV replication can be developed. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. Characterization of an extracellular lipase by Pseudomonas koreensis BK-L07 isolated from soil.

    PubMed

    Anbu, Periasamy

    2014-01-01

    Screening using spirit blue agar revealed that strain BK-L07 had the highest lipase activity. Furthermore, the isolated strain was identified as Pseudomonas sp. based on morphological, physiological, biochemical, and molecular analyses. The 16S rRNA gene sequence of strain BK-L07 shared a high similarity with that of Pseudomonas koreensis (99%). The nutritional conditions and physicochemical properties were influenced by P. koreensis BK-L07. The maximum lipase production was obtained in tryptic soy broth medium at pH 8.0 and a temperature of 25°C after 36 hr of incubation. In addition, the lipase activity was determined using different carbon sources and lipase inducers. The lipase production was greatest when 1% maltose was used as the carbon source and olive oil was used as the lipase inducer. The lipase production was significantly increased approximately threefold in the optimized medium when compared with the original medium. Further, the lipase was purified by ammonium sulfate precipitation and gel filtration chromatography with a purification yield of 10.8%. The molecular mass of lipase was 45 kDa. The optimum temperature and pH were 40°C and 8.0, respectively. The enzyme was stable up to 50°C and at pH from 7 to 9. In addition, the enzyme activity was stimulated by MgSO4 and completely inhibited by ethylenediamine tetraacetic acid (EDTA), indicating the metalloenzyme type. The lipase activity was toward medium to long chain length of fatty acids (C10 to C18). Supplemental materials are available for this article. Go to the publisher's online edition of Preparative Biochemistry and Biotechnology to view the supplemental file.

  6. Hemorrhagic cystitis and possible neurologic disease from BK virus infection in a patient with AIDS.

    PubMed

    Kinnaird, A N; Anstead, G M

    2010-04-01

    BK virus (BKV)-associated hemorrhagic cystitis occurs in bone marrow transplant recipients but is rare among other immunosuppressed patients. We present a rare case of BKV-associated hemorrhagic cystitis in a 48-year-old man with AIDS and previously diagnosed progressive multifocal leukoencephalopathy.

  7. Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing

    PubMed Central

    Kurt, Simone; Sausbier, Matthias; Rüttiger, Lukas; Brandt, Niels; Moeller, Christoph K.; Kindler, Jennifer; Sausbier, Ulrike; Zimmermann, Ulrike; van Straaten, Harald; Neuhuber, Winfried; Engel, Jutta; Knipper, Marlies; Ruth, Peter; Schulze, Holger

    2012-01-01

    Large conductance, voltage- and Ca2+-activated K+ (BK) channels in inner hair cells (IHCs) of the cochlea are essential for hearing. However, germline deletion of BKα, the pore-forming subunit KCNMA1 of the BK channel, surprisingly did not affect hearing thresholds in the first postnatal weeks, even though altered IHC membrane time constants, decreased IHC receptor potential alternating current/direct current ratio, and impaired spike timing of auditory fibers were reported in these mice. To investigate the role of IHC BK channels for central auditory processing, we generated a conditional mouse model with hair cell-specific deletion of BKα from postnatal day 10 onward. This had an unexpected effect on temporal coding in the central auditory system: neuronal single and multiunit responses in the inferior colliculus showed higher excitability and greater precision of temporal coding that may be linked to the improved discrimination of temporally modulated sounds observed in behavioral training. The higher precision of temporal coding, however, was restricted to slower modulations of sound and reduced stimulus-driven activity. This suggests a diminished dynamic range of stimulus coding that is expected to impair signal detection in noise. Thus, BK channels in IHCs are crucial for central coding of the temporal fine structure of sound and for detection of signals in a noisy environment.—Kurt, S., Sausbier, M., Rüttiger, L., Brandt, N., Moeller, C. K., Kindler, J., Sausbier, U., Zimmermann, U., van Straaten, H., Neuhuber, W., Engel, J., Knipper, M., Ruth, P., Schulze, H. Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing. PMID:22691916

  8. Properties of optical breakdown in BK7 glass induced by an extended-cavity femtosecond laser oscillator.

    PubMed

    Do, Binh T; Phillips, Mark C; Miller, Paul A; Kimmel, Mark W; Britsch, Justin; Cho, Seong-Ho

    2009-02-16

    Using an extended-cavity femtosecond oscillator, we investigated optical breakdown in BK7 glass caused by the accumulated action of many laser pulses. By using a pump-probe experiment and collecting the transmitted pump along with the reflected pump and the broadband light generated by the optical breakdown, we measured the build-up time to optical breakdown as a function of the pulse energy, and we also observed the instability of the plasma due to the effect of defocusing and shielding created by the electron gas. The spectrum of the broadband light emitted by the optical breakdown and the origin of the material modification in BK7 glass was studied. We developed a simple model of electromagnetic wave propagation in plasma that is consistent with the observed behavior of the reflection, absorption, and transmission of the laser light.

  9. Bold Plans for School Restructuring: The New American Schools Designs.

    ERIC Educational Resources Information Center

    Stringfield, Sam, Ed.; Ross, Steven, M., Ed.; Smith, Lana, Ed.

    In 1991, the New American Schools (NAS) Development Corporation was founded by a group of business and foundation leaders interested in investing in innovative designs for school transformation. This book describes the first 3 years of development and evaluation of 9 NAS whole-school restructuring designs. The designs were very diverse, as were…

  10. Different behaviour of BK-virus infection in liver transplant recipients

    PubMed Central

    Umbro, Ilaria; Tinti, Francesca; Muiesan, Paolo; Mitterhofer, Anna Paola

    2016-01-01

    Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication. PMID:26819520

  11. BK virus associated pronounced hemorrhagic cystoureteritis after bone marrow transplantation.

    PubMed

    Haab, Alexander C; Keller, Isabelle S; Padevit, Christian; John, Hubert

    2015-10-01

    Ureteral stenosis due to reactivation of the BK virus (BKV) in a state of immunodeficiency is very rare. More common is the appearance of a hemorrhagic cystitis. This report not only shows bilateral ureteral stenosis after bone marrow transplantation, but also presents severe complications as chronic pelvic pain and impaired kidney function as well as irreparable damage to the whole urinary tract leading to nephroureterectomy, subtrigonal cystectomy and orthotopic ileal neobladder. Finally renal transplantation was required. To our knowledge this is the first case in the literature where such a severe course of BKV associated hemorrhagic cystoureteritis is described.

  12. BK-virus nephropathy and simultaneous C4d positive staining in renal allografts.

    PubMed

    Honsová, E; Lodererová, A; Viklický, O; Boucek, P

    2005-10-01

    The role of antibodies in rejection of transplanted kidneys was the subject of debate at the last two Banff meetings and in medical journals. Diffuse C4d positive staining of peritubular capillaries (PTCs) was recognized as a marker of antibody-mediated rejection and this morphological feature was included in the updated Banff schema. At the same time polyomavirus infection of the renal allografts has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. At the present time, BK-virus nephropathy (BKN) represents the most common viral disease affecting renal allografts. BKN was identified in 6 patients in 12 biopsies and 2 graft nephrectomy specimens of 1115 biopsies between September 2000 and December 2003. Definite virus identification was done by immunohistochemistry. The reason for graft nephrectomies was graft failure due to BKN in a recipient after kidney-pancreas transplantation with good function of his pancreas graft and the necessity of continuing immunosuppression. Detection of C4d deposits was performed by immunofluorescence or by immunohistochemistry. In graftectomy samples C4d detection was performed by immunohistochemistry and retrospectively in all cases of BKN. Focal C4d positive PTCs and BKN were found simultaneously in 9 of 12 needle biopsies and in both graft nephrectomy samples. Detection of C4d by immunohistochemistry disclosed focal C4d positive staining in kidney tissue but diffuse in the sites where BK-virus inclusions in tubular epithelial cells were found. The complement system is part of the host defense response and is crucial to our natural ability to ward off infection. In cases of BKN, virus likely gains access to the bloodstream through injured tubular walls and via PTCs. Vascular endothelium in the PTCs represents a potential target antigen for alloresponse, and simultaneously possibly represents an imprint of complement activation or complement production in the places

  13. American Indian Studies as an Academic Discipline

    ERIC Educational Resources Information Center

    Kidwell, Clara Sue

    2011-01-01

    When American Indian/Native American studies (AI/NAS) programs began to emerge in the halls of academia during the late 1960s and early 1970s, some who served as faculty and staff questioned whether they would be one-generation phenomena. Would the programs survive, would they continue to draw students, and could they make an impact on…

  14. The Role of Ca2+ and BK Channels of Locus Coeruleus (LC) Neurons as a Brake to the CO2 Chemosensitivity Response of Rats.

    PubMed

    Imber, Ann N; Patrone, Luis G A; Li, Ke-Yong; Gargaglioni, Luciane H; Putnam, Robert W

    2018-06-15

    The cellular mechanisms by which LC neurons respond to hypercapnia are usually attributed to an "accelerator" whereby hypercapnic acidosis causes an inhibition of K + channels or activation of Na + and Ca +2 channels to depolarize CO 2 -sensitive neurons. Nevertheless, it is still unknown if this "accelerator" mechanism could be controlled by a brake phenomenon. Whole-cell patch clamping, fluorescence imaging microscopy and plethysmography were used to study the chemosensitive response of the LC neurons. Hypercapnic acidosis activates L-type Ca 2+ channels and large conductance Ca-activated K + (BK) channels, which function as a "brake" on the chemosensitive response of LC neurons. Our findings indicate that both Ca 2+ and BK currents develop over the first 2 weeks of postnatal life in rat LC slices and that this brake pathway may cause the developmental decrease in the chemosensitive firing rate response of LC neurons to hypercapnic acidosis. Inhibition of this brake by paxilline (BK channel inhibitor) returns the magnitude of the chemosensitive firing rate response from LC neurons in rats older than P10 to high values similar to those in LC neurons from younger rats. Inhibition of BK channels in LC neurons by bilateral injections of paxilline into the LC results in a significant increase in the hypercapnic ventilatory response of adult rats. Our findings indicate that a BK channel-based braking system helps to determine the chemosensitive respiratory drive of LC neurons and contributes to the hypercapnic ventilatory response. Perhaps, abnormalities of this braking system could result in hypercapnia-induced respiratory disorders and panic responses. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Cytomegalovirus and polyomavirus BK posttransplant.

    PubMed

    Egli, Adrian; Binggeli, Simone; Bodaghi, Sohrab; Dumoulin, Alexis; Funk, Georg A; Khanna, Nina; Leuenberger, David; Gosert, Rainer; Hirsch, Hans H

    2007-09-01

    Virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. This complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. Due to the increasing potency of immunosuppressive regimens, graft rejections have decreased, but susceptibility to infections has increased. Therefore, cytomegalovirus (CMV) remains the most important viral pathogen posttransplant despite availability of effective antiviral drugs and validated strategies for prophylactic, preemptive and therapeutic intervention. CMV replication can affect almost every organ system, with frequent recurrences and increasing rates of antiviral resistance. Together with indirect long-term effects, CMV significantly reduces graft and patient survival after solid organ and hematopoietic stem cell transplantation. The human polyomavirus called BK virus (BKV), on the other hand, only recently surfaced as pathogen with organ tropism largely limited to the reno-urinary tract, manifesting as polyomavirus-associated nephropathy in kidney transplant and hemorrhagic cystitis in hematopoetic stem cell transplant patients. No licensed anti-polyoma viral drugs are available, and treatment relies mainly on improving immune functions to regain control over BKV replication. In this review, we discuss diagnostic and therapeutic aspects of CMV and BKV replication and disease posttransplantation.

  16. An EP2 Agonist Facilitates NMDA-Induced Outward Currents and Inhibits Dendritic Beading through Activation of BK Channels in Mouse Cortical Neurons

    PubMed Central

    Hayashi, Yoshinori; Morinaga, Saori; Liu, Xia; Zhang, Jing; Wu, Zhou; Yokoyama, Takeshi; Nakanishi, Hiroshi

    2016-01-01

    Prostaglandin E2 (PGE2), a major metabolite of arachidonic acid produced by cyclooxygenase pathways, exerts its bioactive responses by activating four E-prostanoid receptor subtypes, EP1, EP2, EP3, and EP4. PGE2 enables modulating N-methyl-D-aspartate (NMDA) receptor-mediated responses. However, the effect of E-prostanoid receptor agonists on large-conductance Ca2+-activated K+ (BK) channels, which are functionally coupled with NMDA receptors, remains unclear. Here, we showed that EP2 receptor-mediated signaling pathways increased NMDA-induced outward currents (I NMDA-OUT), which are associated with the BK channel activation. Patch-clamp recordings from the acutely dissociated mouse cortical neurons revealed that an EP2 receptor agonist activated I NMDA-OUT, whereas an EP3 receptor agonist reduced it. Agonists of EP1 or EP4 receptors showed no significant effects on I NMDA-OUT. A direct perfusion of 3,5′-cyclic adenosine monophosphate (cAMP) through the patch pipette facilitated I NMDA-OUT, which was abolished by the presence of protein kinase A (PKA) inhibitor. Furthermore, facilitation of I NMDA-OUT caused by an EP2 receptor agonist was significantly suppressed by PKA inhibitor. Finally, the activation of BK channels through EP2 receptors facilitated the recovery phase of NMDA-induced dendritic beading in the primary cultured cortical neurons. These results suggest that a direct activation of BK channels by EP2 receptor-mediated signaling pathways plays neuroprotective roles in cortical neurons. PMID:27298516

  17. Interactions of divalent cations with calcium binding sites of BK channels reveal independent motions within the gating ring.

    PubMed

    Miranda, Pablo; Giraldez, Teresa; Holmgren, Miguel

    2016-12-06

    Large-conductance voltage- and calcium-activated K + (BK) channels are key physiological players in muscle, nerve, and endocrine function by integrating intracellular Ca 2+ and membrane voltage signals. The open probability of BK channels is regulated by the intracellular concentration of divalent cations sensed by a large structure in the BK channel called the "gating ring," which is formed by four tandems of regulator of conductance for K + (RCK1 and RCK2) domains. In contrast to Ca 2+ that binds to both RCK domains, Mg 2+ , Cd 2+ , or Ba 2+ interact preferentially with either one or the other. Interaction of cations with their binding sites causes molecular rearrangements of the gating ring, but how these motions occur remains elusive. We have assessed the separate contributions of each RCK domain to the cation-induced gating-ring structural rearrangements, using patch-clamp fluorometry. Here we show that Mg 2+ and Ba 2+ selectively induce structural movement of the RCK2 domain, whereas Cd 2+ causes motions of RCK1, in all cases substantially smaller than those elicited by Ca 2+ By combining divalent species interacting with unique sites, we demonstrate that RCK1 and RCK2 domains move independently when their specific binding sites are occupied. Moreover, binding of chemically distinct cations to both RCK domains is additive, emulating the effect of fully occupied Ca 2+ binding sites.

  18. BK Channel-Mediated Relaxation of Urinary Bladder Smooth Muscle: A Novel Paradigm for Phosphodiesterase Type 4 Regulation of Bladder Function

    PubMed Central

    Xin, Wenkuan; Li, Ning; Cheng, Qiuping

    2014-01-01

    Elevation of intracellular cAMP and activation of protein kinase A (PKA) lead to activation of large conductance voltage- and Ca2+-activated K+ (BK) channels, thus attenuation of detrusor smooth muscle (DSM) contractility. In this study, we investigated the mechanism by which pharmacological inhibition of cAMP-specific phosphodiesterase 4 (PDE4) with rolipram or Ro-20-1724 (C15H22N2O3) suppresses guinea pig DSM excitability and contractility. We used high-speed line-scanning confocal microscopy, ratiometric fluorescence Ca2+ imaging, and perforated whole-cell patch-clamp techniques on freshly isolated DSM cells, along with isometric tension recordings of DSM isolated strips. Rolipram caused an increase in the frequency of Ca2+ sparks and the spontaneous transient BK currents (TBKCs), hyperpolarized the cell membrane potential (MP), and decreased the intracellular Ca2+ levels. Blocking BK channels with paxilline reversed the hyperpolarizing effect of rolipram and depolarized the MP back to the control levels. In the presence of H-89 [N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide dihydrochloride], a PKA inhibitor, rolipram did not cause MP hyperpolarization. Rolipram or Ro-20-1724 reduced DSM spontaneous and carbachol-induced phasic contraction amplitude, muscle force, duration, and frequency, and electrical field stimulation-induced contraction amplitude, muscle force, and tone. Paxilline recovered DSM contractility, which was suppressed by pretreatment with PDE4 inhibitors. Rolipram had reduced inhibitory effects on DSM contractility in DSM strips pretreated with paxilline. This study revealed a novel cellular mechanism whereby pharmacological inhibition of PDE4 leads to suppression of guinea pig DSM contractility by increasing the frequency of Ca2+ sparks and the functionally coupled TBKCs, consequently hyperpolarizing DSM cell MP. Collectively, this decreases the global intracellular Ca2+ levels and DSM contractility in a BK channel

  19. Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA.

    PubMed

    Hoshi, Toshinori; Tian, Yutao; Xu, Rong; Heinemann, Stefan H; Hou, Shangwei

    2013-03-19

    Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.

  20. Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type

    PubMed Central

    de Padua Silva, Leandro; Patah, Poliana A.; Saliba, Rima M.; Szewczyk, Nicholas A.; Gilman, Lisa; Neumann, Joyce; Han, Xiang-Yang; Tarrand, Jeffrey; Ribeiro, Rachel; Gulbis, Alison; Shpall, Elizabeth J.; Jones, Roy; Popat, Uday; Walker, Julia A.; Petropoulos, Demetrios; Chiattone, Alexandre; Stewart, John; El-Zimaity, Maha; Anderlini, Paolo; Giralt, Sergio; Champlin, Richard E; de Lima, Marcos

    2010-01-01

    Background Hemorrhagic cystitis is a common cause of morbidity after allogeneic stem cell transplantation, frequently associated with BK virus infection. We hypothesized that patients with positive BK viruria before unrelated or mismatched related donor allogeneic hematopoietic stem cell transplantation have a higher incidence of hemorrhagic cystitis. Design and Methods To test this hypothesis, we prospectively studied 209 patients (median age 49 years, range 19–71) with hematologic malignancies who received bone marrow (n=78), peripheral blood (n=108) or umbilical cord blood (n=23) allogeneic hematopoietic stem cell transplantation after myeloablative (n=110) or reduced intensity conditioning (n=99). Donors were unrelated (n=201) or haploidentical related (n=8). Results Twenty-five patients developed hemorrhagic cystitis. Pre-transplant BK viruria detected by quantitative PCR was positive in 96 patients. The one-year cumulative incidence of hemorrhagic cystitis was 16% in the PCR-positive group versus 9% in the PCR-negative group (P=0.1). The use of umbilical cord blood or a haploidentical donor was the only significant predictor of the incidence of hemorrhagic cystitis on univariate analysis. There was also a trend for a higher incidence after myeloablative conditioning. Multivariate analysis showed that patients who had a positive PCR pre-transplant and received haploidentical or cord blood grafts with myeloablative conditioning had a significantly higher risk of developing hemorrhagic cystitis (58%) than all other recipients (7%, P<0.001). Conclusions Hemorrhagic cystitis is the result of a complex interaction of donor type, preparative regimen intensity, and BK viruria. PMID:20410183

  1. Inhibitory action of ICI-182,780, an estrogen receptor antagonist, on BK(Ca) channel activity in cultured endothelial cells of human coronary artery.

    PubMed

    Liu, Yen-Chin; Lo, Yi-Ching; Huang, Chin-Wei; Wu, Sheng-Nan

    2003-11-15

    ICI-182,780 is known to be a selective inhibitor of the intracellular estrogen receptors. The effect of ICI-182,780 on ion currents was studied in cultured endothelial cells of human coronary artery. In whole-cell current recordings, ICI-182,780 reversibly decreased the amplitude of K(+) outward currents. The decrease in outward current caused by ICI-182,780 could be counteracted by further application of magnolol or nordihydroguaiaretic acid, yet not by 17beta-estradiol. Under current-clamp condition, ICI-182,780 (3microM) depolarized the membrane potentials of the cells, and magnolol (10 microM) or nordihydroguaiaretic acid (10 microM) reversed ICI-182,780-induced depolarization. In inside-out patches, ICI-182,780 added to the bath did not alter single-channel conductance of large-conductance Ca(2+)-activated K(+) channels (BK(Ca) channels), but decreased their open probability. ICI-182,780 reduced channel activity in a concentration-dependent manner with an IC(50) value of 3 microM. After BK(Ca) channel activity was suppressed by 2-methoxyestradiol (3 microM), subsequent application of ICI-182,780 (3 microM) did not further reduce the channel activity. The application of ICI-182,780 shifted the activation curve of BK(Ca) channels to positive potentials. Its decrease in the open probability primarily involved a reduction in channel open duration. ICI-182,780 also suppressed the proliferation of these endothelial cells with an IC(50) value of 2 microM. However, in coronary smooth muscle cells, a bell-shaped concentration-response curve for the ICI-182,780 effect on BK(Ca) channel activity was observed. This study provides evidence that ICI-182,780 can inhibit BK(Ca) channels in vascular endothelial cells in a mechanism unlikely to be linked to its anti-estrogen activity. The inhibitory effects on these channels may partly contribute to the underlying mechanisms by which ICI-182,780 affects endothelial function.

  2. Clinical and Molecular Characteristics and Burden of Kidney Cancer Among Hispanics and Native Americans: Steps Toward Precision Medicine.

    PubMed

    Batai, Ken; Bergersen, Andrew; Price, Elinora; Hynes, Kieran; Ellis, Nathan A; Lee, Benjamin R

    2018-06-01

    Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary significantly in terms of cancer incidence and mortality rates across geographic regions. This review reports that kidney and renal pelvis cancers are unevenly affecting HAs and NAs compared to European Americans of non-Hispanic origin, and that currently there is significant need for improved data and reporting to be able to advance toward genomic-based precision medicine for the assessment of such cancers in these medically underserved populations. More specifically, in states along the US-Mexico border, HAs and NAs have higher kidney cancer incidence rates as well as a higher prevalence of kidney cancer risk factors, including obesity and chronic kidney disease. They are also more likely to receive suboptimal care compared to European Americans. Furthermore, they are underrepresented in epidemiologic, clinical, and molecular genomic studies of kidney cancer. Therefore, we maintain that progress in precision medicine for kidney cancer care requires an understanding of various factors among HAs and NAs, including the real kidney cancer burden, variations in clinical care, issues related to access to care, and specific clinical and molecular characteristics. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation.

    PubMed

    Mori, Yasuo; Miyamoto, Toshihiro; Kato, Koji; Kamezaki, Kenjiro; Kuriyama, Takuro; Oku, Seido; Takenaka, Katsuto; Iwasaki, Hiromi; Harada, Naoki; Shiratsuchi, Motoaki; Abe, Yasunobu; Nagafuji, Koji; Teshima, Takanori; Akashi, Koichi

    2012-03-01

    Virus-associated hemorrhagic cystitis (HC) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although numerous studies have attempted to identify factors that predispose patients to viral HC, its causes remain controversial. We analyzed retrospectively the results of 266 allogeneic HSCTs to identify factors associated with HC. Of this group, 42 patients (15.8%) were diagnosed with viral HC, because of either adenovirus (ADV; n = 26; 9.8%) or BK virus (BKV; n = 16; 6.0%). ADV-HC was frequently associated with T cell purging, and was less common in patients with acute graft-versus-host-disease (GVHD). Conversely, BKV-HC was more frequently observed in patients with excessive immune reactions such as GVHD, preengraftment immune reaction, and hemophagocytic syndrome. These observations indicate that ADV- and BKV-HC may differ significantly in their risk factors and pathogenesis. Profound immune deficiency is more likely to be associated with ADV-HC, whereas immune hyperactivity might play a key role in BKV-HC. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Choreito formula for BK virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Kawashima, Nozomu; Ito, Yoshinori; Sekiya, Yuko; Narita, Atsushi; Okuno, Yusuke; Muramatsu, Hideki; Irie, Masahiro; Hama, Asahito; Takahashi, Yoshiyuki; Kojima, Seiji

    2015-02-01

    Therapy for BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is limited after hematopoietic stem cell transplantation (HSCT). We examined whether choreito, a formula from Japanese traditional Kampo medicine, is effective for treating BKV-HC. Among children who underwent allogeneic HSCT between October 2006 and March 2014, 14 were diagnosed with BKV-HC (median, 36 days; range, 14 to 330 days) after HSCT, and 6 consecutive children received pharmaceutical-grade choreito extract granules. The hematuria grade before treatment was significantly higher in the choreito group than in the nonchoreito group (P = .018). The duration from therapy to complete resolution was significantly shorter in the choreito group (median, 9 days; range, 4 to 17 days) than in the nonchoreito group (median, 17 days; range, 15 to 66 days; P = .037). In 11 children with macroscopic hematuria, the duration from treatment to resolution of macroscopic hematuria was significantly shorter in the choreito group than in the nonchoreito group (median, 2 days versus 11 days; P = .0043). The BKV load in urine was significantly decreased 1 month after choreito administration. No adverse effects related to choreito administration were observed. Choreito may be a safe and considerably promising therapy for the hemostasis of BKV-HC after HSCT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Behavioural abnormalities of the hyposulphataemic Nas1 knock-out mouse.

    PubMed

    Dawson, Paul Anthony; Steane, Sarah Elizabeth; Markovich, Daniel

    2004-10-05

    We recently generated a sodium sulphate cotransporter knock-out mouse (Nas1-/-) which has increased urinary sulphate excretion and hyposulphataemia. To examine the consequences of disturbed sulphate homeostasis in the modulation of mouse behavioural characteristics, Nas1-/- mice were compared with Nas1+/- and Nas1+/+ littermates in a series of behavioural tests. The Nas1-/- mice displayed significantly (P < 0.001) decreased marble burying behaviour (4.33 +/- 0.82 buried) when compared to Nas1+/+ (7.86 +/- 0.44) and Nas1+/- (8.40 +/- 0.37) animals, suggesting that Nas1-/- mice may have decreased object-induced anxiety. The Nas1-/- mice also displayed decreased locomotor activity by moving less distance (1.53 +/- 0.27 m, P < 0.05) in an open-field test when compared to Nas1+/+ (2.31 +/- 0.24 m) and Nas1+/- (2.15 +/- 0.19 m) mice. The three genotypes displayed similar spatiotemporal and ethological behaviours in the elevated-plus maze and open-field test, with the exception of a decreased defecation frequency by the Nas1-/- mice (40% reduction, P < 0.01). There were no significant differences between Nas1-/- and Nas1+/+ mice in a rotarod performance test of motor coordination and in the forced swim test assessing (anti-)depressant-like behaviours. This is the first study to demonstrate behavioural abnormalities in the hyposulphataemic Nas1-/- mice.

  6. Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels

    PubMed Central

    Hermann, Anton; Sitdikova, Guzel F.; Weiger, Thomas M.

    2015-01-01

    All cells contain ion channels in their outer (plasma) and inner (organelle) membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells), alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK) channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences. PMID:26287261

  7. Conversion from tacrolimus-mycophenolate mofetil to tacrolimus-mTOR immunosuppression after kidney-pancreas transplantation reduces the incidence of both BK and CMV viremia.

    PubMed

    Knight, Richard J; Graviss, Edward A; Nguyen, Duc T; Kuten, Samantha A; Patel, Samir J; Gaber, Lillian; Gaber, A Osama

    2018-04-19

    We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Detection of BK virus and adenovirus in the urine from children after allogeneic stem cell transplantation.

    PubMed

    Hatakeyama, Naoki; Suzuki, Nobuhiro; Yamamoto, Masaki; Kuroiwa, Yuki; Hori, Tsukasa; Mizue, Nobuo; Tsutsumi, Hiroyuki

    2006-01-01

    The development of hemorrhagic cystitis (HC) and urinary excretion of polyoma BK virus (BKV) and adenovirus (ADV) was investigated by polymerase chain reaction in 20 children undergoing allogeneic stem cell transplantation. Five children developed HC, and all of them excreted BKV; however, only 1 excreted ADV, suggesting that BKV is more significant cause of HC than ADV in children undergoing stem cell transplantation.

  9. Numerical Aerodynamic Simulation (NAS)

    NASA Technical Reports Server (NTRS)

    Peterson, V. L.; Ballhaus, W. F., Jr.; Bailey, F. R.

    1983-01-01

    The history of the Numerical Aerodynamic Simulation Program, which is designed to provide a leading-edge capability to computational aerodynamicists, is traced back to its origin in 1975. Factors motivating its development and examples of solutions to successively refined forms of the governing equations are presented. The NAS Processing System Network and each of its eight subsystems are described in terms of function and initial performance goals. A proposed usage allocation policy is discussed and some initial problems being readied for solution on the NAS system are identified.

  10. NAS-current status and future plans

    NASA Technical Reports Server (NTRS)

    Bailey, F. R.

    1987-01-01

    The Numerical Aerodynamic Simulation (NAS) has met its first major milestone, the NAS Processing System Network (NPSN) Initial Operating Configuration (IOC). The program has met its goal of providing a national supercomputer facility capable of greatly enhancing the Nation's research and development efforts. Furthermore, the program is fulfilling its pathfinder role by defining and implementing a paradigm for supercomputing system environments. The IOC is only the begining and the NAS Program will aggressively continue to develop and implement emerging supercomputer, communications, storage, and software technologies to strengthen computations as a critical element in supporting the Nation's leadership role in aeronautics.

  11. Abnormal differentiation, hyperplasia and embryonic/perinatal lethality in BK5-T/t transgenic mice

    PubMed Central

    Chen, Xin; Schneider-Broussard, Robin; Hollowell, Debra; McArthur, Mark; Jeter, Collene R.; Benavides, Fernando; DiGiovanni, John; Tang, Dean G.

    2009-01-01

    The cell-of-origin has a great impact on the types of tumors that develop and the stem/progenitor cells have long been considered main targets of malignant transformation. The SV40 large T and small t antigens (T/t), have been targeted to multiple differentiated cellular compartments in transgenic mice. In most of these studies, transgenic animals develop tumors without apparent defects in animal development. In this study, we used the bovine keratin 5 (BK5) promoter to target the T/t antigens to stem/progenitor cell-containing cytokeratin 5 (CK5) cellular compartment. A transgene construct, BK5-T/t, was made and microinjected into the male pronucleus of FVB/N mouse oocytes. After implanting ∼1700 embryos, only 7 transgenics were obtained, including 4 embryos (E9.5, E13, E15, and E20) and 3 postnatal animals, which died at P1, P2, and P18, respectively. Immunohistological analysis revealed aberrant differentiation and prominent hyperplasia in several transgenic CK5 tissues, especially the upper digestive organs (tongue, oral mucosa, esophagus, and forestomach) and epidermis, the latter of which also showed focal dysplasia. Altogether, these results indicate that constitutive expression of the T/t antigens in CK5 cellular compartment results in abnormal epithelial differentiation and leads to embryonic/perinatal animal lethality. PMID:19272531

  12. Experimental Investigation on Cutting Characteristics in Nanometric Plunge-Cutting of BK7 and Fused Silica Glasses

    PubMed Central

    An, Qinglong; Ming, Weiwei; Chen, Ming

    2015-01-01

    Ductile cutting are most widely used in fabricating high-quality optical glass components to achieve crack-free surfaces. For ultra-precision machining of brittle glass materials, critical undeformed chip thickness (CUCT) commonly plays a pivotal role in determining the transition point from ductile cutting to brittle cutting. In this research, cutting characteristics in nanometric cutting of BK7 and fused silica glasses, including machined surface morphology, surface roughness, cutting force and specific cutting energy, were investigated with nanometric plunge-cutting experiments. The same cutting speed of 300 mm/min was used in the experiments with single-crystal diamond tool. CUCT was determined according to the mentioned cutting characteristics. The results revealed that 320 nm was found as the CUCT in BK7 cutting and 50 nm was determined as the size effect of undeformed chip thickness. A high-quality machined surface could be obtained with the undeformed chip thickness between 50 and 320 nm at ductile cutting stage. Moreover, no CUCT was identified in fused silica cutting with the current cutting conditions, and brittle-fracture mechanism was confirmed as the predominant chip-separation mode throughout the nanometric cutting operation. PMID:28788010

  13. Experimental Investigation on Cutting Characteristics in Nanometric Plunge-Cutting of BK7 and Fused Silica Glasses.

    PubMed

    An, Qinglong; Ming, Weiwei; Chen, Ming

    2015-03-27

    Ductile cutting are most widely used in fabricating high-quality optical glass components to achieve crack-free surfaces. For ultra-precision machining of brittle glass materials, critical undeformed chip thickness (CUCT) commonly plays a pivotal role in determining the transition point from ductile cutting to brittle cutting. In this research, cutting characteristics in nanometric cutting of BK7 and fused silica glasses, including machined surface morphology, surface roughness, cutting force and specific cutting energy, were investigated with nanometric plunge-cutting experiments. The same cutting speed of 300 mm/min was used in the experiments with single-crystal diamond tool. CUCT was determined according to the mentioned cutting characteristics. The results revealed that 320 nm was found as the CUCT in BK7 cutting and 50 nm was determined as the size effect of undeformed chip thickness. A high-quality machined surface could be obtained with the undeformed chip thickness between 50 and 320 nm at ductile cutting stage. Moreover, no CUCT was identified in fused silica cutting with the current cutting conditions, and brittle-fracture mechanism was confirmed as the predominant chip-separation mode throughout the nanometric cutting operation.

  14. Symptomatic BK Virus Infection Is Associated with Kidney Function Decline and Poor Overall Survival in Allogeneic Hematopoietic Stem Cell Recipients

    PubMed Central

    Abudayyeh, Ala; Hamdi, Amir; Lin, Heather; Abdelrahim, Maen; Rondon, Gabriela; Andersson, Borje S; Afrough, Aimaz; Martinez, Charles S; Tarrand, Jeffrey J; Kontoyiannis, Dimitrios P.; Marin, David; Gaber, A. Osama; Salahudeen, Abdulla; Oran, Betul; Chemaly, Roy F.; Olson, Amanda; Jones, Roy; Popat, Uday; Champlin, Richard E; Shpall, Elizabeth J.; Winkelmayer, Wolfgang C.; Rezvani, Katayoun

    2017-01-01

    Nephropathy due to BK virus infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation. We hypothesized that BKV infection was a marker of Kidney Function Decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic hematopoietic stem cell transplantation at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the CKD-EPI equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline and Fine and Gray’s method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic hematopoietic stem cell transplantation, BK viruria was detected in 25% (n=629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease, chronic graft versus host disease, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (P <0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. Post-allogeneic hematopoietic stem cell transplantation, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT. PMID:26608093

  15. Dynamics of Db isotopes formed in reactions induced by 238U, 248Cm, and 249Bk across the Coulomb barrier

    NASA Astrophysics Data System (ADS)

    Kaur, Gurjit; Sandhu, Kirandeep; Kaur, Amandeep; Sharma, Manoj K.

    2018-05-01

    The dynamical cluster decay model is employed to investigate the decay of *265Db and *267Db nuclei, formed in the 27Al+238U , 18O+249Bk , and 19F+248Cm hot fusion reactions at energies around the Coulomb barrier. First, the fission dynamics of the 27Al+238U reaction is explored by investigating the fragmentation and preformation yield of the reaction. The symmetric mass distribution of the fission fragments is observed for *265Db nucleus, when static β2 i deformations are used within hot optimum orientation approach. However, the mass split gets broaden for the use of β2 i-dynamical hot configuration of the fragments and becomes clearly asymmetric for the cold-static-deformed approach. Within the application of cold orientations of fragments, a new fission channel is observed at mass asymmetry η =0.29 . In addition to 238U-induced reaction, the work is carried out to address the fission and neutron evaporation cross sections of *267Db nucleus formed via 19F+248Cm and 18O+249Bk reactions, besides a comprehensive analysis of fusion and capture processes. Higher fusion cross sections and compound nucleus formation probabilities (PCN) are obtained for the 18O+249Bk reaction, as larger mass asymmetry in the entrance channel leads to reduced Coulomb factor. Finally, the role of sticking (IS) and nonsticking (INS) moments of inertia is analyzed for the 4 n and 5 n channels of *267Db nuclear system.

  16. A combination of genistein and magnesium enhances the vasodilatory effect via an eNOS pathway and BK(Ca) current amplification.

    PubMed

    Sun, Lina; Hou, Yunlong; Zhao, Tingting; Zhou, Shanshan; Wang, Xiaoran; Zhang, Liming; Yu, Guichun

    2015-04-01

    The phytoestrogen genistein (GST) and magnesium have been independently shown to regulate vascular tone; however, their individual vasodilatory effects are limited. The aim of this study was to examine the combined effects of GST plus magnesium on vascular tone in mesenteric arteries. The effects of pretreatment with GST (0-200 μmol/L), MgCl2 (0-4.8 mmol/L) and GST plus MgCl2 on 10 μmol/L phenylephrine (PE) precontracted mesenteric arteries in rats were assessed by measuring isometric force. BK(Ca) currents were detected by the patch clamp method. GST caused concentration- and partial endothelium-dependent relaxation. Magnesium resulted in dual adjustment of vascular tone. Magnesium-free solution eliminated the vasodilatation of GST in both endothelium-intact and denuded rings. GST (50 μmol/L) plus magnesium (4.8 mmol/L) caused stronger relaxation in both endothelium-intact and denuded rings. Pretreatment with the nitric oxide synthase (NOS) inhibitor L-N-nitroarginine methyl ester (L-NAME, 100 μmol/L) significantly inhibited the effects of GST, high magnesium, and the combination of GST and magnesium. BK(Ca) currents were amplified to a greater extent when GST (50 μmol/L) was combined with 4.8 versus 1.2 mmol/L Mg(2+). Our data suggest that GST plus magnesium provides enhanced vasodilatory effects in rat mesenteric arteries compared with that observed when either is used separately, which was related to an eNOS pathway and BK(Ca) current amplification.

  17. Cryogenic Temperature-dependent Refractive Index Measurements of N-BK7, BaLKN3, and SF15 for NOTES PDI

    NASA Technical Reports Server (NTRS)

    Frey, Bradley J.; Leviton, Douglas F.; Madison, Timothy J.

    2007-01-01

    In order to enable high quality lens designs using N-BK7, BaLKN3, and SF15 at cryogenic temperatures, we have measured the absolute refractive index of prisms of these three materials using the Cryogenic, High-Accuracy Refraction Measuring System (CHARMS) at NASA's Goddard Space Flight Center, as a function of both wavelength and temperature. For N-BK7, we report absolute refractive index and thermo-optic coefficient (dn/dT) at temperatures ranging from 50 to 300 K at wavelengths from 0.45 to 2.7 micrometers; for BaLKN3 we cover temperatures ranging from 40 to 300 K and wavelengths from 0.4 to 2.6 micrometers; for SF15 we cover temperatures ranging from 50 to 300 K and wavelengths from 0.45 to 2.6 micrometers. We compare our measurements with others in the literature and provide temperature-dependent Sellmeier coefficients based on our data to allow accurate interpolation of index to other wavelengths and temperatures. While we generally find good agreement (plus or minus 2 x 10(exp -4) for N-BK7, less than 1 x 10(exp -4) for the other materials) at room temperature between our measured values and those provided by the vendor, there is some variation between the datasheets provided with the prisms we measured and the catalog values published by the vendor. This underlines the importance of measuring the absolute refractive index of the material when precise knowledge of the refractive index is required.

  18. Comparative evaluation of laboratory developed real-time PCR assays and RealStar(®) BKV PCR Kit for quantitative detection of BK polyomavirus.

    PubMed

    Hasan, Mohammad R; Tan, Rusung; Al-Rawahi, Ghada; Thomas, Eva; Tilley, Peter

    2016-08-01

    Quantitative, viral load monitoring for BK virus (BKV) by real-time PCR is an important tool in the management of polyomavirus associated nephropathy in renal transplant patients. However, variability in PCR results has been reported because of polymorphisms in viral genes among different subtypes of BKV, and lack of standardization of the PCR assays among different laboratories. In this study we have compared the performance of several laboratory developed PCR assays that target highly conserved regions of BKV genome with a commercially available, RealStar(®) BKV PCR Kit. Three real-time PCR assays (i) VP1 assay: selected from the literature that targets the major capsid protein (VP1) gene (ii) VP1MOD assay: VP1 assay with a modified probe, and (iii) BKLTA assay: newly designed assay that targets the large T antigen gene were assessed in parallel, using controls and clinical specimens that were previously tested using RealStar(®) BKV PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany). Nucleic acid from all samples were extracted using the QIA symphony virus/bacteria kit on an automated DNA extraction platform QIA symphony SP (Qiagen). Primer and probe concentration, and reaction conditions for laboratory developed assays were optimized and the limit of detection of different assays was determined. Positive control for laboratory developed BK assays was prepared through construction of a plasmid carrying respective amplicon sequences. The 95% detection limit of VP1, VP1MOD and BKLTA assays were 1.8×10(2), 3×10(3) and 3.5×10(2) genomic copies/ml, respectively, as determined by Probit regression analysis of data obtained by testing a dilution series of a titered patient specimen, using RealStar(®) BKV PCR Kit. The inter-assay and intra-assay, coefficient of variations of these assays using calibrated, plasmid standards were <1%. All assays, including the RealStar(®) BKV PCR assay, were highly specific when tested against a panel of external proficiency

  19. BK Polyomavirus: Clinical Aspects, Immune Regulation, and Emerging Therapies

    PubMed Central

    Ambalathingal, George R.; Francis, Ross S.; Smyth, Mark J.; Smith, Corey

    2017-01-01

    SUMMARY BK polyomavirus (BKV) causes frequent infections during childhood and establishes persistent infections within renal tubular cells and the uroepithelium, with minimal clinical implications. However, reactivation of BKV in immunocompromised individuals following renal or hematopoietic stem cell transplantation may cause serious complications, including BKV-associated nephropathy (BKVAN), ureteric stenosis, or hemorrhagic cystitis. Implementation of more potent immunosuppression and increased posttransplant surveillance has resulted in a higher incidence of BKVAN. Antiviral immunity plays a crucial role in controlling BKV replication, and our increasing knowledge about host-virus interactions has led to the development of improved diagnostic tools and clinical management strategies. Currently, there are no effective antiviral agents for BKV infection, and the mainstay of managing reactivation is reduction of immunosuppression. Development of immune-based therapies to combat BKV may provide new and exciting opportunities for the successful treatment of BKV-associated complications. PMID:28298471

  20. In vivo synthesis of selenium nanoparticles by Halococcus salifodinae BK18 and their anti-proliferative properties against HeLa cell line.

    PubMed

    Srivastava, Pallavee; Braganca, Judith M; Kowshik, Meenal

    2014-01-01

    Nanoparticles synthesis by bacteria and yeasts has been widely reported, however, synthesis using halophilic archaea is still in a nascent stage. This study aimed at the intracellular synthesis of selenium nanoparticles (SeNPs) by the haloarchaeon Halococcus salifodinae BK18 when grown in the presence of sodium selenite. Crystallographic characterization of SeNPs by X-ray diffraction, Selected area electron diffraction, and transmission electron microscopy exhibited rod shaped nanoparticles with hexagonal crystal lattice, a crystallite domain size of 28 nm and an aspect ratio (length:diameter) of 13:1. Energy disruptive analysis of X-ray analysis confirmed the presence of selenium in the nano-preparation. The nitrate reductase enzyme assay and the inhibitor studies indicated the involvement of NADH-dependent nitrate reductase in SeNPs synthesis and metal tolerance. The SeNPs exhibited good anti-proliferative properties against HeLa cell lines while being non-cytotoxic to normal cell line model HaCat, suggesting the use of these SeNPs as cancer chemotherapeutic agent. This is the first study on selenium nanoparticles synthesis by haloarchaea. © 2014 American Institute of Chemical Engineers.

  1. BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

    PubMed

    Lopes da Silva, R; Ferreira, I; Teixeira, G; Cordeiro, D; Mafra, M; Costa, I; Bravo Marques, J M; Abecasis, M

    2011-04-01

    BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient. © 2010 John Wiley & Sons A/S.

  2. Quantification of BK polyoma viruria in Japanese children and adults with hemorrhagic cystitis complicating stem cell transplantation.

    PubMed

    Tanaka, Kaori; Hori, Tsukasa; Hatakeyama, Naoki; Yamamoto, Masaki; Takayama, Rumiko; Yoto, Yuko; Suzuki, Nobuhiro; Hayashi, Toshiaki; Ikeda, Yukiho; Ikeda, Hiroshi; Ishida, Tadao; Tsutsumi, Hiroyuki

    2008-12-01

    Polyoma BK virus (BKV) is frequently found in the urine of stem cell transplantation (SCT) patients with hemorrhagic cystitis (HC), but also occurs in SCT patients without HC. How BK viruria relates to the development of HC in SCT patients, especially in children, has not yet been fully evaluated. In the present study, we analyzed the relationship of several factors including urinary BKV load to HC development in children and adults undergoing SCT. We employed a quantitative PCR assay and evaluated 37 patients (aged 9 months-62 years) of whom 12 developed HC and 25 did not. Older age was a risk factor for the development of HC; however, other factors such as sex, primary disease, type of SCT, conditioning regimen and aGVHD were not. Peak urinary BKV values in HC patients were not higher than those in non-HC patients. Severity of HC also did not correlate with urinary BKV loads. However, in some patients who secreted higher urinary BKV loads, the peak loads were closely related with the onset of HC. Higher BKV loads may be a risk factor for the development of HC in conjunction with other coexisting factors.

  3. BK Virus-Associated Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation in the Pediatric Population.

    PubMed

    Pérez-Huertas, Pablo; Cueto-Sola, Margarita; Escobar-Cava, Paloma; Fernández-Navarro, José María; Borrell-García, Carmela; Albert-Marí, Asunción; López-Briz, Eduardo; Poveda-Andrés, José Luis

    2016-02-22

    To study the incidence, risk factors, and treatment of hemorrhagic cystitis secondary to BK-virus reactivation (HC-BKV) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric population. Case-control study in which all pediatric patients (0-18 years) who underwent allo-HSCT from September 2009 to January 2014 were followed. Twenty-nine patients underwent an allo-HSCT. The median age was 9 years (range = 6 months to 15 years), 61% male. The primary diagnosis was acute lymphoblastic leukemia (72.4%). Six (20.7%) developed HC-BKV. In a multivariate analysis of risk factors, it was observed that the reactivation of BK virus was associated with age more than 10 years (P = .098) and those with positive serology for Epstein-Barr virus (P = .06). Five of the 6 patients with HC-BKV received cidofovir (CDV) at doses of 3 to 5 mg/kg/week. The treatment lasted a median of 3 cycles (range = 2-5). One of the patients (20%) developed nephrotoxicity. Of the 5 patients treated with CDV, 3 (60%) had a complete response, 1 (20%) partial response, and 1 (20%) no response. We conclude that HC-BKV is a frequent complication after allo-HSCT. CDV therapy can be effective but controlled clinical trials are needed. © 2016 by Association of Pediatric Hematology/Oncology Nurses.

  4. BK virus-associated renal problems--clinical implications.

    PubMed

    Pahari, Amitava; Rees, Lesley

    2003-08-01

    BK virus (BKV), a human polyomavirus, infects most of the human population, but clinically relevant infections are usually limited to individuals who are immunosuppressed. After primary infection, BKV remains latent in the kidneys and can be reactivated in immune deficiency conditions, including transplantation. As primary infection occurs in childhood, BKV may be particularly important in the pediatric transplant population. BKV is associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients and hemorrhagic cystitis in bone marrow transplant recipients. There are increasing reports of BKV causing nephropathy and cystitis in non-renal solid organ transplant recipients and other immunodeficiency diseases. This might be related to the use of more potent immunosuppressive regimens or increasing awareness of BKV as an important pathogen. Diagnosis of BKV disease is by biopsy. Histopathological changes in renal biopsy specimens may mimic rejection or drug toxicity, but BKV nuclear inclusions can be seen. Treatment is by reduction of immunosuppression. Antiviral agents such as cidofovir are showing promise. BKV DNA polymerase chain reaction in blood or biopsy may be helpful in monitoring therapy. The impact of BKV disease in children is not well understood and prospective studies are needed to elucidate this further. This article reviews the current understanding of BKV-associated renal problems.

  5. Location of the β4 transmembrane helices in the BK potassium channel

    PubMed Central

    Wu, Roland S.; Chudasama, Neelesh; Zakharov, Sergey I.; Doshi, Darshan; Motoike, Howard; Liu, Guoxia; Yao, Yongneng; Niu, Xiaowei; Deng, Shi-Xian; Landry, Donald W.; Karlin, Arthur; Marx, Steven O.

    2009-01-01

    Large-conductance, voltage- and Ca2+-gated potassium (BK) channels control excitability in a number of cell types. BK channels are composed of α subunits, which contain the voltage-sensor domains and the Ca2+- sensor domains, and form the pore, and often one of four types of β subunits, which modulate the channel in a cell-specific manner. β4 is expressed in neurons throughout the brain. Deletion of β4 in mice causes temporal lobe epilepsy. Compared to channels composed of α alone, channels composed of α and β4 activate and deactivate more slowly. We inferred the locations of the two β4 transmembrane (TM) helices, TM1 and TM2, relative to the seven αTM helices, S0-S6, from the extent of disulfide bond formation between cysteines substituted in the extracellular flanks of these TM helices. We found that β4 TM2 is close to α S0 and that β4 TM1 is close to both α S1 and S2. At least at their extracellular ends, TM1 and TM2 are not close to S3 through S6. In six of eight of the most highly crosslinked cysteine pairs, four crosslinks from TM2 to S0 and one each from TM1 to S1 and S2 had small effects on the V50 and on the rates of activation and deactivation. That disulfide crosslinking caused only small functional perturbations is consistent with the proximity of the extracellular ends of TM2 to S0 and of TM1 to S1 and to S2, in both the open and closed states. PMID:19571123

  6. Native American Death Taboo: Implications for Health Care Providers.

    PubMed

    Colclough, Yoshiko Yamashita

    2017-07-01

    This study was conducted to highlight Native American (NA) perspectives on death taboo in order to examine the cultural appropriateness of hospice services for NA patients, if any. Searching literature that addressed taboo and death from historical, psychological, sociological, and anthropological aspects, a comparison of death perspectives was made between NAs and European Americans. A culturally sensitive transition from palliative care to hospice care was suggested for NA patients and their family.

  7. The SMART-NAS Testbed

    NASA Technical Reports Server (NTRS)

    Aquilina, Rudolph A.

    2015-01-01

    The SMART-NAS Testbed for Safe Trajectory Based Operations Project will deliver an evaluation capability, critical to the ATM community, allowing full NextGen and beyond-NextGen concepts to be assessed and developed. To meet this objective a strong focus will be placed on concept integration and validation to enable a gate-to-gate trajectory-based system capability that satisfies a full vision for NextGen. The SMART-NAS for Safe TBO Project consists of six sub-projects. Three of the sub-projects are focused on exploring and developing technologies, concepts and models for evolving and transforming air traffic management operations in the ATM+2 time horizon, while the remaining three sub-projects are focused on developing the tools and capabilities needed for testing these advanced concepts. Function Allocation, Networked Air Traffic Management and Trajectory Based Operations are developing concepts and models. SMART-NAS Test-bed, System Assurance Technologies and Real-time Safety Modeling are developing the tools and capabilities to test these concepts. Simulation and modeling capabilities will include the ability to assess multiple operational scenarios of the national airspace system, accept data feeds, allowing shadowing of actual operations in either real-time, fast-time and/or hybrid modes of operations in distributed environments, and enable integrated examinations of concepts, algorithms, technologies, and NAS architectures. An important focus within this project is to enable the development of a real-time, system-wide safety assurance system. The basis of such a system is a continuum of information acquisition, analysis, and assessment that enables awareness and corrective action to detect and mitigate potential threats to continuous system-wide safety at all levels. This process, which currently can only be done post operations, will be driven towards "real-time" assessments in the 2035 time frame.

  8. Rheological properties of magnetorheological fluid and its finishing application on large aperture BK7 glass

    NASA Astrophysics Data System (ADS)

    Wang, C.; Wei, Q. L.; Huang, W.; Luo, Q.; He, J. G.; Tang, G. P.

    2013-07-01

    The CeO2 nanoparticles with modified surface and mean sizes distribution during 107.0 nm - 127.7 nm are used as abrasive in magnetorheological finishing (MRF) fluid. The slow rotation dispersion without shearing thinning is better than fast emulsification dispersion. Steady D-shaped finishing spots and high quality precise processing surface with PV=0.1λ, GRMS=0.002λ/cm, Rq=0.83 nm are obtained on a 435 mm x 435 mm BK7 glass under self-developed MRF apparatus.

  9. UAS Integration into the NAS Project

    NASA Technical Reports Server (NTRS)

    Bauer, Jeff

    2010-01-01

    The goal of the UAS Integration in the NAS Project is to contribute capabilities that reduce technical barriers related to the safety and operational challenges associated with enabling routine UAS access to the NAS This goal will be accomplished through a two-phased approach of system-level integration of key concepts, technologies and/or procedures, and demonstrations of integrated capabilities in an operationally relevant environment. Technical objectives include: PHASE 1: a) Validating the key technical areas identified by this project. System-level analyses, a State of the Art Analysis (SOAA), and a ConOps will identify the challenges and barriers preventing routine UAS access to the NAS. b) Developing a national roadmap and gap analysis identifying specific deliverables in the area of operations, procedures, and technologies that will impact future policy decisions. PHASE 2: a) Provide regulators with a methodology for developing airworthiness requirements for UAS and data to support development of certifications standards and regulatory guidance. b) Provide systems-level integrated testing of concepts and/or capabilities that address barriers to routine access to the NAS. Through simulation and flight testing, address issues including separation assurance, communications requirements, and Pilot Aircraft Interfaces (PAIs) in operationally relevant environments

  10. Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK, a metabolically resistant bradykinin B1 agonist, in a rat C6 glioma model

    PubMed Central

    Cardoso, Ronie Cleverson; Lobão-Soares, Bruno; Bianchin, Marino Muxfeldt; Carlotti, Carlos Gilberto; Walz, Roger; Alvarez-Silva, Márcio; Trentin, Andréa Gonçalves; Nicolau, Mauro

    2004-01-01

    Background While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model. Results SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area. Conclusions Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study. PMID:15458573

  11. Polyomavirus BK: possibly associated skin eruption in a patient with hemorrhagic cystitis.

    PubMed

    Medeiros, Patricia V; Abagge, Kerstin T; Carvalho, Vânia O; Bonfim, Carmem M; Raboni, Sonia M

    2011-01-01

    A 14-year-old girl with Fanconi anemia was submitted to allogeneic hematopoietic stem cell transplantation. After 17 days she developed hemorrhagic cystitis due to polyoma BK virus (BKV), confirmed by PCR (polymerase chain reaction). Two weeks after the appearance of the urinary symptoms the patient presented numerous papules and vesicles on both hands and feet. PCR of the skin lesions and plasma was positive for BKV. The relationship of BKV with frequent infections in immunocompromised patients is well established. The positive PCR of vesicular fluid suggests that this was the causative agent of the skin lesion in this case. There are no reports of skin lesions with positive PCR for BKV. © 2011 Wiley Periodicals, Inc.

  12. The Need for Vendor Source Code at NAS. Revised

    NASA Technical Reports Server (NTRS)

    Carter, Russell; Acheson, Steve; Blaylock, Bruce; Brock, David; Cardo, Nick; Ciotti, Bob; Poston, Alan; Wong, Parkson; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    The Numerical Aerodynamic Simulation (NAS) Facility has a long standing practice of maintaining buildable source code for installed hardware. There are two reasons for this: NAS's designated pathfinding role, and the need to maintain a smoothly running operational capacity given the widely diversified nature of the vendor installations. NAS has a need to maintain support capabilities when vendors are not able; diagnose and remedy hardware or software problems where applicable; and to support ongoing system software development activities whether or not the relevant vendors feel support is justified. This note provides an informal history of these activities at NAS, and brings together the general principles that drive the requirement that systems integrated into the NAS environment run binaries built from source code, onsite.

  13. Functional coupling of TRPV4 channels and BK channels in regulating spontaneous contractions of the guinea pig urinary bladder.

    PubMed

    Isogai, Ayu; Lee, Ken; Mitsui, Retsu; Hashitani, Hikaru

    2016-09-01

    We investigated the role of TRPV4 channels (TRPV4) in regulating the contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was examined by fluorescence immunohistochemistry. Changes in the contractility of DSM and MM bundles were measured using isometric tension recording. Intracellular Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while membrane potential changes were recorded using intracellular microelectrode technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM), a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated with a cessation of spontaneous phasic contractions in a manner sensitive to HC-067047 (10 μM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 μM), large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the spontaneous contractions in GSK. The sustained contractions in DSM and MM were reduced by nifedipine (10 μM), a blocker of L-type voltage-dependent Ca(2+) channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90 %. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+) levels and also prevented spontaneous action potential discharge associated with DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4 appears to activate BK channels to suppress spontaneous contractions and thus a functional coupling of TRPV4 with BK channels may act as a self-limiting mechanism for bladder contractility during its storage phase. Despite the membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the tonic contraction.

  14. Unusual presentations of BK virus infections in pediatric renal transplant recipients.

    PubMed

    Drake, Keri A; Najera, Lydia; Reed, Robyn C; Verghese, Priya S

    2013-02-01

    BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients. © 2012 John Wiley & Sons A/S.

  15. Fatal BK virus pneumonia following stem cell transplantation.

    PubMed

    Akazawa, Y; Terada, Y; Yamane, T; Tanaka, S; Aimoto, M; Koh, H; Nakane, T; Koh, K-R; Nakamae, H; Ohsawa, M; Wakasa, K; Hino, M

    2012-12-01

    We report the case of a 39-year-old male patient who died of severe BK virus (BKV) pneumonia 168 days after hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia. After suffering from BKV-associated late-onset hemorrhagic cystitis (HC) with long-term sustained BKV viremia, he died of rapidly progressive pneumonia. On autopsy, numerous viral intranuclear inclusions were seen in his lungs and bladder. An immunohistochemical examination of his lungs was positive for simian virus 40. Based on these pathological results and the high sustained BKV viral load in his blood, we reached a diagnosis of BKV pneumonia. Viral infection can occasionally become life threatening among HSCT recipients. It is widely known that BKV can cause late-onset HC, but BKV-associated pneumonia is rare. Because of its rapid progression and poor prognosis, it is difficult to make an antemortem diagnosis of BKV pneumonia. A treatment strategy for BKV pneumonia also needs to be formulated. Similar to other viral pathogens, BKV can cause pneumonia and the clinician should therefore be aware of it in immunocompromised patients. © 2012 John Wiley & Sons A/S.

  16. BK polyomavirus genotypes Ia and Ib1 exhibit different biological properties in renal transplant recipients.

    PubMed

    Varella, Rafael B; Zalona, Ana Carolina J; Diaz, Nuria C; Zalis, Mariano G; Santoro-Lopes, Guilherme

    2018-01-02

    BK polyomavirus (BKV) is an opportunist agent associated with nephropathy (BKVAN) in 1-10% of kidney transplant recipients. BKV is classified into genotypes or subgroups according to minor nucleotidic variations with unknown biological implications. Studies assessing the possible association between genotypes and the risk of BKVAN in kidney transplant patients have presented conflicting results. In these studies, genotype Ia, which is highly prevalent in Brazil, was less frequently found and, thus, comparative data on the biological properties of this genotype are lacking. In this study, BKV Ia and Ib1 genotypes were compared according to their viral load, genetic evolution (VP1 and NCCR) - in a cohort of renal transplant recipients. The patients infected with Ia (13/23; 56.5%) genotype exhibited higher viral loads in urine [>1.4 log over Ib1 (10/23; 43.5%); p=0.025]. In addition, genotype Ia was associated with diverse mutations at VP1 loops and sites under positive selection outside loops, which were totally absent in Ib1. Although the number of viremic patients was similar, the three patients who had BK nephropathy (BKVAN) were infected with Ia genotype. NCCR architecture (ww or rr) were not distinctive between Ia and Ib1 genotypes. Ia genotype, which is rare in other published BKV cohorts, presented some diverse biological properties in transplanted recipients in comparison to Ib1. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. NASA's UAS NAS Access Project

    NASA Technical Reports Server (NTRS)

    Johnson, Charles W.

    2011-01-01

    The vision of the Unmanned Aircraft System (UAS) Integration in the National Airspace System (NAS) Project is "A global transportation system which allows routine access for all classes of UAS." The goal of the UAS Integration in the NAS Project is to "contribute capabilities that reduce technical barriers related to the safety and operational challenges associated with enabling routine UAS access to the NAS." This goal will be accomplished through a two-phased approach based on development of system-level integration of key concepts, technologies and/or procedures, and demonstrations of integrated capabilities in an operationally relevant environment. Phase 1 will take place the first two years of the Project and Phase 2 will take place the following three years. The Phase 1 and 2 technical objectives are: Phase 1: Developing a gap analysis between current state of the art and the Next Generation Air Transportation System (NextGen) UAS Concept of Operations . Validating the key technical areas identified by this Project . Conducting initial modeling, simulation, and flight testing activities . Completing Sub-project Phase 1 deliverables (spectrum requirements, comparative analysis of certification methodologies, etc.) and continue Phase 2 preparation (infrastructure, tools, etc.) Phase 2: Providing regulators with a methodology for developing airworthiness requirements for UAS, and data to support development of certifications standards and regulatory guidance . Providing systems-level, integrated testing of concepts and/or capabilities that address barriers to routine access to the NAS. Through simulation and flight testing, address issues including separation assurance, communications requirements, and human systems integration in operationally relevant environments. The UAS in the NAS Project will demonstrate solutions in specific technology areas, which will address operational/safety issues related to UAS access to the NAS. Since the resource allocation for

  18. Diffuse gastrointestinal bleeding and BK polyomavirus replication in a pediatric allogeneic haematopoietic stem cell transplant patient.

    PubMed

    Koskenvuo, M; Lautenschlager, I; Kardas, P; Auvinen, E; Mannonen, L; Huttunen, P; Taskinen, M; Vettenranta, K; Hirsch, H H

    2015-01-01

    Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantation, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The polyomavirus BK agnoprotein co-localizes with lipid droplets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Unterstab, Gunhild; Gosert, Rainer; Leuenberger, David

    Agnoprotein encoded by human polyomavirus BK (BKV) is a late cytoplasmic protein of 66 amino acids (aa) of unknown function. Immunofluorescence microscopy revealed a fine granular and a vesicular distribution in donut-like structures. Using BKV(Dunlop)-infected or agnoprotein-transfected cells, we investigated agnoprotein co-localization with subcellular structures. We found that agnoprotein co-localizes with lipid droplets (LD) in primary human renal tubular epithelial cells as well as in other cells supporting BKV replication in vitro (UTA, Vero cells). Using agnoprotein-enhanced green fluorescent protein (EGFP) fusion constructs, we demonstrate that agnoprotein aa 20-42 are required for targeting LD, whereas aa 1-20 or aa 42-66more » were not. Agnoprotein aa 22-40 are predicted to form an amphipathic helix, and mutations A25D and F39E, disrupting its hydrophobic domain, prevented LD targeting. However, changing the phosphorylation site serine-11 to alanine or aspartic acid did not alter LD co-localization. Our findings provide new clues to unravel agnoprotein function.« less

  20. Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

    PubMed Central

    Niu, Xiaowei

    2011-01-01

    Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger. PMID:21576375

  1. Effects of in ovo exposure to benzo[k]fluoranthene (BkF) on CYP1A expression and promoter methylation in developing chicken embryos.

    PubMed

    Brandenburg, Jonas; Head, Jessica A

    2018-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are toxic environmental pollutants that are potent teratogens. Recent research suggests that early life exposure to PAHs can affect health outcomes later in life. Some of these latent responses may be mediated by epigenetic mechanisms such as DNA methylation. The role of DNA methylation in regulating responses to PAHs in birds is currently unknown. Here, we assess the effect of in ovo exposure to the model PAH, benzo[k]fluoranthene (BkF), on aryl hydrocarbon receptor (AHR) mediated cytochrome P4501A (CYP1A) gene expression and promoter methylation in chicken embryos. Fertilized chicken eggs were injected with BkF (0-100μg/kg) prior to incubation. BkF exposure was associated with an increase in CYP1A4 and CYP1A5 mRNA levels at mid-incubation (embryonic day 10), which dropped to baseline levels towards the end of the incubation period (embryonic day 19). The transient induction in CYP1A expression was accompanied by small but significant increases in CYP1A promoter methylation, which persisted until after shortly after hatching. Methylation within the CYP1A promoter was correlated with levels of CYP1A5, but not CYP1A4 mRNA. Characterization of the role of DNA methylation in the AHR response pathway may increase our understanding of the effects of early life exposure to PAHs in birds. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Nucleotide-dependent switch in proteasome assembly mediated by the Nas6 chaperone

    PubMed Central

    Li, Frances; Tian, Geng; Langager, Deanna; Sokolova, Vladyslava; Finley, Daniel; Park, Soyeon

    2017-01-01

    The proteasome is assembled via the nine-subunit lid, nine-subunit base, and 28-subunit core particle (CP). Previous work has shown that the chaperones Rpn14, Nas6, Hsm3, and Nas2 each bind a specific ATPase subunit of the base and antagonize base–CP interaction. Here, we show that the Nas6 chaperone also obstructs base–lid association. Nas6 alternates between these two inhibitory modes according to the nucleotide state of the base. When ATP cannot be hydrolyzed, Nas6 interferes with base–lid, but not base–CP, association. In contrast, under conditions of ATP hydrolysis, Nas6 obstructs base–CP, but not base–lid, association. Modeling of Nas6 into cryoelectron microscopy structures of the proteasome suggests that Nas6 controls both base–lid affinity and base–CP affinity through steric hindrance; Nas6 clashes with the lid in the ATP-hydrolysis–blocked proteasome, but clashes instead with the CP in the ATP-hydrolysis–competent proteasome. Thus, Nas6 provides a dual mechanism to control assembly at both major interfaces of the proteasome. PMID:28137839

  3. Atomic determinants of BK channel activation by polyunsaturated fatty acids

    PubMed Central

    Tian, Yutao; Aursnes, Marius; Hansen, Trond Vidar; Tungen, Jørn Eivind; Galpin, Jason D.; Leisle, Lilia; Ahern, Christopher A.; Xu, Rong; Heinemann, Stefan H.; Hoshi, Toshinori

    2016-01-01

    Docosahexaenoic acid (DHA), a polyunsaturated ω-3 fatty acid enriched in oily fish, contributes to better health by affecting multiple targets. Large-conductance Ca2+- and voltage-gated Slo1 BK channels are directly activated by nanomolar levels of DHA. We investigated DHA–channel interaction by manipulating both the fatty acid structure and the channel composition through the site-directed incorporation of unnatural amino acids. Electrophysiological measurements show that the para-group of a Tyr residue near the ion conduction pathway has a critical role. To robustly activate the channel, ionization must occur readily by a fatty acid for a good efficacy, and a long nonpolar acyl tail with a Z double bond present at the halfway position for a high affinity. The results suggest that DHA and the channel form an ion–dipole bond to promote opening and demonstrate the channel druggability. DHA, a marine-derived nutraceutical, represents a promising lead compound for rational drug design and discovery. PMID:27849612

  4. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A

    PubMed Central

    Goda, Amira A.; Naguib, Khayria M.; Mohamed, Magdy M.; Amra, Hassan A.; Nada, Somaia A.; Abdel-Ghaffar, Abdel-Rahman B.; Gissendanner, Chris R.; El Sayed, Khalid A.

    2016-01-01

    Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST) is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs), inducing neuroprotective effects. Docosahexaenoic acid (DHA) is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU), aspartate (ASP), and gamma amino butyric acid (GABA), with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA), serotonin (5-HT), and norepinephrine (NE) levels were abnormal, Nitric Oxide (NO) and Malondialdehyde (MDA) levels were significantly increased, and total antioxidant capacity (TAC) level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST

  5. Determination of composition of non-homogeneous GaInNAs layers

    NASA Astrophysics Data System (ADS)

    Pucicki, D.; Bielak, K.; Ściana, B.; Radziewicz, D.; Latkowska-Baranowska, M.; Kováč, J.; Vincze, A.; Tłaczała, M.

    2016-01-01

    Dilute nitride GaInNAs alloys grown on GaAs have become perspective materials for so called low-cost GaAs-based devices working within the optical wavelength range up to 1.6 μm. The multilayer structures of GaInNAs/GaAs multi-quantum well (MQW) samples usually are analyzed by using high resolution X-ray diffraction (HRXRD) measurements. However, demands for precise structural characterization of the GaInNAs containing heterostructures requires taking into consideration all inhomogeneities of such structures. This paper describes some of the material challenges and progress in structural characterization of GaInNAs layers. A new algorithm for structural characterization of dilute nitrides which bounds contactless electro-reflectance (CER) or photo-reflectance (PR) measurements and HRXRD analysis results together with GaInNAs quantum well band diagram calculation is presented. The triple quantum well (3QW) GaInNAs/GaAs structures grown by atmospheric-pressure metalorganic vapor-phase epitaxy (AP-MOVPE) were investigated according to the proposed algorithm. Thanks to presented algorithm, more precise structural data including the nonuniformity in the growth direction of GaInNAs/GaAs QWs were achieved. Therefore, the proposed algorithm is mentioned as a nondestructive method for characterization of multicomponent inhomogeneous semiconductor structures with quantum wells.

  6. NATIONAL ALCOHOL SURVEY (NAS)

    EPA Science Inventory

    National Alcohol Survey (NAS) is designed to assess the trends in drinking practices and problems in the national population, including attitudes, norms, treatment and experiences and adverse consequences. It also studies the effects of public policy on drinking practices (i.e., ...

  7. UAS NAS IHITL Test Readiness Review (TRR)

    NASA Technical Reports Server (NTRS)

    Murphy, Jim; Brignola, Michael P.; Rorie, Conrad; Santiago, Confesor; Guminsky, Mike; Cross, Ken

    2014-01-01

    Requesting release of IHITL test readiness review (TRR) charts to ensure UAS-NAS project primary stakeholders, the Federal Aviation Administration through the RTCA special committee -228 and the Office of the Secretary of Defense Sense and Avoid Science and Research Panel, are well informed on the IHITL test plan and expected outcomes as they relate to their needs to safely fly UAS in the NAS.

  8. Influence of Natural American Spirit advertising on current and former smokers' perceptions and intentions.

    PubMed

    Gratale, Stefanie K; Maloney, Erin K; Sangalang, Angeline; Cappella, Joseph N

    2017-10-21

    This study sought to demonstrate causal effects of exposure to Natural American Spirit (NAS) advertising content on misinformed beliefs of current and former smokers, and to empirically establish these beliefs as a mechanism driving intentions to use NAS. Our study employed a randomised experimental design with 1128 adult daily, intermittent and former smokers. We compared participants who were exposed to NAS advertisements or claims made in the advertisements with those in a no-message control group to test the effects of NAS advertising content on inaccurate beliefs about NAS and attitudes and intentions towards the product. One-way analysis of variance revealed that exposure to NAS advertisements produced inaccurate beliefs about the composition of NAS cigarettes among current and former smokers (p<0.05). Planned contrasts indicated a compilation of arguments taken directly from NAS advertisements resulted in significantly greater beliefs that NAS cigarettes are healthier/safer than other cigarettes (for former smokers, t(472)=3.63, p<0.001; for current smokers, t(644)=2.86, p=0.004), demonstrating that suggestive claims used in the brand's marketing have effects on beliefs not directly addressed in the advertisements. Regression and mediation analyses showed that health-related beliefs predict attitudes towards NAS for current and former smokers, and mediate intentions to use NAS. The findings of this study provide causal support for the need for further regulatory action to address the potentially harmful ramifications of claims used in NAS advertising. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP-12.

    PubMed

    Hirsch, H H; Yakhontova, K; Lu, M; Manzetti, J

    2016-03-01

    BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV-specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)- and calcineurin-inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR-SP6-kinase activation. Sirolimus inhibition was rapid and effective up to 24 h postinfection during viral early gene expression, but not thereafter, during viral late gene expression. The mTORC-1 kinase inhibitor torin-1 showed a similar inhibition profile, supporting the notion that early steps of BKPyV replication depend on mTOR activity. Cyclosporine A also inhibited BKPyV replication, while tacrolimus activated BKPyV replication and reversed sirolimus inhibition. FK binding protein 12kda (FKBP-12) siRNA knockdown abrogated sirolimus inhibition and increased BKPyV replication similar to adding tacrolimus. Thus, sirolimus and tacrolimus exert opposite effects on BKPyV replication in renal tubular epithelial cells by a mechanism involving FKBP-12 as common target. Immunosuppressive drugs may therefore contribute directly to the risk of BKPyV replication and nephropathy besides suppressing T cell functions. The data provide rationales for clinical trials aiming at reducing the risk of BKPyV replication and disease in kidney transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. BK polyomavirus encephalitis in a patient with thrombotic microangiopathy after an allogeneic hematopoietic stem cell transplant.

    PubMed

    Jun, Jae-Bum; Choi, Yunsuk; Kim, Hawk; Lee, Sun Ho; Jeong, Joseph; Jung, Jiwon

    2016-12-01

    To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. National Airspace System (NAS) open system architecture and protocols

    DOT National Transportation Integrated Search

    2003-08-14

    This standard establishes the open systems data communications architecture and authorized protocol standards for the National Airspace System (NAS). The NAS will consist of various types of processors and communications networks procured from a vari...

  12. Natural attenuation software (NAS): Assessing remedial strategies and estimating timeframes

    USGS Publications Warehouse

    Mendez, E.; Widdowson, M.; Chapelle, F.; Casey, C.

    2005-01-01

    Natural Attenuation Software (NAS) is a screening tool to estimate remediation timeframes for monitored natural attenuation (MNA) and to assist in decision-making on the level of source zone treatment in conjunction with MNA using site-specific remediation objectives. Natural attenuation processes that NAS models include are advection, dispersion, sorption, non-aqueous phase liquid (NAPL) dissolution, and biodegradation of either petroleum hydrocarbons or chlorinated ethylenes. Newly-implemented enhancements to NAS designed to maximize the utility of NAS for site managers were observed. NAS has expanded source contaminant specification options to include chlorinated ethanes and chlorinated methanes, and to allow for the analysis of any other user-defined contaminants that may be subject to microbially-mediated transformations (heavy metals, radioisotopes, etc.). Included is the capability to model co-mingled plumes, with constituents from multiple contaminant categories. To enable comparison of remediation timeframe estimates between MNA and specific engineered remedial actions , NAS was modified to incorporate an estimation technique for timeframes associated with pump-and-treat remediation technology for comparison to MNA. This is an abstract of a paper presented at the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).

  13. NAS Grid Benchmarks. 1.0

    NASA Technical Reports Server (NTRS)

    VanderWijngaart, Rob; Frumkin, Michael; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    We provide a paper-and-pencil specification of a benchmark suite for computational grids. It is based on the NAS (NASA Advanced Supercomputing) Parallel Benchmarks (NPB) and is called the NAS Grid Benchmarks (NGB). NGB problems are presented as data flow graphs encapsulating an instance of a slightly modified NPB task in each graph node, which communicates with other nodes by sending/receiving initialization data. Like NPB, NGB specifies several different classes (problem sizes). In this report we describe classes S, W, and A, and provide verification values for each. The implementor has the freedom to choose any language, grid environment, security model, fault tolerance/error correction mechanism, etc., as long as the resulting implementation passes the verification test and reports the turnaround time of the benchmark.

  14. New NAS Parallel Benchmarks Results

    NASA Technical Reports Server (NTRS)

    Yarrow, Maurice; Saphir, William; VanderWijngaart, Rob; Woo, Alex; Kutler, Paul (Technical Monitor)

    1997-01-01

    NPB2 (NAS (NASA Advanced Supercomputing) Parallel Benchmarks 2) is an implementation, based on Fortran and the MPI (message passing interface) message passing standard, of the original NAS Parallel Benchmark specifications. NPB2 programs are run with little or no tuning, in contrast to NPB vendor implementations, which are highly optimized for specific architectures. NPB2 results complement, rather than replace, NPB results. Because they have not been optimized by vendors, NPB2 implementations approximate the performance a typical user can expect for a portable parallel program on distributed memory parallel computers. Together these results provide an insightful comparison of the real-world performance of high-performance computers. New NPB2 features: New implementation (CG), new workstation class problem sizes, new serial sample versions, more performance statistics.

  15. The NAS Computational Aerosciences Archive

    NASA Technical Reports Server (NTRS)

    Miceli, Kristina D.; Globus, Al; Lasinski, T. A. (Technical Monitor)

    1995-01-01

    In order to further the state-of-the-art in computational aerosciences (CAS) technology, researchers must be able to gather and understand existing work in the field. One aspect of this information gathering is studying published work available in scientific journals and conference proceedings. However, current scientific publications are very limited in the type and amount of information that they can disseminate. Information is typically restricted to text, a few images, and a bibliography list. Additional information that might be useful to the researcher, such as additional visual results, referenced papers, and datasets, are not available. New forms of electronic publication, such as the World Wide Web (WWW), limit publication size only by available disk space and data transmission bandwidth, both of which are improving rapidly. The Numerical Aerodynamic Simulation (NAS) Systems Division at NASA Ames Research Center is in the process of creating an archive of CAS information on the WWW. This archive will be based on the large amount of information produced by researchers associated with the NAS facility. The archive will contain technical summaries and reports of research performed on NAS supercomputers, visual results (images, animations, visualization system scripts), datasets, and any other supporting meta-information. This information will be available via the WWW through the NAS homepage, located at http://www.nas.nasa.gov/, fully indexed for searching. The main components of the archive are technical summaries and reports, visual results, and datasets. Technical summaries are gathered every year by researchers who have been allotted resources on NAS supercomputers. These summaries, together with supporting visual results and references, are browsable by interested researchers. Referenced papers made available by researchers can be accessed through hypertext links. Technical reports are in-depth accounts of tools and applications research projects

  16. The first transmembrane domain (TM1) of β2-subunit binds to the transmembrane domain S1 of α-subunit in BK potassium channels

    PubMed Central

    Morera, Francisco J.; Alioua, Abderrahmane; Kundu, Pallob; Salazar, Marcelo; Gonzalez, Carlos; Martinez, Agustin D.; Stefani, Enrico; Toro, Ligia; Latorre, Ramon

    2012-01-01

    The BK channel is one of the most broadly expressed ion channels in mammals. In many tissues, the BK channel pore-forming α-subunit is associated to an auxiliary β-subunit that modulates the voltage- and Ca2+-dependent activation of the channel. Structural components present in β-subunits that are important for the physical association with the α-subunit are yet unknown. Here, we show through co-immunoprecipitation that the intracellular C-terminus, the second transmembrane domain (TM2) and the extracellular loop of the β2-subunit are dispensable for association with the α-subunit pointing transmembrane domain 1 (TM1) as responsible for the interaction. Indeed, the TOXCAT assay for transmembrane protein–protein interactions demonstrated for the first time that TM1 of the β2-subunit physically binds to the transmembrane S1 domain of the α-subunit. PMID:22710124

  17. Incidence and Factors Associated with De Novo DSA After BK Viremia in Renal Transplant Recipients.

    PubMed

    Patel, Samir J; Kuten, Samantha A; Knight, Richard J; Graviss, Edward A; Nguyen, Duc; Gaber, A Osama

    2016-01-01

    BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted. Copyright© 2017 by the Terasaki Research Institute.

  18. Prevalence of BK virus subtype I in Germany.

    PubMed

    Krumbholz, Andi; Zell, Roland; Egerer, Renate; Sauerbrei, Andreas; Helming, Andrea; Gruhn, Bernd; Wutzler, Peter

    2006-12-01

    The primary infection with human polyomavirus BK (BKV) occurs in early childhood and leads to viral latency within the urogenital tract. Up to 90% of the adult population are seropositive. In immunosuppressed patients, the BKV may be reactivated resulting in typical disease patterns like hemorrhagic cystitis and tubulointerstitial nephritis. Based on serological and molecular methods, BKV isolates were classified into four subtypes previously. Sixty specimens obtained from German renal and bone marrow transplant recipients were analyzed to gain data on the prevalence of BKV subtypes in Germany. With 90.9%, BKV subtype I was found to be predominant in both patient groups. 6.1% of BKV strains were classified as subtype IV. This pattern of phylogenetic distribution is similar to that demonstrated previously in England, Tanzania, the United States and Japan. Remarkably, there was one German BKV virus with a sequence which clusters together with strain SB in subtype II. The BKV subtype I was found to consist of at least three subgroups designated as Ia, Ib, and Ic. While the majority of the German sequences represent subgroup Ic, most of the Japanese sequences are clearly distinct. These findings support the hypothesis of distinct geographical prevalence of BKV subgroups. For the genotyping region, a relationship of BKV subgroups to disease patterns like hemorrhagic cystitis or tubulointerstitial nephritis could not be demonstrated. (c) 2006 Wiley-Liss, Inc.

  19. Kidney and bladder outcomes in children with hemorrhagic cystitis and BK virus infection after allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Oshrine, Benjamin; Bunin, Nancy; Li, Yimei; Furth, Susan; Laskin, Benjamin L

    2015-01-01

    BK virus (BKV) infection is associated with hemorrhagic cystitis (HC) in hematopoietic stem cell transplant (HSCT) recipients and nephropathy after kidney transplant. We assessed the association between BKV and kidney and bladder complications in children developing HC by retrospectively reviewing 221 consecutive pediatric allogeneic HSCT recipients at the Children’s Hospital of Philadelphia from 2005–2011. We included all patients with BKV PCR testing performed for clinical indication from day 0 until 1 year post-HSCT (N=68). We assessed the association of any BKV infection (urine and/or blood) or peak BK viremia ≥10,000 copies/ml (high viremia) with severe HC (defined as grade IV—bladder catheterization or surgical intervention), the need for dialysis, serum creatinine-estimated glomerular filtration rate (eGFR) at the time of BKV testing, day 100, and day 365, and death. Children with high viremia more likely developed severe HC compared to those with peak viremia <10,000 copies/mL (21% versus 2%; p=0.02). BKV infection of the blood or urine was not associated with the need for dialysis, change in eGFR, or mortality. BKV infection is common after pediatric allogeneic HSCT and plasma testing in those with HC may predict patients who will develop severe bladder injury. PMID:24060406

  20. An Implementation Plan for NFS at NASA's NAS Facility

    NASA Technical Reports Server (NTRS)

    Lam, Terance L.; Kutler, Paul (Technical Monitor)

    1998-01-01

    This document discusses how NASA's NAS can benefit from the Sun Microsystems' Network File System (NFS). A case study is presented to demonstrate the effects of NFS on the NAS supercomputing environment. Potential problems are addressed and an implementation strategy is proposed.

  1. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

    PubMed Central

    Satyanarayana, G.; Marty, F.M.; Tan, C.S.

    2014-01-01

    BK virus (BKV), an ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV- specific cytotoxic T-cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship to clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors. PMID:24834968

  2. A real time genotyping PCR assay for polyomavirus BK.

    PubMed

    Gard, Lilli; Niesters, Hubert G M; Riezebos-Brilman, Annelies

    2015-09-01

    Polyomavirus BK (BKV) may cause nephropathy in renal transplant recipients and hemorrhagic cystitis in bone marrow recipients. We developed real-time PCRs (RT-PCR) to determine easily and rapidly the different BKV genotypes (BKGT) (I-IV). On the VP1 gene a duplex of RT-PCRs was developed and validated to differentiate the four main BKGT. 212 BKV positive samples (21 plasma, 191 urine) were tested with these specific PCRs. Of these 212 samples, 55 PCR results were additionally confirmed by sequencing a VP1 gene fragment (nucleotide 1630-1956). For every genotype, a highly specific, precise and internally controlled assay was developed with a limit of detection of log 3 copies per ml. In 18 (8.5%) of these samples genotyping was not successful due to a low viral load. By sequence analysis, the genotype of 46 out of 55 and 2 out of 4 samples with double infection could be confirmed. This study describes RT-PCRs for detection of the main BKGT. It proved to be rapid, cheap and sensitive compared to sequencing. Double infections can also be detected. This method will be of value to investigate the role of BKV infection in relation to the genotype. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Diagnostic value of JC/BK virus antibody immunohistochemistry staining in urine samples from posttransplant immunosuppressed patients in relation to polyomavirus reactivation.

    PubMed

    Yuste, Rosario Sanchez; Frías, Carolina; López, Ana; Vallejo, Carlos; Martín, Paloma; Bellas, Carmen

    2008-01-01

    To compare the diagnostic value of cytology and immunohistochemistry staining (IHS) of urine samples for polyomavirus reactivation diagnosis. Sixty-eight urine samples collected from 18 immunosuppressed patients were analyzed by Papanicolaou and IHS with a JC/BK virus-specific monoclonal antibody. Overall, polyomavirus BK (BKV) was positive in 11 of 18 patients (61.1%) (3 of whom developed hemorrhagic cystitis) and in 23 of 68 urine samples (28%). Of 23 samples, 4 (17%) were positive by 1 of the 2 techniques, only. Of 23 samples, 19 (83%) were positive by both methods. In matching urine samples from the same patient, the number of BKV-infected positive cells detected by IHS in urine slides was higher than those detected by Papanicolaou staining (71.3%). The main advantage of LHS is that it allowed confirmation of BKV infection diagnosis in urine samples. IHS detected more BKV-infected cells in samples with few positive urothelial cells, which would have gone undetected if only Papanicolaou staining had been used as the BKV screening method. Urine samples testing for BKV by both techniques will improve diagnosis in asymptomatic patients, allowing early therapeutic intervention and a better clinical outcome.

  4. BK Virus and Its Role in Hematopoietic Stem Cell Transplantation: Evolution of a Pathogen.

    PubMed

    delaCruz, Jennifer; Pursell, Kenneth

    2014-08-01

    We reviewed the literature regarding disease induced by BK virus (BKV) in the hematopoietic stem cell transplant (HSCT) population, particularly hemorrhagic cystitis (HC) and nephritis. The association between BKV and HC has been reported over the past four decades. BKV has been clinically implicated and widely accepted as an etiologic agent of HC and nephritis in HSCT and nephropathy in renal transplant patients. We discuss the potential benefit of early initiation of therapy in patients who fail supportive care alone as well as the different treatment strategies for HC induced by BKV. Treatments that have been used such as cidofovir and leflunomide are accompanied by risks, and the benefits are not as concrete as with other viral illness in the HSCT population.

  5. NAS infrastructure management system build 1.5 computer-human interface

    DOT National Transportation Integrated Search

    2001-01-01

    Human factors engineers from the National Airspace System (NAS) Human Factors Branch (ACT-530) of the Federal Aviation Administration William J. Hughes Technical Center conducted an evaluation of the NAS Infrastructure Management System (NIMS) Build ...

  6. Cultural Adaptation, Psychometric Properties, and Outcomes of the Native American Spirituality Scale

    PubMed Central

    Greenfield, Brenna L.; Hallgren, Kevin A.; Venner, Kamilla L.; Hagler, Kylee J.; Simmons, Jeremiah D.; Sheche, Judith N.; Homer, Everett; Lupee, Donna

    2015-01-01

    Spirituality is central to many Native Americans (NAs) and has been associated with recovery from substance use disorders (SUDs). However, no published questionnaire uniquely taps tribal-specific spiritual beliefs and practices. This hinders efforts to integrate traditional NA spirituality into SUD treatment and track spiritual outcomes. As part of a randomized controlled trial examining SUD treatment for NAs, we adapted the Daily Spiritual Experience Scale (DSES) in collaboration with members of a Southwest tribe to create the Native American Spirituality Scale (NASS) and measured changes in the NASS over the course of treatment. The 83 participants (70% male) were from a single Southwest tribe and seeking SUD treatment. They completed the NASS at baseline, four-, eight-, and 12-months. Exploratory factor analysis of the NASS was conducted and its temporal invariance, construct validity, and longitudinal changes in the factor and item scores were examined. The NASS yielded a two-factor structure that was largely invariant across time. Factor 1 reflected behavioral practices, while Factor 2 reflected more global beliefs. Both factors significantly increased across 12 months, albeit at different assessment points. At baseline, Factor 1 was negatively related to substance use and positively associated with measures of tribal identification while Factor 2 was unrelated to these measures. Given the importance of tribal spirituality to many NAs, the development of this psychometrically sound measure is a key precursor and complement to the incorporation of tribal spirituality into treatment, as well as research on mechanisms of change for SUD treatment among NAs and assessment of NA spirituality in relation to other aspects of health. PMID:25961648

  7. Cultural adaptation, psychometric properties, and outcomes of the Native American Spirituality Scale.

    PubMed

    Greenfield, Brenna L; Hallgren, Kevin A; Venner, Kamilla L; Hagler, Kylee J; Simmons, Jeremiah D; Sheche, Judith N; Homer, Everett; Lupee, Donna

    2015-05-01

    Spirituality is central to many Native Americans (NAs) and has been associated with recovery from substance use disorders (SUDs). However, no published questionnaire uniquely taps tribal-specific spiritual beliefs and practices. This hinders efforts to integrate traditional NA spirituality into SUD treatment and track spiritual outcomes. As part of a randomized controlled trial examining SUD treatment for NAs, we adapted the Daily Spiritual Experience Scale (DSES) in collaboration with members of a Southwest tribe to create the Native American Spirituality Scale (NASS) and measured changes in the NASS over the course of treatment. The 83 participants (70% male) were from a single Southwest tribe and seeking SUD treatment. They completed the NASS at baseline, 4, 8, and 12 months. Exploratory factor analysis of the NASS was conducted and its temporal invariance, construct validity, and longitudinal changes in the factor and item scores were examined. The NASS yielded a 2-factor structure that was largely invariant across time. Factor 1 reflected behavioral practices, while Factor 2 reflected more global beliefs. Both factors significantly increased across 12 months, albeit at different assessment points. At baseline, Factor 1 was negatively related to substance use and positively associated with measures of tribal identification while Factor 2 was unrelated to these measures. Given the importance of tribal spirituality to many NAs, the development of this psychometrically sound measure is a key precursor and complement to the incorporation of tribal spirituality into treatment, as well as research on mechanisms of change for SUD treatment among NAs and assessment of NA spirituality in relation to other aspects of health. (c) 2015 APA, all rights reserved).

  8. Investigating the dynamics of the surface roughness of BK7 and TF1 glasses when they are processed by surface lap

    NASA Astrophysics Data System (ADS)

    Obeid, A.

    2005-12-01

    The roughness dynamics of glasses of types BK7 (K8) and TF1 are investigated at the stage of grinding and polishing when they undergo free-lap processing. The relationship is established between the arithmetic-mean roughness and the abrasive graininess at the stage of grinding and the polishing time. It is shown that one can distinguish three stages in the formation of roughness during polishing.

  9. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

    PubMed

    Satyanarayana, G; Marty, F M; Tan, C S

    2014-08-01

    BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. A fast BK-type KCa current acts as a postsynaptic modulator of temporal selectivity for communication signals.

    PubMed

    Kohashi, Tsunehiko; Carlson, Bruce A

    2014-01-01

    Temporal patterns of spiking often convey behaviorally relevant information. Various synaptic mechanisms and intrinsic membrane properties can influence neuronal selectivity to temporal patterns of input. However, little is known about how synaptic mechanisms and intrinsic properties together determine the temporal selectivity of neuronal output. We tackled this question by recording from midbrain electrosensory neurons in mormyrid fish, in which the processing of temporal intervals between communication signals can be studied in a reduced in vitro preparation. Mormyrids communicate by varying interpulse intervals (IPIs) between electric pulses. Within the midbrain posterior exterolateral nucleus (ELp), the temporal patterns of afferent spike trains are filtered to establish single-neuron IPI tuning. We performed whole-cell recording from ELp neurons in a whole-brain preparation and examined the relationship between intrinsic excitability and IPI tuning. We found that spike frequency adaptation of ELp neurons was highly variable. Postsynaptic potentials (PSPs) of strongly adapting (phasic) neurons were more sharply tuned to IPIs than weakly adapting (tonic) neurons. Further, the synaptic filtering of IPIs by tonic neurons was more faithfully converted into variation in spiking output, particularly at short IPIs. Pharmacological manipulation under current- and voltage-clamp revealed that tonic firing is mediated by a fast, large-conductance Ca(2+)-activated K(+) (KCa) current (BK) that speeds up action potential repolarization. These results suggest that BK currents can shape the temporal filtering of sensory inputs by modifying both synaptic responses and PSP-to-spike conversion. Slow SK-type KCa currents have previously been implicated in temporal processing. Thus, both fast and slow KCa currents can fine-tune temporal selectivity.

  11. A Method for Suppressing Line Overload Phenomena Using NAS Battery Systems

    NASA Astrophysics Data System (ADS)

    Ohtaka, Toshiya; Iwamoto, Shinichi

    In this paper, we pay attention to the superior operating control function and instantaneous discharging characteristics of NAS battery systems, and propose a method for determining installation planning and operating control schemes of NAS battery systems for suppressing line overload phenomena. In the stage of planning, a target contingency is identified, and an optimal allocation and capacity of NAS battery systems and an amount of generation changes are determined for the contingency. In the stage of operation, the control strategy of NAS battery system is determined. Simulations are carried out for verifying the validity of the proposed method using the IEEJ 1 machine V system model and an example 2 machine 16 bus system model.

  12. Calibration of BK Virus Nucleic Acid Amplification Testing to the 1st WHO International Standard for BK Virus

    PubMed Central

    Tan, Susanna K.; Milligan, Stephen; Sahoo, Malaya K.; Taylor, Nathaniel

    2017-01-01

    ABSTRACT Significant interassay variability in the quantification of BK virus (BKV) DNA precludes establishing broadly applicable thresholds for the management of BKV infection in transplantation. The 1st WHO International Standard for BKV (primary standard) was introduced in 2016 as a common calibrator for improving the harmonization of BKV nucleic acid amplification testing (NAAT) and enabling comparisons of biological measurements worldwide. Here, we evaluated the Altona RealStar BKV assay (Altona) and calibrated the results to the international unit (IU) using the Exact Diagnostics BKV verification panel, a secondary standard traceable to the primary standard. The primary and secondary standards on Altona had nearly identical linear regression equations (primary standard, Y = 1.05X − 0.28, R2 = 0.99; secondary standard, Y = 1.04X − 0.26, R2 = 0.99) and conversion factors (primary standard, 1.11 IU/copy; secondary standard, 1.09 IU/copy). A comparison of Altona with a laboratory-developed BKV NAAT assay in IU/ml versus copies/ml using Passing-Bablok regression revealed similar regression lines, no proportional bias, and improvement in the systematic bias (95% confidence interval of intercepts: copies/ml, −0.52 to −1.01; IU/ml, 0.07 to −0.36). Additionally, Bland-Altman analyses revealed a clinically significant reduction of bias when results were reported in IU/ml (IU/ml, −0.10 log10; copies/ml, −0.70 log10). These results indicate that the use of a common calibrator improved the agreement between the two assays. As clinical laboratories worldwide use calibrators traceable to the primary standard to harmonize BKV NAAT results, we anticipate improved interassay comparisons with a potential for establishing broadly applicable quantitative BKV DNA load cutoffs for clinical practice. PMID:28053213

  13. More Light than Heat: The Current State of Native American Studies

    ERIC Educational Resources Information Center

    Weaver, Jace

    2007-01-01

    The author mentions some of his recent works that he values and uses, without becoming a kind of academic costermonger cataloguing all the produce for sale in the shop. At the same time, he suggests some substantive things, while not falling prey to mere rant. In his books, the author discusses the characteristics of Native American Studies (NAS).…

  14. Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease

    PubMed Central

    Le Calloch, R.; Ianotto, J. C.; Berthou, C.; Tempescul, A.

    2011-01-01

    Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy. PMID:22937308

  15. Hemorrhagic Cystitis due to BK Reactivation in a Young Female Treated for Hodgkin-Disease.

    PubMed

    Le Calloch, R; Ianotto, J C; Berthou, C; Tempescul, A

    2011-01-01

    Hodgkin's lymphoma is a disease with a high rate of curability under classic chemo-radiotherapy regimes. Complications due to chemotherapy could include viral reactivation due to chronic lymphopenia. BK virus (BKV) is a polyoma virus belonging to the Papovaviridae family with antibody seroprevalences in healthy populations varying from 60% to 80%. Initial infections are asymptomatic usually occur in early childhood, after which the viruses remain latent in the kidneys or urothelium. Reactivation of BKV occurs in individuals with severe immunosuppression during HIV infections, transplantation or, exceptionally, after classical chemotherapy. BKV incidence is approximately 0% to 5% in immunocompetent individuals. Reactivation is associated with nephropathy and haemorrhagic cystitis. Herein, we present a case of a haemorrhagic cystitis due to BKV reactivation in a patient with Hodgkin's disease treated with chemotherapy.

  16. The NAS Alert System: A look at the first eight years

    USGS Publications Warehouse

    Fuller, Pamela L.; Neilson, Matt; Huge, Dane H.

    2013-01-01

    The U.S. Geological Survey's Nonindigenous Aquatic Species (NAS) database program (http://nas.er.usgs.gov) tracks the distribution of introduced aquatic organisms across the United States. Awareness of, and timely response to, novel species introductions by those involved in nonindigenous aquatic species management and research requires a framework for rapid dissemination of occurrence data as it is incorporated into the NAS database. In May 2004, the NAS program developed an alert system to notify registered users of new introductions as part of a national early detection/rapid response system. This article summarizes information on system users and dispatched alerts from the system's inception through the end of 2011. The NAS alert system has registered over 1,700 users, with approximately 800 current subscribers. A total of 1,189 alerts had been transmitted through 2011. More alerts were sent for Florida (134 alerts) than for any other state. Fishes comprise the largest taxonomic group of alerts (440), with mollusks, plants, and crustaceans each containing over 100 alerts. Most alerts were for organisms that were intentionally released (414 alerts), with shipping, escape from captivity, and hitchhiking also representing major vectors. To explore the archive of sent alerts and to register, the search and signup page for the alert system can be found online at http://nas.er.usgs.gov/AlertSystem/default.aspx.

  17. Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation.

    PubMed

    Wong, Anders S Y; Chan, Kwok-Hung; Cheng, Vincent C C; Yuen, Kwok-Yung; Kwong, Yok-Lam; Leung, Anskar Y H

    2007-03-15

    Reactivation of polyoma BK virus (BKV) infection is consistently associated with hemorrhagic cystitis in persons who undergo hematopoietic stem cell transplantation (HSCT). In this study, we examined the relationship of reactivation of BKV infection with pre-HSCT serologic findings of BKV antibody. Serial urine samples (n=1118) obtained from 140 HSCT recipients were prospectively obtained, and BKV loads were quantified by quantitative polymerase chain reaction. Pre-HSCT anti-BKV immunoglobulin G (IgG) levels were determined by indirect immunofluorescence. In 68 patients, there was significant peaking (i.e., > or = 3-log increase) in the urine BKV load (median peak, 1.7x10(9) copies/mL; range, 1.1x10(4) to 3.2x10(14) copies/mL) occurring at a median time of 24.5 days (range, 7-49 days). In 72 patients, low-level BKV viruria occurred without peaking (median BKV load, 10 copies/mL; range, 9.9x10(3) to 1.2x10(10) copies/mL) at a median time of 24.5 days (range, 7-49 days). Pre-HSCT anti-BKV IgG was positively related to elevated urine BKV load during HSCT (P<.001). Binary logistic regression revealed that pre-HSCT anti-BKV IgG level was the only statistically significant factor (P=.009) to be associated with a > or = 3-log increase in the peak urine BKV load (positive and negative predictive values, 69% and 68%, respectively). Nine patients developed hemorrhagic cystitis at a median of 56 days (range, 29-160); 7 of these patients were evaluable and were found to have a > or = 3-log increase in the peak BKV load. In binary logistic regression, peaking of the urine BKV load (P=.026) and graft-versus-host disease (P=.033) were found to be statistically significant risks for hemorrhagic cystitis. The identification of the serologic status of BKV as a significant risk factor for BKV viruria suggests that it should be included as an integral part of the pre-HSCT evaluation.

  18. NAS Panel endorses science center concept

    NASA Astrophysics Data System (ADS)

    Science and technology centers, as proposed by President Ronald Reagan in his January 1987 State of the Union message, could make “significant contributions to science and to the nation's economic competitiveness,” according to a new report by a National Academy of Sciences (NAS) panel. What will be necessary to realize these contributions, the panel cautioned, are proper management, adequate resources, and, “above all, the selection of programs for which the centers are the most effective form of organization.”NSF plans to support science and technology centers, beginning October 1, 1988, which is the start of fiscal year 1988. NSF requested guidance from the NAS panel in implementing the program. Although other government agencies will participate in the program, NSF will play the primary role.

  19. Analysis of Surface and Subsurface Damage Morphology in Rotary Ultrasonic Machining of BK7 Glass

    NASA Astrophysics Data System (ADS)

    Hong-xiang, Wang; Chu, Wang; Jun-liang, Liu; Shi, Gao; Wen-Jie, Zhai

    2017-11-01

    This paper investigates the formation process of surface/subsurface damage in the rotary ultrasonic machining of BK7 glass. The results show that during the milling using the end face of the tool, the cutting depth and the residual height between the abrasive grains constantly change with the high-frequency vibration, generating lots of cracks on both sides of the scratches. The high-frequency vibration accelerates the chips falling from the surface, so that the chips and thermal damage are reduced, causing the grinding surface quality better. A plastic deformation area is formed during the grinding, due to the non-uniform cutting force on the material surface, and the residual stress is produced in the deformation area, inducing the median/lateral cracks.

  20. UAS-NAS Flight Test Series 3: Test Environment Report

    NASA Technical Reports Server (NTRS)

    Hoang, Ty; Murphy, Jim; Otto, Neil

    2016-01-01

    The desire and ability to fly Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) is of increasing urgency. The application of unmanned aircraft to perform national security, defense, scientific, and emergency management are driving the critical need for less restrictive access by UAS to the NAS. UAS represent a new capability that will provide a variety of services in the government (public) and commercial (civil) aviation sectors. The growth of this potential industry has not yet been realized due to the lack of a common understanding of what is required to safely operate UAS in the NAS. NASA's UAS Integration in the NAS Project is conducting research in the areas of Separation Assurance/Sense and Avoid Interoperability (SSI), Human Systems Integration (HSI), and Communications (Comm), and Certification to support reducing the barriers of UAS access to the NAS. This research is broken into two research themes namely, UAS Integration and Test Infrastructure. UAS Integration focuses on airspace integration procedures and performance standards to enable UAS integration in the air transportation system, covering Detect and Avoid (DAA) performance standards, command and control performance standards, and human systems integration. The focus of Test Infrastructure is to enable development and validation of airspace integration procedures and performance standards, including integrated test and evaluation. In support of the integrated test and evaluation efforts, the Project will develop an adaptable, scalable, and schedulable relevant test environment capable of evaluating concepts and technologies for unmanned aircraft systems to safely operate in the NAS. To accomplish this task, the Project is conducting a series of human-in-the-loop (HITL) and flight test activities that integrate key concepts, technologies and/or procedures in a relevant air traffic environment. Each of the integrated events will build on the technical achievements, fidelity, and

  1. The NAS kernel benchmark program

    NASA Technical Reports Server (NTRS)

    Bailey, D. H.; Barton, J. T.

    1985-01-01

    A collection of benchmark test kernels that measure supercomputer performance has been developed for the use of the NAS (Numerical Aerodynamic Simulation) program at the NASA Ames Research Center. This benchmark program is described in detail and the specific ground rules are given for running the program as a performance test.

  2. Ca2+ block and flickering both contribute to the negative slope of the IV curve in BK channels.

    PubMed

    Schroeder, Indra; Thiel, Gerhard; Hansen, Ulf-Peter

    2013-04-01

    Single-channel current-voltage (IV) curves of human large-conductance, voltage- and Ca(2+)-activated K(+) (BK) channels are quite linear in 150 mM KCl. In the presence of Ca(2+) and/or Mg(2+), they show a negative slope conductance at high positive potentials. This is generally explained by a Ca(2+)/Mg(2+) block as by Geng et al. (2013. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.201210955) in this issue. Here, we basically support this finding but add a refinement: the analysis of the open-channel noise by means of β distributions reveals what would be found if measurements were done with an amplifier of sufficient temporal resolution (10 MHz), namely that the block by 2.5 mM Ca(2+) and 2.5 mM Mg(2+) per se would only cause a saturating curve up to +160 mV. Further bending down requires the involvement of a second process related to flickering in the microsecond range. This flickering is hardly affected by the presence or absence of Ca(2+)/Mg(2+). In contrast to the experiments reported here, previous experiments in BK channels (Schroeder and Hansen. 2007. J. Gen. Physiol. http://dx.doi.org/10.1085/jgp.200709802) showed saturating IV curves already in the absence of Ca(2+)/Mg(2+). The reason for this discrepancy could not be identified so far. However, the flickering component was very similar in the old and new experiments, regardless of the occurrence of noncanonical IV curves.

  3. Experimental Study of Tool Wear and Grinding Forces During BK-7 Glass Micro-grinding with Modified PCD Tool

    NASA Astrophysics Data System (ADS)

    Pratap, A.; Sahoo, P.; Patra, K.; Dyakonov, A. A.

    2017-09-01

    This study focuses on the improvement in grinding performance of BK-7 glass using polycrystalline diamond micro-tool. Micro-tools are modified using wire EDM and performance of modified tools is compared with that of as received tool. Tool wear of different types of tools are observed. To quantify the tool wear, a method based on weight loss of tool is introduced in this study. Modified tools significantly reduce tool wear in comparison to the normal tool. Grinding forces increase with machining time due to tool wear. However, modified tools produce lesser forces thus can improve life of the PCD micro-grinding tool.

  4. National Air Space (NAS) Data Exchange Environment Through 2060

    NASA Technical Reports Server (NTRS)

    Roy, Aloke

    2015-01-01

    NASA's NextGen Concepts and Technology Development (CTD) Project focuses on capabilities to improve safety, capacity and efficiency of the National Air Space (NAS). In order to achieve those objectives, NASA sought industry-Government partnerships to research and identify solutions for traffic flow management, dynamic airspace configuration, separation assurance, super density operations, airport surface operations and similar forward-looking air-traffic modernization (ATM) concepts. Data exchanges over NAS being the key enabler for most of these ATM concepts, the Sub-Topic area 3 of the CTD project sought to identify technology candidates that can satisfy air-to-air and air/ground communications needs of the NAS in the year 2060 timeframe. Honeywell, under a two-year contract with NASA, is working on this communications technology research initiative. This report summarizes Honeywell's research conducted during the second year of the study task.

  5. NAS Technical Summaries, March 1993 - February 1994

    NASA Technical Reports Server (NTRS)

    1995-01-01

    NASA created the Numerical Aerodynamic Simulation (NAS) Program in 1987 to focus resources on solving critical problems in aeroscience and related disciplines by utilizing the power of the most advanced supercomputers available. The NAS Program provides scientists with the necessary computing power to solve today's most demanding computational fluid dynamics problems and serves as a pathfinder in integrating leading-edge supercomputing technologies, thus benefitting other supercomputer centers in government and industry. The 1993-94 operational year concluded with 448 high-speed processor projects and 95 parallel projects representing NASA, the Department of Defense, other government agencies, private industry, and universities. This document provides a glimpse at some of the significant scientific results for the year.

  6. UAS-NAS Integrated Human in the Loop: Test Environment Report

    NASA Technical Reports Server (NTRS)

    Murphy, Jim; Otto, Neil; Jovic, Srba

    2015-01-01

    The desire and ability to fly Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) is of increasing urgency. The application of unmanned aircraft to perform national security, defense, scientific, and emergency management are driving the critical need for less restrictive access by UAS to the NAS. UAS represent a new capability that will provide a variety of services in the government (public) and commercial (civil) aviation sectors. The growth of this potential industry has not yet been realized due to the lack of a common understanding of what is required to safely operate UAS in the NAS. NASA's UAS Integration in the NAS Project is conducting research in the areas of Separation Assurance/Sense and Avoid Interoperability (SSI), Human Systems Integration (HSI), and Communication to support reducing the barriers of UAS access to the NAS. This research was broken into two research themes namely, UAS Integration and Test Infrastructure. UAS Integration focuses on airspace integration procedures and performance standards to enable UAS integration in the air transportation system, covering Sense and Avoid (SAA) performance standards, command and control performance standards, and human systems integration. The focus of the Test Infrastructure theme was to enable development and validation of airspace integration procedures and performance standards, including the execution of integrated test and evaluation. In support of the integrated test and evaluation efforts, the Project developed an adaptable, scalable, and schedulable relevant test environment incorporating live, virtual, and constructive elements capable of validating concepts and technologies for unmanned aircraft systems to safely operate in the NAS. To accomplish this task, the Project planned to conduct three integrated events: a Human-in-the-Loop simulation and two Flight Test series that integrated key concepts, technologies and/or procedures in a relevant air traffic environment. Each of

  7. Relative similarity within purine nucleotide and ligand structures operating on nitric oxide synthetase, guanylyl cyclase and potassium (K ATP, BK Ca) channels.

    PubMed

    Williams, W Robert

    2011-01-01

    Purine nucleotides play a central role in signal transduction events initiated at the cell membrane. The NO-cGMP-cGK pathway, in particular, mediates events involving NOS and some classes of K(+) ion channel. The aim of this study is to investigate relative molecular similarity within the ligands binding to NOS, K(ATP), BK(Ca) channels and regulatory nucleotides. Minimum energy conformers of the ligand structures were superimposed and fitted to L-arginine and the nucleotides of adenine and guanine using a computational program. Distinctive patterns were evident in the fitting of NOS isoform antagonists to L-arginine. K(ATP) channel openers and antagonists superimposed on the glycosidic linkage and imidazole ring of the purine nucleotides, and guanidinium and ribose groups of GTP in the case of glibenclamide. The fits of BK(Ca) channel openers and antagonists to cGMP were characterized by the linear dimensions of their structures; distances between terminal oxy groups in respect of dexamethasone and aldosterone. The findings provide structural evidence for the functional interaction between K(+) channel openers/antagonists and the regulatory nucleotides. Use of the purine nucleotide template systematizes the considerable heterogeneity evident within the structures of ligands operating on K(+) ion channels. © 2010 The Author. JPP © 2010 Royal Pharmaceutical Society.

  8. [Clinical significance of monitoring BK polyomavirus in patients after hematopoietic stem cell transplantation].

    PubMed

    Yin, Chang-Xin; Jiang, Qian-Li; He, Han; Yu, Guo-Pan; Xu, Yue; Meng, Fan-Yi; Yang, Mo

    2012-02-01

    This study was aimed to establish a method for rapid detecting BK polyomavirus (BKV) and to investigate the feasibility and value used in leukemia patients undergoing hematopoietic stem cell transplantation. Primers were designed according to BKV gene sequence; the quantitative standards for BKV and a real-time fluorescent quantitative PCR for BKV were established. The BKV level in urine samples from 36 patients after hematopoietic stem cell transplantation were detected by established method. The results showed that the standard of reconstructed plasmid and real time fluorescent quantitative PCR method were successfully established, its good specificity, sensitivity and stability were confirmed by experiments. BKV was found in 55.56% of urine samples, and the BKV load in urine was 2.46 × 10(4) - 7.8 × 10(9) copy/ml. It is concluded that the establishment of real-time fluorescent quantitative PCR for BKV detection provides a method for early diagnosis of the patients with hemorrhagic cystitis after hematopoietic stem cell transplantation.

  9. Bladder transitional cell carcinoma and BK virus in a young kidney transplant recipient.

    PubMed

    Pino, L; Rijo, E; Nohales, G; Frances, A; Ubre, A; Arango, O

    2013-02-01

    Kidney transplant recipients have a heightened risk of developing neoplasms. Immunosuppressive treatments decrease the incidence of transplant rejection but increase the risk of infections, including BK virus (BKV). This infection is acquired in childhood and remains latent in the renal and urinary epithelium. In cases of immunodeficiency, BKV has been implicated as a tumor virus, but the role of BKV in cancer is a controversial topic and is difficult to determine. In the tumor cells, it is possible to detect fragments of the viral genome that could alter the control mechanisms of the cell cycle and DNA repair. We report the case of a kidney transplant recipient who developed BKV nephropathy and carcinoma of the bladder, supporting a possible role for BKV in the oncogenic pathway in this clinical setting, but the role of BKV in cancer remains a controversial topic and difficult to determine. © 2012 John Wiley & Sons A/S.

  10. Hybrid Network Architectures for the Next Generation NAS

    NASA Technical Reports Server (NTRS)

    Madubata, Christian

    2003-01-01

    To meet the needs of the 21st Century NAS, an integrated, network-centric infrastructure is essential that is characterized by secure, high bandwidth, digital communication systems that support precision navigation capable of reducing position errors for all aircraft to within a few meters. This system will also require precision surveillance systems capable of accurately locating all aircraft, and automatically detecting any deviations from an approved path within seconds and be able to deliver high resolution weather forecasts - critical to create 4- dimensional (space and time) profiles for up to 6 hours for all atmospheric conditions affecting aviation, including wake vortices. The 21st Century NAS will be characterized by highly accurate digital data bases depicting terrain, obstacle, and airport information no matter what visibility conditions exist. This research task will be to perform a high-level requirements analysis of the applications, information and services required by the next generation National Airspace System. The investigation and analysis is expected to lead to the development and design of several national network-centric communications architectures that would be capable of supporting the Next Generation NAS.

  11. Characteristics of polyomavirus BK (BKPyV) infection in primary human urothelial cells.

    PubMed

    Li, Ruomei; Sharma, Biswa Nath; Linder, Stig; Gutteberg, Tore Jarl; Hirsch, Hans H; Rinaldo, Christine Hanssen

    2013-05-25

    High-level polyomavirus BK (BKPyV) replication in urothelial cells is a hallmark of polyomavirus-associated hemorrhagic cystitis (PyVHC), a painful condition affecting bone marrow transplant recipients. In kidney transplant recipients, replication in tubular epithelial cells is associated with overt disease whereas high-level urothelial replication is clinically silent. We characterized BKPyV replication in primary human urothelial cells (HUCs) and compared it to replication in renal tubular epithelial cells (RPTECs). HUCs were easily infected, as shown by expression of T-antigens, VP1-3, and agnoprotein, and intranuclear virion production. Compared to RPTECs, progeny release was delayed by ≥24h and reduced. BKPyV-infected HUCs rounded up like "decoy cells" and detached without necrosis as shown by delayed cytokeratin-18 release, real-time viability monitoring and imaging. The data show that BKV infection of HUCs and RPTECs is significantly different and support the notion that PyVHC pathogenesis is not solely due to BKPyV replication, but likely requires urotoxic and immunological cofactors. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. SMART NAS Test Bed Overview

    NASA Technical Reports Server (NTRS)

    Palopo, Kee

    2016-01-01

    These slides presents an overview of SMART NAS Test Bed. The test bed is envisioned to be connected to operational systems and to allow a new concept and technology to be evaluated in its realistic environment. Its role as an accelerator of concepts and technologies development, its use-case-driven development approach, and its state are presented.

  13. NAS Applications and Advanced Algorithms

    NASA Technical Reports Server (NTRS)

    Bailey, David H.; Biswas, Rupak; VanDerWijngaart, Rob; Kutler, Paul (Technical Monitor)

    1997-01-01

    This paper examines the applications most commonly run on the supercomputers at the Numerical Aerospace Simulation (NAS) facility. It analyzes the extent to which such applications are fundamentally oriented to vector computers, and whether or not they can be efficiently implemented on hierarchical memory machines, such as systems with cache memories and highly parallel, distributed memory systems.

  14. BK virus induced nephritis in a boy with acute myeloid leukaemia undergoing bone marrow transplantation

    PubMed Central

    Hoefele, Julia; Rüssmann, Despina; Klein, Barbara; Weber, Lutz T.; Führer, Monika

    2008-01-01

    BK virus (BKV) is a human polyomavirus. The primary infection occurs typically without specific signs or symptoms. Almost 80% of adults are seropositive. Clinically relevant infections are usually limited to individuals who are immunosuppressed. After primary infection, BKV remains latent in the kidneys and can be reactivated in the setting of immunosuppression. BKV is associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients. Furthermore, BKV-induced haemorrhagic cystitis (HC) is a severe complication of bone marrow transplantation (BMT) in children and adults. A combination of HC and tubulointerstitial nephritis in a patient has not been reported so far. We report on an 11-year-old boy with acute myeloid leukaemia undergoing BMT. BKV infection was reactivated during post-transplant immunosuppressive therapy causing HC associated with tubulointerstitial nephritis. PMID:25983928

  15. NASA Advanced Supercomputing (NAS) User Services Group

    NASA Technical Reports Server (NTRS)

    Pandori, John; Hamilton, Chris; Niggley, C. E.; Parks, John W. (Technical Monitor)

    2002-01-01

    This viewgraph presentation provides an overview of NAS (NASA Advanced Supercomputing), its goals, and its mainframe computer assets. Also covered are its functions, including systems monitoring and technical support.

  16. Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation.

    PubMed

    Bogdanovic, G; Priftakis, P; Giraud, G; Kuzniar, M; Ferraldeschi, R; Kokhaei, P; Mellstedt, H; Remberger, M; Ljungman, P; Winiarski, J; Dalianis, T

    2004-11-01

    BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC.

  17. Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production.

    PubMed

    Zhang, Xiaojie; Lu, Chenyang; Bai, Linquan

    2017-09-01

    An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization, fast growth, abundant precursors and energy supply, and a pronounced gene expression. Streptomyces albus BK3-25 is a high-yield industrial strain producing type-I polyketide salinomycin, with a unique ability of bean oil utilization. Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein. Firstly, introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and salinomycin, and subsequent deletion of the salinomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors, including malonyl-CoA, methylmalonyl-CoA, and ethylmalonyl-CoA. Secondly, the energy and reducing force were measured, and the improved accumulation of ATP and NADPH was observed in the mutant. Furthermore, the strength of a series of selected endogenous promoters based on microarray data was assessed at different growth phases, and a strong constitutive promoter was identified, providing a useful tool for further engineered gene expression. Finally, the potential of the BK3-25 derived host ZXJ-6 was evaluated with the introduction of the actinorhodin biosynthetic gene cluster from Streptomyces coelicolor, and the heterologous production of actinorhodin was obtained. This work clearly indicated the potential of the high-yield salinomycin producer as a surrogate host for heterologous production of polyketides, although more genetic manipulation should be conducted to streamline its performance.

  18. BK Lyncis: the oldest old nova and a Bellwether for cataclysmic variable evolution

    NASA Astrophysics Data System (ADS)

    Patterson, Joseph; Uthas, Helena; Kemp, Jonathan; de Miguel, Enrique; Krajci, Thomas; Foote, Jerry; Hambsch, Franz-Josef; Campbell, Tut; Roberts, George; Cejudo, David; Dvorak, Shawn; Vanmunster, Tonny; Koff, Robert; Skillman, David; Harvey, David; Martin, Brian; Rock, John; Boyd, David; Oksanen, Arto; Morelle, Etienne; Ulowetz, Joseph; Kroes, Anthony; Sabo, Richard; Jensen, Lasse

    2013-09-01

    We summarize the results of a 20-yr campaign to study the light curves of BK Lyn, a nova-like star strangely located below the 2 to 3 h orbital-period gap in the family of cataclysmic variables (CVs). Two apparent superhumps dominate the nightly light curves, with periods 4.6 per cent longer, and 3.0 per cent shorter, than the orbital period. The first appears to be associated with the star's brighter states (V ˜ 14), while the second appears to be present throughout and becomes very dominant in the low state (V ˜ 15.7). It is plausible that these arise, respectively, from a prograde apsidal precession and a retrograde nodal precession of the star's accretion disc. Starting in the year 2005, the star's light curve became indistinguishable from that of a dwarf nova - in particular, that of the ER UMa subclass. No such clear transition has ever been observed in a CV before. Reviewing all the star's oddities, we speculate: (a) BK Lyn is the remnant of the probable nova on 101 December 30, and (b) it has been fading ever since, but it has taken ˜2000 yr for the accretion rate to drop sufficiently to permit dwarf-nova eruptions. If such behaviour is common, it can explain other puzzles of CV evolution. One: why the ER UMa class even exists (because all members can be remnants of recent novae). Two: why ER UMa stars and short-period nova-likes are rare (because their lifetimes, which are essentially cooling times, are short). Three: why short-period novae all decline to luminosity states far above their true quiescence (because they are just getting started in their post-nova cooling). Four: why the orbital periods, accretion rates and white dwarf temperatures of short-period CVs are somewhat too large to arise purely from the effects of gravitational radiation (because the unexpectedly long interval of enhanced post-nova brightness boosts the mean mass-transfer rate). And maybe even five: why very old, post-period-bounce CVs are hard to find (because the higher mass

  19. BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis in an unrelated bone marrow transplantation.

    PubMed

    Iwamoto, Shotaro; Azuma, Eiichi; Hori, Hiroki; Hirayama, Masahiro; Kobayashi, Michihiro; Komada, Yoshihiro; Nishimori, Hisashi; Miyahara, Masazumi

    2002-06-01

    The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a frequent and, seldom life-threatening complication after bone marrow transplantation (BMT). The authors report a male with melodysplastic syndrome, who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated BMT. His urine contained epithelial cells with intranuclear inclusion bodies suggestive of BKV infection and was positive for BKV in polymerase chain reaction. He did not respond to any treatment for HC. In addition, he developed BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive disease on day 42. This is the first case in which BKV may be associated with fatal progressive renal failure.

  20. Development of a BK virus real-time quantitative assay using the bioMérieux analyte-specific reagents in plasma specimens.

    PubMed

    Rennert, Hanna; Fernandes, Helen; Gilani, Zahid; Sipley, John

    2015-12-01

    Viral load testing for BK virus (BKV) has become the standard of care for diagnosing BKV infection and monitoring therapy in kidney transplant patients. However, there are currently no US Food and Drug Administration-approved assays and no standardization among available tests. This study evaluated the performance of the analyte-specific reagent (ASR) BKV primers r-gene and probe r-gene reagents (bioMérieux, Marcy l'Étoile, France) soon to become available on the US market for accuracy, linearity, precision, analytical sensitivity, specificity, and correlation with the Qiagen (Germantown, MD) BKV ASR test using commercial material and patient plasma samples. The assay was linear from 204 to 3.92 million (2.31-6.6 log10) DNA copies/mL (coefficient of determination: R(2) =0.999). A dilution series demonstrated limits of detection and quantitation of 2.14 log10 and 2.30 log10 copies/mL (95% hit rate detection), respectively. Interrun precision was highly reproducible, with coefficients of variance ranging from 2.2% to 6.0%. A comparison of 34 matched samples showed a good agreement (R(2) = 0.87) between the bioMérieux BKV laboratory test and the Qiagen BKV ASR assay results, with an average negative bias (-0.28 log10 copies/mL). The laboratory-developed test with bioMérieux BKV reagents is a reliable and sensitive assay for BKV DNA quantitation compared with the Qiagen ASR test. Copyright© by the American Society for Clinical Pathology.

  1. UAS Integration in the NAS: Detect and Avoid

    NASA Technical Reports Server (NTRS)

    Shively, Jay

    2018-01-01

    This presentation will cover the structure of the unmanned aircraft systems (UAS) integration into the national airspace system (NAS) project (UAS-NAS Project). The talk also details the motivation of the project to help develop standards for a detect-and-avoid (DAA) system, which is required in order to comply with requirements in manned aviation to see-and-avoid other traffic so as to maintain well clear. The presentation covers accomplishments reached by the project in Phase 1 of the research, and touches on the work to be done in Phase 2. The discussion ends with examples of the display work developed as a result of the Phase 1 research.

  2. Association between a High BK Virus Load in Urine Samples of Patients with Graft-Versus-Host Disease and Development of Hemorrhagic Cystitis after Hematopoietic Stem Cell Transplantation

    PubMed Central

    Bogdanovic, G.; Priftakis, P.; Giraud, G.; Kuzniar, M.; Ferraldeschi, R.; Kokhaei, P.; Mellstedt, H.; Remberger, M.; Ljungman, P.; Winiarski, J.; Dalianis, T.

    2004-01-01

    BK virus (BKV) load in urine alone or in combination with acute graft-versus-host disease (GVHD) was correlated to development of hemorrhagic cystitis (HC). BKV load in combination with acute GVHD discriminated the best, while BKV and viral load alone, but not GVHD, still showed predictive ability for HC. PMID:15528753

  3. [Methods in neonatal abstinence syndrome (NAS): results of a nationwide survey in Austria].

    PubMed

    Bauchinger, S; Sapetschnig, I; Danda, M; Sommer, C; Resch, B; Urlesberger, B; Raith, W

    2015-08-01

    Neonatal abstinence syndrome (NAS) occurs in neonates whose mothers have taken addictive drugs or were under substitution therapy during pregnancy. Incidence numbers of NAS are on the rise globally, even in Austria NAS is not rare anymore. The aim of our survey was to reveal the status quo of dealing with NAS in Austria. A questionnaire was sent to 20 neonatology departments all over Austria, items included questions on scoring, therapy, breast-feeding and follow-up procedures. The response rate was 95%, of which 94.7% had written guidelines concerning NAS. The median number of children being treated per year for NAS was 4. Finnegan scoring system is used in 100% of the responding departments. Morphine is being used most often, in opiate abuse (100%) as well as in multiple substance abuse (44.4%). The most frequent forms of morphine preparation are morphine and diluted tincture of opium. Frequency as well as dosage of medication vary broadly. 61.1% of the departments supported breast-feeding, regulations concerned participation in a substitution programme and general contraindications (HIV, HCV, HBV). Our results revealed that there is a big west-east gradient in patients being treated per year. NAS is not a rare entity anymore in Austria (up to 50 cases per year in Vienna). Our survey showed that most neonatology departments in Austria treat their patients following written guidelines. Although all of them base these guidelines on international recommendations there is no national consensus. © Georg Thieme Verlag KG Stuttgart · New York.

  4. (GaIn)(NAs) growth using di-tertiary-butyl-arsano-amine (DTBAA)

    NASA Astrophysics Data System (ADS)

    Sterzer, E.; Ringler, B.; Nattermann, L.; Beyer, A.; von Hänisch, C.; Stolz, W.; Volz, K.

    2017-06-01

    III/V semiconductors containing small amounts of Nitrogen (N) are very interesting for a variety of optoelectronic applications. Unfortunately, the conventionally used N precursor 1,1-dimethylhydrazine (UDMHy) has an extremely low N incorporation efficiency in GaAs when grown using metal organic vapor phase epitaxy. Alloying Ga(NAs) with Indium (In) even leads to an exponential reduction of N incorporation. The huge amount of UDMHy in turn changes drastically the growth conditions. Furthermore, the application of this material is still hampered by the large carbon incorporation, most probably originating from the metal organic precursors. Hence, novel precursors for dilute nitride growth are needed. This paper will show (GaIn)(NAs) growth studies with the novel precursor di-tertiary-butyl-arsano-amine in combination with tri-ethyl-gallium and tri-methyl-indium. We show an extremely high N incorporation efficiency in the In containing (GaIn)(NAs). The (GaIn)(NAs) samples investigated in this study have been examined using high resolution X-Ray diffraction, room temperature photoluminescence and atomic force microscope measurements as well as secondary ion mass spectrometry.

  5. Security Controls Hurt Research, NAS Warns.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A National Academy of Sciences (NAS) report found no evidence that leaks of technical information from universities or other research centers have damaged national security. However, in areas where control is warranted, decisions should be based on criteria. These criteria and issues related to security control and technological transfer are…

  6. Low temperature grown GaNAsSb: A promising material for photoconductive switch application

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tan, K. H.; Yoon, S. F.; Wicaksono, S.

    2013-09-09

    We report a photoconductive switch using low temperature grown GaNAsSb as the active material. The GaNAsSb layer was grown at 200 °C by molecular beam epitaxy in conjunction with a radio frequency plasma-assisted nitrogen source and a valved antimony cracker source. The low temperature growth of the GaNAsSb layer increased the dark resistivity of the switch and shortened the carrier lifetime. The switch exhibited a dark resistivity of 10{sup 7} Ω cm, a photo-absorption of up to 2.1 μm, and a carrier lifetime of ∼1.3 ps. These results strongly support the suitability of low temperature grown GaNAsSb in the photoconductivemore » switch application.« less

  7. Six Years of Parallel Computing at NAS (1987 - 1993): What Have we Learned?

    NASA Technical Reports Server (NTRS)

    Simon, Horst D.; Cooper, D. M. (Technical Monitor)

    1994-01-01

    In the fall of 1987 the age of parallelism at NAS began with the installation of a 32K processor CM-2 from Thinking Machines. In 1987 this was described as an "experiment" in parallel processing. In the six years since, NAS acquired a series of parallel machines, and conducted an active research and development effort focused on the use of highly parallel machines for applications in the computational aerosciences. In this time period parallel processing for scientific applications evolved from a fringe research topic into the one of main activities at NAS. In this presentation I will review the history of parallel computing at NAS in the context of the major progress, which has been made in the field in general. I will attempt to summarize the lessons we have learned so far, and the contributions NAS has made to the state of the art. Based on these insights I will comment on the current state of parallel computing (including the HPCC effort) and try to predict some trends for the next six years.

  8. Ultrasonic vibration double scratch morphology and scratching force of BK7 glass

    NASA Astrophysics Data System (ADS)

    Wang, Chu; Wang, Hongxiang; Liu, Junliang; Gao, Shi

    2018-03-01

    In this paper, the damage morphology and scratching force of BK7 glass components were analyzed by ultrasonic vibration double-scratch test. The results showed that there was surface damage caused by plastic flow and brittle fracture during the scratching process, and the scratching depth and the distance between the two scratches had effect on the propagation and overlapping of lateral cracks. When the scratching depth was small, the jagged scratch was produced on the surface, and accompanied by a small amount of tiny pieces of debris off. With the increase in scratching depth, the lateral cracks caused by scratching overlapped and expended to form a mesh sheet, and then fell off from the surface. When the scratching distance was small, the interaction of the cracks caused large slice of material to fall off. With the increase in scratching distance, the area between the two scratches was not easy to occur the overlapping of the lateral cracks. In addition, with the increase of the scratching depth, the scratching force showed a gradual increase trend, and the scratching force of the second scratch would increase with the scratching distance.

  9. Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor

    NASA Astrophysics Data System (ADS)

    Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung

    2014-01-01

    In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

  10. "Legal highs"--toxicity in the clinical and medico-legal aspect as exemplified by suicide with bk-MBDB administration.

    PubMed

    Rojek, Sebastian; Kłys, Małgorzata; Strona, Marcin; Maciów, Martyna; Kula, Karol

    2012-10-10

    The easily available "legal highs", which are products containing psychoactive substances, such as cathinones, piperazines and synthetic cannabinoids, are abused by adolescents in Poland and in the world as alternatives to classic drugs, such as amphetamines or marijuana. The majority of these potentially dangerous substances are still legal and they are associated with a risk of severe poisoning or even death, and provide new challenges in clinical and forensic toxicological practice. Investigations in the field of "designer drugs" may be well illustrated by the case of a suicide of a 21-year old male who ingested a specified dose of a preparation called "Amphi-bi-a" that contains bk-MBDB, chemically 2-methylamino-1-(3,4-methylenedioxyphenyl) butan-1-one, which belongs to the cathinone group, as a synthetic euphoric empathogen and psychoactive stimulant that is chemically similar to MDMA. It is one of more common components of "legal highs" examined in Poland and other countries. The documentation of the case includes a clinical assessment of the patient's health status performed during his almost 4-h hospitalization before death, autopsy and histological examinations supported by toxicological findings revealing bk-MBDB at extremely high concentrations (at 20 mg/l in the blood and 33 mg/kg in the liver); hence, this body of evidence contributes to knowledge in the field of "designer drugs". Inventions of designers of new psychoactive xenobiotics, which are much in demand, especially in view of the dynamic Internet marketing, which drums up narcobusiness, must be balanced by a national strategy developed by medical, legal and educational circles in the modern civilized world in order to prevent the spreading of the phenomenon. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  11. Successful Treatment of BK Virus Hemorrhagic Cystitis (HC) Post Allogenic Hematopoietic Stem Cell Transplantation with Low Dose Cidofovir.

    PubMed

    Arora, R; Jasmita; Singh, M; Garg, A; Gupta, M; Gupta, N

    2017-05-01

    BK virus (BKV) hemorrhagic cystitis (HC) is a serious cause of morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT) in patients with hematological malignancies. Around half of allogenic HSCT patients present with BKV viruria at some point after HSCT; about 5-40% of these patients subsequently develop active HC. Supportive care including bladder irrigation, blood transfusions and symptomatic pain management remains the mainstay of therapy; the acyclic nucleoside analogue cidofovir is currently the front-line drug for BKV-HC treatment. Here we report the first case of severe hemorrhagic cystitis from India who was successfully treated with low dose cidofovir therapy. © Journal of the Association of Physicians of India 2011.

  12. Cytomegalovirus and BK-Virus co-infection of a clinically non-functioning adrenal adenoma: innocent bystanders or new pathogenetic agents?

    PubMed

    Pomara, G; Cappello, F; Barzon, L; Morelli, G; Rappa, F; Benvegna, L; Giannarini, G; Palù, G; Selli, C

    2006-01-01

    We report a case of a 64-year-old woman who underwent left adrenalectomy with removal of a 8,5 cm clinically non-functioning adrenocortical adenoma and a 4-cm myelolipoma. Molecular testing for viral infection demonstrated the presence of cytomegalovirus (CMV) DNA sequences in the adrenal adenoma, but not in the myelolipoma (confirmed by immunohistochemistry). Moreover, the adrenal adenoma was also positive for parvovirus B19, and both adrenal tumor samples were positive for polyomavirus BK (BKV) and adenovirus DNA sequences. This is the first report of co-infection of an adrenocortical adenoma by CMV and BKV. The role of these viruses in adrenal tumorigenesis was postulated.

  13. Successful hyperbaric oxygen therapy for refractory BK virus-associated hemorrhagic cystitis after cord blood transplantation.

    PubMed

    Hosokawa, K; Yamazaki, H; Nakamura, T; Yoroidaka, T; Imi, T; Shima, Y; Ohata, K; Takamatsu, H; Kotani, T; Kondo, Y; Takami, A; Nakao, S

    2014-10-01

    BK virus-associated hemorrhagic cystitis (BKV-HC) is a common and major cause of morbidity in recipients of allogeneic hematopoietic stem cell transplantation. A 32-year-old woman developed severe BKV-HC on day 24 after cord blood transplantation (CBT). Despite supportive therapies - such as hyperhydration, forced diuresis, and urinary catheterization - macroscopic hematuria and bladder irritation persisted for over a month. Hyperbaric oxygen (HBO) therapy at 2.1 atmospheres for 90 min per day was started on day 64 after CBT. Macroscopic hematuria resolved within a week, and microscopic hematuria was no longer detectable within 2 weeks. Hematuria did not recur after 11 sessions of HBO therapy, and no significant side effects were observed during or after treatment. HBO therapy could thus be useful in controlling refractory BKV-HC after CBT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Spatially resolving the outer atmosphere of the M giant BK Virginis in the CO first overtone lines with VLTI/AMBER

    NASA Astrophysics Data System (ADS)

    Ohnaka, K.; Hofmann, K.-H.; Schertl, D.; Weigelt, G.; Malbet, F.; Massi, F.; Meilland, A.; Stee, Ph.

    2012-01-01

    Context. The mass-loss mechanism in normal K-M giant stars with small variability amplitudes is not yet understood, although the majority among red giant stars are precisely of this type. Aims: We present high-spatial and high-spectral resolution observations of the M7 giant BK Vir with AMBER at the Very Large Telescope Interferometer (VLTI). Our aim is to probe the physical properties of the outer atmosphere by spatially resolving the star in the individual CO first overtone lines. Methods: BK Vir was observed between 2.26 and 2.31 μm using the 16-32-48 m telescope configuration with an angular resolution of 9.8 mas and a spectral resolution of 12 000. Results: The uniform-disk diameters observed in the CO first overtone lines are 12 - 31% larger than those measured in the continuum. We also detected asymmetry in the CO line-forming region, which manifests itself as non-zero/non-π differential and closure phases. The data taken 1.5 months apart show possible time variation on a spatial scale of 30 mas (corresponding to 3 × stellar diameter) at the CO band head. Comparison of the observed data with the MARCS photospheric model shows that whereas the observed CO line spectrum can be satisfactorily reproduced by the model, the angular sizes observed in the CO lines are much larger than predicted by the model. Our model with two additional CO layers above the MARCS photosphere reproduces the observed spectrum and interferometric data in the CO lines simultaneously. This model suggests that the inner CO layer at ~1.2 R⋆ is very dense and warm with a CO column density of ~1022 cm-2 and temperatures of 1900 - 2100 K, while the outer CO layer at 2.5-3.0 R⋆ is characterized by column densities of 1019-1020 cm-2 and temperatures of 1500 - 2100 K. Conclusions: Our AMBER observations of BK Vir have spatially resolved the extended molecular outer atmosphere of a normal M giant in the individual CO lines for the first time. The temperatures derived for the CO layers are

  15. Applications Performance on NAS Intel Paragon XP/S - 15#

    NASA Technical Reports Server (NTRS)

    Saini, Subhash; Simon, Horst D.; Copper, D. M. (Technical Monitor)

    1994-01-01

    The Numerical Aerodynamic Simulation (NAS) Systems Division received an Intel Touchstone Sigma prototype model Paragon XP/S- 15 in February, 1993. The i860 XP microprocessor with an integrated floating point unit and operating in dual -instruction mode gives peak performance of 75 million floating point operations (NIFLOPS) per second for 64 bit floating point arithmetic. It is used in the Paragon XP/S-15 which has been installed at NAS, NASA Ames Research Center. The NAS Paragon has 208 nodes and its peak performance is 15.6 GFLOPS. Here, we will report on early experience using the Paragon XP/S- 15. We have tested its performance using both kernels and applications of interest to NAS. We have measured the performance of BLAS 1, 2 and 3 both assembly-coded and Fortran coded on NAS Paragon XP/S- 15. Furthermore, we have investigated the performance of a single node one-dimensional FFT, a distributed two-dimensional FFT and a distributed three-dimensional FFT Finally, we measured the performance of NAS Parallel Benchmarks (NPB) on the Paragon and compare it with the performance obtained on other highly parallel machines, such as CM-5, CRAY T3D, IBM SP I, etc. In particular, we investigated the following issues, which can strongly affect the performance of the Paragon: a. Impact of the operating system: Intel currently uses as a default an operating system OSF/1 AD from the Open Software Foundation. The paging of Open Software Foundation (OSF) server at 22 MB to make more memory available for the application degrades the performance. We found that when the limit of 26 NIB per node out of 32 MB available is reached, the application is paged out of main memory using virtual memory. When the application starts paging, the performance is considerably reduced. We found that dynamic memory allocation can help applications performance under certain circumstances. b. Impact of data cache on the i860/XP: We measured the performance of the BLAS both assembly coded and Fortran

  16. Pharmacists' and prescribers' neonatal abstinence syndrome (NAS) prevention behaviors: a preliminary analysis.

    PubMed

    Hagemeier, Nicholas E; Click, Ivy A; Flippin, Heather; Gilliam, Holly; Ross, Alexandra; Basden, Jeri Ann; Carico, Ronald

    2018-02-01

    Background Maternal opioid use and neonatal abstinence syndrome (NAS) incidence have increased markedly in the US in recent years. Objectives (1) To assess prescribers' and community pharmacists' guideline-based NAS prevention behaviors; (2) to describe providers' perceptions of contraceptive appropriateness in female patients of childbearing age. Method Cross-sectional study of 100 randomly selected primary care physicians, 100 prescribers authorized to engage in in-office treatment of opioid use disorders with buprenorphine, 100 pain management clinic directors, and 100 community pharmacists in Tennessee (N = 400 providers total) to evaluate self-reported engagement in 15 NAS prevention behaviors and perceived appropriateness of 8 contraceptive methods in opioid using women of childbearing age. Results An overall response rate of 17.5% was obtained. Pain clinic directors reported the most engagement in NAS prevention, engaging 80% or more of female patients of childbearing age prescribed an opioid in 11 prevention behaviors, followed by buprenorphine prescribers (8 behaviors), primary care physicians (5 behaviors), and community pharmacists (2 behaviors). Pain clinic directors, primary care physicians, and community pharmacists perceived oral contraceptive pills and patches to be as appropriate as long-acting, reversible forms of contraception (e.g., implants, injectable depots, intrauterine devices). Conclusion Provider engagement in behaviors that could prevent NAS is variable. Interventions should be implemented that equip providers to engage patients in conversations about long-acting, reversible contraception.

  17. Viral drug sensitivity testing using quantitative PCR: effect of tyrosine kinase inhibitors on polyomavirus BK replication.

    PubMed

    Randhawa, Parmjeet S; Farasati, Noush A; Huang, Yuchen; Mapara, Markus Y; Shapiro, Ron

    2010-12-01

    Our objective was to determine whether quantitative polymerase chain reaction (PCR) can be used to measure the effect of tyrosine kinase (TK) inhibition on polyomavirus BK (BKV) replication. The BKV was grown in a cell culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed by amplifying the viral genome using primers directed against the viral capsid 1 protein. Dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and sorafenib all showed antiviral activity at micromolar concentrations. The 50% effective concentration for erlotinib and sorafenib was within blood concentrations readily achieved in human subjects. Quantitative PCR is a convenient method for viral drug sensitivity testing for slow-growing viruses that do not readily produce cytopathic effect. TK inhibitors deserve further consideration as a potential therapeutic option for BKV-associated nephropathy and hemorrhagic cystitis.

  18. The NAS parallel benchmarks

    NASA Technical Reports Server (NTRS)

    Bailey, D. H.; Barszcz, E.; Barton, J. T.; Carter, R. L.; Lasinski, T. A.; Browning, D. S.; Dagum, L.; Fatoohi, R. A.; Frederickson, P. O.; Schreiber, R. S.

    1991-01-01

    A new set of benchmarks has been developed for the performance evaluation of highly parallel supercomputers in the framework of the NASA Ames Numerical Aerodynamic Simulation (NAS) Program. These consist of five 'parallel kernel' benchmarks and three 'simulated application' benchmarks. Together they mimic the computation and data movement characteristics of large-scale computational fluid dynamics applications. The principal distinguishing feature of these benchmarks is their 'pencil and paper' specification-all details of these benchmarks are specified only algorithmically. In this way many of the difficulties associated with conventional benchmarking approaches on highly parallel systems are avoided.

  19. Looking Backward: Parting Reflections on Higher Education Reform from NAS's Founding President

    ERIC Educational Resources Information Center

    Balch, Stephen H.

    2012-01-01

    Twenty-five years at the helm of the National Association of Scholars (NAS) have left the author with vivid memories: of knocks and bruises, peaks of exhilaration and, especially, unforgettable characters. But as for lessons learned, that's a very different story. In this article, the author shares some of the successes that happened in NAS for…

  20. NAS Panel faults export controls

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    A study prepared by a top-level panel says that current export controls on militarily sensitive U.S. technology may be “overcorrecting” previous weaknesses in that system, resulting in “a complex and confusing control system” that makes it more difficult for U.S. businesses to compete in international markets. Moreover, this control system has “an increasingly corrosive effect” on U.S. relations with allies. The panel recommended that the United States concentrate more effort on bringing about uniformity in the export control policies of countries belonging to the Coordinating Committee on Multilateral Export Controls (CoCom), i.e., most of the member nations in NATO (the North Atlantic Treaty Organization) and Japan.The 21-member panel was appointed by the Committee on Science, Engineering, and Public Policy (COSEPUP), a joint unit of the National Academy of Sciences (NAS), the National Academy of Engineering (NAE), and the Institute of Medicine (IOM). The panel, composed of administrators, researchers, and former government officials, was chaired by AGU member Lew Allen, Jr., director of the Jet Propulsion Laboratory (Pasadena, Calif.) and former chief of staff of the U.S. Air Force. Their report was supported by NAS funds, by a number of private organizations (including AGU), by the U.S. Departments of Commerce, Defense, Energy, and State, by the National Science Foundation, and by the National Aeronautics and Space Administration.

  1. An improved NAS-RIF algorithm for image restoration

    NASA Astrophysics Data System (ADS)

    Gao, Weizhe; Zou, Jianhua; Xu, Rong; Liu, Changhai; Li, Hengnian

    2016-10-01

    Space optical images are inevitably degraded by atmospheric turbulence, error of the optical system and motion. In order to get the true image, a novel nonnegativity and support constants recursive inverse filtering (NAS-RIF) algorithm is proposed to restore the degraded image. Firstly the image noise is weaken by Contourlet denoising algorithm. Secondly, the reliable object support region estimation is used to accelerate the algorithm convergence. We introduce the optimal threshold segmentation technology to improve the object support region. Finally, an object construction limit and the logarithm function are added to enhance algorithm stability. Experimental results demonstrate that, the proposed algorithm can increase the PSNR, and improve the quality of the restored images. The convergence speed of the proposed algorithm is faster than that of the original NAS-RIF algorithm.

  2. Unique BK virus non-coding control region (NCCR) variants in hematopoietic stem cell transplant recipients with and without hemorrhagic cystitis.

    PubMed

    Carr, Michael J; McCormack, Grace P; Mutton, Ken J; Crowley, Brendan

    2006-04-01

    Hematopoietic stem cell transplant recipients frequently develop BK virus (BKV)-associated hemorrhagic cystitis, which coincides with BK viruria. However, the precise role of BKV in the etiology of hemorrhagic cystitis in hematopoietic stem cell transplant recipients remains unclear, since approximately 50% of all such adult transplant recipients excrete BKV, yet do not develop this clinical condition. In the present study, BKV were analyzed to determine if mutations in the non-coding control region (NCCR), and specific BKV sub-types defined by sequence analysis of major capsid protein VP1, were associated with development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. The regions encoding VP1 and NCCRs of BKV in urine samples collected from 15 hematopoietic stem cell transplant recipients with hemorrhagic cystitis and 20 without this illness were amplified and sequenced. Sequence variations in the NCCRs of BKV were identified in urine samples from those with and without hemorrhagic cystitis. Furthermore, five unique sequence variations within transcription factor binding sites in the canonical NCCR, O-P-Q-R-S, were identified, representing new BKV variants from a population of cloned quasi-species obtained from patients with and without hemorrhagic cystitis. Thirty-five BKV VP1 sequences were analyzed by phylogenetic analysis but no specific BKV sub-type was associated with hemorrhagic cystitis. Five previously unrecognized naturally occurring variants of the BKV are described which involve amplifications, deletions, and rearrangements of the archetypal BKV NCCRs in individuals with and without hemorrhagic cystitis. Architectural rearrangements in the NCCRs of BKV did not appear to be a prerequisite for development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. Copyright 2006 Wiley-Liss, Inc.

  3. Upgrades to the Probabilistic NAS Platform Air Traffic Simulation Software

    NASA Technical Reports Server (NTRS)

    Hunter, George; Boisvert, Benjamin

    2013-01-01

    This document is the final report for the project entitled "Upgrades to the Probabilistic NAS Platform Air Traffic Simulation Software." This report consists of 17 sections which document the results of the several subtasks of this effort. The Probabilistic NAS Platform (PNP) is an air operations simulation platform developed and maintained by the Saab Sensis Corporation. The improvements made to the PNP simulation include the following: an airborne distributed separation assurance capability, a required time of arrival assignment and conformance capability, and a tactical and strategic weather avoidance capability.

  4. Neonatal Abstinence Syndrome (NAS) in Southwestern Border States: Examining Trends, Population Correlates, and Implications for Policy.

    PubMed

    Hussaini, Khaleel S; Garcia Saavedra, Luigi F

    2018-03-23

    Introduction Neonatal abstinence syndrome (NAS) is withdrawal syndrome in newborns following birth and is primarily caused by maternal drug use during pregnancy. This study examines trends, population correlates, and policy implications of NAS in two Southwest border states. Materials and Methods A cross-sectional analysis of Hospital Inpatient Discharge Data (HIDD) was utilized to examine the incidence of NAS in the Southwest border states of Arizona (AZ) and New Mexico (NM). All inpatient hospital births in AZ and NM from January 1, 2008 through December 31, 2013 with ICD9-CM codes for NAS (779.5), cocaine (760.72), or narcotics (760.75) were extracted. Results During 2008-2013 there were 1472 NAS cases in AZ and 888 in NM. The overall NAS rate during this period was 2.83 per 1000 births (95% CI 2.68-2.97) in AZ and 5.31 (95% CI 4.96-5.66) in NM. NAS rates increased 157% in AZ and 174% in NM. NAS newborns were more likely to have low birth weight, have respiratory distress, more likely to have feeding difficulties, and more likely to be on state Medicaid insurance. AZ border region (border with Mexico) had NAS rates significantly higher than the state rate (4.06 per 1000 births [95% CI 3.68-4.44] vs. 2.83 [95% CI 2.68-2.97], respectively). In NM, the border region rate (2.09 per 1000 births [95% CI 1.48-2.69]) was significantly lower than the state rate (5.31 [95% CI 4.96-5.66]). Conclusions Despite a dramatic increase in the incidence of NAS in the U.S. and, in particular, the Southwest border states of AZ and NM, there is still scant research on the overall incidence of NAS, its assessment in the southwest border, and associated long-term outcomes. The Healthy Border (HB) 2020 binational initiative of the U.S.-Mexico Border Health Commission is an initiative that addresses several public health priorities that not only include chronic and degenerative diseases, infectious diseases, injury prevention, maternal and child health but also mental health and

  5. NAS Parallel Benchmarks. 2.4

    NASA Technical Reports Server (NTRS)

    VanderWijngaart, Rob; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    We describe a new problem size, called Class D, for the NAS Parallel Benchmarks (NPB), whose MPI source code implementation is being released as NPB 2.4. A brief rationale is given for how the new class is derived. We also describe the modifications made to the MPI (Message Passing Interface) implementation to allow the new class to be run on systems with 32-bit integers, and with moderate amounts of memory. Finally, we give the verification values for the new problem size.

  6. Expression of a Diverse Array of Ca2+-Activated K+ Channels (SK1/3, IK1, BK) that Functionally Couple to the Mechanosensitive TRPV4 Channel in the Collecting Duct System of Kidney.

    PubMed

    Li, Yue; Hu, Hongxiang; Butterworth, Michael B; Tian, Jin-Bin; Zhu, Michael X; O'Neil, Roger G

    2016-01-01

    The voltage- and Ca2+-activated, large conductance K+ channel (BK, maxi-K) is expressed in the collecting duct system of kidney where it underlies flow- and Ca2+-dependent K+ excretion. To determine if other Ca2+-activated K+ channels (KCa) may participate in this process, mouse kidney and the K+-secreting mouse cortical collecting duct (CCD) cell line, mCCDcl1, were assessed for TRPV4 and KCa channel expression and cross-talk. qPCR mRNA analysis and immunocytochemical staining demonstrated TRPV4 and KCa expression in mCCDcl1 cells and kidney connecting tubule (CNT) and CCD. Three subfamilies of KCa channels were revealed: the high Ca2+-binding affinity small-conductance SK channels, SK1and SK3, the intermediate conductance channel, IK1, and the low Ca2+-binding affinity, BK channel (BKα subunit). Apparent expression levels varied in CNT/CCD where analysis of CCD principal cells (PC) and intercalated cells (IC) demonstrated differential staining: SK1:PCIC, IK1:PC>IC, BKα:PC = IC, and TRPV4:PC>IC. Patch clamp analysis and fluorescence Ca2+ imaging of mCCDcl1 cells demonstrated potent TRPV4-mediated Ca2+ entry and strong functional cross-talk between TRPV4 and KCa channels. TRPV4-mediated Ca2+ influx activated each KCa channel, as evidenced by selective inhibition of KCa channels, with each active KCa channel enhancing Ca2+ entry (due to membrane hyperpolarization). Transepithelial electrical resistance (TEER) analysis of confluent mCCDcl1 cells grown on permeable supports further demonstrated this cross-talk where TRPV4 activation induce a decrease in TEER which was partially restored upon selective inhibition of each KCa channel. It is concluded that SK1/SK3 and IK1 are highly expressed along with BKα in CNT and CCD and are closely coupled to TRPV4 activation as observed in mCCDcl1 cells. The data support a model in CNT/CCD segments where strong cross talk between TRPV4-mediated Ca2+ influx and each KCa channel leads to enhance Ca2+ entry which

  7. No Evidence for Infection of UK Prostate Cancer Patients with XMRV, BK Virus, Trichomonas vaginalis or Human Papilloma Viruses

    PubMed Central

    Groom, Harriet C. T.; Warren, Anne Y.; Neal, David E.; Bishop, Kate N.

    2012-01-01

    The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer. PMID:22470540

  8. No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses.

    PubMed

    Groom, Harriet C T; Warren, Anne Y; Neal, David E; Bishop, Kate N

    2012-01-01

    The prevalence of specific infections in UK prostate cancer patients was investigated. Serum from 84 patients and 62 controls was tested for neutralisation of xenotropic murine leukaemia virus-related virus (XMRV) Envelope. No reactivity was found in the patient samples. In addition, a further 100 prostate DNA samples were tested for XMRV, BK virus, Trichomonas vaginalis and human papilloma viruses by nucleic acid detection techniques. Despite demonstrating DNA integrity and assay sensitivity, we failed to detect the presence of any of these agents in DNA samples, bar one sample that was weakly positive for HPV16. Therefore we conclude that these infections are absent in this typical cohort of men with prostate cancer.

  9. BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

    PubMed Central

    Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

    2013-01-01

    BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

  10. Operational implications and proposed infrastructure changes for NAS integration of remotely piloted aircraft (RPA)

    DOT National Transportation Integrated Search

    2014-12-01

    The intent of this report is to provide (1) an initial assessment of National Airspace System (NAS) infrastructure affected by continuing development and deployment of unmanned aircraft systems into the NAS, and (2) a description of process challenge...

  11. UAS in the NAS: Survey Responses by ATC, Manned Aircraft Pilots, and UAS Pilots

    NASA Technical Reports Server (NTRS)

    Comstock, James R., Jr.; McAdaragh, Raymon; Ghatas, Rania W.; Burdette, Daniel W.; Trujillo, Anna C.

    2014-01-01

    NASA currently is working with industry and the Federal Aviation Administration (FAA) to establish future requirements for Unmanned Aircraft Systems (UAS) flying in the National Airspace System (NAS). To work these issues NASA has established a multi-center "UAS Integration in the NAS" project. In order to establish Ground Control Station requirements for UAS, the perspective of each of the major players in NAS operations was desired. Three on-line surveys were administered that focused on Air Traffic Controllers (ATC), pilots of manned aircraft, and pilots of UAS. Follow-up telephone interviews were conducted with some survey respondents. The survey questions addressed UAS control, navigation, and communications from the perspective of small and large unmanned aircraft. Questions also addressed issues of UAS equipage, especially with regard to sense and avoid capabilities. From the civilian ATC and military ATC perspectives, of particular interest are how mixed operations (manned / UAS) have worked in the past and the role of aircraft equipage. Knowledge gained from this information is expected to assist the NASA UAS Integration in the NAS project in directing research foci thus assisting the FAA in the development of rules, regulations, and policies related to UAS in the NAS.

  12. UAS in the NAS: Survey Responses by ATC, Manned Aircraft Pilots, and UAS Pilots

    NASA Technical Reports Server (NTRS)

    Comstock, James R., Jr.; McAdaragh, Raymon; Ghatas, Rania W.; Burdette, Daniel W.; Trujillo, Anna C.

    2013-01-01

    NASA currently is working with industry and the Federal Aviation Administration (FAA) to establish future requirements for Unmanned Aircraft Systems (UAS) flying in the National Airspace System (NAS). To work these issues NASA has established a multi-center UAS Integration in the NAS project. In order to establish Ground Control Station requirements for UAS, the perspective of each of the major players in NAS operations was desired. Three on-line surveys were administered that focused on Air Traffic Controllers (ATC), pilots of manned aircraft, and pilots of UAS. Follow-up telephone interviews were conducted with some survey respondents. The survey questions addressed UAS control, navigation, and communications from the perspective of small and large unmanned aircraft. Questions also addressed issues of UAS equipage, especially with regard to sense and avoid capabilities. From the ATC and military ATC perspective, of particular interest is how mixed-operations (manned/UAS) have worked in the past and the role of aircraft equipage. Knowledge gained from this information is expected to assist the NASA UAS in the NAS project in directing research foci thus assisting the FAA in the development of rules, regulations, and policies related to UAS in the NAS.

  13. Comparison of Origin 2000 and Origin 3000 Using NAS Parallel Benchmarks

    NASA Technical Reports Server (NTRS)

    Turney, Raymond D.

    2001-01-01

    This report describes results of benchmark tests on the Origin 3000 system currently being installed at the NASA Ames National Advanced Supercomputing facility. This machine will ultimately contain 1024 R14K processors. The first part of the system, installed in November, 2000 and named mendel, is an Origin 3000 with 128 R12K processors. For comparison purposes, the tests were also run on lomax, an Origin 2000 with R12K processors. The BT, LU, and SP application benchmarks in the NAS Parallel Benchmark Suite and the kernel benchmark FT were chosen to determine system performance and measure the impact of changes on the machine as it evolves. Having been written to measure performance on Computational Fluid Dynamics applications, these benchmarks are assumed appropriate to represent the NAS workload. Since the NAS runs both message passing (MPI) and shared-memory, compiler directive type codes, both MPI and OpenMP versions of the benchmarks were used. The MPI versions used were the latest official release of the NAS Parallel Benchmarks, version 2.3. The OpenMP versiqns used were PBN3b2, a beta version that is in the process of being released. NPB 2.3 and PBN 3b2 are technically different benchmarks, and NPB results are not directly comparable to PBN results.

  14. Positions of the cytoplasmic end of BK α S0 helix relative to S1–S6 and of β1 TM1 and TM2 relative to S0–S6

    PubMed Central

    Liu, Guoxia; Zakharov, Sergey I.; Yao, Yongneng

    2015-01-01

    The large-conductance, voltage- and Ca2+-gated K+ (BK) channel consists of four α subunits, which form a voltage- and Ca2+-gated channel, and up to four modulatory β subunits. The β1 subunit is expressed in smooth muscle, where it slows BK channel kinetics and shifts the conductance–voltage (G-V) curve to the left at [Ca2+] > 2 µM. In addition to the six transmembrane (TM) helices, S1–S6, conserved in all voltage-dependent K+ channels, BK α has a unique seventh TM helix, S0, which may contribute to the unusual rightward shift in the G-V curve of BK α in the absence of β1 and to a leftward shift in its presence. Such a role is supported by the close proximity of S0 to S3 and S4 in the voltage-sensing domain. Furthermore, on the extracellular side of the membrane, one of the two TM helices of β1, TM2, is adjacent to S0. We have now analyzed induced disulfide bond formation between substituted Cys residues on the cytoplasmic side of the membrane. There, in contrast, S0 is closest to the S2–S3 loop, from which position it is displaced on the addition of β1. The cytoplasmic ends of β1 TM1 and TM2 are adjacent and are located between the S2–S3 loop of one α subunit and S1 of a neighboring α subunit and are not adjacent to S0; i.e., S0 and TM2 have different trajectories through the membrane. In the absence of β1, 70% of disulfide bonding of W43C (S0) and L175C (S2–S3) has no effect on V50 for activation, implying that the cytoplasmic end of S0 and the S2–S3 loop move in concert, if at all, during activation. Otherwise, linking them together in one state would obstruct the transition to the other state, which would certainly change V50. PMID:25667410

  15. Nasal allergies in the Latin American population: results from the Allergies in Latin America survey.

    PubMed

    Neffen, Hugo; Mello, Joao F; Sole, Dirceu; Naspitz, Charles K; Dodero, Alberto Eduardo; Garza, Héctor León; Guerra, Edgard Novelo; Baez-Loyola, Carlos; Boyle, John M; Wingertzahn, Mark A

    2010-01-01

    Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >or=4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population. Approximately 7% of the LA population was diagnosed with NAs with two of three respondents stating that their allergies were seasonal or intermittent in nature. A general practice physician or otolaryngologist diagnosed the majority of individuals surveyed. Nasal congestion was the most common and bothersome symptom of NAs. Sufferers indicated that their symptoms affected productivity and sleep and had a negative impact on quality of life. Two-thirds of patients reported taking some type of medication for their NAs, with a roughly equal percentage of patients reporting taking over-the-counter versus prescription medications. Changing medications was most commonly done in those reporting inadequate efficacy. The most common reasons cited for dissatisfaction with current medications were related to inadequate effectiveness, effectiveness wearing off with chronic use, failure to provide 24-hour relief, and bothersome side effects (e.g., unpleasant taste and retrograde drainage into the esophagus). Findings from this cross-national survey on NAs have confirmed a high prevalence of physician-diagnosed NAs and a considerable negative impact on daily quality of life and work productivity as well as substantial disease management challenges in LA. Through identification of disease impact on the LA population and further defining treatment gaps, clinicians in

  16. Effect of antimony on the deep-level traps in GaInNAsSb thin films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Islam, Muhammad Monirul, E-mail: islam.monir.ke@u.tsukuba.ac.jp; Miyashita, Naoya; Ahsan, Nazmul

    2014-09-15

    Admittance spectroscopy has been performed to investigate the effect of antimony (Sb) on GaInNAs material in relation to the deep-level defects in this material. Two electron traps, E1 and E2 at an energy level 0.12 and 0.41 eV below the conduction band (E{sub C}), respectively, were found in undoped GaInNAs. Bias-voltage dependent admittance confirmed that E1 is an interface-type defect being spatially localized at the GaInNAs/GaAs interface, while E2 is a bulk-type defect located around mid-gap of GaInNAs layer. Introduction of Sb improved the material quality which was evident from the reduction of both the interface and bulk-type defects.

  17. Evaluation and utilization of preassembled frozen commercial fast real-time qPCR master mixes for detection of cytomegalovirus and BK virus.

    PubMed

    Glover, William A; Atienza, Ederlyn E; Nesbitt, Shannon; Kim, Woo J; Castor, Jared; Cook, Linda; Jerome, Keith R

    2016-01-01

    Quantitative DNA detection of cytomegalovirus (CMV) and BK virus (BKV) is critical in the management of transplant patients. Quantitative laboratory-developed procedures for CMV and BKV have been described in which much of the processing is automated, resulting in rapid, reproducible, and high-throughput testing of transplant patients. To increase the efficiency of such assays, the performance and stability of four commercial preassembled frozen fast qPCR master mixes (Roche FastStart Universal Probe Master Mix with Rox, Bio-Rad SsoFast Probes Supermix with Rox, Life Technologies TaqMan FastAdvanced Master Mix, and Life Technologies Fast Universal PCR Master Mix), in combination with in-house designed primers and probes, was evaluated using controls and standards from standard CMV and BK assays. A subsequent parallel evaluation using patient samples was performed comparing the performance of freshly prepared assay mixes versus aliquoted frozen master mixes made with two of the fast qPCR mixes (Life Technologies TaqMan FastAdvanced Master Mix, and Bio-Rad SsoFast Probes Supermix with Rox), chosen based on their performance and compatibility with existing PCR cycling conditions. The data demonstrate that the frozen master mixes retain excellent performance over a period of at least 10 weeks. During the parallel testing using clinical specimens, no difference in quantitative results was observed between the preassembled frozen master mixes and freshly prepared master mixes. Preassembled fast real-time qPCR frozen master mixes perform well and represent an additional strategy laboratories can implement to reduce assay preparation times, and to minimize technical errors and effort necessary to perform clinical PCR. © 2015 Wiley Periodicals, Inc.

  18. Prevalence of BK virus replication among recipients of solid organ transplants.

    PubMed

    Muñoz, Patricia; Fogeda, Marta; Bouza, Emilio; Verde, Eduardo; Palomo, Jesus; Bañares, Rafael

    2005-12-15

    BK virus (BKV) has been implicated as a cause of nephritis and graft loss in 2%-9% of kidney transplant recipients, but the prevalence among recipients of other solid organ transplants (SOTs) has not been well established. Our objective was to determine the prevalence of BKV infection for all types of SOT recipients at our medical center. A total of 156 consecutive SOT recipients were studied, of whom 49 received kidney transplants, 43 received heart transplants, and 64 received liver transplants. Samples were obtained a median of 559 days (range, 1-9481 days) after transplantation. Nested polymerase chain reaction was performed for detection of BKV DNA in urine and plasma specimens. BKV was found in 19% of urine specimens and 6% of plasma specimens. The prevalence of viruria after kidney, heart, and liver transplantation was 26.5%, 25.5%, and 7.8%, respectively. BKV viremia was detected in 12.2% of kidney transplant recipients and 7% of heart transplant recipients. Mean creatinine levels were higher in patients with BKV viruria or viremia (1.9 and 3.5 mg/dL, respectively) than in patients with no BKV replication (1.3 mg/dL). Independent factors related to impaired renal function were renal transplantation (odds ratio [OR], 14.4); BKV replication, including viruria or viremia (OR, 3.3); and mycophenolate use (OR, 2.6). BKV is common in all types of SOT recipients, particularly those who have received heart or kidney transplants.

  19. NAS Grid Benchmarks: A Tool for Grid Space Exploration

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael; VanderWijngaart, Rob F.; Biegel, Bryan (Technical Monitor)

    2001-01-01

    We present an approach for benchmarking services provided by computational Grids. It is based on the NAS Parallel Benchmarks (NPB) and is called NAS Grid Benchmark (NGB) in this paper. We present NGB as a data flow graph encapsulating an instance of an NPB code in each graph node, which communicates with other nodes by sending/receiving initialization data. These nodes may be mapped to the same or different Grid machines. Like NPB, NGB will specify several different classes (problem sizes). NGB also specifies the generic Grid services sufficient for running the bench-mark. The implementor has the freedom to choose any specific Grid environment. However, we describe a reference implementation in Java, and present some scenarios for using NGB.

  20. Examination of Frameworks for Safe Integration of Intelligent Small UAS into the NAS

    NASA Technical Reports Server (NTRS)

    Logan, Michael J.

    2012-01-01

    This paper discusses a proposed framework for the safe integration of small unmanned aerial systems (sUAS) into the National Airspace System (NAS). The paper briefly examines the potential uses of sUAS to build an understanding of the location and frequency of potential future flight operations based on the future applications of the sUAS systems. The paper then examines the types of systems that would be required to meet the application-level demand to determine "classes" of platforms and operations. A framework for categorization of the "intelligence" level of the UAS is postulated for purposes of NAS integration. Finally, constraints on the intelligent systems are postulated to ensure their ease of integration into the NAS.

  1. First-principles study on structure stabilities of α-S and Na-S battery systems

    NASA Astrophysics Data System (ADS)

    Momida, Hiroyoshi; Oguchi, Tamio

    2014-03-01

    To understand microscopic mechanisms of charge and discharge reactions in Na-S batteries, there has been increasing needs to study fundamental atomic and electronic structures of elemental S as well as that of Na-S phases. The most stable form of S is known to be an orthorhombic α-S crystal at ambient temperature and pressure, and α-S consists of puckered S8 rings which crystallize in space group Fddd . In this study, the crystal structure of α-S is examined by using first-principles calculations with and without the van der Waals interaction corrections of Grimme's method, and results clearly show that the van der Waals interactions between the S8 rings have crucial roles on cohesion of α-S. We also study structure stabilities of Na2S, NaS, NaS2, and Na2S5 phases with reported crystal structures. Using calculated total energies of the crystal structure models, we estimate discharge voltages assuming discharge reactions from 2Na+ xS -->Na2Sx, and discharge reactions in Na/S battery systems are discussed by comparing with experimental results. This work was partially supported by Elements Strategy Initiative for Catalysts and Batteries (ESICB) of Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan.

  2. Cidofovir for BK virus-associated hemorrhagic cystitis: a retrospective study.

    PubMed

    Cesaro, Simone; Hirsch, Hans H; Faraci, Maura; Owoc-Lempach, Joanna; Beltrame, Angela; Tendas, Andrea; Baltadakis, Ioannis; Dalle, Jean-Hughes; Koc, Yener; Toporski, Jacek; Styczynski, Jan; Yesilipek, M Akif; Heinz, Werner; Caniglia, Maurizio; Rascon, Jelena; Fauser, Axel A; Michallet, Mauricette; Lopez-Corral, Lucia; Neuburger, Stefan; Tridello, Gloria; Einsele, Herman

    2009-07-15

    BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

  3. Neutralization Serotyping of BK Polyomavirus Infection in Kidney Transplant Recipients

    PubMed Central

    Pastrana, Diana V.; Brennan, Daniel C.; Çuburu, Nicolas; Storch, Gregory A.; Viscidi, Raphael P.; Randhawa, Parmjeet S.; Buck, Christopher B.

    2012-01-01

    BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy. PMID:22511874

  4. Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Myhre, Marit Renee; Olsen, Gunn-Hege; Gosert, Rainer

    High-level replication of polyomavirus BK (BKV) in kidney transplant recipients is associated with the emergence of BKV variants with rearranged (rr) non-coding control region (NCCR) increasing viral early gene expression and cytopathology. Cloning and sequencing revealed the presence of a BKV quasispecies which included non-functional variants when assayed in a recombinant virus assay. Here we report that the rr-NCCR of BKV variants RH-3 and RH-12, both bearing a NCCR deletion including the 5' end of the agnoprotein coding sequence, mediated early and late viral reporter gene expression in kidney cells. However, in a recombinant virus they failed to produce infectiousmore » progeny despite large T-antigen and VP1 expression and the formation of nuclear virus-like particles. Infectious progeny was generated when the agnogene was reconstructed in cis or agnoprotein provided in trans from a co-existing BKV rr-NCCR variant. We conclude that complementation can rescue non-functional BKV variants in vitro and possibly in vivo.« less

  5. Data communication requirements for the advanced NAS network

    NASA Technical Reports Server (NTRS)

    Levin, Eugene; Eaton, C. K.; Young, Bruce

    1986-01-01

    The goal of the Numerical Aerodynamic Simulation (NAS) Program is to provide a powerful computational environment for advanced research and development in aeronautics and related disciplines. The present NAS system consists of a Cray 2 supercomputer connected by a data network to a large mass storage system, to sophisticated local graphics workstations, and by remote communications to researchers throughout the United States. The program plan is to continue acquiring the most powerful supercomputers as they become available. In the 1987/1988 time period it is anticipated that a computer with 4 times the processing speed of a Cray 2 will be obtained and by 1990 an additional supercomputer with 16 times the speed of the Cray 2. The implications of this 20-fold increase in processing power on the data communications requirements are described. The analysis was based on models of the projected workload and system architecture. The results are presented together with the estimates of their sensitivity to assumptions inherent in the models.

  6. BK virus DNA detection by real-time polymerase chain reaction in clinical specimens.

    PubMed

    Marchetti, Simona; Graffeo, Rosalia; Siddu, Alessia; Santangelo, Rosaria; Ciotti, Marco; Picardi, Alessandra; Favalli, Cartesio; Fadda, Giovanni; Cattani, Paola

    2007-04-01

    The BK polyomavirus (BKV) is widespread in the general population. In transplant recipients, the patients' weakened immune response may encourage reactivation of latent infection, leading to BKV-related diseases. Rapid and quantitative detection might help to delineate viral reactivation patterns and could thus play an important role in their clinical management. In our study we developed an "in-house" quantitative real-time PCR to detect BKV DNA. The effectiveness of this assay was evaluated by a retrospective analysis of 118 plasma specimens from 22 bone marrow transplant (BMT) recipients and 107 samples from immunocompetent subjects. Eight (36.3%) of the 22 bone marrow transplant recipients tested positive for BKV. The viral load varied from specimen to specimen (10 to 10(5) copies/ml). BKV related disease like hemorrhagic cystitis (HC) was diagnosed in three patients. Specimens from the control group all tested negative. Our results showed the high sensitivity of the real-time PCR, allowing accurate and reproducible measuring of the viral load in order to identify patients at risk for BKV-related diseases. With due caution in interpreting threshold values, the real-time PCR could provide a rapid, sensitive and specific tool for detecting BKV and distinguishing latent and active infection.

  7. Optimization, purification, and characterization of L-asparaginase from Actinomycetales bacterium BkSoiiA.

    PubMed

    Dash, Chitrangada; Mohapatra, Sukanti Bala; Maiti, Prasanta Kumar

    2016-01-01

    Actinobacteria are promising source of a wide range of important enzymes, some of which are produced in industrial scale, with others yet to be harnessed. L-Asparaginase is used as an antineoplastic agent. The present work deals with the production and optimization of L-asparaginase from Actinomycetales bacterium BkSoiiA using submerged fermentation in M9 medium. Production optimization resulted in a modified M9 medium with yeast extract and fructose as carbon and nitrogen sources, respectively, at pH 8.0, incubated for 120 hr at 30 ± 2 °C. The crude enzyme was purified to near homogeneity by ammonium sulfate precipitation following dialysis, ion-exchange column chromatography, and finally gel filtration. The sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) revealed an apparent molecular weight of 57 kD. The enzyme was purified 95.06-fold and showed a final specific activity of 204.37 U/mg with 3.49% yield. The purified enzyme showed maximum activity at a pH 10.0 and was stable at pH 7.0 to 9.0. The enzyme was activated by Mn(2+) and strongly inhibited by Ba(2+). All these preliminary characterization suggests that the L-asparaginase from the source may be a tool useful to pharmaceutical industries after further research.

  8. Clinical effectiveness of hyperbaric oxygen therapy for BK-virus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation.

    PubMed

    Savva-Bordalo, J; Pinho Vaz, C; Sousa, M; Branca, R; Campilho, F; Resende, R; Baldaque, I; Camacho, O; Campos, A

    2012-08-01

    Late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with BK virus (BKV). Antiviral drugs are of limited efficacy and the optimal treatment for HC has not yet been established. Hyperbaric oxygen (HBO) may benefit these patients. We, therefore, retrospectively evaluated the effectiveness of HBO therapy in 16 patients with HC after allogeneic HSCT. All 16 patients had macroscopic hematuria and BKV infection. Patients received 100% oxygen in a hyperbaric chamber at 2.1 atmospheres for 90 min, 5 days per week, with a median 13 treatments (range, 4-84). Fifteen patients (94%) showed complete resolution of hematuria. Median urinary DNA BKV titers declined after HBO (P<0.05). Patients started on HBO earlier after diagnosis of HC responded sooner (P<0.05). HBO was generally well tolerated and proved to be a reliable option for this difficult to manage condition.

  9. Prony series spectra of structural relaxation in N-BK7 for finite element modeling.

    PubMed

    Koontz, Erick; Blouin, Vincent; Wachtel, Peter; Musgraves, J David; Richardson, Kathleen

    2012-12-20

    Structural relaxation behavior of N-BK7 glass was characterized at temperatures 20 °C above and below T(12) for this glass, using a thermo mechanical analyzer (TMA). T(12) is a characteristic temperature corresponding to a viscosity of 10(12) Pa·s. The glass was subject to quick temperature down-jumps preceded and followed by long isothermal holds. The exponential-like decay of the sample height was recorded and fitted using a unique Prony series method. The result of his method was a plot of the fit parameters revealing the presence of four distinct peaks or distributions of relaxation times. The number of relaxation times decreased as final test temperature was increased. The relaxation times did not shift significantly with changing temperature; however, the Prony weight terms varied essentially linearly with temperature. It was also found that the structural relaxation behavior of the glass trended toward single exponential behavior at temperatures above the testing range. The result of the analysis was a temperature-dependent Prony series model that can be used in finite element modeling of glass behavior in processes such as precision glass molding (PGM).

  10. Ubiquity and Diversity of Heterotrophic Bacterial nasA Genes in Diverse Marine Environments

    PubMed Central

    Jiang, Xuexia; Dang, Hongyue; Jiao, Nianzhi

    2015-01-01

    Nitrate uptake by heterotrophic bacteria plays an important role in marine N cycling. However, few studies have investigated the diversity of environmental nitrate assimilating bacteria (NAB). In this study, the diversity and biogeographical distribution of NAB in several global oceans and particularly in the western Pacific marginal seas were investigated using both cultivation and culture-independent molecular approaches. Phylogenetic analyses based on 16S rRNA and nasA (encoding the large subunit of the assimilatory nitrate reductase) gene sequences indicated that the cultivable NAB in South China Sea belonged to the α-Proteobacteria, γ-Proteobacteria and CFB (Cytophaga-Flavobacteria-Bacteroides) bacterial groups. In all the environmental samples of the present study, α-Proteobacteria, γ-Proteobacteria and Bacteroidetes were found to be the dominant nasA-harboring bacteria. Almost all of the α-Proteobacteria OTUs were classified into three Roseobacter-like groups (I to III). Clone library analysis revealed previously underestimated nasA diversity; e.g. the nasA gene sequences affiliated with β-Proteobacteria, ε-Proteobacteria and Lentisphaerae were observed in the field investigation for the first time, to the best of our knowledge. The geographical and vertical distributions of seawater nasA-harboring bacteria indicated that NAB were highly diverse and ubiquitously distributed in the studied marginal seas and world oceans. Niche adaptation and separation and/or limited dispersal might mediate the NAB composition and community structure in different water bodies. In the shallow-water Kueishantao hydrothermal vent environment, chemolithoautotrophic sulfur-oxidizing bacteria were the primary NAB, indicating a unique nitrate-assimilating community in this extreme environment. In the coastal water of the East China Sea, the relative abundance of Alteromonas and Roseobacter-like nasA gene sequences responded closely to algal blooms, indicating that NAB may be

  11. Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent.

    PubMed

    Geetha, Duvuru; Tong, Betty C; Racusen, Lorraine; Markowitz, Jay S; Westra, William H

    2002-06-27

    The BK polyomavirus (BKV) infects most of the human population, but clinically relevant infections are mostly limited to individuals who are immunosuppressed. In transplant recipients, BKV has been associated with ureteral stenosis, interstitial nephritis, and hemorrhagic cystitis. The role of BKV in the development of human tumors is intriguing but uncertain. BKV has been identified in various tumor types including urothelial carcinoma, but the ubiquitous presence of BKV as a latent infection has confounded efforts to validate any causal role in cancer development. We report the case of a simultaneous pancreas and kidney transplant recipient who developed BKV interstitial nephritis and carcinoma of the bladder with widespread metastases. High level expression of BKV large T antigen in the primary and metastatic carcinoma, but not in the nonneoplastic urothelium, implicates BKV as an etiologic agent in the development of this tumor.

  12. Misperceptions of harm among Natural American Spirit smokers: results from wave 1 of the Population Assessment of Tobacco and Health (PATH) study (2013-2014).

    PubMed

    Pearson, Jennifer L; Johnson, Amanda; Villanti, Andrea; Glasser, Allison M; Collins, Lauren; Cohn, Amy; Rose, Shyanika W; Niaura, Raymond; Stanton, Cassandra A

    2017-03-01

    This study estimated differences in cigarette harm perceptions among smokers of the Natural American Spirit (NAS) brand-marketed as 'natural', 'organic' and 'additive-free'-compared to other smokers, and examined correlates of NAS use. Data were drawn from wave 1 of the Population Assessment of Tobacco and Health (PATH) study, a nationally representative study of US adults (2013-2014). Weighted analyses using a subset of current adult smokers (n=10 565) estimated the prevalence of NAS use (vs all other brands) and examined associations between NAS use and sociodemographics, tobacco/substance use, tobacco harm perceptions, quit intentions, quit attempts and mental/behavioural health. Overall, 2.3% of adult smokers (920 000 people in the USA) reported NAS as their usual brand. Nearly 64% of NAS smokers inaccurately believed that their brand is less harmful than other brands compared to 8.3% of smokers of other brands, after controlling for potential confounders (aOR 22.82). Younger age (18-34 vs 35+; aOR 1.54), frequent thinking about tobacco harms (aOR 1.84), past 30-day alcohol use (aOR 1.57), past 30-day marijuana use (aOR 1.87) and sexual orientation (lesbian, gay, bisexual, 'other' or 'questioning' vs heterosexual; aOR 2.07) were also associated with increased odds of smoking NAS. The majority of NAS smokers inaccurately believes that their cigarettes are less harmful than other brands. Given the brand's rapid growth and its more common use in vulnerable groups (eg, young adults, lesbian, gay, bisexual, 'other' or 'questioning' adults), corrective messaging and enforcement action are necessary to correct harm misperceptions of NAS cigarettes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Autotasked Performance in the NAS Workload: A Statistical Analysis

    NASA Technical Reports Server (NTRS)

    Carter, R. L.; Stockdale, I. E.; Kutler, Paul (Technical Monitor)

    1998-01-01

    A statistical analysis of the workload performance of a production quality FORTRAN code for five different Cray Y-MP hardware and system software configurations is performed. The analysis was based on an experimental procedure that was designed to minimize correlations between the number of requested CPUs and the time of day the runs were initiated. Observed autotasking over heads were significantly larger for the set of jobs that requested the maximum number of CPUs. Speedups for UNICOS 6 releases show consistent wall clock speedups in the workload of around 2. which is quite good. The observed speed ups were very similar for the set of jobs that requested 8 CPUs and the set that requested 4 CPUs. The original NAS algorithm for determining charges to the user discourages autotasking in the workload. A new charging algorithm to be applied to jobs run in the NQS multitasking queues also discourages NAS users from using auto tasking. The new algorithm favors jobs requesting 8 CPUs over those that request less, although the jobs requesting 8 CPUs experienced significantly higher over head and presumably degraded system throughput. A charging algorithm is presented that has the following desirable characteristics when applied to the data: higher overhead jobs requesting 8 CPUs are penalized when compared to moderate overhead jobs requesting 4 CPUs, thereby providing a charging incentive to NAS users to use autotasking in a manner that provides them with significantly improved turnaround while also maintaining system throughput.

  14. UAS Integration in the NAS FY15 Annual Review

    NASA Technical Reports Server (NTRS)

    Grindle, Laurie; Randall, Debra; Hackenburg, Davis

    2015-01-01

    This presentation gives insight into the research activities and efforts being executed in order to integrate unmanned aircraft systems into the national airspace system. This briefing is to inform others of the UAS-NAS progress and future directions.

  15. Nas transgenic mouse line allows visualization of Notch pathway activity in vivo

    PubMed Central

    Souilhol, Céline; Cormier, Sarah; Monet, Marie; Vandormael-Pournin, Sandrine; Joutel, Anne; Babinet, Charles; Cohen-Tannoudji, Michel

    2006-01-01

    The Notch signalling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular the precise mapping of its sites of activity, remain unclear. To address this issue, we have generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jκ binding sites. Here we show that this transgenic line, we named NAS for Notch Activity Sensor, displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jκ deficient background indicating that it indeed requires Notch/RBP-Jκ signalling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signalling pathway. PMID:16708386

  16. Investigations of the Optical Properties of GaNAs Alloys by First-Principle.

    PubMed

    Borovac, Damir; Tan, Chee-Keong; Tansu, Nelson

    2017-12-11

    We present a Density Functional Theory (DFT) analysis of the optical properties of dilute-As GaN 1-x As x alloys with arsenic (As) content ranging from 0% up to 12.5%. The real and imaginary parts of the dielectric function are investigated, and the results are compared to experimental and theoretical values for GaN. The analysis extends to present the complex refractive index and the normal-incidence reflectivity. The refractive index difference between GaN and GaNAs alloys can be engineered to be up to ~0.35 in the visible regime by inserting relatively low amounts of As-content into the GaN system. Thus, the analysis elucidates on the birefringence of the dilute-As GaNAs alloys and comparison to other experimentally characterized III-nitride systems is drawn. Our findings indicate the potential of GaNAs alloys for III-nitride based waveguide and photonic circuit design applications.

  17. Nas transgenic mouse line allows visualization of Notch pathway activity in vivo.

    PubMed

    Souilhol, Céline; Cormier, Sarah; Monet, Marie; Vandormael-Pournin, Sandrine; Joutel, Anne; Babinet, Charles; Cohen-Tannoudji, Michel

    2006-06-01

    The Notch signaling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular, the precise mapping of its sites of activity, remain unclear. To address this issue, we generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jkappa binding sites. Here we show that this transgenic line, which we termed NAS (for Notch Activity Sensor), displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jkappa-deficient background, indicating that it indeed requires Notch/RBP-Jkappa signaling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signaling pathway.

  18. Padrões de refluxo nas veias safenas em homens com insuficiência venosa crônica

    PubMed Central

    Engelhorn, Carlos Alberto; Coral, Francisco Eduardo; Soares, Isabela Chaves Monteiro; Corrêa, Gabriel Fernando de Araújo; Ogeda, Jaqueline Pozzolo; Hara, Larissa Yuri; Murasse, Luisa Saemi

    2016-01-01

    Resumo Contexto A insuficiência venosa crônica (IVCr) é frequente e predomina nas mulheres, mas ainda há poucas informações sobre o refluxo nas veias safenas na população masculina. Objetivos Identificar os diferentes padrões de refluxo nas veias safenas magnas (VSMs) e parvas (VSPs) em homens, correlacionando esses dados com a apresentação clínica conforme a classificação Clínica, Etiológica, Anatômica e Fisiopatológica (CEAP). Métodos Foram avaliados 369 membros inferiores de 207 homens pela ultrassonografia vascular (UV) com diagnóstico clínico de IVCr primária. As variáveis analisadas foram a classificação CEAP, o padrão de refluxo nas VSMs e VSPs e a correlação entre os dois. Resultados Nos 369 membros avaliados, 72,9% das VSMs apresentaram refluxo com predominância do padrão segmentar (33,8%). Nas VSPs, 16% dos membros inferiores analisados apresentaram refluxo, sendo o mais frequente o padrão distal (33,9%). Dos membros classificados como C4, C5 e C6, 100% apresentaram refluxo na VSM com predominância do refluxo proximal (25,64%), e 38,46% apresentaram refluxo na VSP com equivalência entre os padrões distal e proximal (33,3%). Refluxo na junção safeno-femoral (JSF) foi detectado em 7,1% dos membros nas classes C0 e C1, 35,6% nas classes C2 e C3, e 64,1% nas classes C4 a C6. Conclusões O padrão de refluxo segmentar é predominante na VSM, e o padrão de refluxo distal é predominante na VSP. A ocorrência de refluxo na JSF é maior em pacientes com IVCr mais avançada. PMID:29930603

  19. One-dimensional carbon-sulfur composite fibers for Na-S rechargeable batteries operating at room temperature.

    PubMed

    Hwang, Tae Hoon; Jung, Dae Soo; Kim, Joo-Seong; Kim, Byung Gon; Choi, Jang Wook

    2013-09-11

    Na-S batteries are one type of molten salt battery and have been used to support stationary energy storage systems for several decades. Despite their successful applications based on long cycle lives and low cost of raw materials, Na-S cells require high temperatures above 300 °C for their operations, limiting their propagation into a wide range of applications. Herein, we demonstrate that Na-S cells with solid state active materials can perform well even at room temperature when sulfur-containing carbon composites generated from a simple thermal reaction were used as sulfur positive electrodes. Furthermore, this structure turned out to be robust during repeated (de)sodiation for ~500 cycles and enabled extraordinarily high rate performance when one-dimensional morphology is adopted using scalable electrospinning processes. The current study suggests that solid-state Na-S cells with appropriate atomic configurations of sulfur active materials could cover diverse battery applications where cost of raw materials is critical.

  20. Object-Oriented Implementation of the NAS Parallel Benchmarks using Charm++

    NASA Technical Reports Server (NTRS)

    Krishnan, Sanjeev; Bhandarkar, Milind; Kale, Laxmikant V.

    1996-01-01

    This report describes experiences with implementing the NAS Computational Fluid Dynamics benchmarks using a parallel object-oriented language, Charm++. Our main objective in implementing the NAS CFD kernel benchmarks was to develop a code that could be used to easily experiment with different domain decomposition strategies and dynamic load balancing. We also wished to leverage the object-orientation provided by the Charm++ parallel object-oriented language, to develop reusable abstractions that would simplify the process of developing parallel applications. We first describe the Charm++ parallel programming model and the parallel object array abstraction, then go into detail about each of the Scalar Pentadiagonal (SP) and Lower/Upper Triangular (LU) benchmarks, along with performance results. Finally we conclude with an evaluation of the methodology used.

  1. 78 FR 12951 - TRICARE; Elimination of the Non-Availability Statement (NAS) Requirement for Non-Emergency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-26

    ... There are no anticipated budgetary health care cost increases. Requiring a NAS for a relatively few non... Inpatient Mental Health Care AGENCY: Office of the Secretary, Department of Defense. ACTION: Final rule... inpatient mental health care in order for a TRICARE Standard beneficiary's claim to be paid. Currently, NAS...

  2. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project FY17 Annual Review

    NASA Technical Reports Server (NTRS)

    Sakahara, Robert; Hackenberg, Davis; Johnson, William

    2017-01-01

    This presentation was presented to the Integrated Aviation Systems Program at the FY17 Annual Review of the UAS-NAS project. The presentation captures the overview of the work completed by the UAS-NAS project and its subprojects.

  3. Parallelization of NAS Benchmarks for Shared Memory Multiprocessors

    NASA Technical Reports Server (NTRS)

    Waheed, Abdul; Yan, Jerry C.; Saini, Subhash (Technical Monitor)

    1998-01-01

    This paper presents our experiences of parallelizing the sequential implementation of NAS benchmarks using compiler directives on SGI Origin2000 distributed shared memory (DSM) system. Porting existing applications to new high performance parallel and distributed computing platforms is a challenging task. Ideally, a user develops a sequential version of the application, leaving the task of porting to new generations of high performance computing systems to parallelization tools and compilers. Due to the simplicity of programming shared-memory multiprocessors, compiler developers have provided various facilities to allow the users to exploit parallelism. Native compilers on SGI Origin2000 support multiprocessing directives to allow users to exploit loop-level parallelism in their programs. Additionally, supporting tools can accomplish this process automatically and present the results of parallelization to the users. We experimented with these compiler directives and supporting tools by parallelizing sequential implementation of NAS benchmarks. Results reported in this paper indicate that with minimal effort, the performance gain is comparable with the hand-parallelized, carefully optimized, message-passing implementations of the same benchmarks.

  4. Quantum dot-like emitters formed due to alloy fluctuations in GaNAs-based nanowires.

    NASA Astrophysics Data System (ADS)

    Buyanova, Irina; Jansson, M.; Filippov, S.; Stehr, J.; Palisaitis, J.; Persson, P.; Ishikawa, F.; Chen, Weimin

    Group III-V semiconductor nanowires with embedded quantum dots (QDs) are currently attracting increasing attention as a highly attractive platform for a variety of advanced applications ranging from third generation photovoltaics to quantum information technologies. In this work, we show that local fluctuations in N composition inside coaxial GaAs/GaNAs nanowires induces three-dimensional confining potentials equivalent to that for QDs thus forming optically active and highly localized states inside the GaNAs shell. Principal quantization axis of these states is concluded to mainly coincide with the nanowire axis, based on the strong polarization of the detected emission orthogonal to the nanowire axis revealed from polarization-resolved micro-photoluminescence studies. This is partly attributed to a predominantly uniaxial tensile strain field in the GaNAs shell caused by lattice mismatch with the GaAs core. GaNAs alloys can, therefore, be used as an active material in hybrid QD-NW structures utilized for fabrication of nanoscale polarized-light sources that are efficient within the near-infrared spectral range. Financial support by the Swedish Energy Agency (Grant # P40119-1) and the Swedish Research Council (Grant # 2015-05532) is greatly appreciated.

  5. Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation.

    PubMed

    Mani, Jiju; Jin, Nan; Schmitt, Michael

    2014-10-01

    Immunosuppression of patients after hematopoietic stem cell or kidney transplantation potentially leads to reactivation of JC and BK polyomaviruses. In hematopoietic stem cell transplantation, the reactivation rate of BKV can be up to 60%, resulting in severe complications of the urogenital tract, particularly hemorrhagic cystitis and renal dysfunction. After kidney transplantation, BKV reactivation can cause a loss of the graft. JCV can cause progressive multifocal leukoencephalopathy, a lethal disease. Adoptive transfer of donor-derived polyomavirus-specific T cells is an attractive and promising treatment that restores virus-specific cellular immunity. Pioneering work in the early 1990s on the reconstitution of cellular immunity against cytomegalovirus and recent development in the field of monitoring and isolation of antigen-specific T cells paved the way toward a personalized T-cell therapy. Multimer technology and magnetic beads are available to produce untouched T cells in a single-step, good manufacturing practice-compliant procedure. Another exciting aspect of T-cell therapy against polyomaviruses is the fact that both JCV and BKV can be targeted simultaneously because of their high sequence homology. Finally, "designer T cells" can be redirected to recognize polyomavirus antigens with high-affinity T-cell receptors. This review summarizes the state-of-the art technologies and gives an outlook of future developments in the field. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  6. Orientations and Proximities of the Extracellular Ends of Transmembrane Helices S0 and S4 in Open and Closed BK Potassium Channels

    PubMed Central

    Wu, Roland S.; Chudasama, Neelesh; Zakharov, Sergey I.; Karlin, Arthur; Marx, Steven O.

    2013-01-01

    The large-conductance potassium channel (BK) α subunit contains a transmembrane (TM) helix S0 preceding the canonical TM helices S1 through S6. S0 lies between S4 and the TM2 helix of the regulatory β1 subunit. Pairs of Cys were substituted in the first helical turns in the membrane of BK α S0 and S4 and in β1 TM2. One such pair, W22C in S0 and W203C in S4, was 95% crosslinked endogenously. Under voltage-clamp conditions in outside-out patches, this crosslink was reduced by DTT and reoxidized by a membrane-impermeant bis-quaternary ammonium derivative of diamide. The rate constants for this reoxidation were not significantly different in the open and closed states of the channel. Thus, these two residues are approximately equally close in the two states. In addition, 90% crosslinking of a second pair, R20C in S0 and W203C in S4, had no effect on the V50 for opening. Taken together, these findings indicate that separation between residues at the extracellular ends of S0 and S4 is not required for voltage-sensor activation. On the contrary, even though W22C and W203C were equally likely to form a disulfide in the activated and deactivated states, relative immobilization by crosslinking of these two residues favored the activated state. Furthermore, the efficiency of recrosslinking of W22C and W203C on the cell surface was greater in the presence of the β1 subunit than in its absence, consistent with β1 acting through S0 to stabilize its immobilization relative to α S4. PMID:23472181

  7. Implementation of NAS Parallel Benchmarks in Java

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael; Schultz, Matthew; Jin, Hao-Qiang; Yan, Jerry

    2000-01-01

    A number of features make Java an attractive but a debatable choice for High Performance Computing (HPC). In order to gauge the applicability of Java to the Computational Fluid Dynamics (CFD) we have implemented NAS Parallel Benchmarks in Java. The performance and scalability of the benchmarks point out the areas where improvement in Java compiler technology and in Java thread implementation would move Java closer to Fortran in the competition for CFD applications.

  8. An Association between BK Virus Replication in Bone Marrow and Cytopenia in Kidney-Transplant Recipients

    PubMed Central

    Pambrun, Emilie; Mengelle, Catherine; Fillola, Geneviève; Laharrague, Patrick; Esposito, Laure; Cardeau-Desangles, Isabelle; Del Bello, Arnaud; Izopet, Jacques; Rostaing, Lionel; Kamar, Nassim

    2014-01-01

    The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was observed. Hematological disorders disappeared in all patients after doses of immunosuppressants were reduced. In conclusion, an association between BKV replication in bone marrow and hematological disorders, especially neutropenia, was observed. Further studies are needed to confirm these findings. PMID:24868448

  9. Epidemiologic Study and Genotyping of BK Virus in Renal Transplant Recipients.

    PubMed

    Cobos, M; Aquilia, L; Garay, E; Ochiuzzi, S; Alvarez, S; Flores, D; Raimondi, C

    2018-03-01

    BK virus (BKV) infection occurs during childhood and remains latent in the urinary tract. The virus is reactivated in immunosuppressed patients, particularly in those with cellular immunity deficiency, allowing its detection in urine and blood. Nephropathy caused by the virus in renal transplantation recipients may lead to graft failure. The purpose of this study is to know the prevalence of BKV variables in renal transplantation recipients and to evaluate their clinical evolution through molecular methods of "in house" development. Urine and peripheral blood samples from 66 renal transplantation recipients from the province of Buenos Aires, Argentina, were systematically analyzed every 3 months as well as when there was graft dysfunction. Renal biopsies, which were included in the BKV detection study, were performed on those patients with graft dysfunction. Genotyping of 24 BKVs was performed, and the following distribution was found: 21 (87.5%) belonged to subtype I, 3 (12.5%) to subtype II. BKV belonging to subtypes III or IV were not found. As regards subtype I subgroups, the following were identified: 1 (4.76%) from Ia, 10 (47.61%) from Ib1 and 10 (47.61%) from Ib2. Presence of subgroup Ic was not shown. Viremia presented in 33.33% of cases, whereas 75% corresponded to subgroup Ib 1. Genotype Ib1 is prevailing in Southeast Asia, while Ib2 is prominent in Europe. Although an important proportion of the inhabitants of the province of Buenos Aires are European descendants, the prevailing genotype is Ib1, the Asian type. Genotyping might be related to the evolution of the disease in the recipient. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Functional Reorganization of Promyelocytic Leukemia Nuclear Bodies during BK Virus Infection

    PubMed Central

    Jiang, Mengxi; Entezami, Pouya; Gamez, Monica; Stamminger, Thomas; Imperiale, Michael J.

    2011-01-01

    BK virus (BKV) is the causative agent for polyomavirus-associated nephropathy, a severe disease found in renal transplant patients due to reactivation of a persistent BKV infection. BKV replication relies on the interactions of BKV with many nuclear components, and subnuclear structures such as promyelocytic leukemia nuclear bodies (PML-NBs) are known to play regulatory roles during a number of DNA virus infections. In this study, we investigated the relationship between PML-NBs and BKV during infection of primary human renal proximal tubule epithelial (RPTE) cells. While the levels of the major PML-NB protein components remained unchanged, BKV infection of RPTE cells resulted in dramatic alterations in both the number and the size of PML-NBs. Furthermore, two normally constitutive components of PML-NBs, Sp100 and hDaxx, became dispersed from PML-NBs. To define the viral factors responsible for this reorganization, we examined the cellular localization of the BKV large tumor antigen (TAg) and viral DNA. TAg colocalized with PML-NBs during early infection, while a number of BKV chromosomes were adjacent to PML-NBs during late infection. We demonstrated that TAg alone was not sufficient to reorganize PML-NBs and that active viral DNA replication is required. Knockdown of PML protein did not dramatically affect BKV growth in culture. BKV infection, however, was able to rescue the growth of an ICP0-null herpes simplex virus 1 mutant whose growth defect was partially due to its inability to disrupt PML-NBs. We hypothesize that the antiviral functions of PML-NBs are inactivated through reorganization during normal BKV infection. PMID:21304169

  11. Applications Performance Under MPL and MPI on NAS IBM SP2

    NASA Technical Reports Server (NTRS)

    Saini, Subhash; Simon, Horst D.; Lasinski, T. A. (Technical Monitor)

    1994-01-01

    On July 5, 1994, an IBM Scalable POWER parallel System (IBM SP2) with 64 nodes, was installed at the Numerical Aerodynamic Simulation (NAS) Facility Each node of NAS IBM SP2 is a "wide node" consisting of a RISC 6000/590 workstation module with a clock of 66.5 MHz which can perform four floating point operations per clock with a peak performance of 266 Mflop/s. By the end of 1994, 64 nodes of IBM SP2 will be upgraded to 160 nodes with a peak performance of 42.5 Gflop/s. An overview of the IBM SP2 hardware is presented. The basic understanding of architectural details of RS 6000/590 will help application scientists the porting, optimizing, and tuning of codes from other machines such as the CRAY C90 and the Paragon to the NAS SP2. Optimization techniques such as quad-word loading, effective utilization of two floating point units, and data cache optimization of RS 6000/590 is illustrated, with examples giving performance gains at each optimization step. The conversion of codes using Intel's message passing library NX to codes using native Message Passing Library (MPL) and the Message Passing Interface (NMI) library available on the IBM SP2 is illustrated. In particular, we will present the performance of Fast Fourier Transform (FFT) kernel from NAS Parallel Benchmarks (NPB) under MPL and MPI. We have also optimized some of Fortran BLAS 2 and BLAS 3 routines, e.g., the optimized Fortran DAXPY runs at 175 Mflop/s and optimized Fortran DGEMM runs at 230 Mflop/s per node. The performance of the NPB (Class B) on the IBM SP2 is compared with the CRAY C90, Intel Paragon, TMC CM-5E, and the CRAY T3D.

  12. Analysis of decay chains of superheavy nuclei produced in the 249Bk+48Ca and 243Am+48Ca reactions

    NASA Astrophysics Data System (ADS)

    Zlokazov, V. B.; Utyonkov, V. K.

    2017-07-01

    The analysis of decay chains starting at superheavy nuclei 293Ts and 289Mc is presented. The spectroscopic properties of nuclei identified during the experiments using the 249Bk+48Ca and 243Am+48Ca reactions studied at the gas-filled separators DGFRS, TASCA and BGS are considered. We present the analysis of decay data using widely adopted statistical methods and applying them to the short decay chains of parent odd-Z nuclei. We find out that the recently suggested method of analyzing decay chains by Forsberg et al may lead to questionable conclusions when applied for the analysis of radioactive decays. Our discussion demonstrates reasonable congruence of α-particle energies and decay times of nuclei assigned to isotopes 289Mc, 285Nh and 281Rg observed in both reactions.

  13. An Integrated Gate Turnaround Management Concept Leveraging Big Data Analytics for NAS Performance Improvements

    NASA Technical Reports Server (NTRS)

    Chung, William W.; Ingram, Carla D.; Ahlquist, Douglas Kurt; Chachad, Girish H.

    2016-01-01

    "Gate Turnaround" plays a key role in the National Air Space (NAS) gate-to-gate performance by receiving aircraft when they reach their destination airport, and delivering aircraft into the NAS upon departing from the gate and subsequent takeoff. The time spent at the gate in meeting the planned departure time is influenced by many factors and often with considerable uncertainties. Uncertainties such as weather, early or late arrivals, disembarking and boarding passengers, unloading/reloading cargo, aircraft logistics/maintenance services and ground handling, traffic in ramp and movement areas for taxi-in and taxi-out, and departure queue management for takeoff are likely encountered on the daily basis. The Integrated Gate Turnaround Management (IGTM) concept is leveraging relevant historical data to support optimization of the gate operations, which include arrival, at the gate, departure based on constraints (e.g., available gates at the arrival, ground crew and equipment for the gate turnaround, and over capacity demand upon departure), and collaborative decision-making. The IGTM concept provides effective information services and decision tools to the stakeholders, such as airline dispatchers, gate agents, airport operators, ramp controllers, and air traffic control (ATC) traffic managers and ground controllers to mitigate uncertainties arising from both nominal and off-nominal airport gate operations. IGTM will provide NAS stakeholders customized decision making tools through a User Interface (UI) by leveraging historical data (Big Data), net-enabled Air Traffic Management (ATM) live data, and analytics according to dependencies among NAS parameters for the stakeholders to manage and optimize the NAS performance in the gate turnaround domain. The application will give stakeholders predictable results based on the past and current NAS performance according to selected decision trees through the UI. The predictable results are generated based on analysis of the

  14. Statistical Analysis of NAS Parallel Benchmarks and LINPACK Results

    NASA Technical Reports Server (NTRS)

    Meuer, Hans-Werner; Simon, Horst D.; Strohmeier, Erich; Lasinski, T. A. (Technical Monitor)

    1994-01-01

    In the last three years extensive performance data have been reported for parallel machines both based on the NAS Parallel Benchmarks, and on LINPACK. In this study we have used the reported benchmark results and performed a number of statistical experiments using factor, cluster, and regression analyses. In addition to the performance results of LINPACK and the eight NAS parallel benchmarks, we have also included peak performance of the machine, and the LINPACK n and n(sub 1/2) values. Some of the results and observations can be summarized as follows: 1) All benchmarks are strongly correlated with peak performance. 2) LINPACK and EP have each a unique signature. 3) The remaining NPB can grouped into three groups as follows: (CG and IS), (LU and SP), and (MG, FT, and BT). Hence three (or four with EP) benchmarks are sufficient to characterize the overall NPB performance. Our poster presentation will follow a standard poster format, and will present the data of our statistical analysis in detail.

  15. NAS technical summaries. Numerical aerodynamic simulation program, March 1992 - February 1993

    NASA Technical Reports Server (NTRS)

    1994-01-01

    NASA created the Numerical Aerodynamic Simulation (NAS) Program in 1987 to focus resources on solving critical problems in aeroscience and related disciplines by utilizing the power of the most advanced supercomputers available. The NAS Program provides scientists with the necessary computing power to solve today's most demanding computational fluid dynamics problems and serves as a pathfinder in integrating leading-edge supercomputing technologies, thus benefitting other supercomputer centers in government and industry. The 1992-93 operational year concluded with 399 high-speed processor projects and 91 parallel projects representing NASA, the Department of Defense, other government agencies, private industry, and universities. This document provides a glimpse at some of the significant scientific results for the year.

  16. NAS technical summaries: Numerical aerodynamic simulation program, March 1991 - February 1992

    NASA Technical Reports Server (NTRS)

    1992-01-01

    NASA created the Numerical Aerodynamic Simulation (NAS) Program in 1987 to focus resources on solving critical problems in aeroscience and related disciplines by utilizing the power of the most advanced supercomputers available. The NAS Program provides scientists with the necessary computing power to solve today's most demanding computational fluid dynamics problems and serves as a pathfinder in integrating leading-edge supercomputing technologies, thus benefiting other supercomputer centers in Government and industry. This report contains selected scientific results from the 1991-92 NAS Operational Year, March 4, 1991 to March 3, 1992, which is the fifth year of operation. During this year, the scientific community was given access to a Cray-2 and a Cray Y-MP. The Cray-2, the first generation supercomputer, has four processors, 256 megawords of central memory, and a total sustained speed of 250 million floating point operations per second. The Cray Y-MP, the second generation supercomputer, has eight processors and a total sustained speed of one billion floating point operations per second. Additional memory was installed this year, doubling capacity from 128 to 256 megawords of solid-state storage-device memory. Because of its higher performance, the Cray Y-MP delivered approximately 77 percent of the total number of supercomputer hours used during this year.

  17. Design handbook : energy efficiency and water conservation in NAS facilities

    DOT National Transportation Integrated Search

    1997-09-30

    This handbook was created to provide definitive energy efficiency and water conservation design criteria for the design of NAS facilities. FAA-HDBK-001 provides implementation strategies and tools to comply with E.O. 12902, Energy and Water Conservat...

  18. De Novo Collapsing Glomerulopathy in Renal Allograft in Association with BK Virus Nephropathy in a Child and Stabilization of Renal Function by Elimination of Viremia.

    PubMed

    Gera, D N; Shah, M K; Ghodela, V A; Kute, V B; Trivedi, H L

    2017-01-01

    Well-recognized association between HIV 1 infection and collapsing glomerulopathy (CG) raises the possibility that intrarenal infection by other viruses may also contribute to the development of this lesion in native or post-transplant kidneys. There is evidence in literature about association of these lesions with cytomegalovirus, Epstein-Barr virus, hepatitis C virus, and parvovirus B19 infections. Here, we present a case report of post-transplant BK virus nephropathy in a male child who was found to have CG in subsequent biopsy 2 months later. His renal function and proteinuria were stabilized on elimination of viremia.

  19. Benefits of a Unified LaSRS++ Simulation for NAS-Wide and High-Fidelity Modeling

    NASA Technical Reports Server (NTRS)

    Glaab, Patricia; Madden, Michael

    2014-01-01

    The LaSRS++ high-fidelity vehicle simulation was extended in 2012 to support a NAS-wide simulation mode. Since the initial proof-of-concept, the LaSRS++ NAS-wide simulation is maturing into a research-ready tool. A primary benefit of this new capability is the consolidation of the two modeling paradigms under a single framework to save cost, facilitate iterative concept testing between the two tools, and to promote communication and model sharing between user communities at Langley. Specific benefits of each type of modeling are discussed along with the expected benefits of the unified framework. Current capability details of the LaSRS++ NAS-wide simulations are provided, including the visualization tool, live data interface, trajectory generators, terminal routing for arrivals and departures, maneuvering, re-routing, navigation, winds, and turbulence. The plan for future development is also described.

  20. UAS Integration in the NAS Project - FY 14 Annual Review

    NASA Technical Reports Server (NTRS)

    Grindle, Laurie; Randall, Debra; Hackenberg, Davis

    2014-01-01

    This briefing gives insight into the research activities and efforts being executed in order to integrate unmanned aircraft systems into the national airspace system. This briefing is to inform others of the UAS-NAS Projects progress and future directions.

  1. DOE Radiation Research Program is floundering - NAS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lobsenz, G.

    1994-04-20

    The Energy Department's radiation health effects research program is floundering in a morass of administrative confusion due to an ill-considered 1990 joint management agreement between DOE and the Health and Human Services Department, a National Academy of Sciences panel says. The NAS panel said the [open quotes]administrative difficulties[close quotes] created by the DOE-HHS agreement appear to be [open quotes]stifling creativity and efficiency within DOE's Epidemiology Research Program, delaying the completion and publication of research.[close quotes] The panel also expressed concern that DOE has failed to adequately fund or staff its health research office, and that the department had no mastermore » research plan to identify research needs or set forth uniform, scientifically rigorous data collection procedures. The panel said DOE's lack of commitment was particularly evident in its failure to set up an effective health surveillance program for its nuclear work force. In addition, the panel said DOE had fallen short on promises to create a comprehensive computer bank of health research data that would be continually updated with new information gleaned from an ongoing worker surveillance program. While recommending enhancements, the NAS panel emphasized that DOE's health research program would not be able to function effectively until the department revamped its joint management agreement with HHS.« less

  2. Transcriptome Analysis of the Role of GlnD/GlnBK in Nitrogen Stress Adaptation by Sinorhizobium meliloti Rm1021

    PubMed Central

    Yurgel, Svetlana N.; Rice, Jennifer; Kahn, Michael L.

    2013-01-01

    Transcriptional changes in the nitrogen stress response (NSR) of wild type S. meliloti Rm1021, and isogenic strains missing both PII proteins, GlnB and GlnK, or carrying a ΔglnD-sm2 mutation were analyzed using whole-genome microarrays. This approach allowed us to identify a number of new genes involved in the NSR and showed that the response of these bacteria to nitrogen stress overlaps with other stress responses, including induction of the fixK2 transcriptional activator and genes that are part of the phosphate stress response. Our data also show that GlnD and GlnBK proteins may regulate many genes that are not part of the NSR. Analysis of transcriptome profiles of the Rm1021 ΔglnD-sm2 strain allowed us to identify several genes that appear to be regulated by GlnD without the participation of the PII proteins. PMID:23516427

  3. Meeting of Experts on NASA's Unmanned Aircraft System (UAS) Integration in the National Airspace Systems (NAS) Project

    NASA Technical Reports Server (NTRS)

    Wolfe, Jean; Bauer, Jeff; Bixby, C.J.; Lauderdale, Todd; Shively, Jay; Griner, James; Hayhurst, Kelly

    2010-01-01

    Topics discussed include: Aeronautics Research Mission Directorate Integrated Systems Research Program (ISRP) and UAS Integration in the NAS Project; UAS Integration into the NAS Project; Separation Assurance and Collision Avoidance; Pilot Aircraft Interface Objectives/Rationale; Communication; Certification; and Integrated Tests and Evaluations.

  4. Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases.

    PubMed

    Toptas, Tayfur; Kaygusuz-Atagunduz, Isik; Kani, Haluk Tarik; Adiguzel, Cafer; Firatli-Tuglular, Tulin

    2014-10-01

    BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC.

  5. QNAP 1263U Network Attached Storage (NAS)/ Storage Area Network (SAN) Device Users Guide

    DTIC Science & Technology

    2016-11-01

    standard Ethernet network. Operating either a NAS or SAN is vital for the integrity of the data stored on the drives found in the device. Redundant...speed of the network itself. Many standards are in place for transferring data, including more standard ones such as File Transfer Protocol and Server ...following are the procedures for connecting to the NAS administrative web page: 1) Open a web browser and browse to 192.168.40.8:8080. 2) Enter the

  6. Frequency and subtype of BK virus infection in Iranian patients infected with HIV.

    PubMed

    Akhgari, Shahla; Mohraz, Minoo; Azadmanesh, Kayhan; Vahabpour, Rouhollah; Kazemimanesh, Monireh; Aghakhani, Arezoo; Jozpanahi, Manizheh; Banifazl, Mohammad; Bavand, Anahita; Ramezani, Amitis

    2016-02-01

    Human polyomavirus BK virus (BKV) is a double-stranded DNA virus that infects approximately 90 % of the general population as a subclinical or mild infection. In immunosuppressed patients, such as HIV cases, BKV may be reactivated resulting hemorrhagic cystitis and tubulointerstitial nephritis. However, there are limited studies on prevalence and molecular epidemiology of BKV in Iran. We therefore aimed to evaluate the prevalence and subtypes of BKV in Iranian HIV patients. A total of 99 patients with HIV infection were enrolled in the study. Presence of BKV DNA in plasma was evaluated by nested PCR. PCR products were sequenced directly, and phylogenetic analysis was performed. BKV DNA was detected in 8.08 % of HIV patients. BKV viremia presented in 4 out of 25 patients (16 %) not receiving antiretroviral therapy in comparison with 4 out 74 of HAART-treated patients (5.4 %) (P = 0.023). In patients with CD4 counts ≥200 cells/mm(3), viremia was found more commonly (7/80 = 8.8 %) than in those with lower counts (1/19 = 5.2 %) (not significant). All sequenced BKV isolates belonged to subtype Ib-2. Our findings indicated that the prevalence of BKV viremia is relatively prevalent in patients with HIV infection and significantly higher in naïve than HAART-treated cases. Therefore, HAART can eliminate BKV infection from plasma and reduce viremia although the actual implication of BKV viremia in HIV patients is not clear.

  7. Implementation of the NAS Parallel Benchmarks in Java

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael A.; Schultz, Matthew; Jin, Haoqiang; Yan, Jerry; Biegel, Bryan (Technical Monitor)

    2002-01-01

    Several features make Java an attractive choice for High Performance Computing (HPC). In order to gauge the applicability of Java to Computational Fluid Dynamics (CFD), we have implemented the NAS (NASA Advanced Supercomputing) Parallel Benchmarks in Java. The performance and scalability of the benchmarks point out the areas where improvement in Java compiler technology and in Java thread implementation would position Java closer to Fortran in the competition for CFD applications.

  8. Unstructured Adaptive (UA) NAS Parallel Benchmark. Version 1.0

    NASA Technical Reports Server (NTRS)

    Feng, Huiyu; VanderWijngaart, Rob; Biswas, Rupak; Mavriplis, Catherine

    2004-01-01

    We present a complete specification of a new benchmark for measuring the performance of modern computer systems when solving scientific problems featuring irregular, dynamic memory accesses. It complements the existing NAS Parallel Benchmark suite. The benchmark involves the solution of a stylized heat transfer problem in a cubic domain, discretized on an adaptively refined, unstructured mesh.

  9. UAS Integration in the NAS Project: Integrated Test and Evaluation (IT&E) Flight Test 3. Revision E

    NASA Technical Reports Server (NTRS)

    Marston, Michael

    2015-01-01

    The desire and ability to fly Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) is of increasing urgency. The application of unmanned aircraft to perform national security, defense, scientific, and emergency management are driving the critical need for less restrictive access by UAS to the NAS. UAS represent a new capability that will provide a variety of services in the government (public) and commercial (civil) aviation sectors. The growth of this potential industry has not yet been realized due to the lack of a common understanding of what is required to safely operate UAS in the NAS. NASA's UAS Integration into the NAS Project is conducting research in the areas of Separation Assurance/Sense and Avoid Interoperability, Human Systems Integration (HSI), and Communication to support reducing the barriers of UAS access to the NAS. This research is broken into two research themes namely, UAS Integration and Test Infrastructure. UAS Integration focuses on airspace integration procedures and performance standards to enable UAS integration in the air transportation system, covering Sense and Avoid (SAA) performance standards, command and control performance standards, and human systems integration. The focus of Test Infrastructure is to enable development and validation of airspace integration procedures and performance standards, including the integrated test and evaluation. In support of the integrated test and evaluation efforts, the Project will develop an adaptable, scalable, and schedulable relevant test environment capable of evaluating concepts and technologies for unmanned aircraft systems to safely operate in the NAS. To accomplish this task, the Project will conduct a series of Human-in-the-Loop and Flight Test activities that integrate key concepts, technologies and/or procedures in a relevant air traffic environment. Each of the integrated events will build on the technical achievements, fidelity and complexity of the previous tests and

  10. Compositional dependence of the band gap in Ga(NAsP) quantum well heterostructures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jandieri, K., E-mail: kakhaber.jandieri@physik.uni-marburg.de; Ludewig, P.; Wegele, T.

    We present experimental and theoretical studies of the composition dependence of the direct band gap energy in Ga(NAsP)/GaP quantum well heterostructures grown on either (001) GaP- or Si-substrates. The theoretical description takes into account the band anti-crossing model for the conduction band as well as the modification of the valence subband structure due to the strain resulting from the pseudomorphic epitaxial growth on the respective substrate. The composition dependence of the direct band gap of Ga(NAsP) is obtained for a wide range of nitrogen and phosphorus contents relevant for laser applications on Si-substrate.

  11. Self-assembled GaInNAs/GaAsN quantum dot lasers: solid source molecular beam epitaxy growth and high-temperature operation

    PubMed Central

    Liu, CY; Sun, ZZ; Yew, KC

    2006-01-01

    Self-assembled GaInNAs quantum dots (QDs) were grown on GaAs (001) substrate using solid-source molecular-beam epitaxy (SSMBE) equipped with a radio-frequency nitrogen plasma source. The GaInNAs QD growth characteristics were extensively investigated using atomic-force microscopy (AFM), photoluminescence (PL), and transmission electron microscopy (TEM) measurements. Self-assembled GaInNAs/GaAsN single layer QD lasers grown using SSMBE have been fabricated and characterized. The laser worked under continuous wave (CW) operation at room temperature (RT) with emission wavelength of 1175.86 nm. Temperature-dependent measurements have been carried out on the GaInNAs QD lasers. The lowest obtained threshold current density in this work is ∼1.05 kA/cm2from a GaInNAs QD laser (50 × 1,700 µm2) at 10 °C. High-temperature operation up to 65 °C was demonstrated from an unbonded GaInNAs QD laser (50 × 1,060 µm2), with high characteristic temperature of 79.4 K in the temperature range of 10–60 °C.

  12. Cidofovir in the Treatment of BK Virus-Associated Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Philippe, Michael; Ranchon, Florence; Gilis, Lila; Schwiertz, Vérane; Vantard, Nicolas; Ader, Florence; Labussiere-Wallet, Hélène; Thomas, Xavier; Nicolini, Franck-Emmanuel; Wattel, Eric; Ducastelle-Leprêtre, Sophie; Barraco, Fiorenza; Lebras, Laure; Salles, Gilles; Michallet, Mauricette; Rioufol, Catherine

    2016-04-01

    After allogeneic hematopoietic stem cell transplantation (HSCT), BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication. Although supportive measures have been the standard of care for many years, several studies suggested the efficacy of cidofovir. The aim of this study was to assess the safety profile and efficacy of cidofovir. A retrospective study was conducted on all patients treated with cidofovir in our HSCT unit between March 2011 and May 2013. Data for efficacy (partial [PR] or complete response [CR]), prescription (dose, frequency, number of doses, and administration route), and toxicity were collected from published reports and medical files. Renal toxicity was evaluated using creatinine clearance calculated with the Cockcroft and Gault formula. A parallel literature search using PubMed (last search, May 2015) was performed. From March 2011 to June 2013, 27 of 181 patients undergoing allogeneic HSCT in our department received cidofovir for BKV-HC: 24 (88.9%) intravenously, 1 intravesically, and 2 via both routes. Mean dose was 5 mg/kg per administration, for a median of 4 injections (range, 1 to 11), from twice a week to once every 2 weeks. CR was achieved in 22 patients (81.5%), PR in 2, and no response in 2 patients. Eight patients presented renal failure (29.6%): 6 moderate (creatinine clearance < 60 mL/min) and 2 severe (creatinine clearance < 30 mLmin). Mean decrease in creatinine clearance after cidofovir was 27% (35 mL/min; range, 2 to 159). In 3 cases renal insufficiency and hematologic toxicity led to discontinuation of treatment or switch to intravesical instillation. For 3 patients cidofovir dose was reduced because of nephrotoxicity. Thirteen studies have reported on the use of cidofovir for BKV-HC (204 patients) since 2005. Intravenous cidofovir was used for 91.3% of patients, with doses ranging from .5 to 5 mg/kg. The main toxicity reported was renal failure (9% to 50% in 9 studies). Between 60% and 100% of CRs

  13. UAS in the NAS Flight Test Series 3 Overview

    NASA Technical Reports Server (NTRS)

    Murphy, James R.

    2015-01-01

    The UAS Integration in the NAS Project is conducting a series of flight tests to acheive the following objectives: 1.) Validate results previously collected during project simulations with live data 2.) Evaluate TCAS IISS interoperability 3.) Test fully integrated system in a relevant live test environment 4.) Inform final DAA and C2 MOPS 5.) Reduce risk for Flight Test Series 4.

  14. Levofloxacin for the treatment of severe refractory BK virus-associated hemorrhagic cystitis in hematopoietic stem cell transplantation recipients: A report of three cases

    PubMed Central

    TOPTAS, TAYFUR; KAYGUSUZ-ATAGUNDUZ, ISIK; KANI, HALUK TARIK; ADIGUZEL, CAFER; FIRATLI-TUGLULAR, TULIN

    2014-01-01

    BK-virus (BKV) is an important etiological agent for late-onset hemorrhagic cystitis (HC) in patients undergoing hematopoietic stem cell transplantation. Late-onset HC causes significant morbidity among these patients. Therapeutic approaches remain predominantly symptomatic. Several treatment options have been used with variable success rates. Cidofovir has the highest specificity against BKV; however, its lack of availability in the majority of countries, high costs and potential nephrotoxic effects limit its use. The present study reports three cases of severe and prolonged BKV-associated HC (BKHC). HC was resolved in all three of the patients using oral levofloxacin. Thus, levofloxacin may be an effective treatment modality for achieving complete clinical and molecular response in patients with refractory, severe BKHC. PMID:25202408

  15. Yaughan and Curriboo Plantations: Studies in Afro-American Archaeology.

    DTIC Science & Technology

    1983-04-01

    dogwood, briars, shrubs , and vines . The only site approaching a native habitat before testing was 38BK76, which had been covered by an oak-hickory forest...1974 Basic statistical methods, fourth edition. Harper and Row, Mew York. Drewel, Henry 1980 Personal communication. Art historian, University of Indiana ...South Carolina. Lofstrom, Edward Urling * 1976 A seriation of historic ceramics in the midwest , 1780-1870. Paper presented at the Joint Plains Midwest

  16. Transformation of primary human embryonic kidney cells to anchorage independence by a combination of BK virus DNA and the Harvey-ras oncogene

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pater, A.; Pater, M.M.

    Primary human embryonic kidney (HEK) cells were transformed by a focus assay with BK virus (BKV) DNA molecularly cloned at its unique EcoRI site. Both viral DNA sequences and viral tumor antigens were present and expressed in all the foci that the authors examined. However, cells isolated from foci were incapable of growth in soft agar. They then examined the transformation of HEK cells after their transfection with a combination of BKV DNA and either the normal or the activated form of the human Ha-ras oncogene (EJ c-Ha-ras-1). Only the cells transfected with a combination of BKV DNA and themore » activated form of Ha-ras DNAs were present in the transformed colonies. BKV tumor antigens and the Ha-ras p21 protein were also expressed.« less

  17. Integrative Approach for Computationally Inferring Interactions between the Alpha and Beta Subunits of the Calcium-Activated Potassium Channel (BK): a Docking Study

    PubMed Central

    González, Janneth; Gálvez, Angela; Morales, Ludis; Barreto, George E.; Capani, Francisco; Sierra, Omar; Torres, Yolima

    2013-01-01

    Three-dimensional models of the alpha- and beta-1 subunits of the calcium-activated potassium channel (BK) were predicted by threading modeling. A recursive approach comprising of sequence alignment and model building based on three templates was used to build these models, with the refinement of non-conserved regions carried out using threading techniques. The complex formed by the subunits was studied by means of docking techniques, using 3D models of the two subunits, and an approach based on rigid-body structures. Structural effects of the complex were analyzed with respect to hydrogen-bond interactions and binding-energy calculations. Potential interaction sites of the complex were determined by referencing a study of the difference accessible surface area (DASA) of the protein subunits in the complex. PMID:23492851

  18. UAS-NAS Project Demo - Mini HITL Week 2 Stats

    NASA Technical Reports Server (NTRS)

    Murphy, James R.; Fern, Lisa C.; Rorie, Robert C.; Shively, Robert; Jovic, Srboljub

    2016-01-01

    The UAS-NAS Project demo will showcase recent research efforts to ensure the interoperability between proposed UAS detect and avoid (DAA) human machine interface requirements (developed within RTCA SC-228) and existing collision avoidance displays. Attendees will be able to view the current state of the art of the DAA pilot traffic, alerting and guidance displays integrated with Traffic advisory and Collision Avoidance (TCAS) II in the UAS-NAS Project's research UAS ground control station (developed in partnership with the Air Force Research Laboratory). In addition, attendees will have the opportunity to interact with the research UAS ground control station and "fly" encounters, using the DAA and TCAS II displays to avoid simulated aircraft. The display of the advisories will be hosted on a laptop with an external 30" monitor, running the Vigilant Spirit system. DAA advisories will be generated by the JADEM software tool, connected to the system via the LVC Gateway. A repeater of the primary flight display will be shown on a 55" monitor mounted on a stand at the back of the booth to show the pilot interaction to the passersby.

  19. Greenhouse policy study from NAS

    NASA Astrophysics Data System (ADS)

    Maggs, William Ward

    The National Academy of Sciences will produce a study for the Environmental Protection Agency on policy responses to global warming. The report is due out before the end of 1990.Dan J. Evans, former U.S. Senator and former Governor of Washington, will chair a panel of the Commission on Science, Engineering, and Public Policy, a body of the councils of the NAS, National Academy of Engineering, and Institute of Medicine. Evans is a registered civil engineer and previously chaired the Pacific Northwest Electric Power and Conservation Planning Council.The 13-person panel includes AGU members Stephen Schneider of the National Center for Atmospheric Research and Robert Frosch, Vice President of Research Laboratores at General Motors Corp., Jessica Mathews, Vice President of the World Resources Institute, and Sir Crispin Tickell, the United Kingdom's Ambassador to the United Nations.

  20. Production and investigation of thin films of metal actinides (Pu, Am, Cm, Bk, Cf)

    NASA Astrophysics Data System (ADS)

    Radchenko, V. M.; Ryabinin, M. A.; Stupin, V. A.

    2010-03-01

    Under limited availability of transplutonium metals some special techniques and methods of their production have been developed that combine the process of metal reduction from a chemical compound and preparation of a sample for examination. In this situation the evaporation and condensation of metal onto a substrate becomes the only possible technology. Thin film samples of metallic 244Cm, 248Cm and 249Bk were produced by thermal reduction of oxides with thorium followed by deposition of the metals in the form of thin layers on tantalum substrates. For the production of 249Cf metal in the form of a thin layer the method of thermal reduction of oxide with lanthanum was used. 238Pu and 239Pu samples in the form of films were prepared by direct high temperature evaporation and condensation of the metal onto a substrate. For the production of 241Am films a gram sample of plutonium-241 metal was used containing about 18 % of americium at the time of production. Thermal decomposition of Pt5Am intermetallics in vacuum was used to produce americium metal with about 80% yield. Resistivity of the metallic 249Cf film samples was found to decrease exponentially with increasing temperature. The 249Cf metal demonstrated a tendency to form preferably a DHCP structure with the sample mass increasing. An effect of high specific activity on the crystal structure of 238Pu nuclide thin layers was studied either.

  1. Functional Requirements Document for HALE UAS Operations in the NAS: Step 1. Version 3

    NASA Technical Reports Server (NTRS)

    2006-01-01

    The purpose of this Functional Requirements Document (FRD) is to compile the functional requirements needed to achieve the Access 5 Vision of "operating High Altitude, Long Endurance (HALE) Unmanned Aircraft Systems (UAS) routinely, safely, and reliably in the national airspace system (NAS)" for Step 1. These functional requirements could support the development of a minimum set of policies, procedures and standards by the Federal Aviation Administration (FAA) and various standards organizations. It is envisioned that this comprehensive body of work will enable the FAA to establish and approve regulations to govern safe operation of UAS in the NAS on a routine or daily "file and fly" basis. The approach used to derive the functional requirements found within this FRD was to decompose the operational requirements and objectives identified within the Access 5 Concept of Operations (CONOPS) into the functions needed to routinely and safely operate a HALE UAS in the NAS. As a result, four major functional areas evolved to enable routine and safe UAS operations for an on-demand basis in the NAS. These four major functions are: Aviate, Navigate, Communicate, and Avoid Hazards. All of the functional requirements within this document can be directly traceable to one of these four major functions. Some functions, however, are traceable to several, or even all, of these four major functions. These cross-cutting functional requirements support the "Command / Control: function as well as the "Manage Contingencies" function. The requirements associated to these high-level functions and all of their supporting low-level functions are addressed in subsequent sections of this document.

  2. An in-house assay for BK polyomavirus quantification using the Abbott m2000 RealTime system.

    PubMed

    Muldrew, Kenneth L; Lovett, Jennie L

    2013-11-01

    BK polyomavirus (BKPyV) quantification is useful for monitoring renal transplant patient response to therapy. The Abbott m2000 RealTime System employed by some clinical laboratories to perform US Food and Drug Administration-approved assays can also be used to develop in-house assays such as the one presented here. This study aimed to validate an in-house quantitative real-time PCR assay targeting the BKPyV major capsid VP1 gene for assessment of viral load using the Abbott m2000 RealTime System. BKPyV load was measured in 95 urine and plasma samples previously tested for BKPyV by one of three laboratories (46 BKPyV-positive samples consisting of 35 plasma and 11 urine samples; 49 samples negative for BKPyV consisting of 47 plasma and two urine samples). Two additional plasma specimens from the College of American Pathologists proficiency testing survey were also analysed. Precision studies were performed by diluting a high-viral-titre patient sample into BKPyV-negative pooled plasma to create high-positive (6.16 log10 copies ml(-1)) and low-positive (3.16 log10 copies ml(-1)) samples. For precision studies of inter-assay variability, a high-positive (7.0 log10 copies ml(-1)) and a low-positive (3.0 log10 copies ml(-1)) sample were measured in 20 separate runs. The assay's limit of quantification and limit of detection were 2.70 and 2.25 log10 copies ml(-1), respectively. The assay was linear from 2.70 to 9.26 log10 copies ml(-1). Of the 48 known positives, 43 were detected as positive, with three reported by the reference laboratory as values lower than the limit of detection. Two known positives at 3.27 and 3.80 log10 copies ml(-1) tested negative by the m2000 BKPyV assay. Of the 49 known negative samples, 48 were negative by the m2000 BKPyV load assay, with one sample confirmed positive by a reference laboratory. Qualitative analysis prior to discrepancy testing demonstrated a sensitivity of 89.58 % and a specificity of 97.96 %. Precision studies

  3. The CAS-NAS forum for new leaders in space science

    NASA Astrophysics Data System (ADS)

    Smith, David H.

    The space science community is thoroughly international, with numerous nations now capable of launching scientific payloads into space either independently or in concert with others. As such, it is important for national space-science advisory groups to engage with like-minded groups in other spacefaring nations. The Space Studies Board of the US National Academy of Sciences' (NAS') National Research Council has provided scientific and technical advice to NASA for more than 50 years. Over this period, the Board has developed important multilateral and bilateral partnerships with space scientists around the world. The primary multilateral partner is COSPAR, for which the Board serves as the US national committee. The Board's primary bilateral relationship is with the European Science Foundation’s European Space Science Committee. Burgeoning Chinese space activities have resulted in several attempts in the past decade to open a dialogue between the Board and space scientists in China. On each occasion, the external political environment was not conducive to success. The most recent efforts to engage the Chinese space researchers began in 2011 and have proved particularly successful. Although NASA is currently prohibited from engaging in bilateral activities with China, the Board has established a fruitful dialogue with its counterpart in the Chinese Academy of Sciences (CAS). A joint NAS-CAS activity, the Forum for New Leaders in Space Science, has been established to provide opportunities for a highly select group of young space scientists from China and the United States to discuss their research activities in an intimate and collegial environment at meetings to be held in both nations. The presentation will describe the current state of US-China space relations, discuss the goals of the joint NAS-CAS undertaking and report on the activities at the May, 2014, Forum in Beijing and the planning for the November, 2014, Forum in Irvine, California.

  4. Polyomavirus BK-specific CD8+ T cell responses in patients after allogeneic stem cell transplant.

    PubMed

    Schneidawind, Dominik; Schmitt, Anita; Wiesneth, Markus; Mertens, Thomas; Bunjes, Donald; Freund, Mathias; Schmitt, Michael

    2010-06-01

    Polyomavirus BK (BKV) is known as an important etiologic agent in the development of hemorrhagic cystitis (HC) after allogeneic stem cell transplant (SCT). To define T cell epitopes of the BKV proteins VP1 and sT, eight potential HLA-A2-binding peptides were synthesized based on computer algorithms. These peptides were co-incubated with CD8 + T cells from the peripheral blood (PB) of 25 healthy volunteers and seven patients suffering from HC after allogeneic SCT in a mixed-lymphocyte peptide culture (MLPC), which were subsequently screened by enzyme-linked immunospot (ELISPOT) assays and fluorescence-activated cell sorting (FACS) analysis. We found that CD8 + T cells from five of seven (71%) patients with HC presensitized with the BKV peptide VP1 p108 (LLMWEAVTV) specifically recognized T2 cells pulsed with VP1 p108. In contrast, only seven of 25 (28%) healthy volunteers had CD8 + T cells reactive with VP1 p108-pulsed T2 cells. The presence of VP1 p108-specific T cells could be confirmed by FACS analysis. The BKV peptide VP1 p108 seems to play an important role as an immunodominant peptide in the pathogenesis of HC in patients after allogeneic SCT, and might be a promising target for immunotherapies or even strategies to prevent the development of BKV-associated HC.

  5. BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

    PubMed

    Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

    2016-07-13

    Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

  6. Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression.

    PubMed

    Bernhoff, E; Gutteberg, T J; Sandvik, K; Hirsch, H H; Rinaldo, C H

    2008-07-01

    The human polyomavirus BK (BKV) causes nephropathy and hemorrhagic cystitis in kidney and bone marrow transplant patients, respectively. The anti-viral cidofovir (CDV) has been used in small case series but the effects on BKV replication are unclear, since polyomaviruses do not encode viral DNA polymerases. We investigated the effects of CDV on BKV(Dunlop) replication in primary human renal proximal tubule epithelial cells (RPTECs). CDV inhibited the generation of viral progeny in a dose-dependent manner yielding a 90% reduction at 40 microg/mL. Early steps such as receptor binding and entry seemed unaffected. Initial large T-antigen transcription and expression were also unaffected, but subsequent intra-cellular BKV DNA replication was reduced by >90%. Late viral mRNA and corresponding protein levels were also 90% reduced. In uninfected RPTECs, CDV 40 microg/mL reduced cellular DNA replication and metabolic activity by 7% and 11% in BrdU and WST-1 assays, respectively. BKV infection increased DNA replication to 142% and metabolic activity to 116%, respectively, which were reduced by CDV 40 microg/mL to levels of uninfected untreated RPTECs. Our results show that CDV inhibits BKV DNA replication downstream of large T-antigen expression and involves significant host cell toxicity. This should be considered in current treatment and drug development.

  7. Comparative Evaluation of Three Nucleic Acid-Based Assays for BK Virus Quantification

    PubMed Central

    Descamps, Veronique; Martin, Elodie; Morel, Virginie; François, Catherine; Helle, François; Duverlie, Gilles; Castelain, Sandrine

    2015-01-01

    With the growing importance of BK virus (BKV), effective and efficient screening for BKV replication in plasma and urine samples is very important for monitoring renal transplant and hematopoietic stem cell transplant recipients, who are at increased risk of BKV-associated diseases. However, recent assays proposed by many manufacturers have not been tested, and the available tests have not been standardized. The aim of the present study was to evaluate and compare the performances of three commercially available kits, R-gene, GeneProof, and RealStar, on plasma and urine specimens from patients infected with various genotypes and to determine the correlations with the results from a reference laboratory. A qualitatively excellent global agreement (96.8%) was obtained. RealStar PCR tended to give a higher sensitivity, especially for subtype Ib1 samples. Comparison of 30 plasma samples and 53 urine samples showed a good agreement between the three assays, with Spearman's Rho correlation coefficient values falling between 0.92 and 0.98 (P < 0.001). Moreover, a perfect correlation was obtained for comparison of the assay performances with the AcroMetrix BKV panel (P < 0.001 for all comparisons). According to Bland-Altman analysis, more than 95% (240/249 comparisons) of sample comparisons were situated in the range of the mean ± 2 standard deviations (SD). The greatest variability between assays was observed for 10.2% of subtype Ib2 samples, with differences of >1 log10 copies/ml. In conclusion, this study demonstrated the reliable and comparable performances of the R-gene, GeneProof, and RealStar real-time PCR systems for quantification of BKV in urine and plasma samples. All three real-time PCR assays are appropriate for screening of BKV replication in patients. PMID:26424842

  8. Fluoroquinolones inhibit human polyomavirus BK (BKV) replication in primary human kidney cells.

    PubMed

    Sharma, Biswa Nath; Li, Ruomei; Bernhoff, Eva; Gutteberg, Tore Jarl; Rinaldo, Christine Hanssen

    2011-10-01

    Reactivation of human polyomavirus BK (BKV) may cause polyomavirus-associated nephropathy or polyomavirus-associated hemorrhagic cystitis in renal- or bone marrow-transplant patients, respectively. Lack of treatment options has led to exploration of fluoroquinolones that inhibit topoisomerase II and IV in prokaryotes and possibly large T-antigen (LT-ag) helicase activity in polyomavirus. We characterized the effects of ofloxacin and levofloxacin on BKV replication in the natural host cells - primary human renal proximal tubular epithelial cells (RPTECs). Ofloxacin and levofloxacin inhibited BKV load in a dose-dependent manner yielding a ∼90% inhibition at 150 μg/ml. Ofloxacin at 150 μg/ml inhibited LT-ag mRNA and protein expression from 24h post infection (hpi). BKV genome replication was 77% reduced at 48 hpi and a similar reduction was found in VP1 and agnoprotein expression. At 72 hpi, the reduction in genome replication and protein expression was less pronounced. A dose-dependent cytostatic effect was noted. In infected cells, 150 μg/ml ofloxacin led to a 26% and 6% inhibition of cellular DNA replication and total metabolic activity, respectively while 150 μg/ml levofloxacin affected this slightly more, particularly in uninfected cells. Cell counting and xCELLigence results revealed that cell numbers were not reduced. In conclusion, ofloxacin and levofloxacin inhibit but do not eradicate BKV replication in RPTECs. At a concentration of ofloxacin giving ∼90% inhibition in BKV load, no significant cytotoxicity was observed. This concentration can be achieved in urine and possibly in the kidneys. Our results support a mechanism involving inhibition of LT-ag expression or functions but also suggest inhibition of cellular enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. UAS in the NAS - Analysis Results and Recommendations for Integration of CNPC and ATC Communications Simulation Report

    NASA Technical Reports Server (NTRS)

    Kubat, Gregory

    2016-01-01

    This report addresses a deliverable to the UAS-in-the-NAS project for recommendations for integration of CNPC and ATC communications based on analysis results from modeled radio system and NAS-wide UA communication architecture simulations. For each recommendation, a brief explanation of the rationale for its consideration is provided with any supporting results obtained or observed in our simulation activity.

  10. Descriptive drinking norms in Native American and non-Hispanic White college students.

    PubMed

    Hagler, Kylee J; Pearson, Matthew R; Venner, Kamilla L; Greenfield, Brenna L

    2017-09-01

    College students tend to overestimate how much their peers drink, which is associated with higher personal alcohol use. However, research has not yet examined if this phenomenon holds true among Native American (NA) college students. This study examined associations between descriptive norms and alcohol use/consequences in a sample of NA and non-Hispanic White (NHW) college students. NA (n=147, 78.6% female) and NHW (n=246, 67.8% female) undergraduates completed an online survey. NAs NHWs showed similar descriptive norms such that the "typical college student," "typical NA student," and "typical NHW student" were perceived to drink more than "best friends." "Best friends" descriptive norms (i.e., estimations of how many drinks per week were consumed by participants' best friends) were the most robust predictors of alcohol use/consequences. Effect size estimates of the associations between drinking norms and participants' alcohol use were consistently positive and ranged from r=0.25 to r=0.51 across the four reference groups. Negative binomial hurdle models revealed that all descriptive norms tended to predict drinking, and "best friends" drinking norms predicted alcohol consequences. Apart from one interaction effect, likely due to familywise error rate, these associations were not qualified by interactions with racial/ethnic group. We found similar patterns between NAs and NHWs both in the pattern of descriptive norms across reference groups and in the strength of associations between descriptive norms and alcohol use/consequences. Although these results suggest that descriptive norms operate similarly among NAs as other college students, additional research is needed to identify whether other norms (e.g., injunctive norms) operate similarly across NA and NHW students. Copyright © 2017. Published by Elsevier Ltd.

  11. Supercomputing 2002: NAS Demo Abstracts

    NASA Technical Reports Server (NTRS)

    Parks, John (Technical Monitor)

    2002-01-01

    The hyperwall is a new concept in visual supercomputing, conceived and developed by the NAS Exploratory Computing Group. The hyperwall will allow simultaneous and coordinated visualization and interaction of an array of processes, such as a the computations of a parameter study or the parallel evolutions of a genetic algorithm population. Making over 65 million pixels available to the user, the hyperwall will enable and elicit qualitatively new ways of leveraging computers to accomplish science. It is currently still unclear whether we will be able to transport the hyperwall to SC02. The crucial display frame still has not been completed by the metal fabrication shop, although they promised an August delivery. Also, we are still working the fragile node issue, which may require transplantation of the compute nodes from the present 2U cases into 3U cases. This modification will increase the present 3-rack configuration to 5 racks.

  12. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project KDP-C Review

    NASA Technical Reports Server (NTRS)

    Grindle, Laurie; Sakahara, Robert; Hackenberg, Davis; Johnson, William

    2017-01-01

    The topics discussed are the UAS-NAS project life-cycle and ARMD thrust flow down, as well as the UAS environments and how we operate in those environments. NASA's Armstrong Flight Research Center at Edwards, CA, is leading a project designed to help integrate unmanned air vehicles into the world around us. The Unmanned Aircraft Systems Integration in the National Airspace System project, or UAS in the NAS, will contribute capabilities designed to reduce technical barriers related to safety and operational challenges associated with enabling routine UAS access to the NAS. The project falls under the Integrated Systems Research Program office managed at NASA Headquarters by the agency's Aeronautics Research Mission Directorate. NASA's four aeronautics research centers - Armstrong, Ames Research Center, Langley Research Center, and Glenn Research Center - are part of the technology development project. With the use and diversity of unmanned aircraft growing rapidly, new uses for these vehicles are constantly being considered. Unmanned aircraft promise new ways of increasing efficiency, reducing costs, enhancing safety and saving lives 460265main_ED10-0132-16_full.jpg Unmanned aircraft systems such as NASA's Global Hawks (above) and Predator B named Ikhana (below), along with numerous other unmanned aircraft systems large and small, are the prime focus of the UAS in the NAS effort to integrate them into the national airspace. Credits: NASA Photos 710580main_ED07-0243-37_full.jpg The UAS in the NAS project envisions performance-based routine access to all segments of the national airspace for all unmanned aircraft system classes, once all safety-related and technical barriers are overcome. The project will provide critical data to such key stakeholders and customers as the Federal Aviation Administration and RTCA Special Committee 203 (formerly the Radio Technical Commission for Aeronautics) by conducting integrated, relevant system-level tests to adequately address

  13. Theoretical studies of optical gain tuning by hydrostatic pressure in GaInNAs/GaAs quantum wells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gladysiewicz, M.; Wartak, M. S.; Department of Physics and Computer Science, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5

    In order to describe theoretically the tuning of the optical gain by hydrostatic pressure in GaInNAs/GaAs quantum wells (QWs), the optical gain calculations within kp approach were developed and applied for N-containing and N-free QWs. The electronic band structure and the optical gain for GaInNAs/GaAs QW were calculated within the 10-band kp model which takes into account the interaction of electron levels in the QW with the nitrogen resonant level in GaInNAs. It has been shown that this interaction increases with the hydrostatic pressure and as a result the optical gain for GaInNAs/GaAs QW decreases by about 40% and 80%more » for transverse electric and transverse magnetic modes, respectively, for the hydrostatic pressure change from 0 to 40 kilobars. Such an effect is not observed for N-free QWs where the dispersion of electron and hole energies remains unchanged with the hydrostatic pressure. This is due to the fact that the conduction and valence band potentials in GaInAs/GaAs QW scale linearly with the hydrostatic pressure.« less

  14. Where Are We Today? A Survey of Current German Teaching Methods in American Colleges and Universities.

    ERIC Educational Resources Information Center

    Helt, Richard C.; Woloshin, David J.

    1982-01-01

    Reports on survey of beginning German at colleges and universities in the U.S. Results show grammatical knowledge is most important objective followed by speaking, listening, and reading comprehension, cultural awareness, then writing. Results indicate growth within the profession. (BK)

  15. NAS Requirements Checklist for Job Queuing/Scheduling Software

    NASA Technical Reports Server (NTRS)

    Jones, James Patton

    1996-01-01

    The increasing reliability of parallel systems and clusters of computers has resulted in these systems becoming more attractive for true production workloads. Today, the primary obstacle to production use of clusters of computers is the lack of a functional and robust Job Management System for parallel applications. This document provides a checklist of NAS requirements for job queuing and scheduling in order to make most efficient use of parallel systems and clusters for parallel applications. Future requirements are also identified to assist software vendors with design planning.

  16. Optical Properties of A GaInNAs Multi-Quantum Well Semiconductor

    NASA Astrophysics Data System (ADS)

    Hughes, Timothy S.; Ren, Shang-Fen; Jiang, De-Sheng; Xiaogan, Liang

    2002-03-01

    Optoelectronic devices used today depend on lasers that have wavelengths in the optical fiber transmission window of 1.3 to 1.55 micrometers. When using GaAs substrate semiconductor lasers, we typically see this range of light emission. Quaternary materials, such as GaInNAs grown on this substrate, not only allow us to control the output wavelength, but it also allows us to manipulate the lattice constant. Further research has potential to produce low-costing highly efficient Vertical Cavity Surface Emitting Lasers (VCSEL). Using a Fourier-Transform Spectrometer, a method of using a Michelson Interferometer to measure the interference between two coherent beams, we measured and analyzed the photoluminescence spectra of a GaInNAs multi-quantum well semiconductor, grown using the Molecular Beam Epitaxy (MBE) growth technique. The experiments of this research were carried out in an undergraduate international research experience at the Chinese Semiconductor Institute supported by the Division of International Programs of NSF.

  17. A Descriptive Analysis of Nursing Staff Behaviors in a Teaching Nursing Home: Differences among NAs, LPNs, and RNs.

    ERIC Educational Resources Information Center

    Burgio, Louis D.; And Others

    1990-01-01

    Various staff behaviors in nursing home were sampled 7 times a day, 5 days a week over 37 months and were coded separately for registered nurses (RNs), licensed practical nurses (LPNs), and nurses' aides (NAs). Found LPNs displayed significantly more patient care behaviors and NAs significantly more nonwork behaviors than other nursing staff. RNs…

  18. Concepts of Integration for UAS Operations in the NAS

    NASA Technical Reports Server (NTRS)

    Consiglio, Maria C.; Chamberlain, James P.; Munoz, Cesar A.; Hoffler, Keith D.

    2012-01-01

    One of the major challenges facing the integration of Unmanned Aircraft Systems (UAS) in the National Airspace System (NAS) is the lack of an onboard pilot that can comply with the legal requirement identified in the US Code of Federal Regulations (CFR) that pilots see and avoid other aircraft. UAS will be expected to demonstrate the means to perform the function of see and avoid while preserving the safety level of the airspace and the efficiency of the air traffic system. This paper introduces a Sense and Avoid (SAA) concept for integration of UAS into the NAS that is currently being developed by the National Aeronautics and Space Administration (NASA) and identifies areas that require additional experimental evaluation to further inform various elements of the concept. The concept design rests on interoperability principles that take into account both the Air Traffic Control (ATC) environment as well as existing systems such as the Traffic Alert and Collision Avoidance System (TCAS). Specifically, the concept addresses the determination of well clear values that are large enough to avoid issuance of TCAS corrective Resolution Advisories, undue concern by pilots of proximate aircraft and issuance of controller traffic alerts. The concept also addresses appropriate declaration times for projected losses of well clear conditions and maneuvers to regain well clear separation.

  19. The role of N-H complexes in the control of localized center recombination in hydrogenated GaInNAs (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Whiteside, Vincent R.; Fukuda, Miwa; Estes, Nicholas J.; Wang, Bin; Brown, Collin R.; Hossain, Khalid; Golding, Terry D.; Leroux, Mathieu; Al Khalfioui, Mohamed; Tischler, Joseph G.; Ellis, Chase T.; Glaser, Evan R.; Sellers, Ian R.

    2017-04-01

    A significant improvement in the quality of dilute nitrides has recently led to the ability to reveal depletion widths in excess of 1 μm at 1 eV [1]. The real viability of dilute nitrides for PV has been recently demonstrated with the reporting of a record efficiency of 43.5% from a 4J MJSC including GaInNAs(Sb) [2]. Despite the progress made, these materials remain poorly understood and work continues to improve their lifetime and reproducibility. We have investigated the possibility of improving the functionality of GaInNAs using hydrogenation to selectively passivate mid-gap defects, while preserving the substitutional nitrogen. Temperature dependent photoluminescence measurements of the intrinsic region of a GaInNAs p-i-n solar cell show a classic "s-shape" associated with localization prior to hydrogenation. No sign of this "s-shape" is evident after hydrogenation, despite the retention of substitutional nitrogen as evidenced by the band absorption of 1 eV. The absence of an "s-shape" at low-temperature in hydrogenated GaInNAs is rather curious since, even in high quality nitrides this behavior is due to the emission of isoelectronic centers created via N-As substitution [3]. The potential origins of this behavior will be discussed. The promise of this process for GaInNAs solar cells was demonstrated by a three-fold improvement in the performance of a hydrogenated device with respect to an as-grown reference [4]. [1] "Wide-depletion width GaInNAs solar cells by thermal annealing," I. R. Sellers, W-S. Tan, K. Smith, S. Hooper, S. Day and M. Kauer, Applied Physics Letters 99, 151111 (2011) [2] "43.5% efficient lattice matched solar cells," M. Wiemer, V. Sabnis, and H. Yuen, Proc. SPIE 8108, 810804 (2011) [3]"Probing the nature of carrier localization in GaInNAs, epilayers using optical methods," T. Ysai, B. Barman, T. Scarce, G. Lindberg, M. Fukuda, V. R. Whiteside, J. C. Keay, M. B. Johnson, I. R. Sellers, M. Al Khalfioui, M. Leroux, B. A. Weinstein and A

  20. Limited Variation in BK Virus T-Cell Epitopes Revealed by Next-Generation Sequencing

    PubMed Central

    Sahoo, Malaya K.; Tan, Susanna K.; Chen, Sharon F.; Kapusinszky, Beatrix; Concepcion, Katherine R.; Kjelson, Lynn; Mallempati, Kalyan; Farina, Heidi M.; Fernández-Viña, Marcelo; Tyan, Dolly; Grimm, Paul C.; Anderson, Matthew W.; Concepcion, Waldo

    2015-01-01

    BK virus (BKV) infection causing end-organ disease remains a formidable challenge to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV-specific treatments are limited, immunologic-based therapies may be a promising and novel therapeutic option for transplant recipients with persistent BKV infection. Here, we describe a whole-genome, deep-sequencing methodology and bioinformatics pipeline that identify BKV variants across the genome and at BKV-specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted CD8 T-cell epitopes. BKV whole genomes were amplified using long-range PCR with four inverse primer sets, and fragmentation libraries were sequenced on the Ion Torrent Personal Genome Machine (PGM). An error model and variant-calling algorithm were developed to accurately identify rare variants. A total of 65 samples from 18 pediatric HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing. Limited genetic variation was observed. The median number of amino acid variants identified per sample was 8 (range, 2 to 37; interquartile range, 10), with the majority of variants (77%) detected at a frequency of <5%. When normalized for length, there was no statistical difference in the median number of variants across all genes. Similarly, the predominant virus population within samples harbored T-cell epitopes similar to the reference BKV strain that was matched for the BKV genotype. Despite the conservation of epitopes, low-level variants in T-cell epitopes were detected in 77.7% (14/18) of patients. Understanding epitope variation across the whole genome provides insight into the virus-immune interface and may help guide the development of protocols for novel immunologic-based therapies. PMID:26202116

  1. Neonatal Abstinence Syndrome (NAS): Transitioning Methadone Treated Infants From An Inpatient to an Outpatient Setting

    PubMed Central

    Backes, Carl H.; Backes, Carl R.; Gardner, Debra; Nankervis, Craig A.; Giannone, Peter J.; Cordero, Leandro

    2013-01-01

    Background Each year in the US approximately 50,000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS). Objective To compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program. Design/Methods Retrospective review (2007-9). Infants were born to mothers maintained on methadone or buprenorphine in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 pts) was inpatient while the combined group (46 pts) was outpatient. Results Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, GA and the incidence of prematurity (34 & 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25d; p < 0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21d, p<0.01), the cumulative methadone dose was similar (3.6 vs 3.1mg/kg, p 0.42). Follow-up: Information was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤ 72 hours from hospital discharge. Breast feeding was more common among infants in the combined group (24 vs. 8% p<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (<37w GA) was the only predictor for hospital readmission for NAS in both groups (p 0.02, OR 5). Average hospital cost for each infant in the combined group was $13,817 less than in the traditional group. Conclusions A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long term benefits of the combined approach on infants and their families. PMID:21852772

  2. Prevalence of Polyoma BK Virus (BKPyV), Epstein-Barr Virus (EBV) and Human Papilloma Virus (HPV) in Oropharyngeal Cancer.

    PubMed

    Polz-Gruszka, Dorota; Morshed, Kamal; Jarzyński, Adrian; Polz-Dacewicz, Małgorzata

    2015-01-01

    The aim of this study was to analyze the prevalence of BK virus, Human Papillomavirus and Epstein-Barr virus in oropharyngeal cancer, and to test our hypothesis that BKV/HPV/EBV co-infection plays a role in oropharyngeal squamous cell carcinoma. The correlation between viral infection, OSCC, anatomic location, pre-treatment staging, evidence of metastases to lymph nodes, and grading was also investigated. The examination samples were collected from 62 patients from paraffin tissue blocks. Males (90.3%) with, smoking (83.9%) and alcohol abuse (67.7%) problems prevailed in the studied group. G2 histological type was recognized in 80.6% cases. T4 (77.4%) and N2 (56.5%) traits occurred in the majority of patients. No cases of metastasis were observed (M0 100%). HPV - 24.2%, EBV - 27.4% and BKV 17.7% were detected in the studied samples. We observed co-infection EBV/BKV in 8% of cases, HPV/BKV in 4.8%, and HPV/EBV in 9% cases. Only in two cases co-infection of all three viruses was found.

  3. NAS (Host/ARTS) IIIA to VME Modem Interface ATC Interface Hardware Manual

    DOT National Transportation Integrated Search

    1990-10-01

    This document is reference material for personnel using the National Airspace : System (NAS) (HOST or ARTS IIIA) Air Traffic Control (ATC) Interface Subsystem. : It was originally developed to be part of the Data Link Test and Analysis System : (DATA...

  4. The temperature dependence of atomic incorporation characteristics in growing GaInNAs films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Jingling; Gao, Fangliang; Wen, Lei

    We have systematically studied the temperature dependence of incorporation characteristics of nitrogen (N) and indium (In) in growing GaInNAs films. With the implementation of Monte-Carlo simulation, the low N adsorption energy (−0.10 eV) is demonstrated. To understand the atomic incorporation mechanism, temperature dependence of interactions between Group-III and V elements are subsequently discussed. We find that the In incorporation behaviors rather than that of N are more sensitive to the T{sub g}, which can be experimentally verified by exploring the compositional modulation and structural changes of the GaInNAs films by means of high-resolution X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscope,more » and secondary ion mass spectroscopy.« less

  5. Elevated K+ channel activity opposes vasoconstrictor response to serotonin in cerebral arteries of the Fawn Hooded Hypertensive rat.

    PubMed

    Pabbidi, Mallikarjuna R; Roman, Richard J

    2017-01-01

    Previous studies suggest that middle cerebral arteries (MCAs) of Fawn Hooded Hypertensive (FHH) rats exhibit impaired myogenic response and introgression of a small region of Brown Norway chromosome 1 containing 15 genes restored the response in FHH.1 BN congenic rat. The impaired myogenic response in FHH rats is associated with an increase in the activity of the large conductance potassium (BK) channel in vascular smooth muscle cells (VSMCs). The present study examined whether the increased BK channel function in FHH rat alters vasoconstrictor response to serotonin (5-HT). Basal myogenic tone and spontaneous myogenic response of the MCA was attenuated by about twofold and about fivefold, respectively in FHH compared with FHH.1 BN rats. 5-HT (0.1 μM)-mediated vasoconstriction was about twofold lower, and inhibition of the BK channel increased the vasoconstrictor response by about threefold in FHH compared with FHH.1 BN rats. 5-HT (3 μM) decreased BK channel and spontaneous transient outward currents in VSMCs isolated from FHH.1 BN but had no effect in FHH rats. 5-HT significantly depolarized the membrane potential in MCAs of FHH.1 BN than FHH rats. Blockade of the BK channel normalized 5-HT-induced depolarization in MCAs of FHH rats. The 5-HT-mediated increase in cytosolic calcium concentration was significantly reduced in plateau phase in the VSMCs of FHH relative to FHH.1 BN rats. These findings suggest that sequence variants in the genes located in the small region of FHH rat chromosome 1 impairs 5-HT-mediated vasoconstriction by decreasing its ability to inhibit BK channel activity, depolarize the membrane and blunt the rise in cytosolic calcium concentration. Copyright © 2017 the American Physiological Society.

  6. Shadow Mode Assessment Using Realistic Technologies for the National Airspace (SMART NAS)

    NASA Technical Reports Server (NTRS)

    Kopardekar, Parimal H.

    2014-01-01

    Develop a simulation and modeling capability that includes: (a) Assessment of multiple parallel universes, (b) Accepts data feeds, (c) Allows for live virtual constructive distribute environment, (d) Enables integrated examinations of concepts, algorithms, technologies and National Airspace System (NAS) architectures.

  7. BK virus (BKV) quantification in urine samples of bone marrow transplanted patients is helpful for diagnosis of hemorrhagic cystitis, although wide individual variations exist.

    PubMed

    Priftakis, Peter; Bogdanovic, Gordana; Kokhaei, Parviz; Mellstedt, Håkan; Dalianis, Tina

    2003-01-01

    Hemorrhagic cystitis (HC) in allogeneic bone marrow transplanted (BMT) patients is associated with BK virus (BKV) reactivation manifested as BK viruria. However, since 77-90% of all adult BMT patients excrete BKV, viral reactivation alone cannot be responsible for HC. Recently, a significant overrepresentation of C-->G mutations in the Sp1 binding site in the non-coding control region (NCCR) of BKV was shown to be present in HC patients and absent in non-HC patients. We aimed to investigate if this mutation resulted in excessive BKV excretion in HC patients. A Real-Time PCR was developed and used to quantify BKV in urine samples from 21 patients with HC, with and without the mutations, as well as from patients without HC. Quantification of BKV was successful in 18 of 21 urine patients (six with and six without C-->G mutations) and six patients without HC. A mean of 3.0 x 10(6) BKV copies/microl was detected in urine samples of HC patients with C-->G mutations, compared to a mean of 1.5 x 10(6) BKV copies/microl in HC patients without C-->G mutations and a mean of 1.0 x 10(6) BKV copies/microl in patients without HC. The obtained differences were however not statistically significant, due to one individual non-HC patient with an extremely high BKV copy number. Nevertheless, while 50% of the samples in the HC groups expressed 1 x 10(6) copies/microl or more, only one of the samples in the non-HC group contained a virus quantity higher than 5 x 10(5) copies. Although we could not confirm that the C-->G mutations in the Sp1 site of BKV were responsible for an increased viral load in patients with HC, our data suggest that levels of BKV above 10(4) copies/microl may indicate a risk for HC.

  8. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models.

    PubMed

    Teng, S; Tebby, C; Barcellini-Couget, S; De Sousa, G; Brochot, C; Rahmani, R; Pery, A R R

    2016-08-15

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro - in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-time cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Strain relaxation induced surface morphology of heterogeneous GaInNAs layers grown on GaAs substrate

    NASA Astrophysics Data System (ADS)

    Gelczuk, Ł.; Jóźwiak, G.; Moczała, M.; Dłużewski, P.; Dąbrowska-Szata, M.; Gotszalk, T. P.

    2017-07-01

    The partially-relaxed heterogeneous GaInNAs layers grown on GaAs substrate by atmospheric pressure vapor phase epitaxy (AP-MOVPE) were investigated by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The planar-view TEM image shows a regular 2D network of misfit dislocations oriented in two orthogonal 〈1 1 0〉 crystallographic directions at the (0 0 1) layer interface. Moreover, the cross-sectional view TEM image reveals InAs-rich and V-shaped precipitates in the near surface region of the GaInNAs epitaxial layer. The resultant undulating surface morphology, known as a cross-hatch pattern, is formed as observed by AFM. The numerical analysis of the AFM image of the GaInNAs layer surface with the well-defined cross-hatch morphology enabled us to determine a lower bound of actual density of misfit dislocations. However, a close correspondence between the asymmetric distribution of interfacial misfit dislocations and undulating surface morphology is observed.

  10. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project - Systems Integration and Operationalization (SIO) Demonstration

    NASA Technical Reports Server (NTRS)

    Swieringa, Kurt

    2018-01-01

    The UAS-NAS Project hosted a Systems Integration Operationalization (SIO) Industry Day for the SIO Request for Information (RFI) on November 30, 2017 in San Diego, California. This presentation is being presented to the same group as a follow up regarding the progress that the UAS-NAS project has made on the SIO RFI. The presentation will be virtual with a teleconference

  11. Analytical characterization of three cathinone derivatives, 4-MPD, 4F-PHP and bk-EPDP, purchased as bulk powder from online vendors.

    PubMed

    Apirakkan, Orapan; Frinculescu, Anca; Shine, Trevor; Parkin, Mark C; Cilibrizzi, Agostino; Frascione, Nunzianda; Abbate, Vincenzo

    2018-02-01

    Novel emerging drugs of abuse, also referred as new psychoactive substances, constitute an ever-changing mixture of chemical compounds designed to circumvent legislative controls by means of chemical modifications of previously banned recreational drugs. One such class, synthetic cathinones, namely β-keto derivatives of amphetamines, has been largely abused over the past decade. A number of new synthetic cathinones are detected each year, either in bulk powders/crystals or in biological matrices. It is therefore important to continuously monitor the supply of new synthetic derivatives and promptly report them. By using complementary analytical techniques (i.e. one- and two-dimensional NMR, FT-IR, GC-MS, HRMS and HPLC-UV), this study investigates the detection, identification and full characterization of 1-(4-methylphenyl)-2-(methylamino)pentanone (4-methylpentedrone, 4-MPD), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl)hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP), three emerging cathinone derivatives. Copyright © 2017 John Wiley & Sons, Ltd.

  12. UAS Integration in the NAS Project: Integrated Test and LVC Infrastructure

    NASA Technical Reports Server (NTRS)

    Murphy, Jim; Hoang, Ty

    2015-01-01

    Overview presentation of the Integrated Test and Evaluation sub-project of the Unmanned Aircraft System (UAS) in the National Airspace System (NAS). The emphasis of the presentation is the Live, Virtual, and Constructive (LVC) system (a broadly used name for classifying modeling and simulation) infrastructure and use of external assets and connection.

  13. Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant.

    PubMed

    Savona, M R; Newton, D; Frame, D; Levine, J E; Mineishi, S; Kaul, D R

    2007-06-01

    In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC). In our institution, HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly cidofovir. Microbiological response was defined as at least a one log reduction in urinary BKV viral load; clinical response was defined as improvement in symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a mean of 68.7 days after transplant. A clinical response was detected in 16/19 (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10 nonresponders had a BKV viral load above the upper limit of the assay before treatment). Fourteen out of nineteen (74%) patients had no significant increase in serum creatinine. Five patients with renal dysfunction resolved after completion of the therapy and removal of other nephrotoxic agents. We conclude that weekly low-dose cidofovir appears to be a safe treatment option for BKV-associated HC. Although the efficacy of low-dose cidofovir is not proven, a prospective trial is warranted.

  14. UAS Integration in the NAS Project: Flight Test 3 Data Analysis of JADEM-Autoresolver Detect and Avoid System

    NASA Technical Reports Server (NTRS)

    Gong, Chester; Wu, Minghong G.; Santiago, Confesor

    2016-01-01

    The Unmanned Aircraft Systems Integration in the National Airspace System project, or UAS Integration in the NAS, aims to reduce technical barriers related to safety and operational challenges associated with enabling routine UAS access to the NAS. The UAS Integration in the NAS Project conducted a flight test activity, referred to as Flight Test 3 (FT3), involving several Detect-and-Avoid (DAA) research prototype systems between June 15, 2015 and August 12, 2015 at the Armstrong Flight Research Center (AFRC). This report documents the flight testing and analysis results for the NASA Ames-developed JADEM-Autoresolver DAA system, referred to as 'Autoresolver' herein. Four flight test days (June 17, 18, 22, and July 22) were dedicated to Autoresolver testing. The objectives of this test were as follows: 1. Validate CPA prediction accuracy and detect-and-avoid (DAA, formerly known as self-separation) alerting logic in realistic flight conditions. 2. Validate DAA trajectory model including maneuvers. 3. Evaluate TCAS/DAA interoperability. 4. Inform final Minimum Operating Performance Standards (MOPS). Flight test scenarios were designed to collect data to directly address the objectives 1-3. Objective 4, inform final MOPS, was a general objective applicable to the UAS in the NAS project as a whole, of which flight test is a subset. This report presents analysis results completed in support of the UAS in the NAS project FT3 data review conducted on October 20, 2015. Due to time constraints and, to a lesser extent, TCAS data collection issues, objective 3 was not evaluated in this analysis.

  15. Many-body design of highly strained GaInNAs electroabsorption modulators on GaInAs ternary substrates

    NASA Astrophysics Data System (ADS)

    Fujisawa, Takeshi; Arai, Masakazu; Kano, Fumiyoshi

    2010-05-01

    Electroabsorption in highly strained GaInAs and GaInNAs quantum wells (QWs) grown on GaInAs or quasi-GaInAs substrates is investigated by using microscopic many-body theory. The effects of various parameters, such as strain, barrier height, substrate composition, and temperature are thoroughly examined. It is shown that the value of the absorption coefficient strongly depends on the depth of the QWs under large bias electric field due to the small overlap integral of wave functions between the conduction and valence bands. The use of GaInNAs QWs makes the strain in the well layer very small. Further, the effective quantum-well depth is increased in GaInNAs QWs due to the anticrossing interaction between the conduction and N-resonant bands, making it possible to obtain larger absorption coefficient under large bias electric fields without using wide-band gap materials for barriers.

  16. Antiviral effects of artesunate on polyomavirus BK replication in primary human kidney cells.

    PubMed

    Sharma, Biswa Nath; Marschall, Manfred; Henriksen, Stian; Rinaldo, Christine Hanssen

    2014-01-01

    Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2'-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G0 or G2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.

  17. Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

    PubMed Central

    Sharma, Biswa Nath; Marschall, Manfred; Henriksen, Stian

    2014-01-01

    Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2′-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G0 or G2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions. PMID:24145549

  18. UAS Integration in the NAS Project: Detect and Avoid Display UNITED Demo

    NASA Technical Reports Server (NTRS)

    Roberts, Zachary

    2017-01-01

    This demo shows the UAS-NAS project's Vigilant Spirit Control Station developed in partnership with the U.S. Air Force Research Lab. Attendees will be able to view encounters and see how the DAA and TCAS II alerting and guidance displays are used to avoid simulated aircraft.

  19. Performance and Scalability of the NAS Parallel Benchmarks in Java

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael A.; Schultz, Matthew; Jin, Haoqiang; Yan, Jerry; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    Several features make Java an attractive choice for scientific applications. In order to gauge the applicability of Java to Computational Fluid Dynamics (CFD), we have implemented the NAS (NASA Advanced Supercomputing) Parallel Benchmarks in Java. The performance and scalability of the benchmarks point out the areas where improvement in Java compiler technology and in Java thread implementation would position Java closer to Fortran in the competition for scientific applications.

  20. NASA UAS Integration into the NAS Project: Human Systems Integration

    NASA Technical Reports Server (NTRS)

    Shively, Jay

    2016-01-01

    This presentation provides an overview of the work the Human Systems Integration (HSI) sub-project has done on detect and avoid (DAA) displays while working on the UAS (Unmanned Aircraft System) Integration into the NAS project. The most recent simulation on DAA interoperability with Traffic Collision Avoidance System (TCAS) is discussed in the most detail. The relationship of the work to the larger UAS community and next steps are also detailed.

  1. Solubility of NaCl in water and its melting point by molecular dynamics in the slab geometry and a new BK3-compatible force field

    NASA Astrophysics Data System (ADS)

    Kolafa, Jiří

    2016-11-01

    Saturated concentration of rock salt in water is determined by a simulation of brine in contact with a crystal in the slab geometry. The NaCl crystals are rotated to expose facets with higher Miller indices than [001] to brine. The rock salt melting point is obtained by both the standard and adiabatic simulations in the slab geometry with attention paid to finite size effects as well as to a possible influence of facets with higher Miller indices and applied stress. Two force fields are used, the Lennard-Jones-based model by Young and Cheatham with SPC/E water and the Kiss and Baranyai polarizable model with BK3 water. The latter model is refitted to thermomechanical properties of crystal NaCl leading to better values of solubility and the melting point.

  2. Solubility of NaCl in water and its melting point by molecular dynamics in the slab geometry and a new BK3-compatible force field.

    PubMed

    Kolafa, Jiří

    2016-11-28

    Saturated concentration of rock salt in water is determined by a simulation of brine in contact with a crystal in the slab geometry. The NaCl crystals are rotated to expose facets with higher Miller indices than [001] to brine. The rock salt melting point is obtained by both the standard and adiabatic simulations in the slab geometry with attention paid to finite size effects as well as to a possible influence of facets with higher Miller indices and applied stress. Two force fields are used, the Lennard-Jones-based model by Young and Cheatham with SPC/E water and the Kiss and Baranyai polarizable model with BK3 water. The latter model is refitted to thermomechanical properties of crystal NaCl leading to better values of solubility and the melting point.

  3. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project Subcommittee Final

    NASA Technical Reports Server (NTRS)

    Johnson, Chuck; Griner, James H.; Hayhurst, Kelly J.; Shively, Robert J.; Consiglio, Maria; Muller, Eric; Murphy, James; Kim, Sam

    2012-01-01

    UAS Integration in the NAS Project overview with details from each of the subprojects. Subprojects include: Communications, Certification, Integrated Test and Evaluation, Human Systems Integration, and Separation Assurance/Sense and Avoid Interoperability.

  4. Phylogenetic reconstruction and polymorphism analysis of BK virus VP2 gene isolated from renal transplant recipients in China

    PubMed Central

    WANG, ZHANG-YANG; HONG, WEI-LONG; ZHU, ZHE-HUI; CHEN, YUN-HAO; YE, WEN-LE; CHU, GUANG-YU; LI, JIA-LIN; CHEN, BI-CHENG; XIA, PENG

    2015-01-01

    BK polyomavirus (BKV) is important pathogen for kidney transplant recipients, as it is frequently re-activated, leading to nephropathy. The aim of this study was to investigate the phylogenetic reconstruction and polymorphism of the VP2 gene in BKV isolated from Chinese kidney transplant recipients. Phylogenetic analysis was carried out in the VP2 region from 135 BKV-positive samples and 28 reference strains retrieved from GenBank. The unweighted pair-group method with arithmetic mean (UPGMA) grouped all strains into subtypes, but failed to subdivide strains into subgroups. Among the plasma and urine samples, all plasma (23/23) and 82 urine samples (82/95) were identified to contain subtype I; the other 10 urine samples contained subtype IV. A 86-bp fragment was identified as a highly conserved sequence. Following alignment with 36 published BKV sequences from China, 92 sites of polymorphism were identified, including 11 single nucleotide polymorphisms (SNPs) prevalent in Chinese individuals and 30 SNPs that were specific to the two predominant subtypes I and IV. The limitations of the VP2 gene segment in subgrouping were confirmed by phylogenetic analysis. The conserved sequence and polymorphism identified in this study may be helpful in the detection and genotyping of BKV. PMID:26640547

  5. Surface deformation and friction characteristic of nano scratch at ductile-removal regime for optical glass BK7.

    PubMed

    Li, Chen; Zhang, Feihu; Ding, Ye; Liu, Lifei

    2016-08-20

    Nano scratch for optical glass BK7 based on the ductile-removal regime was carried out, and the influence rule of scratch parameters on surface deformation and friction characteristic was analyzed. Experimental results showed that, with increase of normal force, the deformation of burrs in the edge of the scratch was more obvious, and with increase of the scratch velocity, the deformation of micro-fracture and burrs in the edge of the scratch was more obvious similarly. The residual depth of the scratch was measured by atomic force microscope. The experimental results also showed that, with increase of normal force, the residual depth of the scratch increased linearly while the elastic recovery rate decreased. Furthermore, with increase of scratch velocity, the residual depth of the scratch decreased while the elastic recovery rate increased. The scratch process of the Berkovich indenter was divided into the cutting process of many large negative rake faces based on the improved cutting model, and the friction characteristic of the Berkovich indenter and the workpiece was analyzed. The analysis showed that the coefficient of friction increased and then tended to be stable with the increase of normal force. Meanwhile, the coefficient of friction decreased with the increase of scratch velocity, and the coefficients, k ln(v) and μ0, were introduced to improve the original formula of friction coefficient.

  6. Evaluating the Information Power Grid using the NAS Grid Benchmarks

    NASA Technical Reports Server (NTRS)

    VanderWijngaartm Rob F.; Frumkin, Michael A.

    2004-01-01

    The NAS Grid Benchmarks (NGB) are a collection of synthetic distributed applications designed to rate the performance and functionality of computational grids. We compare several implementations of the NGB to determine programmability and efficiency of NASA's Information Power Grid (IPG), whose services are mostly based on the Globus Toolkit. We report on the overheads involved in porting existing NGB reference implementations to the IPG. No changes were made to the component tasks of the NGB can still be improved.

  7. 76 FR 75870 - Approval for Subzone Expansion and Expansion of Manufacturing Authority; Foreign-Trade Subzone...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... and Expansion of Manufacturing Authority; Foreign-Trade Subzone 124B; North American Shipbuilding, LLC (Shipbuilding); Larose, Houma, and Port Fourchon, Louisiana Pursuant to its authority under the Foreign-Trade... North American Shipbuilding, LLC (NAS), operator of Subzone 124B at the NAS shipbuilding facilities in...

  8. Optimization of nas lemoore scheduling to support a growing aircraft population

    DTIC Science & Technology

    2017-03-01

    requirements, and, without knowing the other squadrons’ flight plans , creates his or her squadron’s flight schedule. Figure 2 illustrates the process each...Lemoore, they do not communicate their flight schedules among themselves; hence, the daily flight plan generated by each squadron is independently...manual process for aircraft flight scheduling at Naval Air Station (NAS) Lemoore accommodates the independent needs of 16 fighter resident squadrons as

  9. Identification of B-K near edge x-ray absorption fine structure peaks of boron nitride thin films prepared by sputtering deposition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Niibe, Masahito; Miyamoto, Kazuyoshi; Mitamura, Tohru

    2010-09-15

    Four {pi}{sup *} resonance peaks were observed in the B-K near edge x-ray absorption fine structure spectra of boron nitride thin films prepared by magnetron sputtering. In the past, these peaks have been explained as the K-absorption of boron atoms, which are present in environment containing nitrogen vacancies, the number of which is 1-3 corresponding to the three peaks at higher photon energy. However, the authors found that there was a strong correlation between the intensities of these three peaks and that of O-K absorption after wide range scanning and simultaneous measurement of nitrogen and oxygen K-absorptions of the BNmore » films. Therefore, the authors conclude that these three peaks at the higher energy side correspond to boron atoms bound to one-to-three oxygen atoms instead of three nitrogen atoms surrounding the boron atom in the h-BN structure. The result of the first-principles calculation with a simple cluster model supported the validity of this explanation.« less

  10. Web Prep: How to Prepare NAS Reports For Publication on the Web

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela; Balakrishnan, Prithika; Clucas, Jean; McCabe, R. Kevin; Felchle, Gail; Brickell, Cristy

    1996-01-01

    This document contains specific advice and requirements for NASA Ames Code IN authors of NAS reports. Much of the information may be of interest to other authors writing for the Web. WebPrep has a graphic Table of Contents in the form of a WebToon, which simulates a discussion between a scientist and a Web publishing consultant. In the WebToon, Frequently Asked Questions about preparing reports for the Web are linked to relevant text in the body of this document. We also provide a text-only Table of Contents. The text for this document is divided into chapters: each chapter corresponds to one frame of the WebToons. The chapter topics are: converting text to HTML, converting 2D graphic images to gif, creating imagemaps and tables, converting movie and audio files to Web formats, supplying 3D interactive data, and (briefly) JAVA capabilities. The last chapter is specifically for NAS staff authors. The Glossary-Index lists web related words and links to topics covered in the main text.

  11. The Performance of the NAS HSPs in 1st Half of 1994

    NASA Technical Reports Server (NTRS)

    Bergeron, Robert J.; Walter, Howard (Technical Monitor)

    1995-01-01

    During the first six months of 1994, the NAS (National Airspace System) 16-CPU Y-MP C90 Von Neumann (VN) delivered an average throughput of 4.045 GFLOPS while the ACSF (Aeronautics Consolidated Supercomputer Facility) 8-CPU Y-MP C90 Eagle averaged 1.658 GFLOPS. The VN rate represents a machine efficiency of 26.3% whereas the Eagle rate corresponds to a machine efficiency of 21.6%. VN displayed a greater efficiency than Eagle primarily because the stronger workload demand for its CPU cycles allowed it to devote more time to user programs and less time to idle. An additional factor increasing VN efficiency was the ability of the UNICOS 8.0 Operating System to deliver a larger fraction of CPU time to user programs. Although measurements indicate increasing vector length for both workloads, insufficient vector lengths continue to hinder HSP (High Speed Processor) performance. To improve HSP performance, NAS should continue to encourage the HSP users to modify their codes to increase program vector length.

  12. 48 CFR 852.236-82 - Payments under fixed-price construction contracts (without NAS).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...-conditioning system (Specified under 600 Sections) 5 Entire boiler plant system (Specified under 700 Sections... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Payments under fixed-price construction contracts (without NAS). 852.236-82 Section 852.236-82 Federal Acquisition Regulations System...

  13. 48 CFR 852.236-83 - Payments under fixed-price construction contracts (including NAS).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (cold, constant temperature) 5 Entire air-conditioning system (Specified under 600 Sections) 5 Entire... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Payments under fixed-price construction contracts (including NAS). 852.236-83 Section 852.236-83 Federal Acquisition Regulations System...

  14. NAS Decadal Review Town Hall

    NASA Astrophysics Data System (ADS)

    The National Academies of Sciences, Engineering and Medicine is seeking community input for a study on the future of materials research (MR). Frontiers of Materials Research: A Decadal Survey will look at defining the frontiers of materials research ranging from traditional materials science and engineering to condensed matter physics. Please join members of the study committee for a town hall to discuss future directions for materials research in the United States in the context of worldwide efforts. In particular, input on the following topics will be of great value: progress, achievements, and principal changes in the R&D landscape over the past decade; identification of key MR areas that have major scientific gaps or offer promising investment opportunities from 2020-2030; and the challenges that MR may face over the next decade and how those challenges might be addressed. This study was requested by the Department of Energy and the National Science Foundation. The National Academies will issue a report in 2018 that will offer guidance to federal agencies that support materials research, science policymakers, and researchers in materials research and other adjoining fields. Learn more about the study at http://nas.edu/materials.

  15. Pressure and PL study of dilute-N GaInNAs films for applications in photovoltaics

    NASA Astrophysics Data System (ADS)

    Lindberg, George; Fukuda, Miwa; Al Khalfioui, M.; Hossain, Khalid; Sellers, Ian; Weinstein, Bernard

    2013-03-01

    Multi-junction photovoltaic devices employing dilute-N GaInNAs alloys are currently of high interest for efficient solar energy conversion. The negative band-bowing produced by introducing a few percent N into GaInAs provides a convenient way to match the 1eV component of the solar spectrum, providing recombination losses in localized states can be reduced while maintaining favorable carrier extraction. High pressure photoluminescence (PL) experiments exploring the localization of band-edge excitons in dilute-N GaInNAs films grown by plasma assisted MBE will be discussed. The effects of post-growth annealing and hydrogen incorporation on the PL spectra of the films are considered. Research supported by Amethyst Research Inc. through the State of Oklahoma, ONAP program.

  16. Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors.

    PubMed

    Egli, Adrian; Infanti, Laura; Dumoulin, Alexis; Buser, Andreas; Samaridis, Jacqueline; Stebler, Christine; Gosert, Rainer; Hirsch, Hans H

    2009-03-15

    The replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, but the behavior of these viruses in immunocompetent individuals has hardly been characterized. We used EIA to study samples obtained from 400 healthy blood donors aged 20-59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction. IgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20-29 years) to 71% (71 of 100) in the oldest group (aged 50-59 years) (P = .006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P = .06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P < .001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma. Our study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiology.

  17. Analysis of real-time mixture cytotoxicity data following repeated exposure using BK/TD models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Teng, S.; Tebby, C.

    Cosmetic products generally consist of multiple ingredients. Thus, cosmetic risk assessment has to deal with mixture toxicity on a long-term scale which means it has to be assessed in the context of repeated exposure. Given that animal testing has been banned for cosmetics risk assessment, in vitro assays allowing long-term repeated exposure and adapted for in vitro – in vivo extrapolation need to be developed. However, most in vitro tests only assess short-term effects and consider static endpoints which hinder extrapolation to realistic human exposure scenarios where concentration in target organs is varies over time. Thanks to impedance metrics, real-timemore » cell viability monitoring for repeated exposure has become possible. We recently constructed biokinetic/toxicodynamic models (BK/TD) to analyze such data (Teng et al., 2015) for three hepatotoxic cosmetic ingredients: coumarin, isoeugenol and benzophenone-2. In the present study, we aim to apply these models to analyze the dynamics of mixture impedance data using the concepts of concentration addition and independent action. Metabolic interactions between the mixture components were investigated, characterized and implemented in the models, as they impacted the actual cellular exposure. Indeed, cellular metabolism following mixture exposure induced a quick disappearance of the compounds from the exposure system. We showed that isoeugenol substantially decreased the metabolism of benzophenone-2, reducing the disappearance of this compound and enhancing its in vitro toxicity. Apart from this metabolic interaction, no mixtures showed any interaction, and all binary mixtures were successfully modeled by at least one model based on exposure to the individual compounds. - Highlights: • We could predict cell response over repeated exposure to mixtures of cosmetics. • Compounds acted independently on the cells. • Metabolic interactions impacted exposure concentrations to the compounds.« less

  18. Room-temperature electron spin amplifier based on Ga(In)NAs alloys.

    PubMed

    Puttisong, Yuttapoom; Buyanova, Irina A; Ptak, Aaron J; Tu, Charles W; Geelhaar, Lutz; Riechert, Henning; Chen, Weimin M

    2013-02-06

    The first experimental demonstration of a spin amplifier at room temperature is presented. An efficient, defect-enabled spin amplifier based on a non-magnetic semiconductor, Ga(In)NAs, is proposed and demonstrated, with a large spin gain (up to 2700% at zero field) for conduction electrons and a high cut-off frequency of up to 1 GHz. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Thickness and marking quality of different occlusal contact registration strips

    PubMed Central

    TOLEDO, Maria Fernanda de Souza Mauá Serapião; JÓIAS, Renata Pilli; MARQUES-IASI, Yves Santini; NEVES, Ana Christina Claro; RODE, Sigmar de Mello

    2014-01-01

    Objectives Evaluate the thickness and the marking quality of different occlusal contact registration strips (OCRS) and a possible correlation between them. Material and Methods The following OCRS were selected: Accufilm II, BK20, BK21, BK22, BK23, BK28, and BK31. The thickness was measured in three points of the OCRS with an electronic measuring device (TESA), and the mean was calculated. To produce the marks on the strips, composite resin specimens were adapted to a universal testing machine (Versat 2000) with 40 kgf load cell at a speed of 1.0 mm/min. The mark images were photographed with a stereoscopic microscope (Stemi SV11) and processed and analyzed by the 550-Leica Qwin® analyzer. Results Values (μm) found in the 1st and 2nd thickness measurements were: Accufilm II - 16.4 and 14.2; BK20 - 10.0 and 8.1; BK21 - 9.5 and 8.0; BK22 - 9.7 and 8.7; BK23 - 9.8 and 7.9; BK28 - 12.8 and 10.0; and BK31 - 8.4 and 8.0, respectively. The mean (mm2) values found in the mark areas were: Accufilm II - 0.078; BK20 - 0.035; BK21 - 0.045; BK22 - 0.012; BK23 - 0.022; BK28 - 0.024; and BK31 - 0.024. The results were submitted to the Kruskal-Wallis (p<0.05) and Pearson’s correlation tests. Conclusions Only in the 2nd measurement, the OCRS thickness observed was similar to the value indicated by the manufacturers; the Accufilm II and the BK28 strips showed the better marks; and no correlation was found between the thickness and the marking area. PMID:25591020

  20. Ciprofloxacin decreased polyoma BK virus load in patients who underwent allogeneic hematopoietic stem cell transplantation.

    PubMed

    Leung, Anskar Y H; Chan, Maggie T L; Yuen, Kwok-Yung; Cheng, Vincent C C; Chan, Kwok-Hung; Wong, Chris L P; Liang, Raymond; Lie, Albert K W; Kwong, Yok-Lam

    2005-02-15

    Polyoma BK virus (BKV) is associated with hemorrhagic cystitis during hematopoietic stem cell transplantation (HSCT). The objective of this study was to test whether standard-dose ciprofloxacin might suppress reactivation of BKV infection during HSCT. Sixty-eight patients received ciprofloxacin or a cephalosporin as antibiotic prophylaxis after undergoing allogeneic HSCT. Urine samples were collected weekly from day 7 before HSCT to day 50 after HSCT. Laboratory investigations included quantification of BKV load and urinary ciprofloxacin levels and in vitro drug sensitivity of BKV. Twenty-two patients received ciprofloxacin, 21 received cephalosporins, 12 received concomitant corticosteroids and antibiotics (9 received ciprofloxacin, and 3 received cephalosporins), and 13 received interrupted ciprofloxacin therapy. Ciprofloxacin recipients developed a significantly lower peak BKV load, compared with cephalosporin recipients (median, 3x10(5) copies/mL vs. 2.6x10(9) copies/mL; P=.021), irrespective of concomitant receipt of corticosteroid therapy. Fewer ciprofloxacin recipients than cephalosporin recipients (P=.013) developed BKV viruria with a > or =3-log increase in BKV load during HSCT, which was associated with significantly more cases of hemorrhagic cystitis (8 of 29 patients with a peak increase of > or =3 log vs. 0 of 39 patients without a peak increase of this level; P<.001). Ciprofloxacin recipients excreted ciprofloxacin in urine at a mean 24-h rate of 71.7 microg/mL (range, 23.0-152.9 microg/mL), which was comparable with the in vitro inhibitory concentration of 125-250 microg/mL of ciprofloxacin found for 3 of 7 BKV isolates. Ciprofloxacin decreased urinary BKV reactivation after HSCT.

  1. Polyomavirus BK and JC in individuals with chronic kidney failure, kidney transplantation, and healthy controls.

    PubMed

    Castro, Talita; Fink, Maria Cristina Domingues; Figueiredo, Marilia; Braz-Silva, Paulo Henrique; Pannuti, Cláudio Mendes; Ortega, Karem Lopez; Gallottini, Marina

    2017-04-01

    New clinical approaches to diagnose and monitor individuals with systemic diseases have been employed through the use of oral fluids. Polyomavirus BK (BKPyV) and JC (JCPyV) infect asymptomatically around 80% of general population worldwide remaining latent in the body. In case of immunosuppression, a replication can occur, leading to diseases. The aim of this study was to detect and quantify BKPyV and JCPyV in oral fluids of individuals with chronic kidney failure (CKF), kidney transplantation (KT) and controls compared with their detection in blood and urine, traditionally used for this test. Forty six subjects were included and distributed into 3 groups: 14 with CKF (Group 1), 12 with KT (Group 2) and 20 healthy individuals (Group 3). In a total, 315 samples were collected and analyzed through RT-PCR, being 151 of gingival crevicular fluid, 46 of saliva, 46 of mouthwash, 43 of blood and 29 of urine. All subjects from group 1 were positive for BKPyV in at least one collected samples and 14% were positive for JCPyV. In Group 2, 91.7% were positive for BKPyV and 51.7% for JCPyV. Among subjects of Group 3, 80% were positive for BKPyV and 45% for JCPyV. Oral fluids exhibited high prevalence of BKPyV and JCPyV and were equally efficient compared to urine and blood. The use of oral fluids to detect these polyomaviruses enhances positivity in screening, even in cases of absence of viremia and especially in individuals who are not able to urinate. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 48 CFR 852.236-82 - Payments under fixed-price construction contracts (without NAS).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... “Network Analysis System (NAS).” Payments Under Fixed-Price Construction Contracts (APR 1984) The clause..., as applied to each branch, shall equal the total cost of such branch. The total cost of all branches... readily available for inspection and inventory by the resident engineer. (4) Such materials and/or...

  3. 48 CFR 852.236-82 - Payments under fixed-price construction contracts (without NAS).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... “Network Analysis System (NAS).” Payments Under Fixed-Price Construction Contracts (APR 1984) The clause..., as applied to each branch, shall equal the total cost of such branch. The total cost of all branches... readily available for inspection and inventory by the resident engineer. (4) Such materials and/or...

  4. 48 CFR 852.236-82 - Payments under fixed-price construction contracts (without NAS).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... “Network Analysis System (NAS).” Payments Under Fixed-Price Construction Contracts (APR 1984) The clause..., as applied to each branch, shall equal the total cost of such branch. The total cost of all branches... readily available for inspection and inventory by the resident engineer. (4) Such materials and/or...

  5. 48 CFR 852.236-82 - Payments under fixed-price construction contracts (without NAS).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... “Network Analysis System (NAS).” Payments Under Fixed-Price Construction Contracts (APR 1984) The clause..., as applied to each branch, shall equal the total cost of such branch. The total cost of all branches... readily available for inspection and inventory by the resident engineer. (4) Such materials and/or...

  6. Polyomavirus Reactivation and Immune Responses to Kidney-Specific Self-Antigens in Transplantation.

    PubMed

    Seifert, Michael E; Gunasekaran, Muthukumar; Horwedel, Timothy A; Daloul, Reem; Storch, Gregory A; Mohanakumar, Thalachallour; Brennan, Daniel C

    2017-04-01

    Humoral immune responses against donor antigens are important determinants of long-term transplant outcomes. Reactivation of the polyomavirus BK has been associated with de novo antibodies against mismatched donor HLA antigens in kidney transplantation. The effect of polyomavirus reactivation (BK viremia or JC viruria) on antibodies to kidney-specific self-antigens is unknown. We previously reported excellent 5-year outcomes after minimization of immunosuppression for BK viremia and after no intervention for JC viruria. Here, we report the 10-year results of this trial ( n =193) along with a nested case-control study ( n =40) to explore associations between polyomavirus reactivation and immune responses to the self-antigens fibronectin (FN) and collagen type-IV (Col-IV). Consistent with 5-year findings, subjects taking tacrolimus, compared with those taking cyclosporin, had less acute rejection (11% versus 22%, P =0.05) and graft loss (9% versus 22%, P =0.01) along with better transplant function (eGFR 65±19 versus 50±24 ml/min per 1.73 m 2 , P <0.001) at 10 years. Subjects undergoing immunosuppression reduction for BK viremia had 10-year outcomes similar to those without viremia. In the case-control study, antibodies to FN/Col-IV were more prevalent during year 1 in subjects with polyomavirus reactivation than in those without reactivation (48% versus 11%, P= 0.04). Subjects with antibodies to FN/Col-IV had more acute rejection than did those without these antibodies (38% versus 8%, P =0.02). These data demonstrate the long-term safety and effectiveness of minimizing immunosuppression to treat BK viremia. Furthermore, these results indicate that polyomavirus reactivation associates with immune responses to kidney-specific self-antigens that may increase the risk for acute rejection through unclear mechanisms. Copyright © 2017 by the American Society of Nephrology.

  7. 48 CFR 852.236-83 - Payments under fixed-price construction contracts (including NAS).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... shall show on the critical path method (CPM) network the total cost of the guarantee period services in... prescribed in 832.111, insert the following clause in contracts that contain a section entitled “Network...) Failure either to meet schedules in Section Network Analysis System (NAS), or to process the Interim Arrow...

  8. 48 CFR 852.236-83 - Payments under fixed-price construction contracts (including NAS).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... shall show on the critical path method (CPM) network the total cost of the guarantee period services in... prescribed in 832.111, insert the following clause in contracts that contain a section entitled “Network...) Failure either to meet schedules in Section Network Analysis System (NAS), or to process the Interim Arrow...

  9. 48 CFR 852.236-83 - Payments under fixed-price construction contracts (including NAS).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... shall show on the critical path method (CPM) network the total cost of the guarantee period services in... prescribed in 832.111, insert the following clause in contracts that contain a section entitled “Network...) Failure either to meet schedules in Section Network Analysis System (NAS), or to process the Interim Arrow...

  10. Remotely Operated Aircraft (ROA) Impact on the National Airspace System (NAS) Work Package: Automation Impacts of ROA's in the NAS

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The purpose of this document is to analyze the impact of Remotely Operated Aircraft (ROA) operations on current and planned Air Traffic Control (ATC) automation systems in the En Route, Terminal, and Traffic Flow Management domains. The operational aspects of ROA flight, while similar, are not entirely identical to their manned counterparts and may not have been considered within the time-horizons of the automation tools. This analysis was performed to determine if flight characteristics of ROAs would be compatible with current and future NAS automation tools. Improvements to existing systems / processes are recommended that would give Air Traffic Controllers an indication that a particular aircraft is an ROA and modifications to IFR flight plan processing algorithms and / or designation of airspace where an ROA will be operating for long periods of time.

  11. American Women and American Studies.

    ERIC Educational Resources Information Center

    Chmaj, Betty E.

    The American Studies Association (ASA) is an interprofessional group, representing a cross-section of persons from American literature, American history, the social sciences, philosophy, archeology, Black Studies, Urban Studies, American Studies, and others. This document by the ASA Commission on the Status of Women includes: (1) a report of the…

  12. Validation of the nursing workload scoring systems "Nursing Activities Score" (NAS), and "Therapeutic Intervention Scoring System For Critically Ill Children" (TISS-C) in a Greek Paediatric Intensive Care Unit.

    PubMed

    Nieri, Alexandra-Stavroula; Manousaki, Kalliopi; Kalafati, Maria; Padilha, Katia Grilio; Stafseth, Siv K; Katsoulas, Theodoros; Matziou, Vasiliki; Giannakopoulou, Margarita

    2018-04-11

    To assess the reliability and validity of the Greek version of Nursing Activities Score (NAS), and Therapeutic Intervention Scoring System for Critically Ill Children (TISS-C) in a Greek Paediatric Intensive Care Unit (PICU). A methodological study was performed in one PICU of the largest Paediatric Hospital in Athens-Greece. The culturally adapted and validated Greek NAS version, enriched according to the Norwegian paediatric one (P-NAS), was used. TISS-C and Norwegian paediatric interventions were translated to Greek language and backwards. Therapeutic Intervention Scoring System (TISS-28) was used as a gold standard. Two independent observers simultaneously recorded 30 daily P-NAS and TISS-C records. Totally, 188 daily P-NAS, TISS-C and TISS-28 reports in a sample of 29 patients have been obtained during 5 weeks. Descriptive statistics, reliability and validity measures were applied using SPSS (ver 22.0) (p ≤ 0.05). Kappa was 0.963 for P-NAS and 0.9895 for TISS-C (p < 0.001) and Intraclass Correlation Coefficient for all scale items of TISS-C was 1.00 (p < 0.001). P-NAS, TISS-28 and TISS-C measurements were significantly correlated (0.680 ≤ rho ≤ 0.743, p < 0.001). The mean score(±SD) for TISS-28, P-NAS and TISS-C was 23.05(±5.72), 58.14(±13.98) and 20.21(±9.66) respectively. These results support the validity of P-NAS and TISS-C scales to be used in Greek PICUs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Navigation in Grid Space with the NAS Grid Benchmarks

    NASA Technical Reports Server (NTRS)

    Frumkin, Michael; Hood, Robert; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    We present a navigational tool for computational grids. The navigational process is based on measuring the grid characteristics with the NAS Grid Benchmarks (NGB) and using the measurements to assign tasks of a grid application to the grid machines. The tool allows the user to explore the grid space and to navigate the execution at a grid application to minimize its turnaround time. We introduce the notion of gridscape as a user view of the grid and show how it can be me assured by NGB, Then we demonstrate how the gridscape can be used with two different schedulers to navigate a grid application through a rudimentary grid.

  14. Angiotensin I-converting enzyme inhibitors potentiate bradykinin's inotropic effects independently of blocking its inactivation.

    PubMed

    Minshall, R D; Erdös, E G; Vogel, S M

    1997-08-04

    The positive inotropic effects of bradykinin (BK) and 2 analogs resistant to angiotensin I-converting enzyme (ACE) were potentiated on isolated guinea pig atrial preparations by enalaprilat. The stable BK analogs, dextran-BK and [Hyp3-Tyr(Me)8]-BK, were as active as BK. Pretreatment for 5 min with enalaprilat augmented the maximal positive inotropic effect of [Hyp3-Tyr(Me)8]-BK 2.8-fold, from 19% to 53% and that of BK from 28% to 42% over baseline; inotropic responses to dextran-BK (1 microM) were similarly increased. The activity of atrial ACE, a zinc-requiring enzyme, was completely inhibited by 8-hydroxyquinoline-5-sulfonic acid (QSA, 10 mM), which raised the maximal inotropic effect of BK to 39% above baseline. This value rose to 67% when in addition to QSA, 1 microM enalaprilat was added; enalaprilat thus, potentiated the effects of BK independently of enzyme inhibition. The positive inotropic effects to BK and its analogs decline with time in the presence of these agonists. After 10 min of exposure, the response to 1 microM [Hyp3-Tyr(Me)8]-BK decreased to about half, and after 20 min, to 0. Enalaprilat, when present in the tissue bath, prevented the decline in inotropy; even after tachyphylaxis occurred, it reversed this decrease in activity when added. The effects of 1 microM [Hyp3-Tyr(Me)8]-BK, in the absence or presence of enalaprilat, were abolished by the BK B2 receptor antagonist icatibant (0.75 microM). The results indicate that ACE inhibitors, by potentiating the BK effects and blocking BK B2-receptor desensitization, may contribute to the beneficial cardiac effects of BK independently of blocking its inactivation.

  15. NASA's UAS Integration into the NAS: A Report on the Human Systems Integration Phase 1 Simulation Activities

    NASA Technical Reports Server (NTRS)

    Fern, Lisa; Rorie, R. Conrad; Shively, R. Jay

    2014-01-01

    In 2011 the National Aeronautics and Space Administration (NASA) began a five-year Project to address the technical barriers related to routine access of Unmanned Aerial Systems (UAS) in the National Airspace System (NAS). Planned in two phases, the goal of the first phase was to lay the foundations for the Project by identifying those barriers and key issues to be addressed to achieve integration. Phase 1 activities were completed two years into the five-year Project. The purpose of this paper is to review activities within the Human Systems Integration (HSI) subproject in Phase 1 toward its two objectives: 1) develop GCS guidelines for routine UAS access to the NAS, and 2) develop a prototype display suite within an existing Ground Control Station (GCS). The first objective directly addresses a critical barrier for UAS integration into the NAS - a lack of GCS design standards or requirements. First, the paper describes the initial development of a prototype GCS display suite and supporting simulation software capabilities. Then, three simulation experiments utilizing this simulation architecture are summarized. The first experiment sought to determine a baseline performance of UAS pilots operating in civil airspace under current instrument flight rules for manned aircraft. The second experiment examined the effect of currently employed UAS contingency procedures on Air Traffic Control (ATC) participants. The third experiment compared three GCS command and control interfaces on UAS pilot response times in compliance with ATC clearances. The authors discuss how the results of these and future simulation and flight-testing activities contribute to the development of GCS guidelines to support the safe integration of UAS into the NAS. Finally, the planned activities for Phase 2, including an integrated human-in-the-loop simulation and two flight tests are briefly described.

  16. 77 FR 20321 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... Deutschland GmbH (ECD) MBB-BK 117 A-3, MBB-BK 117 A-4, MBB- BK B-1, MBB-BK 117 B-2, and MBB-BK C-1 helicopters... Eurocopter Deutschland GmbH (ECD) Model MBB-BK 117 A-4 model. The EASA AD makes no mention of this model. The...

  17. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project

    NASA Technical Reports Server (NTRS)

    Griner, James H.

    2013-01-01

    NASA's UAS Integration in the NAS project, has partnered with Rockwell Collins to develop a concept Control and Non-Payload Communication system prototype radio, operating on recently allocated UAS frequency spectrum bands. The prototype radio will be used to validate initial proposed performance requirements for UAS control communications. This presentation will give an overview of the current status of the design, development, and flight test planning for this prototype radio.

  18. Enhancement of photoluminescence from GaInNAsSb quantum wells upon annealing: improvement of material quality and carrier collection by the quantum well.

    PubMed

    Baranowski, M; Kudrawiec, R; Latkowska, M; Syperek, M; Misiewicz, J; Sarmiento, T; Harris, J S

    2013-02-13

    In this study we apply time resolved photoluminescence and contactless electroreflectance to study the carrier collection efficiency of a GaInNAsSb/GaAs quantum well (QW). We show that the enhancement of photoluminescence from GaInNAsSb quantum wells annealed at different temperatures originates not only from (i) the improvement of the optical quality of the GaInNAsSb material (i.e., removal of point defects, which are the source of nonradiative recombination) but it is also affected by (ii) the improvement of carrier collection by the QW region. The total PL efficiency is the product of these two factors, for which the optimal annealing temperatures are found to be ~700 °C and ~760 °C, respectively, whereas the optimal annealing temperature for the integrated PL intensity is found to be between the two temperatures and equals ~720 °C. We connect the variation of the carrier collection efficiency with the modification of the band bending conditions in the investigated structure due to the Fermi level shift in the GaInNAsSb layer after annealing.

  19. Up-Regulatory Effects of Curcumin on Large Conductance Ca2+-Activated K+ Channels

    PubMed Central

    Hei, Hongya; Li, Fangping; Wang, Yunman; Peng, Wen; Zhang, Xuemei

    2015-01-01

    Large conductance Ca2+-activated potassium channels (BK) are targets for research that explores therapeutic means to various diseases, owing to the roles of the channels in mediating multiple physiological processes in various cells and tissues. We investigated the pharmacological effects of curcumin, a compound isolated from the herb Curcuma longa, on BK channels. As recorded by whole-cell patch-clamp, curcumin increased BK (α) and BK (α+β1) currents in transfected HEK293 cells as well as the current density of BK in A7r5 smooth muscle cells in a dose-dependent manner. By incubating with curcumin for 24 hours, the current density of exogenous BK (α) in HEK293 cells and the endogenous BK in A7r5 cells were both enhanced notably, though the steady-state activation of the channels did not shift significantly, except for BK (α+β1). Curcumin up-regulated the BK protein expression without changing its mRNA level in A7r5 cells. The surface expression and the half-life of BK channels were also increased by curcumin in HEK293 cells. These effects of curcumin were abolished by MG-132, a proteasome inhibitor. Curcumin also increased ERK 1/2 phosphorylation, while inhibiting ERK by U0126 attenuated the curcumin-induced up-regulation of BK protein expression. We also observed that the curcumin-induced relaxation in the isolated rat aortic rings was significantly attenuated by paxilline, a BK channel specific blocker. These results show that curcumin enhances the activity of the BK channels by interacting with BK directly as well as enhancing BK protein expression through inhibiting proteasomal degradation and activating ERK signaling pathway. The findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and the underlying mechanisms. PMID:26672753

  20. Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach.

    PubMed

    Blazquez-Navarro, Arturo; Schachtner, Thomas; Stervbo, Ulrik; Sefrin, Anett; Stein, Maik; Westhoff, Timm H; Reinke, Petra; Klipp, Edda; Babel, Nina; Neumann, Avidan U; Or-Guil, Michal

    2018-05-01

    BK virus (BKV) associated nephropathy affects 1-10% of kidney transplant recipients, leading to graft failure in about 50% of cases. Immune responses against different BKV antigens have been shown to have a prognostic value for disease development. Data currently suggest that the structural antigens and regulatory antigens of BKV might each trigger a different mode of action of the immune response. To study the influence of different modes of action of the cellular immune response on BKV clearance dynamics, we have analysed the kinetics of BKV plasma load and anti-BKV T cell response (Elispot) in six patients with BKV associated nephropathy using ODE modelling. The results show that only a small number of hypotheses on the mode of action are compatible with the empirical data. The hypothesis with the highest empirical support is that structural antigens trigger blocking of virus production from infected cells, whereas regulatory antigens trigger an acceleration of death of infected cells. These differential modes of action could be important for our understanding of BKV resolution, as according to the hypothesis, only regulatory antigens would trigger a fast and continuous clearance of the viral load. Other hypotheses showed a lower degree of empirical support, but could potentially explain the clearing mechanisms of individual patients. Our results highlight the heterogeneity of the dynamics, including the delay between immune response against structural versus regulatory antigens, and its relevance for BKV clearance. Our modelling approach is the first that studies the process of BKV clearance by bringing together viral and immune kinetics and can provide a framework for personalised hypotheses generation on the interrelations between cellular immunity and viral dynamics.

  1. Ultramicroporous Carbon through an Activation-Free Approach for Li-S and Na-S Batteries in Carbonate-Based Electrolyte.

    PubMed

    Hu, Lei; Lu, Yue; Zhang, Tianwen; Huang, Tao; Zhu, Yongchun; Qian, Yitai

    2017-04-26

    We report an activation-free approach for fabricating ultramicroporous carbon as an accommodation of sulfur molecules for Li-S and Na-S batteries applications in carbonate-based electrolyte. Because of the high specific surface area of 967 m 2 g -1 , as well as 51.8% of the pore volume is contributed by ultramicropore with pore size less than 0.7 nm, sulfur cathode exhibits superior electrochemical behavior in carbonate-based electrolyte with a capacity of 507.9 mA h g -1 after 500 cycles at 2 C in Li-S batteries and 392 mA h g -1 after 200 cycles at 1 C in Na-S batteries, respectively.

  2. A new structurally atypical bradykinin-potentiating peptide isolated from Crotalus durissus cascavella venom (South American rattlesnake).

    PubMed

    Lopes, Denise M; Junior, Norberto E G; Costa, Paula P C; Martins, Patrícia L; Santos, Cláudia F; Carvalho, Ellaine D F; Carvalho, Maria D F; Pimenta, Daniel C; Cardi, Bruno A; Fonteles, Manassés C; Nascimento, Nilberto R F; Carvalho, Krishnamurti M

    2014-11-01

    Venom glands of some snakes synthesize bradykinin-potentiating peptides (BPP's) which increase bradykinin-induced hypotensive effect and decrease angiotensin I vasopressor effect by angiotensin-converting enzyme (ACE) inhibition. The present study shows a new BPP (BPP-Cdc) isolated from Crotalus durissus cascavella venom: Pro-Asn-Leu-Pro-Asn-Tyr-Leu-Gly-Ile-Pro-Pro. Although BPP-Cdc presents the classical sequence IPP in the C-terminus, it has a completely atypical N-terminal sequence, which shows very low homology with all other BPPs isolated to date. The pharmacological effects of BPP-Cdc were compared to BBP9a from Bothrops jararaca and captopril. BPP-Cdc (1 μM) significantly increased BK-induced contractions (BK; 1 μM) on the guinea pig ileum by 267.8% and decreased angiotensin I-induced contractions (AngI; 10 nM) by 62.4% and these effects were not significantly different from those of BPP9a (1 μM) or captopril (200 nM). Experiments with 4-week hypertensive 2K-1C rats show that the vasopressor effect of AngI (10 ng) was decreased by 50 μg BPP-Cdc (69.7%), and this result was similar to that obtained with 50 μg BPP9a (69.8%). However, the action duration of BPP-Cdc (60 min) was 2 times greater than that of BPP-9a (30 min). On the other hand, the hypotensive effect of BK (250 ng) was significantly increased by 176.6% after BPP-Cdc (50 μg) administration, value 2.5 times greater than that obtained with BPP9a administered at the same doses (71.4%). In addition, the duration of the action of BPP-Cdc (120 min) was also at least 4 times greater than that of BPP-9a (30 min). Taken together, these results suggest that BPP-Cdc presents more selective action on arterial blood system than BPP9a. Besides the inhibition of ACE, it may present other mechanisms of action yet to be elucidated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Electronic Structure and Properties of Berkelium Iodates.

    PubMed

    Silver, Mark A; Cary, Samantha K; Garza, Alejandro J; Baumbach, Ryan E; Arico, Alexandra A; Galmin, Gregory A; Chen, Kuan-Wen; Johnson, Jason A; Wang, Jamie C; Clark, Ronald J; Chemey, Alexander; Eaton, Teresa M; Marsh, Matthew L; Seidler, Kevin; Galley, Shane S; van de Burgt, Lambertus; Gray, Ashley L; Hobart, David E; Hanson, Kenneth; Van Cleve, Shelley M; Gendron, Frédéric; Autschbach, Jochen; Scuseria, Gustavo E; Maron, Laurent; Speldrich, Manfred; Kögerler, Paul; Celis-Barros, Cristian; Páez-Hernández, Dayán; Arratia-Pérez, Ramiro; Ruf, Michael; Albrecht-Schmitt, Thomas E

    2017-09-27

    The reaction of 249 Bk(OH) 4 with iodate under hydrothermal conditions results in the formation of Bk(IO 3 ) 3 as the major product with trace amounts of Bk(IO 3 ) 4 also crystallizing from the reaction mixture. The structure of Bk(IO 3 ) 3 consists of nine-coordinate Bk III cations that are bridged by iodate anions to yield layers that are isomorphous with those found for Am III , Cf III , and with lanthanides that possess similar ionic radii. Bk(IO 3 ) 4 was expected to adopt the same structure as M(IO 3 ) 4 (M = Ce, Np, Pu), but instead parallels the structural chemistry of the smaller Zr IV cation. Bk III -O and Bk IV -O bond lengths are shorter than anticipated and provide further support for a postcurium break in the actinide series. Photoluminescence and absorption spectra collected from single crystals of Bk(IO 3 ) 4 show evidence for doping with Bk III in these crystals. In addition to luminescence from Bk III in the Bk(IO 3 ) 4 crystals, a broad-band absorption feature is initially present that is similar to features observed in systems with intervalence charge transfer. However, the high-specific activity of 249 Bk (t 1/2 = 320 d) causes oxidation of Bk III and only Bk IV is present after a few days with concomitant loss of both the Bk III luminescence and the broadband feature. The electronic structure of Bk(IO 3 ) 3 and Bk(IO 3 ) 4 were examined using a range of computational methods that include density functional theory both on clusters and on periodic structures, relativistic ab initio wave function calculations that incorporate spin-orbit coupling (CASSCF), and by a full-model Hamiltonian with spin-orbit coupling and Slater-Condon parameters (CONDON). Some of these methods provide evidence for an asymmetric ground state present in Bk IV that does not strictly adhere to Russel-Saunders coupling and Hund's Rule even though it possesses a half-filled 5f 7 shell. Multiple factors contribute to the asymmetry that include 5f electrons being present in

  4. Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation

    PubMed Central

    Lee, Seung-Shin; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

    2015-01-01

    Background/Aims BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Methods Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Results Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Conclusions Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC. PMID:25750563

  5. Treatment of BK virus-associated hemorrhagic cystitis with low-dose intravenous cidofovir in patients undergoing allogeneic hematopoietic cell transplantation.

    PubMed

    Lee, Seung-Shin; Ahn, Jae-Sook; Jung, Sung-Hoon; Ahn, Seo-Yeon; Kim, Jae-Yong; Jang, Hee-Chang; Kang, Seung-Ji; Jang, Mi-Ok; Yang, Deok-Hwan; Kim, Yeo-Kyeoung; Lee, Je-Jung; Kim, Hyeoung-Joon

    2015-03-01

    BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.

  6. The determination and arrangement of a combination of enzyme lactate dehydrogenase of bacteria Acinetobacter sp. as a device the identity important bacteria agent composts

    NASA Astrophysics Data System (ADS)

    Sukmawati, D.; Puspitaningrum, R.; Muzajjanah

    2017-07-01

    The number of garbage generated by the industry or society is a usual problem encountered by almost all urban centers, especially large cities such as Jakarta. Waste prevention strategy required quickly and accurately. One strategy for tackling the Junk was getting lactic acid-producing bacteria. It has been shown that lactic acid can increase the acceleration of organic matter such as an overhaul of lignin and cellulose as well as out causing toxic compounds arising from decay. This research will be conducted on the determination and characterization of the enzyme-producing compost bacteria LDH lactate dehydrogenase LDH - which in isolation from the garbage Landfill Rawasari. Methodology: Research carried out consists: isolation of lactic acid-producing bacteria; identification of microscopic, macroscopic and staining Gram; cellulose assay, and optimization of PCR conditions LDH enzymes producing bacteria. Isolation is performed by dilution method and the direct method. As many as 5-point sampling. Each stage is conducted from 10 grams of soil from the top surface of the compost. Isolation results obtained 100 isolate the bacteria. Base on the characteristic of macroscopic and microscopic observations retrieved 14 isolates of bacteria have shaped rods and brought forth a negative kind of Gram positive staining. Bacterial isolates with codes (BK1; BK3; BK4; BK5; BK6; BK7; BK8; BK9; BK10; BK11: BK12; BK 13). The potential bacteria with ability produce lactate dehydrogenase was BK1 and BK3. Base for analysis phylogenetic there was identification bacteria bak1 and bak3 where Acinetobacter sp.

  7. The OpenMP Implementation of NAS Parallel Benchmarks and its Performance

    NASA Technical Reports Server (NTRS)

    Jin, Hao-Qiang; Frumkin, Michael; Yan, Jerry

    1999-01-01

    As the new ccNUMA architecture became popular in recent years, parallel programming with compiler directives on these machines has evolved to accommodate new needs. In this study, we examine the effectiveness of OpenMP directives for parallelizing the NAS Parallel Benchmarks. Implementation details will be discussed and performance will be compared with the MPI implementation. We have demonstrated that OpenMP can achieve very good results for parallelization on a shared memory system, but effective use of memory and cache is very important.

  8. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project: KDP-A for Phase 2 Minimum Operational Performance Standards

    NASA Technical Reports Server (NTRS)

    Grindle, Laurie; Hackenberg, Davis L.

    2016-01-01

    UAS Integration in the NAS Project has: a) Developed Technical Challenges that are crucial to UAS integration, aligned with NASA's Strategic Plan and Thrusts, and support FAA standards development. b) Demonstrated rigorous project management processes through the execution of previous phases. c) Defined Partnership Plans. d) Established path to KDP-C. Request approval of Technical Challenges, execution of partnerships and plans, and execution of near-term FY17 activities. There is an increasing need to fly UAS in the NAS to perform missions of vital importance to National Security and Defense, Emergency Management, and Science. There is also an emerging need to enable commercial applications such as cargo transport (e.g. FedEx). Unencumbered NAS Access for Civil/Commercial UAS. Provide research findings, utilizing simulation and flight tests, to support the development and validation of DAA and C2 technologies necessary for integrating Unmanned Aircraft Systems into the National Airspace System.

  9. Electrochemical layer-by-layer approach to fabricate mechanically stable platinum black microelectrodes using a mussel-inspired polydopamine adhesive.

    PubMed

    Kim, Raeyoung; Nam, Yoonkey

    2015-04-01

    Platinum black (PtBK) has long been used for microelectrode fabrication owing to its high recording performance of neural signals. The porous structure of PtBK enlarges the surface area and lowers the impedance, which results in background noise reduction. However, the brittleness of PtBK has been a problem in practice. In this work, we report mechanically stable PtBK microelectrodes using a bioinspired adhesive film, polydopamine (pDA), while maintaining the low impedance of PtBK. The pDA layer was incorporated into the PtBK structure through electrochemical layer-by-layer deposition. Varying the number of layers and the order of materials, multi-layered pDA-PtBK hybrids were fabricated and the electrical properties, both impedance and charge injection limit, were evaluated. Multilayered pDA-PtBK hybrids had electrical impedances as low as PtBK controls and charge injection limit twice larger than controls. For the 30 min-ultrasonication agitation test, impedance levels rarely changed for some of the pDA-PtBK hybrids indicating that the pDA improved the mechanical property of the PtBK structures. The pDA-PtBK hybrid microelectrodes readily recorded neural signals of cultured hippocampal neurons, where background noise levels and signal-to-noise were 2.43 ∼ 3.23 μVrms and 28.4 ∼ 69.1, respectively. The developed pDA-PtBK hybrid microelectrodes are expected to be applicable to neural sensors for neural prosthetic studies.

  10. Electrochemical layer-by-layer approach to fabricate mechanically stable platinum black microelectrodes using a mussel-inspired polydopamine adhesive

    NASA Astrophysics Data System (ADS)

    Kim, Raeyoung; Nam, Yoonkey

    2015-04-01

    Objective. Platinum black (PtBK) has long been used for microelectrode fabrication owing to its high recording performance of neural signals. The porous structure of PtBK enlarges the surface area and lowers the impedance, which results in background noise reduction. However, the brittleness of PtBK has been a problem in practice. In this work, we report mechanically stable PtBK microelectrodes using a bioinspired adhesive film, polydopamine (pDA), while maintaining the low impedance of PtBK. Approach. The pDA layer was incorporated into the PtBK structure through electrochemical layer-by-layer deposition. Varying the number of layers and the order of materials, multi-layered pDA-PtBK hybrids were fabricated and the electrical properties, both impedance and charge injection limit, were evaluated. Main results. Multilayered pDA-PtBK hybrids had electrical impedances as low as PtBK controls and charge injection limit twice larger than controls. For the 30 min-ultrasonication agitation test, impedance levels rarely changed for some of the pDA-PtBK hybrids indicating that the pDA improved the mechanical property of the PtBK structures. The pDA-PtBK hybrid microelectrodes readily recorded neural signals of cultured hippocampal neurons, where background noise levels and signal-to-noise were 2.43 ∼ 3.23 μVrms and 28.4 ∼ 69.1, respectively. Significance. The developed pDA-PtBK hybrid microelectrodes are expected to be applicable to neural sensors for neural prosthetic studies.

  11. Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function.

    PubMed

    Korth, Johannes; Widera, Marek; Dolff, Sebastian; Guberina, Hana; Bienholz, Anja; Brinkhoff, Alexandra; Anastasiou, Olympia Evdoxia; Kribben, Andreas; Dittmer, Ulf; Verheyen, Jens; Wilde, Benjamin; Witzke, Oliver

    2018-02-01

    BK polyomavirus (BKPyV)-associated nephropathy (PyVAN) is a significant cause of premature renal transplant failure. High-level BKPyV viremia is predictive for PyVAN; however, low-level BKPyV viremia does not necessarily exclude the presence of PyVAN. As data are limited regarding whether or not low-level BKPyV viremia has an effect on intermediate-term graft outcome, this study analyzes the impact of low-level BKPyV viremia on intermediate-term graft function and outcome compared with high-level viremia and non-viremic patients. All renal transplant patients received follow-up examinations at the Department of Nephrology, University Hospital Essen. Patients were screened for BKPyV viremia and stratified into three groups according to their maximum BKPyV load in serum (low-level viremia, high-level viremia, and no viremia). In 142 of 213 (67%) patients, BKPyV was never detected in serum; 42 of 213 (20%) patients were found positive for low-level viremia (≤10 4 copies/mL); and 29 of 213 (13%) patients showed high-level viremia (>10 4 copies/mL). No significant differences regarding transplant function and graft failure were observed between patients without BKPyV viremia (delta estimated glomerular filtration rate [eGFR] +0.1 mL/min [month 1 vs last visit at month 44]) and patients with low-level BKPyV viremia (delta eGFR -1.7 mL/min). In patients with high-level viremia, transplant function was significantly restricted (delta eGFR -6.5 mL/min) compared with low-level viremia until the last visit at 44 ± 9.7 months after transplantation. Although the graft function and graft loss were worse in the high-level viremia group compared with no viremia (eGFR 37 vs 45 mL/min), the difference was not significant. High-level viremia was associated with impaired graft function. In contrast, low-level BKPyV viremia had no significant impact on intermediate-term graft function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Differences in iris thickness among African Americans, Caucasian Americans, Hispanic Americans, Chinese Americans, and Filipino-Americans.

    PubMed

    Lee, Roland Y; Huang, Guofu; Porco, Travis C; Chen, Yi-Chun; He, Mingguang; Lin, Shan C

    2013-12-01

    To evaluate the capability of iris thickness parameters to explain the difference in primary angle-closure glaucoma prevalence among the different racial groups. In this prospective study, 436 patients with open and narrow angles that met inclusion criteria were consecutively recruited from the UCSF general ophthalmology and glaucoma clinics to receive anterior segment optical coherence tomography imaging under standardized dark conditions. Images from 11 patients were removed due to poor visibility of the scleral spurs and the remaining images were analyzed using the Zhongshan Angle Assessment Program to assess the following measurements for the nasal and temporal angle of the anterior chamber: iris thickness at 750 and 2000 μm from the scleral spurs and the maximum iris thickness at middle one third of the iris. Iris thickness parameters were compared among and within the following 5 different racial groups: African Americans, Caucasian Americans, Hispanic Americans, Chinese Americans, and Filipino-Americans. In comparing iris parameters among the open-angle racial groups, significant differences were found for nasal iris thickness at 750 and 2000 μm from the scleral spurs in which Chinese Americans displayed the highest mean value (P=0.01, P<0.0001). Among the narrow-angle racial groups, significant difference was found for nasal iris thickness at 2000 μm from the scleral in which Chinese Americans showed the highest mean value (P<0.0001). Significant difference was also found for temporal maximum iris thickness at middle one third of the iris in which African Americans exhibited the highest mean value (P=0.021). Iris thickness was modeled as a function of angle status using linear mixed-effects regression, adjusting for age, sex, pupil diameter, spherical equivalent, ethnicity, and the use of both eyes in patients. The iris thickness difference between the narrow-angle and open-angle groups was significant (P=0.0007). Racial groups that historically showed

  13. 77 FR 44116 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-27

    ... Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA... Eurocopter Deutschland GmbH (ECD) MBB-BK 117 A-3, MBB-BK 117 A-4, MBB- BK B-1, MBB-BK 117 B-2, and MBB-BK C-1... directive (AD): 2012-14-14 Eurocopter Deutschland GmbH Helicopters: Amendment 39- 17128; Docket No. FAA-2012...

  14. NAS (Numerical Aerodynamic Simulation Program) technical summaries, March 1989 - February 1990

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Given here are selected scientific results from the Numerical Aerodynamic Simulation (NAS) Program's third year of operation. During this year, the scientific community was given access to a Cray-2 and a Cray Y-MP supercomputer. Topics covered include flow field analysis of fighter wing configurations, large-scale ocean modeling, the Space Shuttle flow field, advanced computational fluid dynamics (CFD) codes for rotary-wing airloads and performance prediction, turbulence modeling of separated flows, airloads and acoustics of rotorcraft, vortex-induced nonlinearities on submarines, and standing oblique detonation waves.

  15. JC polyoma viruria associates with protection from chronic kidney disease independently from apolipoprotein L1 genotype in African Americans.

    PubMed

    Freedman, Barry I; Kistler, Amy L; Skewes-Cox, Peter; Ganem, Don; Spainhour, Mitzie; Turner, Jolyn; Divers, Jasmin; Langefeld, Carl D; Murea, Mariana; Hicks, Pamela J; Hemal, Ashok K; Snipes, James A; Zhao, Lihong; Abend, Johanna R; Lyles, Douglas S; Ma, Lijun; Skorecki, Karl L

    2018-02-06

    Viral infections can trigger chronic kidney disease (CKD) and the urine virome may inform risk. The Natural History of APOL1-Associated Nephropathy Study (NHAANS) reported that urine JC polyomavirus (JCPyV) associated with a lower risk of APOL1-associated nephropathy in African Americans. Herein, association was assessed between urine JCPyV with CKD in African Americans independent from the APOL1 genotype. Quantitative polymerase chain reaction was performed for urinary detection of JCPyV and BK polyoma virus (BKPyV) in 200 newly recruited nondiabetic African Americans. A combined analysis was performed in these individuals plus 300 NHAANS participants. In the 200 new participants, urine JCPyV was present in 8.8% of CKD cases and 45.8% of nonnephropathy controls (P = 3.0 × 10-8). In those with APOL1 renal-risk genotypes, JCPyV was detected in 5.1% of cases and 40.0% of controls (P = 0.0002). In those lacking APOL1 renal-risk genotypes, JCPyV was detected in 12.2% of cases and 48.8% of controls (P = 8.5 × 10-5). BKPyV was detected in 1.3% of cases and 0.8% of controls (P  =  0.77). In a combined analysis with 300 NHAANS participants (n = 500), individuals with urine JCPyV had a 63% lower risk of CKD compared with those without urine JCPyV (odds ratio 0.37; P = 4.6 × 10-6). RNA fluorescence in situ hybridization confirmed the presence of JCPyV genomic DNA and JCPyV messenger RNA (mRNA) in nondiseased kidney. Inverse relationships exist between JCPyV viruria and non-diabetic CKD. Future studies should determine whether renal inflammation associated with CKD is less permissive for JCPyV reactivation/replication or whether JCPyV is a marker of reduced host immune responsiveness that diminishes immune pathologic contributions to CKD. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project

    NASA Technical Reports Server (NTRS)

    Fern, Lisa

    2017-01-01

    This presentation summarizes the simulation work conducted by the Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project. It focuses on the contribution of that research to the development of RTCA Special Committee 228's (SC-228) Minimum Operational Performance Standards (MOPS) for UAS. The research objectives and primary findings from four different human-in-the-loop simulations are discussed, along with the specific requirements these studies led to in the final MOPS document.

  17. [Inventive activity of the Department of Metabolism Regulation of the Palladin Institute of Biochemistry of NAS of Ukraine].

    PubMed

    Danilova, V M; Vynogradova, R P; Chernysh, I G; Petrenko, T M

    2016-01-01

    The article is devoted to the inventive activity of the Department of Metabolism Regulation of the Palladin Institute of Biochemistry of NAS of Ukraine in the context of the history of its inception, development and the research activities of its founder, academician of NAS of Ukraine M. F. Guly as well as his students and followers. It briefly tells about practical achievements of M. F. Guly which were as significant, immense and diverse as his scientific accomplishments. The paper analyses in detail the practical results of scientific research of his students and followers aimed to solve practical problems of medicine, food-processing, agriculture, and which are essentially a continuation of the ideas and projects of M. F. Guly.

  18. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project FY16 Annual Review

    NASA Technical Reports Server (NTRS)

    Grindle, Laurie; Hackenberg, Davis

    2016-01-01

    This presentation gives insight into the research activities and efforts being executed in order to integrate unmanned aircraft systems into the national airspace system. This briefing is to inform others of the UAS-NAS FY16 progress and future directions.

  19. The Peoples Multicultural Almanac: America from the 1400s to Present. 365 Days of Contributions by African Americans, Asian Americans, Hispanic Americans, Native Americans, European Americans.

    ERIC Educational Resources Information Center

    Taylor, Earl J., Jr.; And Others

    The Peoples Multicultural Almanac provides five entries for each day in the school year, September through May, organized for the following ethnic groups: (1) African Americans; (2) Asian Americans; (3) European Americans; (4) Hispanic Americans; and (5) Native Americans. The entries highlight significant social, political, historical, cultural,…

  20. Amorphous MoS3 as the sulfur-equivalent cathode material for room-temperature Li-S and Na-S batteries.

    PubMed

    Ye, Hualin; Ma, Lu; Zhou, Yu; Wang, Lu; Han, Na; Zhao, Feipeng; Deng, Jun; Wu, Tianpin; Li, Yanguang; Lu, Jun

    2017-12-12

    Many problems associated with Li-S and Na-S batteries essentially root in the generation of their soluble polysulfide intermediates. While conventional wisdom mainly focuses on trapping polysulfides at the cathode using various functional materials, few strategies are available at present to fully resolve or circumvent this long-standing issue. In this study, we propose the concept of sulfur-equivalent cathode materials, and demonstrate the great potential of amorphous MoS 3 as such a material for room-temperature Li-S and Na-S batteries. In Li-S batteries, MoS 3 exhibits sulfur-like behavior with large reversible specific capacity, excellent cycle life, and the possibility to achieve high areal capacity. Most remarkably, it is also fully cyclable in the carbonate electrolyte under a relatively high temperature of 55 °C. MoS 3 can also be used as the cathode material of even more challenging Na-S batteries to enable decent capacity and good cycle life. Operando X-ray absorption spectroscopy (XAS) experiments are carried out to track the structural evolution of MoS 3 It largely preserves its chain-like structure during repetitive battery cycling without generating any free polysulfide intermediates.

  1. Identification of nitrogen- and host-related deep-level traps in n-type GaNAs and their evolution upon annealing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gelczuk, Ł., E-mail: lukasz.gelczuk@pwr.edu.pl; Kudrawiec, R., E-mail: robert.kudrawiec@pwr.edu.pl; Henini, M.

    2014-07-07

    Deep level traps in as-grown and annealed n-GaNAs layers (doped with Si) of various nitrogen concentrations (N=0.2%, 0.4%, 0.8%, and 1.2%) were investigated by deep level transient spectroscopy. In addition, optical properties of GaNAs layers were studied by photoluminescence and contactless electroreflectance. The identification of N- and host-related traps has been performed on the basis of band gap diagram [Kudrawiec, Appl. Phys. Lett. 101, 082109 (2012)], which assumes that the activation energy of electron traps of the same microscopic nature decreases with the rise of nitrogen concentration in accordance with the N-related shift of the conduction band towards trap levels.more » The application of this diagram has allowed to investigate the evolution of donor traps in GaNAs upon annealing. In general, it was observed that the concentration of N- and host-related traps decreases after annealing and PL improves very significantly. However, it was also observed that some traps are generated due to annealing. It explains why the annealing conditions have to be carefully optimized for this material system.« less

  2. Functional characterization of BK virus-specific CD4+ T cells with cytotoxic potential in seropositive adults.

    PubMed

    Zhou, Wendi; Sharma, Madeva; Martinez, Joy; Srivastava, Tumul; Diamond, Don J; Knowles, Wendy; Lacey, Simon F

    2007-09-01

    BK polyomavirus (BKV) reactivation is associated with a failure of T cell immunity in kidney transplant patients, and may lead to BKV-associated nephropathy (BKVN) and loss of the allograft. BKV reactivation in hematopoietic stem cell transplant recipients is associated with hemorrhagic cystitis. We have investigated T cell responses to overlapping peptide mixtures corresponding to the whole BKV major T antigen (TAg) and major capsid protein (VP1) in peripheral blood mononuclear cell samples from a cohort of healthy BKV-seropositive subjects. The majority of these individuals possessed populations of both CD8(+) and CD4(+) T cells specific for these BKV antigens. After expansion in culture, the majority of the BKV-specific CD4(+) T cells, in addition to expressing CD40L (CD154), secreted both interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, contained both granzyme A and granzyme B, and degranulated/mobilized CD107 in response to antigen-specific stimulation. These T cells thus represent potentially functional BKV-specific cytotoxic CD4(+) T lymphocytes. Secretion of both TNF-alpha and IFN-gamma by CD154(+)CD4(+) T cells on BKV-specific stimulation was associated with higher levels of granzyme B and a higher proportion of degranulating cells compared with CD154(+)CD4(+) T cells producing only IFN-gamma or neither cytokine. These healthy subjects also harbored populations of functional CD8(+) T cells specific for one or more of three newly defined HLA-A 02-restricted cytotoxic T lymphocyte epitopes within the BKV TAg as well as two HLA-A 02-restricted epitopes within the BKV VP1 we have previously described. The BKV-specific CD4(+) T cells characterized in this study may play a part in maintaining persistent memory T cell responses to the virus and thus contribute to the immune control of BKV in healthy individuals.

  3. Help-Seeking Experiences and Attitudes among African American, Asian American, and European American College Students

    ERIC Educational Resources Information Center

    Masuda, Akihiko; Anderson, Page L.; Twohig, Michael P.; Feinstein, Amanda B.; Chou, Ying-Yi; Wendell, Johanna W.; Stormo, Analia R.

    2009-01-01

    The study examined African American, Asian American, and European American college students' previous direct and indirect experiences of seeking professional psychological services and related attitudes. Survey data were collected from 254 European American, 182 African American and 82 Asian American college students. Results revealed that fewer…

  4. Effects of growth rate on structural property and adatom migration behaviors for growth of GaInNAs/GaAs (001) by molecular beam epitaxy

    NASA Astrophysics Data System (ADS)

    Li, Jingling; Gao, Peng; Zhang, Shuguang; Wen, Lei; Gao, Fangliang; Li, Guoqiang

    2018-03-01

    We have investigated the structural properties and the growth mode of GaInNAs films prepared at different growth rates (Rg) by molecular beam epitaxy. The crystalline structure is studied by high resolution X-ray diffraction, and the evolution of GaInNAs film surface morphologies is studied by atomic force microscopy. It is found that both the crystallinity and the surface roughness are improved by increasing Rg, and the change in the growth mode is attributed to the adatom migration behaviors particularly for In atoms, which is verified by elemental analysis. In addition, we have presented some theoretical calculation results related to the N adsorption energy to show the unique N migration behavior, which is instructive to interpret the growth mechanism of GaInNAs films.

  5. Asian Americans: Chinese-Americans, Japanese-Americans, Korean-Americans. Staff Development Module.

    ERIC Educational Resources Information Center

    Panter, Keiko; And Others

    This staff development module is designed to: (1) introduce significant facts basic to understanding the cultural and historical heritage of three Asian-American cultures; (2) develop an accurate knowledge and awareness of the experiences of Asian-Americans; and (3) relate the geography and past history of China, Korea, and Japan to the United…

  6. BK virus-specific T cells for use in cellular therapy show specificity to multiple antigens and polyfunctional cytokine responses.

    PubMed

    Blyth, Emily; Clancy, Leighton; Simms, Renee; Gaundar, Shivashni; O'Connell, Philip; Micklethwaite, Kenneth; Gottlieb, David J

    2011-11-27

    BK virus (BKV) infection causes hemorrhagic cystitis posthemopoietic stem-cell transplant and graft loss in renal transplant recipients. Reactivation occurs in up to 60% of patients in both groups. Treatment-related cellular immunosuppression is a major contributor to the development of BKV-related disease, but the targets of the immune response are not well characterized. Immunotherapy by adoptive transfer of cellular effectors has been shown to be effective in controlling and preventing some virus-related diseases in transplant recipients, particularly Epstein-Barr virus and cytomegalovirus. Infusion of BKV-specific T cells may potentially reconstitute functional BKV immunity and reduce clinical complications of BKV infection. BKV-specific T cells for clinical use in adoptive immunotherapy were generated using monocyte-derived dendritic cells pulsed with overlapping peptide mixes spanning the five BKV proteins VP1, VP2, VP3, large T antigen, and small T antigen. Phenotypic and functional characteristics of the cells were investigated as well as their antigen specificity. Expanded CD4(+) and CD8(+) cells responded to restimulation with BKV peptides principally from VP1, large T, or small T antigens; produced multiple cytokines; and showed cytotoxic activity against antigen-coated targets. Possible clinical uses for BKV-specific T cells generated using this method include immune reconstitution posthemopoietic stem-cell transplantation or prophylaxis and treatment of immune deficiency in renal transplant recipients, fulfilling the need for effective therapy for BKV-related hemorrhagic cystitis and renal dysfunction.

  7. Potentiation of kinin analogues by ramiprilat is exclusively related to their degradation.

    PubMed

    Dendorfer, A; Reibetamann, S; Wolfrum, S; Raasch, W; Dominiak, P

    2001-07-01

    The potentiation of kinin actions represents a cardioprotective property of ACE inhibitors. Although a clear contribution to this effect is related to the inhibition of bradykinin (BK) breakdown, the high efficacy of potentiation and the ability of ACE inhibitors to provoke a B(2)-receptor-mediated response even after receptor desensitization has also triggered hypotheses concerning additional mechanisms of kinin potentiation. The application of kinin analogues with enhanced metabolic stability for the demonstration of degradation-independent mechanisms of potentiation, however, has yielded inconsistent results. Therefore, the relation between the susceptibility of B(2)-agonists to ACE and the potentiation of their actions by ACE inhibitors was investigated with the use of minimally modified kinin derivatives that varied in their degree of ACE resistance. The B(2)-agonists BK, D-Arg-[Hyp(3)]-BK, [Hyp,(3) Tyr(Me)(8)]-BK, [DeltaPhe(5)]-BK, [D-NMF(7)]-BK, and [Phe(8)psi(CH(2)-NH)Arg(9)]-BK were tested for degradation by purified rabbit ACE and for their potency in contracting the endothelium-denuded rabbit jugular vein in the absence and presence of ramiprilat. Purified ACE degraded D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK at 81% and 71% of BK degradation activity, respectively, whereas other peptides were highly ([DeltaPhe(5)]-BK) or completely ([D-NMF(7)]-BK, [Phe(8)psi(CH(2)-NH)Arg(9)]-BK) resistant. The EC(50) of BK-induced venoconstriction (1.15+/-0.2 nmol/L) was reduced by a factor of 5.7 in the presence of ramiprilat. Likewise, D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK were both significantly potentiated by a factor of 4.4, whereas the activities of the other agonists were not affected. Ramiprilat exerted no influence on the maximum contraction induced by any of the agonists. It is concluded that the potentiation of kinin analogues during ACE inhibition correlates quantitatively with the susceptibility of each substance to degradation by ACE. As such

  8. A Framework for Safe Integration of Small UAS Into the NAS

    NASA Technical Reports Server (NTRS)

    Logan, Michael J.; Bland, Geoffrey; Murray, Jennifer

    2011-01-01

    This paper discusses a proposed framework for the safe integration of small unmanned aerial systems (sUAS) into the National Airspace System (NAS). The paper examines the potential uses of sUAS to build an understanding of the location and frequency of potential future flight operations based on the future applications of the sUAS systems. The paper then examines the types of systems that would be required to meet the application-level demand to determine classes of platforms and operations. Finally, a framework is proposed for both airworthiness and operations that attempts to balance safety with utility for these important systems.

  9. Ethnic differences in inter- and intra-situational blood pressure variation: Comparisons among African-American, Hispanic-American, Asian-American, and European-American women.

    PubMed

    James, Gary D; Bovbjerg, Dana H; Hill, Leah A

    2016-11-01

    The purpose of this study was to compare the daily inter- and intra-situational ambulatory blood pressure (BP) variation by ethnicity in women. The African-American (N = 82; Age = 39.7 + 8.9), Hispanic-American (N = 25; age = 37.5 + 9.4), Asian-American (N = 22; Age = 35.2 + 8.6), and European-American (N = 122; Age = 37.2+ 9.4) women in this study all worked in similar positions at two major medical centers in NYC. Each wore an ambulatory monitor during the course of one mid-week workday. Proportional BP changes from work or home to sleep, intra-situational BP variation (standard deviation [SD]) and mean situational BP levels were compared among the groups using ANOVA models. African-American and Asian-American women had significantly smaller proportional work-sleep systolic changes than either European- (P < 0.05) or Hispanic-American (P < 0.05) women, but the Asian-American women's changes tended to be smallest. The variability (SD) of diastolic BP at work was significantly greater among African- and Hispanic-American women compared to Asian- and European-American women (all P < 0.05). African-American women had greater sleep variability than European-American women (P < 0.05). Asian-American women had the highest level of sleep diastolic pressure (all comparisons P < 0.05). African-American and Asian-American women have an attenuated proportional BP decline from waking environments to sleep compared to European-American and Hispanic-American women. Asian-American nocturnal BP may be elevated relative to all other groups. Am. J. Hum. Biol. 28:932-935, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Contractile effects of bradykinin on the isolated human small bronchus.

    PubMed

    Molimard, M; Martin, C A; Naline, E; Hirsch, A; Advenier, C

    1994-01-01

    Bradykinin (Bk) induced a contraction in all small bronchi samples (diameter, 0.5 to 1 mm) from 20 patients. pD2 was 7.7 +/- 0.1 (pD2 = -log EC50) and maximal effect (Emax) was 36.2 +/- 4.7% of the maximal response to acetylcholine. The B2 agonist [Hyp3TyrMe8]Bk contracted airway smooth muscle with a pD2 of 7.8 +/- 0.2 and an Emax of 39 +/- 9%. The B1 agonist [Sar1dPhe8desArg9]Bk induced only a weak contraction at 10(-6) M. The effect of Bk was abolished by the B2 (Hoe 140) but not by the B1 [Leu8desArg9]Bk receptor antagonist. Indomethacin 10(-6) M abolished Bk-induced contraction, suggesting that cyclooxygenase products are involved in Bk action. Capsaicin 10(-5) M, which selectively depletes C fibers from airway mediators through the ruthenium red pathway, and ruthenium red 10(-5) M significantly inhibited the concentration-response curves to Bk. However, tetrodotoxin (+/-)-CP-96,345, SR 48968, and atropine did not significantly affect Bk concentration-response curves, suggesting that nerve conduction, substance P (SP), neurokinin A (NKA), and acetylcholine release are not involved in Bk action. Our data indicate that Bk contracts human distal airway smooth muscle through the Bk B2 receptor and a cyclooxygenase pathway. This effect appears to involve capsaicin and ruthenium red pathways but neither acetylcholine nor NKA and SP release.

  11. UAS Integration Into the NAS: An Examination of Baseline Compliance in the Current Airspace System

    NASA Technical Reports Server (NTRS)

    Fern, Lisa; Kenny, Caitlin A.; Shively, Robert J.; Johnson, Walter

    2012-01-01

    As a result of the FAA Modernization and Reform Act of 2012, Unmanned Aerial Systems (UAS) are expected to be integrated into the National Airspace System (NAS) by 2015. Several human factors challenges need to be addressed before UAS can safely and routinely fly in the NAS with manned aircraft. Perhaps the most significant challenge is for the UAS to be non-disruptive to the air traffic management system. Another human factors challenge is how to provide UAS pilots with intuitive traffic information in order to support situation awareness (SA) of their airspace environment as well as a see-and-avoid capability comparable to manned aircraft so that a UAS pilot could safely maneuver the aircraft to maintain separation and collision avoidance if necessary. A simulation experiment was conducted to examine baseline compliance of UAS operations in the current airspace system. Researchers also examined the effects of introducing a Cockpit Situation Display (CSD) into a UAS Ground Control Station (GCS) on UAS pilot performance, workload and situation awareness while flying in a positively controlled sector. Pilots were tasked with conducting a highway patrol police mission with a Medium Altitude Long Endurance (MALE) UAS in L.A. Center airspace with two mission objectives: 1) to reroute the UAS when issued new instructions from their commander, and 2) to communicate with Air Traffic Control (ATC) to negotiate flight plan changes and respond to vectoring and altitude change instructions. Objective aircraft separation data, workload ratings, SA data, and subjective ratings regarding UAS operations in the NAS were collected. Results indicate that UAS pilots were able to comply appropriately with ATC instructions. In addition, the introduction of the CSD improved pilot SA and reduced workload associated with UAS and ATC interactions.

  12. Angioedema attacks in patients with hereditary angioedema: Local manifestations of a systemic activation process.

    PubMed

    Hofman, Zonne L M; Relan, Anurag; Zeerleder, Sacha; Drouet, Christian; Zuraw, Bruce; Hack, C Erik

    2016-08-01

    Hereditary angioedema (HAE) caused by a deficiency of functional C1-inhibitor (C1INH) becomes clinically manifest as attacks of angioedema. C1INH is the main inhibitor of the contact system. Poor control of a local activation process of this system at the site of the attack is believed to lead to the formation of bradykinin (BK), which increases local vasopermeability and mediates angioedema on interaction with BK receptor 2 on the endothelium. However, several observations in patients with HAE are difficult to explain from a pathogenic model claiming a local activation process at the site of the angioedema attack. Therefore we postulate an alternative model for angioedema attacks in patients with HAE, which assumes a systemic, fluid-phase activation of the contact system to generate BK and its breakdown products. Interaction of these peptides with endothelial receptors that are locally expressed in the affected tissues rather than with receptors constitutively expressed by the endothelium throughout the whole body explains that such a systemic activation process results in local manifestations of an attack. In particular, BK receptor 1, which is induced on the endothelium by inflammatory stimuli, such as kinins and cytokines, meets the specifications of the involved receptor. The pathogenic model discussed here also provides an explanation for why angioedema can occur at multiple sites during an attack and why HAE attacks respond well to modest increases of circulating C1INH activity levels because inhibition of fluid-phase Factor XIIa and kallikrein requires lower C1INH levels than inhibition of activator-bound factors. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. Differences in obsessive-compulsive symptoms and obsessive beliefs: a comparison between African Americans, Asian Americans, Latino Americans, and European Americans.

    PubMed

    Wheaton, Michael G; Berman, Noah C; Fabricant, Laura E; Abramowitz, Jonathan S

    2013-01-01

    Clinical research has increasingly considered ethnic group differences in the expression of anxiety disorders, but to date few investigations have focused specifically on the symptoms of obsessive-compulsive disorder (OCD). We examined group differences in OC symptoms, related cognitions ("obsessive beliefs"), and their associations. The sample included European American (N = 1199), African American (N = 215), Asian American (N = 116), and Latino American (N = 72) participants. African American and Asian American participants reported more contamination-related OC symptoms than did European Americans. Asian Americans also reported elevated levels of obsessive beliefs. Moreover, group membership moderated the relationship between obsessive beliefs and certain dimensions of OC symptoms. These findings suggest group differences in the experience of OC symptoms and related cognitions, and that the cognitive-behavioral model of some OC symptoms could be refined and tailored for groups underrepresented in OCD research to date.

  14. Redshift and blueshift of GaNAs/GaAs multiple quantum wells induced by rapid thermal annealing

    NASA Astrophysics Data System (ADS)

    Sun, Yijun; Cheng, Zhiyuan; Zhou, Qiang; Sun, Ying; Sun, Jiabao; Liu, Yanhua; Wang, Meifang; Cao, Zhen; Ye, Zhi; Xu, Mingsheng; Ding, Yong; Chen, Peng; Heuken, Michael; Egawa, Takashi

    2018-02-01

    The effects of rapid thermal annealing (RTA) on the optical properties of GaNAs/GaAs multiple quantum wells (MQWs) grown by chemical beam epitaxy (CBE) are studied by photoluminescence (PL) at 77 K. The results show that the optical quality of the MQWs improves significantly after RTA. With increasing RTA temperature, PL peak energy of the MQWs redshifts below 1023 K, while it blueshifts above 1023 K. Two competitive processes which occur simultaneously during RTA result in redshift at low temperature and blueshift at high temperature. It is also found that PL peak energy shift can be explained neither by nitrogen diffusion out of quantum wells nor by nitrogen reorganization inside quantum wells. PL peak energy shift can be quantitatively explained by a modified recombination coupling model in which redshift nonradiative recombination and blueshift nonradiative recombination coexist. The results obtained have significant implication on the growth and RTA of GaNAs material for high performance optoelectronic device application.

  15. Culture and Personality Among European American and Asian American Men

    PubMed Central

    Eap, Sopagna; DeGarmo, David S.; Kawakami, Ayaka; Hara, Shelley N.; Hall, Gordon C.N.; Teten, Andra L.

    2009-01-01

    Personality differences between Asian American (N = 320) and European American men (N = 242) and also among Asian American ethnic groups (Korean, Chinese, Japanese, Filipino, and mixed Asian) are examined on the Big Five personality dimension. Personality structures for Asian Americans and European Americans closely replicate established norms. However, congruence is greater for European American and highly acculturated Asian American men than for low acculturated Asian American men. Similar patterns are found for the construct loss of face (LOF). Asian American men with a high concern for LOF are less similar in their personality structure to European American men than Asian American men with low LOF concern. Mean differences are also found among Asian American and European American men, who differ significantly on Extraversion, Conscientiousness, Openness, and Neuroticism. Results indicate that acculturation and LOF are significantly associated with these four personality dimensions for both Asian American and European American men. PMID:19169434

  16. NAS Demand Predictions, Transportation Systems Analysis Model (TSAM) Compared with Other Forecasts

    NASA Technical Reports Server (NTRS)

    Viken, Jeff; Dollyhigh, Samuel; Smith, Jeremy; Trani, Antonio; Baik, Hojong; Hinze, Nicholas; Ashiabor, Senanu

    2006-01-01

    The current work incorporates the Transportation Systems Analysis Model (TSAM) to predict the future demand for airline travel. TSAM is a multi-mode, national model that predicts the demand for all long distance travel at a county level based upon population and demographics. The model conducts a mode choice analysis to compute the demand for commercial airline travel based upon the traveler s purpose of the trip, value of time, cost and time of the trip,. The county demand for airline travel is then aggregated (or distributed) to the airport level, and the enplanement demand at commercial airports is modeled. With the growth in flight demand, and utilizing current airline flight schedules, the Fratar algorithm is used to develop future flight schedules in the NAS. The projected flights can then be flown through air transportation simulators to quantify the ability of the NAS to meet future demand. A major strength of the TSAM analysis is that scenario planning can be conducted to quantify capacity requirements at individual airports, based upon different future scenarios. Different demographic scenarios can be analyzed to model the demand sensitivity to them. Also, it is fairly well know, but not well modeled at the airport level, that the demand for travel is highly dependent on the cost of travel, or the fare yield of the airline industry. The FAA projects the fare yield (in constant year dollars) to keep decreasing into the future. The magnitude and/or direction of these projections can be suspect in light of the general lack of airline profits and the large rises in airline fuel cost. Also, changes in travel time and convenience have an influence on the demand for air travel, especially for business travel. Future planners cannot easily conduct sensitivity studies of future demand with the FAA TAF data, nor with the Boeing or Airbus projections. In TSAM many factors can be parameterized and various demand sensitivities can be predicted for future travel. These

  17. Characterization of kinin receptors by bioassays.

    PubMed

    Gobeil, F; Regoli, D

    1994-08-01

    1. Using the classical pharmacological criteria recommended by Schild, namely the order of potency of selective agonists (e.g., bradykinin, desArg9-bradykinin, [Hyp3]BK and [Aib7]BK) and the apparent affinity of competitive antagonists (e.g., DArg[Hyp3,DPhe7,Leu8]BK and WIN 64338), we have attempted to characterize B2 receptor subtypes. It has been shown that vascular tissues (e.g., dog carotid and renal arteries, rabbit jugular vein and rabbit aorta) are very sensitive to kinin agonists and antagonists (pD2 and pA2 values for BK and HOE 140 on B2 receptors are 8.5-10.1 and 9.2-9.4, respectively, and for desArg9BK and desArg9[Leu8]BK on B1 receptors they are 7.3-8.6 and 7.3-7.8, respectively). Mechanisms of action of kinins differ between pharmacological preparations. Kinin may act directly on the smooth muscle (e.g., rabbit jugular vein and rabbit aorta) as well as indirectly through other endogenous mediators such as nitric oxide (EDRF) (e.g., dog carotid and renal arteries) and prostaglandins (e.g., dog renal artery). 2. Pharmacological analysis of rabbit jugular vein (RJV) and guinea pig ileum (GPI) has revealed different sensitivities to certain synthetic analogs of BK and to competitive B2 receptor antagonists between the two tissues. 3. Agonist order of potency ([Hyp3]BK > BK > [Aib7]BK) obtained for RJV differed from that obtained for GPI (BK > or = [Aib7]BK > [Hyp3]BK). Competitive antagonists such as DArg[Hyp3, DPhe7, Leu8]BK and WIN 64338 discriminate in favor of B2A (RJV) and B2B (GPI) receptor subtypes, respectively. These data demonstrate the existence of B2 receptor subtypes. Correlation between data obtained in the present study and those reported for binding to the human B2 receptor support the view that the human receptor is similar to that of the rabbit.

  18. Enhancement of photocurrent in epitaxial lift-off thin-film GaInNAsSb solar cells due to light-confinement structure

    NASA Astrophysics Data System (ADS)

    Miyashita, Naoya; Behaghel, Benoît; Guillemoles, Jean-François; Okada, Yoshitaka

    2018-07-01

    This work focuses on the characterization of GaInNAsSb solar cells whose substrates are removed via the epitaxial lift-off (ELO) technique. As a result of the substrate removal, increases in the photocurrent and the interference feature were clearly observed. This is clear evidence of the light-confinement effect, whereby some of the unabsorbed photons at the rear metal contact were reflected back towards the front side of the ELO thin-film cell. We successfully demonstrated that the ELO technique can be applied for the GaInNAsSb cell, and the light management should add flexibility in designing the cell structures.

  19. Bradykinin regulates human colonic ion transport in vitro

    PubMed Central

    Baird, A W; Skelly, M M; O'Donoghue, D P; Barrett, K E; Keely, S J

    2008-01-01

    Background and purpose: Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle-stripped human colonic tissue and cultured T84-cell monolayers to study bradykinin (BK) actions on human intestinal ion transport. Experimental approach: Ion transport was measured as changes in short-circuit current (Isc) across colonic epithelia mounted in Ussing chambers. Key results: In intact tissue, there was a distinct polarity to BK-elicited Isc responses. Whereas basolateral BK stimulated sustained responses (EC50=0.5±0.1 μM), those to apical BK were more rapid and transient (EC50=4.1±1.2 nM). In T84 cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross-desensitization between apical and basolateral domains was not observed. BK-induced responses were largely due to Cl− secretion as shown by their sensitivity to bumetanide and removal of Cl− from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B2 receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 μM), atropine (1 μM), capsaicin (100 μM) and piroxicam (10 μM). BK-stimulated prostaglandin (PG)E2 release from colonic tissue. Conclusions: BK stimulates human colonic Cl− secretion by activation of apical and basolateral B2 receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis. PMID:18604228

  20. Bradykinin regulates osteoblast differentiation by Akt/ERK/NFκB signaling axis.

    PubMed

    Srivastava, Swati; Sharma, Kirti; Kumar, Narender; Roy, Partha

    2014-12-01

    Bradykinin (BK), a well known mediator of pain and inflammation, is also known to be involved in the process of bone resorption. The present study therefore evaluated the role of BK in osteoblast lineage commitment. Our data showed that BK inhibits the migration of bone marrow mesenchymal stem cells, but does not affect their viability. Moreover, BK also inhibits osteoblastic differentiation by significantly downregulating the levels of mRNAs for osteopontin, runX2, col24, osterix, osteocalcin genes and bone mineralization (P < 0.05). Further, BK was found to elicit the BK receptors (BDKR1 and BDKR2) mediated activation of ERK1/2 and Akt pathways, which finally led to the activation of NFκB. BK also promoted the osteoclast differentiation of bone marrow derived preosteoclast cells by upregulating the expression of c-fos, NFATC1, TRAP, clcn7, cathK, and OSCAR genes and increasing TRAP activity through NFκB pathway. In conclusion, our data suggest that BK decreases the differentiation of osteoblasts with concomitant increase in osteoclast formation and thus provides new insight into the mechanism of action of BK in modulating bone resorption. © 2014 Wiley Periodicals, Inc.

  1. Close relationships between Asian American and European American college students.

    PubMed

    Chen, C; Edwards, K; Young, B; Greenberger, E

    2001-02-01

    The authors examined attitudes and behaviors regarding close relationships between European and Asian Americans, with a particular emphasis on 5 major subgroups of Asian Americans (Chinese, Japanese, Korean, Vietnamese, and Filipino Americans). Participants were 218 Asian American college students and 171 European American college students attending a culturally diverse university. The European Americans did not differentiate among the various subgroups of Asian Americans. Their attitudes regarding close relationships were less positive toward Asian Americans than toward Mexican and African Americans, a finding contrary to the prediction of social exchange theory (H. Tajfel, 1975). In contrast to the European Americans' view of homogeneity among Asian Americans, the 5 major subgroups of Asian Americans expressed a distinctive hierarchy of social preference among themselves. Results are discussed in terms of their implications for future research on interethnic relations involving Asian Americans.

  2. Unmanned Aircraft Systems (UAS): Addressing the Regulatory Issues for National Airspace System (NAS) Integration

    DTIC Science & Technology

    2009-04-01

    terms of IFR operations or passenger enplanements. The configuration of each Class B airspace area is individually tailored and consists of a surface...are serviced by a radar approach control, and that have a certain number of IFR operations or passenger enplanements. Although the configuration of...ft MSL Figure 3 depicts DoD UASs operating in their respective NAS classifications: Global Hawk Predator B Transponder See & Avoid DME IFR

  3. Computed tomography findings of human polyomavirus BK (BKV)-associated cystitis in allogeneic hematopoietic stem cell transplant recipients.

    PubMed

    Schulze, M; Beck, R; Igney, A; Vogel, M; Maksimovic, O; Claussen, C D; Faul, C; Horger, M

    2008-12-01

    Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and increased mucosal enhancement. These findings are not specific for

  4. Clinical Characteristics and Outcomes of Late-Onset BK Virus Nephropathy in Kidney and Kidney-Pancreas Transplant Recipients.

    PubMed

    Imlay, Hannah; Whitaker, Kathryn; Fisher, Cynthia E; Limaye, Ajit P

    2018-05-29

    BK virus nephropathy (BKPyVAN) is a major complication in kidney transplant recipients (KTR) and typically occurs within 1 year of transplant. Guidelines vary in recommendations for BKPyV screening beyond 1 year. A systematic characterization of risk factors and outcomes of late-onset (>1 year) BKPyVAN has not previously been reported. We retrospectively compared characteristics and outcomes of early- (<1 year) and late-onset BKPyVAN (definitive [biopsy-confirmed] or presumptive [plasma BKPyV >10,000 copies/mL]) in a cohort of 671 KTR and simultaneous kidney-pancreas transplant (SPK) recipients between 2008 and 2013 at a single US transplant center. Proportions were compared using Chi square or Fisher's exact test with p < 0.05 considered significant. BKPyVAN was diagnosed in 96 (14.3%) patients (proven 16.7%, presumptive 83.3%): 79 (82.3%) early- and 17 (17.7%) late-onset. The proportion with late-onset BKPyVAN was significantly higher among SPK than KTR (4 of 7 [57.1%] vs 13 of 89 [14.6%], p=0.017). Late-onset represented "de novo" infection (no BKPyV detection within the first year) in 14 (82.4%) and progression of earlier lower-grade BKPyV reactivation in 3 (17.6%). Clinical outcomes were similar for early- and late-onset BKPyVAN (p>0.05 all comparisons). In a pooled analysis of prior studies of BKPyVAN in SPK recipients, 62.9% (17 of 27) were late-onset. A significant proportion of BKPyVAN is late-onset, especially among SPK recipients, and supports a longer duration of BKPyV monitoring for SPK recipients than recommended in some guidelines. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Operational Overview for Unmanned Aircraft Systems (UAS) Integration in the National Airspace (NAS) Project Flight Test Series 3

    NASA Technical Reports Server (NTRS)

    Valkov, Steffi

    2017-01-01

    This presentation is a high level overview of the flight testing that took place in 2015 for the UAS-NAS project. All topics in the presentation discussed at a high level and no technical details are provided.

  6. Human plasma kallikrein-kinin system: Physiological and biochemical parameters

    PubMed Central

    Bryant, J.W.; Shariat-Madar, z

    2016-01-01

    The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity. PMID:19689262

  7. Neurophysiological mechanisms of bradykinin-evoked mucosal chloride secretion in guinea pig small intestine.

    PubMed

    Qu, Mei-Hua; Ji, Wan-Sheng; Zhao, Ting-Kun; Fang, Chun-Yan; Mao, Shu-Mei; Gao, Zhi-Qin

    2016-02-15

    To investigate the mechanism for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. Muscle-stripped guinea pig ileal preparations were mounted in Ussing flux chambers for the recording of short-circuit current (Isc). Basal Isc and Isc stimulated by BK when preincubated with the BK receptors antagonist and other chemicals were recorded using the Ussing chamber system. Prostaglandin E2 (PGE2) production in the intestine was determined by enzyme immunologic assay (EIA). Application of BK or B2 receptor (B2R) agonist significantly increased the baseline Isc compared to the control. B2R antagonist, tetrodotoxin and scopolamine (blockade of muscarinic receptors) significantly suppressed the increase in Isc evoked by BK. The BK-evoked Isc was suppressed by cyclooxygenase (COX)-1 or COX-2 specific inhibitor as well as nonselective COX inhibitors. Preincubation of submucosa/mucosa preparations with BK for 10 min significantly increased PGE2 production and this was abolished by the COX-1 and COX-2 inhibitors. The BK-evoked Isc was suppressed by nonselective EP receptors and EP4 receptor antagonists, but selective EP1 receptor antagonist did not have a significant effect on the BK-evoked Isc. Inhibitors of PLC, PKC, calmodulin or CaMKII failed to suppress BK-induced PGE2 production. The results suggest that BK stimulates neurogenic chloride secretion in the guinea pig ileum by activating B2R, through COX increasing PGE2 production. The post-receptor transduction cascade includes activation of PLC, PKC, CaMK, IP3 and MAPK.

  8. Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

    PubMed

    Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

    2008-08-01

    A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

  9. Large-conductance voltage- and Ca2+-activated K+ channel regulation by protein kinase C in guinea pig urinary bladder smooth muscle

    PubMed Central

    Hristov, Kiril L.; Smith, Amy C.; Parajuli, Shankar P.; Malysz, John

    2013-01-01

    Large-conductance voltage- and Ca2+-activated K+ (BK) channels are critical regulators of detrusor smooth muscle (DSM) excitability and contractility. PKC modulates the contraction of DSM and BK channel activity in non-DSM cells; however, the cellular mechanism regulating the PKC-BK channel interaction in DSM remains unknown. We provide a novel mechanistic insight into BK channel regulation by PKC in DSM. We used patch-clamp electrophysiology, live-cell Ca2+ imaging, and functional studies of DSM contractility to elucidate BK channel regulation by PKC at cellular and tissue levels. Voltage-clamp experiments showed that pharmacological activation of PKC with PMA inhibited the spontaneous transient BK currents in native freshly isolated guinea pig DSM cells. Current-clamp recordings revealed that PMA significantly depolarized DSM membrane potential and inhibited the spontaneous transient hyperpolarizations in DSM cells. The PMA inhibitory effects on DSM membrane potential were completely abolished by the selective BK channel inhibitor paxilline. Activation of PKC with PMA did not affect the amplitude of the voltage-step-induced whole cell steady-state BK current or the single BK channel open probability (recorded in cell-attached mode) upon inhibition of all major Ca2+ sources for BK channel activation with thapsigargin, ryanodine, and nifedipine. PKC activation with PMA elevated intracellular Ca2+ levels in DSM cells and increased spontaneous phasic and nerve-evoked contractions of DSM isolated strips. Our results support the concept that PKC activation leads to a reduction of BK channel activity in DSM via a Ca2+-dependent mechanism, thus increasing DSM contractility. PMID:24352333

  10. Neutral endopeptidase up-regulation in isolated human umbilical artery: involvement in desensitization of bradykinin-induced vasoconstrictor effects.

    PubMed

    Pelorosso, Facundo Germán; Halperin, Ana Verónica; Palma, Alejandro Martín; Nowak, Wanda; Errasti, Andrea Emilse; Rothlin, Rodolfo Pedro

    2007-02-01

    Previous reports show that bradykinin B(2) receptors mediate contractile responses induced by bradykinin (BK) in human umbilical artery (HUA). However, although it has been reported that BK-induced responses can desensitize in several inflammatory models, the effects of prolonged in vitro incubation on BK-induced vasoconstriction in HUA have not been studied. In isolated HUA rings, BK-induced responses after a 5-h in vitro incubation showed a marked desensitization compared with responses at 2 h. Inhibition of either angiotensin-converting enzyme (ACE) or neutral endopeptidase (NEP), both BK-inactivating enzymes, failed to modify responses to BK at 2 h. After 5 h, ACE inhibition produced only a slight potentiation of BK-induced responses. In contrast, BK-induced vasoconstriction at 5 h was markedly potentiated by NEP inhibition. Moreover, NEP activity, measured by hydrolysis of its synthetic substrate (Z-Ala-Ala-Leu-p-nitroanilide), showed a 2.4-fold increase in 5-h incubated versus 2-h incubated tissues, which was completely reversed by cycloheximide (CHX) treatment. Furthermore, CHX significantly potentiated BK-induced responses, suggesting that NEP-mediated kininase activity increase at 5 h depends on de novo protein synthesis. In addition, under NEP inhibition, CHX treatment failed to produce an additional potentiation of BK-induced vasoconstriction. Still, NEP up-regulation was confirmed by Western blot, showing a 2.1-fold increase in immunoreactive NEP in 5-h incubated versus 2-h incubated HUA. In summary, the present study provides strong pharmacological evidence that NEP is up-regulated and plays a key role in desensitization of BK-induced vasoconstriction after prolonged in vitro incubation in HUA. Our results provide new insights into the possible mechanisms involved in BK-induced response desensitization during sustained inflammatory conditions.

  11. American Science Advocacy Organizations: Examining Their Strategies and Engagements with Religion

    NASA Astrophysics Data System (ADS)

    Rodriguez, Jason T.

    Over the past several decades, science advocacy organizations have increasingly participated in discussions of the relationship between science and religion to the public, mainly to counteract the resurgence of anti-evolution activities across the country, to address misconceptions and misunderstandings about science and religion, and to help make science more palatable and less threatening to religious believers. These engagements with religion have primarily involved four organizations: the American Association for the Advancement of Science (AAAS), the National Academy of Sciences (NAS), the National Center for Science Education (NCSE), and the Smithsonian National Museum of Natural History (SNMNH). In their engagements with religion, each of these organizations has simultaneously employed two distinct lines of operation: (1) defending science against anti-science religions and movements and (2) engaging science-friendly religions and the religious public. These lines of operation are driven by key objectives and supported by specific strategies and tactics to achieve those objectives, which this paper seeks to explore and analyze. Key findings and recommendations for science advocacy organizations' ongoing and future engagements with religion are provided.

  12. Discipline behaviors of Chinese American and European American mothers.

    PubMed

    Hulei, Elaine; Zevenbergen, Andrea A; Jacobs, Sue C

    2006-09-01

    In any society, parenting beliefs are a reflection of that society's cultural values and traditions (J. U. Ogbu, 1981). Verbosity, a parenting behavior considered dysfunctional in European American culture, may not be problematic in Chinese culture. The authors recruited 31 Chinese American and 30 European American mothers and used questionnaires to measure parenting behaviors and child behavior problems. The Chinese American mothers also completed a questionnaire assessing their acculturation level. The Chinese American mothers had higher levels of verbosity than did the European American mothers; however, there were no differences between the groups in child behavior problems. The results also revealed higher levels of laxness in the Chinese American mothers compared to the European American mothers. Acculturation level did not predict verbosity or laxness levels. Results suggest that the effectiveness of a parenting style should be defined relative to cultural context.

  13. Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project. NASA Contributions to the SARP WC Definition

    NASA Technical Reports Server (NTRS)

    Randall, Debra K.; Consiglio, Maria Cristina; Santiago, Confesor

    2014-01-01

    To better inform sense and avoid research needs and to understand ongoing investigation of potential solutions that ultimately lead to the assisting the FAA with their Congressional mandate to fly UAS in the NAS.

  14. Remotely Operated Aircraft (ROA) Impact on the National Airspace System (NAS) Work Package, 2005: Composite Report on FAA Flight Plan and Operational Evaluation Plan. Version 7.0

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The purpose of this document is to present the findings that resulted from a high-level analysis and evaluation of the following documents: (1) The OEP (Operational Evolution Plan) Version 7 -- a 10-year plan for operational improvements to increase capacity and efficiency in U.S. air travel and transport and other use of domestic airspace. The OEP is the FAA commitment to operational improvements. It is outcome driven, with clear lines of accountability within FAA organizations. The OEP concentrates on operational solutions and integrates safety, certification, procedures, staffing, equipment, avionics and research; (2) The Draft Flight Plan 2006 through 2010 -- a multi-year strategic effort, setting a course for the FAA through 2001, to provide the safest and most efficient air transportation system in the world; (3) The NAS System Architecture Version 5 -- a blueprint for modernizing the NAS and improving NAS services and capabilities through the year 2015; and (4) The NAS-SR-1000 System Requirements Specification (NASSRS) -- a compilation of requirements which describe the operational capabilities for the NAS. The analysis is particularly focused on examining the documents for relevance to existing and/or planned future UAV operations. The evaluation specifically focuses on potential factors that could materially affect the development of a commercial ROA industry, such as: (1) Design limitations of the CNS/ATM system, (2) Human limitations, The information presented was taken from program specifications or program office lead personnel.

  15. Immunochemical characterization of the O antigens of two Proteus strains, O8-related antigen of Proteus mirabilis 12 B-r and O2-related antigen of Proteus genomospecies 5/6 12 B-k, infecting a hospitalized patient in Poland.

    PubMed

    Drzewiecka, Dominika; Shashkov, Alexander S; Arbatsky, Nikolay P; Knirel, Yuriy A

    2016-05-01

    A hospitalized 73-year-old woman was infected with a Proteus mirabilis strain, 12 B-r, isolated from the place of injection of a blood catheter. Another strain, 12 B-k, recognized as Proteus genomospecies 5 or 6, was isolated from the patient's faeces, which was an example of a nosocomial infection rather than an auto-infection. Serological investigation using ELISA and Western blotting showed that strain 12 B-k from faeces belonged to the Proteus O2 serogroup. Strain 12 B-r from the wound displayed cross-reactions with several Proteus O serogroups due to common epitopes on the core or O-specific parts of the lipopolysaccharide. Studies of the isolated 12 B-r O-specific polysaccharide by NMR spectroscopy revealed its close structural similarity to that of Proteus O8. The only difference in 12 B-r was the presence of an additional GlcNAc-linked phosphoethanolamine residue, which creates a putative epitope responsible for the cross-reactivity with Pt. mirabilis O16. The new O-antigen form could appear as a result of adaptation of the bacterium to a changing environment. On the basis of the data obtained, we suggest division of the O8 serogroup into two subgroups: O8a for strains of various Proteus species that have been previously classified into the O8 serogroup, and O8a,b for Pt. mirabilis 12 B-r, where 'a' is a common epitope and 'b' is a phosphoethanolamine-associated epitope. These findings further confirm serological and structural heterogeneity of O antigens of Proteus strains isolated lately from patients in Poland.

  16. BK Virus-Hemorrhagic Cystitis Following Allogeneic Stem Cell Transplantation: Clinical Characteristics and Utility of Leflunomide Treatment

    PubMed Central

    Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

    2016-01-01

    Objective: BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. Materials and Methods: From January 2005 to June 2014, among the 69 patients that underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Results: HC was observed in 30 patients (43.5%), and among them, 18 of the cases (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (minimum-maximum: 13-63). Patients received Allo-SCT for acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1). The donor types were human leukocyte antigen (HLA)-matched sibling donor for six patients, HLA-matched unrelated donor for nine, and haploidentical familial donor for two. The median onset and duration of BKV-HC was on day 21 after transplantation (minimum-maximum: 7-97) and 22 days (minimum-maximum: 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response, one had partial response, and five had no response. Among the five nonresponders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, achieving complete response (n=2) and partial response (n=2). The median duration from the start of leflunomide therapy to response was 13 days (minimum-maximum: 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. Conclusion: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who do not respond to supportive

  17. BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: Clinical characteristics and utility of leflunomide treatment.

    PubMed

    Park, Young Hoon; Lim, Joo Han; Yi, Hyeon Gyu; Lee, Moon Hee; Kim, Chul Soo

    2016-04-18

    BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. Hemorrhagic cystitis (HC) was observed in 30 patients (43.5%), and among them, 18 patients (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (range, 13-63). Patients received Allo-SCT from acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1).The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97) after transplantation and 22 days (range, 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response (CR), one partial response (PR), and five no response (NR). Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2) and PR (n=2). The median duration from the start of leflunomide therapy to response was 13 days (range, 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity.

  18. EPA's Reanalysis of Key Issues Related to Dioxin Toxicity and Response to NAS Comments (External Review Draft)

    EPA Science Inventory