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Sample records for cells rescue cardiomyoblasts

  1. Ascorbic acid improves embryonic cardiomyoblast cell survival and promotes vascularization in potential myocardial grafts in vivo

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    Martinez, E. C.; Wang, J; Gan, S U; Singh, R.; Lee, C. N.; Kofidis, T

    2010-01-01

    Organ restoration via cell therapy and tissue transplantation is limited by impaired graft survival. We tested the hypothesis that ascorbic acid (AA) reduces cell death in myocardial grafts both in vitro and in vivo and introduced a new model of autologous graft vascularization for later transplantation. Luciferase (Fluc)- and green fluorescent protein (GFP)-expressing H9C2 cardiomyoblasts were seeded in gelatin scaffolds to form myocardial artificial grafts (MAGs). MAGs were supplemented wit...

  2. Protective effects of clovamide against H2O2-induced stress in rat cardiomyoblasts H9c2 cell line.

    Science.gov (United States)

    Zamperone, Andrea; Pietronave, Stefano; Colangelo, Donato; Antonini, Silvia; Locatelli, Monica; Travaglia, Fabiano; Coïsson, Jean Daniel; Arlorio, Marco; Prat, Maria

    2014-10-01

    Cocoa contains phenolic compounds with known antioxidant and antiradical properties beneficial in different pathologies, including cardiovascular diseases. Herein, we have evaluated the protective effects of clovamide, a minor cocoa component, against oxidative stress induced in the rat cardiomyoblast cell line, also comparing it to its bio-isosteric form, rosmarinic acid, and to the main monomeric flavan-3-ol from low-molecular-weight polyphenol in cocoa, i.e. epicatechin. At nano-micro-molar concentrations, the three compounds inhibited the production of reactive oxygen species and apoptosis, evaluated under different aspects, namely, annexin V positivity, DNA fragmentation, caspase release and activation. These molecules can, thus, be considered for their bioactive beneficial activity in the context of cardiovascular pathologies and, particularly, in the protection towards oxidative stress that follows ischemic injury. Clovamide may, thus, be the primary compound for the development of innovative nutraceutical strategies towards cardiovascular diseases. PMID:25133994

  3. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    International Nuclear Information System (INIS)

    Highlights: ► We administered human CLCs in a swine model of MI via intracoronary artery. ► Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. ► Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. ► Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer’s solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of human specific alpha-cardiac actin. Human alpha cardiac actin-positive cells also expressed cardiac

  4. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  5. Allicin protects rat cardiomyoblasts (H9c2 cells) from hydrogen peroxide-induced oxidative injury through inhibiting the generation of intracellular reactive oxygen species.

    Science.gov (United States)

    Chan, Jackie Yan-Yan; Tsui, Hei-Tung; Chung, Ivan Ying-Ming; Chan, Robbie Yat-Kan; Kwan, Yiu-Wa; Chan, Shun-Wan

    2014-11-01

    Oxidative stress is considered an important factor that promotes cell death in response to a variety of pathophysiological conditions. This study investigated the antioxidant properties of allicin, the principle ingredient of garlic, on preventing oxidative stress-induced injury. The antioxidant capacities of allicin were measured by using 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay and hydrogen peroxide (H(2)O(2))-induced cell damage on H9c2 cardiomyoblasts. Allicin (0.3-10 μM) pre-incubation could concentration-dependently attenuate the intracellular reactive oxygen species (ROS) increase induced by H(2)O(2) on H9c2 cells. It could also protect H9c2 cells against H(2)O(2)-induced cell damage. However, the DPPH free radical scavenging activity of allicin was shown to be low. Therefore, it is believed that the protective effect of allicin on H9c2 cells could inhibit intracellular ROS production instead of scavenging extracellular H(2)O(2) or free radicals. For the observed protective effect on H9c2 cells, allicin might also be effective in reducing free radical-induced myocardial cell death in ischemic condition. PMID:24945597

  6. Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species

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    Rajitha T Kolamunne

    2013-01-01

    Full Text Available Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H with and without reoxygenation (H/R in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS, we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2−• scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2−·.To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4 h hypoxia with and without 2 h of reoxygenation and although cellular glutathione (GSH was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage.

  7. Rescue of marker phenotypes mediated by somatic cell hybridization

    International Nuclear Information System (INIS)

    The effect of irradiation prior to virus-induced cell fusion on the frequency of hybrid production has been measured as a function of radiation dose. The Chinese hamster line wg3h (HGPRT-) was crossed with the TK- mutants; Chinese hamster A23 or mouse 3T34E, and hybrids were selected in HAT medium. Irradiation of one (marker rescue) or both (mutual rescue) partners before fusion yielded qualitatively different results. After X-irradiation, marker rescue curves were of single-hit type, with D0 values about five-fold greater than the irradiated parent cell. Mutual rescue curves were of the multi-hit type, with zero-dose extrapolation value (n) greater than that of the more resistant partner, but no significant alteration in D0. Qualitatively similar results were obtained after U.V.- irradiation, but the probability of rescue per surviving parent cell was

  8. Modulation of NF-KB in rescued irradiated cells

    International Nuclear Information System (INIS)

    Studies by different groups on the rescue effect, where unirradiated bystander cells mitigated the damages in the irradiated cells, since its discovery by the authors' group in 2011 were first reviewed. The properties of the rescue effect were then examined using a novel experimental set-up to physically separate the rescue signals from the bystander signals. The authors' results showed that the rescue effect was mediated through activation of the nuclear factor-KB (NF-KB) response pathway in the irradiated cells, and that the NF-KB activation inhibitor BAy-11-7082 did not affect the activation of this response pathway in the irradiated cells induced by direct irradiation. (authors)

  9. Quercetin Reduces Inflammatory Responses in LPS-Stimulated Cardiomyoblasts

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    Cristina Angeloni

    2012-01-01

    Full Text Available Flavonoids possess several biological and pharmacological activities. Quercetin (Q, a naturally occurring flavonoid, has been shown to downregulate inflammatory responses and provide cardioprotection. However, the mechanisms behind the anti-inflammatory properties of Q in cardiac cells are poorly understood. In inflammation, nitric oxide (NO acts as a proinflammatory mediator and is synthesized by inducible nitric oxide synthase (iNOS in response to pro-inflammatory agents such as lipopolysaccharide (LPS, a causative agent in myocardial depression during sepsis. In the present study, we evaluated the protective effect of Q on rat cardiac dysfunction during sepsis induced by LPS. Pretreatment of H9c2 cardiomyoblasts with Q inhibited LPS-induced iNOS expression and NO production and counteracted oxidative stress caused by the unregulated NO production that leads to the generation of peroxynitrite and other reactive nitrogen species. In addition, Q pretreatment significantly counteracted apoptosis cell death as measured by immunoblotting of the cleaved caspase 3 and caspase 3 activity. Q also inhibited the LPS-induced phosphorylation of the stress-activated protein kinases (JNK/SAPK and p38 MAP kinase that are involved in the inhibition of cell growth as well as the induction of apoptosis. In conclusion, these results suggest that Q might serve as a valuable protective agent in cardiovascular inflammatory diseases.

  10. Stimulating basal mitochondrial respiration decreases doxorubicin apoptotic signaling in H9c2 cardiomyoblasts.

    Science.gov (United States)

    Deus, Cláudia M; Zehowski, Cheryl; Nordgren, Kendra; Wallace, Kendall B; Skildum, Andrew; Oliveira, Paulo J

    2015-08-01

    Doxorubicin (DOX) is currently used in cancer chemotherapy, however, its use often results in adverse effects highlighted by the development of cardiomyopathy and ultimately heart failure. Interestingly, DOX cardiotoxicity is decreased by resveratrol or by physical activity, suggesting that increased mitochondrial activity may be protective. Conversely, recent studies showed that troglitazone, a PPARγ agonist, increases the cytotoxicity of DOX against breast cancer cells by up-regulating mitochondrial biogenesis. The hypothesis for the current investigation was that DOX cytotoxicity in H9c2 cardiomyoblasts is decreased when mitochondrial capacity is increased. We focused on several end-points for DOX cytotoxicity, including loss of cell mass, apoptotic signaling and alterations of autophagic-related proteins. Our results show that a galactose-based, modified cell culture medium increased H9c2 basal mitochondrial respiration, protein content, and mtDNA copy number without increasing maximal or spare respiratory capacity. H9c2 cardiomyoblasts cultured in the galactose-modified media showed lower DOX-induced activation of the apoptotic pathway, measured by decreased caspase-3 and -9 activation, and lower p53 expression, although ultimately loss of cells was not prevented. Treatment with the PPARγ agonist troglitazone had no effect on DOX toxicity in this cardiac cell line, which agrees with the fact that troglitazone did not increase mitochondrial DNA content or capacity at the concentrations and duration of exposure used in this investigation. Our results show that mitochondrial remodeling caused by stimulating basal rates of oxidative phosphorylation decreased DOX-induced apoptotic signaling and increased DOX-induced autophagy in H9c2 cardiomyoblasts. The differential effect on cytotoxicity in cardiac versus breast cancer cell lines suggests a possible overall improvement in the clinical efficacy for doxorubicin in treating cancer. PMID:25997894

  11. Propagation of elite rescue dogs by somatic cell nuclear transfer.

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    Oh, Hyun Ju; Choi, Jin; Kim, Min Jung; Kim, Geon A; Jo, Young Kwang; Choi, Yoo Bin; Lee, Byeong Chun

    2016-01-01

    The objective of the present study was to compare the efficiency of two oocyte activation culture media to produce cloned dogs from an elite rescue dog and to analyze their behavioral tendencies. In somatic cell nuclear transfer procedure, fused couplets were activated by calcium ionophore treatment for 4 min, cultured in two media: modified synthetic oviduct fluid (mSOF) with 1.9 mmol/L 6-dimethylaminopyridine (DMAP) (SOF-DMAP) or porcine zygote medium (PZM-5) with 1.9 mmol/L DMAP (PZM-DMAP) for 4 h, and then were transferred into recipients. After embryo transfer, pregnancy was detected in one out of three surrogate mothers that received cloned embryos from the PZM-DMAP group (33.3%), and one pregnancy (25%) was detected in four surrogate mothers receiving cloned embryos from the SOF-DMAP group. Each pregnant dog gave birth to one healthy cloned puppy by cesarean section. We conducted the puppy aptitude test with two cloned puppies; the two cloned puppies were classified as the same type, accepting humans and leaders easily. The present study indicated that the type of medium used in 6-DMAP culture did not increase in cloning efficiency and dogs cloned using donor cells derived from one elite dog have similar behavioral tendencies. PMID:26387964

  12. A Stem Cell-rescue Operation in a Nuclear Devastation

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    Editorial

    2011-01-01

    Full Text Available Dear friends, The aftermath of one of the most devastating post earthquake- tsunamis in the history of mankind, the March 2011 post-earthquake-tsunami-hitnuclear accident in Fukushima, Japan, has brought to fore several questions throughout the world on the safety of nuclearinstallations. Such Calamities,which are far beyond our comprehension, has left all nations with such installations and those planning to expand their nuclear power plant programmes in a dilemma. However, the recent news that the Japanese authorities are considering to harvest and store bone marrow stem cells for transfusion to radiation-exposed workers has ushered in a new ray of hope. The hematopoietic stem cells will be harvested before exposure and in case of bone marrow depletion after radiation exposure; these cells can be immediately retrieved from storage and transfused to the radiation-exposed worker so that they have the potential to re-constitute the entire bone marrow in the patient. This will be a great life-saver and game-changer as bone marrow depletion is one of the major consequences of high levels of radiation exposure. This strategy can be prescribed as a routine procedure in all the countries with such nuclear installations, especially for workers at very high risk of radiation exposure. In future, such preventive strategies should be considered for implementation to not only the workers in the facility, but also the rescue team and the vulnerable population in the radiation zone.The regenerative potential of hematopoietic stem cell (HSC is the key factor to be considered now. This is high time that the studies on optimal in vitro expansion of HSCs and ways of successful engraftment of the transfused cells to a niche of radiation-exposed host environment should be attempted in all earnestness by the regenerative medicine community at present. Natural calamities like this help man to realise that the millions of scientific discoveries and inventions can

  13. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function. PMID:26041660

  14. Canstatin inhibits isoproterenol-induced apoptosis through preserving mitochondrial morphology in differentiated H9c2 cardiomyoblasts.

    Science.gov (United States)

    Okada, Muneyoshi; Morioka, Suiri; Kanazawa, Hiroki; Yamawaki, Hideyuki

    2016-08-01

    Canstatin, a non-collagenous fragment, is cleaved from type IV collagen α2 chain, an essential component of basement membrane surrounding cardiomyocytes. Although canstatin is known as an endogenous anti-angiogenic factor, its effects on cardiomyocytes have not been clarified. This study examined the effects of canstatin on isoproterenol-induced apoptosis in differentiated H9c2 cardiomyoblasts. Retinoic acid was used to differentiate H9c2 myoblast to cardiomyocyte-like phenotype. Cell viability was determined by a cell counting assay. Western blotting was performed to detect expression of cleaved casepase-3 and phosphorylation of dynamin related protein (Drp)1 at Ser637 which regulates mitochondrial fission. Mito Sox Red staining was performed to examine a mitochondria-dependent production of reactive oxygen species (ROS). Mitochondrial morphology was detected by Mito Tracker Red staining. Isoproterenol (100 μM, 48 h) significantly decreased cell viability and increased cleaved caspase-3 expression, which were inhibited by canstatin (10-250 ng/ml) in a concentration-dependent manner. Canstatin suppressed the isoproterenol-induced mitochondrial fission but not ROS. Canstatin also inhibited the isoproterenol-induced dephosphorylation of Drp1 at Ser637. In conclusion, canstatin inhibits isoproterenol-induced apoptosis through the inhibition of mitochondrial fission via the suppression of dephosphorylation of Drp1 at Ser637 in differentiated H9c2 cardiomyoblasts. PMID:27315818

  15. Effect of doxycycline on connexin 43 protein expression of cardiomyoblast cells in anoxic rat%多西环素对缺氧大鼠心肌细胞缝隙连接蛋白43表达的影响

    Institute of Scientific and Technical Information of China (English)

    罗刚; 巫相宏; 安迪; 黄文

    2013-01-01

    目的 探讨多西环素对缺氧大鼠H9c2心肌细胞缝隙连接蛋白43 (connexin 43,Cx 43)表达的影响及其可能的机制.方法 培养大鼠H9c2心肌细胞,用Western Blotting法检测缺氧6h、12h、24h后Cx43总蛋白的表达量及基质金属酶抑制剂(多西环素)、PI3K抑制剂(LY294002)、ERK1/2抑制剂(U0126)干预缺氧H9c2心肌细胞后Cx43总蛋白的表达量改变.结果 缺氧组较空白对照组Cx43总蛋白表达量明显降低,差异有统计学意义(P<0.01).缺氧6h时,多西环素和U0126干预组较缺氧组Cx43总蛋白表达量明显增高,差异有统计学意义(P<0.05);缺氧12h时,U0126干预组Cx43总蛋白表达量仍较缺氧组增高,差异有统计学意义(P<0.05);缺氧24 h时,多西环素和U0126干预后Cx43总蛋白表达量与缺氧组比较,差异无统计学意义(P>0.0.05).LY294002干预组Cx43总蛋白表达量在观察时间范围内均较缺氧组显著降低,差异有统计学意义(P<0.01).结论 在培养的大鼠H9c2心肌细胞中,多西环素通过抑制基质金属酶增加缺氧心肌细胞Cx43总蛋白表达量,该作用至少部分抑制由ERK1/2信号介导的传导通路.%Objectives To investigate the effects and the possible mechanisms of doxycycline on the expression of connexin 43 (Cx43) in rat H9c2 cardiomyoblast cells under hypoxic conditions.Methods H9c2 cardiomyoblast cells were cultured with hypoxia treatment for 6 h,12 h and 24 h.Expressions of Cx43 in cardiomyocytes were quantified by Western Blotting,as well as the changes intervened by matrix metalloproteinases (MMPs) inhibitor (doxycycline),PI3K inhibitor (LY294002),ERK1/2 inhibitor (U0126) under hypoxic conditions.Results Expression of Cx43 in hypoxia group was obviously lower than that in normal control group (P<0.01).Expressions of Cx43 in doxycycline group and U0126 group were obviously higher than that in hypoxia group after 6 h of hypoxia (P<0.05).Expression of Cx43 in U0126 group was still obviously

  16. Rescuing the duty to rescue.

    Science.gov (United States)

    Rulli, Tina; Millum, Joseph

    2016-04-01

    Clinicians and health researchers frequently encounter opportunities to rescue people. Rescue cases can generate a moral duty to aid those in peril. As such, bioethicists have leveraged a duty to rescue for a variety of purposes. Yet, despite its broad application, the duty to rescue is underanalysed. In this paper, we assess the state of theorising about the duty to rescue. There are large gaps in bioethicists' understanding of the force, scope and justification of the two most cited duties to rescue-the individual duty of easy rescue and the institutional rule of rescue. We argue that the duty of easy rescue faces unresolved challenges regarding its force and scope, and the rule of rescue is indefensible. If the duty to rescue is to help solve ethical problems, these theoretical gaps must be addressed. We identify two further conceptions of the duty to rescue that have received less attention-an institutional duty of easy rescue and the professional duty to rescue. Both provide guidance in addressing force and scope concerns and, thereby, traction in answering the outstanding problems with the duty to rescue. We conclude by proposing research priorities for developing accounts of duties to rescue in bioethics. PMID:24790055

  17. Iptakalim rescues human pulmonary artery endothelial cells from hypoxia-induced nitric oxide system dysfunction

    OpenAIRE

    Zong, Feng; Zuo, Xiang-Rong; Wang, Qiang; ZHANG, SHI-JIANG; Xie, Wei-Ping; Wang, Hong

    2011-01-01

    The aim of this study was to assess whether hypoxia inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production, and whether iptakalim may rescue human pulmonary artery endothelial cells (HPAECs) from hypoxia-induced NO system dysfunction. HPAECs were cultured under hypoxic conditions in the absence or presence of 0.1, 10 and 1,000 μM iptakalim or the combination of 10 μM iptakalim and 1, 10 and 100 μM glibenclamide for 24 h, and the eNOS activity and NO levels...

  18. Mesenchymal stem cell transplantation ameliorates motor function deterioration of spinocerebellar ataxia by rescuing cerebellar Purkinje cells

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    Ma Wei-Hsien

    2011-08-01

    Full Text Available Abstract Background Spinocerebellar ataxia (SCA refers to a disease entity in which polyglutamine aggregates are over-produced in Purkinje cells (PCs of the cerebellum as well as other neurons in the central nervous system, and the formation of intracellular polyglutamine aggregates result in the loss of neurons as well as deterioration of motor functions. So far there is no effective neuroprotective treatment for this debilitating disease although numerous efforts have been made. Mesenchymal stem cells (MSCs possess multi-lineage differentiation potentials as well as immuno-modulatory properties, and are theoretically good candidates for SCA treatment. The purpose of this study is to investigate whether transplantation of human MSCs (hMSCs can rescue cerebellar PCs and ameliorate motor function deterioration in SCA in a pre-clinical animal model. Method Transgenic mice bearing poly-glutamine mutation in ataxin-2 gene (C57BL/6J SCA2 transgenic mice were serially transplanted with hMSCs intravenously or intracranially before and after the onset of motor function loss. Motor function of mice was evaluated by an accelerating protocol of rotarod test every 8 weeks. Immunohistochemical stain of whole brain sections was adopted to demonstrate the neuroprotective effect of hMSC transplantation on cerebellar PCs and engraftment of hMSCs into mice brain. Results Intravenous transplantation of hMSCs effectively improved rotarod performance of SCA2 transgenic mice and delayed the onset of motor function deterioration; while intracranial transplantation failed to achieve such neuroprotective effect. Immunohistochemistry revealed that intravenous transplantation was more effective in the preservation of the survival of cerebellar PCs and engraftment of hMSCs than intracranial injection, which was compatible to rotarod performance of transplanted mice. Conclusion Intravenous transplantation of hMSCs can indeed delay the onset as well as improve the motor

  19. Rescue of salivary gland function after stem cell transplantation in irradiated glands.

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    Isabelle M A Lombaert

    Full Text Available Head and neck cancer is the fifth most common malignancy and accounts for 3% of all new cancer cases each year. Despite relatively high survival rates, the quality of life of these patients is severely compromised because of radiation-induced impairment of salivary gland function and consequential xerostomia (dry mouth syndrome. In this study, a clinically applicable method for the restoration of radiation-impaired salivary gland function using salivary gland stem cell transplantation was developed. Salivary gland cells were isolated from murine submandibular glands and cultured in vitro as salispheres, which contained cells expressing the stem cell markers Sca-1, c-Kit and Musashi-1. In vitro, the cells differentiated into salivary gland duct cells and mucin and amylase producing acinar cells. Stem cell enrichment was performed by flow cytrometric selection using c-Kit as a marker. In vitro, the cells differentiated into amylase producing acinar cells. In vivo, intra-glandular transplantation of a small number of c-Kit(+ cells resulted in long-term restoration of salivary gland morphology and function. Moreover, donor-derived stem cells could be isolated from primary recipients, cultured as secondary spheres and after re-transplantation ameliorate radiation damage. Our approach is the first proof for the potential use of stem cell transplantation to functionally rescue salivary gland deficiency.

  20. Disruption of microtubule network rescues aberrant actin comets in dynamin2-depleted cells.

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    Yuji Henmi

    Full Text Available A large GTPase dynamin, which is required for endocytic vesicle formation, regulates the actin cytoskeleton through its interaction with cortactin. Dynamin2 mutants impair the formation of actin comets, which are induced by Listeria monocytogenes or phosphatidylinositol-4-phosphate 5-kinase. However, the role of dynamin2 in the regulation of the actin comet is still unclear. Here we show that aberrant actin comets in dynamin2-depleted cells were rescued by disrupting of microtubule networks. Depletion of dynamin2, but not cortactin, significantly reduced the length and the speed of actin comets induced by Listeria. This implies that dynamin2 may regulate the actin comet in a cortactin-independent manner. As dynamin regulates microtubules, we investigated whether perturbation of microtubules would rescue actin comet formation in dynamin2-depleted cells. Treatment with taxol or colchicine created a microtubule-free space in the cytoplasm, and made no difference between control and dynamin2 siRNA cells. This suggests that the alteration of microtubules by dynamin2 depletion reduced the length and the speed of the actin comet.

  1. Rescue stem cell mobilization with plerixafor economizes leukapheresis in patients with multiple myeloma.

    Science.gov (United States)

    Hundemer, Michael; Engelhardt, Melanie; Bruckner, Thomas; Kraeker, Sandra; Schmitt, Anita; Sauer, Sandra; Neben, Kai; Witzens-Harig, Mathias; Goldschmidt, Hartmut; Ho, Anthony D; Wuchter, Patrick

    2014-12-01

    While extensive data demonstrated that plerixafor improves stem cell harvest in difficult-to-mobilize patients, economic concerns limit a broader application. We retrospectively assessed the effect of an early plerixafor rescue regimen for mobilization in patients with multiple myeloma. Patients were intended for high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ABSCT) and therefore received cyclophosphamide-based mobilization chemotherapy and consecutive stimulation with granulocyte colony-stimulating factor (G-CSF). Fifteen patients with poor stem cell harvest in the first leukapheresis session received plerixafor. Data were compared with a matched historic control group of 45 patients who also had a poor stem cell yield in the first apheresis session, but continued mobilization with G-CSF alone. Patients in the plerixafor group collected significantly more CD34+ cells in total (median 4.9 vs. 3.7 [range 1.6-14.1 vs. 1.1-8.0] × 10(6) CD34+ cells /kg bw; P 2.0 vs. 4.0 [range 2-3 vs. 2-9] procedures; P < 0.001). The efficiency of the collected stem cells in terms of hematologic engraftment after ABSCT was found to be equal in both groups. These data demonstrate that rescue mobilization with plerixafor triggered by a low stem cell yield in the first leukapheresis session is effective. Although the actual economic benefit may vary depending on the local leukapheresis costs, the median saving of two leukapheresis procedures offsets most of the expenses for the substance in this setting. An exemplary cost calculation is provided to illustrate this effect. PMID:24771277

  2. p66Shc signaling is involved in stress responses elicited by anthracycline treatment of rat cardiomyoblasts.

    Science.gov (United States)

    Sampaio, Susana F; Branco, Ana F; Wojtala, Aleksandra; Vega-Naredo, Ignacio; Wieckowski, Mariusz R; Oliveira, Paulo J

    2016-07-01

    The adaptor protein p66Shc modulates cellular redox status integrating oxidative stress with mitochondrial stress responses. Upon oxidative stress, p66Shc is translocated to mitochondria or mitochondria-associated membranes in a multi-step process, resulting in locally increased reactive oxygen species production. This signaling pathway is believed to be important in the context of drug-induced organ toxicity. The use of anthracyclines as anticancer agents is limited due to a dose-dependent and cumulative toxicity resulting in cardiomyopathy. Treatment with the anthracycline doxorubicin (DOX) results in a dose-dependent and cumulative cardiotoxicity which is mediated, at least in part, by increased oxidative stress. In the present study, we investigated for the first time whether p66Shc signaling is activated during DOX treatment of the rat cardiomyoblast H9c2 cell line. We further tested whether the transcriptional factor FoxO3a, which activates target genes responsible for apoptosis and cell cycle arrest, is also involved in p66Shc-dependent redox signaling pathway. Our results suggest that DOX treatment induces p66Shc protein up-regulation specifically in nuclear fractions. Increased nuclear expression of FoxO3a was also detected in H9c2 cells after DOX treatment. Treatment with the antioxidant and protein kinase C (PKC-β) inhibitor hispidin decreased DOX-induced activation of caspase 9 and p66Shc alterations. Taking together, we hypothesize that p66Shc signaling is involved in the activation of stress/toxicity responses elicited by the treatment of H9c2 cells with DOX. Hence, the selective inhibition of this redox pathway may be a promising therapeutic approach to circumvent DOX cardiotoxicity. PMID:26318906

  3. NKS/SRV seminar on Barents Rescue 2001 LIVEX. Gamma search cell

    International Nuclear Information System (INIS)

    At the seminar, results from the Gamma Search Cell of the Barents Rescue 2001 LIVEX were presented and the performance and experiences of airborne and car-borne teams that took part in the exercise were evaluated. In the Gamma Search Cell, the mobile teams found about 50 % of a large number of radioactive sources hidden within the exercise area. The exercise demonstrated that it is necessary to practise and test equipment under out-door conditions. By which method a source is found is important information in the evaluation of the result. Complementary methods are necessary to find hidden sources. For heavily shielded sources methods based on scattered radiation should be developed. (au)

  4. NKS/SRV seminar on Barents Rescue 2001 LIVEX. Gamma search cell

    Energy Technology Data Exchange (ETDEWEB)

    Ulvsand, T. [Swedish Defense Research Agency, Stockholm (Sweden); Finck, R.R. [Swedish Radiation Protection Authority, Stockholm (Sweden); Lauritzen, N. [Risoe National Lab., Roskilde (Denmark)](eds.)

    2002-04-01

    At the seminar, results from the Gamma Search Cell of the Barents Rescue 2001 LIVEX were presented and the performance and experiences of airborne and car-borne teams that took part in the exercise were evaluated. In the Gamma Search Cell, the mobile teams found about 50 % of a large number of radioactive sources hidden within the exercise area. The exercise demonstrated that it is necessary to practise and test equipment under out-door conditions. By which method a source is found is important information in the evaluation of the result. Complementary methods are necessary to find hidden sources. For heavily shielded sources methods based on scattered radiation should be developed. (au)

  5. Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death

    International Nuclear Information System (INIS)

    One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries. (author)

  6. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy.

    Science.gov (United States)

    Ahmad, Tanveer; Mukherjee, Shravani; Pattnaik, Bijay; Kumar, Manish; Singh, Suchita; Kumar, Manish; Rehman, Rakhshinda; Tiwari, Brijendra K; Jha, Kumar A; Barhanpurkar, Amruta P; Wani, Mohan R; Roy, Soumya S; Mabalirajan, Ulaganathan; Ghosh, Balaram; Agrawal, Anurag

    2014-05-01

    There is emerging evidence that stem cells can rejuvenate damaged cells by mitochondrial transfer. Earlier studies show that epithelial mitochondrial dysfunction is critical in asthma pathogenesis. Here we show for the first time that Miro1, a mitochondrial Rho-GTPase, regulates intercellular mitochondrial movement from mesenchymal stem cells (MSC) to epithelial cells (EC). We demonstrate that overexpression of Miro1 in MSC (MSCmiro(Hi)) leads to enhanced mitochondrial transfer and rescue of epithelial injury, while Miro1 knockdown (MSCmiro(Lo)) leads to loss of efficacy. Treatment with MSCmiro(Hi) was associated with greater therapeutic efficacy, when compared to control MSC, in mouse models of rotenone (Rot) induced airway injury and allergic airway inflammation (AAI). Notably, airway hyperresponsiveness and remodeling were reversed by MSCmiro(Hi) in three separate allergen-induced asthma models. In a human in vitro system, MSCmiro(Hi) reversed mitochondrial dysfunction in bronchial epithelial cells treated with pro-inflammatory supernatant of IL-13-induced macrophages. Anti-inflammatory MSC products like NO, TGF-β, IL-10 and PGE2, were unchanged by Miro1 overexpression, excluding non-specific paracrine effects. In summary, Miro1 overexpression leads to increased stem cell repair. PMID:24431222

  7. BNC Protects H9c2 Cardiomyoblasts from H2O2-Induced Oxidative Injury through ERK1/2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Fangbo Zhang

    2013-01-01

    Full Text Available Buchang naoxintong capsule (BNC is a traditional Chinese medicine approved for the treatment of cerebrovascular and cardiovascular diseases. However, little is known about the specific protective function or mechanism by which BNC protects against myocardial injury. This research was designed to investigate the cardioprotective effects of BNC in vitro model of hydrogen peroxide (H2O2-induced H9c2 rat cardiomyoblasts. BNC intestinal absorption liquid was used in this study instead of drug-containing serum or extracting solution. Our study revealed that BNC preconditioning enhanced antioxidant function by increasing the activities of total-antioxygen capacity, total-superoxide dismutase, and catalase and by decreasing the production of reactive oxygen species and malondialdehyde. BNC preconditioning also activated extracellular signal-regulated kinases (ERK1/2 and inhibited apoptosis-related proteins such as poly ADP-ribose polymerase (PARP and caspase-3. Additionally, preincubation with BNC reduced intracellular Ca2+ concentration, improved mitochondrial membrane potential, and decreased the apoptosis rate of H9c2 cells in a dose-dependent manner. These data demonstrated that BNC protects H9c2 cardiomyoblasts from H2O2-induced oxidative injury by increasing antioxidant abilities, activating ERK1/2, and blocking Ca2+-dependent and mitochondria-mediated apoptosis. Based on our results, the potency of BNC for protecting H9c2 cells from oxidative damage is comparable to that of trimetazidine.

  8. Prolactin Rescues Immature B-Cells from Apoptosis Induced by B-Cell Receptor Cross-Linking

    Science.gov (United States)

    Flores-Fernández, Rocio; Blanco-Favela, Francisco; Fuentes-Pananá, Ezequiel M.; Chávez-Sánchez, Luis; Gorocica-Rosete, Patricia; Pizaña-Venegas, Alberto; Chávez-Rueda, Adriana Karina

    2016-01-01

    Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease. PMID:27314053

  9. TGF-β Inhibition Rescues Hematopoietic Stem Cell Defects and Bone Marrow Failure in Fanconi Anemia.

    Science.gov (United States)

    Zhang, Haojian; Kozono, David E; O'Connor, Kevin W; Vidal-Cardenas, Sofia; Rousseau, Alix; Hamilton, Abigail; Moreau, Lisa; Gaudiano, Emily F; Greenberger, Joel; Bagby, Grover; Soulier, Jean; Grompe, Markus; Parmar, Kalindi; D'Andrea, Alan D

    2016-05-01

    Fanconi anemia (FA) is an inherited DNA repair disorder characterized by progressive bone marrow failure (BMF) from hematopoietic stem and progenitor cell (HSPC) attrition. A greater understanding of the pathogenesis of BMF could improve the therapeutic options for FA patients. Using a genome-wide shRNA screen in human FA fibroblasts, we identify transforming growth factor-β (TGF-β) pathway-mediated growth suppression as a cause of BMF in FA. Blocking the TGF-β pathway improves the survival of FA cells and rescues the proliferative and functional defects of HSPCs derived from FA mice and FA patients. Inhibition of TGF-β signaling in FA HSPCs results in elevated homologous recombination (HR) repair with a concomitant decrease in non-homologous end-joining (NHEJ), accounting for the improvement in cellular growth. Together, our results suggest that elevated TGF-β signaling contributes to BMF in FA by impairing HSPC function and may be a potential therapeutic target for the treatment of FA. PMID:27053300

  10. Fibroblast growth factor rescues brain endothelial cells lacking presenilin 1 from apoptotic cell death following serum starvation.

    Science.gov (United States)

    Gama Sosa, Miguel A; De Gasperi, Rita; Hof, Patrick R; Elder, Gregory A

    2016-01-01

    Presenilin 1 (Psen1) is important for vascular brain development and is known to influence cellular stress responses. To understand the role of Psen1 in endothelial stress responses, we investigated the effects of serum withdrawal on wild type (wt) and Psen1-/- embryonic brain endothelial cells. Serum starvation induced apoptosis in Psen1-/- cells but did not affect wt cells. PI3K/AKT signaling was reduced in serum-starved Psen1-/- cells, and this was associated with elevated levels of phospho-p38 consistent with decreased pro-survival AKT signaling in the absence of Psen1. Fibroblast growth factor (FGF1 and FGF2), but not vascular endothelial growth factor (VEGF) rescued Psen1-/- cells from serum starvation induced apoptosis. Inhibition of FGF signaling induced apoptosis in wt cells under serum withdrawal, while blocking γ-secretase activity had no effect. In the absence of serum, FGF2 immunoreactivity was distributed diffusely in cytoplasmic and nuclear vesicles of wt and Psen1-/- cells, as levels of FGF2 in nuclear and cytosolic fractions were not significantly different. Thus, sensitivity of Psen1-/- cells to serum starvation is not due to lack of FGF synthesis but likely to effects of Psen1 on FGF release onto the cell surface and impaired activation of the PI3K/AKT survival pathway. PMID:27443835

  11. Desmodium gangeticum (Linn.) DC. exhibits antihypertrophic effect in isoproterenol-induced cardiomyoblasts via amelioration of oxidative stress and mitochondrial alterations.

    Science.gov (United States)

    Sankar, Vandana; Pangayarselvi, Balasubramaniam; Prathapan, Ayyappan; Raghu, Kozhiparambil Gopalan

    2013-01-01

    Cardiac hypertrophy occurs in response to increased workload, such as hypertension or valvular heart disease. Oxidative stress has been implicated in cardiac hypertrophy and in its transition to heart failure. This study was taken up with the objective to evaluate the role of oxidative stress in cardiomyoblast hypertrophy and its modulation by Desmodium gangeticum (DG) that has been traditionally used in Ayurveda, an Indian system of medicine. The methanolic root extract was analyzed for total phenolic content and tested for antioxidant potential. Hypertrophy was induced by exposing H9c2 cell line to β-adrenergic receptor agonist, isoproterenol (ISO), for 96 hours. Analyses of reactive oxygen species (ROS) generation, mitochondrial transmembrane potential ([INCREMENT]Ψm), and integrity of permeability transition were performed in ISO as well as Desmodium and ISO-cotreated cells. The results demonstrated potent free radical scavenging activity of DG. Cell line studies showed significant increase in ROS generation, dissipation of [INCREMENT]Ψm, and permeability transition pore opening in ISO-treated cells. Desmodium was found to attenuate ISO-induced hypertrophy by reduction of ROS generation, restoration of [INCREMENT]Ψm, and prevention of permeability transition pore opening. This study is the first documentation of the modulatory effect of DG on cardiac hypertrophy. PMID:23052030

  12. Rescuing axons from degeneration does not affect retinal ganglion cell death

    Directory of Open Access Journals (Sweden)

    S. de Lima

    2016-01-01

    Full Text Available After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD, an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18 treated with an exogenous calpain inhibitor (20 mM administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05 and an increase in the number of preserved fibers (P<0.05 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.

  13. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

    Directory of Open Access Journals (Sweden)

    Yongjun Fan

    2014-05-01

    Full Text Available Hereditary Spastic Paraplegia (HSP is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials.

  14. miR-16 rescues F508del-CFTR function in native cystic fibrosis epithelial cells.

    Science.gov (United States)

    Kumar, P; Bhattacharyya, S; Peters, K W; Glover, M L; Sen, A; Cox, R T; Kundu, S; Caohuy, H; Frizzell, R A; Pollard, H B; Biswas, R

    2015-11-01

    Cystic fibrosis (CF) is due to mutations in the CFTR gene, which prevents correct folding, trafficking and function of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. The dysfunctional effect of CFTR mutations, principally the F508del-CFTR mutant, is further manifested by hypersecretion of the pro-inflammatory chemokine interleukin-8 into the airway lumen, which further contributes to morbidity and mortality. We have hypothesized that microRNA (miR)-based therapeutics could rescue the dysfunctional consequences of mutant CFTR. Here we report that a miR-16 mimic can effectively rescue F508del-CFTR protein function in airway cell lines and primary cultures, of differentiated human bronchial epithelia from F508del homozygotes, which express mutant CFTR endogenously. We also identify two other miRs, miR-1 and miR-302a, which are also active. Although miR-16 is expressed at basal comparable levels in CF and control cells, miR-1 and miR-302a are undetectable. When miR mimics are expressed in CF lung or pancreatic cells, the expression of the F508del-CFTR protein is significantly increased. Importantly, miR-16 promotes functional rescue of the cyclic AMP-activated apical F508del-CFTR chloride channel in primary lung epithelial cells from CF patients. We interpret these findings to suggest that these miRs may constitute novel targets for CF therapy. PMID:26133785

  15. Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

    DEFF Research Database (Denmark)

    Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida;

    2012-01-01

    of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin......Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients...... and mitochondrial dysfunction in this neurodegenerative disease....

  16. Partial rescue of mucopolysaccharidosis type VII mice with a lifelong engraftment of allogeneic stem cells in utero.

    Science.gov (United States)

    Ihara, Norimasa; Akihiro, Umezawa; Onami, Naoko; Tsumura, Hideki; Inoue, Eisuke; Hayashi, Satoshi; Sago, Haruhiko; Mizutani, Shuki

    2015-02-01

    In utero hematopoietic cell transplantation (IUHCT) has been performed in Mucopolysaccharidosis Type VII (MPSVII) mice, but a lifelong engraftment of allogeneic donor cells has not been achieved. In this study, we sought to confirm a lifelong engraftment of allogeneic donor cells immunologically matched to the mother and to achieve partial rescue of phenotypes in the original MPSVII strain through IUHCT by intravenous injection. We performed in vitro fertilization in a MPSVII murine model and transferred affected embryos to ICR/B6-GFP surrogate mothers in cases where fetuses receiving IUHCT were all homozygous. Lineage-depleted cells from ICR/B6-GFP mice were injected intravenously at E14.5. Chimerism was confirmed by flow cytometry at 4 weeks after birth, and β-glucuronidase activity in serum and several phenotypes were assessed at 8 weeks of age or later. Donor cells in chimeric mice from ICR/B6-GFP mothers were detected at death, and were confirmed in several tissues including the brains of sacrificed chimeric mice. Although the serum enzyme activity of chimeric mice was extremely low, the engraftment rate of donor cells correlated with enzyme activity. Furthermore, improvement of bone structure and rescue of reproductive ability were confirmed in our limited preclinical study. We confirmed the lifelong engraftment of donor cells in an original immunocompetent MPSVII murine model using intravenous IUHCT with cells immunologically matched to the mother without myeloablation, and the improvement of several phenotypes. PMID:25421592

  17. Rescue by peripheral blood mononuclear cells in dogs from bone marrow failure after total-body irradiation

    International Nuclear Information System (INIS)

    In order to determine the minimum dose of buffy coat cells necessary to achieve hematopoietic rescue following supralethal irradiation, mongrel dogs under general anesthesia were subjected to leukacytapheresis using three different techniques of cell separation. The buffy coats were frozen with dimethylsulfoxide and stored at -196 degrees C until transfused. Sixteen dogs were irradiated with 800 rads and were supported with antibiotics and transfusions of irradiated homologous blood. They were transfused with the frozen and thawed buffy coat cells, and, if they survived, they were followed for 100 days, sacrificed, and their tissues studied. The mean yield of mononuclear cells during leukocytapheresis ranged from 4.1 +/- 2.0 X 10(9) (mean +/- SD) to 6.0 +/- 4.0 X 10(9) for the three leukacytapheresis methods; one technique was not as satisfactory as the other two. Six of the 16 dogs fully recovered with evidence of marrow rescue; however, only one had a dose of mononuclear cells less than 11.1 X 10(9). These data indicate that seven to 17 leukacytapheresis procedures would be required to reconstitute a 70 kilogram patient. These preliminary findings suggest that, because the yields of transplantable cells with current technology are not adequate, the transplantation potential of buffy coat cells exposed to mobilizing agents should be evaluated

  18. Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death.

    Science.gov (United States)

    Yin, Ming Zhe; Park, Seok-Woo; Kang, Tae Wook; Kim, Kyung Soo; Yoo, Hae Young; Lee, Junho; Hah, J Hun; Sung, Myung Hun; Kim, Sung Joon

    2016-01-01

    Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca(2+) ([Ca(2+)]i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca(2+)-activated K(+) channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 µM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca(2+)-activated Cl(-) channels (Ano-1) and Ca(2+)-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K(+) current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC. PMID:26807020

  19. Maritime Rescue

    Directory of Open Access Journals (Sweden)

    Constantin Anechitoae

    2012-05-01

    Full Text Available The maritime rescue, as any other legal institution related to maritime events - collision, crash, etc.- has its distinctive features. The maritime rescue may be considered as the operation that arises frommaritime collision, because, while collision stems from a breach of a negative duty necessary in maritimenavigation, i.e. of not harming the other, the maritime rescue is the implementation of positive obligationsrequired to vessel captains by the material requirements of the marine life that adds to the elements of thelegal concept which can be summed up as follows: to go to the aid of a vessel in danger, provided that thevessel does not expose itself, through this action, to a serious danger. The institution of maritime rescueencourages maritime commercial activities by the fact that, thus, there are governed such clear rights andobligations saving life at sea and shipping goods.

  20. Cloning of adeno-associated virus into pBR322: Rescue of intact virus from the recombinant plasmid in human cells

    OpenAIRE

    1982-01-01

    We have cloned intact duplex adeno-associated virus (AAV) DNA into the bacterial plasmid pBR322. The AAV genome could be rescued from the recombinant plasmid by transfection of the plasmid DNA into human cells with adenovirus 5 as helper. The efficiency of rescue from the plasmid was sufficiently high to produce yields of AAV DNA comparable to those observed after transfection with equal amounts of purified virion DNA. Thus, the recombinant plasmid itself may be a model for studying the rescu...

  1. Light can rescue auxin-dependent synchrony of cell division in a tobacco cell line

    Czech Academy of Sciences Publication Activity Database

    Qiao, F.; Petrášek, Jan; Nick, P.

    2010-01-01

    Roč. 61, č. 2 (2010), s. 503-510. ISSN 0022-0957 Institutional research plan: CEZ:AV0Z50380511 Keywords : Auxin transport * cell division * NPA Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.818, year: 2010 http://jxb.oxfordjournals.org/content/61/2/503.abstract

  2. High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma†

    OpenAIRE

    Dunkel, Ira J.; Gardner, Sharon L.; Garvin, James H.; Goldman, Stewart; Shi, Weiji; Finlay, Jonathan L.

    2010-01-01

    Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0–M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m2/day) on days −8 to −6, and thiotepa (300 mg/m2/day) and etoposide (250 mg/m2/day) on days −5 to −3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6–44.7 years (...

  3. Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

    Science.gov (United States)

    Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

    2016-07-01

    Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

  4. MIRACLE RESCUE

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ Atotal of 115 workers had been miraculously retrieved from the flooded Wangjialing Coal Mine in north China's Shanxi Province by the afternoon of April 5, after being trapped underground for more than a week. "It is a miracle in the history of Chinese mining rescues," said Luo Lin, Director of the State Administration of Work Safety, who stood waiting at the pit entrance. "The trapped miners displayed an unwavering determination to survive for eight days and eight nights."

  5. 1070 myeloablative megatherapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions

    International Nuclear Information System (INIS)

    1070 myeloablative procedures followed by stem cell rescue for neuroblastoma are reviewed. These 1070 procedures are part of the European Group for Blood and Marrow Transplant (EBMTG) registry from the last 17 years (in 4536 patients). In 1070 neuroblastoma patients, survival at 2 years was 49%, at 5 years, 33% and relapses were observed as late as 7 years post-BMT (bone marrow transplant). However, 5-year survivors after megatherapy with BMT for stage 4 disease do have an 80% chance of becoming a long-term survivor. When BMT had been used in first complete response (CR1) no salvage was possible, whereas 15% survivors may be seen if BMT is used for the first time at relapse. Infants with stage 4 neuroblastoma had a 17% toxic death rate and indication in this group is exceptional and not recommended. In a matched cohort (17 allogeneic and 34 autologous), autologous stem cell rescue (SCR) was shown to be at least equal to allogeneic SCR. Multivariate analysis of clinical prognostic factors in children with stage 4 disease over 1 year showed that event-free survival was mainly influenced by two adverse factors before the megatherapy procedure: persisting skeleton lesions (99Tc and/or mIBG scan positive) as well as persisting bone marrow (BM) involvement. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  6. Mapping of the vaccinia virus DNA polymerase gene by marker rescue and cell-free translation of selected RNA

    International Nuclear Information System (INIS)

    The previous demonstration that a phosphonoacetate (PAA)-resistant (PAA/sup r/) vaccinia virus mutant synthesized an altered DNA polymerase provided the key to mapping this gene. Marker rescue was performed in cells infected with wild-type PAA-sensitive (PAA/sup s/) vaccinia by transfecting with calcium phosphate-precipitated DNA from a PAA/sup r/ mutant virus. Formation of PAA/sup r/ recombinants was measured by plaque assay in the presence of PAA. Of the 12 HindIII fragments cloned in plasmid or cosmid vectors, only fragment E conferred the PAA/sup r/ phenotype. Successive subcloning of the 15-kilobase HindIII fragment E localized the marker within a 7.5-kilobase BamHI-HindIII fragment and then within a 2.9-kilobase EcoRI fragment. The location of the DNA polymerase gene, about 57 kilobases from the left end of the genome, was confirmed by cell-free translation of mRNA selected by hybridization to plasmids containing regions of PAA/sup r/ vaccinia DNA active in marker rescue. A 100,000-dalton polypeptide that comigrated with authentic DNA polymerase was synthesized. Correspondence of the in vitro translation product with purified vaccinia DNA polymerase was established by peptide mapping

  7. DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose

    Science.gov (United States)

    Liu, Zhi; Chen, Tian; Sun, Wenhua; Yuan, Zongyi; Yu, Mei; Chen, Guoqing; Guo, Weihua; Xiao, Jingang; Tian, Weidong

    2016-01-01

    Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2′-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway. PMID:27273319

  8. Bone marrow transplantation enhances trafficking of host-derived myelomonocytic cells that rescue intestinal mucosa after whole body radiation

    International Nuclear Information System (INIS)

    Background: Bone marrow (BM)-derived cells were demonstrated within intestines after radiation damage and were reported to be responsible for intestine repair. However, there was a discrepancy between intestine epithelial clonogenic regeneration, and mouse survival after BM transplantation (BMT) and radiation. The contribution of BM to acute intestine repair after radiation needed further investigation. Methods: Mouse survival, intestine microcolony assay, immunohistochemical studies of both intestine and BM were evaluated in mice after whole body irradiation (WBI) and BMT. Immunoblotting, flowcytometry, and double immunostaining were used to evaluate the amount and the character of stroma cells within intestines of recipient mice after receiving gender-mismatched BMT or BMT from green fluorescence donors. Results: Stromal cell proliferation within the lamina propria correlated with the beneficial effect of BMT to intestine recovery and day-8 survival of mice. Few donor-derived cells were found before the completion of intestine repair. The number of host but not donor-derived myelomonocytic and stromal cells increased dramatically within one week after radiation and BMT. Depletion of myelomonocytic cells of recipient mice abolished the mitigating effect of BMT. Conclusions: Besides rescuing injured BM from aplasia, BMT triggers trafficking of host CD11b(+) myelomonocytic cells from the host marrow to the radiation-injured intestinal mucosa, enhancing the proliferation of intestinal stroma cells, leading secondarily to epithelial regeneration.

  9. ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation

    Science.gov (United States)

    de Jong, Petrus R.; Taniguchi, Koji; Harris, Alexandra R.; Bertin, Samuel; Takahashi, Naoki; Duong, Jen; Campos, Alejandro D.; Powis, Garth; Corr, Maripat; Karin, Michael; Raz, Eyal

    2016-01-01

    The ERK1/2 MAPK signalling module integrates extracellular cues that induce proliferation and differentiation of epithelial lineages, and is an established oncogenic driver, particularly in the intestine. However, the interrelation of the ERK1/2 module relative to other signalling pathways in intestinal epithelial cells and colorectal cancer (CRC) is unclear. Here we show that loss of Erk1/2 in intestinal epithelial cells results in defects in nutrient absorption, epithelial cell migration and secretory cell differentiation. However, intestinal epithelial cell proliferation is not impeded, implying compensatory mechanisms. Genetic deletion of Erk1/2 or pharmacological targeting of MEK1/2 results in supraphysiological activity of the ERK5 pathway. Furthermore, targeting both pathways causes a more effective suppression of cell proliferation in murine intestinal organoids and human CRC lines. These results suggest that ERK5 provides a common bypass route in intestinal epithelial cells, which rescues cell proliferation upon abrogation of ERK1/2 signalling, with therapeutic implications in CRC. PMID:27187615

  10. Copper and bezafibrate cooperate to rescue cytochrome c oxidase deficiency in cells of patients with sco2 mutations

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    Casarin Alberto

    2012-04-01

    Full Text Available Abstract Background Mutations in SCO2 cause cytochrome c oxidase deficiency (COX and a fatal infantile cardioencephalomyopathy. SCO2 encodes a protein involved in COX copper metabolism; supplementation with copper salts rescues the defect in patients’ cells. Bezafibrate (BZF, an approved hypolipidemic agent, ameliorates the COX deficiency in mice with mutations in COX10, another COX-assembly gene. Methods We have investigated the effect of BZF and copper in cells with SCO2 mutations using spectrophotometric methods to analyse respiratory chain activities and a luciferase assay to measure ATP production.. Results Individual mitochondrial enzymes displayed different responses to BZF. COX activity increased by about 40% above basal levels (both in controls and patients, with SCO2 cells reaching 75-80% COX activity compared to untreated controls. The increase in COX was paralleled by an increase in ATP production. The effect was dose-dependent: it was negligible with 100 μM BZF, and peaked at 400 μM BZF. Higher BZF concentrations were associated with a relative decline of COX activity, indicating that the therapeutic range of this drug is very narrow. Combined treatment with 100 μM CuCl2 and 200 μM BZF (which are only marginally effective when administered individually achieved complete rescue of COX activity in SCO2 cells. Conclusions These data are crucial to design therapeutic trials for this otherwise fatal disorder. The additive effect of copper and BZF will allow to employ lower doses of each drug and to reduce their potential toxic effects. The exact mechanism of action of BZF remains to be determined.

  11. tmRNA-mediated trans-translation as the major ribosome rescue system in a bacterial cell

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    Hyouta eHimeno

    2014-04-01

    Full Text Available tmRNA (transfer messenger RNA; also known as 10Sa RNA or SsrA RNA is a small RNA molecule that is conserved among bacteria. It has structural and functional similarities to tRNA: it has an upper half of the tRNA-like structure, its 5’ end is processed by RNase P, it has typical tRNA-specific base modifications, it is aminoacylated with alanine, it binds to EF-Tu after aminoacylation and it enters the ribosome with EF-Tu and GTP. However, tmRNA lacks an anticodon, and instead it has a coding sequence for a short peptide called tag-peptide. An elaborate interplay of actions of tmRNA as both tRNA and mRNA with the help of a tmRNA-binding protein, SmpB, facilitates trans-translation, which produces a single polypeptide from two mRNA molecules. Initially alanyl-tmRNA in complex with EF-Tu and SmpB enters the vacant A-site of the stalled ribosome like aminoacyl-tRNA but without a codon-anticodon interaction, and subsequently truncated mRNA is replaced with the tag-encoding region of tmRNA. During these processes, not only tmRNA but also SmpB structurally and functionally mimics both tRNA and mRNA. Thus trans-translation rescues the stalled ribosome, thereby allowing recycling of the ribosome. Since the tag-peptide serves as a target of AAA+ proteases, the trans-translation products are preferentially degraded so that they do not accumulate in the cell. Although alternative rescue systems have recently been revealed, trans-translation is the only system that universally exists in bacteria. Furthermore, it is unique in that it employs a small RNA and that it prevents accumulation of nonfunctional proteins from truncated mRNA in the cell. It might play the major role in rescuing the stalled translation in the bacterial cell.

  12. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts

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    Elena Grossini

    2016-01-01

    Full Text Available Objective: To examine the effects of asenapine on nitric oxide (NO release and Ca2+ transients in H9C2 cell line, which were either subjected to peroxidation or not. Materials and Methods: H9C2 were treated with asenapine alone or in presence of intracellular kinase blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes. Results: In H9C2, asenapine differently modulated NO release and Ca2+ movements depending on peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors, and voltage Ca2+ channels blockers.Conclusions: On the basis of our findings, we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance when considering their role in cardiac function modulation.

  13. Gata3 Hypomorphic Mutant Mice Rescued with a Yeast Artificial Chromosome Transgene Suffer a Glomerular Mesangial Cell Defect.

    Science.gov (United States)

    Moriguchi, Takashi; Yu, Lei; Otsuki, Akihito; Ainoya, Keiko; Lim, Kim-Chew; Yamamoto, Masayuki; Engel, James Douglas

    2016-09-01

    GATA3 is a zinc finger transcription factor that plays a crucial role in embryonic kidney development, while its precise functions in the adult kidney remain largely unexplored. Here, we demonstrate that GATA3 is specifically expressed in glomerular mesangial cells and plays a critical role in the maintenance of renal glomerular function. Newly generated Gata3 hypomorphic mutant mice exhibited neonatal lethality associated with severe renal hypoplasia. Normal kidney size was restored by breeding the hypomorphic mutant with a rescuing transgenic mouse line bearing a 662-kb Gata3 yeast artificial chromosome (YAC), and these animals (termed G3YR mice) survived to adulthood. However, most of the G3YR mice showed degenerative changes in glomerular mesangial cells, which deteriorated progressively during postnatal development. Consequently, the G3YR adult mice suffered severe renal failure. We found that the 662-kb Gata3 YAC transgene recapitulated Gata3 expression in the renal tubules but failed to direct sufficient GATA3 activity to mesangial cells. Renal glomeruli of the G3YR mice had significantly reduced amounts of platelet-derived growth factor receptor (PDGFR), which is known to participate in the development and maintenance of glomerular mesangial cells. These results demonstrate a critical role for GATA3 in the maintenance of mesangial cells and its absolute requirement for prevention of glomerular disease. PMID:27296697

  14. Rescue of heavy metal effects on cell physiology of the algal model system Micrasterias by divalent ions.

    Science.gov (United States)

    Volland, Stefanie; Bayer, Elisabeth; Baumgartner, Verena; Andosch, Ancuela; Lütz, Cornelius; Sima, Evelyn; Lütz-Meindl, Ursula

    2014-01-15

    Recent studies have shown that metals such as copper, zinc, aluminum, cadmium, chromium, iron and lead cause severe dose-dependent disturbances in growth, morphogenesis, photosynthetic and respiratory activity as well as on ultrastructure and function of organelles in the algal model system Micrasterias denticulata (Volland et al., 2011, 2012; Andosch et al., 2012). In the present investigation we focus on amelioration of these adverse effects of cadmium, chromium and lead by supplying the cells with different antioxidants and essential micronutrients to obtain insight into metal uptake mechanisms and subcellular metal targets. This seems particularly interesting as Micrasterias is adapted to extremely low-concentrated, oligotrophic conditions in its natural bog environment. The divalent ions of iron, zinc and calcium were able to diminish the effects of the metals cadmium, chromium and lead on Micrasterias. Iron showed most ameliorating effects on cadmium and chromium in short- and long-term treatments and improved cell morphogenesis, ultrastructure, cell division rates and photosynthesis. Analytical transmission electron microscopic (TEM) methods (electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI)) revealed that chromium uptake was decreased when Micrasterias cells were pre-treated with iron, which resulted in no longer detectable intracellular chromium accumulations. Zinc rescued the detrimental effects of chromium on net-photosynthesis, respiration rates and electron transport in PS II. Calcium and gadolinium were able to almost completely compensate the inhibiting effects of lead and cadmium on cell morphogenesis after mitosis, respectively. These results indicate that cadmium is taken up by calcium and iron transporters, whereas chromium appears to enter the algae cells via iron and zinc carriers. It was shown that lead is not taken up into Micrasterias at all but exerts its adverse effects on cell growth by substituting cell

  15. Rescue of heavy metal effects on cell physiology of the algal model system Micrasterias by divalent ions

    Science.gov (United States)

    Volland, Stefanie; Bayer, Elisabeth; Baumgartner, Verena; Andosch, Ancuela; Lütz, Cornelius; Sima, Evelyn; Lütz-Meindl, Ursula

    2014-01-01

    Recent studies have shown that metals such as copper, zinc, aluminum, cadmium, chromium, iron and lead cause severe dose-dependent disturbances in growth, morphogenesis, photosynthetic and respiratory activity as well as on ultrastructure and function of organelles in the algal model system Micrasterias denticulata (Volland et al., 2011, 2012; Andosch et al., 2012). In the present investigation we focus on amelioration of these adverse effects of cadmium, chromium and lead by supplying the cells with different antioxidants and essential micronutrients to obtain insight into metal uptake mechanisms and subcellular metal targets. This seems particularly interesting as Micrasterias is adapted to extremely low-concentrated, oligotrophic conditions in its natural bog environment. The divalent ions of iron, zinc and calcium were able to diminish the effects of the metals cadmium, chromium and lead on Micrasterias. Iron showed most ameliorating effects on cadmium and chromium in short- and long-term treatments and improved cell morphogenesis, ultrastructure, cell division rates and photosynthesis. Analytical transmission electron microscopic (TEM) methods (electron energy loss spectroscopy (EELS) and electron spectroscopic imaging (ESI)) revealed that chromium uptake was decreased when Micrasterias cells were pre-treated with iron, which resulted in no longer detectable intracellular chromium accumulations. Zinc rescued the detrimental effects of chromium on net-photosynthesis, respiration rates and electron transport in PS II. Calcium and gadolinium were able to almost completely compensate the inhibiting effects of lead and cadmium on cell morphogenesis after mitosis, respectively. These results indicate that cadmium is taken up by calcium and iron transporters, whereas chromium appears to enter the algae cells via iron and zinc carriers. It was shown that lead is not taken up into Micrasterias at all but exerts its adverse effects on cell growth by substituting cell

  16. Calcium influx rescues adenylate cyclase-hemolysin from rapid cell membrane removal and enables phagocyte permeabilization by toxin pores.

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    Radovan Fiser

    Full Text Available Bordetella adenylate cyclase toxin-hemolysin (CyaA penetrates the cytoplasmic membrane of phagocytes and employs two distinct conformers to exert its multiple activities. One conformer forms cation-selective pores that permeabilize phagocyte membrane for efflux of cytosolic potassium. The other conformer conducts extracellular calcium ions across cytoplasmic membrane of cells, relocates into lipid rafts, translocates the adenylate cyclase enzyme (AC domain into cells and converts cytosolic ATP to cAMP. We show that the calcium-conducting activity of CyaA controls the path and kinetics of endocytic removal of toxin pores from phagocyte membrane. The enzymatically inactive but calcium-conducting CyaA-AC⁻ toxoid was endocytosed via a clathrin-dependent pathway. In contrast, a doubly mutated (E570K+E581P toxoid, unable to conduct Ca²⁺ into cells, was rapidly internalized by membrane macropinocytosis, unless rescued by Ca²⁺ influx promoted in trans by ionomycin or intact toxoid. Moreover, a fully pore-forming CyaA-ΔAC hemolysin failed to permeabilize phagocytes, unless endocytic removal of its pores from cell membrane was decelerated through Ca²⁺ influx promoted by molecules locked in a Ca²⁺-conducting conformation by the 3D1 antibody. Inhibition of endocytosis also enabled the native B. pertussis-produced CyaA to induce lysis of J774A.1 macrophages at concentrations starting from 100 ng/ml. Hence, by mediating calcium influx into cells, the translocating conformer of CyaA controls the removal of bystander toxin pores from phagocyte membrane. This triggers a positive feedback loop of exacerbated cell permeabilization, where the efflux of cellular potassium yields further decreased toxin pore removal from cell membrane and this further enhances cell permeabilization and potassium efflux.

  17. Radiation response and cell cycle regulation of p53 rescued malignant keratinocytes

    International Nuclear Information System (INIS)

    Mutations in the tumor suppressor gene p53 were found in more than 90% of all human squamous cell carcinomas (SCC). To study the function of p53 in a keratinocyte background, a tetracycline-controlled p53 transgene was introduced into a human SCC cell line (SCC15), lacking endogenous p53. Conditional expression of wild-type p53 protein upon withdrawal of tetracycline was accompanied with increased expression of p21WAF1/Cip1 resulting in reduced cell proliferation. Flow-cytometric analysis revealed that these cells were transiently arrested in the G1/S phase of the cell cycle. However, when SCC15 cells expressing p53 were exposed to ionizing radiation (IR), a clear shift from a G1/S to a G2/M cell cycle arrest was observed. This effect was greatly depending on the presence of wild-type p53, as it was not observed to the same extent in SCC15 cells lacking p53. Unexpectedly, the p53- and IR-dependent G2/M cell cycle arrest in the keratinocyte background was not depending on increased expression or stabilization of 14-3-3σ, a p53-regulated effector of G2/M progression in colorectal cancer cells. In keratinocytes, 14-3-3σ (stratifin) is involved in terminal differentiation and its cell cycle function in this cell type might diverge from the one it fulfills in other cellular backgrounds

  18. Human embryonic mesenchymal stem cell-derived conditioned medium rescues kidney function in rats with established chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Arianne van Koppen

    Full Text Available Chronic kidney disease (CKD is a major health care problem, affecting more than 35% of the elderly population worldwide. New interventions to slow or prevent disease progression are urgently needed. Beneficial effects of mesenchymal stem cells (MSC have been described, however it is unclear whether the MSCs themselves or their secretome is required. We hypothesized that MSC-derived conditioned medium (CM reduces progression of CKD and studied functional and structural effects in a rat model of established CKD. CKD was induced by 5/6 nephrectomy (SNX combined with L-NNA and 6% NaCl diet in Lewis rats. Six weeks after SNX, CKD rats received either 50 µg CM or 50 µg non-CM (NCM twice daily intravenously for four consecutive days. Six weeks after treatment CM administration was functionally effective: glomerular filtration rate (inulin clearance and effective renal plasma flow (PAH clearance were significantly higher in CM vs. NCM-treatment. Systolic blood pressure was lower in CM compared to NCM. Proteinuria tended to be lower after CM. Tubular and glomerular damage were reduced and more glomerular endothelial cells were found after CM. DNA damage repair was increased after CM. MSC-CM derived exosomes, tested in the same experimental setting, showed no protective effect on the kidney. In a rat model of established CKD, we demonstrated that administration of MSC-CM has a long-lasting therapeutic rescue function shown by decreased progression of CKD and reduced hypertension and glomerular injury.

  19. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Zhou, Ling [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Zhang, Yan-ling [School of Biotechnology, Southern Medical University, Guangzhou 510515 (China); Huang, Bi-jun; Ke, Miao-la; Chen, Jie-min [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Li, Li-xia [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010 (China); Fu, Xiang; Wu, Jiang-xue [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Huang, Wenlin, E-mail: hwenl@mail.sysu.edu.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060 (China); Guangdong Provincial Key Laboratory of Tumor-Targeted Drug, Doublle Bioproducts Inc., Guangzhou 510663 (China)

    2013-12-13

    Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.

  20. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Science.gov (United States)

    Claveria-Gimeno, Rafael; Vega, Sonia; Grazu, Valeria; de la Fuente, Jesús M; Lanas, Angel; Velazquez-Campoy, Adrian; Abian, Olga

    2015-01-01

    In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 μM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule. PMID:25834436

  1. Transient overexpression of Werner protein rescues starvation induced autophagy in Werner syndrome cells.

    Science.gov (United States)

    Maity, Jyotirindra; Bohr, Vilhelm A; Laskar, Aparna; Karmakar, Parimal

    2014-12-01

    Reduced autophagy may be associated with normal and pathological aging. Here we report a link between autophagy and Werner protein (WRNp), mutated in Werner syndrome, the human premature aging Werner syndrome (WS). WRN mutant fibroblast AG11395 and AG05229 respond weakly to starvation induced autophagy compared to normal cells. While the fusion of phagosomes with lysosome is normal, WS cells contain fewer autophagy vacuoles. Cellular starvation autophagy in WS cells is restored after transfection with full length WRN. Further, siRNA mediated silencing of WRN in the normal fibroblast cell line WI-38 results in decreased autophagy and altered expression of autophagy related proteins. Thus, our observations suggest that WRN may have a role in controlling autophagy and hereby cellular maintenance. PMID:25257404

  2. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients

    Directory of Open Access Journals (Sweden)

    Isabel Sada-Ovalle

    2015-10-01

    Full Text Available Introduction: T cell immunoglobulin and mucin domain (Tim 3 and programmed death 1 (PD-1 are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction. High expression of Tim-3 and PD-1 is induced after chronic antigen-specific stimulation of T cells during HIV infection. We have previously demonstrated that the interaction of Tim-3 with its ligand galectin-9 induces macrophage activation and killing of Mycobacterium tuberculosis. Our aim in this study was to analyze the Tim-3 expression profile before and after six months of antiretroviral therapy and the impact of Tim-3 and PD-1 blocking on immunity against M. tuberculosis. Materials and methods: HIV+ patients naïve to anti-retroviral therapy (ART were followed up for six months. Peripheral immune-cell phenotype (CD38/HLA-DR/galectin-9/Tim-3 and PD-1 was assessed by flow cytometry. Supernatants were analyzed with a multiplex cytokine detection system (human Th1/Th2 cytokine Cytometric Bead Array by flow cytometry. Control of bacterial growth was evaluated by using an in vitro experimental model in which virulent M. tuberculosis-infected macrophages were cultured with T cells in the presence or absence of Tim-3 and PD-1 blocking antibodies. Interleukin-1 beta treatment of infected macrophages was evaluated by enumerating colony-forming units. Results: We showed that HIV+ patients had an increased expression of Tim-3 in T cells and were able to control bacterial growth before ART administration. By blocking Tim-3 and PD-1, macrophages and T cells recovered their functionality and had a higher ability to control bacterial growth; this result was partially dependent on the restitution of cytokine production. Conclusions: In this study, we demonstrated that increased Tim-3 expression can limit the ability of the immune system to control the infection of intracellular bacteria such as M. tuberculosis. The use of ART and

  3. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    International Nuclear Information System (INIS)

    Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  4. BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

    Energy Technology Data Exchange (ETDEWEB)

    Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

  5. Transcriptional activators HAP/NF-Y rescue a cytochrome c oxidase defect in yeast and human cells.

    Science.gov (United States)

    Fontanesi, Flavia; Jin, Can; Tzagoloff, Alexander; Barrientos, Antoni

    2008-03-15

    Cell survival and energy production requires a functional mitochondrial respiratory chain. Biogenesis of cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is a very complicated process and requires the assistance of a large number of accessory factors. Defects in COX assembly alter cellular respiration and produce severe human encephalomyopathies. Mutations in SURF1, a COX assembly factor of exact unknown function, produce Leigh's syndrome (LS), the most frequent cause of COX deficiency in infants. In the yeast Saccharomyces cerevisiae, deletion of the SURF1 homologue SHY1 results in a similar COX deficiency. In order to identify genetic modifiers of the shy1 mutant phenotype, we have explored for genetic interactions involving SHY1. Here we report that overexpression of Hap4p, the catalytic subunit of the CCAAT binding transcriptional activator Hap2/3/4/5p complex, suppresses the respiratory defect of yeast shy1 mutants by increasing the expression of nuclear-encoded COX subunits that interact with the mitochondrially encoded Cox1p. Analogously, overexpression of the Hap complex human homologue NF-YA/B/C transcription complex in SURF1-deficient fibroblasts from an LS patient efficiently rescues their COX deficiency. PMID:18045776

  6. Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia

    Science.gov (United States)

    Jung, Christian B; Moretti, Alessandra; Mederos y Schnitzler, Michael; Iop, Laura; Storch, Ursula; Bellin, Milena; Dorn, Tatjana; Ruppenthal, Sandra; Pfeiffer, Sarah; Goedel, Alexander; Dirschinger, Ralf J; Seyfarth, Melchior; Lam, Jason T; Sinnecker, Daniel; Gudermann, Thomas; Lipp, Peter; Laugwitz, Karl-Ludwig

    2012-01-01

    Coordinated release of calcium (Ca2+) from the sarcoplasmic reticulum (SR) through cardiac ryanodine receptor (RYR2) channels is essential for cardiomyocyte function. In catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease characterized by stress-induced ventricular arrhythmias in young patients with structurally normal hearts, autosomal dominant mutations in RYR2 or recessive mutations in calsequestrin lead to aberrant diastolic Ca2+ release from the SR causing arrhythmogenic delayed after depolarizations (DADs). Here, we report the generation of induced pluripotent stem cells (iPSCs) from a CPVT patient carrying a novel RYR2 S406L mutation. In patient iPSC-derived cardiomyocytes, catecholaminergic stress led to elevated diastolic Ca2+ concentrations, a reduced SR Ca2+ content and an increased susceptibility to DADs and arrhythmia as compared to control myocytes. This was due to increased frequency and duration of elementary Ca2+ release events (Ca2+ sparks). Dantrolene, a drug effective on malignant hyperthermia, restored normal Ca2+ spark properties and rescued the arrhythmogenic phenotype. This suggests defective inter-domain interactions within the RYR2 channel as the pathomechanism of the S406L mutation. Our work provides a new in vitro model to study the pathogenesis of human cardiac arrhythmias and develop novel therapies for CPVT. PMID:22174035

  7. Evaluation of FTA(®) card for the rescue of infectious foot-and-mouth disease virus by chemical transfection of extracted RNA in cultured cells.

    Science.gov (United States)

    Biswal, Jitendra K; Subramaniam, Saravanan; Ranjan, Rajeev; Pattnaik, Bramhadev

    2016-08-01

    Foot-and-mouth disease (FMD) is a highly contagious epidemic disease of transboundary importance. Inadequate storage and shipment of suspected clinical samples can compromise the ability to detect and characterise FMD virus (FMDV) in endemic countries, thereby, leading to the loss of valuable virological and epidemiological data. This study, investigates the potential of using FTA(®) cards for dry transportation of clinical samples and subsequent recovery of infectious FMDV by chemical transfection of FTA(®) card fixed RNA as an alternative to the conventional cell culture based virus isolation method. A higher proportion of infectious FMDV was rescued from clinical samples (cell culture isolates, tongue epithelial suspension and impression smears) by the FTA(®) card fixed RNA transfection method (76%) compared to the conventional cell culture based virus isolation (56%), suggesting a better performance of the current RNA transfection procedure. Furthermore, it was possible to rescue live virus by the transfection of RNA extracted from FTA(®) card impregnated with clinical samples that had been stored at varying temperature (4-37 °C) up to a period of six weeks. The VP1 sequence data and antigenic relationships with the vaccine strains, between viruses rescued by FTA(®) card fixed RNA transfection and conventional cell culture, were comparable. Therefore, these results support the use of the FTA(®) card for the economic, dry, non-hazardous transport of FMD suspected clinical samples from the site of collection to national/international reference laboratories. PMID:27321701

  8. Norepinephrine reuptake inhibition promotes mobilization in mice: potential impact to rescue low stem cell yields

    OpenAIRE

    Lucas, Daniel; Bruns, Ingmar; Battista, Michela; Mendez-Ferrer, Simon; Magnon, Claire; Kunisaki, Yuya; Frenette, Paul S.

    2012-01-01

    The mechanisms mediating hematopoietic stem and progenitor cell (HSPC) mobilization by G-CSF are complex. We have found previously that G-CSF–enforced mobilization is controlled by peripheral sympathetic nerves via norepinephrine (NE) signaling. In the present study, we show that G-CSF likely alters sympathetic tone directly and that methods to increase adrenergic activity in the BM microenvironment enhance progenitor mobilization. Peripheral sympathetic nerve neurons express the G-CSF recept...

  9. Identification of Compounds that Rescue IKBKAP Expression in Familial Dysautonomia-iPS Cells

    OpenAIRE

    Lee, Gabsang; Ramirez, Christina N.; Kim, Hyesoo; Zeltner, Nadja; Liu, Becky; Radu, Constantin; Bhinder, Bhavneet; Kim, Yong Jun; Choi, Inyoung; Mukherjee-Clavin, Bipasha; Djaballah, Hakim; Studer, Lorenz

    2012-01-01

    Patient-specific induced pluripotent stem cells (iPSCs) represent a novel system for modeling human genetic disease and could develop into a key drug discovery platform. We recently reported disease-specific phenotypes in iPSCs from familial dysautonomia (FD) patients. FD is a rare but fatal genetic disorder affecting neural crest lineages. Here we demonstrate the feasibility of performing a primary screen in FD-iPSC derived neural crest precursors. Out of 6,912 compounds tested we characteri...

  10. Gene targeting of X chromosome-linked chronic granulomatous disease locus in a human myeloid leukemia cell line and rescue by expression of recombinant gp91phox.

    OpenAIRE

    Zhen, L.; KING, A.A.; Xiao, Y.; Chanock, S. J.; Orkin, S H; Dinauer, M.C.

    1993-01-01

    The X chromosome-linked chronic granulomatous disease (X-CGD) locus, which encodes the gp91phox subunit of the phagocyte respiratory-burst oxidase cytochrome b, was disrupted by homologous recombination in the PLB-985 human myeloid cell line to develop an in vitro model of X-CGD. Superoxide formation was absent in targeted cells after differentiation to granulocytes but was rescued by stable transfection and expression of wild-type gp91phox cDNA. The targeted cell line should be useful in exp...

  11. Stem cell factor rescues dark epidermal pigmentation in discreet anatomic locations in albino and fair-skinned mice

    Science.gov (United States)

    Vanover, Jillian C.; Spry, Malinda L.; Hamilton, Laura; Wakamatsu, Kazumasa; Ito, Shosuke; D’Orazio, John A.

    2016-01-01

    We previously reported a transgenic animal model of variant pigmentation based on epidermal expression of stem cell factor (SCF) and well-characterized coat color genes bred into the C57Bl/6 background. In this system, constitutive expression of SCF by epidermal keratinocytes results in the maintenance of epidermal melanocytes in the interfollicular basal epidermal layer and subsequent pigmentation of the epidermis itself. In this report, we describe extending this animal model by developing a compound mutant transgenic amelanotic animal defective at both the melanocortin 1 receptor (Mc1r) and tyrosinase (Tyr) loci. We have observed SCF-dependent pigment deposition in specific anatomic regions regardless of tyrosinase (Tyr) or Mc1r genetic status. Thus, in the presence of K14-Scf, tyrosinase-null animals (previously thought incapable of synthesizing melanin) exhibited progressive robust epidermal pigmentation with age in the ears and tails. Furthermore, in the presence of the K14-Scf transgene, Tyr-defective animals demonstrated tyrosinase activity, suggesting that the c2j Tyr promoter defect is leaky and that Tyr expression can be rescued in part by SCF in the ears and tail. Lastly, we found that UV sensitivity of K14-Scf congenic animals differing only at the Mc1r or Tyr loci depended mainly on the amount of eumelanin present in the skin. These findings suggest that c-kit signaling can overcome the c2j Tyr promoter mutation in the ears and tails of aging animals but that UV resistance depends on accumulation of epidermal eumelanin. PMID:19682281

  12. Rescue vehicle Stirling engine

    Energy Technology Data Exchange (ETDEWEB)

    David Hainsworth; Pete Nicolay [CSIRO Exploration & Mining (Australia)

    2001-03-15

    The aim of this project was to develop a proof-of-concept Stirling engine and heat cell for use in the mining industry, primarily for underground applications. In particular, the Stirling engine, being an external combustion engine, offers the potential to operate on stored heat in low-oxygen or inert underground atmospheres. This makes it attractive for rescue vehicles, which are required to operate in such environments. A prototype Stirling engine with power output in the 15kW range was constructed and tested. Experimental measurements showed that this output was not achieved. While the basic thermodynamic principles of the design were valid, achieved output was well below the required value. The conclusion is that, because of the lack of commercial Stirling cycle-based products and the difficulty experienced in this project in overcoming the problem of high temperature seal implementation to produce a working prototype, the short term potential of the Stirling engine for mine rescue applications is limited.

  13. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy.

    Science.gov (United States)

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; Del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-06-15

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing dramatic extension of lifespan and global clinical-pathological rescue in a relevant GLD murine model. We show that timely and long-lasting delivery of functional GALC in affected tissues ensured by the exclusive complementary mode of action of the treatments underlies the outstanding benefit. In particular, the contribution of neural stem cell transplantation and IC GT during the early asymptomatic stage of the disease is instrumental to enhance long-term advantage upon BMT. We clarify the input of central nervous system, peripheral nervous system and periphery to the disease, and the relative contribution of treatments to the final therapeutic outcome, with important implications for treatment strategies to be tried in human patients. This study gives proof-of-concept of efficacy, tolerability and clinical relevance of the combined gene/cell therapies proposed here, which may constitute a feasible and effective therapeutic opportunity for children affected by GLD. PMID:25749991

  14. Inhibiting calpain, rescuing cells.

    OpenAIRE

    Robinson, A.

    1996-01-01

    Drs. John Elce and Peter Davies, biochemists at Queen's University, Kingston, Ont., are investigating the molecular structure of calpain, an enzyme that has been implicated in the cellular damage that occurs after such events as myocardial infarction and stroke. This damage is precipitated by an imbalance in the regulation of calpain that arises as an indirect result of ischemia. Elce and Davies hope that their research, which involves techniques such as recombinant DNA technology and x-ray c...

  15. Tgf-β1 inhibits Cftr biogenesis and prevents functional rescue of ΔF508-Cftr in primary differentiated human bronchial epithelial cells.

    Directory of Open Access Journals (Sweden)

    Steven M Snodgrass

    Full Text Available CFTR is an integral transmembrane glycoprotein and a cAMP-activated Cl(- channel. Mutations in the CFTR gene lead to Cystic Fibrosis (CF-an autosomal recessive disease with majority of the morbidity and mortality resulting from airway infection, inflammation, and fibrosis. The most common disease-associated mutation in the CFTR gene-deletion of Phe508 (ΔF508 leads to a biosynthetic processing defect of CFTR. Correction of the defect and delivery of ΔF508-CFTR to the cell surface has been highly anticipated as a disease modifying therapy. Compared to promising results in cultured cell this approach was much less effective in CF patients in an early clinical trial. Although the cause of failure to rescue ΔF508-CFTR in the clinical trial has not been determined, presence of factor(s that interfere with the rescue in vivo could be considered. The cytokine TGF-β1 is frequently elevated in CF patients. TGF-β1 has pleiotropic effects in different disease models and genetic backgrounds and little is known about TGF-β1 effects on CFTR in human airway epithelial cells. Moreover, there are no published studies examining TGF-β1 effects on the functional rescue of ΔF508-CFTR. Here we found that TGF-β1 inhibits CFTR biogenesis by reducing mRNA levels and protein abundance in primary differentiated human bronchial epithelial (HBE cells from non-CF individuals. TGF-β1 inhibits CFTR biogenesis without compromising the epithelial phenotype or integrity of HBE cells. TGF-β1 also inhibits biogenesis and impairs the functional rescue of ΔF508-CFTR in HBE cells from patients homozygous for the ΔF508 mutation. Our data indicate that activation of TGF-β1 signaling may inhibit CFTR function in non-CF individuals and may interfere with therapies directed at correcting the processing defect of ΔF508-CFTR in CF patients.

  16. Lignan Glycosides from Gentianella Acuta (Michx. Hulten. and Their Protective Effects Against H 2O 2-Induced Apoptosis in H9c2 Cardiomyoblasts

    Directory of Open Access Journals (Sweden)

    Ying Yu

    2014-05-01

    Full Text Available T wo new lignan glycosides named acutosides A (1 and B (2 have been isolated from the whole plant of Gentianella acute (Michx Hulten. and t heir structures were determined as (--(7 R ,8S,7'E-4-hydroxy-3, 3 '-dimethoxy-7,4'-epoxy-8, 5 '-neolign-7'-ene-9,9'-diol 9'-ethyl ether -4-O-β-D- glucopyranosid e and (--(7 R ,8S,7'E-4-hydroxy-3, 3 '-dimethoxy-7,4'-epoxy-8, 5 '-neolign-7'-ene-9,9'-diol 9-ethyl ether -9 ' -O-β-D- glucopyranosid e by means of 1D-, 2D-NMR , HR -ESI -MS , CD techniques and chemical reactions. Along with the above two new compounds we got six known ones: (7R,8S-dehydrodiconiferyl alcohol-4,9 ' -di-O-β-D- glucopyranosid e (3 , alaschanisoside A (4 , citrusin A (5 , 8,4',9'-trihydroxy-3,3'-dimethoxy-9,7'-epoxylignan 4-O- β -D- glucopyranosid e (6 , l eptolepisol D (7 and acanthoside D (8 . The cardioprotective effects of compounds 1-8 were evaluated by measuring the viability of the compounds 1-8 pretreated H9c2 cardiomyoblasts after exposure to H 2O 2-induced apoptosis, the results showed that compounds 1,3,6,8 which could increase cell viability >15% at 200 μM had remarkably protective influence against H 2O 2-induced apoptosis. All the compounds were tested for cytotoxicity against two human tumor cell lines: gastric cancer SGC-7901 and breast cancer MCF-7. But they were inactive (IC 50>40 μM.

  17. Enhanced Rescue Lift Capability

    Science.gov (United States)

    Young, Larry A.

    2007-01-01

    The evolving and ever-increasing demands of emergency response and disaster relief support provided by rotorcraft dictate, among other things, the development of enhanced rescue lift capability for these platforms. This preliminary analysis is first-order in nature but provides considerable insight into some of the challenges inherent in trying to effect rescue using a unique form of robotic rescue device deployed and operated from rotary-wing aerial platforms.

  18. Proposed strategy for the use of high-dose chemotherapy with stem cell rescue and intrathecal topotecan without whole-brain irradiation for infantile classic medulloblastoma.

    Science.gov (United States)

    Yamada, Ai; Moritake, Hiroshi; Kamimura, Sachiyo; Yamashita, Shinji; Takeshima, Hideo; Nunoi, Hiroyuki

    2014-12-01

    We describe a 6-month-old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate-based chemotherapy. After undergoing resection, high-dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high-dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole-brain irradiation for infantile classic medulloblastoma. PMID:25174961

  19. Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) is a promising treatment approach for B-cell lymphomas. This is our first opportunity to report long-term follow-up data and late toxicities in 29 patients treated with myeloablative doses of iodine-131-anti-CD20 antibody (anti-B1) and autologous stem-cell rescue. PATIENTS AND METHODS: Trace-labeled biodistribution studies first determined the ability to deliver higher absorbed radiation doses to tumor sites than to lung, liver, or kidney at varying amounts of anti-B1 protein (0.35, 1.7, or 7 mg/kg). Twenty- nine patients received therapeutic infusions of single-agent (131)I- anti-B1, given at the protein dose found optimal in the biodistribution study, labeled with amounts of (131)I (280 to 785 mCi[10.4 to 29.0 GBq]) calculated to deliver specific absorbed radiation doses to the normal organs, followed by autologous stem-cell support. RESULTS: Major responses occurred in 25 patients (86%), with 23 complete responses (CRs; 79%). The nonhematopoietic do se-limiting toxicity was reversible cardiopulmonary insufficiency, which occurred in two patients at RIT doses that delivered > or = 27 Gy to the lungs. With a median follow-up time of 42 months, the estimated overall and progression-free survival rates are 68% and 42%, respectively. Currently, 14 of 29 patients remain in unmaintained remissions that range from 27+ to 87+ months after RIT. Late toxicities have been uncommon except for elevated thyroid-stimulating hormone (TSH) levels found in approximately 60% of the subjects. Two patients developed second malignancies, but none have developed myelodysplasia (MDS). CONCLUSION: Myeloablative (131)I-anti- B1 RIT is relatively well tolerated when given with autologous stem- cell support and often results in prolonged remission durations with few late toxicities

  20. Hi-tech Rescue

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Following the May 12 earthquake in Sichuan Province,rescue teams from across China have been racing against time to save as many people in the disaster area as possible.Among them is a squad clad in eye-catching orange uniforms whose members are better equipped than other rescuers and demonstrate higher levels of skill. It is the country’s best- trained earthquake emergency response team—the China National Earthquake Disaster Emergency Response and Rescue Team,also known as the China International Search and Rescue Team when it performs missions abroad.

  1. Rescue of DNA-PK Signaling and T-Cell Differentiation by Targeted Genome Editing in a prkdc Deficient iPSC Disease Model.

    Directory of Open Access Journals (Sweden)

    Shamim H Rahman

    2015-05-01

    Full Text Available In vitro disease modeling based on induced pluripotent stem cells (iPSCs provides a powerful system to study cellular pathophysiology, especially in combination with targeted genome editing and protocols to differentiate iPSCs into affected cell types. In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID, a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK activity. Our results demonstrate that gene editing in RS-SCID fibroblasts rescued DNA-PK dependent signaling to overcome radiosensitivity. Furthermore, in vitro T-cell differentiation from iPSCs was employed to model the stage-specific T-cell maturation block induced by the disease causing mutation. Genetic correction of the RS-SCID iPSCs restored T-lymphocyte maturation, polyclonal V(DJ recombination of the T-cell receptor followed by successful beta-selection. In conclusion, we provide proof that iPSC-based in vitro T-cell differentiation is a valuable paradigm for SCID disease modeling, which can be utilized to investigate disorders of T-cell development and to validate gene therapy strategies for T-cell deficiencies. Moreover, this study emphasizes the significance of designer nucleases as a tool for generating isogenic disease models and their future role in producing autologous, genetically corrected transplants for various clinical applications.

  2. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    Science.gov (United States)

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium. PMID:26726947

  3. Hypoxia/Reoxygenation-Preconditioned Human Bone Marrow-Derived Mesenchymal Stromal Cells Rescue Ischemic Rat Cortical Neurons by Enhancing Trophic Factor Release.

    Science.gov (United States)

    Kim, Young Seo; Noh, Min Young; Cho, Kyung Ah; Kim, Hyemi; Kwon, Min-Soo; Kim, Kyung Suk; Kim, Juhan; Koh, Seong-Ho; Kim, Seung Hyun

    2015-08-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent a promising tool for stem cell-based therapies. However, the majority of MSCs fail to reach the injury site and have only minimal therapeutic effect. In this study, we assessed whether hypoxia/reoxygenation (H/R) preconditioning of human BM-MSCs could increase their functional capacity and beneficial effect on ischemic rat cortical neurons. Human BM-MSCs were cultured under hypoxia (1% O2) and with long-term reoxygenation for various times to identify the optimal conditions for increasing their viability and proliferation. The effects of H/R preconditioning on the BM-MSCs were assessed by analyzing the expression of prosurvival genes, trophic factors, and cell migration assays. The functionally improved BM-MSCs were cocultured with ischemic rat cortical neurons to compare with normoxic cultured BM-MSCs. Although the cell viability and proliferation of BM-MSCs were reduced after 1 day of hypoxic culture (1% O2), when this was followed by 5-day reoxygenation, the BM-MSCs recovered and multiplied extensively. The immunophenotype and trilineage differentiation of BM-MSCs were also maintained under this H/R preconditioning. In addition, the preconditioning enhanced the expression of prosurvival genes, the messenger RNA (mRNA) levels of various trophic factors and migration capacity. Finally, coculture with the H/R-preconditioned BM-MSCs promoted the survival of ischemic rat cortical neurons. H/R preconditioning of BM-MSCs increases prosurvival signals, trophic factor release, and cell migration and appears to increase their ability to rescue ischemic cortical neurons. This optimized H/R preconditioning procedure could provide the basis for a new strategy for stem cell therapy in ischemic stroke patients. PMID:25288154

  4. Reexpression of glial fibrillary acidic protein rescues the ability of astrocytoma cells to form processes in response to neurons

    OpenAIRE

    1994-01-01

    Astroglial cells play an important role in orchestrating the migration and positioning of neurons during central nervous system development. Primary astroglia, as well as astrocytoma cells will extend long stable processes when co-cultured with granule neurons. In order to determine the function of the glial fibrillary acidic protein (GFAP), the major intermediate filament protein in astroglia and astrocytoma cells, we suppressed the expression of GFAP by stable transfection of an anti- sense...

  5. Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells

    OpenAIRE

    Altarche-Xifro, Wassim; Di Vicino, Umberto; Muñoz-Martin, Maria Isabel; Bortolozzi, Analía; Bové, Jordi; Vila, Miquel; Cosma, Maria Pia

    2016-01-01

    Parkinson's disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinson's disease,...

  6. Inefficient boosting of antitumor CD8+ T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions

    OpenAIRE

    Zhi-Iong Ma, Joel; Yang, Jianping; Qin, Jim S.; Richter, Antonia; PERRET, Rachel; El-Deiry, Wafik S.; Finnberg, Niklas; Ronchese, Franca

    2012-01-01

    Dendritic cells (DCs) are powerful activators of primary and secondary immune responses and have promising activity as anticancer vaccines. However, various populations of immune cells, including natural killer cells, regulatory T cells and especially cytotoxic T lymphocytes (CTLs), can inhibit DC function through cytotoxic clearance. Spontaneous tumor-specific CTL responses are frequently observed in patients before immunotherapy, and it is unclear how such pre-existing responses may affect ...

  7. Xenografted Islet Cell Clusters From INSLEA29Y Transgenic Pigs Rescue Diabetes and Prevent Immune Rejection in Humanized Mice

    OpenAIRE

    Klymiuk, Nikolai; van Buerck, Lelia; Bähr, Andrea; Offers, Monika; Kessler, Barbara; Wuensch, Annegret; Kurome, Mayuko; Thormann, Michael; Lochner, Katharina; Nagashima, Hiroshi; Herbach, Nadja; Wanke, Rüdiger; Seissler, Jochen; Wolf, Eckhard

    2012-01-01

    Islet transplantation is a potential treatment for type 1 diabetes, but the shortage of donor organs limits its routine application. As potential donor animals, we generated transgenic pigs expressing LEA29Y, a high-affinity variant of the T-cell costimulation inhibitor CTLA-4Ig, under the control of the porcine insulin gene promoter. Neonatal islet cell clusters (ICCs) from INSLEA29Y transgenic (LEA-tg) pigs and wild-type controls were transplanted into streptozotocin-induced hyperglycemic N...

  8. Therapeutic envelope vaccination in combination with antiretroviral therapy temporarily rescues SIV-specific CD4⁺ T-cell-dependent natural killer cell effector responses in chronically infected rhesus macaques.

    Science.gov (United States)

    Vargas-Inchaustegui, Diego A; Xiao, Peng; Demberg, Thorsten; Pal, Ranajit; Robert-Guroff, Marjorie

    2015-06-01

    Natural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4(+) T-cell co-operative immune responses exist in long-term simian immunodeficiency virus (SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy (ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11 weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4(+) T cells in all macaques, and increased T-cell-dependent envelope- and gag-specific interferon-γ and tumour necrosis factor-α production by circulatory CD56(+) NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals. PMID:25626488

  9. The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy

    Science.gov (United States)

    Foldvari, Marianna; Chen, Ding Wen

    2016-01-01

    Regeneration of damaged retinal ganglion cells (RGC) and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufficient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also discuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efficient and representative in vitro models for rapid and reliable screening in the drug development process.

  10. Electroacupuncture at ST36 ameliorates gastric emptying and rescues networks of interstitial cells of Cajal in the stomach of diabetic rats.

    Directory of Open Access Journals (Sweden)

    Yan Chen

    Full Text Available Depletion of interstitial cells of Cajal (ICC is certified in the stomach of diabetic patients. Though electroacupuncture (EA at ST36 is an effective therapy to regulate gastric motility, the mechanisms of EA at ST36 on gastric emptying and networks of ICC remain to be elucidated. The aims of this study were to investigate the effects of EA on gastric emptying and on the alterations of ICC networks. Rats were randomized into the control, diabetic rats (DM, diabetic rats with sham EA (DM+SEA, diabetic rats with low frequency EA (DM+LEA and diabetic rats with high frequency EA groups (DM+HEA. The expression of c-kit in each layer of gastric wall was assessed by western blotting. The proliferation of ICC was identified by immunolabeling of c-kit and Ki67 as the apoptosis of ICC was examined by TUNEL staining. The results were as follows: (1 Gastric emptying was severely delayed in the DM group, but accelerated in the LEA and HEA group, especially in the LEA group. (2 The expression of c-kit in each layer was reduced apparently in the DM group, but also up-regulated in the LEA and HEA group. (3 Plentiful proliferated ICC (c-kit+/Ki67+ forming bushy networks with c-kit+ cells were observed in the LEA and HEA group, while the apoptotic cells (c-kit+/TUNEL+ were hardly captured in the LEA and HEA group. Collectively, low and high frequency EA at ST36 rescue the damaged networks of ICC by inhibiting the apoptosis and enhancing the proliferation in the stomach of diabetic rats, resulting in an improved gastric emptying.

  11. Electroacupuncture at ST36 ameliorates gastric emptying and rescues networks of interstitial cells of Cajal in the stomach of diabetic rats.

    Science.gov (United States)

    Chen, Yan; Xu, Juan Juan; Liu, Shi; Hou, Xiao Hua

    2013-01-01

    Depletion of interstitial cells of Cajal (ICC) is certified in the stomach of diabetic patients. Though electroacupuncture (EA) at ST36 is an effective therapy to regulate gastric motility, the mechanisms of EA at ST36 on gastric emptying and networks of ICC remain to be elucidated. The aims of this study were to investigate the effects of EA on gastric emptying and on the alterations of ICC networks. Rats were randomized into the control, diabetic rats (DM), diabetic rats with sham EA (DM+SEA), diabetic rats with low frequency EA (DM+LEA) and diabetic rats with high frequency EA groups (DM+HEA). The expression of c-kit in each layer of gastric wall was assessed by western blotting. The proliferation of ICC was identified by immunolabeling of c-kit and Ki67 as the apoptosis of ICC was examined by TUNEL staining. The results were as follows: (1) Gastric emptying was severely delayed in the DM group, but accelerated in the LEA and HEA group, especially in the LEA group. (2) The expression of c-kit in each layer was reduced apparently in the DM group, but also up-regulated in the LEA and HEA group. (3) Plentiful proliferated ICC (c-kit+/Ki67+) forming bushy networks with c-kit+ cells were observed in the LEA and HEA group, while the apoptotic cells (c-kit+/TUNEL+) were hardly captured in the LEA and HEA group. Collectively, low and high frequency EA at ST36 rescue the damaged networks of ICC by inhibiting the apoptosis and enhancing the proliferation in the stomach of diabetic rats, resulting in an improved gastric emptying. PMID:24391842

  12. Follicle-stimulating hormone-induced rescue of cumulus cell apoptosis and enhanced development ability of buffalo oocytes.

    Science.gov (United States)

    Jain, A; Jain, T; Kumar, P; Kumar, M; De, S; Gohain, M; Kumar, R; Datta, T K

    2016-04-01

    The effect of follicle-stimulating hormone (FSH) on apoptotic status of cumulus cells, expression of proapoptotic and antiapoptotic genes, and development rate of in vitro fertilization-produced buffalo embryos were investigated. FSH supplementation in in vitro maturation-medium resulted in a dose-dependent reduction in the expression of proapoptotic genes namely, BCL2-associated X protein (BAX), cytochrome c, and caspase-3 and increase in the expression of antiapoptotic genes such as B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) in cumulus cells of mature oocyte. Cumulus expansion, oocyte maturation, cleavage, and blastocyst development rates were significantly higher (P FSH-supplemented groups as compared with control. Significant increase in the expression of FSH receptor messenger RNA was also found with 5 and 10-μg/mL FSH (P oocytes was reduced in the FSH-treated groups as compared with control (P FSH may attenuate apoptosis in cumulus cells via mitochondria-dependent apoptotic pathway by increasing XIAP expression, resulting in a more favorable ratio of BCL2/BAX expression and decreasing the cytochrome c and caspase-3 expression, eventually contributing to developmental competence of oocytes. The information generated will help in improving the in vitro embryo production program in buffalo. PMID:26774556

  13. Molecular Events Accompanying Rous Sarcoma Virus Rescue from Rodent Cells and the Role of Viral Gene Complementation

    Czech Academy of Sciences Publication Activity Database

    Lounková, Anna; Dráberová, Eduarda; Šenigl, Filip; Trejbalová, Kateřina; Geryk, Josef; Hejnar, Jiří; Svoboda, Jan

    2014-01-01

    Roč. 88, č. 6 (2014), s. 3505-3515. ISSN 0022-538X R&D Projects: GA ČR GAP502/11/2207; GA ČR GAP302/12/1673 Institutional support: RVO:68378050 Keywords : Rous sarcoma virus * heterotransmission * cell non-permissiveness Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.439, year: 2014

  14. Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage.

    Science.gov (United States)

    Maure, Jean-François; Moser, Sandra C; Jaffray, Ellis G; F Alpi, Arno; Hay, Ronald T

    2016-01-01

    SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways. PMID:27185577

  15. Palmitic acid interferes with energy metabolism balance by adversely switching the SIRT1-CD36-fatty acid pathway to the PKC zeta-GLUT4-glucose pathway in cardiomyoblasts.

    Science.gov (United States)

    Chen, Yeh-Peng; Tsai, Chia-Wen; Shen, Chia-Yao; Day, Cecilia-Hsuan; Yeh, Yu-Lan; Chen, Ray-Jade; Ho, Tsung-Jung; Padma, V Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2016-05-01

    Metabolic regulation is inextricably linked with cardiac function. Fatty acid metabolism is a significant mechanism for creating energy for the heart. However, cardiomyocytes are able to switch the fatty acids or glucose, depending on different situations, such as ischemia or anoxia. Lipotoxicity in obesity causes impairments in energy metabolism and apoptosis in cardiomyocytes. We utilized the treatment of H9c2 cardiomyoblast cells palmitic acid (PA) as a model for hyperlipidemia to investigate the signaling mechanisms involved in these processes. Our results show PA induces time- and dose-dependent lipotoxicity in H9c2 cells. Moreover, PA enhances cluster of differentiation 36 (CD36) and reduces glucose transporter type 4 (GLUT4) pathway protein levels following a short period of treatment, but cells switch from CD36 back to the GLUT4 pathway after during long-term exposure to PA. As sirtuin 1 (SIRT1) and protein kinase Cζ (PKCζ) play important roles in CD36 and GLUT4 translocation, we used the SIRT1 activator resveratrol and si-PKCζ to identify the switches in metabolism. Although PA reduced CD36 and increased GLUT4 metabolic pathway proteins, when we pretreated cells with resveratrol to activate SIRT1 or transfected si-PKCζ, both were able to significantly increase CD36 metabolic pathway proteins and reduce GLUT4 pathway proteins. High-fat diets affect energy metabolism pathways in both normal and aging rats and involve switching the energy source from the CD36 pathway to GLUT4. In conclusion, PA and high-fat diets cause lipotoxicity in vivo and in vitro and adversely switch the energy source from the CD36 pathway to the GLUT4 pathway. PMID:27133433

  16. Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost.

    OpenAIRE

    S.M. Lee; Radford, J. A.; Dobson, L.; Huq, T.; Ryder, W. D.; Pettengell, R; Morgenstern, G. R.; Scarffe, J. H.; Crowther, D.

    1998-01-01

    In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995. Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n ...

  17. Cell-Assisted Lipotransfer Improves Volume Retention in Irradiated Recipient Sites and Rescues Radiation-Induced Skin Changes

    Science.gov (United States)

    Luan, Anna; Duscher, Dominik; Whittam, Alexander J.; Paik, Kevin J.; Zielins, Elizabeth R.; Brett, Elizabeth A.; Atashroo, David A.; Hu, Michael S.; Lee, Gordon K.; Gurtner, Geoffrey C.; Longaker, Michael T.; Wan, Derrick C.

    2016-01-01

    Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy. PMID:26661694

  18. Restoration of Progranulin Expression Rescues Cortical Neuron Generation in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Susanna Raitano

    2015-01-01

    Full Text Available To understand how haploinsufficiency of progranulin (PGRN causes frontotemporal dementia (FTD, we created induced pluripotent stem cells (iPSCs from patients carrying the GRNIVS1+5G > C mutation (FTD-iPSCs. FTD-iPSCs were fated to cortical neurons, the cells most affected in FTD. Although generation of neuroprogenitors was unaffected, their further differentiation into CTIP2-, FOXP2-, or TBR1-TUJ1 double-positive cortical neurons, but not motorneurons, was significantly decreased in FTD-neural progeny. Zinc finger nuclease-mediated introduction of GRN cDNA into the AAVS1 locus corrected defects in cortical neurogenesis, demonstrating that PGRN haploinsufficiency causes inefficient cortical neuron generation. RNA sequencing analysis confirmed reversal of the altered gene expression profile following genetic correction. We identified the Wnt signaling pathway as one of the top defective pathways in FTD-iPSC-derived neurons, which was reversed following genetic correction. Differentiation of FTD-iPSCs in the presence of a WNT inhibitor mitigated defective corticogenesis. Therefore, we demonstrate that PGRN haploinsufficiency hampers corticogenesis in vitro.

  19. Trehalose rescues glial cell dysfunction in striatal cultures from HD R6/1 mice at early postnatal development.

    Science.gov (United States)

    Perucho, Juan; Gómez, Ana; Muñoz, María Paz; de Yébenes, Justo García; Mena, María Ángeles; Casarejos, María José

    2016-07-01

    The pathological hallmark of Huntington disease (HD) is the intracellular aggregation of mutant huntingtin (mHTT) in striatal neurons and glia associated with the selective loss of striatal medium-sized spiny neurons. Up to the present, the role of glia in HD is poorly understood and has been classically considered secondary to neuronal disorder. Trehalose is a disaccharide known to possess many pharmacological properties, acting as an antioxidant, a chemical chaperone, and an inducer of autophagy. In this study, we analyzed at an early postnatal development stage the abnormalities observed in striatal glial cell cultures of postnatal R6/1 mice (HD glia), under baseline and stressing conditions and the protective effects of trehalose. Our data demonstrate that glial HD alterations already occur at early stages of postnatal development. After 20 postnatal days in vitro, striatal HD glia cultures showed more reactive astrocytes with increased expression of glial fibrillary acidic protein (GFAP) but with less replication capacity, less A2B5(+) glial progenitors and more microglia than wild-type (WT) cultures. HD glia had lower levels of intracellular glutathione (GSH) and was more susceptible to H2O2 and epoxomicin insults. The amount of expressed GDNF and secreted mature-BDNF by HD astrocytes were much lower than by WT astrocytes. In addition, HD glial cultures showed a deregulation of the major proteolytic systems, the ubiquitin-proteasomal system (UPS), and the autophagic pathway. This produces a defective protein quality control, indicated by the elevated levels of ubiquitination and p62 protein. Interestingly, we show that trehalose, through its capacity to induce autophagy, inhibited p62/SQSTM1 accumulation and facilitated the degradation of cytoplasmic aggregates from mHTT and α-synuclein proteins. Trehalose also reduced microglia activation and reversed the disrupted cytoskeleton of astrocytes accompanied with an increase in the replication capacity. In

  20. Periplasmic expression of soluble single chain T cell receptors is rescued by the chaperone FkpA

    Directory of Open Access Journals (Sweden)

    Bogen Bjarne

    2010-02-01

    Full Text Available Abstract Background Efficient expression systems exist for antibody (Ab molecules, which allow for characterization of large numbers of individual Ab variants. In contrast, such expression systems have been lacking for soluble T cell receptors (TCRs. Attempts to generate bacterial systems have generally resulted in low yields and material which is prone to aggregation and proteolysis. Here we present an optimized periplasmic bacterial expression system for soluble single chain (sc TCRs. Results The effect of 1 over-expression of the periplasmic chaperon FkpA, 2 culture conditions and 3 molecular design was investigated. Elevated levels of FkpA allowed periplasmic soluble scTCR expression, presumably by preventing premature aggregation and inclusion body formation. Periplasmic expression enables disulphide bond formation, which is a prerequisite for the scTCR to reach its correct fold. It also enables quick and easy recovery of correctly folded protein without the need for time-consuming downstream processing. Expression without IPTG induction further improved the periplasmic expression yield, while addition of sucrose to the growth medium showed little effect. Shaker flask yield of mg levels of active purified material was obtained. The Vαβ domain orientation was far superior to the Vβα domain orientation regarding monomeric yield of functionally folded molecules. Conclusion The general expression regime presented here allows for rapid production of soluble scTCRs and is applicable for 1 high yield recovery sufficient for biophysical characterization and 2 high throughput screening of such molecules following molecular engineering.

  1. The rule of rescue.

    Science.gov (United States)

    McKie, John; Richardson, Jeff

    2003-06-01

    Jonsen coined the term "Rule of Rescue"(RR) to describe the imperative people feel to rescue identifiable individuals facing avoidable death. In this paper we attempt to draw a more detailed picture of the RR, identifying its conflict with cost-effectiveness analysis, the preference it entails for identifiable over statistical lives, the shock-horror response it elicits, the preference it entails for lifesaving over non-lifesaving measures, its extension to non-life-threatening conditions, and whether it is motivated by duty or sympathy. We also consider the measurement problems it raises, and argue that quantifying the RR would probably require a two-stage procedure. In the first stage the size of the individual utility gain from a health intervention would be assessed using a technique such as the Standard Gamble or the Time Trade-Off, and in the second the social benefits arising from the RR would be quantified employing the Person Trade-Off. We also consider the normative status of the RR. We argue that it can be defended from a utilitarian point of view, on the ground that rescues increase well-being by reinforcing people's belief that they live in a community that places great value upon life. However, utilitarianism has long been criticised for failing to take sufficient account of fairness, and the case is no different here: fairness requires that we do not discriminate between individuals on morally irrelevant grounds, whereas being "identifiable" does not seem to be a morally relevant ground for discrimination. PMID:12742604

  2. AIR / SEA RESCUE LAUNCHES

    Directory of Open Access Journals (Sweden)

    W.H. Rice

    2012-02-01

    Full Text Available The Motor Boat Wing of the South African Air Force was inaugurated some thirty eight years ago.With its main base at Gordon's Bay, the wing was formed to operate the various marine craft used to provide a service to the flying component of the South African Air Force. Its main function was to be air/sea rescue, but it also had to man and maintain armoured target boats, seaplane tenders, marine tenders and the 'bomb scows', used for recovering practise bombs and missiles and for laying and lifting moorings.

  3. Stimulation of adenosine A2A receptors reduces intracellular cholesterol accumulation and rescues mitochondrial abnormalities in human neural cell models of Niemann-Pick C1.

    Science.gov (United States)

    Ferrante, A; De Nuccio, C; Pepponi, R; Visentin, S; Martire, A; Bernardo, A; Minghetti, L; Popoli, P

    2016-04-01

    Niemann Pick C 1 (NPC1) disease is an incurable, devastating lysosomal-lipid storage disorder characterized by hepatosplenomegaly, progressive neurological impairment and early death. Current treatments are very limited and the research of new therapeutic targets is thus mandatory. We recently showed that the stimulation of adenosine A2A receptors (A2ARs) rescues the abnormal phenotype of fibroblasts from NPC1 patients suggesting that A2AR agonists could represent a therapeutic option for this disease. However, since all NPC1 patients develop severe neurological symptoms which can be ascribed to the complex pathology occurring in both neurons and oligodendrocytes, in the present paper we tested the effects of the A2AR agonist CGS21680 in human neuronal and oligodendroglial NPC1 cell lines (i.e. neuroblastoma SH-SY5Y and oligodendroglial MO3.13 transiently transfected with NPC1 small interfering RNA). The down-regulation of the NPC1 protein effectively resulted in intracellular cholesterol accumulation and altered mitochondrial membrane potential. Both effects were significantly attenuated by CGS21680 (500 nM). The protective effects of CGS were prevented by the selective A2AR antagonist ZM241385 (500 nM). The involvement of calcium modulation was demonstrated by the ability of Bapta-AM (5-7 μM) in reverting the effect of CGS. The A2A-dependent activity was prevented by the PKA-inhibitor KT5720, thus showing the involvement of the cAMP/PKA signaling. These findings provide a clear in vitro proof of concept that A2AR agonists are promising potential drugs for NPC disease. PMID:26631535

  4. [Importance of helicopter rescue].

    Science.gov (United States)

    Hofer, G; Voelckel, W G

    2014-03-01

    Helicopter emergency medical service (HEMS) have become a main part of prehospital emergency medical services over the last 40 years. Recently, an ongoing discussion about financial shortage and personal shortcomings question the role of cost-intensive air rescue. Thus, the value of HEMS must be examined and discussed appropriately. Since the number of physician-staffed ground ambulances may decrease due to the limited availability of qualified physicians, HEMS may fill the gap. In addition patient transfer to specialized hospitals will require an increasing number of air transports in order to minimize prehospital time. The higher risk ratio for HEMS missions when compared with ground rescue requires a rigorous quality management system. When it comes to missions in remote and exposed areas, the scope of medical treatment must be adjusted to the individual situation. Medical competence is key in order to balance guideline compliant or maximal care versus optimal care characterized as a mission-specific, individualized emergency care concept. Although, medical decision making and treatment is typically based on the best scientific evidence, personal skills, competence, and the mission scenario will determine the scope of interventions suitable to improve outcome. Thus, the profile of requirements for the HEMS medical crew is high. PMID:24618925

  5. Sex, Deportation and Rescue

    DEFF Research Database (Denmark)

    Plambech, Sine

    2016-01-01

    This contribution explores the economies interlinked by the migration of Nigerian women sex workers. The literature and politics of sex work migration and human trafficking economies are commonly relegated to the realm that focuses on profits for criminal networks and pimps, in particular...... recirculating the claim that human trafficking is the “third largest” criminal economy after drugs and weapons. Based on ethnographic fieldwork among Nigerian sex worker migrants conducted in Benin City, Nigeria, in 2011 and 2012, this study brings together four otherwise isolated migration economies...... – facilitation, remittances, deportation, and rescue – and suggests that we have to examine multiple sites and relink these in order to more fully understand the complexity of sex work migration. Drawing upon literature within transnational feminist analysis, critical human trafficking studies, and migration...

  6. High dose chemotherapy and stem cell rescue for aggressive non-Hodgkin's lymphoma: pattern of failure and implications for involved-field radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate the pattern of failure and outcome of patients with aggressive non-Hodgkin's lymphoma (NHL) undergoing high-dose chemotherapy (HDCT) and autologous stem cell rescue (SCR) with an emphasis on the role of adjuvant involved-field radiotherapy (IFRT). Method and Materials: Fifty-three adult patients with aggressive NHL (46 intermediate-and 7 high-grade) underwent HDCT with SCR. All patients underwent induction chemotherapy prior to high dose intensification. Seven (13.2%) received IFRT to 10 disease sites either prior to or following HDCT. Indication included symptomatic or bulky disease, persistent disease, or to consolidate a complete response (CR). Sites of relapse were designated as old (involved prior to HDCT) or new (previously uninvolved). Median followup was 20.1 months (range, 1.2-69.3 months). Results: The 4-year actuarial progression-free (PFS) and cause-specific (CSS) survivals of the entire group were 30.0 and 50.2%, respectively. Excluding toxic deaths, 24 patients (52.2%) relapsed. Sixteen (34.7%) failed in old and 15 (32.6%) in new sites. Patients treated with IFRT had a lower rate of relapse in old sites (0 vs. 41%) (p = 0.04) than patients treated with HDCT alone. Of the 141 sites present prior to induction, 127 (90.1%) were amenable to IFRT. Excluding irradiated sites, the overall 4-year local control (LC) of all amenable sites was 61.1%. Amenable sites failing to achieve a CR to induction had a poorer LC (32.0 vs. 95.1%) (p < 0.0001) than sites in CR. The 4-year LC of sites failing to achieve a CR to HDCT was 29.4%. Adjuvant IFRT improved the 4-year LC of all sites (100 vs. 61.1%) (p = 0.05), persistent sites following induction (100 vs. 32.0%) (p = 0.01) and persistent sites following HDCT (100 vs. 29.4%) (p = 0.01). Adjuvant IFRT was not associated with any untoward acute or late toxicity. Conclusions: The predominant site of relapse in patients with aggressive NHL undergoing HDCT and SCR is in sites of disease present prior

  7. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Directory of Open Access Journals (Sweden)

    Claveria-Gimeno R

    2015-03-01

    with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself. The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 µM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule. Keywords: primary and secondary screenings, drug activity, antiviral compounds, cyclodextrins, vehiculization, drug delivery, hepatitis C, NS3 protease, virus replicon system

  8. Bone marrow‑derived mesenchymal stem cells rescue injured H9c2 cells via transferring intact mitochondria through tunneling nanotubes in an in vitro simulated ischemia/reperfusion model.

    Science.gov (United States)

    Han, Hui; Hu, Jinquan; Yan, Qiang; Zhu, Jinzhou; Zhu, Zhengbin; Chen, Yanjia; Sun, Jiateng; Zhang, Ruiyan

    2016-02-01

    The transplantation of mesenchymal stem cells (MSCs) is considered to be a promising treatment for ischemic heart disease; however, the therapeutic effects and underlying mechanisms of action require further evaluation. Mitochondrial dysfunction is a key event in simulated ischemia/reperfusion (SI/R) injury. The purpose of the present study was to investigate the mechanism of mitochondrial transfer, which may be involved the antiapoptotic action of co-culture with MSCs. An in vitro model of simulated ischemia/reperfusion (SI/R) was used in the present study. The apoptotic indexes were significantly increased when H9c2 cardiomyocytes were induced in the SI/R group. Following co-culture with bone marrow-derived (BM)‑MSCs, H9c2 cells exhibited marked resistance against the SI/R-induced apoptotic process. Besides, mitochondrial transfer via a tunneling nanotube (TNT) like structure was detected by confocal fluorescent microscopy. In addition, following pretreated with latrunculin-A (LatA), an inhibitor of TNT formation, the BM-MSCs were not able to rescue injured H9c2 cells from apoptosis, as previously observed. In conclusion, the anti‑apoptotic ability of BM‑MSCs may be partially attributed to the recovery of mitochondrial dysfunction in SI/R, and the formation of TNTs appears to be involved in this action of mitochondrial transfer between adjacent cells. PMID:26718099

  9. Plant natriuretic peptides: Systemic regulators of plant homeostasis and defense that can affect cardiomyoblasts

    KAUST Repository

    Gehring, Christoph A

    2010-09-01

    Immunologic evidence has suggested the presence of biologically active natriuretic peptide (NPs) hormones in plants because antiatrial NP antibodies affinity purify biologically active plant NPs (PNP). In the model plant, an Arabidopsis thaliana PNP (AtPNP-A) has been identified and characterized. AtPNP-A belongs to a novel class of molecules that share some similarity with the cell wall loosening expansins but do not contain the carbohydrate-binding wall anchor thus suggesting that PNPs and atrial natriuretic peptides are heterologs. AtPNP-A acts systemically, and this is consistent with its localization in the apoplastic extracellular space and the conductive tissue. Furthermore, AtPNP-A signals via the second messenger cyclic guanosine 3′,5′-monophosphate and modulates ion and water transport and homeostasis. It also plays a critical role in host defense against pathogens. AtPNP-A can be classified as novel paracrine plant hormone because it is secreted into the apoplastic space in response to stress and can enhance its own expression. Interestingly, purified recombinant PNP induces apo-ptosis in a dose-dependent manner and was most effective on cardiac myoblast cell lines. Because PNP is mimicking the effect of ANP in some instances, PNP may prove to provide useful leads for development of novel therapeutic NPs. Copyright © 2013 by The American Federation for Medical Research.

  10. Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

    International Nuclear Information System (INIS)

    Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC50 (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC50 (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

  11. How competition affects evolutionary rescue

    OpenAIRE

    Osmond, Matthew Miles; de Mazancourt, Claire

    2013-01-01

    Populations facing novel environments can persist by adapting. In nature, the ability to adapt and persist will depend on interactions between coexisting individuals. Here we use an adaptive dynamic model to assess how the potential for evolutionary rescue is affected by intra- and interspecific competition. Intraspecific competition (negative density-dependence) lowers abundance, which decreases the supply rate of beneficial mutations, hindering evolutionary rescue. On the other hand, inters...

  12. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy

    OpenAIRE

    Ricca, Alessandra; Rufo, Nicole; Ungari, Silvia; Morena, Francesco; Martino, Sabata; Kulik, Wilem; Alberizzi, Valeria; Bolino, Alessandra; Bianchi, Francesca; del Carro, Ubaldo; Biffi, Alessandra; Gritti, Angela

    2015-01-01

    Globoid cell leukodystrophy (GLD) is a lysosomal storage disease caused by deficient activity of β-galactocerebrosidase (GALC). The infantile forms manifest with rapid and progressive central and peripheral demyelination, which represent a major hurdle for any treatment approach. We demonstrate here that neonatal lentiviral vector-mediated intracerebral gene therapy (IC GT) or transplantation of GALC-overexpressing neural stem cells (NSC) synergize with bone marrow transplant (BMT) providing ...

  13. Radiation therapy for consolidation of metastatic or recurrent sarcomas in children treated with intensive chemotherapy and stem cell rescue. A feasibility study

    International Nuclear Information System (INIS)

    Purpose: To assess the role of consolidative radiation therapy (CRT) in conjunction with myeloablative therapy with or without total body irradiation (TBI) in children and young adults with metastatic or recurrent sarcoma. Methods and Materials: Twenty-one pediatric sarcoma patients with metastatic or recurrent disease were entered on a prospective feasibility study of intensive myeloablative therapy with or without TBI. Median patient age was 17.8 years (range, 9.4-24.7 years). Primary histologies included Ewing's, PNET, and other soft tissue sarcomas. Twenty patients received induction chemotherapy. Myeloablative therapy consisted of TBI in 11 patients with either high dose melphalan/etoposide or high dose cytoxan/thiotepa. TBI consisted of 12 Gy in 2 Gy fractions delivered twice daily over 3 days. Ten patients received high dose chemotherapy alone, either with thiotepa/carboplatinum/etoposide or cytoxan/carboplatinum. Myeloablative therapy was followed by autologous stem cell rescue (ASCR) 24 to 48 hours after completing chemotherapy. Fourteen patients (67%) received CRT either prior to or following myeloablative therapy. Median CRT dose was 37.2 Gy (range, 20-60). Fifty-one disease sites were present prior to myeloablative therapy. Twelve (24%) were bulky (> 8 cm) and 18 (35%) underwent surgical debulking. The median follow-up of surviving patients was 15 months (range, 8-20) with 25% of patients having been followed for more than 20 months. Results: The 3-year actuarial disease-free (DFS) and overall survival (OS) rates for the entire group were 36% and 27%, respectively. Following myeloablative treatment, responses were: 11 complete, 6 partial, 1 stable, and 3 progressive disease. Sixteen patients (71%) have relapsed. The most common site of relapse was the lung. Of the 51 disease sites present prior to myeloablative therapy, 36 sites (71%) were amenable to CRT. Non-amenable sites were: multiple lung metastases and bone marrow. Twenty-six amenable sites (51

  14. Joseph Conrad's tormented Rescue (fantasy).

    Science.gov (United States)

    Freedman, William

    2014-02-01

    Joseph Conrad was a notoriously tormented writer for whom the creative act was often a punishment severe enough to drive him into paralyzing depressions that delayed the completion of his novels, sometimes for years. By far the most agonizing of these projects was The Rescue, a novel he began in 1898, abandoned a year later, tried unsuccessfully to continue several times over the next two decades, but was only able to resume in 1918 and to complete, after another tortured two-year struggle, in 1920. An explanation for this incapacity, that is powerfully suggested by the novel's evocative title and perhaps unintentionally ironic subtitle (A Romance of the Shallows) has not yet been explored. Using Freud's 1910 essay on the rescue fantasy, "Contributions to the Psychology of Love: A Special Type of Choice of Object Made by Men," and Emanuel Berman's instructive revision and expansion of the concept in his 2003 American Imago essay, "Ferenczi, Rescue, and Utopia," I argue that a substantial explanation for Conrad's tormented history with The Rescue is ascribable to its quite remarkably faithful treatment of a rescue fantasy with deep and disabling resonance for its author. More specifically, the difficulty was compounded by the novel's dramatization of the soul-crushing conflict between two such fantasies: one in the service of the masculine ideal of unflinching dedication to a heroic purpose, the other promising satisfaction to the equally potent demands of emotional and sexual desire. Features of Conrad's narrative fit so tightly and consistently with the theory as Freud (and Abraham) proposed and as Berman elaborated it that The Rescue offers itself as one of those rare and reinforcing instances wherein the literary text seems to validate the psychoanalytic theory at least as persuasively as the theory "understands" the text. PMID:24555549

  15. Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.

    Directory of Open Access Journals (Sweden)

    Mary Ann Cheatham

    Full Text Available A knockin (KI mouse expressing mutated prestinV499G/Y501H (499 prestin was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification.

  16. CERN Fire Brigade rescue simulation

    CERN Multimedia

    Maximilien Brice

    2004-01-01

    The CERN Fire Brigade is made up of experienced firemen from all of the 20 Member States. In these images they are seen at a 'Discovery Monday' held at the Microcosm exhibition. Here visitors learn how the Fire Brigade deal with various situations, including a simulated cave rescue performed by the Hazardous Environments Response Team.

  17. Self-Rescue Mask Training

    CERN Multimedia

    2013-01-01

    Nine new self-rescue mask instructors have been trained since early 2013, which provides CERN with a total of 26 self-rescue mask instructors to date. This will allow us to meet the increasing training needs caused by the Long Shut Down LS1.   The self-rescue mask instructors have trained 1650 persons in 2012 and about 500 persons since the beginning of the year on how to wear the masks properly. We thank all the instructors and all the persons that made this training possible. Please remember that the self-rescue masks training sessions are scheduled as follows: Basic course: Tuesday and Thursday mornings (2 sessions – 8.30 AM and 10.30 AM), duration:  1.30 hour, in French and English – registration via CERN online training catalogue – Course code 077Y00. Refresher training : Monday mornings (2 sessions – 8.30 AM and 10.30 AM), duration: 1.30 hour , in French and English – registration via CERN online training catalogue &...

  18. 78 FR 39531 - Mine Rescue Teams

    Science.gov (United States)

    2013-07-01

    ... Rescue Teams; CFR Correction #0;#0;Federal Register / Vol. 78 , No. 126 / Monday, July 1, 2013 / Rules... Rescue Teams CFR Correction In Title 30 of the Code of Federal Regulations, Parts 1 to 199, revised as of... Miner Act Requirements for Underground Coal Mine Operators and Mine Rescue Teams Type of mine...

  19. Mitochondrial transfer mechanism of bone marrow mesenchymal stem cells for rescue of tissue injury%骨髓间充质干细胞治疗组织损伤的线粒体转移机制

    Institute of Scientific and Technical Information of China (English)

    彭懿; 舒畅; 符州

    2014-01-01

    BACKGROUND:Bone marrow mesenchymal stem cells have beneficial effects on the treatment of various diseases. Mitochondria transfer is newly proposed and its specific mechanisms of action and control factors remain unclear. OBJECTIVE:To review the studies about stem cells and mitochondrial transfer, then to discuss its value on clinical. METHODS:The PubMed, VIP and Wanfang databases were searched for related articles concerning stem cells and mitochondrial transfer. Key words were“stem cell, embryonic stem cell, progenitor cell, mitochondria”in Chinese and“Stem cell[s], Mother cell[s], Progenitor cell[s], Colony-Forming Unit[s], Colony Forming Unit[s], Mitochondria[l] transfer”in English. Thirteen articles were found initial y, and using the citation tracking method, final y 42 articles were determined. RESULTS AND CONCLUSION:Studies have shown that mitochondrial transfer from bone marrow mesenchymal stem cells is associated with rescue of aerobic respiration and restoration of mitochondrial function in the injured somatic cells. Bone marrow mesenchymal stem cells and recipient cells form tunneling nanotubes for mitochondrial transfer. Movement of mitochondria between cells is regulated and directed by Miro1. The successful transfer of mitochondria may be accompanied with the clearance of damaged mitochondria. The rescue of mitochondrial function in early stages may provide a valuable therapeutic strategy for various diseases include acute lung injury.%背景:骨髓间充质干细胞对多种疾病具有治疗价值,其治疗疾病的线粒体转移机制是近年来被提出的新概念,具体作用机制及调控因素尚不明确。  目的:对现有关于干细胞及线粒体转移相关文章进行综述,并对其未来临床实际应用进行展望。  方法:第一作者应用计算机检索PubMed数据、维普、万方数据库中所有关于干细胞与线粒体转移相关文章。中文检索词为“干细胞、胚胎干细

  20. 骨髓间充质干细胞治疗组织损伤的线粒体转移机制%Mitochondrial transfer mechanism of bone marrow mesenchymal stem cells for rescue of tissue injury

    Institute of Scientific and Technical Information of China (English)

    彭懿; 舒畅; 符州

    2014-01-01

    BACKGROUND:Bone marrow mesenchymal stem cells have beneficial effects on the treatment of various diseases. Mitochondria transfer is newly proposed and its specific mechanisms of action and control factors remain unclear. OBJECTIVE:To review the studies about stem cells and mitochondrial transfer, then to discuss its value on clinical. METHODS:The PubMed, VIP and Wanfang databases were searched for related articles concerning stem cells and mitochondrial transfer. Key words were“stem cell, embryonic stem cell, progenitor cell, mitochondria”in Chinese and“Stem cell[s], Mother cell[s], Progenitor cell[s], Colony-Forming Unit[s], Colony Forming Unit[s], Mitochondria[l] transfer”in English. Thirteen articles were found initial y, and using the citation tracking method, final y 42 articles were determined. RESULTS AND CONCLUSION:Studies have shown that mitochondrial transfer from bone marrow mesenchymal stem cells is associated with rescue of aerobic respiration and restoration of mitochondrial function in the injured somatic cells. Bone marrow mesenchymal stem cells and recipient cells form tunneling nanotubes for mitochondrial transfer. Movement of mitochondria between cells is regulated and directed by Miro1. The successful transfer of mitochondria may be accompanied with the clearance of damaged mitochondria. The rescue of mitochondrial function in early stages may provide a valuable therapeutic strategy for various diseases include acute lung injury.%背景:骨髓间充质干细胞对多种疾病具有治疗价值,其治疗疾病的线粒体转移机制是近年来被提出的新概念,具体作用机制及调控因素尚不明确。  目的:对现有关于干细胞及线粒体转移相关文章进行综述,并对其未来临床实际应用进行展望。  方法:第一作者应用计算机检索PubMed数据、维普、万方数据库中所有关于干细胞与线粒体转移相关文章。中文检索词为“干细胞、胚胎干细

  1. Molecular genetics of vaccinia virus: demonstration of marker rescue.

    OpenAIRE

    Nakano, E.; Panicali, D; E. Paoletti

    1982-01-01

    Two genomic variants of vaccinia virus isolated from serially propagated stocks were used to demonstrate marker rescue. The smaller (S variant) virus contains a 6.3 megadalton (MDal) deletion of unique DNA sequences present in the 123-MDal larger (L variant) virus. The deletion was mapped at 6.85 MDal from the left terminus of the genome, just outside of the inverted terminal repetition. Rescue of the unique deleted DNA sequences by infectious S variant virus was obtained in CV-1 cells by usi...

  2. GIS Support for Flood Rescue

    DEFF Research Database (Denmark)

    Liang, Gengsheng; Mioc, Darka; Anton, François

    2007-01-01

    Under flood events, the ground traffic is blocked in and around the flooded area due to damages to roads and bridges. The traditional transportation network may not always help people to make a right decision for evacuation. In order to provide dynamic road information needed for flood rescue, we...... developed an adaptive web-based transportation network application using Oracle technology. Moreover, the geographic relationships between the road network and flood areas are taken into account. The overlay between the road network and flood polygons is computed on the fly. This application allows users to...... retrieve the shortest and safest route in Fredericton road network during flood event. It enables users to make a timely decision for flood rescue. We are using Oracle Spatial to deal with emergency situations that can be applied to other constrained network applications as well....

  3. Toward a behavioral ecology of rescue behavior.

    Science.gov (United States)

    Hollis, Karen L; Nowbahari, Elise

    2013-01-01

    Although the study of helping behavior has revolutionized the field of behavioral ecology, scientific examination of rescue behavior remains extremely rare, except perhaps in ants, having been described as early as 1874. Nonetheless, recent work in our laboratories has revealed several new patterns of rescue behavior that appear to be much more complex than previously studied forms. This precisely-directed rescue behavior bears a remarkable resemblance to what has been labeled empathy in rats, and thus raises numerous philosophical and theoretical questions: How should rescue behavior (or empathy) be defined? What distinguishes rescue from other forms of altruism? In what ways is rescue behavior in ants different from, and similar to, rescue in other non-human animals? What selection pressures dictate its appearance? In this paper, we review our own experimental studies of rescue in both laboratory and field, which, taken together, begin to reveal some of the behavioral ecological conditions that likely have given rise to rescue behavior in ants. Against this background, we also address important theoretical questions involving rescue, including those outlined above. In this way, we hope not only to encourage further experimental analysis of rescue behavior, but also to highlight important similarities and differences in very distant taxa. PMID:23864298

  4. In-vitro rescue and recovery studies of human melanoma (BLM) cell growth, adhesion and migration functions after treatment with progesterone

    OpenAIRE

    Leder, Douglas C; Brown, Jason R; Ramaraj, Pandurangan

    2015-01-01

    Treatment of human melanoma (BLM) cells for 48 hrs with progesterone resulted in a significant inhibition of cell growth. The mechanism of growth inhibition was due to autophagy and this action of progesterone was not mediated through progesterone receptor. As cells were floating during treatment, adhesion assay was performed, which showed complete loss of adhesion. When cells were allowed to recover after treatment by culturing in growth medium without progesterone, there was recovery in cel...

  5. Collaboration mechanism of intercity emergency rescue ecosystem

    Institute of Scientific and Technical Information of China (English)

    Jiang Yiping; Zhao Lindu

    2009-01-01

    With the development of metropolitan regions and the appearance of urban agglomerations,cities have been more closely related.For the restricted emergency rescue resource in a single city,it has become more and more imminent for the demand of the intercity collaborative resistance to major accident,so as to improve the protection capacity of urban security.In order to find an effective intercity emergency rescue collaborative system,this paper introduces the concept and analysis method of ecosystem theory into intercity emergency rescue.Based on theanalysis of the formation-process of emergency rescue individual,population and community,a three-level intercity emergency rescue collaborative system is constructed according to the characteristics of dynamics and structure of intercity emergency rescue ecosystem,then the collaboration mechanism of information,resource and process in the intercity emergency rescue ecosystem is also studied in this paper,so as to offer available strategy and method for the ecosystem theory applied to intercity emergency rescue.Through the studies of intercity emergency rescue eco,system,it illuminates that the proposed emergency system can not only cope with the major accident more timely and effectively,but also integrate the intercity information resources and emergency rescue resource and process optimi,zation.

  6. Glutamine Reduces the Apoptosis of H9C2 Cells Treated with High-Glucose and Reperfusion through an Oxidation-Related Mechanism

    OpenAIRE

    Kai Li; Yong-Chun Cui; Hong Zhang; Xiao-Peng Liu; Dong Zhang; Ai-Li Wu; Jian-Jun Li; Yue Tang

    2015-01-01

    Mitochondrial overproduction of reactive oxygen species (ROS) in diabetic hearts during ischemia/reperfusion injury and the anti-oxidative role of glutamine have been demonstrated. However, in diabetes mellitus the role of glutamine in cardiomyocytes during ischemia/reperfusion injury has not been explored. To examine the effects of glutamine and potential mechanisms, in the present study, rat cardiomyoblast H9C2 cells were exposed to high glucose (33 mM) and hypoxia-reoxygenation. Cell viabi...

  7. The Data Rescue @ Home Project

    Science.gov (United States)

    Stickler, A.; Allan, R.; Valente, M. A.; Tinz, B.; Brönnimann, S.

    2012-04-01

    Climate science as a whole as well as reanalyses as a special case can significantly profit from the recovery, imaging and digitisation of historical observations. The importance of this fact is reflected in large, global data rescue projects and initiatives such as the Atmospheric Circulation Reconstructions over the Earth (ACRE, www.met-acre.org) or the EU FP7 ERA-CLIM project (www.era-clim.eu). From the time before 1957, there are still large amounts of surface data e.g. from former colonies and from overseas territories of European countries )e.g. Portugal, France and Germany) that need to be rescued. Also in case of the very early upper-air observations before the 1930s, even Europe and North America still hold an important quantity of data to be recovered in digital form. Here, we present the web platform "Data Rescue @ Home" (www.data-rescue-at-home.org), which has been developed at ETH Zurich and Oeschger Centre for Climate Change Research, and which has been designed to take advantage of the voluntary assistance of the thousands of people on the web who are interested in climate or old weather data. On the website, these volunteers can enter meteorological data shown on digital images into entry masks that resemble the original. By registering, the users get access to their personal digitisation statistics and help optimising the project. At the moment, 4 digitisation projects are online: One project is dealing with German upper-air data from the Second World War period. In a second project, station data from Tulagi (Solomon Islands) is being digitised. Finally, two collaborative projects have been included: One in cooperation with the Instituto Dom Luiz (Univ. Lisbon, Portugal), where Portuguese station data from Angra (Azores) is digitised, and a further one in cooperation with the German Meteorological Service (DWD), in which precipitation data from former German colonies is being digitised. On our poster, we will report on the status of the projects

  8. Newly identifi ed message for rescue and repair from necrotic cell: Biology and clinical relevance of“endokine, HMGB1”

    OpenAIRE

    Maruyama, Ikuro; Ito, Takashi; HASHIGUCHI, Teruto

    2007-01-01

    Responses to stimuli in cellar level are diverse and such hierarchical as secretion of stored factors,synthesis of lipid mediators and protein synthesis through genomic transcription. However, how can the cellsrespond in the case of necrosis? Recently a characteristic intranuclear protein, high-mobility group box 1 protein(HMGB1) is released from necrotic cells. The protein is an abundant nuclear protein with a dual functionboth inside and outside the cells. In physiological state, HMGB1 is p...

  9. Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET.

    Science.gov (United States)

    Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; van Bokhoven, Hans; Wiman, Klas G; Zhou, Huiqing; Aberdam, Daniel; Petit, Isabelle

    2013-02-01

    Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18(+) cells but failed to further differentiate into K14(+) cells (epidermis/limbus) or K3/K12(+) cells (corneal epithelium). APR-246 (PRIMA-1(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves the way for future therapy of EEC. PMID:23355677

  10. Disruption of Interleukin-1β Autocrine Signaling Rescues Complex I Activity and Improves ROS Levels in Immortalized Epithelial Cells with Impaired Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Function

    OpenAIRE

    Clauzure, Mariángeles; Valdivieso, Angel G.; Massip Copiz, María M.; Schulman, Gustavo; Teiber, María Luz; Santa-Coloma, Tomás A.

    2014-01-01

    Patients with cystic fibrosis (CF) have elevated concentration of cytokines in sputum and a general inflammatory condition. In addition, CF cells in culture produce diverse cytokines in excess, including IL-1β. We have previously shown that IL-1β, at low doses (∼30 pM), can stimulate the expression of CFTR in T84 colon carcinoma cells, through NF-κB signaling. However, at higher doses (>2.5 ng/ml, ∼150 pM), IL-1β inhibit CFTR mRNA expression. On the other hand, by using differential display, ...

  11. Rescue of Notch signaling in cells incapable of GDP-l-fucose synthesis by gap junction transfer of GDP-l-fucose in Drosophila

    OpenAIRE

    Ayukawa, Tomonori; Matsumoto, Kenjiroo; Ishikawa, Hiroyuki O.; Ishio, Akira; Yamakawa, Tomoko; Aoyama, Naoki; Suzuki, Takuya; Matsuno, Kenji

    2012-01-01

    Notch (N) is a transmembrane receptor that mediates cell–cell interactions to determine many cell-fate decisions. N contains EGF-like repeats, many of which have an O-fucose glycan modification that regulates N-ligand binding. This modification requires GDP-l-fucose as a donor of fucose. The GDP-l-fucose biosynthetic pathways are well understood, including the de novo pathway, which depends on GDP-mannose 4,6 dehydratase (Gmd) and GDP-4-keto-6-deoxy-d-mannose 3,5-epimerase/4-reductase (Gmer)....

  12. 30 CFR 49.18 - Training for mine rescue teams.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training for mine rescue teams. 49.18 Section... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.18 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an...

  13. Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET

    OpenAIRE

    Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; Van Bokhoven, Hans; Wiman, Klas G.; Zhou, Huiqing; Aberdam, Daniel; PETIT Isabelle

    2013-01-01

    Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. ...

  14. Rescue coronary stenting in acute myocardial infarction

    Science.gov (United States)

    Barbieri, Enrico; Meneghetti, Paolo; Molinari, Gionata; Zardini, Piero

    1996-01-01

    Failed rescue coronary angioplasty is a high risk situation because of high mortality. Coronary stent has given us the chance of improving and maintaining the patency of the artery. We report our preliminary experience of rescue stenting after unsuccessful coronary angioplasty.

  15. Teaching Holocaust Rescue: A Problematic Pedagogy

    Science.gov (United States)

    Lindquist, David H.

    2008-01-01

    Determining how to teach about rescue during the Holocaust presents many dilemmas to teachers as they plan Holocaust curricula. Rescue is often overemphasized, and faulty perspectives about rescuers and their actions may cause students to develop distorted views about this aspect of Holocaust history. This article explores several factors that…

  16. Simvastatin rescues homocysteine-induced apoptosis of osteocytic MLO-Y4 cells by decreasing the expressions of NADPH oxidase 1 and 2.

    Science.gov (United States)

    Takeno, Ayumu; Kanazawa, Ippei; Tanaka, Ken-Ichiro; Notsu, Masakazu; Yokomoto-Umakoshi, Maki; Sugimoto, Toshitsugu

    2016-04-25

    Clinical studies have shown that hyperhomocysteinemia is associated with bone fragility. Homocysteine (Hcy) induces apoptosis of osteoblastic cell lineage by increasing oxidative stress, which may contribute to Hcy-induced bone fragility. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, ameliorate oxidative stress by regulating oxidant and anti-oxidant enzymes. However, the effects of statins on Hcy-induced apoptosis of osteocytes are unknown. This study was thus aimed to investigate whether or not statins prevent Hcy-induced apoptosis of osteocytic MLO-Y4 cells and regulate NADPH oxidase (Nox) expression. TUNEL staining showed that 5 mM Hcy induced apoptosis of MLO-Y4 cells, and that co-incubation of 10(-9) or 10(-8) M simvastatin significantly suppressed the apoptotic effect. Moreover, we confirmed the beneficial effect of simvastatin against Hcy's apoptotic effect by using a DNA fragment ELISA assay. However, TUNEL staining showed no significant effects of pravastatin, a hydrophilic statin, on the Hcy-induced apoptosis. Real-time PCR showed that Hcy increased the mRNA expressions of Nox1 and Nox2, whereas simvastatin inhibited the stimulation of Nox1 and Nox2 expressions by Hcy. In contrast, neither Hcy nor simvastatin had any effect on Nox4 expression. These findings indicate that simvastatin prevents the detrimental effects of Hcy on the apoptosis of osteocytes by regulating the expressions of Nox1 and Nox2, suggesting that statins may be beneficial for preventing Hcy-induced osteocyte apoptosis and the resulting bone fragility. PMID:26842590

  17. PTEN Loss in E-Cadherin-Deficient Mouse Mammary Epithelial Cells Rescues Apoptosis and Results in Development of Classical Invasive Lobular Carcinoma.

    Science.gov (United States)

    Boelens, Mirjam C; Nethe, Micha; Klarenbeek, Sjoerd; de Ruiter, Julian R; Schut, Eva; Bonzanni, Nicola; Zeeman, Amber L; Wientjens, Ellen; van der Burg, Eline; Wessels, Lodewyk; van Amerongen, Renée; Jonkers, Jos

    2016-08-23

    Invasive lobular carcinoma (ILC) is an aggressive breast cancer subtype with poor response to chemotherapy. Besides loss of E-cadherin, a hallmark of ILC, genetic inactivation of PTEN is frequently observed in patients. Through concomitant Cre-mediated inactivation of E-cadherin and PTEN in mammary epithelium, we generated a mouse model of classical ILC (CLC), the main histological ILC subtype. While loss of E-cadherin induced cell dissemination and apoptosis, additional PTEN inactivation promoted cell survival and rapid formation of invasive mammary tumors that recapitulate the histological and molecular features, estrogen receptor (ER) status, growth kinetics, metastatic behavior, and tumor microenvironment of human CLC. Combined inactivation of E-cadherin and PTEN is sufficient to cause CLC development. These CLCs showed significant tumor regression upon BEZ235-mediated inhibition of PI3K signaling. In summary, this mouse model provides important insights into CLC development and suggests inhibition of phosphatidylinositol 3-kinase (PI3K) signaling as a potential therapeutic strategy for targeting CLC. PMID:27524621

  18. Rescue of the mucocutaneous manifestations by human cord blood derived nonhematopoietic stem cells in a mouse model of recessive dystrophic epidermolysis bullosa.

    Science.gov (United States)

    Liao, Yanling; Ivanova, Larisa; Zhu, Hongwen; Yahr, Ashlin; Ayello, Janet; van de Ven, Carmella; Rashad, Ahmed; Uitto, Jouni; Christiano, Angela M; Cairo, Mitchell S

    2015-06-01

    Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin blistering disease caused by mutations in COL7A1-encoding type VII collagen (C7). Currently, there is no curative therapy for patients with RDEB. Our previous studies demonstrated that human umbilical cord blood (HUCB) derived unrestricted somatic stem cells (USSCs) express C7 and facilitate wound healing in a murine wounding model. The primary objective of this study is to investigate the therapeutic functions of USSCs in the C7 null (Col7a1(-/-) ) C57BL6/J mice, a murine model of RDEB. We demonstrated that intrahepatic administration of USSCs significantly improved the blistering phenotype and enhanced the life span in the recipients. The injected USSCs trafficked to the sites of blistering and were incorporated in short-term in the recipients' skin and gastrointestinal tract. Consistent with an overall histological improvement in the epidermal-dermal adherence following USSC treatment, the expression of C7 at the basement membrane zone was detected and the previously disorganized integrin α6 distribution was normalized. We also demonstrated that USSCs treatment induced an infiltration of macrophages with a regenerative "M2" phenotype. Our data suggest that HUCB-derived USSCs improved the RDEB phenotype through multiple mechanisms. This study has warranted future clinical investigation of USSCs as a novel and universal allogeneic stem cell donor source in selected patients with RDEB. PMID:25640200

  19. Designing allosteric control into enzymes by chemical rescue of structure

    OpenAIRE

    Deckert, Katelyn; Budiardjo, S. Jimmy; Brunner, Luke C.; Lovell, Scott; Karanicolas, John

    2012-01-01

    Ligand-dependent activity has been engineered into enzymes for purposes ranging from controlling cell morphology to reprogramming cellular signaling pathways. Where these successes have typically fused a naturally allosteric domain to the enzyme of interest, here we instead demonstrate an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruptio...

  20. Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Natalie R.S. Goldberg

    2015-11-01

    Full Text Available Accumulation of α-synuclein (α-syn into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson’s disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF, which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies.

  1. Neuronal nitric oxide synthase-rescue of dystrophin/utrophin double knockout mice does not require nNOS localization to the cell membrane.

    Directory of Open Access Journals (Sweden)

    Michelle Wehling-Henricks

    Full Text Available Survival of dystrophin/utrophin double-knockout (dko mice was increased by muscle-specific expression of a neuronal nitric oxide synthase (nNOS transgene. Dko mice expressing the transgene (nNOS TG+/dko experienced delayed onset of mortality and increased life-span. The nNOS TG+/dko mice demonstrated a significant decrease in the concentration of CD163+, M2c macrophages that can express arginase and promote fibrosis. The decrease in M2c macrophages was associated with a significant reduction in fibrosis of heart, diaphragm and hindlimb muscles of nNOS TG+/dko mice. The nNOS transgene had no effect on the concentration of cytolytic, CD68+, M1 macrophages. Accordingly, we did not observe any change in the extent of muscle fiber lysis in the nNOS TG+/dko mice. These findings show that nNOS/NO (nitric oxide-mediated decreases in M2c macrophages lead to a reduction in the muscle fibrosis that is associated with increased mortality in mice lacking dystrophin and utrophin. Interestingly, the dramatic and beneficial effects of the nNOS transgene were not attributable to localization of nNOS protein at the cell membrane. We did not detect any nNOS protein at the sarcolemma in nNOS TG+/dko muscles. This important observation shows that sarcolemmal localization is not necessary for nNOS to have beneficial effects in dystrophic tissue and the presence of nNOS in the cytosol of dystrophic muscle fibers can ameliorate the pathology and most importantly, significantly increase life-span.

  2. A New Antibiotic to the Rescue?

    Science.gov (United States)

    ... the Rescue? Experimental drug shows promise against MRSA superbug in animal trials To use the sharing features ... successfully treated animals infected with the so-called "superbug" MRSA -- methicillin-resistant staphylococcus aureus . The results are " ...

  3. Search and Rescue Mission Using Multicopters

    OpenAIRE

    Steen, Thor Audun

    2014-01-01

    Search and rescue operations can greatly benefit from the use of autonomous unmanned aerial systems to survey the environment and collect evidence about the positions of missing persons. This thesis considers the design of an autonomous multicopter system for use in a search and rescue mission. The ArduPilot Mega is used as the autopilot and is presented together with detailed information about the utilized hardware and software. The design of a low- level control interface is implemented as ...

  4. RoboCupRescue - Robot League Team RescueRobots Freiburg (Germany)

    OpenAIRE

    Kleiner, Alexander; Dornhege, Christian; Kümmerle, Rainer; Ruhnke, Michael; Steder, Bastian; Nebel, Bernhard; Doherty, Patrick; Wzorek, Mariusz; Rudol, Piotr; Conte, Gianpaolo; Duranti, Simone; Lundström, David

    2006-01-01

    This paper describes the approach of the RescueRobots Freiburg team. RescueRobots Freiburg is a team of students from the university of Freiburg, that originates from the former CS Freiburg team (RoboCupSoccer) and the ResQ Freiburg team (RoboCupRescue Simulation). Due to the high versatility of the RoboCupRescue competition we tackle the three arenas by a a twofold approach: On the one hand we want to introduce robust vehicles that can safely be teleoperated through rubble and building debri...

  5. Hubble Space Telescope Crew Rescue Analysis

    Science.gov (United States)

    Hamlin, Teri L.; Canga, Michael A.; Cates, Grant R.

    2010-01-01

    In the aftermath of the 2003 Columbia accident, NASA removed the Hubble Space Telescope (HST) Servicing Mission 4 (SM4) from the Space Shuttle manifest. Reasons cited included concerns that the risk of flying the mission would be too high. The HST SM4 was subsequently reinstated and flown as Space Transportation System (STS)-125 because of improvements in the ascent debris environment, the development of techniques for astronauts to perform on orbit repairs to damaged thermal protection, and the development of a strategy to provide a viable crew rescue capability. However, leading up to the launch of STS-125, the viability of the HST crew rescue capability was a recurring topic. For STS-125, there was a limited amount of time available to perform a crew rescue due to limited consumables (power, oxygen, etc.) available on the Orbiter. The success of crew rescue depended upon several factors, including when a problem was identified; when and what actions, such as powering down, were begun to conserve consumables; and where the Launch on Need (LON) vehicle was in its ground processing cycle. Crew rescue success also needed to be weighed against preserving the Orbiter s ability to have a landing option in case there was a problem with the LON vehicle. This paper focuses on quantifying the HST mission loss of crew rescue capability using Shuttle historical data and various power down strategies. Results from this effort supported NASA s decision to proceed with STS-125, which was successfully completed on May 24th 2009.

  6. 30 CFR 49.8 - Training for mine rescue teams.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Training for mine rescue teams. 49.8 Section 49... TRAINING MINE RESCUE TEAMS § 49.8 Training for mine rescue teams. (a) Prior to serving on a mine rescue team each member shall complete, at a minimum, an initial 20-hour course of instruction as...

  7. 30 CFR 49.12 - Availability of mine rescue teams.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Availability of mine rescue teams. 49.12... TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.12 Availability of mine rescue teams. (a) Except where alternative compliance is permitted for small and remote mines (§ 49.13),...

  8. VEGETATIVE RESCUE OF Anadenanthera macrocarpa TREES

    Directory of Open Access Journals (Sweden)

    Poliana Coqueiro Dias

    2015-03-01

    Full Text Available The objective of this work was to evaluate the vegetative rescue of adult Anadenanthera macrocarpa trees through the induction of epicormic shoots from tree severance and stem ringing, as well as the efficiency of cutting technique on the propagation of the species. The experimental design used was random plots, in a 2 X 2 factorial arrangement, constituted by two techniques for the induction of basal shoots (tree severance and stem ringing and cuttings types (herbaceous cuttings and semihardwoods cuttings, in four replicates and plots of 12 cuttings per repetition. The tree severance and stem ringing were efficient in the induction of basal shoots in adult A. macrocarpa trees. However, the tree severance provided higher emission of basal shoots. The herbaceous cuttings presented higher rooting percentages, independent of vegetative rescue technique. In general, we conclude that the vegetative rescue and the vegetative propagation of A. macrocarpa adult trees are technically efficient.

  9. RESCU: A real space electronic structure method

    Science.gov (United States)

    Michaud-Rioux, Vincent; Zhang, Lei; Guo, Hong

    2016-02-01

    In this work we present RESCU, a powerful MATLAB-based Kohn-Sham density functional theory (KS-DFT) solver. We demonstrate that RESCU can compute the electronic structure properties of systems comprising many thousands of atoms using modest computer resources, e.g. 16 to 256 cores. Its computational efficiency is achieved from exploiting four routes. First, we use numerical atomic orbital (NAO) techniques to efficiently generate a good quality initial subspace which is crucially required by Chebyshev filtering methods. Second, we exploit the fact that only a subspace spanning the occupied Kohn-Sham states is required, and solving accurately the KS equation using eigensolvers can generally be avoided. Third, by judiciously analyzing and optimizing various parts of the procedure in RESCU, we delay the O (N3) scaling to large N, and our tests show that RESCU scales consistently as O (N2.3) from a few hundred atoms to more than 5000 atoms when using a real space grid discretization. The scaling is better or comparable in a NAO basis up to the 14,000 atoms level. Fourth, we exploit various numerical algorithms and, in particular, we introduce a partial Rayleigh-Ritz algorithm to achieve efficiency gains for systems comprising more than 10,000 electrons. We demonstrate the power of RESCU in solving KS-DFT problems using many examples running on 16, 64 and/or 256 cores: a 5832 Si atoms supercell; a 8788 Al atoms supercell; a 5324 Cu atoms supercell and a small DNA molecule submerged in 1713 water molecules for a total 5399 atoms. The KS-DFT is entirely converged in a few hours in all cases. Our results suggest that the RESCU method has reached a milestone of solving thousands of atoms by KS-DFT on a modest computer cluster.

  10. "Rescue" regimens after Helicobacter pylori treatment failure

    Institute of Scientific and Technical Information of China (English)

    Javier P Gisbert

    2008-01-01

    Helicobacter pylori (H pylori)infection is the main cause of gastritis,gastroduodenal ulcer disease,and gastric cancer.After more than 20 years of experience in Hpylori treatment,in my opinion,the ideal regimen to treat this infection is still to be found.Currently,apart from having to know first-line eradication regimens well,we must also be prepared to face lyeatment failures.Therefore,in designing a treatment strategy we should not focus on the results of primary therapy alone,but also on the final (overall) eradication rate.The choice of a "rescue" treatment depends on which treatment is used initially.If a clarithromycinbased regimen was used initially,a subsequent metronidazole-based treatment (quadruple therapy)may be used afterwards,and then a levofloxacinbased combination would be a third "rescue" option.Alternatively,it has recently been suggested that levofloxacin-based rescue therapy constitutes an encouraging second-line strategy,representing an alternative to quadruple therapy in patients with previous PPI-clarithromycin-amoxicillin failure,with the advantage of efficacy,simplicity and safety.In this case,a quadruple regimen may be reserved as a third-line rescue option.Finally,rifabutin-based rescue therapy constitutes an encouraging empirical fourthline strategy after multiple previous eradication failures with key antibiotics such as amoxicillin,clarithromycin,metronidazole,tetracycline,and levofloxacin.Even after two consecutive failures,several studies have demonstrated that H pylor/eradication can finally be achieved in almost all patients if several rescue therapies are consecutively given.Therefore,the attitude in H pylori eradication therapy failure,even after two or more unsuccessful attempts,should be to fight and not to surrender.

  11. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey.

    Science.gov (United States)

    Kuçi, Zyrafete; Bönig, Halvard; Kreyenberg, Hermann; Bunos, Milica; Jauch, Anna; Janssen, Johannes W G; Škifić, Marijana; Michel, Kristina; Eising, Ben; Lucchini, Giovanna; Bakhtiar, Shahrzad; Greil, Johann; Lang, Peter; Basu, Oliver; von Luettichau, Irene; Schulz, Ansgar; Sykora, Karl-Walter; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Seifried, Erhard; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2016-08-01

    To circumvent donor-to-donor heterogeneity which may lead to inconsistent results after treatment of acute graft-versus-host disease with mesenchymal stromal cells generated from single donors we developed a novel approach by generating these cells from pooled bone marrow mononuclear cells of 8 healthy "3(rd)-party" donors. Generated cells were frozen in 209 vials and designated as mesenchymal stromal cell bank. These vials served as a source for generation of clinical grade mesenchymal stromal cell end-products, which exhibited typical mesenchymal stromal cell phenotype, trilineage differentiation potential and at later passages expressed replicative senescence-related markers (p21 and p16). Genetic analysis demonstrated their genomic stability (normal karyotype and a diploid pattern). Importantly, clinical end-products exerted a significantly higher allosuppressive potential than the mean allosuppressive potential of mesenchymal stromal cells generated from the same donors individually. Administration of 81 mesenchymal stromal cell end-products to 26 patients with severe steroid-resistant acute graft-versus-host disease in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 77% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (96% grade III/IV and only 4% grade II graft-versus-host disease), after treatment with mesenchymal stromal cell end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in graft-versus-host disease clinical studies, in which mesenchymal stromal cells were derived from single donors. Mesenchymal stromal cell end-products may, therefore, provide a novel therapeutic tool for the effective treatment of severe acute graft-versus-host disease. PMID:27175026

  12. Mesenchymal stromal cells from pooled mononuclear cells of multiple bone marrow donors as rescue therapy in pediatric severe steroid-refractory graft-versus-host disease: a multicenter survey

    Science.gov (United States)

    Kuçi, Zyrafete; Bönig, Halvard; Kreyenberg, Hermann; Bunos, Milica; Jauch, Anna; Janssen, Johannes W.G.; Škifić, Marijana; Michel, Kristina; Eising, Ben; Lucchini, Giovanna; Bakhtiar, Shahrzad; Greil, Johann; Lang, Peter; Basu, Oliver; von Luettichau, Irene; Schulz, Ansgar; Sykora, Karl-Walter; Jarisch, Andrea; Soerensen, Jan; Salzmann-Manrique, Emilia; Seifried, Erhard; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

    2016-01-01

    To circumvent donor-to-donor heterogeneity which may lead to inconsistent results after treatment of acute graft-versus-host disease with mesenchymal stromal cells generated from single donors we developed a novel approach by generating these cells from pooled bone marrow mononuclear cells of 8 healthy “3rd-party” donors. Generated cells were frozen in 209 vials and designated as mesenchymal stromal cell bank. These vials served as a source for generation of clinical grade mesenchymal stromal cell end-products, which exhibited typical mesenchymal stromal cell phenotype, trilineage differentiation potential and at later passages expressed replicative senescence-related markers (p21 and p16). Genetic analysis demonstrated their genomic stability (normal karyotype and a diploid pattern). Importantly, clinical end-products exerted a significantly higher allosuppressive potential than the mean allosuppressive potential of mesenchymal stromal cells generated from the same donors individually. Administration of 81 mesenchymal stromal cell end-products to 26 patients with severe steroid-resistant acute graft-versus-host disease in 7 stem cell transplant centers who were refractory to many lines of treatment, induced a 77% overall response at the primary end point (day 28). Remarkably, although the cohort of patients was highly challenging (96% grade III/IV and only 4% grade II graft-versus-host disease), after treatment with mesenchymal stromal cell end-products the overall survival rate at two years follow up was 71±11% for the entire patient cohort, compared to 51.4±9.0% in graft-versus-host disease clinical studies, in which mesenchymal stromal cells were derived from single donors. Mesenchymal stromal cell end-products may, therefore, provide a novel therapeutic tool for the effective treatment of severe acute graft-versus-host disease. PMID:27175026

  13. Gateway for migrant rescue in the Mediterranean

    OpenAIRE

    Zarb Adami, Kris; Duca, Edward

    2015-01-01

    Malta should set up a coastal over-the-horizon radar (developed at ISSA-Institute of Space Science and Astronomy) with the capability of detecting small fast-moving vessels within a 1000km radius. http://www.um.edu.mt/think/gateway-for-migrant-rescue-in-the-mediterranean/

  14. Emergency Medical Rescue in a Radiation Environment

    Energy Technology Data Exchange (ETDEWEB)

    Briesmeister, L.; Ellington, Y.; Hollis, R.; Kunzman, J.; McNaughton, M.; Ramsey, G.; Somers, B.; Turner, A.; Finn, J.

    1999-09-14

    Previous experience with emergency medical rescues in the presence of radiation or contamination indicates that the training provided to emergency responders is not always appropriate. A new course developed at Los Alamos includes specific procedures for emergency response in a variety of radiological conditions.

  15. Emergency Medical Rescue in a Radiation Environment

    International Nuclear Information System (INIS)

    Previous experience with emergency medical rescues in the presence of radiation or contamination indicates that the training provided to emergency responders is not always appropriate. A new course developed at Los Alamos includes specific procedures for emergency response in a variety of radiological conditions

  16. Minimizing extinction risk through genetic rescue

    Directory of Open Access Journals (Sweden)

    Waite, T. A.

    2005-12-01

    Full Text Available According to the genetic rescue hypothesis, immigrants can improve population persistence through their genetic contribution alone. We investigate the potential for such rescue using small, inbred laboratory populations of the bean beetle (Callosobruchus maculatus. We ask how many migrants per generation (MPG are needed to minimize the genetic component of extinction risk. During Phase 1, population size was made to fluctuate between 6 and 60 (for 10 generations. During this phase, we manipulated the number of MPG, replacing 0, 1, 3, or 5 females every generation with immigrant females. During Phase 2, we simply set an upper limit on population size (.10. Compared with the 0-MPG treatment, the other treatments were equivalently effective at improving reproductive success and reducing extinction risk. A single MPG was sufficient for genetic rescue, apparently because effective migration rate was inflated dramatically during generations when population size was small. An analysis of quasi-extinction suggests that replicate populations in the 1-MPG treatment benefited from initial purging of inbreeding depression. Populations in this treatment performed so well apparently because they received the dual benefit of purging followed by genetic infusion. Our results suggest the need for further evaluation of alternative schemes for genetic rescue.

  17. Point-of-care ultrasonography during rescue operations on board a Polish Medical Air Rescue helicopter.

    Science.gov (United States)

    Darocha, Tomasz; Gałązkowski, Robert; Sobczyk, Dorota; Żyła, Zbigniew; Drwiła, Rafał

    2014-12-01

    Point-of-care ultrasound examination has been increasingly widely used in pre-hospital care. The use of ultrasound in rescue medicine allows for a quick differential diagnosis, identification of the most important medical emergencies and immediate introduction of targeted treatment. Performing and interpreting a pre-hospital ultrasound examination can improve the accuracy of diagnosis and thus reduce mortality. The authors' own experiences are presented in this paper, which consist in using a portable, hand-held ultrasound apparatus during rescue operations on board a Polish Medical Air Rescue helicopter. The possibility of using an ultrasound apparatus during helicopter rescue service allows for a full professional evaluation of the patient's health condition and enables the patient to be brought to a center with the most appropriate facilities for their condition. PMID:26674604

  18. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group

    DEFF Research Database (Denmark)

    Geisler, C.H.; Kolstad, A.; Laurell, A.;

    2008-01-01

    purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole...... progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered...

  19. 30 CFR 49.2 - Availability of mine rescue teams.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Availability of mine rescue teams. 49.2 Section... TRAINING MINE RESCUE TEAMS § 49.2 Availability of mine rescue teams. (a) Except where alternative... teams which are available at all times when miners are underground; or (2) Enter into an arrangement...

  20. 78 FR 58567 - Criteria to Certify Coal Mine Rescue Teams

    Science.gov (United States)

    2013-09-24

    ... Safety and Health Administration Criteria to Certify Coal Mine Rescue Teams AGENCY: Mine Safety and... mine rescue team training. MSHA prescribes training materials through the issuance of instruction guides. Existing standards for coal mine rescue teams include criteria for mine operators to certify...

  1. Ensemble-based computational approach discriminates functional activity of p53 cancer and rescue mutants.

    Directory of Open Access Journals (Sweden)

    Özlem Demir

    2011-10-01

    Full Text Available The tumor suppressor protein p53 can lose its function upon single-point missense mutations in the core DNA-binding domain ("cancer mutants". Activity can be restored by second-site suppressor mutations ("rescue mutants". This paper relates the functional activity of p53 cancer and rescue mutants to their overall molecular dynamics (MD, without focusing on local structural details. A novel global measure of protein flexibility for the p53 core DNA-binding domain, the number of clusters at a certain RMSD cutoff, was computed by clustering over 0.7 µs of explicitly solvated all-atom MD simulations. For wild-type p53 and a sample of p53 cancer or rescue mutants, the number of clusters was a good predictor of in vivo p53 functional activity in cell-based assays. This number-of-clusters (NOC metric was strongly correlated (r(2 = 0.77 with reported values of experimentally measured ΔΔG protein thermodynamic stability. Interpreting the number of clusters as a measure of protein flexibility: (i p53 cancer mutants were more flexible than wild-type protein, (ii second-site rescue mutations decreased the flexibility of cancer mutants, and (iii negative controls of non-rescue second-site mutants did not. This new method reflects the overall stability of the p53 core domain and can discriminate which second-site mutations restore activity to p53 cancer mutants.

  2. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism.

    NARCIS (Netherlands)

    Robben, J.H.; Sze, M.; Knoers, N.V.A.M.; Deen, P.M.T.

    2006-01-01

    Because missense mutations in genetic diseases of membrane proteins often result in endoplasmic reticulum (ER) retention of functional proteins, drug-induced rescue of their cell surface expression and understanding the underlying mechanism are of clinical value. To study this, we tested chemical ch

  3. Launch-Off-Need Shuttle Hubble Rescue Mission: Medical Issues

    Science.gov (United States)

    Hamilton, Douglas; Gillis, David; Ilcus, Linda; Perchonok, Michele; Polk, James; Brandt, Keith; Powers, Edward; Stepaniak, Phillip

    2008-01-01

    The Space Shuttle Hubble repair mission (STS-125) is unique in that a rescue mission (STS-400) has to be ready to launch before STS-125 life support runs out should the vehicle become stranded. The shuttle uses electrical power derived from fuel cells that use cryogenic oxygen and hydrogen (CRYO) to run all subsystems including the Environmental Control System. If the STS-125 crew cannot return to Earth due to failure of a critical subsystem, they must power down all nonessential systems and wait to be rescued by STS-400. This power down will cause the cabin temperature to be 60 F or less and freeze the rest of the vehicle, preventing it from attempting a reentry. After an emergency has been declared, STS-125 must wait at least 7 days to power down since that is the earliest that STS-400 can be launched. Problem The delayed power down of STS-125 causes CYRO to be consumed at high rates and limits the survival time after STS-400 launches to 10 days or less. CRYO will run out sooner every day that the STS-400 launch is delayed (weather at launch, technical issues etc.). To preserve CRYO and lithium hydroxide (LiOH - carbon dioxide removal) the crew will perform no exercise to reduce their metabolic rates, yet each deconditioned STS-125 crewmember must perform an EVA to rescue himself. The cabin may be cold for 10 days, which may cause shivering, increasing the metabolic rate of the STS-125 crew. Solution To preserve LiOH, the STS-125 manifest includes nutrition bars with low carbohydrate content to maintain crew respiratory quotient (RQ) below 0.85 as opposed to the usual shuttle galley food which is rich in carbohydrates and keeps the RQ at approximately 0.95. To keep the crew more comfortable in the cold vehicle warm clothing also has been included. However, with no exercise and limited diet, the deconditioned STS-125 crew returning on STS-400 may not be able to egress the vehicle autonomously requiring a supplemented crash-and-rescue capability.

  4. Nitric oxide rescues thalidomide mediated teratogenicity

    OpenAIRE

    Siamwala, Jamila H; Veeriah, Vimal; Priya, M. Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Shunmugam; T, Pradeep; Chatterjee, Suvro

    2012-01-01

    Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated lim...

  5. SARMApp: Search and Rescue Mapping Application

    OpenAIRE

    Burkinshaw, Joseph P.

    2010-01-01

    In Search and Rescue (SAR) operations, the search team must know how to scan their search area efficiently with limited resources. Advances in mobile technology are driving the rapid growth of location based services (LBS) and this dissertation project investigates the feasibility of an LBS to support SAR operations. The LBS requires the ability to locate search team members, perform visibility analysis on-the-fly, and dynamically convey this information back to the user on a variety of mobil...

  6. Rescuing Political Theory From Fact-Insensitivity

    OpenAIRE

    Kai Nielsen

    2012-01-01

    G. A. Cohen, in his Rescuing Justice and Equality, argues that fundamental moral principles do not rest on factual grounds. I contest that and argue instead that all fundamental moral principles (indeed, all moral principles) are fact-sensitive. They are the most deeply embedded principles in an interdependent web of beliefs—beliefs which include factual beliefs. Indeed, all functioning moral beliefs, moral principles and moral practices are in such interdependent webs. There are no fundament...

  7. Disaster Prevention and Rescue Information Service Platforms

    Directory of Open Access Journals (Sweden)

    Wen-Ray Su

    2011-12-01

    Full Text Available Because of its special hydrology and physiographic environmental conditions, Taiwan experiences a wide range of natural disasters, such as typhoons, floods, slope collapses, debris flows, and earthquakes, resulting in the loss of many lives and properties. Integration of disaster-related information, such as data and models, and the analysis and application of the information are crucial to reduce the damage caused by natural disasters. Therefore, the National Science and Technology Center for Disaster Reduction introduced the information service platform technology of the Research Development and Evaluation Commission to integrate the information of related ministerial departments for added value and use. Related technologies have integrated information of disaster prevention and rescues, assisted the government in disaster prevention and rescue, and effectively reduced the time required for information integration. Additionally, the added value of information applications enabled situational analysis and process handling during natural disasters. This study uses responses to typhoons as examples, and describes how the service application platform of disaster prevention and rescue is used to integrate various data in the response processes and employs related systems to provide users real-time information as a reference for subsequent decision-making.

  8. A formulated red ginseng extract rescues PC12 cells from PCB-induced oxidative cell death through Nrf2-mediated upregulation of heme oxygenase-1 and glutamate cysteine ligase

    International Nuclear Information System (INIS)

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that display a broad spectrum of biological and toxicological properties. There has been compelling evidence supporting that PCB-induced cytotoxicity is mediated through generation of reactive oxygen species (ROS). Considerable attention has been focused on identifying naturally occurring phytochemicals that are able to scavenge excess ROS, thereby protecting against oxidative cell death. Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. In this study, we have investigated the effect of red ginseng extract (RGE) on PCB126-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. PC12 cells treated with PCB126 exhibited increased accumulation of intracellular ROS and underwent apoptosis as determined by positive in situ terminal end-labeling (TUNEL staining) and the perturbation of the mitochondrial membrane potential (ΔΨm). RGE treatment attenuated PCB126-induced cytotoxicity, apoptotic features and intracellular ROS accumulation. RGE treatment upregulated heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCLC) that are key antioxidant enzymes essential for cellular defense against oxidative stress. To elucidate the molecular mechanisms underlying RGE-mediated HO-1 and GCLC induction, we have examined the possible involvement of NF-E2-related factor 2 (Nrf2), a redox-sensitive transcription factor, that plays an important role in the transcriptional regulation of diverse antioxidative genes via interaction with the antioxidant response element (ARE). Treatment of PC12 cells with RGE increased the nuclear translocation, ARE-binding and transcriptional activity of Nrf2. Moreover, U0126 and LY294002, pharmacological inhibitors of MEK1/2 and phosphatidylinositol 3-kinase

  9. Bone marrow transplantation restores epidermal basement membrane protein expression and rescues epidermolysis bullosa model mice

    OpenAIRE

    Fujita, Yasuyuki; Abe, Riichiro; Inokuma, Daisuke; Sasaki, Mikako; Hoshina, Daichi; Natsuga, Ken; Nishie, Wataru; McMillan, James R.; Nakamura, Hideki; Shimizu, Tadamichi; Akiyama, Masashi; Sawamura, Daisuke; Shimizu, Hiroshi

    2010-01-01

    Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. However, it is considered more difficult to restore structural proteins than to restore secretory enzymes. This study aims to clarify whether bone marrow transplantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) ...

  10. Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism.

    OpenAIRE

    Robben, J.H.; Sze, M.; Knoers, N.V.A.M.; Deen, P. M. T.

    2006-01-01

    Because missense mutations in genetic diseases of membrane proteins often result in endoplasmic reticulum (ER) retention of functional proteins, drug-induced rescue of their cell surface expression and understanding the underlying mechanism are of clinical value. To study this, we tested chemical chaperones and sarco(endo)plasmic reticulum Ca2+ ATPase pump inhibitors on Madin-Darby canine kidney cells expressing nine ER-retained vasopressin type-2 receptor (V2R) mutants involved in nephrogeni...

  11. Rescue MIKE: An Automatic Commentary System for Disaster Simulation

    Science.gov (United States)

    Kubo, Takenori; Morishita, Takuya; Shimora, Hiroki; Kawarabayashi, Tomomi; Odaka, Tomohiro; Ogura, Hisakazu; Frank, Ian; Tanaka-Ishii, Kumiko; Tadokoro, Satoshi; Matsubara, Hitoshi

    We designed the system, Rescue-MIKE, and implemented to the RoboCup Rescue Simulation System. The Rescue MIKE system aims to communicate with large numbers of relief workers and controllers working in a rescue domain. The system has an ability to report the situation of the domain like a newscaster. Our system consists of multiple agents. The system collects information from a simulated disaster scenario, and then produces a dialogue that fits to the actions of the agents in the domain. We described the design policy, implementation of our system, and Rescue-MIKE's facility. Rescue-MIKE initial version can provide aural information that helps to explain the unfolding scenarios to onlookers. We discussed the future applications of our system, including knowledge elicitation about disaster relief control methods, automated relief support systems, and public education about the dangers of large natural disasters such as earthquakes, floods or volcanic eruptions.

  12. Lipid rescue in children: The prompt decision.

    Science.gov (United States)

    Eizaga Rebollar, Ramón; García Palacios, María V; Morales Guerrero, Javier; Torres Morera, Luis M

    2016-08-01

    We report the case of a 17-month-old child who underwent laparotomy under general anesthesia and caudal block. Electrocardiogram ST-T changes were observed after local anesthetic injection. The prompt use of Intralipid 30% was successful in normalizing ECG alterations. Our experience is consistent with previous literature, mainly carried out in adults. Thereby, we conduct a brief review of the subject in pediatrics. As a major conclusion, we strongly recommend the "fast-track" lipid rescue as soon as this severe complication is detected. PMID:27290983

  13. A competency framework for the business rescue practitioner profession

    OpenAIRE

    Marius Pretorius

    2014-01-01

    Orientation: Business Rescue Practitioner (BRP) tasks are complex and involve a wide range of knowledge, tacit skills and experience not accessible to novices.Research purpose: Competencies required by business rescue practitioners (BRPs) to navigate a distressed venture were investigated. What BRPs actually ‘do’ during a rescue guided the development of a competency framework to inform future qualification guidelines for BRP education and accreditation.Motivation for the study: To investigat...

  14. The Pain and the Gain of Rescuing Historic Science Data: The Nimbus Data Rescue Project

    Science.gov (United States)

    Gallaher, D. W.; Campbell, G. G.

    2015-12-01

    While technology of our satellite systems have greatly improved the quality of observations over the past 50 years, it is the legacy of the first global coverage environment satellites, the Nimbus systems launched by NASA in the mid-1960s, that marks the beginning of a unique perspective from space. Such early data can extend our climate record and provide important context in longer-term climate changes. Unfortunately, the Nimbus data nearly disappeared before its value was recognized and attempts to recover the data were undertaken. While the Nimbus data was never truly lost, it was in a form that could not be read and was not organized in a way that could be accessed with modern computer systems. The rescue and recovery of the Nimbus data began in 2007 with an initiative by the NASA Goddard Space Flight Center. Without the Goddard efforts, the early Nimbus data might be forever dark. The Nimbus Rescue Project has just completed processing and archival of the Nimbus 4 visible and infrared observations from 1970 and 1971. This adds to our rescue efforts from Nimbus 1, 2 and 3 for 1964, 1966 and 1969. The procedures to recover the Nimbus data, from both film and tape, could be used by other data rescue projects, however the algorithms presented will tend to be Nimbus specific. The compositing of the mapped minimum brightness over weekly intervals resulted in never before seen views of the Polar Regions, such as a visible light view of the Antarctic ice extent from October 1970 (Figure 1). The Nimbus data recovery and reprocessing into modern formats was important, however it was the utility of the data as a part of the satellite climate record that made it valuable. Data rescue projects are often both difficult and time consuming but the data they bring back to the science community makes these efforts worthwhile.

  15. Leadership lessons from the Chilean mine rescue.

    Science.gov (United States)

    Rashid, Faaiza; Edmondson, Amy C; Leonard, Herman B

    2013-01-01

    Three years ago, when a cave-in at the San José mine in Chile trapped 33 men under 700,000 metric tons of rock, experts estimated the probability of getting them out alive at less than 1%. Yet, after spending a record 69 days underground, all 33 were hoisted up to safety. The inspiring story of their rescue is a case study in how to lead in situations where the stakes, risk, and uncertainty are incredibly high and time pressure is intense. Today executives often find themselves in similar straits. When they do, many feel torn. Should they be directive, taking charge and commanding action? Or should they be empowering, enabling innovation and experimentation? As the successful example of André Sougarret, the chief of the mine rescue operation, shows, the answer is yes--to both. The choice is a false dichotomy. Implementing this dual approach involves three key tasks. Each has directive and enabling components. The first task is envisioning, which requires instilling both realism and hope. The second task is enrolling, which means setting clear boundaries for who is on and off the team, but inviting in helpful collaborators. The third task is engaging--leading disciplined execution while encouraging innovation and experimentation. The authors of this article describe how Sougarret ably juggled all of these tasks, orchestrating the efforts of hundreds of people from different organizations, areas of expertise, and countries in an extraordinary mission that overcame impossible odds. PMID:24730174

  16. 30 CFR 49.17 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines § 49.17 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by...

  17. Phosphodiesterase inhibition rescues chronic cognitive deficits induced by traumatic brain injury.

    Science.gov (United States)

    Titus, David J; Sakurai, Atsushi; Kang, Yuan; Furones, Concepcion; Jergova, Stanislava; Santos, Rosmery; Sick, Thomas J; Atkins, Coleen M

    2013-03-20

    Traumatic brain injury (TBI) modulates several cell signaling pathways in the hippocampus critical for memory formation. Previous studies have found that the cAMP-protein kinase A signaling pathway is downregulated after TBI and that treatment with a phosphodiesterase (PDE) 4 inhibitor rolipram rescues the decrease in cAMP. In the present study, we examined the effect of rolipram on TBI-induced cognitive impairments. At 2 weeks after moderate fluid-percussion brain injury or sham surgery, adult male Sprague Dawley rats received vehicle or rolipram (0.03 mg/kg) 30 min before water maze acquisition or cue and contextual fear conditioning. TBI animals treated with rolipram showed a significant improvement in water maze acquisition and retention of both cue and contextual fear conditioning compared with vehicle-treated TBI animals. Cue and contextual fear conditioning significantly increased phosphorylated CREB levels in the hippocampus of sham animals, but not in TBI animals. This deficit in CREB activation during learning was rescued in TBI animals treated with rolipram. Hippocampal long-term potentiation was reduced in TBI animals, and this was also rescued with rolipram treatment. These results indicate that the PDE4 inhibitor rolipram rescues cognitive impairments after TBI, and this may be mediated through increased CREB activation during learning. PMID:23516287

  18. 30 CFR 57.4362 - Underground rescue and firefighting operations.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Underground rescue and firefighting operations... METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Fire Prevention and Control Firefighting Procedures/alarms/drills § 57.4362 Underground rescue...

  19. 46 CFR 108.565 - Stowage of rescue boats.

    Science.gov (United States)

    2010-10-01

    ... operation of any survival craft at any other launching station. (4) Each rescue boat that is also a lifeboat... rescue boat batteries from the unit's power supply at a supply voltage not exceeding 50 volts. (c) Each... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS...

  20. 46 CFR 133.140 - Stowage of rescue boats.

    Science.gov (United States)

    2010-10-01

    ... survival craft at any other launching station. (b) Each rescue boat must be provided a means for recharging the rescue boat batteries from the OSV's power supply at a supply voltage not exceeding 50 volts. (c... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OFFSHORE SUPPLY VESSELS...

  1. 78 FR 79010 - Criteria to Certify Coal Mine Rescue Teams

    Science.gov (United States)

    2013-12-27

    ... training. MSHA published a notice in the Federal Register (78 FR 58567) announcing the availability of the... Safety and Health Administration Criteria to Certify Coal Mine Rescue Teams AGENCY: Mine Safety and... Safety and Health Administration (MSHA) has updated the coal mine rescue team certification criteria....

  2. Evolution of rescue personnel recovery for a new environment

    OpenAIRE

    Meggett, David C.

    2007-01-01

    R missions in support of a variety of customers. This thesis examines the changing environment in which Combat Rescue forces are employed; evaluates the ability of these forces to perform PR tasks within an Irregular Warfare campaign; and makes recommendations regarding where and under whose control rescue assets should be employed.

  3. Nitric oxide rescues thalidomide mediated teratogenicity.

    Science.gov (United States)

    Siamwala, Jamila H; Veeriah, Vimal; Priya, M Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Shunmugam; Pradeep, T; Chatterjee, Suvro

    2012-01-01

    Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities. PMID:22997553

  4. Air and sea rescue via satellite systems

    Science.gov (United States)

    Scales, W. C.; Swanson, R.

    1984-03-01

    Two approaches to a satellite system for air and sea rescue to be put into use by the 1990s, one employing polar-orbiting satellites and the other using fixed geosynchronous satellites over the equator, are discussed. A battery-powered transmitter on a ship or aircraft would be activated in an accident to emit a low-power omnidirectional signal that would be relayed by a satellite to an earth station. The polar-orbiting approach, now being evaluated on a small-scale with the Cospas-Sarsat system, allows complete coverage of the earth, including the poles, and provides a fix on the origin of the distress signals by means of the Doppler shift. A parallel effort for the testing of geostationary satellites to measure system sensitivity to various interference sources, to optimize design, and to measure land and sea performance is reviewed.

  5. Disaster Rescue Simulation based on Complex Adaptive Theory

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2013-05-01

    Full Text Available Disaster rescue is one of the key measures of disaster reduction. The rescue process is a complex process with the characteristics of large scale, complicate structure, non-linear. It is hard to describe and analyze them with traditional methods. Based on complex adaptive theory, this paper analyzes the complex adaptation of the rescue process from seven features: aggregation, nonlinearity, mobility, diversity, tagging, internal model and building block. With the support of Repast platform, an agent-based model including rescue agents and victim agents was proposed. Moreover, two simulations with different parameters are employed to examine the feasibility of the model. As a result, the proposed model has been shown that it is efficient in dealing with the disaster rescue simulation and can provide the reference for making decisions.

  6. Research of Insertion Mechanism of Flexible Search and Rescue Robot

    Directory of Open Access Journals (Sweden)

    Shen Linyong

    2015-01-01

    Full Text Available Due to various factors, the global scope disaster events occur inevitably every year. Terrorism, natural disasters or destructive earthquakes tend to cause a large number of people buried in the ruins of buildings. The research of search and rescue instruments research is mainly focused on snake-like robot and life detector both at home and abroad. The endoscopic search and rescue robot in this paper combines the characteristics of these two kinds of search and rescue equipment. This thesis mainly studies the insertion mechanism of endoscopic flexible search and rescue robot. Based on the mechanics characteristics of the flexible robot body, this paper analyzes several common failure modes during the insertion into the ruins. This article puts forward the scheme of segmented gradual pulling-pushing, which plays an important role in promoting search and rescue work.

  7. Posture manipulation for rescue activity via small traction robots

    International Nuclear Information System (INIS)

    We discuss a conceptual design of rescue robots against nuclear-power plant accidents. We claim that the rescue robots in nuclear-power plants should have the following properties. (1) The size is small. (2) The structure is simple. (3) The number of the robots is large. This paper studies the rescue robots to rescue people in an area polluted with radioactive leakage in nuclear power institutions. In particular, we propose a rescue system which consists of a group of small mobile robots. First, small traction robots set the posture of the fainted victims to carry easily, and carry them to the safety space with the mobile robots for the stretcher composition. In this paper, we describe the produced small traction robots. And, we confirm that the robots can manipulate a 40 kg dummy doll's posture. We also examine the optimal number of robots from a perspective of working efficiency in the assumption spot. (author)

  8. Rubella-Associated Arthritis: Rescue of Rubella Virus from Peripheral Blood Lymphocytes Two Years Postvaccination

    OpenAIRE

    Chantler, J. K.; Ford, D K; Tingle, A. J.

    1981-01-01

    Rubella virus was isolated from the peripheral lymphocytes of a patient with rubella-associated arthritis 2 years after rubella vaccination. The rescue of the virus was carried out by stimulating the lymphocytes with mitogens for several days in cultures and then cocultivating them with RK13 cells at 35°C. Rubella virus was detected by a variety of techniques, including electron microscopy, indirect immunofluorescence, polyacrylamide gel analysis of labeled viral proteins, and microfocus assa...

  9. Impaired Infectivity of Ritonavir-resistant HIV Is Rescued by Heat Shock Protein 90AB1*

    OpenAIRE

    Joshi, Pheroze; Stoddart, Cheryl A.

    2011-01-01

    Certain ritonavir resistance mutations impair HIV infectivity through incomplete Gag processing by the mutant viral protease. Analysis of the mutant virus phenotype indicates that accumulation of capsid-spacer peptide 1 precursor protein in virus particles impairs HIV infectivity and that the protease mutant virus is arrested during the early postentry stage of HIV infection before proviral DNA synthesis. However, activation of the target cell can rescue this defect, implying that specific ho...

  10. Rescue of an In Vitro Neuron Phenotype Identified in Niemann-Pick Disease, Type C1 Induced Pluripotent Stem Cell-Derived Neurons by Modulating the WNT Pathway and Calcium Signaling

    OpenAIRE

    Efthymiou, Anastasia G.; Steiner, Joe; Pavan, William J.; Wincovitch, Stephen; Larson, Denise M.; Porter, Forbes D.; Rao, Mahendra S; Malik, Nasir

    2015-01-01

    This study involved the generation of an induced pluripotent stem cell line from a subject homozygous for the most frequent Niemann-Pick disease, type C1 (NPC1) mutation and the subsequent creation of a stable line of neural stem cells as a disease model for NPC1. The clear readout from these cells makes them ideal candidates for high-throughput screening and is a valuable tool to better understand the development of NPC1 and to develop better therapeutic options.

  11. Medical rescue of naval combat:challenge and future

    Institute of Scientific and Technical Information of China (English)

    Hai Jin; Li-Jun Hou; Xiao-Bing Fu

    2015-01-01

    There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what chal-lenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health services, medical training and future medical research programs. We also discuss the characteristics of modern naval combat, medical rescue challenges, medical treatment highlights and future develop-ments of medical rescue at sea.

  12. Guidance of Autonomous Amphibious Vehicles for Flood Rescue Support

    OpenAIRE

    Shankarachary Ragi; ChingSeong Tan; Chong, Edwin K. P.

    2013-01-01

    We develop a path-planning algorithm to guide autonomous amphibious vehicles (AAVs) for flood rescue support missions. Specifically, we develop an algorithm to control multiple AAVs to reach/rescue multiple victims (also called targets) in a flood scenario in 2D, where the flood water flows across the scene and the targets move (drifted by the flood water) along the flood stream. A target is said to be rescued if an AAV lies within a circular region of a certain radius around the target. The ...

  13. Computer Security: DNS to the rescue!

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2016-01-01

    Why you should be grateful to the Domain Name System at CERN.   Incidents involving so-called “drive-by” infections and “ransomware” are on the rise. Whilst an up-to-date and fully patched operating system is essential; whilst running anti-virus software with current virus signature files is a must; whilst “stop --- think --- don’t click” surely helps, we can still go one step further in better protecting your computers: DNS to the rescue. The DNS, short for Domain Name System, translates the web address you want to visit (like “http://cern.ch”) to a machine-readable format (the IP address, here: “188.184.9.234”). For years, we have automatically monitored the DNS translation requests made by your favourite web browser (actually by your operating system, but that doesn’t matter here), and we have automatically informed you if your computer tried to access a website known to hos...

  14. Equipment of medical backpacks in mountain rescue.

    Science.gov (United States)

    Elsensohn, Fidel; Soteras, Inigo; Resiten, Oliver; Ellerton, John; Brugger, Hermann; Paal, Peter

    2011-01-01

    We conducted a survey of equipment in medical backpacks for mountain rescuers and mountain emergency physicians. The aim was to investigate whether there are standards for medical equipment in mountain rescue organizations associated with the International Commission for Mountain Emergency Medicine (ICAR MEDCOM). A questionnaire was completed by 18 member organizations from 14 countries. Backpacks for first responders are well equipped to manage trauma, but deficiencies in equipment to treat medical emergencies were found. Paramedic and physicians' backpacks were well equipped to provide advanced life support and contained suitable drugs. We recommend that medical backpacks should be equipped in accordance with national laws, the medical emergencies in a given region, and take into account the climate, geography, medical training of rescuers, and funding of the organization. Automated external defibrillator provision should be improved. The effects of temperature on the drugs and equipment should be considered. Standards for training in the use and maintenance of medical tools should be enforced. First responders and physicians should only use familiar tools and drugs. PMID:22206560

  15. Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescue.

    Science.gov (United States)

    Sobolewski, Anastasia; Rudarakanchana, Nung; Upton, Paul D; Yang, Jun; Crilley, Trina K; Trembath, Richard C; Morrell, Nicholas W

    2008-10-15

    Heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II receptor cause familial pulmonary arterial hypertension (PAH). We previously demonstrated that the substitution of cysteine residues in the ligand-binding domain of this receptor prevents receptor trafficking to the cell membrane. Here we demonstrate the potential for chemical chaperones to rescue cell-surface expression of mutant BMPR-II and restore function. HeLa cells were transiently transfected with BMPR-II wild type or mutant (C118W) receptor constructs. Immunolocalization studies confirmed the retention of the cysteine mutant receptor mainly in the endoplasmic reticulum. Co-immunoprecipitation studies of Myc-tagged BMPR-II confirmed that the cysteine-substituted ligand-binding domain mutation, C118W, is able to associate with BMP type I receptors. Furthermore, following treatment with a panel of chemical chaperones (thapsigargin, glycerol or sodium 4-phenylbutyrate), we demonstrated a marked increase in cell-surface expression of mutant C118W BMPR-II by FACS analysis and confocal microscopy. These agents also enhanced the trafficking of wild-type BMPR-II, though to a lesser extent. Increased cell-surface expression of mutant C118W BMPR-II was associated with enhanced Smad1/5 phosphorylation in response to BMPs. These findings demonstrate the potential for rescue of mutant BMPR-II function from the endoplasmic reticulum. For the C118W mutation in the ligand-binding domain of BMPR-II, cell-surface rescue leads to at least partial restoration of BMP signalling. We conclude that enhancement of cell-surface trafficking of mutant and wild-type BMPR-II may have therapeutic potential in familial PAH. PMID:18647753

  16. Laminin γ2 knockout mice rescued with the human protein exhibit enamel maturation defects.

    Science.gov (United States)

    Wazen, Rima M; Viegas-Costa, Luiz C; Fouillen, Aurélien; Moffatt, Pierre; Adair-Kirk, Tracy L; Senior, Robert M; Nanci, Antonio

    2016-01-01

    The epithelial ameloblasts are separated from the maturing enamel by an atypical basement membrane (BM) that is enriched in laminin 332 (LM-332). This heterotrimeric protein (α3, ß3 and γ2 chains) provides structural integrity to BMs and influences various epithelial cell processes including cell adhesion and differentiation. Mouse models that lack expression of individual LM-332 chains die shortly after birth. The lethal phenotype of laminin γ2 knockout mice can be rescued by human laminin γ2 (LAMC2) expressed using a doxycycline-inducible (Tet-on) cytokeratin 14 promoter-rtTA. These otherwise normal-looking rescued mice exhibit white spot lesions on incisors. We therefore investigated the effect of rescue with human LAMC2 on enamel maturation and structuring of the atypical BM. The maturation stage enamel organ in transgenic mice was severely altered as compared to wild type controls, a structured BM was no longer discernible, dystrophic matrix appeared in the maturing enamel layer, and there was residual enamel matrix late into the maturation stage. Microtomographic scans revealed excessive wear of occlusal surfaces on molars, chipping of enamel on incisor tips, and hypomineralization of the enamel layer. No structural alterations were observed at other epithelial sites, such as skin, palate and tongue. These results indicate that while this humanized mouse model is capable of rescue in various epithelial tissues, it is unable to sustain structuring of a proper BM at the interface between ameloblasts and maturing enamel. This failure may be related to the atypical composition of the BM in the maturation stage and reaffirms that the atypical BM is essential for enamel maturation. PMID:26956061

  17. Search and Rescue Plan: Swan Lake National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This plan will provide guidance to help efficiently handle a search and rescue (SAR) operation on Swan Lake National Wildlife Refuge. The purpose of this plan is to...

  18. The Cognitive Dissonance between Child Rescue and Child Protection

    NARCIS (Netherlands)

    K.E. Cheney (Kristen)

    2015-01-01

    textabstract‘Saving orphans’ has become an industry that irrevocably harms children and undermines the development of child welfare systems. We must replace the drive to rescue with the desire to protect.

  19. Search and Rescue Radar Transponder under Dynamic Operating Conditions

    OpenAIRE

    Ivančić, Paško; Kasum, Josip; Peraković, Dragan

    2015-01-01

    The Search and Rescue Radar Transponder (SART) operates in the frequency range from 9.2 GHz to 9.5 GHz. The SART is used on conventional and, partly, nonconventional vessels in search and rescue operations at sea. It is also used, to a certain extent, on inland waterways, rivers and lakes. As for their construction and design, SART transponders are self-contained, portable units. With regard to their technical characteristics and design requirements, they comply with the regulations of local ...

  20. PHENOMENON OF RESCUING VICTIMS OF NAZI REGIME UNDER THE HOLOCAUST

    OpenAIRE

    Stets, Oleg; Kovtun, Alexander

    2015-01-01

    In this article problems devoted to participation of the local Ukrainian population at the rescue of Jewry victims of the Nazi occupation regime is examined. Question of violation of human rights is analyzed and it is given description a concept «the phenomenon of rescuing». It was concluded on social and legal support rescuers Jewish people during the Second World War on the territory of modern Ukraine.

  1. 30 CFR Appendix to Subpart B - Optional Form for Certifying Mine Rescue Teams

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Optional Form for Certifying Mine Rescue Teams... EDUCATION AND TRAINING MINE RESCUE TEAMS Mine Rescue Teams for Underground Coal Mines Pt. 49, Subpt. B, App. Appendix to Subpart B—Optional Form for Certifying Mine Rescue Teams ER08FE08.000 ER08FE08.001...

  2. 78 FR 35974 - Proposed Information Collection; Comment Request; Coal Mine Rescue Teams; Arrangements for...

    Science.gov (United States)

    2013-06-14

    ... Safety and Health Administration Proposed Information Collection; Comment Request; Coal Mine Rescue Teams... protecting the safety and health of miners. 30 CFR Part 49, Mine Rescue Teams, Subpart B--Mine Rescue Teams for Underground Coal Mines, sets standards related to the availability of mine rescue teams;...

  3. 30 CFR 49.7 - Physical requirements for mine rescue team.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Physical requirements for mine rescue team. 49... EDUCATION AND TRAINING MINE RESCUE TEAMS § 49.7 Physical requirements for mine rescue team. (a) Each member of a mine rescue team shall be examined annually by a physician who shall certify that each person...

  4. 30 CFR 49.60 - Requirements for a local mine rescue contest.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Requirements for a local mine rescue contest... for a local mine rescue contest. (a) A local mine rescue contest is one that— (1) Is conducted in the... apparatus while participating in a simulated mine rescue team exercise; and (6) Includes contest judges...

  5. Increasing DNA repair methyltransferase levels via bone marrow stem cell transduction rescues mice from the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic alkylating agent.

    OpenAIRE

    R. Maze; Carney, J P; Kelley, M R; Glassner, B J; Williams, D.A.; Samson, L

    1996-01-01

    The chloroethylnitrosourea (CNU) alkylating agents are commonly used for cancer chemotherapy, but their usefulness is limited by severe bone marrow toxicity that causes the cumulative depletion of all hematopoietic lineages (pancytopenia). Bone marrow CNU sensitivity is probably due to the inefficient repair of CNU-induced DNA damage; relative to other tissues, bone marrow cells express extremely low levels of the O6-methylguanine DNA methyltransferase (MGMT) protein that repairs cytotoxic O6...

  6. Overexpression of MIP2, a novel WD-repeat protein, promotes proliferation of H9c2 cells

    International Nuclear Information System (INIS)

    WD40 repeat proteins have a wide range of diverse biological functions including signal transduction, cell cycle regulation, RNA splicing, and transcription. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a novel member of the WD40 repeat proteins superfamily that contains five WD40 repeats. Little is known about its biological role, and the purpose of this study was to determine the role of MIP2 in regulating cellular proliferation. Transfection and constitutive expression of MIP2 in the rat cardiomyoblast cell line H9c2 results in enhanced growth of those cells as measured by cell number and is proportional to the amount of MIP2 expressed. Overexpression of MIP2 results in a shorter cell cycle, as measured by flow cytometry. Collectively, these data suggest that MIP2 may participate in the progression of cell proliferation in H9c2 cells.

  7. Characterization and rescue of telomeric abnormalities in ICF syndrome type I fibroblasts.

    Directory of Open Access Journals (Sweden)

    Shiran eYehezkel

    2013-02-01

    Full Text Available Mutations in the human DNA methyltransferase 3B (DNMT3B gene lead to ICF (immunodeficiency, centromeric region instability, facial anomalies syndrome type I. We have previously described a telomere-related phenotype in cells from these patients, involving severe hypomethylation of subtelomeric regions, abnormally short telomeres and high levels of telomeric-repeat-containing RNA (TERRA. Here we demonstrate that ICF-patient fibroblasts carry abnormally short telomeres at a low population doubling and enter senescence prematurely. Accordingly, we attempted to rescue the senescence phenotype by ectopic expression of human telomerase, which led to elongated telomeres with hypomethylated subtelomeres. The senescence phenotype was overcome under these conditions, thus dissociating subtelomeric-DNA hypomethylation per se from the senescence phenotype. In addition, we examined whether the subtelomeric methylation could be restored by expression of a normal copy of full length DNMT3B1 in ICF fibroblasts. Ectopic expression of DNMT3B1 failed to rescue the abnormal hypomethylation at subtelomeres. However, partial rescue of subtelomeric-hypomethylation was achieved by co-expression of DNMT3B1 together with DNA methyltransferase 3-like (DNMT3L, encoding a protein that functions as a stimulator of DNMT3A and DNMT3B. DNMT3B1 and DNMT3L are predominantly expressed during early embryonic development, suggesting that de novo subtelomeric DNA methylation during crucial stages of human embryonic development may be necessary for setting and maintaining normal telomere length.

  8. An evaluation of coordination relationships during earthquake emergency rescue using entropy theory

    OpenAIRE

    Huang Rong; Liang Xuedong; Zeng Guizhi; Ye Yulin; Wang Da

    2015-01-01

    Emergency rescue after an earthquake is complex work which requires the participation of relief and social organizations. Studying earthquake emergency coordination efficiency can not only help rescue organizations to define their own rescue missions, but also strengthens inter-organizational communication and collaboration tasks, improves the efficiency of emergency rescue, and reduces loss. In this paper, collaborative entropy is introduced to study earthquake emergency rescue operations. T...

  9. Rescue of foot-and-mouth disease viruses that are pathogenic for cattle from preserved viral RNA samples.

    Directory of Open Access Journals (Sweden)

    Graham J Belsham

    Full Text Available BACKGROUND: Foot and mouth disease is an economically important disease of cloven-hoofed animals including cattle, sheep and pigs. It is caused by a picornavirus, foot-and-mouth disease virus (FMDV, which has a positive sense RNA genome which, when introduced into cells, can initiate virus replication. PRINCIPAL FINDINGS: A system has been developed to rescue infectious FMDV from RNA preparations generated from clinical samples obtained under experimental conditions and then applied to samples collected in the "field". Clinical samples from suspect cases of foot-and-mouth disease (FMD were obtained from within Pakistan and Afghanistan. The samples were treated to preserve the RNA and then transported to National Veterinary Institute, Lindholm, Denmark. Following RNA extraction, FMDV RNA was quantified by real-time RT-PCR and samples containing significant levels of FMDV RNA were introduced into susceptible cells using electroporation. Progeny viruses were amplified in primary bovine thyroid cells and characterized using antigen ELISA and also by RT-PCR plus sequencing. FMD viruses of three different serotypes and multiple lineages have been successfully rescued from the RNA samples. Two of the rescued viruses (of serotype O and Asia 1 were inoculated into bull calves under high containment conditions. Acute clinical disease was observed in each case which spread rapidly from the inoculated calves to in-contact animals. Thus the rescued viruses were highly pathogenic. The availability of the rescued viruses enabled serotyping by antigen ELISA and facilitated genome sequencing. CONCLUSIONS: The procedure described here should improve the characterization of FMDVs circulating in countries where the disease is endemic and thus enhance disease control globally.

  10. Rescue of newborn ants by older Cataglyphis cursor adult workers.

    Science.gov (United States)

    Nowbahari, Elise; Amirault, Céline; Hollis, Karen L

    2016-05-01

    Cataglyphis cursor worker ants are capable of highly sophisticated rescue behaviour in which individuals are able to identify what has trapped a nestmate and to direct their behaviour towards that obstacle. Nonetheless, rescue behaviour is constrained by workers' subcaste: whereas foragers, the oldest workers, are able both to give and to receive the most help, the youngest workers, inactives, neither give nor receive any help whatsoever; nurses give and receive intermediate levels of aid, reflecting their intermediate age. Such differences in rescue behaviour across subcastes suggest that age and experience play a critical role. In this species, as in many others in which a sensitive period for nestmate recognition exists, newly enclosed ants, called callows, are adopted by ants belonging not only to different colonies but also to different species; foreign callows receive nearly the same special care provided to resident newborns. Because callows are younger than inactives, which are incapable of soliciting rescue, we wondered whether entrapped callows would receive such aid. In the present study, we artificially ensnared individual callows from their own colony (homocolonial), from a different colony (heterocolonial), and from a different species (heterospecific), and tested each one with groups of five potential C. cursor rescuers, either all foragers or all nurses. Our results show that all three types of callows are able to elicit rescue behaviour from both foragers and nurses. Nonetheless, nurse rescuers are better able to discriminate between the three types of callow victims than are foragers. PMID:26846232

  11. Development of a Mine Rescue Drilling System (MRDS) :

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, David W.; Gaither, Katherine N.; Polsky, Yarom; Knudsen, Steven D.; Broome, Scott Thomas; Su, Jiann-Cherng; Blankenship, Douglas A.; Costin, Laurence S.

    2014-06-01

    Sandia National Laboratories (Sandia) has a long history in developing compact, mobile, very high-speed drilling systems and this technology could be applied to increasing the rate at which boreholes are drilled during a mine accident response. The present study reviews current technical approaches, primarily based on technology developed under other programs, analyzes mine rescue specific requirements to develop a conceptual mine rescue drilling approach, and finally, proposes development of a phased mine rescue drilling system (MRDS) that accomplishes (1) development of rapid drilling MRDS equipment; (2) structuring improved web communication through the Mine Safety & Health Administration (MSHA) web site; (3) development of an improved protocol for employment of existing drilling technology in emergencies; (4) deployment of advanced technologies to complement mine rescue drilling operations during emergency events; and (5) preliminary discussion of potential future technology development of specialized MRDS equipment. This phased approach allows for rapid fielding of a basic system for improved rescue drilling, with the ability to improve the system over time at a reasonable cost.

  12. An unmanned search and rescue mission

    Science.gov (United States)

    Novaro Mascarello, Laura; Quagliotti, Fulvia; Bertini, Mario

    2016-04-01

    The Remotely Piloted Aircraft Systems (RPAS) are becoming more and more powerful and innovative and they have an increased interest in civil applications, in particular, after natural hazard phenomena. The RPAS is useful in search and rescue missions in high mountain where scenarios are unfriendly and the use of helicopters is often not profitable. First, the unmanned configuration is safer because there is no hazards for human life that is not on board. Moreover, it is cheaper due to the use of electric propulsion instead of internal combustion engine and to its small dimensions and weights. Finally, the use of the RPAS is faster while the helicopter is often not available because is involved in other missions or it cannot be used if the search mission is in impervious scenario, such as forests with thick vegetation. For instance, the RPAS can be used after an avalanche when victims have little time to be saved before the death by hypothermia. In most conditions, the body maintains a healthy temperature. However, if it is exposed to cold temperatures, especially with a high cooling factor from wind and high humidity, for extended periods, the control mechanisms of the body may not be able to maintain a normal body temperature. When you lose more heat than the body can generate, it takes over hypothermia, defined as a body temperature below 35° C. Wet clothing, fall into cold water or not adequately cover themselves during the cold season, are all factors that can increase the chances of hypothermia. Signs and symptoms (tremor, slurred speech, breathing abnormally slow, cold and pale skin, loss of coordination, fatigue, lethargy or apathy, confusion or memory loss) usually develop slowly. People with hypothermia typically experience a gradual loss of mental acuity and physical capacity, and realize that you have need of emergency medical care. For these reasons, the use of an RPAS could be crucial for the survival of disappeared people in high mountain. In

  13. Structures of oncogenic, suppressor and rescued p53 core-domain variants: mechanisms of mutant p53 rescue

    Energy Technology Data Exchange (ETDEWEB)

    Wallentine, Brad D.; Wang, Ying; Tretyachenko-Ladokhina, Vira; Tan, Martha; Senear, Donald F. [University of California, Irvine, Irvine, CA 92697 (United States); Luecke, Hartmut, E-mail: hudel@uci.edu [University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States); University of California, Irvine, Irvine, CA 92697 (United States); Universidad del Pais Vasco, 48940 Leioa (Spain)

    2013-10-01

    X-ray crystallographic structures of four p53 core-domain variants were determined in order to gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53. To gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53, X-ray crystallographic structures of four p53 core-domain variants were determined. These include an oncogenic mutant, V157F, two single-site suppressor mutants, N235K and N239Y, and the rescued cancer mutant V157F/N235K/N239Y. The V157F mutation substitutes a smaller hydrophobic valine with a larger hydrophobic phenylalanine within strand S4 of the hydrophobic core. The structure of this cancer mutant shows no gross structural changes in the overall fold of the p53 core domain, only minor rearrangements of side chains within the hydrophobic core of the protein. Based on biochemical analysis, these small local perturbations induce instability in the protein, increasing the free energy by 3.6 kcal mol{sup −1} (15.1 kJ mol{sup −1}). Further biochemical evidence shows that each suppressor mutation, N235K or N239Y, acts individually to restore thermodynamic stability to V157F and that both together are more effective than either alone. All rescued mutants were found to have wild-type DNA-binding activity when assessed at a permissive temperature, thus pointing to thermodynamic stability as the critical underlying variable. Interestingly, thermodynamic analysis shows that while N239Y demonstrates stabilization of the wild-type p53 core domain, N235K does not. These observations suggest distinct structural mechanisms of rescue. A new salt bridge between Lys235 and Glu198, found in both the N235K and rescued cancer mutant structures, suggests a rescue mechanism that relies on stabilizing the

  14. Structures of oncogenic, suppressor and rescued p53 core-domain variants: mechanisms of mutant p53 rescue

    International Nuclear Information System (INIS)

    X-ray crystallographic structures of four p53 core-domain variants were determined in order to gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53. To gain insights into the mechanisms by which certain second-site suppressor mutations rescue the function of a significant number of cancer mutations of the tumor suppressor protein p53, X-ray crystallographic structures of four p53 core-domain variants were determined. These include an oncogenic mutant, V157F, two single-site suppressor mutants, N235K and N239Y, and the rescued cancer mutant V157F/N235K/N239Y. The V157F mutation substitutes a smaller hydrophobic valine with a larger hydrophobic phenylalanine within strand S4 of the hydrophobic core. The structure of this cancer mutant shows no gross structural changes in the overall fold of the p53 core domain, only minor rearrangements of side chains within the hydrophobic core of the protein. Based on biochemical analysis, these small local perturbations induce instability in the protein, increasing the free energy by 3.6 kcal mol−1 (15.1 kJ mol−1). Further biochemical evidence shows that each suppressor mutation, N235K or N239Y, acts individually to restore thermodynamic stability to V157F and that both together are more effective than either alone. All rescued mutants were found to have wild-type DNA-binding activity when assessed at a permissive temperature, thus pointing to thermodynamic stability as the critical underlying variable. Interestingly, thermodynamic analysis shows that while N239Y demonstrates stabilization of the wild-type p53 core domain, N235K does not. These observations suggest distinct structural mechanisms of rescue. A new salt bridge between Lys235 and Glu198, found in both the N235K and rescued cancer mutant structures, suggests a rescue mechanism that relies on stabilizing the β-sandwich scaffold. On the

  15. Synthetic Aperture Radar: The NCCS Enables Search and Rescue

    Science.gov (United States)

    2002-01-01

    For as long as planes have gone down, dedicated men and women have used ever-improving technologies to aid their search for survivors. Nearly 2,000 general aviation crashes occur each year in U.S.-and many, like the Montana incident, occur without witnesses. On average, every day in the U.S. one airplane is reported missing. The Air Force Rescue Coordination Center (AFRCC) organizes search missions for about 100 aircraft each year. Some of these are not found before the searches called off, and are discovered only by chance long after the crash. In some cases, the crash site is never found. NASA Search and Rescue Mission is using NCCS rescues to develop tools for processing radar data that can help these effort

  16. How quantum brain biology can rescue conscious free will.

    Science.gov (United States)

    Hameroff, Stuart

    2012-01-01

    Conscious "free will" is problematic because (1) brain mechanisms causing consciousness are unknown, (2) measurable brain activity correlating with conscious perception apparently occurs too late for real-time conscious response, consciousness thus being considered "epiphenomenal illusion," and (3) determinism, i.e., our actions and the world around us seem algorithmic and inevitable. The Penrose-Hameroff theory of "orchestrated objective reduction (Orch OR)" identifies discrete conscious moments with quantum computations in microtubules inside brain neurons, e.g., 40/s in concert with gamma synchrony EEG. Microtubules organize neuronal interiors and regulate synapses. In Orch OR, microtubule quantum computations occur in integration phases in dendrites and cell bodies of integrate-and-fire brain neurons connected and synchronized by gap junctions, allowing entanglement of microtubules among many neurons. Quantum computations in entangled microtubules terminate by Penrose "objective reduction (OR)," a proposal for quantum state reduction and conscious moments linked to fundamental spacetime geometry. Each OR reduction selects microtubule states which can trigger axonal firings, and control behavior. The quantum computations are "orchestrated" by synaptic inputs and memory (thus "Orch OR"). If correct, Orch OR can account for conscious causal agency, resolving problem 1. Regarding problem 2, Orch OR can cause temporal non-locality, sending quantum information backward in classical time, enabling conscious control of behavior. Three lines of evidence for brain backward time effects are presented. Regarding problem 3, Penrose OR (and Orch OR) invokes non-computable influences from information embedded in spacetime geometry, potentially avoiding algorithmic determinism. In summary, Orch OR can account for real-time conscious causal agency, avoiding the need for consciousness to be seen as epiphenomenal illusion. Orch OR can rescue conscious free will. PMID:23091452

  17. How quantum brain biology can rescue conscious free will

    Directory of Open Access Journals (Sweden)

    Stuart Hameroff

    2012-10-01

    Full Text Available Conscious ‘free will’ is problematic because 1 brain mechanisms causing consciousness are unknown, 2 measurable brain activity correlating with conscious perception apparently occurs too late for real-time conscious response, consciousness thus being considered ‘epiphenomenal illusion’, and 3 determinism, i.e. our actions and the world around us seem algorithmic and inevitable. The Penrose-Hameroff theory of ‘orchestrated objective reduction’ (‘Orch OR’ identifies discrete conscious moments with quantum computations in microtubules inside brain neurons, e.g. 40 per second in concert with gamma synchrony EEG. Microtubules organize neuronal interiors and regulate synapses. In Orch OR, microtubule quantum computations occur in integration phases in dendrites and cell bodies of integrate-and-fire brain neurons connected and synchronized by gap junctions, allowing entanglement of microtubules among many neurons. Quantum computations in entangled microtubules terminate by Penrose ‘objective reduction’ (‘OR’, a proposal for quantum state reduction and conscious moments linked to fundamental spacetime geometry. Each OR reduction selects microtubule states which can trigger axonal firings, and control behavior. The quantum computations are ‘orchestrated’ by synaptic inputs and memory (thus ‘Orch OR’. If correct, Orch OR can account for conscious causal agency, resolving problem 1. Regarding problem 2, Orch OR can cause temporal non-locality, sending quantum information backward in classical time, enabling conscious control of behavior. Three lines of evidence for brain backward time effects are presented. Regarding problem 3 Penrose OR (and Orch OR invoke non-computable influences from information embedded in spacetime geometry, potentially avoiding algorithmic determinism. In summary, Orch OR can account for real-time conscious causal agency, avoiding the need for consciousness to be seen as epiphenomenal illusion. Orch

  18. Infectious diseases in dogs rescued during dogfighting investigations.

    Science.gov (United States)

    Cannon, S H; Levy, J K; Kirk, S K; Crawford, P C; Leutenegger, C M; Shuster, J J; Liu, J; Chandrashekar, R

    2016-05-01

    Dogs used for dogfighting often receive minimal preventive health care, and the potential for spread of infectious diseases is high. The purpose of this study was to describe the prevalence of infectious diseases in dogs rescued from fighting operations to guide medical protocols for their immediate and long-term care. A total of 269 pit bull-type dogs were seized in a multi-state investigation. Fleas were present on most dogs, but few ticks were observed. Testing performed at intake included packed cell volume (PCV), serology and PCR for vector-borne pathogens, and fecal analysis. The most common infections were Babesia gibsoni (39%), 'Candidatus Mycoplasma haematoparvum' (32%), Mycoplasma haemocanis (30%), Dirofilaria immitis (12%), and Ancylostoma (23%). Anemia was associated with B. gibsoni infection (63% of infected dogs, odds ratio = 2.5, P Ancylostoma. Pit bull heritage and dogfighting are known risk factors for B. gibsoni infection, possibly via blood transmission from bites and vertical transmission. Hemotropic mycoplasmas have a similar risk pattern. Empirical care for dogs from dogfighting cases should include broad-spectrum internal and external parasiticides and monitoring for anemia. Dogfighting case responders should be prepared for mass screening and treatment of B. gibsoni and heartworm infections and should implement protocols to prevent transmission of infectious and zoonotic diseases in the shelter and following adoption. Former fighting dogs and dogs with possible dog bite scars should not be used as blood donors due to the risk of vector-borne pathogens that can escape detection and for which curative treatment is difficult to document. PMID:27056107

  19. A Practice of Rescue Robot Contest in Junior High Schools

    Science.gov (United States)

    Kawada, Kazuo; Nagamatsu, Masayasu; Yamamoto, Toru

    The rescue robot contest for junior high school students was created to give students an opportunity to design a robot to rescue the victims under large scale disasters. The activity was not only intended as an humanitarian project but also aiming at students to : (1) take the role of victims and imagining the situation from his or her perspective, (2) enhance thinking skills, creativity through the problem solving processes and, (3) work cooperatively in groups. From results of questionnaire for the participated students, important factors for further implementation as curriculum of technology education are implied.

  20. Protective equipment for emergency rescue in alpine-cold region

    Institute of Scientific and Technical Information of China (English)

    Ma Tian; Feng Xinxing; Wang Qizhi; Hao Limin

    2013-01-01

    Alpine-cold regions are characterized as hypoxia,strong wind,heavy rain,cold climate,huge temperature difference between day and night,and vertical climate.All these make it difficult for an emergency rescue when a natural disaster such as earthquake happens.Based on the characteristics of emergency rescue in alpinecold region,several multifunctional protective equipments have been developed by the Quartermaster Equipment Institute of General Logistics Department (GLD) of the Chinese People' s Liberation Army (CPLA).These equipments are lightweight,durable and environment adaptable.

  1. First steps towards rescuing Las-infected citrus germplasm

    Science.gov (United States)

    Huanglongbing (HLB) disease is having significant impact on the USDA citrus breeding program as it has shown up in a number of trees which exist only in a virtually irreplaceable collection of diverse citrus types. It is critical that we rescue HLB-free budwood from elite germplasm that is HLB-patho...

  2. Instructional Alternatives: Rescue Strategies for At-Risk Students.

    Science.gov (United States)

    Wircenski, Jerry L.; And Others

    1990-01-01

    An instructional plan to rescue at-risk students must be based on a curriculum intended to serve all students. The creation of a functional curriculum, the promotion of employability skills, and an emphasis on improving study skills are instructional patterns that seem to be effective in reducing the number of student dropouts. Two alternatives…

  3. Evaluating a multimodal interface for firefighting rescue tasks

    NARCIS (Netherlands)

    Streefkerk, J.W.; Vos, W.K.; Smets, N.J.J.M.

    2012-01-01

    Firefighters searching for victims work in hazardous environments with limited visibility, obstacles and uncertain navigation paths. In rescue tasks, extra sensor information from infrared cameras, indoor radar and gas sensors could improve vision, orientation and navigation. A visual and tactile in

  4. Intelligent Robot-assisted Humanitarian Search and Rescue System

    Directory of Open Access Journals (Sweden)

    Henry Y. K. Lau

    2009-11-01

    Full Text Available The unprecedented scale and number of natural and man-made disasters in the past decade has urged international emergency search and rescue communities to seek for novel technology to enhance operation efficiency. Tele-operated search and rescue robots that can navigate deep into rubble to search for victims and to transfer critical field data back to the control console has gained much interest among emergency response institutions. In response to this need, a low-cost autonomous mini robot equipped with thermal sensor, accelerometer, sonar, pin-hole camera, microphone, ultra-bright LED and wireless communication module is developed to study the control of a group of decentralized mini search and rescue robots. The robot can navigate autonomously between voids to look for living body heat and can send back audio and video information to allow the operator to determine if the found object is a living human. This paper introduces the design and control of a low-cost robotic search and rescue system based on an immuno control framework developed for controlling decentralized systems. Design and development of the physical prototype and the immunity-based control system are described in this paper.

  5. Bezpieczeństwo i ratownictwo = Security and rescue

    OpenAIRE

    Red. Telak, Jerzy; Red. Zieliński, Ewa

    2015-01-01

    Wyższa Szkoła Nauk o Zdrowiu w Bydgoszczy University of Health Sciences in Bydgoszcz                                       BEZPIECZEŃSTWO I RATOWNICTWO Security and rescue             Redakcja naukowa Edited by   Jerzy Telak Ewa Zieliń...

  6. "Denmark 1943": Using Music to Teach Holocaust Rescue

    Science.gov (United States)

    Lindquist, David H.

    2007-01-01

    Addressing the topic of rescue efforts poses particular challenges for teachers planning Holocaust curricula. While the issue leads many students to develop an engaged empathy with rescuers, teachers must avoid overemphasizing what was a limited occurrence within the overall Holocaust. This article presents a plan for using music to teach about…

  7. Organization and implementation of mass medical rescue after an earthquake.

    Science.gov (United States)

    Zhang, Yan-Ling

    2014-01-01

    On May 12, 2008, an 8.0-magnitude earthquake occurred in Wenchuan, Sichuan Province. In this disaster, 69,000 people were killed, 18,000 people were reported missing, and 37,000 people were injured, including more than 10,000 who were seriously injured. Trauma was the most commonly observed type of injury, with fractures accounting for 74% of all injury cases. On April 14, 2010, a 7.1-magnitude earthquake occurred in Yushu of Qinghai Province. In this disaster, 2,698 people were killed, 270 people were reported missing, and 11,000 people were injured, including more than 3,100 who were seriously injured. Fracture injury accounted for 58.4% of all injury cases. After each earthquake, the Chinese Army Medical Services responded promptly, according to the previously established guidelines, and sent out elite forces to the disaster areas, with the objectives of organizing, coordinating and participating in an efficient and evidence-based medical rescue effort. After the Wenchuan earthquake, 397 mobile medical service teams including 7,061 health workers were sent to the disaster areas. A total of 69,000 casualties were treated, and 22,000 surgeries were performed. After the Yushu earthquake, 25 mobile medical service teams involving 2,025 health workers were sent. They performed 1,635 surgeries and created an astounding outcome of "zero deaths" in the aftermath of the earthquake during their treatment of casualties in a high-altitude region. Within a week after each earthquake, the military teams rescued approximately 60% of the total number of rescued casualties and evacuated approximately 80% of the total number of evacuated sick or wounded victims, playing a critical role and making invaluable contributions to earthquake relief. The experience and lessons learned from the rescue efforts of the Chinese military after the two earthquakes have highlighted several key aspects in emergency medical rescue: (1) medical rescue theories must be updated; (2) military

  8. An evaluation of coordination relationships during earthquake emergency rescue using entropy theory

    Directory of Open Access Journals (Sweden)

    Huang Rong

    2015-05-01

    Full Text Available Emergency rescue after an earthquake is complex work which requires the participation of relief and social organizations. Studying earthquake emergency coordination efficiency can not only help rescue organizations to define their own rescue missions, but also strengthens inter-organizational communication and collaboration tasks, improves the efficiency of emergency rescue, and reduces loss. In this paper, collaborative entropy is introduced to study earthquake emergency rescue operations. To study the emergency rescue coordination relationship, collaborative matrices and collaborative entropy functions are established between emergency relief work and relief organizations, and the collaborative efficiency of the emergency rescue elements is determined based on this entropy function. Finally, the Lushan earthquake is used as an example to evaluate earthquake emergency rescue coordination efficiency.

  9. Creation of the program to rescue data from NTFS partition with Linux

    OpenAIRE

    Březina, Tomáš

    2014-01-01

    This bachelor thesis deals with the topic of data rescue from NTFS partition under Linux. The BASH program for data rescue from Windows partitions is created and tested in different live Linux distributions.

  10. Development of Space Shuttle Rescue and Recovery Operations

    Science.gov (United States)

    Chandler, Michael

    2011-01-01

    As the first Space Shuttle launch was still in our future, many from NASA, the Department of Defense (DoD) and NASA contractors were busy planning for not only a nominal launch and return, but contingency operations at the launch pad and landing sites. Prior to the first launch, detailed coordination, planning and simulations were conducted at all three locations and internal rescue procedures were taught at Kennedy Space Center (KSC). Later in the Program, the Transoceanic Abort Landing (TAL) sites were added in Europe and Africa. For the 51L mission a new TAL site was brought on line in Morocco. However, upon launch, the Shuttle Program experienced it's first lost. During the following months a complete review of all contingency operations (launch and landing) was completed. Many enhancements were made based on the reviews following. A Mode VIII water rescue was developed for NASA by the DoD before the STS-26 launch. Different concepts were explored and being debated by NASA. Training of the contingency forces was required before final decisions were made forcing the teaching of two different sets of procedures. To assist with training, a video was developed for the fire/crash/rescue personnel. This accompanied the detailed extraction procedures that were developed by a combination of KSC and DoD firemen. Training for the fire/crash/rescue personnel at Vandenberg AFB was also being planned before the accident happen. The fire/crash/rescue mockup that was being built at Chanute AFB was diverted to Edwards AFB. Educational Objectives: With the emphasis on Commercial Crew Programs for Space flight it is important that all involved understand what is required to prepare for contingencies. Cost effective means of being prepared for contingencies are needed. Questions: 1. When should planning for nominal and contingency operations begin? 2. What type of training aids are needed for contingency operations? 3. Who were the major contributors to Shuttle contingency

  11. Mapping and Exploration for Search and Rescue with Humans and Mobile Robots

    OpenAIRE

    Kleiner, Alexander

    2009-01-01

    Urban Search And Rescue (USAR) is a time critical task since all survivors have to be rescued within the first 72 hours. One goal in Rescue Robotics is to support emergency response by mixed-initiative teams consisting of humans and robots. Their task is to explore the disaster area rapidly while reporting victim locations and hazardous areas to a central station, which then can be utilized for planning rescue missions. To fulfill this task efficiently, humans and robots have to map disaster ...

  12. Heat shock protein 90AB1 and hyperthermia rescue infectivity of HIV with defective cores.

    Science.gov (United States)

    Joshi, Pheroze; Sloan, Barbara; Torbett, Bruce E; Stoddart, Cheryl A

    2013-02-01

    We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1(E42A+D88A), restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacological inhibition of HSP90AB1. In agreement with Roesch et al. (2012), we found that culturing HIV at 39.5°C enhanced viral infectivity up to 30-fold in human peripheral blood mononuclear cells (p=0.002) and rescued CA-mutant infectivity in nonactivated cells, concurrent with elevated expression of HSP90AB1 during hyperthermia. In sum, the transdominant effect of HSP90AB1 on CA-mutant HIV infectivity suggests a potential role for this class of cellular chaperones in HIV core stability and uncoating. PMID:23200770

  13. Transcriptional Analysis of Apoptotic Cerebellar Granule Neurons Following Rescue by Gastric Inhibitory Polypeptide

    Directory of Open Access Journals (Sweden)

    Barbara Maino

    2014-04-01

    Full Text Available Apoptosis triggered by exogenous or endogenous stimuli is a crucial phenomenon to determine the fate of neurons, both in physiological and in pathological conditions. Our previous study established that gastric inhibitory polypeptide (Gip is a neurotrophic factor capable of preventing apoptosis of cerebellar granule neurons (CGNs, during its pre-commitment phase. In the present study, we conducted whole-genome expression profiling to obtain a comprehensive view of the transcriptional program underlying the rescue effect of Gip in CGNs. By using DNA microarray technology, we identified 65 genes, we named survival related genes, whose expression is significantly de-regulated following Gip treatment. The expression levels of six transcripts were confirmed by real-time quantitative polymerase chain reaction. The proteins encoded by the survival related genes are functionally grouped in the following categories: signal transduction, transcription, cell cycle, chromatin remodeling, cell death, antioxidant activity, ubiquitination, metabolism and cytoskeletal organization. Our data outline that Gip supports CGNs rescue via a molecular framework, orchestrated by a wide spectrum of gene actors, which propagate survival signals and support neuronal viability.

  14. 77 FR 64360 - Proposed Extension of Existing Information Collection; Mine Rescue Teams for Underground Metal...

    Science.gov (United States)

    2012-10-19

    ... Safety and Health Administration Proposed Extension of Existing Information Collection; Mine Rescue Teams...) to publish regulations which provide that mine rescue teams be available for rescue and recovery work... arrangements for such teams are to be borne by the operator of each such mine. II. Desired Focus of...

  15. Current research, key performances and future development of search and rescue robots

    Institute of Scientific and Technical Information of China (English)

    LIU Jinguo; WANG Yuechao; LI Bin; MA Shugen

    2007-01-01

    Frequent natural disasters and man-made catastrophes have threatened the safety of citizens and have attracted much more attention. The rescue mission under disaster environment is very complicated and dangerous for a rescue team. Search and rescue (SAR) robots can not only improve the efficiency of rescue operations but also reduce the casualty of rescuers. Robots can help rescue teams and even replace rescuers to perform dangerous missions. Search and rescue robots will play a more and more important role in the rescue operations. A survey of the research status of search and rescue robots in Japan, USA, China and other countries has been provided. According to current research,experiences and the lessons learned from applications, the five key performances of a search and rescue robot are survivability, mobility, sensing, communicability and operability.Multi-technique fusion and multi-agent intelligent network are considered to be requirements for the future development of the search and rescue robot. Disaster prevention, disaster reduction and disaster rescue are the important parts of national public safety. They are also crucial for the safety of citizens and their estates. Search and rescue robotic technique is an urgent needed, strategic and core technique for national development. It will be important and strategic for national economy and safety.

  16. Muskmelon embryo rescue techniques using in vitro embryo culture.

    Science.gov (United States)

    Nuñez-Palenius, Hector Gordon; Ramírez-Malagón, Rafael; Ochoa-Alejo, Neftalí

    2011-01-01

    Among the major cucurbit vegetables, melon (Cucumis melo) has one of the greatest polymorphic fruit types and botanical varieties. Some melon fruits have excellent aroma, variety of flesh colors, deeper flavor, and more juice compared to other cucurbits. Despite numerous available melon cultivars, some of them are exceedingly susceptible to several diseases. The genetic background carrying the genes for tolerance and/or resistance for those diseases is found in wild melon landraces. Unfortunately, the commercial melon varieties are not able to produce viable hybrids when crossed with their wild melon counterparts. Plant tissue culture techniques are needed to surpass those genetic barriers. In vitro melon embryo rescue has played a main role to obtain viable hybrids originated from commercial versus wild melon crosses. In this chapter, an efficient and simple embryo rescue melon protocol is thoroughly described. PMID:21207265

  17. Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique

    OpenAIRE

    Mohammed Amine Benatta; Ariane Desjeux; Marc Barthet; Jean Charles Grimaud; Mohamed Gasmi

    2016-01-01

    A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone com...

  18. A change of attitude: From rescue to prevention

    International Nuclear Information System (INIS)

    The qualitative and quantitative leap recorded by economical companies after the Romanian Revolution occurred in 1989, has positively influenced the functioning of the workplaces and working environment by increasing the employees' occupational safety, well being, health and results of their activities. In fact it has determined a new approach of safety culture. This has resulted in a change of attitude: from rescue to prevention. (author)

  19. Medical rescue of naval combat: challenges and future

    OpenAIRE

    Jin, Hai; Hou, Li-Jun; Fu, Xiao-Bing

    2015-01-01

    There has been no large-scale naval combat in the last 30 years. With the rapid development of battleships, weapons manufacturing and electronic technology, naval combat will present some new characteristics. Additionally, naval combat is facing unprecedented challenges. In this paper, we discuss the topic of medical rescue at sea: what challenges we face and what we could do. The contents discussed in this paper contain battlefield self-aid buddy care, clinical skills, organized health servi...

  20. Fitness small fire-rescue vehicles to fire rescuers action

    OpenAIRE

    Кропивницький, Віталій Станіславович

    2016-01-01

    In connection with the development of coastal infrastructure becomes increasingly important task of ensuring domestic small fleet of specialized vessels working, especially those that can quickly to help everyone who needs help in emergency situations at these sites. These emergencies related to fire and other possible industrial accidents and disasters, which are designed to eliminate a number of modern innovative complexes, among which should be mentioned fire rescue boat UMS-1000. There is...

  1. An analysis of leadership characteristics of search and rescue volunteers

    OpenAIRE

    Gurer, Burak; ADILOGULLARI, Ilhan

    2015-01-01

    The main purpose of this study was to analyze the leadership behaviors of volunteer leaders in search and rescue field. 118 volunteer leaders attended this study on a volunteer basis. Data were collected through the use of the Multifactor Leadership Questionnaire, which was developed by Bass & Avolio (1985) and adapted into Turkish by Demir & Okan. 20 items were used to measure transformational leadership while 16 of them were applied for transactional leadership. One Way Anova and T-...

  2. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A.

    Directory of Open Access Journals (Sweden)

    Fayçal Guedj

    Full Text Available Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG - a member of a natural polyphenols family, found in great amount in green tea leaves - is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice.

  3. Vulture rescue and rehabilitation in South Africa: An urban perspective

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2011-04-01

    Full Text Available SouthAfrica is home to 9 vulture species, of which 7 are endangered. While the cause of the population declines remains largely speculative, a vast amount of effort has been dedicated towards the protection of populations by ensuring sustainable and safe food sources for the various colonies. Limited focus was placed in the past on efforts related to the rescue and/or rehabilitation (R&R of injured birds and the release of these birds back into the wild. This paper provides an overview of the causes, the impact and success of 3 organisations involved in R&R efforts of vultures in the Magaliesberg mountain range and surrounding areas over a period of 10 years. Study material included 162 Cape griffon (CGV and 38 African white-backed (AWBV vultures. Datasets include the number, sex and age of birds received, the reason the vultures were brought in for R&R, surgical interventions performed and outcomes of rescue efforts. The CGV dominated the rehabilitation attempts. Results further show that a large number of apparently healthy birds were presented for veterinary treatment. The R&R data clearly indicate that the major cause of injuries was birds colliding with overhead pylons, as a high number of soft tissue and skeletal injuries were observed. The study also shows that successful releases of rescued birds are possible. It is concluded that urbanisation has had a major negative impact on vultures around the Magaliesberg mountain range.

  4. Efficient transgenesis mediated by pigmentation rescue in zebrafish.

    Science.gov (United States)

    Harrold, Itrat; Carbonneau, Seth; Moore, Bethany M; Nguyen, Gina; Anderson, Nicole M; Saini, Amandeep S; Kanki, John P; Jette, Cicely A; Feng, Hui

    2016-01-01

    The zebrafish represents a revolutionary tool in large-scale genetic and small-molecule screens for gene and drug discovery. Transgenic zebrafish are often utilized in these screens. Many transgenic fish lines are maintained in the heterozygous state due to the lethality associated with homozygosity; thus, their progeny must be sorted to ensure a population expressing the transgene of interest for use in screens. Sorting transgenic embryos under a fluorescence microscope is very labor-intensive and demands fine-tuned motor skills. Here we report an efficient transgenic method of utilizing pigmentation rescue of nacre mutant fish for accurate naked-eye identification of both mosaic founders and stable transgenic zebrafish. This was accomplished by co-injecting two constructs with the I-SceI meganuclease enzyme into pigmentless nacre embryos: I-SceI-mitfa:mitfa-I-SceI to rescue the pigmentation and I-SceI-zpromoter:gene-of-interest-I-SceI to express the gene of interest under a zebrafish promoter (zpromoter). Pigmentation rescue reliably predicted transgene integration. Compared with other transgenic techniques, our approach significantly increases the overall percentage of founders and facilitates accurate naked-eye identification of stable transgenic fish, greatly reducing laborious fluorescence microscope sorting and PCR genotyping. Thus, this approach is ideal for generating transgenic fish for large-scale screens. PMID:26757807

  5. Rescue and Preliminary Application of a Recombinant Newcastle Disease Virus Expressing Green Fluorescent Protein Gene

    Institute of Scientific and Technical Information of China (English)

    Shun-lin HU; Qin SUN; Qu-zhi WANG; Yul-iang LIU; Yan-tao WU; Xiu-fan LIU

    2007-01-01

    Based on the complete genome sequence of Newcastle disease virus (NDV) ZJI strain,seven pairs of primers were designed to amplify a cDNA fragment for constructing the plasmid pNDV/ZJI,which contained the full-length cDNA of the NDV ZJI strain.The pNDV/ZJI,with three helper plasmids,pCIneoNP,pCIneoP and pCIneoL,were then cotransfected into BSR-T7/5 cells expressing T7 RNA polymerase.After inoculation of the transfected cell culture supernatant into embryonated chicken eggs from specific-pathogen-free (SPF) flock,an infectious NDV ZJI strain was successfully rescued.Green fluorescent protein (GFP) gene was amplified and inserted into the NDV full-length cDNA to generate a GFP-tagged recombinant plasmid pNDV/ZJIGFP.After cotransfection of the resultant plasmid and the three support plasmids into BSR-T7/5 cells,the recombinant NDV,NDV/ZJIGFP,was rescued.Specific green fluorescence was observed in BSR-T7/5 and chicken embryo fibroblast (CEF) cells 48h post-infection,indicating that the GFP gene was expressed at a relatively high level.NDV/ZJIGFP was inoculated into 10-day-old SPF chickens by oculonasal route.Four days post-infection,strong green fluorescence could be detected in the kidneys and tracheae,indicating that the recombinant GFP-tagged NDV could be a very useful tool for analysis of NDV dissemination and pathogenesis.

  6. Space safety and rescue 1979-1981: Worldwide disaster response, rescue and safety employing space-borne systems

    Science.gov (United States)

    Brown, J. W. (Editor)

    1983-01-01

    Selected papers from the 1979, 1980, and 1981 IAA symposia on space safety and rescue and on worldwide disaster response, safety, and rescue employing spaceborne systems are presented. Available papers published elsewhere and those presented at the 1976, 1977, and 1978 symposia are presented in abstract form. Subjects discussed include man-made space debris, nuclear-waste disposal in space, space-station safety design, psychological training, the introduction of female crewmembers, analysis of the November 23, 1980 earthquake as a design basis for satellite emergency communication, disaster warning using the GOES satellite, and satellite communications for disaster relief operations. Three reviews of the application of space technology to emergency and disaster relief and prevention, given at other symposia in 1981, are presented in an appendix. No individual items are abstracted in this volume

  7. Amsterdam Oxford joint rescue forces - Team description paper - Virtual Robot competition - Rescue Simulation league - RoboCup 2011

    OpenAIRE

    Dijkshoorn, N.; Flynn, H.; Formsma, O.; Noort, van, F.R.; Weelden, van, C.; Bastiaan, C.; Out, N.; Zwennes, O.; Otárola, S.S.; Hoog, de, R.; Cameron, S.; Visser, A.

    2011-01-01

    With the progress made in active exploration, the robots of the Joint Rescue Forces are capable of making deliberative decisions about the distribution of exploration locations over the team. Experiments have been done which include information exchange between team-members at rendez-vous points and dynamic role switching between relays and explorers. In the previous competition exploration was demonstrated with large robots with advanced mobility, such as the Kenaf and the AirRobot. This yea...

  8. Beta tubulin isoforms are not interchangeable for rescuing impaired radial migration due to Tubb3 knockdown.

    Science.gov (United States)

    Saillour, Yoann; Broix, Loïc; Bruel-Jungerman, Elodie; Lebrun, Nicolas; Muraca, Giuseppe; Rucci, Julien; Poirier, Karine; Belvindrah, Richard; Francis, Fiona; Chelly, Jamel

    2014-03-15

    Over the last years, the critical role of cytoskeletal proteins in cortical development including neuronal migration as well as in neuronal morphology has been well established. Inputs from genetic studies were provided through the identification of several mutated genes encoding either proteins associated with microtubules (DCX, LIS1, KIF2A, KIF5C, DYNC1H1) or tubulin subunits (TUBA1A, TUBB2B, TUBB5 and TUBG1), in malformations of cortical development (MCD). We also reported the identification of missense mutations in TUBB3, the postmitotic neuronal specific tubulin, in six different families presenting either polymicrogyria or gyral disorganization in combination with cerebellar and basal ganglial abnormalities. Here, we investigate further the association between TUBB3 mutations and MCDs by analyzing the consequences of Tubb3 knockdown on cortical development in mice. Using the in utero-electroporation approach, we demonstrate that Tubb3 knockdown leads to delayed bipolar morphology and radial migration with evidence, suggesting that the neuronal arrest is a transient phenomenon overcome after birth. Silenced blocked cells display a round-shape and decreased number of processes and a delay in the acquisition of the bipolar morphology. Also, more Tbr2 positive cells are observed, although less cells express the proliferation marker Ki67, suggesting that Tubb3 inactivation might have an indirect effect on intermediate progenitor proliferation. Furthermore, we show by rescue experiments the non-interchangeability of other beta-tubulins which are unable to rescue the phenotype. Our study highlights the critical and specific role of Tubb3 on the stereotyped morphological changes and polarization processes that are required for initiating radial migration to the cortical plate. PMID:24179174

  9. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Directory of Open Access Journals (Sweden)

    Yan M

    2015-10-01

    Full Text Available Meng Yan,1 Kaiping Zhang,1 Yanhui Shi,1 Lifang Feng,1 Lin Lv,1 Baoxin Li1,2 1Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China Abstract: Berberine (BBR, an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293 cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652 and phenylalanine (Phe656 in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. Keywords: berberine, hERG, cavoline-1, cardiotoxicity, LQTS, pharmacological rescue

  10. Human Bacterial Artificial Chromosome (BAC) Transgenesis Fully Rescues Noradrenergic Function in Dopamine β-Hydroxylase Knockout Mice

    Science.gov (United States)

    Cubells, Joseph F.; Schroeder, Jason P.; Barrie, Elizabeth S.; Manvich, Daniel F.; Sadee, Wolfgang; Berg, Tiina; Mercer, Kristina; Stowe, Taylor A.; Liles, L. Cameron; Squires, Katherine E.; Mezher, Andrew; Curtin, Patrick; Perdomo, Dannie L.; Szot, Patricia; Weinshenker, David

    2016-01-01

    Dopamine β-hydroxylase (DBH) converts dopamine (DA) to norepinephrine (NE) in noradrenergic/adrenergic cells. DBH deficiency prevents NE production and causes sympathetic failure, hypotension and ptosis in humans and mice; DBH knockout (Dbh -/-) mice reveal other NE deficiency phenotypes including embryonic lethality, delayed growth, and behavioral defects. Furthermore, a single nucleotide polymorphism (SNP) in the human DBH gene promoter (-970C>T; rs1611115) is associated with variation in serum DBH activity and with several neurological- and neuropsychiatric-related disorders, although its impact on DBH expression is controversial. Phenotypes associated with DBH deficiency are typically treated with L-3,4-dihydroxyphenylserine (DOPS), which can be converted to NE by aromatic acid decarboxylase (AADC) in the absence of DBH. In this study, we generated transgenic mice carrying a human bacterial artificial chromosome (BAC) encompassing the DBH coding locus as well as ~45 kb of upstream and ~107 kb of downstream sequence to address two issues. First, we characterized the neuroanatomical, neurochemical, physiological, and behavioral transgenic rescue of DBH deficiency by crossing the BAC onto a Dbh -/- background. Second, we compared human DBH mRNA abundance between transgenic lines carrying either a “C” or a “T” at position -970. The BAC transgene drove human DBH mRNA expression in a pattern indistinguishable from the endogenous gene, restored normal catecholamine levels to the peripheral organs and brain of Dbh -/- mice, and fully rescued embryonic lethality, delayed growth, ptosis, reduced exploratory activity, and seizure susceptibility. In some cases, transgenic rescue was superior to DOPS. However, allelic variation at the rs1611115 SNP had no impact on mRNA levels in any tissue. These results indicate that the human BAC contains all of the genetic information required for tissue-specific, functional expression of DBH and can rescue all measured Dbh

  11. Human Bacterial Artificial Chromosome (BAC) Transgenesis Fully Rescues Noradrenergic Function in Dopamine β-Hydroxylase Knockout Mice.

    Science.gov (United States)

    Cubells, Joseph F; Schroeder, Jason P; Barrie, Elizabeth S; Manvich, Daniel F; Sadee, Wolfgang; Berg, Tiina; Mercer, Kristina; Stowe, Taylor A; Liles, L Cameron; Squires, Katherine E; Mezher, Andrew; Curtin, Patrick; Perdomo, Dannie L; Szot, Patricia; Weinshenker, David

    2016-01-01

    Dopamine β-hydroxylase (DBH) converts dopamine (DA) to norepinephrine (NE) in noradrenergic/adrenergic cells. DBH deficiency prevents NE production and causes sympathetic failure, hypotension and ptosis in humans and mice; DBH knockout (Dbh -/-) mice reveal other NE deficiency phenotypes including embryonic lethality, delayed growth, and behavioral defects. Furthermore, a single nucleotide polymorphism (SNP) in the human DBH gene promoter (-970C>T; rs1611115) is associated with variation in serum DBH activity and with several neurological- and neuropsychiatric-related disorders, although its impact on DBH expression is controversial. Phenotypes associated with DBH deficiency are typically treated with L-3,4-dihydroxyphenylserine (DOPS), which can be converted to NE by aromatic acid decarboxylase (AADC) in the absence of DBH. In this study, we generated transgenic mice carrying a human bacterial artificial chromosome (BAC) encompassing the DBH coding locus as well as ~45 kb of upstream and ~107 kb of downstream sequence to address two issues. First, we characterized the neuroanatomical, neurochemical, physiological, and behavioral transgenic rescue of DBH deficiency by crossing the BAC onto a Dbh -/- background. Second, we compared human DBH mRNA abundance between transgenic lines carrying either a "C" or a "T" at position -970. The BAC transgene drove human DBH mRNA expression in a pattern indistinguishable from the endogenous gene, restored normal catecholamine levels to the peripheral organs and brain of Dbh -/- mice, and fully rescued embryonic lethality, delayed growth, ptosis, reduced exploratory activity, and seizure susceptibility. In some cases, transgenic rescue was superior to DOPS. However, allelic variation at the rs1611115 SNP had no impact on mRNA levels in any tissue. These results indicate that the human BAC contains all of the genetic information required for tissue-specific, functional expression of DBH and can rescue all measured Dbh deficiency

  12. Tactical mobile robots for urban search and rescue

    Science.gov (United States)

    Blitch, John; Sidki, Nahid; Durkin, Tim

    2000-07-01

    Few disasters can inspire more compassion for victims and families than those involving structural collapse. Video clips of children's bodies pulled from earthquake stricken cities and bombing sties tend to invoke tremendous grief and sorrow because of the totally unpredictable nature of the crisis and lack of even the slightest degree of negligence (such as with those who choose to ignore storm warnings). Heartbreaking stories of people buried alive for days provide a visceral and horrific perspective of some of greatest fears ever to be imagined by human beings. Current trends toward urban sprawl and increasing human discord dictates that structural collapse disasters will continue to present themselves at an alarming rate. The proliferation of domestic terrorism, HAZMAT and biological contaminants further complicates the matter further and presents a daunting problem set for Urban Search and Rescue (USAR) organizations around the world. This paper amplifies the case for robot assisted search and rescue that was first presented during the KNOBSAR project initiated at the Colorado School of Mines in 1995. It anticipates increasing technical development in mobile robot technologies and promotes their use for a wide variety of humanitarian assistance missions. Focus is placed on development of advanced robotic systems that are employed in a complementary tool-like fashion as opposed to traditional robotic approaches that portend to replace humans in hazardous tasks. Operational challenges for USAR are presented first, followed by a brief history of mobiles robot development. The paper then presents conformal robotics as a new design paradigm with emphasis on variable geometry and volumes. A section on robot perception follows with an initial attempt to characterize sensing in a volumetric manner. Collaborative rescue is then briefly discussed with an emphasis on marsupial operations and linked mobility. The paper concludes with an emphasis on Human Robot Interface

  13. Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique

    Directory of Open Access Journals (Sweden)

    Mohammed Amine Benatta

    2016-01-01

    Full Text Available A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone complex. Using this method disengagement of the whole fractured basket/stone complex was achieved without need of surgery. It is the third case reported in the English literature.

  14. Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique.

    Science.gov (United States)

    Benatta, Mohammed Amine; Desjeux, Ariane; Barthet, Marc; Grimaud, Jean Charles; Gasmi, Mohamed

    2016-01-01

    A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone complex. Using this method disengagement of the whole fractured basket/stone complex was achieved without need of surgery. It is the third case reported in the English literature. PMID:27293442

  15. Impacted and Fractured Biliary Basket: A Second Basket Rescue Technique

    Science.gov (United States)

    Benatta, Mohammed Amine; Desjeux, Ariane; Barthet, Marc; Grimaud, Jean Charles; Gasmi, Mohamed

    2016-01-01

    A 59-year-old woman was treated with ERCP, ES, and biliary plastic stent, for large and multiple common bile duct stones. During a second ERCP basket extraction was impacted with a round entrapped stone. The basket handle was cut off; a metal sheath of extraendoscopic lithotriptor was advanced over the basket. The mechanical lithotripsy was complicated with basket traction wires fracturing, without breakage of the stone. A rescue standard basket was pushed until it caught the basket/stone complex. Using this method disengagement of the whole fractured basket/stone complex was achieved without need of surgery. It is the third case reported in the English literature. PMID:27293442

  16. ECMO for Cardiac Rescue after Accidental Intravenous Mepivacaine Application

    Directory of Open Access Journals (Sweden)

    Michael Froehle

    2012-01-01

    Full Text Available Mepivacaine is a potent local anaesthetic and used for infiltration and regional anaesthesia in adults and pediatric patients. Intoxications with mepivacaine affect mainly the CNS and the cardiovascular system. We present a case of accidental intravenous mepivacaine application and intoxication of an infant resulting in seizure, broad complex bradyarrhythmia, arterial hypotension and finally cardiac arrest. The patient could be rescued by prolonged resuscitations and a rapid initiation of ECMO and survived without neurological damage. The management strategies of this rare complication including promising other treatment options with lipid emulsions are discussed.

  17. Kriisiopas Finn Rescue -muodostelman pelastuskoiraryhmälle

    OpenAIRE

    Palmu, Timo-Pekka

    2016-01-01

    Opinnäytetyöni käsittelee katastrofialueilla tehtävää etsintä- ja pelastustyötä ja tähän työskentelyyn liittyvää palvelusstressiä ja traumaattisten tilanteiden kohtaamista ja niiden käsittelyä. Projektin varsinainen kohderyhmä ovat Finn Rescue (FRF) -muodostelman CMC-koiraryhmän (Crisis Management Center) hälytysvalmiudessa olevat pelastuskoiran ohjaajat ja ryhmänjohtajat. Projektin tarkoitus on parantaa CMC-koiraryhmän mahdollisuuksia varautua kokonaisvaltaisesti työskentelyyn katastrofialue...

  18. Establishment of a Rescue System for Canine Distemper Virus

    OpenAIRE

    Gassen, Uta; Collins, Fergal M.; Duprex, W. Paul; Rima, Bert K.

    2000-01-01

    Canine distemper virus (CDV) has been rescued from a full-length cDNA clone. Besides Measles virus (MV) and Rinderpest virus, a third morbillivirus is now available for genetic analysis using reverse genetics. A plasmid p(+)CDV was constructed by sequential cloning using the Onderstepoort vaccine strain large-plaque-forming variant. The presence of a T7 promoter allowed transcription of full-length antigenomic RNA by a T7 RNA polymerase, which was provided by a host range mutant of vaccinia v...

  19. Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

    Science.gov (United States)

    Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

    2016-04-01

    Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomeraseTertgene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- andTert-deficient mice). We find that a high dose of AAV9-Terttargets the bone marrow compartment, including hematopoietic stem cells. AAV9-Terttreatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. PMID:26903545

  20. Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief

    OpenAIRE

    Huang, Junhua; Liu, Qunying; Li, Jinliang (Eric); Li, Xuejiang; You, Jin; Zhang, Liang; Tian, Changfu; Luan, Rongsheng

    2013-01-01

    Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12th, 2008. Pos...

  1. Research on problems in nuclear accident emergency rescue for nuclear power submarine

    International Nuclear Information System (INIS)

    This paper presents a description of nuclearpowered submarine accident types and an analysis of accident emergency rescue characteristics, including a special number of problems associated with emergencyrescue, such as emergency situation and emergency planning zone, technical rescue resources and task, protection against compound radiation inside and outside port plume zone, on-sea nuclear rescue equipment and technical assurance capacity, and other problesms related to in-accident nuclear submarine disposal. (authors)

  2. A critical review of the Mediterranean sea turtle rescue network: a web looking for a weaver

    OpenAIRE

    Judith Ullmann; Michael Stachowitsch

    2015-01-01

    A key issue in conservation biology is recognizing and bridging the gap between scientific results and specific action. We examine sea turtles—charismatic yet endangered flagship species—in the Mediterranean, a sea with historically high levels of exploitation and 22 coastal nations. We take sea turtle rescue facilities as a visible measure for implemented conservation action. Our study yielded 34 confirmed sea turtle rescue centers, 8 first-aid stations, and 7 informal rescue institutions cu...

  3. Decision Making and Emergency Communication System in Rescue Simulation for People with Disabilities

    OpenAIRE

    Kohei Arai; Tran Xuan Sang

    2013-01-01

    Decision making and emergency communication system play important roles in rescue process when emergency situations happen. The rescue process will be more effective if we have appropriate decision making method and accessible emergency communication system. In this paper, we propose a centralized rescue model for people with disabilities. The decision making method to decide which volunteers should help which disabled persons is proposed by utilizing the auction mechanism. The GIS data are u...

  4. National First-Aid and Mine Rescue Contest, Buffalo, NY, October 5-7, 1959

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, H.F.; Alden, D.M.

    1960-01-01

    Report describes the National First-Aid and Mine Rescue Contest, the fifth after a lapse of 21 years, held in the Memorial Auditorium in Buffalo, under auspices of Bureau and Joseph A. Holmes Safety Association. Nine teams from 4 States participated in the mine rescue contest, and 43 teams from 8 States in the first-aid contest. Six teams entered as combination teams, participating in both mine rescue and first-aid contests.

  5. Model and algorithm for optimization of rescue center location of emergent catastrophe

    Institute of Scientific and Technical Information of China (English)

    WANG Ding-wei; ZHANG Guo-xiang

    2006-01-01

    The location of rescue centers is a key problem in optimal resource allocation and logistics in emergency response.We propose a mathematical model for rescue center location with the considerations of emergency occurrence probability,catastrophe diffusion function and rescue function.Because the catastrophe diffusion and rescue functions are both nonlinear and time-variable,it cannot be solved by common mathematical programming methods.We develop a heuristic embedded genetic algorithm for the special model solution.The computation based on a large number of examples with practical data has shown us satisfactory results.

  6. Rescue and Stabilization of Acetylcholinesterase in Skeletal Muscle by N-terminal Peptides Derived from the Noncatalytic Subunits.

    Science.gov (United States)

    Ruiz, Carlos A; Rossi, Susana G; Rotundo, Richard L

    2015-08-21

    The vast majority of newly synthesized acetylcholinesterase (AChE) molecules do not assemble into catalytically active oligomeric forms and are rapidly degraded intracellularly by the endoplasmic reticulum-associated protein degradation pathway. We have previously shown that AChE in skeletal muscle is regulated in part post-translationally by the availability of the noncatalytic subunit collagen Q, and others have shown that expression of a 17-amino acid N-terminal proline-rich attachment domain of collagen Q is sufficient to promote AChE tetramerization in cells producing AChE. In this study we show that muscle cells, or cell lines expressing AChE catalytic subunits, incubated with synthetic proline-rich attachment domain peptides containing the endoplasmic reticulum retrieval sequence KDEL take up and retrogradely transport them to the endoplasmic reticulum network where they induce assembly of AChE tetramers. The peptides act to enhance AChE folding thereby rescuing them from reticulum degradation. This enhanced folding efficiency occurs in the presence of inhibitors of protein synthesis and in turn increases total cell-associated AChE activity and active tetramer secretion. Pulse-chase studies of isotopically labeled AChE molecules show that the enzyme is rescued from intracellular degradation. These studies provide a mechanistic explanation for the large scale intracellular degradation of AChE previously observed and indicate that simple peptides alone can increase the production and secretion of this critical synaptic enzyme in muscle tissue. PMID:26139603

  7. GIS plays key role in NYC Rescue and Relief Operation

    Science.gov (United States)

    Showstack, Randy

    New York City, Sept. 17—The posters of missing loved ones are pasted onto New York City walls and street signs six days after 2 hijacked commercial airlines destroyed the World Trade Center in lower Manhattan on September 11. Several miles uptown from “ground zero,” heightened security hovers around the city's Office of Emergency Management rescue and relief command center, an around-the-clock operation. Police, firefighters, military, officials with the Federal Emergency Management Agency, communications technicians, and a beehive of others work in controlled chaos in this cavernous, convention center-sized hall, lined with computers and adorned with several American flags.After the original command center at 7 World Trade Center collapsed to rubble as an after-effect of the plane strikes, city officials scrambled to recreate it. Alan Leidner, director of New York's citywide geographic information systems (GIS), and who is with the Department of Information Technology and Telecommunications, knew that maps would be an integral component of the rescue and relief efforts. Maps provide emergency workers and others with accurate and detailed scientific data in the form of visual aids upon which they can make informed decisions.

  8. VEGETATIVE RESCUE AND CUTTINGS PROPAGATION OF Araucaria angustifolia (Bertol. Kuntze

    Directory of Open Access Journals (Sweden)

    Ivar Wendling

    2015-02-01

    Full Text Available Brazilian pine or araucaria (Araucaria angustifolia is a coniferous tree with great economic, social and environmental importance in southern Brazil, being exploited for both wood production and for its edible pine nuts. However, no efficient cloning techniques are available and, therefore, the purpose of this study was to evaluate the effectiveness of vegetative rescue methods for cuttings propagation of the species. Shoots/cuttings were generated in two ways: 26 years old trees underwent coppicing and 20 years old trees had the primary branches on the upper third of crown pruned at 2, 20 and 50 cm from the main trunk. Orthotropic shoots were rooted after application of indole-3-butyric acid (IBA at 0, 2, 4 and 6 g.L-1. Coppicing produced 47 cuttings per plant with 90% orthotropic shoots, while pruning resulted in 182 cuttings per plant with 44% orthotropic shoots. Rooting success indexes were low with no influence of IBA, although they are slightly superior to the ones available in the literature for the species, ranging from 12 to 30% for the coppice shoots and from 0 to 28% for the branches shoots. We conclude that both vegetative rescue techniques are viable and have potentially important applications. Coppicing is recommended for the propagation aiming the production of wood, while shoots derived from the side branches of the crown are more appropriate for seeds orchards formation.

  9. Biobotic insect swarm based sensor networks for search and rescue

    Science.gov (United States)

    Bozkurt, Alper; Lobaton, Edgar; Sichitiu, Mihail; Hedrick, Tyson; Latif, Tahmid; Dirafzoon, Alireza; Whitmire, Eric; Verderber, Alexander; Marin, Juan; Xiong, Hong

    2014-06-01

    The potential benefits of distributed robotics systems in applications requiring situational awareness, such as search-and-rescue in emergency situations, are indisputable. The efficiency of such systems requires robotic agents capable of coping with uncertain and dynamic environmental conditions. For example, after an earthquake, a tremendous effort is spent for days to reach to surviving victims where robotic swarms or other distributed robotic systems might play a great role in achieving this faster. However, current technology falls short of offering centimeter scale mobile agents that can function effectively under such conditions. Insects, the inspiration of many robotic swarms, exhibit an unmatched ability to navigate through such environments while successfully maintaining control and stability. We have benefitted from recent developments in neural engineering and neuromuscular stimulation research to fuse the locomotory advantages of insects with the latest developments in wireless networking technologies to enable biobotic insect agents to function as search-and-rescue agents. Our research efforts towards this goal include development of biobot electronic backpack technologies, establishment of biobot tracking testbeds to evaluate locomotion control efficiency, investigation of biobotic control strategies with Gromphadorhina portentosa cockroaches and Manduca sexta moths, establishment of a localization and communication infrastructure, modeling and controlling collective motion by learning deterministic and stochastic motion models, topological motion modeling based on these models, and the development of a swarm robotic platform to be used as a testbed for our algorithms.

  10. SOCIAL MEDIA MANAGEMENT FOR A BAND : Case: Husky Rescue

    OpenAIRE

    Koskinen, Sampo

    2010-01-01

    The  goal  of  the  project  thesis  was  to  create,  produce  and  manage  the social  media  presence  of  a   Finnish  band  called  Husky  Rescue.  Husky Rescue  is  a  band  that  has  had  moderate  international   success.  The  thesis also  discusses  the  feasibility  of  starting  a  business  that  would  provide social   media  and  online  marketing  services  to  Finnish  artists. The  development  of  the  Internet  from  a  network  of  static  websites  to  a dynamic  co...

  11. Native flora rescue program: GASENE project case study

    Energy Technology Data Exchange (ETDEWEB)

    Serricchio, Claudio; Caldas, Flaviana V. [PETROBRAS, Rio de Janeiro, RJ (Brazil); Akahori, Lisa [Telsan, Rio de Janeiro, RJ (Brazil); Jacomelli Junior, Jose Almir [AGF Engenharia, Araucaria, PR (Brazil)

    2009-07-01

    Concerning the surrounding flora, the implementation of pipelines may cause fragmentation and isolation of the remaining natural vegetation, possibly changing the forest structure; thus raising the border effect; modifying the ratio of species and life forms, decreasing the vegetal diversity and/or causing a lack of connectivity among the remaining indigenous forest resources. In the case of pipelines, the most important environmental measure intended to mitigate the damage caused to the flora is the adoption of Indigenous Flora Rescue Programs. This paper is aimed at analyzing the programs currently applied during the implementation of the GASENE project, by conducting a case study. The main targets of such program are obtaining seeds and fruits with a view to subsidize the potential production of sapling to be further employed in the recovery of areas impacted by the pipeline works; and then relocate the most significant samples of species rescued from the suppressed areas in order to comprise forest areas adjacent to the pipeline's right-of-way. The programs had little differences in their methodology while being implemented, however, we consider that up to the present moment the results obtained in the preservation of species of native flora have been satisfactory. (author)

  12. Influencing factors of embryo rescue in seedless grape

    International Nuclear Information System (INIS)

    In this study, we investigated the impact of inoculating stage, medium type and concentration of plant growth regulators on embryo rescue effectiveness by L25(5)6 orthogonal design using selfed ovules of Venus Seedless as the testing material. The main results were as follows. The most important factor influencing ovule germination was inoculating stage. Ovule germinating rate gradually increased as inoculating being postponed. The highest germinating rate appeared when inoculation was done 55d after flowering. Other influencing factors were IBA concentration, exogenous amino acid, 6-BA concentration, GA3 concentration and medium type in descending order. The best embryo rescue result was based on Nitsch medium including 1.0 mg/L IBA, 0.1 mg/L GA3, 0.7 mg /L 6-BA and 2.0 mmol/L glutamine using ovules inoculated 55d after flowering. The highest germinating rate reached 41.25%, and a batch of seedlings was also obtained. (author)

  13. Mountain Search and Rescue with Remotely Piloted Aircraft Systems

    Science.gov (United States)

    Silvagni, Mario; Tonoli, Andrea; Zenerino, Enrico; Chiaberge, Marcello

    2016-04-01

    Remotely Piloted Aircraft Systems (RPAS) also known as Unmanned Aerial Systems (UAS) are nowadays becoming more and more popular in several applications. Even though a complete regulation is not yet available all over the world, researches, tests and some real case applications are wide spreading. These technologies can bring many benefits also to the mountain operations especially in emergencies and harsh environmental conditions, such as Search and Rescue (SAR) and avalanche rescue missions. In fact, during last decade, the number of people practicing winter sports in backcountry environment is increased and one of the greatest hazards for recreationists and professionals are avalanches. Often these accidents have severe consequences leading, mostly, to asphyxia-related death, which is confirmed by the hard drop of survival probability after ten minutes from the burying. Therefore, it is essential to minimize the time of burial. Modern avalanche beacon (ARTVA) interface guides the rescuer during the search phase reducing its time. Even if modern avalanche beacons are valid and reliable, the seeking range influences the rescue time. Furthermore, the environment and morphologic conditions of avalanches usually complicates the rescues. The recursive methodology of this kind of searching offers the opportunity to use automatic device like drones (RPAS). These systems allow performing all the required tasks autonomously, with high accuracy and without exposing the rescuers to additional risks due to secondary avalanches. The availability of highly integrated electronics and subsystems specifically meant for the applications, better batteries, miniaturized payload and, in general, affordable prices, has led to the availability of small RPAS with very good performances that can give interesting application opportunities in unconventional environments. The present work is one of the outcome from the experience made by the authors in RPAS fields and in Mechatronics

  14. Lanthionine ketimine ethyl ester partially rescues neurodevelopmental defects in unc-33 (DPYSL2/CRMP2) mutants.

    Science.gov (United States)

    Hubbard, Caleb; Benda, Erica; Hardin, Tyler; Baxter, Taylor; St John, Elizabeth; O'Brien, Sean; Hensley, Kenneth; Holgado, Andrea M

    2013-09-01

    Lanthionine ketimine (LK) is a natural sulfur amino acid metabolite with potent neurotrophic activity. Proteomics indicate that LK interacts with collapsin response mediator protein-2 (CRMP2/DPYSL2/UNC-33), a brain-enriched protein that was shown to regulate cytoskeletal remodeling, neuronal morphology, and synaptic function. To elucidate further the molecular interplay and biological action of LK and UNC-33, we began examining the nervous system of Caenorhabditis elegans nematodes in which both LK concentrations and UNC-33 protein were manipulated. To this end, a cell-permeable LK-ester (LKE) was administered to developing C. elegans engineered to express yellow fluorescent protein (YFP) in cholinergic neurons (strain RM3128) or green fluorescent protein (GFP) in GABAergic neurons (strain CZ1200), and neural morphology was assessed. Fluorescent imaging analyses show that LKE exposure to wild-type animals induced neural commissure outgrowth, crossing over, and bundling in both neurites from GABAergic and cholinergic motor neurons. Additionally, when unc-33(e204) hypomorph mutant nematodes (D389N substitution mutants) were exposed to LKE, both the neuroanatomical defects of incomplete dorsoventral neural commissures and the ventral nerve cord gaps were partially rescued. In contrast, LKE did not rescue ventral nerve cord gaps found in unc-33(mn407) null mutant. Together these data suggest possible functions for LK as a regulator of neuritic elongation, corroborate roles for UNC-33/CRMP2 in the mechanism of LKE activity, and suggest the potential of LKE as a therapeutic molecule for neurological diseases involving CRMP2 dysfunction. PMID:23825043

  15. Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.

    Science.gov (United States)

    Sztainberg, Yehezkel; Chen, Hong-mei; Swann, John W; Hao, Shuang; Tang, Bin; Wu, Zhenyu; Tang, Jianrong; Wan, Ying-Wooi; Liu, Zhandong; Rigo, Frank; Zoghbi, Huda Y

    2015-12-01

    Copy number variations have been frequently associated with developmental delay, intellectual disability and autism spectrum disorders. MECP2 duplication syndrome is one of the most common genomic rearrangements in males and is characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. The broad range of deficits caused by methyl-CpG-binding protein 2 (MeCP2) overexpression poses a daunting challenge to traditional biochemical-pathway-based therapeutic approaches. Accordingly, we sought strategies that directly target MeCP2 and are amenable to translation into clinical therapy. The first question that we addressed was whether the neurological dysfunction is reversible after symptoms set in. Reversal of phenotypes in adult symptomatic mice has been demonstrated in some models of monogenic loss-of-function neurological disorders, including loss of MeCP2 in Rett syndrome, indicating that, at least in some cases, the neuroanatomy may remain sufficiently intact so that correction of the molecular dysfunction underlying these disorders can restore healthy physiology. Given the absence of neurodegeneration in MECP2 duplication syndrome, we propose that restoration of normal MeCP2 levels in MECP2 duplication adult mice would rescue their phenotype. By generating and characterizing a conditional Mecp2-overexpressing mouse model, here we show that correction of MeCP2 levels largely reverses the behavioural, molecular and electrophysiological deficits. We also reduced MeCP2 using an antisense oligonucleotide strategy, which has greater translational potential. Antisense oligonucleotides are small, modified nucleic acids that can selectively hybridize with messenger RNA transcribed from a target gene and silence it, and have been successfully used to correct deficits in different mouse models. We find that antisense oligonucleotide treatment induces a broad phenotypic rescue in adult

  16. A Place to Call Home——Rescued moon bears get to live a decent life

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    On February 8, 2006, a piece of sad news came out of the Moon Bear Rescue Center in Chengdu, capital city of southwest China's Sichuan Province. Andrew, the first moon bear rescued by the Animals Asia Foundation, which sponsors the center, died of liver cancer, thought to have arisen from the massive infec-

  17. 75 FR 18888 - Mine Rescue Teams and Arrangements for Emergency Medical Assistance and Transportation for...

    Science.gov (United States)

    2010-04-13

    ... Safety and Health Administration Mine Rescue Teams and Arrangements for Emergency Medical Assistance and... teams for underground coal mines on February 8, 2008. The United Mine Workers of America challenged the... revised its requirements for mine rescue teams for underground coal mines on June 17, 2009. The 2008...

  18. Functional phenotypic rescue of Caenorhabditis elegans neuroligin-deficient mutants by the human and rat NLGN1 genes.

    Directory of Open Access Journals (Sweden)

    Fernando Calahorro

    Full Text Available Neuroligins are cell adhesion proteins that interact with neurexins at the synapse. This interaction may contribute to differentiation, plasticity and specificity of synapses. In humans, single mutations in neuroligin encoding genes lead to autism spectrum disorder and/or mental retardation. Caenorhabditis elegans mutants deficient in nlg-1, an orthologue of human neuroligin genes, have defects in different behaviors. Here we show that the expression of human NLGN1 or rat Nlgn1 cDNAs in C. elegans nlg-1 mutants rescues the fructose osmotic strength avoidance and gentle touch response phenotypes. Two specific point mutations in NLGN3 and NLGN4 genes, involved in autistic spectrum disorder, were further characterized in this experimental system. The R451C allele described in NLGN3, was analyzed with both human NLGN1 (R453C and worm NLG-1 (R437C proteins, and both were not functional in rescuing the osmotic avoidance behavior and the gentle touch response phenotype. The D396X allele described in NLGN4, which produces a truncated protein, was studied with human NLGN1 (D432X and they did not rescue any of the behavioral phenotypes analyzed. In addition, RNAi feeding experiments measuring gentle touch response in wild type strain and worms expressing SID-1 in neurons (which increases the response to dsRNA, both fed with bacteria expressing dsRNA for nlg-1, provided evidence for a postsynaptic in vivo function of neuroligins both in muscle cells and neurons, equivalent to that proposed in mammals. This finding was further confirmed generating transgenic nlg-1 deficient mutants expressing NLG-1 under pan-neuronal (nrx-1 or pan-muscular (myo-3 specific promoters. All these results suggest that the nematode could be used as an in vivo model for studying particular synaptic mechanisms with proteins orthologues of humans involved in pervasive developmental disorders.

  19. Rescue for sexually abused girls in Costa Rica.

    Science.gov (United States)

    Treguear, T; Peters, L

    1995-01-01

    In San Jose, Costa Rica, the nongovernmental organization PROCAL has established two rescue homes for sexually abused girls 10-15 years of age. One of these homes is devoted to the care of pregnant girls. In almost all cases, the perpetrator was a male relative. Since girls are taught they must obey older male relatives, they are powerless to stop the abuse. When girls become pregnant as a result of sexual abuse, they face social ostracism and are blamed for their participation in sexual activity. PROCAL counsels the girls that they are victims of their own lack of power and provides them with skills and education they need to return to society and start a new life. The stories of two young girls who became pregnant as a result of sexual abuse and were helped by PROCAL are presented. PMID:12319363

  20. Scene recognition for mine rescue robot localization based on vision

    Institute of Scientific and Technical Information of China (English)

    CUI Yi-an; CAI Zi-xing; WANG Lu

    2008-01-01

    A new scene recognition system was presented based on fuzzy logic and hidden Markov model(HMM) that can be applied in mine rescue robot localization during emergencies. The system uses monocular camera to acquire omni-directional images of the mine environment where the robot locates. By adopting center-surround difference method, the salient local image regions are extracted from the images as natural landmarks. These landmarks are organized by using HMM to represent the scene where the robot is, and fuzzy logic strategy is used to match the scene and landmark. By this way, the localization problem, which is the scene recognition problem in the system, can be converted into the evaluation problem of HMM. The contributions of these skills make the system have the ability to deal with changes in scale, 2D rotation and viewpoint. The results of experiments also prove that the system has higher ratio of recognition and localization in both static and dynamic mine environments.

  1. Financing Corporate Rescues, Where Does the UK Stand?

    Directory of Open Access Journals (Sweden)

    Akpareva Aruoriwo

    2014-05-01

    Full Text Available In this paper Akpareva Aruoriwo aims to evaluate the adequacy of the framework available for the financing of corporate rescues in the UK. She examines the legal provision made for prioritising creditors who get involved after an insolvency has been declared, with reference to examples from America and Canada. Without post-insolvency funding, companies may find it very difficult to survive, and without protection for post-insolvency creditors, those creditors may not wish to provide this sort of funding. The author examines the arguments for and against this kind of creditor protection, looking at past calls for reforms to the law and the preparedness of the UK to adopt any reforms.

  2. Microbes Promote Amino Acid Harvest to Rescue Undernutrition in Drosophila

    Directory of Open Access Journals (Sweden)

    Ryuichi Yamada

    2015-02-01

    Full Text Available Microbes play an important role in the pathogenesis of nutritional disorders such as protein-specific malnutrition. However, the precise contribution of microbes to host energy balance during undernutrition is unclear. Here, we show that Issatchenkia orientalis, a fungal microbe isolated from field-caught Drosophila melanogaster, promotes amino acid harvest to rescue the lifespan of undernourished flies. Using radioisotope-labeled dietary components (amino acids, nucleotides, and sucrose to quantify nutrient transfer from food to microbe to fly, we demonstrate that I. orientalis extracts amino acids directly from nutrient-poor diets and increases protein flux to the fly. This microbial association restores body mass, protein, glycerol, and ATP levels and phenocopies the metabolic profile of adequately fed flies. Our study uncovers amino acid harvest as a fundamental mechanism linking microbial and host metabolism, and highlights Drosophila as a platform for quantitative studies of host-microbe relationships.

  3. Test Report : GS battery, EPC power HES RESCU.

    Energy Technology Data Exchange (ETDEWEB)

    Rose, David Martin; Schenkman, Benjamin L.; Borneo, Daniel R.

    2013-10-01

    The Department of Energy Office of Electricity (DOE/OE), Sandia National Laboratories (SNL) and the Base Camp Integration Lab (BCIL) partnered together to incorporate an energy storage system into a microgrid configured Forward Operating Base to reduce the fossil fuel consumption and to ultimately save lives. Energy storage vendors will be sending their systems to SNL Energy Storage Test Pad (ESTP) for functional testing and then to the BCIL for performance evaluation. The technologies that will be tested are electro-chemical energy storage systems comprising of lead acid, lithium-ion or zinc-bromide. GS Battery and EPC Power have developed an energy storage system that utilizes zinc-bromide flow batteries to save fuel on a military microgrid. This report contains the testing results and some limited analysis of performance of the GS Battery, EPC Power HES RESCU.

  4. Multi-robot Task Allocation for Search and Rescue Missions

    International Nuclear Information System (INIS)

    Many researchers from academia and industry are attracted to investigate how to design and develop robust versatile multi-robot systems by solving a number of challenging and complex problems such as task allocation, group formation, self-organization and much more. In this study, the problem of multi-robot task allocation (MRTA) is tackled. MRTA is the problem of optimally allocating a set of tasks to a group of robots to optimize the overall system performance while being subjected to a set of constraints. A generic market-based approach is proposed in this paper to solve this problem. The efficacy of the proposed approach is quantitatively evaluated through simulation and real experimentation using heterogeneous Khepera-III mobile robots. The results from both simulation and experimentation indicate the high performance of the proposed algorithms and their applicability in search and rescue missions

  5. Neuroprotective and nootropic drug noopept rescues α-synuclein amyloid cytotoxicity.

    Science.gov (United States)

    Jia, Xueen; Gharibyan, Anna L; Öhman, Anders; Liu, Yonggang; Olofsson, Anders; Morozova-Roche, Ludmilla A

    2011-12-16

    Parkinson's disease is a common neurodegenerative disorder characterized by α-synuclein (α-Syn)-containing Lewy body formation and selective loss of dopaminergic neurons in the substantia nigra. We have demonstrated the modulating effect of noopept, a novel proline-containing dipeptide drug with nootropic and neuroprotective properties, on α-Syn oligomerization and fibrillation by using thioflavin T fluorescence, far-UV CD, and atomic force microscopy techniques. Noopept does not bind to a sterically specific site in the α-Syn molecule as revealed by heteronuclear two-dimensional NMR analysis, but due to hydrophobic interactions with toxic amyloid oligomers, it prompts their rapid sequestration into larger fibrillar amyloid aggregates. Consequently, this process rescues the cytotoxic effect of amyloid oligomers on neuroblastoma SH-SY5Y cells as demonstrated by using cell viability assays and fluorescent staining of apoptotic and necrotic cells and by assessing the level of intracellular oxidative stress. The mitigating effect of noopept against amyloid oligomeric cytotoxicity may offer additional benefits to the already well-established therapeutic functions of this new pharmaceutical. PMID:21986202

  6. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease.

    Science.gov (United States)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie; Li, Xiaojie; Chandler-Militello, Devin; Mauceri, Joseph; Burm, Hayley B; Toner, Michael; Osipovitch, Mikhail; Jim Xu, Qiwu; Ding, Fengfei; Wang, Fushun; Kang, Ning; Kang, Jian; Curtin, Paul C; Brunner, Daniela; Windrem, Martha S; Munoz-Sanjuan, Ignacio; Nedergaard, Maiken; Goldman, Steven A

    2016-01-01

    The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder. PMID:27273432

  7. CO{sub 2} in underground openings and mine rescue training

    Energy Technology Data Exchange (ETDEWEB)

    Weyer, J. [Freiburg Univ. of Mining and Technology (Germany). Inst. of Mining Engineering and Special Civil Engineering

    2010-07-01

    Mine rescue training procedures related to dangerous gases in mines were discussed. Methods of detecting carbon dioxide (CO{sub 2}) in abandoned opening and old adits were presented. High concentrations of CO{sub 2} combine with hemoglobin and lead to a lack of oxygen supply to the inner organs. Nitric acid forms in the alveoli and can lead to injuries or death after a period of 4 to 12 hours. Exposure to very high concentrations of CO{sub 2} can cause people to immediately lose consciousness. CO{sub 2} concentrations in the blood can change pH blood values. Members of mine rescue teams should be equipped with breathing equipment and be between 18 and 40 years old. Training rescue operations should be conducted 4 times per year. While larger mines have their own rescue teams, smaller mines must ensure that guest rescue teams are familiar with their mines. Various mine training activities were reviewed. 5 refs.

  8. Robot-Assisted Risky Intervention, Search, Rescue and Environmental Surveillance

    Directory of Open Access Journals (Sweden)

    Maki K. Habib

    2010-02-01

    Full Text Available Technology has become the solution to many long-standing problems, and while current technologies may be effective, it is far from fully addressing the hug, complex, difficult and challenging tasks associated with disaster missions and risky intervention. The challenge is in finding creative, reliable and applicable technical solutions in such highly constrained and uncertain environment. In addition, it is necessary to overcome constrains on resources by developing innovative, cost effective and practical technology. Robotics can play important intelligent and technological roles that support first response equipment in harsh and dangerous environments while replacing rescue personnel from entering unreachable or unsafe places. Robotics solutions that are well adapted to local conditions of unstructured and unknown environment can greatly improve safety and security of personnel as well as work efficiency, productivity and flexibility. Solving and fulfilling the needs of such tasks presents challenges in robotic mechanical structure and mobility, sensors and sensor fusion, autonomous and semi autonomous control, planning and navigation, and machine intelligence. This paper categorizes the source of disasters and associated missions, and highlights the needs for suitable and reliable technology and technical and functional requirements of robotic systems to fulfill task objectives. In addition, it shows that robotic technologies can be used for disasters prevention or early warning, intervention and recovery efforts during disasters with all possible kinds of relevant missions while ensuring quality of service and safety of human beings. Some of these missions may include: demining, search and rescue, surveillance, reconnaissance and risk assessment, evacuation assistance, intrusion/victim detection and assessment, etc.

  9. Fast track antibody V-gene rescue, recombinant expression in plants and characterization of a PfMSP4-specific antibody

    OpenAIRE

    Kapelski, Stephanie; Boes, Alexander; Spiegel, Holger; de Almeida, Melanie; Klockenbring, Torsten; Reimann, Andreas; Fischer, Rainer; Barth, Stefan; Fendel, Rolf

    2015-01-01

    Background Monoclonal antibodies (mAbs) are essential tools in biological research, diagnosis and therapy, and are conventionally produced in murine hybridoma cell lines. Professional applications of mAbs depend on the steady supply of material. Because hybridoma cultures can stop producing the antibody or even die, preservation of the unique epitope specificity of mAbs by rescue of the sequences encoding the antibody variable domains (V regions) is important. The availability of these sequen...

  10. Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus.

    Science.gov (United States)

    Smith, Emery; Janovick, Jo Ann; Bannister, Thomas D; Shumate, Justin; Scampavia, Louis; Conn, P Michael; Spicer, Timothy P

    2016-09-01

    Pharmacoperones correct the folding of otherwise misfolded protein mutants, restoring function (i.e., providing "rescue") by correcting their trafficking. Currently, most pharmacoperones possess intrinsic antagonist activity because they were identified using methods initially aimed at discovering such functions. Here, we describe an ultra-high-throughput homogeneous cell-based assay with a cAMP detection system, a method specifically designed to identify pharmacoperones of the vasopressin type 2 receptor (V2R), a GPCR that, when mutated, is associated with nephrogenic diabetes insipidus. Previously developed methods to identify compounds capable of altering cellular trafficking of V2R were modified and used to screen a 645,000 compound collection by measuring the ability of library compounds to rescue a mutant hV2R [L83Q], using a cell-based luminescent detection system. The campaign initially identified 3734 positive modulators of cAMP. The confirmation and counterscreen identified only 147 of the active compounds with an EC50 of ≤5 µM. Of these, 83 were reconfirmed as active through independently obtained pure samples and were also inactive in a relevant counterscreen. Active and tractable compounds within this set can be categorized into three predominant structural clusters, described here, in the first report detailing the results of a large-scale pharmacoperone high-throughput screening campaign. PMID:27280550

  11. Enhancing the survival of grafted cardiac stem cells for long-term imaging

    Energy Technology Data Exchange (ETDEWEB)

    Le, Uyenchi N.; Tae, Seong Ho; Bom, Hee Seung; Min, Jung Joon [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-07-01

    Heat shock treatment is known to induce the protection for cells from various environmental insults. Akt (protein kinase B) - with anti-apoptotic activity - has presently been reemerged as a critical enzyme in several signal transduction pathways involved in cell proliferation and programmed cell death. We hypothesized that thermotic treatment and Akt activity in genetically modified cardiomyoblasts would improve their survival after transplantation. Embryonic rat H9c2 cardiomyoblasts were simultaneously transfected with adenovirus containing luciferase reporter gene (MOl 50) and another containing Akt gene [MOl (0 100) ]. 5x106 harvested cells were i.m. implanted into murine skeletal muscles. Bioluminescence imaging was acquired for everyday and luciferase assay was performed to validate the imaging data. For thermotic challenge, adenovirus-mediated flue expressing H9c2 cells were subjected to great heat of 42 .deg. C for 1 hr and re-cultured at 37 .deg. C for 18 hours. Expression of heat shock protein in cells was detected in vitro by Western-blotting. 5x106 normal and shocked cells were implanted into mouse thigh (n = 5) and the animals were imaged with bioluminescence imaging system. In vitro evidences showed a high level expression of Akt and HSP in transfected H9c2 cells. Animals carrying Akt expressed bioluminescence signals until day 34 of post-implantation. The Flue activity was significantly higher in the shocked H9c2 cell-implanted rats and detected over 10 days as compared with the control group. The graft cell death was reduced by 73% at day 2 (1.46+ 10-7 p/s/cm{sup 2}/sr), 51% at day 3 (1.02+10-7 p/s/cm{sup 2}/sr), and 8% at day 10 (1.62+ 10-6 p/s/cm{sup 2}/sr). We revealed here improvement of donor cell's survival induced by the anti-apoptotic means of Akt genetic therapy or heat shock. Utility of bioluminescence imaging resulted in a potential to noninvasively and repetitively monitor implanted cardiac myoblasts over time.

  12. Human cathepsin L rescues the neurodegeneration and lethality incathepsin B/L double deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Sevenich, Lisa; Pennacchio, Len A.; Peters, Christoph; Reinheckel, Thomas

    2006-01-09

    Cathepsin B (CTSB) and cathepsin L (CTSL) are two widelyexpressed cysteine proteases thought to predominantly reside withinlysosomes. Functional analysis of CTSL in humans is complicated by theexistence of two CTSL-like homologues (CTSL and CTSL2), in contrast tomice which contain only one CTSL enzyme. Thus transgenic expression ofhuman CTSL in CTSL deficient mice provides an opportunity to study the invivo functions of this human protease without interference by its highlyrelated homologue. While mice with single gene deficiencies for murineCTSB or CTSL survive without apparent neuromuscular impairment, murineCTSB/CTSL double deficient mice display degeneration of cerebellarPurkinje cells and neurons of the cerebral cortex, resulting in severehypotrophy, motility defects, and lethality during their third to fourthweek of life. Here we show that expression of human CTSL through agenomic transgene results in widespread expression of human CTSL in themouse which is capable of rescuing the lethality found in CTSB/CTSLdouble-deficient animals. Human CTSL is expressed in the brain of thesecompound mutants predominantly in neurons of the cerebral cortex and inPurkinje cells of the cerebellum, where it appears to prevent neuronalcell death.

  13. Rescue of Newcastle disease virus from cloned cDNA using an RNA polymerase II promoter.

    Science.gov (United States)

    Li, Bao-Yu; Li, Xue-Rui; Lan, Xi; Yin, Xiang-Pin; Li, Zhi-Yong; Yang, Bin; Liu, Ji-Xing

    2011-06-01

    A new system was developed to improve the efficiency and simplify the procedure of recovery of Newcastle disease virus (NDV) from cloned cDNA. A full-length cDNA clone of mesogenic NDV vaccine strain Mukteswar was assembled from five subgenomic cDNA fragments and cloned into a plasmid allowing transcription driven by cellular RNA polymerase II. The full-length viral cDNA was flanked by hammerhead ribozyme (HamRz) and hepatitis delta virus ribozyme (HdvRz) sequences, resulted in the synthesis of antigenomic RNA with exact termini. Without supplying T7 RNA polymerase, infectious NDV could be generated efficiently in some eukaryotic cell lines by simultaneous transcription of antigenomic RNA from the full-length plasmid and expression of NP, P and L proteins from helper plasmids introduced by cotransfection. The efficiency of recovery with the conventional T7 promoter system based on BRS-T7 cells and the cytomegalovirus (CMV) promoter system was compared, and the results demonstrate that the new system facilitates the generation of recombinant NDV and more efficient than the T7 rescue system using BRS-T7. PMID:21327786

  14. Curcumin Rescues Diabetic Renal Fibrosis by Targeting Superoxide-Mediated Wnt Signaling Pathways.

    Science.gov (United States)

    Ho, Cheng; Hsu, Yung-Chien; Lei, Chen-Chou; Mau, Shu-Ching; Shih, Ya-Hsueh; Lin, Chun-Liang

    2016-03-01

    The purposes of this study were to investigate whether curcumin can weaken diabetic nephropathy by modulating both oxidative stress and renal injury from Wnt signaling mediation. Wnt5a/β-catenin depression and induction of superoxide synthesis are associated with high glucose (HG) induced transforming growth factor (TGF)-β1 and fibronectin expression in mesangial cells. Curcumin resumes HG depression of Wnt/β-catenin signaling and alleviates HG induction of superoxide, TGF-β1 and fibronectin expression in renal mesangial cell. Exogenous curcumin alleviated urinary total proteinuria and serum superoxide level in diabetic rats. Based on laser-captured microdissection for quantitative real-time polymerase chain reaction, it was found that diabetes significantly increased TGF-β1 and fibronectin expression in line with depressed Wnt5a expression. Curcumin treatment reduced the TGF-β1 and fibronectin activation and the inhibiting effect of diabetes on Wnt5a/β-catenin expression in renal glomeruli. Immunohistochemistry showed that curcumin treatment significantly reduced 8-hydroxy-2'-deoxyguanosine, TGF-β1 and fibronectin, and was in line with the restoration of the suppressed Wnt5a expression immunoreactivities in glomeruli of diabetic rats. Curcumin alleviated extracellular matrix accumulation in diabetic nephropathy by not only preventing the diabetes-mediated superoxide synthesis but also resuming downregulation of Wnt/β-catenin signaling. These findings suggest that regulation of Wnt activity by curcumin is a feasible alternative strategy to rescue diabetic renal injury. PMID:26992258

  15. Study on the Programming Standard for Ecological Rescue in General Land Use Planning

    Institute of Scientific and Technical Information of China (English)

    Bai Wei; Hao Jinmin; Zhang Qiuping

    2006-01-01

    This paper aims at establishing the operation idea based on the analysis of the connotation, principles and reference indexes for programming standard for ecological rescue. The paper puts forward that the programming standard should take into account the natural, social and economic reference indexes, and modifies the scale and distribution of the ecological rescue according to the order of ecological safety, social safety and economic development. The paper suggests that the land planning department should strengthen the study and datum accumulation in order to establish the technology regulations of programming standard of the ecological rescue.

  16. [Model and enlightenment from rescue of August 2nd Kunshan explosion casualty].

    Science.gov (United States)

    Tan, Q; Qiu, H B; Sun, B W; Shen, Y M; Nie, L J; Zhang, H W

    2016-01-01

    On August 2nd, 2014, a massive dust explosion occurred in a factory of Kunshan, resulting in a mass casualty involving 185 burn patients. They were transported to 20 medical institutions in Jiangsu province and Shanghai. More than one thousand of medical personnel of our country participated in this emergency rescue, and satisfactory results were achieved. In this paper, the characteristics of this accident were analyzed, the positive effects of interdisciplinary cooperation were affirmed, and the contingency plan, rescue process and pattern, and reserve, organization and management of talents during this rescue process were reviewed retrospectively. PMID:27426066

  17. Mission requirements: Skylab rescue mission SL-R

    Science.gov (United States)

    1973-01-01

    The Skylab Program includes three low earth orbit missions. These missions are designated SL-1/SL-2,SL-3 and SL-4. In addition to the three nominal Skylab missions, the program includes the Skylab Rescue Mission (SL-R). The SL-R mission is designed to provide a safe return of the Skylab crew in the event the Command Service Module (CSM) becomes disabled while docked to the Saturn Workshop (SWS). Mission requirements for the SL-R mission only are presented. SL-R mission configuration will be a CSM (modified with a field installed kit) manned by two crewmen launched on a Saturn IB Launch Vechicle. The SL-R CSM will rendezvous and dock with the SWS (or Orbital Assembly (OA), consisting of the SWS and disabled CSM, if the disabled CSM has not previously been jettisoned). The SWS configuration includes a Multiple Docking Adapter (MDA), Apollo Telescope Mount (ATM), Airlock Module (AM), and an S-IVB stage (modified as an Orbital Workshop (OWS), previously launched and inserted into orbit on a two-stage Saturn V Launch Vehicle for the SL-1/SL-2 mission.

  18. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

    Full Text Available We have previously shown that adenosine amine congener (ADAC, a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg was administered intraperitoneally to Wistar rats (8–10 weeks old at intervals (6–72 hours after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours. Hearing sensitivity was assessed using auditory brainstem responses (ABR before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz. Pharmacokinetic studies demonstrated a short (5 min half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

  19. Performance standards for urban search and rescue robots

    Science.gov (United States)

    Messina, Elena; Jacoff, Adam

    2006-05-01

    In this paper, we describe work in performance standards for urban search and rescue (USAR) robots begun in 2004 by the Department of Homeland Security. This program is being coordinated by the National Institute of Standards and Technology and will result in consensus standards developed through ASTM International, under the Operational Equipment Subcommittee of their Homeland Security Committee. The first phase of the program involved definition of requirements by subject matter experts. Responders participated in a series of workshops to identify deployment categories for robots, performance categories, and ranges of acceptable or target performance in the various categories. Over one hundred individual requirements were identified, within main categories such as Human-System Interaction, Logistics, Operating Environment, and System (which includes Chassis, Communications, Mobility, Payload, Power, and Sensing). To ensure that the robot developers and eventual end users work closely together, "responders meet robots" events at situationally relevant sites are being held to refine and extend the performance requirements and develop standard test methods. The results of these standard performance tests will be captured in a compendium of existing and developmental robots with classifications and descriptors to differentiate particular robotic capabilities. This, along with ongoing efforts to categorize situational USAR constraints such as building collapse types or the presence of hazardous materials, will help responders match particular robotic capabilities to response needs. In general, these efforts will enable responders to effectively use robotic tools to enhance their effectiveness while reducing risk to personnel during disasters.

  20. Knowledge of Glasgow coma scale by air-rescue physicians

    Directory of Open Access Journals (Sweden)

    Heim Catherine

    2009-09-01

    Full Text Available Abstract Objective To assess the theoretical and practical knowledge of the Glasgow Coma Scale (GCS by trained Air-rescue physicians in Switzerland. Methods Prospective anonymous observational study with a specially designed questionnaire. General knowledge of the GCS and its use in a clinical case were assessed. Results From 130 questionnaires send out, 103 were returned (response rate of 79.2% and analyzed. Theoretical knowledge of the GCS was consistent for registrars, fellows, consultants and private practitioners active in physician-staffed helicopters. The clinical case was wrongly scored by 38 participants (36.9%. Wrong evaluation of the motor component occurred in 28 questionnaires (27.2%, and 19 errors were made for the verbal score (18.5%. Errors were made most frequently by registrars (47.5%, p = 0.09, followed by fellows (31.6%, p = 0.67 and private practitioners (18.4%, p = 1.00. Consultants made significantly less errors than the rest of the participating physicians (0%, p Conclusion Although the theoretical knowledge of the GCS by out-of-hospital physicians is correct, significant errors were made in scoring a clinical case. Less experienced physicians had a higher rate of errors. Further emphasis on teaching the GCS is mandatory.

  1. Strategic Step for Environmental Rescue: A Theoretical Legal Studies

    Directory of Open Access Journals (Sweden)

    Bambang Sutrisno

    2014-01-01

    Full Text Available Indonesia is among the developing countries that are struggling to develop in the field of industrial development. The logical consequence of any development process, especially industrial development is the emergence of associated impacts that greatly affect the durability and sustainability of the environment. Developing the equitable industry in order to create public welfare is important. However, maintaining the security and preservation of the environment is also very important, because it is only with the availability of a good environment and healthy living that human beings can perform daily living. The availability of good and healthy environment is the constitutional responsibility of the government, as well as part of the human rights of all citizens which must be given by the State. Efforts to create a good environment and healthy living will be effective if controlled by State government and institutions who understand the objective conditions on the ground. In this regard, the granting of the authority on environmental control to regional government autonomously is the right, very smart policy choice. How To Cite: Sutrisno, B. (2016. Strategic Step for Environmental Rescue: A Theoretical Legal Studies. Rechtsidee, 1(1, 27-58. doi:http://dx.doi.org/10.21070/jihr.v1i1.98

  2. Ginkgo Biloba Extract Ameliorates Oxidative Phosphorylation Performance and Rescues Aβ-Induced Failure

    Science.gov (United States)

    Rhein, Virginie; Giese, Maria; Baysang, Ginette; Meier, Fides; Rao, Stefania; Schulz, Kathrin L.; Hamburger, Matthias; Eckert, Anne

    2010-01-01

    Background Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Aβ) in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Aβ-induced defects in energy metabolism. Methodology/Principal Findings We used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector) and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS) levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Aβ-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Aβ and oxidative stress level. Conclusions/Significance Although the underlying

  3. Ginkgo biloba extract ameliorates oxidative phosphorylation performance and rescues abeta-induced failure.

    Directory of Open Access Journals (Sweden)

    Virginie Rhein

    Full Text Available BACKGROUND: Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD. Recently, we demonstrated that chronic exposure to amyloid-beta (Abeta in human neuroblastoma cells over-expressing human wild-type amyloid precursor protein (APP resulted in (i activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS and in (ii a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE is able to rescue Abeta-induced defects in energy metabolism. METHODOLOGY/PRINCIPAL FINDINGS: We used a high-resolution respiratory protocol to evaluate OXPHOS respiratory capacity under physiological condition in control (stably transfected with the empty vector and APP cells after treatment with GBE. In addition, oxygen consumption of isolated mitochondria, activities of mitochondrial respiratory enzymes, ATP and reactive oxygen species (ROS levels as well as mitochondrial membrane mass and mitochondrial DNA content were determined. We observed a general antioxidant effect of GBE leading to an increase of the coupling state of mitochondria as well as energy homeostasis and a reduction of ROS levels in control cells and in APP cells. GBE effect on OXPHOS was even preserved in mitochondria after isolation from treated cells. Moreover, these functional data were paralleled by an up-regulation of mitochondrial DNA. Improvement of the OXPHOS efficiency was stronger in APP cells than in control cells. In APP cells, the GBE-induced amelioration of oxygen consumption most likely arose from the modulation and respective normalization of the Abeta-induced disturbance in the activity of mitochondrial complexes III and IV restoring impaired ATP levels possibly through decreasing Abeta and oxidative stress level. CONCLUSIONS

  4. Versatile Cosmid Vectors for the Isolation, Expression, and Rescue of Gene Sequences: Studies with the Human α -globin Gene Cluster

    Science.gov (United States)

    Lau, Yun-Fai; Kan, Yuet Wai

    1983-09-01

    We have developed a series of cosmids that can be used as vectors for genomic recombinant DNA library preparations, as expression vectors in mammalian cells for both transient and stable transformations, and as shuttle vectors between bacteria and mammalian cells. These cosmids were constructed by inserting one of the SV2-derived selectable gene markers-SV2-gpt, SV2-DHFR, and SV2-neo-in cosmid pJB8. High efficiency of genomic cloning was obtained with these cosmids and the size of the inserts was 30-42 kilobases. We isolated recombinant cosmids containing the human α -globin gene cluster from these genomic libraries. The simian virus 40 DNA in these selectable gene markers provides the origin of replication and enhancer sequences necessary for replication in permissive cells such as COS 7 cells and thereby allows transient expression of α -globin genes in these cells. These cosmids and their recombinants could also be stably transformed into mammalian cells by using the respective selection systems. Both of the adult α -globin genes were more actively expressed than the embryonic zeta -globin genes in these transformed cell lines. Because of the presence of the cohesive ends of the Charon 4A phage in the cosmids, the transforming DNA sequences could readily be rescued from these stably transformed cells into bacteria by in vitro packaging of total cellular DNA. Thus, these cosmid vectors are potentially useful for direct isolation of structural genes.

  5. Fish Health Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. All fresh mortalities larger than 100 mm are sent to Fish Health for...

  6. Fish Culture Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Raw data on rearing density, loading density, water temperature, ration,...

  7. Production Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Information on the number of smolts received into the program is...

  8. Broodyear Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Data is collected by broodyear on % survival to adult, % maturity as two...

  9. 15 CFR 270.202 - Coordination with search and rescue efforts.

    Science.gov (United States)

    2010-01-01

    ... efforts being undertaken at the site of the building failure, including FEMA urban search and rescue teams, local emergency management agencies, and local emergency response groups. Upon arrival at a...

  10. Wearing properties of flameproof clothing for mine rescue and gas protection personnel

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, R.; Tejmar, J.

    1981-04-01

    Apart from the safety requirements stated in DIN 23320 for flameproof clothing for mine rescue and gas protection personnel, also the wearing properties of these suits is important. Flameproof suits must be worn either for an 8-hour shift under normal working conditions or for the periods stated in the relevant regulations under unfavourable conditions in order to qualify as flame protection clothing. The wearing characteristics of flameproof suits for mine rescue and gas protection personnel according to DIN 23320 (2) under unfavourable climatic conditions were investigated at the Saar Central Office for Mine Rescue; the flameproof suits Proban, FPT, Nomex, and Pyrovatex were tested. Methods of measurement and criteria of assessment are described in detail. The findings suggest that the Nomex-III suit should be recommended as flameproof suit for mine rescue and gas protection personnel.

  11. Growth Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. The fork length to the nearest mm and weight to the nearest gram of a...

  12. Research on preferences for participation in search and rescue activities: “Akut” search and rescue association sample

    Directory of Open Access Journals (Sweden)

    Burak Gürer

    2014-10-01

    Full Text Available Current study aimed to identify why AKUT Search and Rescue (SAR Association Members participate in SAR, specify expectations and examine activities in terms of various demographics. 126 AKUT members (103 male, 23 female participated in the study. Data with .84 reliability coefficient was collected with a survey. Data analysis included frequencies, percentage distribution, t-test and ANOVA. Level of statistical significance was .05. Although results didn’t pinpoint distinctive reasons for participating in SAR, prominent elements affecting members were identified as “Existence of trainers in immediate vicinity” (19% and “Impact of friends/peer groups” (17.5%. Results showed that impact of family (73% was not important but age was. It was also found that single individuals inclined towards SAR to a higher extent. Reasons for continuing activities were “Caring for SAR” (50% and “Awareness of positive contributions” (48.4%. Contributing to financial income was found to have no relationship with SAR (90.5%. No relationship was detected between reasons participating in SAR and demographic characteristics. Expectations from SAR were mostly related to “being a trainer” (53.2%. Expectations and age were found to be related. Younger and single members had higher expectations for being trainers in future. Results showed that volunteerism had important implications in current study.

  13. Dynamics of evolutionary rescue in changing environments and the emergence of antibiotic resistance.

    Science.gov (United States)

    Wu, Yue; Saddler, Clare A; Valckenborgh, Frank; Tanaka, Mark M

    2014-01-01

    Populations can go extinct when their environments deteriorate, but evolutionary rescue occurs when a shrinking population adapts to the new environmental conditions. The emergence of resistance from a drug sensitive bacterial population under treatment can be regarded as an instance of evolutionary rescue. Understanding evolutionary rescue in a particular context such as drug resistance requires knowledge of how the environment changes and how selection coefficients change as a result. In this study, we propose a model for evolutionary rescue under three different scenarios of environmental change: abrupt change, periodic fluctuation and gradual decay. The model makes use of the notion of reaction norms to describe fitness values that depend on both genotype and environmental state. We find that although drug sensitive bacterial populations may be large, allowing them to generate resistant mutants frequently, a harsh abrupt change due to the drug usually drives them extinct. Evolutionary rescue occurs far more frequently under the milder forms of environmental change we investigated. Rescue is favoured when the absolute fitnesses of individuals remain sufficiently high over the range of environment qualities experienced by the population. The minimum environment quality, which is inversely related to drug dose in the antibiotic context, is thus an important factor. Interestingly, in the periodic fluctuation model, the inter-dose period is less influential in promoting rescue through resistance unless the minimum environment quality is in a particular range. We also investigated fitness trade-offs across environments including the case of a resistant allele not subject to any trade-off (a "superbug"). This fitness trade-off affects the probability of rescue in decaying environments, but surprisingly has only a weak effect in the periodic fluctuation scenario. Finally, we use the model to show how niche construction, whereby organisms are the source of environmental

  14. Surviving Rescue: A Feminist Reading of Scott O'Dell's "Island of the Blue Dolphins"

    Science.gov (United States)

    Baecker, Diann L.

    2007-01-01

    Scott O'Dell's "Island of the Blue Dolphins" tells the archetypal story of the young, virgin, orphan girl who is vulnerable to either debauchery or rescue. That such a girl must succumb to either one or the other is a necessary element of the archetype. In O'Dell's work--one intended, after all, for children--the heroine is rescued by a…

  15. Helicopter emergency medical rescue for the traumatized: experience in the metropolitan region of Campinas, Brazil

    OpenAIRE

    Ricardo Galesso Cardoso; Carina Fontana Francischini; Jorge Michel Ribera; Ricardo Vanzetto; Gustavo Pereira Fraga

    2014-01-01

    OBJECTIVE: To analyze the profile of patients served by the air medical rescue system in the Metropolitan Region of Campinas, evaluating: triage and mobilization criteria; response time; on-site care and transport time; invasive procedures performed in the Pre-Hospital Care (PHC); severity of patients; morbidity and mortality. METHODS: We conducted a prospective, descriptive study in which we analyzed medical records of patients rescued between July 2010 and December 2012. During this pe...

  16. Rescue of end fragments of yeast artificial chromosomes by homologous recombination in yeast.

    OpenAIRE

    Hermanson, G G; Hoekstra, M F; McElligott, D. L.; Evans, G A

    1991-01-01

    Yeast artificial chromosomes (YACs) provide a powerful tool for the isolation and mapping of large regions of mammalian chromosomes. We developed a rapid and efficient method for the isolation of DNA fragments representing the extreme ends of YAC clones by the insertion of a rescue plasmid into the YAC vector by homologous recombination. Two rescue vectors were constructed containing a yeast LYS2 selectable gene, a bacterial origin of replication, an antibiotic resistance gene, a polylinker c...

  17. Search and Rescue Operations using a Fixed-Wing UAV Equipped with an Automatically Controlled Gimbal

    OpenAIRE

    Mathisen, Carl Magnus

    2014-01-01

    This paper describes the development of methods to be used in search and rescue operations when using fixed wing unmanned aerial vehicles (UAVs) with a controllable gimbal, including methods for using the gimbal in an object-tracking scenario. A complete payload system to be used on a wide range of different UAVs has been developed and thoroughly tested. The level of autonomy of the system reduces the need for onsite personnel, and encourages increased effort in the rescue part of the operati...

  18. Pain, health perception and sleep: impact on the quality of life of firefighters/rescue professionals

    OpenAIRE

    Rafael Silva Marconato; Maria Ines Monteiro

    2015-01-01

    Objective: to evaluate the quality of life of firefighters and rescue professionals, and characterize their socio-demographic, health, work and lifestyle profile. Methods: cross-sectional study that used a socio-demographic, lifestyle, health, work data questionnaire and the WHOQOL-BREF quality of life aspects, in Fire Department bases, Civil Air Patrol Group of the Military Police and Rescue Group of Emergency Services. Results: ninety professionals participated in this study - 71 firef...

  19. [The principles of aviation support for rescue-evacuation operations in eliminating the consequences of disasters].

    Science.gov (United States)

    Berezhnov, E S; Golovchits, V N

    1993-01-01

    Analysing practical results of an Air Force participation in liquidation of the earthquake consequences in Armenia, 1988, and after technological catastrophe in Bashkiria, 1989, the authors substantiate the role and significance of air transportation in the system of rescue and evacuation measures, define main tasks for aviation, propose methods for calculation of required number of aircraft and its types. The data cited in this article have formed a basis for the principles of air support during rescue and evacuation procedures. PMID:8484227

  20. Burnout selected members of the Integrated Rescue System in South County

    OpenAIRE

    KUBOUŠEK, Ladislav

    2015-01-01

    The bachelor's thesis is concerning on the burnout syndrom in particular parts of integrated rescues system. In the theoretical part of the bachelor's thesis is defined the term of burnout syndrom, its causes, subsequent prevention, support and the treatment. The practical part is focused on findings of burnout syndrom among the components of the integrated rescues system, that is the Police, Fire Brigade and Ambulance Service, using the semi-standardized interview, questionnaire and qulitati...

  1. Rescue Operations in Underground Mass Transport Systems at Fires and Deliberate Attacks

    OpenAIRE

    Kumm, Mia; Palm, Anders

    2012-01-01

    Fire and rescue operations in mass transport systems underground often constitute a great challengefor the first responders. In rush-hour traffic at important junctions thousands of people can be locatedat a relatively small area. At underground fires or deliberate attacks in these premises the need forassistance or rescue can be extensive and the possibilities to reach those in distress are limited. In caseof deliberate attacks with explosives the risk for a second delayed attack, aimed at t...

  2. KCC2 rescues functional deficits in human neurons derived from patients with Rett syndrome.

    Science.gov (United States)

    Tang, Xin; Kim, Julie; Zhou, Li; Wengert, Eric; Zhang, Lei; Wu, Zheng; Carromeu, Cassiano; Muotri, Alysson R; Marchetto, Maria C N; Gage, Fred H; Chen, Gong

    2016-01-19

    Rett syndrome is a severe form of autism spectrum disorder, mainly caused by mutations of a single gene methyl CpG binding protein 2 (MeCP2) on the X chromosome. Patients with Rett syndrome exhibit a period of normal development followed by regression of brain function and the emergence of autistic behaviors. However, the mechanism behind the delayed onset of symptoms is largely unknown. Here we demonstrate that neuron-specific K(+)-Cl(-) cotransporter2 (KCC2) is a critical downstream gene target of MeCP2. We found that human neurons differentiated from induced pluripotent stem cells from patients with Rett syndrome showed a significant deficit in KCC2 expression and consequently a delayed GABA functional switch from excitation to inhibition. Interestingly, overexpression of KCC2 in MeCP2-deficient neurons rescued GABA functional deficits, suggesting an important role of KCC2 in Rett syndrome. We further identified that RE1-silencing transcriptional factor, REST, a neuronal gene repressor, mediates the MeCP2 regulation of KCC2. Because KCC2 is a slow onset molecule with expression level reaching maximum later in development, the functional deficit of KCC2 may offer an explanation for the delayed onset of Rett symptoms. Our studies suggest that restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome. PMID:26733678

  3. Chemical chaperones improve protein secretion and rescue mutant factor VIII in mice with hemophilia A.

    Directory of Open Access Journals (Sweden)

    Stefanie D Roth

    Full Text Available Inefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII, which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P. We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking.

  4. Histone Deacetylase Inhibition Rescues Maternal Deprivation-Induced GABAergic Metaplasticity through Restoration of AKAP Signaling.

    Science.gov (United States)

    Authement, Michael E; Kodangattil, Jayaraj N; Gouty, Shawn; Rusnak, Milan; Symes, Aviva J; Cox, Brian M; Nugent, Fereshteh S

    2015-06-01

    Adverse early-life experiences such as child neglect and abuse increase the risk of developing addiction and stress-related disorders through alterations in motivational systems including the mesolimbic dopamine (DA) pathway. Here we investigated whether a severe early-life stress (i.e., maternal deprivation, MD) promotes DA dysregulation through an epigenetic impairment of synaptic plasticity within ventral tegmental area (VTA) DA neurons. Using a single 24-hr episode of MD and whole-cell patch clamp recording in rat midbrain slices, we show that MD selectively induces long-term depression (LTD) and shifts spike timing-dependent plasticity (STDP) toward LTD at GABAergic synapses onto VTA DA neurons through epigenetic modifications of postsynaptic scaffolding A-kinase anchoring protein 79/150 (AKAP79/150) signaling. Histone deacetylase (HDAC) inhibition rescues GABAergic metaplasticity and normalizes AKAP signaling in MD animals. MD-induced reversible HDAC-mediated GABAergic dysfunction within the VTA may be a mechanistic link for increased propensity to mental health disorders following MD. PMID:26050042

  5. MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome.

    Science.gov (United States)

    Li, Yue; Stockton, Michael E; Bhuiyan, Ismat; Eisinger, Brian E; Gao, Yu; Miller, Jessica L; Bhattacharyya, Anita; Zhao, Xinyu

    2016-04-27

    Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome. PMID:27122614

  6. Environmental enrichment rescues memory in mice deficient for the polysialytransferase ST8SiaIV.

    Science.gov (United States)

    Zerwas, Meike; Trouche, Stéphanie; Richetin, Kevin; Escudé, Timothé; Halley, Hélène; Gerardy-Schahn, Rita; Verret, Laure; Rampon, Claire

    2016-04-01

    The neural cell adhesion molecule NCAM and its association with the polysialic acid (PSA) are believed to contribute to brain structural plasticity that underlies memory formation. Indeed, the attachment of long chains of PSA to the glycoprotein NCAM down-regulates its adhesive properties by altering cell-cell interactions. In the brain, the biosynthesis of PSA is catalyzed by two polysialyltransferases, which are differentially regulated during lifespan. One of them, ST8SiaIV (PST), is predominantly expressed during adulthood whereas the other one, ST8SiaII (STX), dominates during embryonic and post-natal development. To understand the role played by ST8SiaIV during learning and memory and its underlying hippocampal plasticity, we used knockout mice deleted for the enzyme ST8SiaIV (PST-ko mice). At adult age, PST-ko mice show a drastic reduction of PSA-NCAM expression in the hippocampus and intact hippocampal adult neurogenesis. We found that these mice display impaired long-term but not short-term memory in both, spatial and non-spatial behavioral tasks. Remarkably, memory deficits of PST-ko mice were abolished by exposure to environmental enrichment that was also associated with an increased number of PSA-NCAM expressing new neurons in the dentate gyrus of these mice. Whether the presence of a larger pool of immature, likely plastic, new neurons favored the rescue of long-term memory in PST-ko mice remains to be determined. Our findings add new evidence to the role played by PSA in memory consolidation. They also suggest that PSA synthesized by PST critically controls the tempo of new neurons maturation in the adult hippocampus. PMID:25596866

  7. Minocycline Rescues from Zinc-Induced Nigrostriatal Dopaminergic Neurodegeneration: Biochemical and Molecular Interventions.

    Science.gov (United States)

    Kumar, Vinod; Singh, Brajesh Kumar; Chauhan, Amit Kumar; Singh, Deepali; Patel, Devendra Kumar; Singh, Chetna

    2016-07-01

    Accumulation of zinc (Zn) in dopaminergic neurons is implicated in Parkinson's disease (PD), and microglial activation plays a critical role in toxin-induced Parkinsonism. Oxidative stress is accused in Zn-induced dopaminergic neurodegeneration; however, its connection with microglial activation is still not known. This study was undertaken to elucidate the role and underlying mechanism of microglial activation in Zn-induced nigrostriatal dopaminergic neurodegeneration. Male Wistar rats were treated intraperitoneally with/without zinc sulphate (20 mg/kg) in the presence/absence of minocycline (30 mg/kg), a microglial activation inhibitor, for 2-12 weeks. While neurobehavioral and biochemical indexes of PD and number of dopaminergic neurons were reduced, the number of microglial cells was increased in the substantia nigra of the Zn-exposed animals. Similarly, Zn elevated lipid peroxidation (LPO) and activities of superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; however, catalase activity was reduced. Besides, Zn increased an association of NADPH oxidase subunit p67(phox) with membrane, cytochrome c release from the mitochondria and cleavage of pro-caspase 3. Zn attenuated the expression of tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) while augmented the expression of dopamine transporter (DAT) and heme oxygenase-1 (HO-1). Minocycline alleviated Zn-induced behavioural impairments, loss of TH-positive neurons, activated microglial cells and biochemical indexes and modulated the expression of studied genes/proteins towards normalcy. The results demonstrate that minocycline reduces the number of activated microglial cells and oxidative stress, which rescue from Zn-induced changes in the expression of monoamine transporter and nigrostriatal dopaminergic neurodegeneration. PMID:25764516

  8. Gas Concentration Prediction Based on the Measured Data of a Coal Mine Rescue Robot

    Directory of Open Access Journals (Sweden)

    Xiliang Ma

    2016-01-01

    Full Text Available The coal mine environment is complex and dangerous after gas accident; then a timely and effective rescue and relief work is necessary. Hence prediction of gas concentration in front of coal mine rescue robot is an important significance to ensure that the coal mine rescue robot carries out the exploration and search and rescue mission. In this paper, a gray neural network is proposed to predict the gas concentration 10 meters in front of the coal mine rescue robot based on the gas concentration, temperature, and wind speed of the current position and 1 meter in front. Subsequently the quantum genetic algorithm optimization gray neural network parameters of the gas concentration prediction method are proposed to get more accurate prediction of the gas concentration in the roadway. Experimental results show that a gray neural network optimized by the quantum genetic algorithm is more accurate for predicting the gas concentration. The overall prediction error is 9.12%, and the largest forecasting error is 11.36%; compared with gray neural network, the gas concentration prediction error increases by 55.23%. This means that the proposed method can better allow the coal mine rescue robot to accurately predict the gas concentration in the coal mine roadway.

  9. Air-Q laryngeal airway for rescue and tracheal intubation.

    Science.gov (United States)

    Ads, Ayman; Auerbach, Frederic; Ryan, Kelly; El-Ganzouri, Abdel R

    2016-08-01

    We report the successful use of the Air-Q laryngeal airway (Air-Q LA) as a ventilatory device and a conduit for tracheal intubation to rescue the airway in a patient with difficult airway and tracheal stenosis. This is the first case report of the device to secure the airway after two episodes of hypoxemia in the operating room and intensive care unit. Consent for submission of this case report was obtained from our institution's human studies institutional review board given that the patient died a few months after his discharge from the hospital before his personal consent could be obtained and before preparation of this report. All personal identifiers that could lead to his identification have been removed from this report. A 59-year-old man was scheduled for a flexible and rigid bronchoscopy with possible laser excision of tracheal stenosis. He had a history of hypertension, atrial fibrillation, and diabetes. Assessment of airway revealed a thyromental distance of 6.5 cm, Mallampati class II, and body weight of 110 kg. He had hoarseness and audible inspiratory/expiratory stridor with Spo2 90% breathing room air. After induction and muscle relaxation, tracheal intubation and flexible bronchoscopy were achieved without incident. The patient was then extubated and a rigid bronchoscopy was attempted but failed with Spo2 dropping to 92%; rocuronium 60 mg was given, and reintubation was accomplished with a 7.5-mm endotracheal tube. A second rigid bronchoscopy attempt failed, with Spo2 dropping to 63%. Subsequent direct laryngoscopy revealed a bloody hypopharynx. A size 4.5 Air-Q LA was placed successfully and confirmed with capnography, and Spo2 returned to 100%. The airway was suctioned through the Air-Q LA device, and the airway was secured using a fiberoptic bronchoscope to place an endotracheal tube of 7.5-mm internal diameter. The case was canceled because of edema of the upper airway from multiple attempts with rigid bronchoscopy. The patient was transported

  10. Simulations suggest pharmacological methods for rescuing long-term potentiation.

    Science.gov (United States)

    Smolen, Paul; Baxter, Douglas A; Byrne, John H

    2014-11-01

    Congenital cognitive dysfunctions are frequently due to deficits in molecular pathways that underlie the induction or maintenance of synaptic plasticity. For example, Rubinstein-Taybi syndrome (RTS) is due to a mutation in cbp, encoding the histone acetyltransferase CREB-binding protein (CBP). CBP is a transcriptional co-activator for CREB, and induction of CREB-dependent transcription plays a key role in long-term memory (LTM). In animal models of RTS, mutations of cbp impair LTM and late-phase long-term potentiation (LTP). As a step toward exploring plausible intervention strategies to rescue the deficits in LTP, we extended our previous model of LTP induction to describe histone acetylation and simulated LTP impairment due to cbp mutation. Plausible drug effects were simulated by model parameter changes, and many increased LTP. However no parameter variation consistent with a effect of a known drug class fully restored LTP. Thus we examined paired parameter variations consistent with effects of known drugs. A pair that simulated the effects of a phosphodiesterase inhibitor (slowing cAMP degradation) concurrent with a deacetylase inhibitor (prolonging histone acetylation) restored normal LTP. Importantly these paired parameter changes did not alter basal synaptic weight. A pair that simulated the effects of a phosphodiesterase inhibitor and an acetyltransferase activator was similarly effective. For both pairs strong additive synergism was present. The effect of the combination was greater than the summed effect of the separate parameter changes. These results suggest that promoting histone acetylation while simultaneously slowing the degradation of cAMP may constitute a promising strategy for restoring deficits in LTP that may be associated with learning deficits in RTS. More generally these results illustrate how the strategy of combining modeling and empirical studies may provide insights into the design of effective therapies for improving long-term synaptic

  11. Data Management and Rescue at a State Geological Survey

    Science.gov (United States)

    Hills, D. J.; McIntyre-Redden, M. R.

    2015-12-01

    As new technologies are developed to utilize data more fully, and as shrinking budgets mean more needs to be done with less, well-documented and discoverable legacy data is vital for continued research and economic growth. Many governmental agencies are mandated to maintain scientific data, and the Geological Survey of Alabama (GSA) is no different. As part of the mandate to explore for, characterize, and report Alabama's mineral, energy, water, and biological resources for the betterment of Alabama's citizens, communities, and businesses, the GSA has increasingly been called upon to make our data (including samples) more accessible to stakeholders. The GSA has been involved in several data management, preservation, and rescue projects, including the National Geothermal Data System and the National Geological and Geophysical Data Preservation Program. GSA staff utilizes accepted standards for metadata, such as those found at the US Geoscience Information Network (USGIN). Through the use of semi-automated workflows, these standards can be applied to legacy data records. As demand for more detailed information on samples increases, especially so that a researcher can do a preliminary assessment prior to a site visit, it has become critical for the efficiency of the GSA to have better systems in place for sample tracking and data management. Thus, GSA is in the process of registering cores and related samples for International Geo Sample Numbers (IGSNs) through the System for Earth Sample Registration. IGSNs allow the GSA to use asset management software to better curate the physical samples and provide more accurate information to stakeholders. Working with other initiatives, such as EarthCube's iSamples project, will ensure that GSA continues to use best practices and standards for sample identification, documentation, citation, curation, and sharing.

  12. Mechanism Based Approaches for Rescuing and Enhancing Cognition

    Directory of Open Access Journals (Sweden)

    ChristineMGall

    2013-08-01

    Full Text Available Progress towards pharmacological means for enhancing memory and cognition has been retarded by the widely discussed failure of behavioral studies in animals to predict human outcomes. As a result, a number of groups have targeted cognition-related neurobiological mechanisms in animal models, with the assumption that these basic processes are highly conserved across mammals. Here we survey one such approach that begins with a form of synaptic plasticity intimately related to memory encoding in animals and likely operative in humans. An initial section will describe a detailed hypothesis concerning the signaling and structural events (a ‘substrate map’ that convert learning associated patterns of afferent activity into extremely stable increases in fast, excitatory transmission. We next describe results suggesting that all instances of intellectual impairment so far tested in rodent models involve a common endpoint failure in the substrate map. This will be followed by a clinically plausible proposal for obviating the ultimate defect in these models. We then take up the question of whether it is reasonable to expect, from either general principles or a very limited set of experimental results, that enhancing memory will expand the cognitive capabilities of high functioning brains. The final section makes several suggestions about how to improve translation of behavioral results from animals to humans. Collectively, the material covered here points to the following: 1 enhancement, in the sense of rescue, is not an unrealistic possibility for a broad array of neuropsychiatric disorders; 2 serendipity aside, developing means for improving memory in normals will likely require integration of information about mechanisms with new behavioral testing strategies; 3 a shift in emphasis from synapses to networks is a next, logical step in the evolution of the cognition enhancement field.

  13. Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

    Science.gov (United States)

    Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

    2015-01-01

    We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors. PMID:25981636

  14. Partial Rescue of pos5 Mutants by YEF1 and UTR1 Genes in Saccharomyces cerevisiae

    Institute of Scientific and Technical Information of China (English)

    Yong-Fu LI; Feng SHI

    2006-01-01

    Three NAD kinase homologs, encoded by UTR1, POS5 and YEF1 genes, are found in the yeast Saccharomyces cerevisiae and proven to be important sources of NADPH for the cell. Pos5p, existing in the mitochondrial matrix, is critical for higher temperature endurance and mitochondrial functions, such as glycerol usability and arginine biosynthesis. Through constructing the high-copy expression plasmids of YEF1 and UTR1, which contained the green fluorescent protein reporter tag at their 3' terminus, and introducing them into POS5 gene deletion mutants (i.e. pos5, utr1pos5, yef1pos5 and utr1yef1pos5), the high-copy YEF1 and UTR1 plasmids carrying transformants for pos5 mutants were obtained. Their temperature sensitivity and growth phenotype on media with glycerol as the sole carbon source, or on media without arginine, were checked. Results showed the partial rescue of mitochondrial dysfunctions and temperature sensitivity of pos5 mutants by the high-copy YEF1 gene, and of glycerol growth defect and temperature sensitivity by the high-copy UTR1 gene, which confirmed the potential supplying ability of Yef1p and Utr1p for mitochondrial NADP(H) and implied the weak transport of NADP from cytosol to mitochondria. However, even through the green fluorescent protein reporter label, the subcellular localization of Yef1p and Utr1p in yeast cells could not be observed, which indicated the low expression level of these two NAD kinase homologs.

  15. Transmission of feline immunodeficiency virus (FIV) among cohabiting cats in two cat rescue shelters.

    Science.gov (United States)

    Litster, Annette L

    2014-08-01

    Conflicting accounts have been published in the veterinary literature regarding transmission of feline immunodeficiency virus (FIV) between cohabiting cats in mixed households, and the mechanics of possible casual transmission, if it occurs, are poorly understood. Similarly, there are conflicting reports of vertical transmission of FIV. The aim of the present study was to document the FIV serological status of cats taken into two rescue shelters. At rescue shelter 1 (Rescue 1), cats cohabited in a multi-cat household of FIV-negative and naturally-infected, FIV-positive cats. A study was performed that combined a retrospective review of records of FIV serological status at intake (Test 1) and prospective FIV serological testing (Tests 2 and 3). Retrospective records were analyzed at rescue shelter 2 (Rescue 2), where FIV-positive queens with litters of nursing kittens were taken into the shelter, before being rehomed. FIV serology was performed on all kittens after weaning. Initial test results (Test 1) for 138 cohabiting cats from Rescue 1 showed that there were 130 FIV-negative cats and eight FIV-positive cats (six male neutered and two female spayed). A second test (Test 2), performed in 45 of the FIV-negative and five of the FIV-positive cats at median 28 months after Test 1 (range, 1 month to 8.8 years) showed that results were unchanged. Similarly, a third test (Test 3), performed in four of the original FeLV-negative cats and one remaining FIV-positive cat at median 38 months after Test 1 (range, 4 months to 4 years), also showed that results were unchanged. These results show a lack of evidence of FIV transmission, despite years of exposure to naturally-infected, FIV-positive cats in a mixed household. At Rescue 2, records were available from five FIV-positive queens with 19 kittens. All 19 kittens tested FIV-negative, suggesting that vertical transmission had not occurred. PMID:24698667

  16. Rescue of foot-and-mouth disease viruses that are pathogenic for cattle from preserved viral RNA samples

    DEFF Research Database (Denmark)

    Belsham, Graham; Jamal, Syed Muhammad; Tjørnehøj, Kirsten;

    2011-01-01

    Background: Foot and mouth disease is an economically important disease of cloven-hoofed animals including cattle, sheep and pigs. It is caused by a picornavirus, foot-and-mouth disease virus (FMDV), which has a positive sense RNA genome which, when introduced into cells, can initiate virus...... replication. Principal Findings: A system has been developed to rescue infectious FMDV from RNA preparations generated from clinical samples obtained under experimental conditions and then applied to samples collected in the ‘‘field’’. Clinical samples from suspect cases of foot-and-mouth disease (FMD) were...... obtained from within Pakistan and Afghanistan. The samples were treated to preserve the RNA and then transported to National Veterinary Institute, Lindholm, Denmark. Following RNA extraction, FMDV RNA was quantified by real-time RT-PCR and samples containing significant levels of FMDV RNA were introduced...

  17. Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases.

    Science.gov (United States)

    Wang, Fan; Song, Wensi; Brancati, Giovanna; Segatori, Laura

    2011-12-16

    Lysosomal storage disorders are often caused by mutations that destabilize native folding and impair trafficking of secretory proteins. We demonstrate that endoplasmic reticulum (ER)-associated degradation (ERAD) prevents native folding of mutated lysosomal enzymes in patient-derived fibroblasts from two clinically distinct lysosomal storage disorders, namely Gaucher and Tay-Sachs disease. Prolonging ER retention via ERAD inhibition enhanced folding, trafficking, and activity of these unstable enzyme variants. Furthermore, combining ERAD inhibition with enhancement of the cellular folding capacity via proteostasis modulation resulted in synergistic rescue of mutated enzymes. ERAD inhibition was achieved by cell treatment with small molecules that interfere with recognition (kifunensine) or retrotranslocation (eeyarestatin I) of misfolded substrates. These different mechanisms of ERAD inhibition were shown to enhance ER retention of mutated proteins but were associated with dramatically different levels of ER stress, unfolded protein response activation, and unfolded protein response-induced apoptosis. PMID:22006919

  18. Rescue of NBD2 mutants N1303K and S1235R of CFTR by small-molecule correctors and transcomplementation.

    Directory of Open Access Journals (Sweden)

    Daniele Rapino

    Full Text Available Although, the most common Cystic Fibrosis mutation, ΔF508, in the cystic fibrosis transmembrane regulator. (CFTR, is located in nucleotide binding domain (NBD1, disease-causing mutations also occur in NBD2. To provide information on potential therapeutic strategies for mutations in NBD2, we studied, using a combination of biochemical approaches and newly created cell lines, two disease-causing NBD2 mutants, N1303K and S1235R. Surprisingly, neither was rescued by low temperature. Inhibition of proteasomes with MG132 or aggresomes with tubacin rescued the immature B and mature C bands of N1303K and S1235R, indicating that degradation occurs via proteasomes and aggresomes. We found no effect of the lysosome inhibitor E64. Thus, our results show that these NBD2 mutants are processing mutants with unique characteristics. Several known correctors developed to rescue ΔF508-CFTR, when applied either alone or in combination, significantly increased the maturation of bands B and C of both NBD 2 mutants. The best correction occurred with the combinations of C4 plus C18 or C3 plus C4. Co-transfection of truncated CFTR (∆27-264 into stably transfected cells was also able to rescue them. This demonstrates for the first time that transcomplementation with a truncated version of CFTR can rescue NBD2 mutants. Our results show that the N1303K mutation has a more profound effect on NBD2 processing than S1235R and that small-molecule correctors increase the maturation of bands B and C in NBD2 mutants. In addition, ∆27-264 was able to transcomplement both NDB2 mutants. We conclude that differences and similarities occur in the impact of mutations on NBD2 when compared to ΔF508-CFTR suggesting that individualized strategies may be needed to restore their function. Finally our results are important because they suggest that gene or corrector molecule therapies either alone or in combination individualized for NBD2 mutants may be beneficial for patients bearing

  19. Rescuing Food from the Organics Waste Stream to Feed the Food Insecure: An Economic and Environmental Assessment of Australian Food Rescue Operations Using Environmentally Extended Waste Input-Output Analysis

    OpenAIRE

    Christian John Reynolds; Julia Piantadosi; John Boland

    2015-01-01

    In this paper we investigate the economic and environmental efficiency of charities and NGO’s “rescuing†food waste, using a 2008 case study of food rescue organisations in Australia. We quantify the tonnages, costs, and environmental impact of food rescued, and then compare food rescue to other food waste disposal methods composting and landfill. To our knowledge this is the first manuscript to comprehend the psychical flows of charity within an Input-Output framework—treating the cha...

  20. Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sun Hong; Roh, Eunmiri [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Hyun Soo [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Baek, Seung-Il [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Choi, Nam Song [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Kim, Narae; Hwang, Bang Yeon; Han, Sang-Bae [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Youngsoo, E-mail: youngsoo@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2013-12-13

    Highlights: •Lonicerae flos extract (HS-23) is a clinical candidate, Phase I for sepsis treatment. •Here, HS-23 or its major constituents rescued LPS-induced septic mortality in mice. •As a mechanism, they directly inhibited IRAK-4-catalyzed kinase activity. •Thus, they suppressed LPS-induced expression of NF-κB/AP-1-target inflammatory genes. -- Abstract: Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J mice under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4.

  1. Bortezomib (PS-341 treatment decreases inflammation and partially rescues the expression of the dystrophin-glycoprotein complex in GRMD dogs.

    Directory of Open Access Journals (Sweden)

    Karla P C Araujo

    Full Text Available Golden retriever muscular dystrophy (GRMD is a genetic myopathy corresponding to Duchenne muscular dystrophy (DMD in humans. Muscle atrophy is known to be associated with degradation of the dystrophin-glycoprotein complex (DGC via the ubiquitin-proteasome pathway. In the present study, we investigated the effect of bortezomib treatment on the muscle fibers of GRMD dogs. Five GRMD dogs were examined; two were treated (TD- Treated dogs with the proteasome inhibitor bortezomib, and three were control dogs (CD. Dogs were treated with bortezomib using the same treatment regimen used for multiple myeloma. Pharmacodynamics were evaluated by measuring the inhibition of 20S proteasome activity in whole blood after treatment and comparing it to that in CD. We performed immunohistochemical studies on muscle biopsy specimens to evaluate the rescue of dystrophin and dystrophin-associated proteins in the muscles of GRMD dogs treated with bortezomib. Skeletal tissue from TD had lower levels of connective tissue deposition and inflammatory cell infiltration than CD as determined by histology, collagen morphometry and ultrastructural analysis. The CD showed higher expression of phospho-NFκB and TGF-β1, suggesting a more pronounced activation of anti-apoptotic factors and inflammatory molecules and greater connective tissue deposition, respectively. Immunohistochemical analysis demonstrated that dystrophin was not present in the sarcoplasmic membrane of either group. However, bortezomib-TD showed higher expression of α- and β-dystroglycan, indicating an improved disease histopathology phenotype. Significant inhibition of 20S proteasome activity was observed 1 hour after bortezomib administration in the last cycle when the dose was higher. Proteasome inhibitors may thus improve the appearance of GRMD muscle fibers, lessen connective tissue deposition and reduce the infiltration of inflammatory cells. In addition, proteasome inhibitors may rescue some

  2. Search and Rescue Operations of Aircraft in Africa: Some Compelling Issues

    Science.gov (United States)

    Abeyratne, Ruwantissa I. R.

    2002-01-01

    The world aviation community has felt the compelling need for a well-coordinated global programme for search and rescue operations of aircraft ever since commercial aviation was regulated in 1944. Guidelines and plans of action for search and rescue have therefore been considered critical in the event of an aircraft accident. This fact is eminently brought to bear in the continental regions of Africa and South America in particular, where vast expanses of land are still uninhabited or sparsely populated and controlled flight into terrain (CFIT-where an aircraft may crash on land while still under the control of technical crew) is a common occurrence. There are numerous guidelines that have been adopted under the umbrella of the International Civil Aviation Organization which are already in place for the provision of search and rescue operations pertaining to aircraft. However, when an accident occurs in the territory of a State, there are sensitivities involving the State in which the aircraft concerned was registered and issues of sovereignty which have to be considered. Additionally. issues such as the voluntary nature of the search and rescue services offered. confidentiality, timeliness of such operations, fairness and uniformity all play a critical role. This article addresses the issue of search and rescue operations in Africa and examines in some detail where the world aviation community is right now and where it is headed in this important field of human endeavour.

  3. Persistent organic pollutants in 9/11 World Trade Center rescue workers

    Energy Technology Data Exchange (ETDEWEB)

    Dahlgren, J. [UCLA School of Medicine, CA (United States); Schecter, A. [Univ. of Texas School of Public Health, Dallas, TX (United States); Takhar, H. [Comprehensive Health Screening Services, Santa Monica, CA (United States); Paepke, O. [ERGO Lab., Hamburg (Germany)

    2004-09-15

    Rescue workers, including firefighters present at the World Trade Center (WTC) following the September 11, 2001 terrorist attacks were exposed to large quantities of dust, smoke and fumes from the collapse and fire. The fire at the WTC site burned for months. Firefighters, paramedics, police and other personnel labored for weeks and months in the immediate vicinity of the WTC. Personal Protective Equipment (PPE) was not available or was ineffective in preventing the rescue workers from absorbing contaminants. This is based on the rescue workers who reported working without any protection from inhalation, ingestion or dermal exposure to the contaminants. In addition many of the rescue workers developed coughs, headaches, memory disturbance and other symptoms while working on the site. USEPA measurements of benzene, dioxins and polychlorinated biphenyls (PCBs) were elevated in the air in the weeks after the collapse. Dioxins slowly returned to normal background levels after three months. The New York (NY) Department of Environmental Conservation (DEC) analyzed dust/ash samples collected close to the WTC site after September 11, 2001. The purpose of this study was to characterize body burdens of polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dioxins (PCDDs) from 11 rescue workers who worked at the WTC the day of the collapse and afterwards.

  4. Complex alpine extrication: case report of mountain and speleological rescue cooperation.

    Science.gov (United States)

    Sette, Piersandro; Carlini, Mauro; Berti, Damiano; Rucci, Igor; Marchiori, Francesco; Toffali, Fausto; Schonsberg, Alberto; Ricci, Giorgio; Tardivo, Stefano

    2015-06-01

    Mountain sporting activities are an increasingly popular practice that exposes mountaineers to a high risk of adverse events. This report describes a unique case of recovery in an austere environment that involved explosives. In June 2012, a 52-year-old man ascended a cliff tower in the Eastern Alps, Italy. A landslide occurred, and a boulder crushed the climber against a large stone located farther down the cliff, causing compression of the lower limbs and the pelvis with consequent severe musculoskeletal trauma. The National Alpine and Cave Rescue Unit (NACRU) arrived and proceeded with stabilization of the injured climber, which took 6 hours and involved a difficult extrication supported by the Cave Rescue division of NACRU. Unfortunately, during transport to the trauma center of Borgo Trento, Verona, the patient exhibited signs of progressive traumatic shock because of crush syndrome, hypovolemia, and acidosis, which led to cardiac arrest and death. Based on an extensive literature review, this report was determined to be the only one of a mountain rescue using explosives for the extrication of a victim in the Northeast Italian Alps. This case describes how a rescue in austere environments can represent a high-risk situation, and it shows how improvisation and cooperation between rescue teams are crucial for a successful recovery. PMID:25747541

  5. Austrian Daily Climate Data Rescue and Quality Control

    Science.gov (United States)

    Jurkovic, A.; Lipa, W.; Adler, S.; Albenberger, J.; Lechner, W.; Swietli, R.; Vossberg, I.; Zehetner, S.

    2010-09-01

    Checked climate datasets are a "conditio sine qua non" for all projects that are relevant for environment and climate. In the framework of climate change studies and analysis it is essential to work with quality controlled and trustful data. Furthermore these datasets are used as input for various simulation models. In regard to investigations of extreme events, like strong precipitation periods, drought periods and similar ones we need climate data in high temporal resolution (at least in daily resolution). Because of the historical background - during Second World War the majority of our climate sheets were sent to Berlin, where the historical sheets were destroyed by a bomb attack and so important information got lost - only several climate sheets, mostly duplicates, before 1939 are available and stored in our climate data archive. In 1970 the Central Institute for Meteorology and Geodynamics in Vienna started a first attempt to digitize climate data by means of punch cards. With the introduction of a routinely climate data quality control in 1984 we can speak of high-class-checked daily data (finally checked data, quality flag 6). Our group is working on the processing of digitization and quality control of the historical data for the period 1872 to 1983 for 18 years. Since 2007 it was possible to intensify the work (processes) in the framework of an internal project, namely Austrian Climate Data Rescue and Quality Control. The aim of this initiative was - and still is - to supply daily data in an outstanding good and uniform quality. So this project is a kind of pre-project for all scientific projects which are working with daily data. In addition to routine quality checks (that are running since 1984) using the commercial Bull Software we are testing our data with additional open source software, namely ProClim.db. By the use of this spatial and statistical test procedure, the elements air temperature and precipitation - for several sites in Carinthia - could

  6. Persistence in epidemic metapopulations: quantifying the rescue effects for measles, mumps, rubella and whooping cough.

    Science.gov (United States)

    Metcalf, C Jessica E; Hampson, Katie; Tatem, Andrew J; Grenfell, Bryan T; Bjørnstad, Ottar N

    2013-01-01

    Metapopulation rescue effects are thought to be key to the persistence of many acute immunizing infections. Yet the enhancement of persistence through spatial coupling has not been previously quantified. Here we estimate the metapopulation rescue effects for four childhood infections using global WHO reported incidence data by comparing persistence on island countries vs all other countries, while controlling for key variables such as vaccine cover, birth rates and economic development. The relative risk of extinction on islands is significantly higher, and approximately double the risk of extinction in mainland countries. Furthermore, as may be expected, infections with longer infectious periods tend to have the strongest metapopulation rescue effects. Our results quantitate the notion that demography and local community size controls disease persistence. PMID:24040325

  7. Research on 3G-based Mobile Self-rescue System for Medical Emergency

    Directory of Open Access Journals (Sweden)

    Weihui Dai

    2011-08-01

    Full Text Available With the development of economy and society, people become more fluid, and in the meanwhile there is increasing demand for medical service in mobile environment. Especially when an outdoor accident or Paroxysmal disease happens, the earliest and most effective rescue is offered not by the medical staffs, but by people themselves. At that moment, if the first-aid instruction can be provided by medical experts in time, casualties are expected to be minimized.In combination with 3G communication network, streaming media technology, E-expert system as well as the knowledge about medical diagnostics and emergent treatment, this paper explored a mobile self-rescue system for medical emergency. This system can connect the doctors and patients who are physically separated, and thus help the patients realize self-rescue through the 3G-based mobile communications at anytime and anywhere.

  8. Persistence in epidemic metapopulations: quantifying the rescue effects for measles, mumps, rubella and whooping cough.

    Directory of Open Access Journals (Sweden)

    C Jessica E Metcalf

    Full Text Available Metapopulation rescue effects are thought to be key to the persistence of many acute immunizing infections. Yet the enhancement of persistence through spatial coupling has not been previously quantified. Here we estimate the metapopulation rescue effects for four childhood infections using global WHO reported incidence data by comparing persistence on island countries vs all other countries, while controlling for key variables such as vaccine cover, birth rates and economic development. The relative risk of extinction on islands is significantly higher, and approximately double the risk of extinction in mainland countries. Furthermore, as may be expected, infections with longer infectious periods tend to have the strongest metapopulation rescue effects. Our results quantitate the notion that demography and local community size controls disease persistence.

  9. Post-traumatic stress disorder status in a rescue group after the Wenchuan earthquake relief

    Institute of Scientific and Technical Information of China (English)

    Junhua Huang; Qunying Liu; Jinliang Li; Xuejiang Li; Jin You; Liang Zhang; Changfu Tian; Rongsheng Luan

    2013-01-01

    Previous studies have suggested that the incidence of post-traumatic stress disorder in earthquake rescue workers is relatively high. Risk factors for this disorder include demographic characteristics, earthquake-related high-risk factors, risk factors in the rescue process, personality, social support and coping style. This study examined the current status of a unit of 1 040 rescue workers who participated in earthquake relief for the Wenchuan earthquake that occurred on May 12th, 2008. Post-traumatic stress disorder was diagnosed primarily using the Clinician-Administered Post-traumatic Stress Disorder Scale during structured interviews. Univariate and multivariate sta-tistical analyses were used to examine major risk factors that contributed to the incidence of post-traumatic stress disorder. Results revealed that the incidence of this disorder in the rescue group was 5.96%. The impact factors in univariate analysis included death of family members, contact with corpses or witnessing of the deceased or seriously injured, near-death experience, severe injury or mental trauma in the rescue process and working at the epicenter of the earthquake. Correlation analysis suggested that post-traumatic stress disorder was positively correlated with psychotic and neurotic personalities, negative coping and low social support. Impact factors in mul-tivariate logistic regression analysis included near-death experience, severe injury or mental trauma, working in the epicenter of the rescue, neurotic personality, negative coping and low social support, among which low social support had the largest odds ratio of 20.42. Findings showed that the oc-currence of post-traumatic stress disorder was the result of the interaction of multiple factors.

  10. MOLECULAR MECHANISMS OF FUNCTIONAL RESCUE MEDIATED BY P53 TUMOR SUPPRESSOR MUTATIONS

    OpenAIRE

    Tan, Yu-Hong; Chen, Y. Morris; Ye, Xiang; Lu, Qiang; Tretyachenko-Ladokhina, Vira; Yang, Wei; Senear, Donald F.; Luo, Ray

    2009-01-01

    We have utilized both molecular dynamics simulations and solution biophysical measurements to investigate the rescue mechanism of mutation N235K, which plays a key role in the recently identified global suppressor motif of K235/Y239/R240 in the human p53 DNA-binding domain (DBD). Previous genetic analysis indicates that N235K alone rescues five out of six destabilized cancer mutants. However, the solution biophysical measurement shows that N235K generates only a slight increase to the stabili...

  11. Experience in System Design for Human-Robot Teaming in Urban Search & Rescue

    OpenAIRE

    Kruijff, G.J.M.; Janíček, M.; Keshavdas, S.; Larochelle, B.; Zender, H.; Smets, N.J.J.M.; Mioch, T.; Neerincx, M.A.; Diggelen, J. van; Colas, F.; Liu, M.(Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China; Department of Modern Physics, University of Science and Technology of China, Hefei, Anhui, China; Department of Physics, Nanjing University, Nanjing, Jiangsu, China; School of Physics, Shandong University, Jinan, Shandong, China; Physics Department, Shanghai Jiao Tong University, Shanghai, China); Pomerleau, F.; Svoboda, T.; Petriček, T.; Pirri, F.

    2012-01-01

    The paper describes experience with applying a user-centric design methodology in developing systems for human-robot teaming in Urban Search & Rescue. A human-robot team consists of several semi-autonomous robots (rovers/UGVs, microcopter/UAVs), several humans at an off-site command post (mission commander, UGV operators) and one on-site human (UAV operator). This system has been developed in close cooperation with several rescue organizations, and has been deployed in a real-life tunnel acci...

  12. Advanced Rescue System for Industrial Monitoring Using ZIGBEE GSM and FPGA

    OpenAIRE

    T. Ariyathangam

    2014-01-01

    The increase of greed in people has paved way to civil-wars and natural disasters. A swift action has to betaken in the relief work of the aftermath of earthquake affected areas, such that any delay in the rescue could lead the death toll to rise. The same can be applied to war fields too. The project focuses on human beings who are alive and struggling for their lives either in the war field or due to natural disasters like earthquakes, to be recognized and rescued in a much fast...

  13. Mortality in free range rescued wild animals of Shivalik Hills in Himachal Pradesh, India

    OpenAIRE

    Vijay Kumar; Vipin Kumar; Anshu Raj

    2012-01-01

    The present study was conducted on 143 free range wild animals of 12 different species rescued from different locations in Shivalik Hills since Jan 2004 to June 2011. Mortality was reported in 79.02% (113) of rescued wild animals. Mortality in Herbivores, Carnivores, Pheasants and Omnivores was 84.74% (50), 79.06% (34) 72.72% (24) and 62.50% (05) respectively. Post mortem was conducted at field level to determine causes of mortality in all the 113 died wild animals. Necropsy findings revealed...

  14. Caring for the injured and otherwise handicapped Raptors (Falconiformes) and owls (Strigiformes) in rescue centers

    OpenAIRE

    DOBIÁŠOVÁ, Kristýna

    2014-01-01

    At least half of our raptors and owls are classified into three categories the list of specially protected animals. Electricity poles, traffic and landscape changes have led to the disappearance many individuals of raptors and owls in the wild. This work evaluates range and success of the return raptors and owls into the wild. All information about adopted raptors and owls were compiled by selected rescue station for animals ČSOP Vlašim. Rescue station records served as basis in the range of ...

  15. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden

    Directory of Open Access Journals (Sweden)

    Abisambra Jose F

    2010-11-01

    Full Text Available Abstract Background It has traditionally been thought that the pathological accumulation of tau in Alzheimer's disease and other tauopathies facilitates neurodegeneration, which in turn leads to cognitive impairment. However, recent evidence suggests that tau tangles are not the entity responsible for memory loss, rather it is an intermediate tau species that disrupts neuronal function. Thus, efforts to discover therapeutics for tauopathies emphasize soluble tau reductions as well as neuroprotection. Results Here, we found that neuroprotection alone caused by methylene blue (MB, the parent compound of the anti-tau phenothiaziazine drug, Rember™, was insufficient to rescue cognition in a mouse model of the human tauopathy, progressive supranuclear palsy (PSP and fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP17: Only when levels of soluble tau protein were concomitantly reduced by a very high concentration of MB, was cognitive improvement observed. Thus, neurodegeneration can be decoupled from tau accumulation, but phenotypic improvement is only possible when soluble tau levels are also reduced. Conclusions Neuroprotection alone is not sufficient to rescue tau-induced memory loss in a transgenic mouse model. Development of neuroprotective agents is an area of intense investigation in the tauopathy drug discovery field. This may ultimately be an unsuccessful approach if soluble toxic tau intermediates are not also reduced. Thus, MB and related compounds, despite their pleiotropic nature, may be the proverbial "magic bullet" because they not only are neuroprotective, but are also able to facilitate soluble tau clearance. Moreover, this shows that neuroprotection is possible without reducing tau levels. This indicates that there is a definitive molecular link between tau and cell death cascades that can be disrupted.

  16. Intrathecal gene therapy rescues a model of demyelinating peripheral neuropathy.

    Science.gov (United States)

    Kagiava, Alexia; Sargiannidou, Irene; Theophilidis, George; Karaiskos, Christos; Richter, Jan; Bashiardes, Stavros; Schiza, Natasa; Nearchou, Marianna; Christodoulou, Christina; Scherer, Steven S; Kleopa, Kleopas A

    2016-04-26

    Inherited demyelinating peripheral neuropathies are progressive incurable diseases without effective treatment. To develop a gene therapy approach targeting myelinating Schwann cells that can be translatable, we delivered a lentiviral vector using a single lumbar intrathecal injection and a myelin-specific promoter. The human gene of interest, GJB1, which is mutated in X-linked Charcot-Marie-Tooth Disease (CMT1X), was delivered intrathecally into adult Gjb1-null mice, a genetically authentic model of CMT1X that develops a demyelinating peripheral neuropathy. We obtained widespread, stable, and cell-specific expression of connexin32 in up to 50% of Schwann cells in multiple lumbar spinal roots and peripheral nerves. Behavioral and electrophysiological analysis revealed significantly improved motor performance, quadriceps muscle contractility, and sciatic nerve conduction velocities. Furthermore, treated mice exhibited reduced numbers of demyelinated and remyelinated fibers and fewer inflammatory cells in lumbar motor roots, as well as in the femoral motor and sciatic nerves. This study demonstrates that a single intrathecal lentiviral gene delivery can lead to Schwann cell-specific expression in spinal roots extending to multiple peripheral nerves. This clinically relevant approach improves the phenotype of an inherited neuropathy mouse model and provides proof of principle for treating inherited demyelinating neuropathies. PMID:27035961

  17. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  18. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  19. Analysis of factors related to military training injury and the effect of self-rescue and buddy rescue on the final result of the injury in tank crew of the armored forces

    Directory of Open Access Journals (Sweden)

    Rong-bin ZHOU

    2011-09-01

    Full Text Available Objective To analyze the factors related to military training injury and the effect of self-rescue and buddy rescue on the result of the injury in the soldiers.Methods All data were statistically classified with cluster sampling according to the diagnosis standard of Chinese PLA for analysis.Investigation was conducted in 1028 soldiers of the armored forces with questionnaire,and non-condition logistic regression analysis was applied.Results The total incidence of military training injury was 40.2%.Of all the injured soldiers,36.80% of them served for one year only,and the incidence of injury was obviously higher than those who had served in armed forces for 2 or 3 years.Unconditioned regression analysis revealed that the main causes related to military training injury in the soldiers were as follows: the items of training,the terrain feature,motion sickness,self-rescue and buddy rescue training,and whether the action consistent with the standards.The rehabilitation rate within one month was significantly higher in those who underwent self-rescue or buddy rescue(93.8% and 94.2%,respectively than those who did not undergo self-rescue or buddy rescue(76.3%,76.7%,respectively,P < 0.001.Conclusions The incidence of military training injury in the armored forces is high.It should be emphysized that soldiers with one year of military service should be partioularly taken care to prevent from injuries.Many factors may influence the military training injury,and protective measures should be taken.Those who have the knowledge of self-rescue or undergo buddy rescue will have higher rehabilitation rate within one month.

  20. Overexpression of a novel gene, Cms1, can rescue the growth arrest of a Saccharomyces cerevisiae mcm10 suppressor

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    MCM10 protein is an essential replication factor involved in the initiation of DNA replication. A mcm10 mutant (mcm10-1) of budding yeast shows a growth arrest at 37℃. In the present work, we have isolated a mcm10-1 suppressor strain, which grows at 37℃. Interestingly, this mcm10-1 suppressor undergoes cell cycle arrest at 14℃. A novel gene, YLR003c, is identified by high-copy complementation of this suppressor. We called it as Cmsl (Complementation of Mcm 10 Suppressor). Furthermore, the experiments of transformation show that cells of mcm10-1 suppressor with high-copy plasmid but not low-copy plasmid grow at 14℃, indicating that overexpression of Cmsl can rescue the growth arrest of this mcm10 suppressor at non-permissive temperature. These results suggest that CMS1 protein may functionally interact with MCM10 protein and play a role in the regulation of DNA replication and cell cycle control.

  1. The 'Rule of Rescue' in Medical Priority Setting: Ethical Plausibilities and Implausibilities

    Directory of Open Access Journals (Sweden)

    Bettina Schoene-Seifert

    2009-01-01

    Full Text Available Not infrequently, the so-called Rule of Rescue gets invoked as an allegedly self-evident constraint to the CBE-goal of maximizing health benefit with a given health budget. In this paper this constraint is critically analyzed. It will be argued that some of its implications are worth considering - but not the inherently vague Rule as such.

  2. Self-efficacy moderates the relationship between stress appraisal and quality of life among rescue workers.

    Science.gov (United States)

    Prati, Gabriele; Pietrantoni, Luca; Cicognani, Elvira

    2010-07-01

    Rescue workers are frequently exposed to highly stressful situations during their everyday work activity. Stress and coping theory emphasizes the interaction between primary and secondary appraisal in determining coping responses to stressful events and quality of life. According to Social Cognitive Theory, stress reactions depend on self-appraisal of coping capabilities. The present study investigated whether self-efficacy moderates the relationship between stress appraisal and professional quality of life. A self-administered questionnaire was submitted to a sample of 451 Italian rescue workers (firefighters, paramedics, and medical technicians), including the Professional Quality of Life Scale, which measures three dimensions of emergency workers' quality of working life: compassion fatigue, burnout, and compassion satisfaction. Multiple regression analyses indicated that the relationship between stress appraisal and professional quality of life was significant only among rescue workers with low levels of self-efficacy but not among those with higher levels of self-efficacy. These results confirmed the expectations based on Social Cognitive Theory that self-efficacy buffers the impact of perceived stressful encounters on professional quality of life. Results suggest the usefulness of interventions aimed at increasing rescue workers' psychosocial skills. PMID:19937503

  3. Real time modeling of the cognitive load of an Urban Search And Rescue robot operator

    NARCIS (Netherlands)

    Colin, T. R.; Smets, N. J.; Mioch, T.; Neerincx, M. A.

    2014-01-01

    Urban Search And Rescue (USAR) robots are used to find and save victims in the wake of disasters such as earthquakes or terrorist attacks. The operators of these robots are affected by high cognitive load; this hinders effective robot usage. This paper presents a cognitive task load model for real-t

  4. New refresher training in the use of self-rescue masks

    CERN Multimedia

    HSE Unit

    2012-01-01

    Photos of the training session for self-rescue mask instructors held on 21 March 2012 – 10 new instructors followed the coursePhotos of the training session for self-rescue mask instructors held on 21 March 2012 – 10 new instructors followed the course   A refresher course in the use of self-rescue masks has been added to the CERN training catalogue. Sign up! More than 3500 people have followed the course since it was introduced in 2009. Taking account of the forthcoming long shutdown, requests for follow-up training from course participants and recent changes in the course content, the HSE Unit has decided to place a three-year limit on the validity of the initial training and to introduce a refresher course. The new refresher course is open to all personnel having completed the initial course at least 2 years ago. The course, "Recyclage Formation masque auto-sauveteur » / "Refresher course Self-Rescue Mask Training", (code No. 077...

  5. PSO-Based Robot Path Planning for Multisurvivor Rescue in Limited Survival Time

    Directory of Open Access Journals (Sweden)

    N. Geng

    2014-01-01

    Full Text Available Since the strength of a trapped person often declines with time in urgent and dangerous circumstances, adopting a robot to rescue as many survivors as possible in limited time is of considerable significance. However, as one key issue in robot navigation, how to plan an optimal rescue path of a robot has not yet been fully solved. This paper studies robot path planning for multisurvivor rescue in limited survival time using a representative heuristic, particle swarm optimization (PSO. First, the robot path planning problem including multiple survivors is formulated as a discrete optimization one with high constraint, where the number of rescued persons is taken as the unique objective function, and the strength of a trapped person is used to constrain the feasibility of a path. Then, a new integer PSO algorithm is presented to solve the mathematical model, and several new operations, such as the update of a particle, the insertion and inversion operators, and the rapidly local search method, are incorporated into the proposed algorithm to improve its effectiveness. Finally, the simulation results demonstrate the capacity of our method in generating optimal paths with high quality.

  6. 46 CFR 108.575 - Survival craft and rescue boat equipment.

    Science.gov (United States)

    2010-10-01

    ... DRILLING UNITS DESIGN AND EQUIPMENT Lifesaving Equipment § 108.575 Survival craft and rescue boat equipment... Fishing kit 1 1 12 Flashlight 1 1 1 1 1 1 13 Hatchet 2 2 14 Heaving line 2 1 2 2 1 2 15 Instruction card 1.... 2 Bilge pumps are not required for boats of self-bailing design. 3 Not required for inflated...

  7. 30 CFR 49.50 - Certification of coal mine rescue teams.

    Science.gov (United States)

    2010-07-01

    ...(30 CFR) (1) Team is available at all times when miners are underground 49.12(a); 49.12(g) (2) Except... Qualification Criteria(30 CFR) (1) Members are properly trained annually 49.18(b) (2) Members are familiar with... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Certification of coal mine rescue teams....

  8. An Application of the Social Support Deterioration Deterrence Model to Rescue Workers

    Science.gov (United States)

    Prati, Gabriele; Pietrantoni, Luca

    2010-01-01

    This study examined the role of social support in promoting quality of life in the aftermath of critical incidents involvement. Participants were a sample of 586 Italian rescue workers. Structural equation modelling was used to test the social support deterioration deterrence model. Results showed that the impact of critical incident involvement…

  9. Collaboration and Interconnectivity: Nottinghamshire Fire and Rescue Services and Higher Education Institutions in Nottingham

    Science.gov (United States)

    Murphy, Peter; Greenhalgh, Kirsten; Parkin, Craig

    2013-01-01

    This article will describe the developing relationship between Nottinghamshire Fire and Rescue Services and the two higher education institutions in Nottingham. It will chronicle how a very traditional relationship has been transformed, initially by a simple consultancy project, into a much closer working relationship characterised by a much…

  10. New simulated gas detector offers realistic training for mine rescue teams

    International Nuclear Information System (INIS)

    The National Institute for Occupational Safety and Health, together with LightsOn Safety Solutions, evaluated 2 versions of a multi-gas simulated gas monitor system (GMS) in separate field trials with mine rescue teams. This paper described the GMS wireless simulation tool along with its development and testing. It also described the GMS functions for the initial phase of testing as well as plans for the next phase of research which may introduce tracking and automation features. The GMS requires a personal computer and uses a wireless local area network. The GMS teaches mine rescue members about gas detection and helps them understand the importance of gas concentrations. In addition, it promotes decision-making actions by team members and offers a more realistic method of receiving gas concentration readings using a simulated hand-held gas detector. The purpose of the evaluation was to determine if the electronic placard in the GMS could be used by mine rescue teams instead of the currently used cardboard placards, and if the functionality of the device was suitable, reliable and practical. Results from the second field trial demonstrated improvements with the GMS over the original prototype technology, particularly with regards to wireless and connectivity issues. The GMS was successfully incorporated into the mine rescue exercises as planned, with very few problems encountered. 4 refs., 2 figs.

  11. A Phenomenological Study of Urban Search and Rescue Members Who Responded to a Disaster

    Science.gov (United States)

    Kerns, Terry L.

    2012-01-01

    The complicated world of disaster management requires urban search and rescue (US&R) members to be well trained to respond to complex, unpredictable, and difficult to manage disasters anywhere in the world on short notice. Disasters are becoming more complex and difficult to manage as was witnessed by the multi-faceted disaster in Japan in…

  12. Revealing unexpected effects of rescue robots’ team-membership in a virtual environment

    NARCIS (Netherlands)

    Horsch, C.H.G.; Smets, N.J.J.M.; Neerincx, M.A.; Cuijpers, R.H.

    2013-01-01

    In urban search and rescue (USAR) situations resources are limited and workload is high. Robots that act as team players instead of tools could help in these situations. A Virtual Reality (VR) experiment was set up to test if team performance of a human-robot team increases when the robot act as suc

  13. The Rescue911 Emergency Response Information System (ERIS): A Systems Development Project Case

    Science.gov (United States)

    Cohen, Jason F.; Thiel, Franz H.

    2010-01-01

    This teaching case presents a systems development project useful for courses in object-oriented analysis and design. The case has a strong focus on the business, methodology, modeling and implementation aspects of systems development. The case is centered on a fictitious ambulance and emergency services company (Rescue911). The case describes that…

  14. Collaboration between Extension and Industry: Coordination and Assessment of Technical Large Animal Emergency Rescue Training

    Science.gov (United States)

    Porr, C. A. Shea; Shultz, Alyx M.; Gimenez, Rebecca; Splan, Rebecca K.

    2016-01-01

    Rescuing large animals from emergency situations can be fraught with dangers not only to the animals but also to the rescuers. People involved at the scene of such an emergency are most likely to include first responders, horse owners, and veterinarians. These groups need to be aware of how they can best work together to effect a safe and…

  15. Resolving Ethical Dilemmas in Suicide Prevention: The Case of Telephone Helpline Rescue Policies

    Science.gov (United States)

    Mishara, Brian L.; Weisstub, David N.

    2010-01-01

    The ethical basis of suicide prevention is illustrated by contrasting helpline emergency rescue policies of the Samaritans and the AAS and the U.S. National Suicide Prevention Lifeline network. We contrast moralist, relativist, and libertarian ethical premises and question whether suicide can be rational. Samaritans respect a caller's right to…

  16. Tracing the origins of rescued chimpanzees reveals widespread chimpanzee hunting in Cameroon

    OpenAIRE

    Gadsby Elizabeth L; Fotso Roger; de Vries Simone; Akih Akih E; Kiyang John A; Lankester Felix; Ghobrial Lora; Jenkins Peter D; Gonder Mary K

    2010-01-01

    Abstract Background While wild chimpanzees are experiencing drastic population declines, their numbers at African rescue and rehabilitation projects are growing rapidly. Chimpanzees follow complex routes to these refuges; and their geographic origins are often unclear. Identifying areas where hunting occurs can help law enforcement authorities focus scarce resources for wildlife protection planning. Efficiently focusing these resources is particularly important in Cameroon because this countr...

  17. An unusual mechanism for EF-Tu activation during tmRNA-mediated ribosome rescue

    OpenAIRE

    Miller, Mickey R; Buskirk, Allen R.

    2014-01-01

    When ribosomes are stalled on truncated mRNAs in prokaryotes, they are rescued by the tmRNA/SmpB complex. It has been unclear how EF-Tu is activated by this complex. This manuscript analyzes this problem, and the results indicate that the normal EF-Tu GTPase cycle does not appear to apply in this specialized situation.

  18. The boat people of Vietnam. Rescue on the South China Sea.

    Science.gov (United States)

    Hayes, T J; Thomas, D; Dewar, E P

    1990-01-01

    Poor economic conditions in Vietnam have encouraged large numbers of people seeking a better life in the West to join the flow of political refugees leaving the country as "boat people". We report the events surrounding one such group of people who were rescued from the South China Sea by the Outback 88 Task Group. PMID:2374108

  19. Exogenous BDNF rescues rat spiral ganglion neurons in vivo

    OpenAIRE

    Sarah L. McGuinness; Shepherd, Robert K.

    2005-01-01

    The loss of hair cells resulting in a sensorineural hearing loss (SNHL) also leads to the secondary degeneration of spiral ganglion neurons (SGNs). The effectiveness of cochlear implantation in patients with a profound SNHL relies, in part, upon the survival of SGNs; therefore any therapy that can prevent or halt the loss of these neurons would be of potential clinical benefit. Previous research has shown that intracochlear infusion with neurotrophins can provide trophic support to SGNs in de...

  20. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    OpenAIRE

    Luciano Rezende Vilela; Lindisley Ferreira Gomides; Bruna Araújo David; Maísa Mota Antunes; Ariane Barros Diniz; Fabrício de Araújo Moreira; Gustavo Batista Menezes

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hyd...

  1. Rescue of Long-Tail Data from the Ocean Bottom to the Moon

    Science.gov (United States)

    Hsu, L.; Lehnert, K. A.; Carbotte, S. M.; Ferrini, V.; Delano, J. W.; Gill, J. B.; Tivey, M.

    2013-12-01

    IEDA (Integrated Earth Data Applications, www.iedadata.org), the NSF facility that operates EarthChem, the Marine Geoscience Data System, and the System for Earth Sample Registration, launched a Data Rescue Initiative in 2013 to advance preservation and re-use of valuable legacy datasets that are in danger of being lost. As part of this initiative, IEDA established a competition for Data Rescue Mini-Awards that provide modest funds to investigators to properly compile, document, and transfer legacy data sets to IEDA. Applications from late-career and near-retirement investigators were specifically encouraged. Awardees were given approximately six months to complete their data rescue activities. Three projects were awarded in 2013: (1) Geochemistry of Lunar Glasses: assembly of major element, trace element, volatile element, and isotope ratio data for lunar volcanic glasses and lunar impact glasses, (2) Geochemical and Geochronological data from Fiji, Izu-Bonin-Marianas, and Endeavor segment: assembly of published and unpublished data and metadata from large rock sample collections, and (3) Near-bottom Magnetic Data: curation and archival of 35 years of high-resolution, near-bottom magnetic field data from deeptowed platforms, submersibles, and ROVs. IEDA is working closely with the awardees to guide and support the data rescue effort and to assist with specific challenges related to outdated storage media or technology, diversity of platforms over decades of research, and the lack of established standards for data documentation. In this contribution we describe procedures and tools used for each project, summarize lessons learned and best practices, and present the final output of each data rescue project. Depending on the experiences of this first year and the availability of funds, we plan to continue the competition in future years.

  2. A combined method for rescue of modified enteroviruses by mutagenic primers, long PCR and T7 RNA polymerase-driven in vivo transcription.

    Science.gov (United States)

    Heikkilä, Outi; Kainulainen, Markus; Susi, Petri

    2011-01-01

    The current methods for manipulation of enteroviral RNA genomes and production of modified virus particles include stepwise subcloning procedures and in vitro transcription and RNA transfection steps that are both time-consuming and inefficient. Several enteroviral cDNA clones with 5'-terminal T7 promoter and coxsackievirus A9 (CAV9) PCR product with the T7 promoter were transfected successfully into target cells expressing T7 RNA polymerase for the rescue of virus particles. This demonstrated the overall feasibility of the in vivo transcription method. Furthermore, a rapid method using high-fidelity DNA polymerase, Phusion™, for amplification and mutagenesis of CAV9 cDNA was generated. A long PCR method was employed together with mutagenic primers for direct introduction of a unique restriction enzyme site into the VP1-2A junction of the CAV9 cDNA clone during the PCR amplification process. Enhanced green fluorescent protein was subcloned to that site, and CAV9-eGFP cDNA was transfected to the target cells for in vivo transcription and successful rescue of CAV9-eGFP particles. The method allowed a straightforward mutagenesis and in vivo production of infectious enteroviral particles, and may be applicable routinely for rapid production of the modified picornaviruses over the use of the traditional subcloning protocols. PMID:20974179

  3. J亚型禽白血病病毒的拯救与鉴定%Rescue and identification of the infectious clone of subgroup J avian leucosis virus

    Institute of Scientific and Technical Information of China (English)

    王超; 缪华先; 谢宝婵; 张伟伟; 吴润; 刘光清

    2011-01-01

    为鉴定含J亚群禽白血病病毒(ALV-J)全长cDNA分子克隆(pBlALV)的感染性,首先将pBlALV转染CEF细胞,拯救出病毒(rALV),然后连续传代3次,对拯救病毒进行增殖培养.分别利用RT-PCR、western blot、IFA等方法,对拯救病毒进行鉴定,并应用实时荧光定量PCR方法对拯救病毒的复制动力学进行了测定.研究结果证明,本研究成功拯救出了具有感染性的rALV-J,为研究禽白血病的致病机理和探讨新的防制措施等提供了良好的ALV的反向遗传操作技术平台.%To confirm the infectivity of the fiill-length cDNA clone (pBlALV) of subgroup J avian leucosis virus (ALV-J) HPRS103 strain, pBlALV was transfected into chicken embryo fibroblast (CEF) cells and the ALV was rescued. The rescued ALV (rALV-J) was identified by RT-PCR, western blot and indirect immunofiuorescence assay, respectively. Besides, the real-time PCR was applied to evaluate the replication dynamic of the rescued virus. The results showed that the rALV-J was able to well replicate in CEF. This study provides an useful platform for investigation of the pathogenesis and molecular biology of ALV-J.

  4. Degeneration and atrophy of the thymus of lethally irradiated dogs, rescued by transfusion of cryopreserved autologous blood leukocytes

    International Nuclear Information System (INIS)

    Dogs exposed to a fatal radiation dose of 12 Gy were rescued by transfusion of autologous blood leukocytes. A severe acute and long-lasting damage to the thymus was observed. The acute damage, as observed on the tenth day, consisted of a marked reduction in the number of lymphocytes, degeneration of Hassall's bodies, and hemorrhage. Long-term effects, observed several months after irradiation, were partial to total atrophy of the thymus. Regeneration, when it occurred, was limited to a few small isolated areas in which lymphopoiesis was supported by epithelial reticular cells. In contrast, the lymph nodes of all dogs had abundant cortical lymphopoiesis. The abundant hemopoiesis present in the marrow from the tenth day after irradiation until the end of the observation period should have provided sufficient circulating precursor cells to seed the thymus and regenerate the organ to the same extent as that observed in the other blood-forming organs. The impairment of lymphopoietic regeneration in the thymus seems to be due, therefore, to damage caused by irradiation on the specific stroma of the organ, which is not able to support such activity

  5. Drosophila simulans Lethal hybrid rescue mutation (Lhr) rescues inviable hybrids by restoring X chromosomal dosage compensation and causes fluctuating asymmetry of development

    Indian Academy of Sciences (India)

    R. N. Chatterjee; P. Chatterjee; A. Pal; M. Pal-Bhadra

    2007-12-01

    The Drosophila simulans Lhr rescues lethal hybrids from the cross of D. melanogaster and D. simulans. We describe here, the phenotypes of Lhr dependent rescue hybrids and demonstrate the effects of Lhr on functional morphology of the salivary chromosomes in the hybrids. Our results reveal that the phenotypes of the ‘Lhr dependent rescued’ hybrids were largely dependent on the genetic background and the dominance in species and hybrids, and not on Lhr. Cytological examination reveal that while the salivary chromosome of ‘larval lethal’ male carrying melanogaster X chromosome was unusually thin and contracted, in ‘rescued’ hybrid males (C$_{mel}_{mel}_{sim}$;A$_{mel}_{sim}$) the X chromosome showed typical pale staining, enlarged diameter and incorporated higher rate of 3H-uridine in presence of one dose Lhr in the genome. In hybrid males carrying simulans X chromosome (C$_{mel}_{sim}_{mel}$;A$_{mel}_{sim}$), enlarged width of the polytene X chromosome was noted in most of the nuclei, in Lhr background, and transcribed at higher rate than that of the single X chromosome of male. In hybrid females (both viable, e.g., C$_{mel}$ X$_{mel}$ X$_{sim}$; A$_{mel}$ A$_{sim}$ and rescued, e.g., C$_{mel}$ X$_{mel}$ X$_{mel}$; A$_{mel}$ A$_{sim}$), the functional morphology of the X chromosomes were comparable to that of diploid autosomes in presence of one dose of Lhr. In hybrid metafemales, (C$_{mel}_{mel}_{mel}_{sim}$; A$_{mel}_{sim}$), two dose of melanogaster X chromosomes and one dose of simulans X chromosome were transcribed almost at ‘female’ rate in hybrid genetic background in presence of one dose of Lhr. In rescued hybrid males, the melanogaster-derived X chromosome appeared to complete its replication faster than autosomes. These results together have been interpreted to have suggested that Lhr suppresses the lethality of hybrids by regulating functional activities of the X chromosome(s) for dosage compensation.

  6. Emergency Preparedness and Role Clarity among Rescue Workers during the Terror Attacks in Norway July 22, 2011

    Science.gov (United States)

    Pedersen, May Janne Botha; Gjerland, Astrid; Rund, Bjørn Rishovd; Ekeberg, Øivind; Skogstad, Laila

    2016-01-01

    Background Few studies address preparedness and role clarity in rescue workers after a disaster. On July 22, 2011, Norway was struck by two terror attacks; 77 people were killed and many injured. Healthcare providers, police officers and firefighters worked under demanding conditions. The aims of this study were to examine the level of preparedness, exposure and role clarity. In addition, the relationship between demographic variables, preparedness and exposure and a) role clarity during the rescue operations and; b) achieved mastering for future disaster operations. Methods In this cross-sectional study, healthcare providers (n = 859), police officers (n = 252) and firefighters (n = 102) returned a questionnaire approximately 10 months after the terror attacks. Results The rescue personnel were trained and experienced, and the majority knew their professional role (healthcare providers M = 4.1 vs. police officers: M = 3.9 vs. firefighters: M = 4.2, p 5 fatalities (OR 1.6, p < .05) were all associated with role clarity, together with a feeling of control, not being obstructed in work and perceiving the rescue work as a success. Moreover, independent predictors of being more prepared for future operations were arousal during the operation (OR 2.0, p < .001) and perceiving the rescue work as a success (OR 1.5, p < .001). Conclusion Most of the rescue workers were experienced and knew their professional role. Training and everyday-work-experience must be a focal point when preparing rescue workers for disaster. PMID:27280520

  7. Satellite-Based Technologies in Use for Extreme Nocturnal Mountain Rescue Operations: a Synergetic Approach Applying Geophysical Principles

    Science.gov (United States)

    Buchroithner, Manfred F.; Ehlert, Guido; Hetze, Bernd; Kohlschmidt, Horst; Prechtel, Nikolas

    2014-06-01

    Mountain-rescue operations require rapid response whilst also ensuring the security of the rescue teams. Rescuing people in a big rock-face is even more difficult if night or fog prevent sight. The paper presents a technical solution to optimally support, under these aggravated conditions, the location of the casualties and the navigation of the rescue team(s) in a rock-face from a coordination station. In doing so, standard components like a smartphones with GPS functionality, a data communication on a client-server basis and VR visualisation software have been adapted to the specific requirements. Remote support of the navigation in steep rocky terrain requires a highly accurate wall model which permits the local experts of the coordination station to dependably estimate geometry and structure of the rock along the rescue route and to convey necessary directives to the retrieval team. Based on terrestrial laser-scans from different locations, such a model has been generated for the mighty Dachstein South Face (Austria) and texturised with digital photographs. Over a twelve-month period, a transdisciplinary team of the Dresden University of Technology (Informatics, Electrical Engineering, Cartography) developed and integrated the various technical modules of the mountain-rescue support-system (digital rock-face model, optimised GPS data transmission between mobile device, server and client, data filtering, and dynamic visualisation component). In summer 2011 the proper functioning of the prototype was demonstrated in a rescue exercise under foggy dusk conditions.

  8. The emergence of the rescue effect from explicit within and between-patch dynamics in a metapopulation

    KAUST Repository

    Eriksson, Anders

    2014-02-12

    Immigration can rescue local populations from extinction, helping to stabilize a metapopulation. Local population dynamics is important for determining the strength of this rescue effect, but the mechanistic link between local demographic parameters and the rescue effect at the metapopulation level has received very little attention by modellers. We develop an analytical framework that allows us to describe the emergence of the rescue effect from interacting local stochastic dynamics. We show this framework to be applicable to a wide range of spatial scales, providing a powerful and convenient alternative to individual-based models for making predictions concerning the fate of metapopulations. We show that the rescue effect plays an important role in minimizing the increase in local extinction probability associated with high demographic stochasticity, but its role is more limited in the case of high local environmental stochasticity of recruitment or survival. While most models postulate the rescue effect, our framework provides an explicit mechanistic link between local dynamics and the emergence of the rescue effect, and more generally the stability of the whole metapopulation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  9. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  10. Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

    Science.gov (United States)

    Hildyard, J C W; Lacey, E; Booler, H; Hopkinson, M; Wells, D J; Brown, S C

    2016-01-01

    LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20-100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window. PMID:27467128

  11. Cannabidiol rescues acute hepatic toxicity and seizure induced by cocaine.

    Science.gov (United States)

    Vilela, Luciano Rezende; Gomides, Lindisley Ferreira; David, Bruna Araújo; Antunes, Maísa Mota; Diniz, Ariane Barros; Moreira, Fabrício de Araújo; Menezes, Gustavo Batista

    2015-01-01

    Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD), protects against cocaine toxicity. URB597 (1.0 mg/kg) abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg) reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen) increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse. PMID:25999668

  12. Application and Research Software Design on Rescue Communication System of Embedded Mine-Underground

    Directory of Open Access Journals (Sweden)

    ZU Guojian

    2013-05-01

    Full Text Available This design has been made the module division according to its function. It including video display, three party service (volume control and environment parameters display warning information as well as data storage module. Furthermore, this application software uses the multithreading to realize the modulation, which including the receive thread (It receives the video and audio data as well as environment parameters data, the display thread and the warning judgment thread. This application software construction is based on the S3C6410 platform with embedded WinCE 6.0 operating systems in the VS2005 development environment to realize the system function. From the above, it can transfer the environment, the video and audio information to the rescuer and the underground base and the rescue command center instantaneously and accurately. In a word, it’s helpful for command center to know underground rescue situations instantaneously and can implement command well.

  13. Using the RESCUE technique to investigate the soil-structure interaction for a nuclear reactor

    International Nuclear Information System (INIS)

    This paper reports on an ongoing program to develop an experimental technique for shaking soil- structure systems to large-amplitude earthquake-like ground motions. The technique, called repeatable earth shaking by controlled underground expansion (RESCUE), produces pulses of ground motion by controlled expansion of an array of rubber bladders buried in the ground. At small scale, the technique can be used to conduct carefully controlled scale-model experiments to study the dynamic response of soil-structure systems to ground motion and to help verify computer codes. At large scale, the technique has the potential for investigating dynamic response of in situ structures. This paper describes the RESCUE experimental technique and its application to testing of large and small-scale in-situ nuclear reactor models

  14. Flight tests with enhanced/synthetic vision system for rescue helicopter

    Science.gov (United States)

    Tsuda, Hiroka; Funabiki, Kohei; Iijima, Tomoko; Tawada, Kazuho; Yoshida, Takashi

    2011-06-01

    JAXA (Japan Aerospace Exploration Agency) has been conducting a research project named SAVERH (Situation Awareness and Visual Enhancer for Rescue Helicopter) with Shimadzu Corporation and NEC from 2008. SAVERH aims at inventing a method of presenting suitable information to the pilot to support search and rescue missions. An integrated system comprising an HMD (Helmet-Mounted Display) and a FLIR (Forward Looking Infrared) sensor were installed in a JAXA research helicopter, and a series of flight tests was conducted to evaluate the benefit of presenting FLIR images on the HMD in night flight. Three pilots evaluated the display system during six night flights, considering terrain and position awareness. The tests showed that use of FLIR gave better route tracking performance, and the effectiveness of head-slaved FLIR on an approach task was shown by subjective pilot rating.

  15. A mental health program for ground zero rescue and recovery workers: cases and observations.

    Science.gov (United States)

    Katz, Craig L; Smith, Rebecca; Silverton, Marsha; Holmes, Anastasia; Bravo, Carlos; Jones, Kristina; Kiliman, Marta; Lopez, Norma; Malkoff, Laurie; Marrone, Kathryn; Neuman, Alla; Stephens, Tricia; Tavarez, Wendy; Yarowsky, Anne; Levin, Stephen; Herbert, Robin

    2006-09-01

    Clinical vignettes from the World Trade Center Worker and Volunteer Mental Health Monitoring and Treatment Program at the Mount Sinai Medical Center in New York City are presented. The hospital-based program pairs mental health screenings with federally funded occupational medical screenings to identify persons with mental health problems related to their rescue and recovery roles. The program also provides on-site mental health treatment. The cases illustrate the diverse mental health needs of the rescue and recovery workers, some of whom initially sought treatment years after September 11, 2001. The cases show that in addition to symptoms of posttraumatic stress disorder, workers experienced survivor guilt, distressing memories of childhood trauma, shame associated with intense feelings, substance abuse relapse, psychosis, and problems with family relationships. PMID:16968767

  16. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    Science.gov (United States)

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  17. FEMA Urban Search and Rescue Teams : Considering an Improved Strategy for an Evolving Homeland Security Enterprise

    OpenAIRE

    Poirier, Alfred

    2012-01-01

    Approved for public release; distribution is unlimited The United States governments role in preparing for, preventing, responding to, and recovering from all domestic disasters is coordinated by the Federal Emergency Management Agency (FEMA). Further, FEMA is designated as the primary agency responsible for coordinating Structural Collapse (Urban) Search and Rescue (US and R) situations in the National Response Framework. Since the inception of FEMA resources intended for response to US a...

  18. JAK2 inhibition prevents innate immune responses and rescues animals from sepsis

    OpenAIRE

    Peña, Geber; Cai, Bolin; Deitch, Edwin A.; Ulloa, Luis

    2010-01-01

    Sepsis, a leading cause of death in hospitalized patients, is characterized by lethal systemic inflammatory responses. JAK2 is an essential tyrosine kinase modulating immune responses. However, the implications of JAK2 in infectious disorders remain undetermined. Here, we report that JAK2 inhibitors rescue animals from polymicrobial sepsis in a clinically relevant time frame. JAK2 inhibition with AG490 prevents NF-κB activation, modulates macrophage activation, and restrains the production of...

  19. Exogenous FGF8 rescues development of mouse diastemal vestigial tooth ex vivo

    OpenAIRE

    Li, Lu; Yuan, Guohua; Liu, Chao; Zhang, Lu; Zhang, Yanding; Chen, Yiping; Chen, Zhi

    2011-01-01

    Regression of vestigial tooth buds results in the formation of the toothless diastema, a unique feature of the mouse dentition. Revitalization of the diastemal vestigial tooth bud provides an excellent model for studying tooth regeneration and replacement. It was shown previously that suppression of FGF signaling in the diastema is a causative of vestigial tooth bud regression. In this study, we report that application of exogenous FGF8 to the mouse embryonic diastemal region rescues diastema...

  20. Rescue, rehabilitation, and release of marine mammals: An analysis of current views and practices.

    OpenAIRE

    St. Aubin, David J.; Geraci, Joseph R.; Lounsbury, Valerie J.

    1996-01-01

    Stranded marine mammals have long attracted public attention. Those that wash up dead are, for all their value to science, seldom seen by the public as more than curiosities. Animals that are sick, injured, orphaned or abandoned ignite a different response. Generally, public sentiment supports any effort to rescue, treat and return them to sea. Institutions displaying marine mammals showed an early interest in live-stranded animals as a source of specimens -- in 1948, Marine Studios in...

  1. Rifaximin Plus Levofloxacin-Based Rescue Regimen for the Eradication of Helicobacter pylori

    OpenAIRE

    Yun, Sang-Pil; Seon, Han Gyung; Ok, Chang Soo; Yoo, Kwang Ho; Kang, Min Kyung; Kim, Won Hee; Kwon, Chang Il; Ko, Kwang Hyun; Hwang, Seong Gyu; Park, Pil Won; Hong, Sung Pyo

    2012-01-01

    Background/Aims This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori. Methods We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrat...

  2. AN SOA BASED REAL TIME INFORMATION EXCHANGE BETWEEN MILITARY AND GOVERNMENT OWNED RESCUE SERVICES

    OpenAIRE

    Dr. Muhammd Awais Bhatti; Fatima Hussain; Dr. Veera Pandiyan KalianiSundram

    2012-01-01

    The purpose of this study is to examine an SOA based real time information exchange between military and government owned rescue services. Information sharing is always not an easy approach for any organization. In case of military and government owned sectors, it becomes more fragile. There should be some quality and well standard approach that can be used for the secure sharing of information. A detailed proposed architectures and real time scenarios have used to clarify the essential need ...

  3. A Novel Technique of Rescuing Capsulorhexis Radial Tear-out using a Cystotome

    OpenAIRE

    Karim, Shah M. R.; Ong, Chin T.; Miah, Mizanur R.; Sleep, Tamsin; Hanifudin, Abdul

    2011-01-01

    Part 1 : Purpose: To demonstrate a capsulorhexis radial tear out rescue technique using a cystotome on a virtual reality cataract surgery simulator and in a human eye. Part 2 : Method: Steps: When a capsulorhexis begins to veer radially towards the periphery beyond the pupillary margin the following steps should be applied without delay. 2.1) Stop further capsulorhexis manoeuvre and reassess the situation. 2.2) Fill the anterior chamber with ophthalmic viscosurgical device (OVD). We recommend...

  4. In vitro embryo rescue of interspecific hybrids of oil palm (Elaeis oleifera x Elaeis guineensis)

    OpenAIRE

    Sergio Augusto Oliveira Alves; Oriel Filgueira de Lemos; Benedito Gomes dos Santos Filho; André Luís Lopes da Silva

    2011-01-01

    The oil palm (Elaeis guineennsis Jacq.) is the plant with major oil yield in tropical areas over the world. Pará state is the major producer of Brazil. However, the production of resistant hybrids (Elaeis oleifera x Elaeis guinennsis) to several diseases is necessary, in spite of less productive, is a viable alternative for areas where occur more aggressive diseases. The aim of this research was to rescue in vitro embryos of four varieties of interspecific hybrids of oil palm (Elaeis oleifera...

  5. Randomised trial of elective continuous positive airway pressure (CPAP) compared with rescue CPAP after extubation

    OpenAIRE

    Robertson, N; Hamilton, P

    1998-01-01

    AIM—To determine if a weaning regimen on flow driver continuous positive airway pressure (CPAP) would decrease the number of ventilator days but increase the number of CPAP days when compared with a rescue regimen.
METHODS—Fifty eight babies of 24-32 weeks gestation with respiratory distress syndrome (RDS) were studied prospectively. After extubation they were randomly allocated to receive CPAP for 72 hours (n=29) according to a weaning regimen, or were placed in headbox ...

  6. Intelligent systems for urban search and rescue: challenges and lessons learned

    Science.gov (United States)

    Jacoff, Adam; Messina, Elena; Weiss, Brian A.

    2003-09-01

    Urban search and rescue (USAR) is one of the most dangerous and time-critical non-wartime activities. Researchers have been developing hardware and software to enable robots to perform some search and rescue functions so as to minimize the exposure of human rescue personnel to danger and maximize the survival of victims. Significant progress has been achieved, but much work remains. USAR demands a blending of numerous specialized technologies. An effective USAR robot must be endowed with key competencies, such as being able to negotiate collapsed structures, find victims and assess their condition, identify potential hazards, generate maps of the structure and victim locations, and communicate with rescue personnel. These competencies bring to bear work in numerous sub-disciplines of intelligent systems (or artificial intelligence) such as sensory processing, world modeling, behavior generation, path planning, and human-robot interaction, in addition to work in communications, mechanism design and advanced sensors. In an attempt to stimulate progress in the field, reference USAR challenges are being developed and propagated worldwide. In order to make efficient use of finite research resources, the robotic USAR community must share a common understanding of what is required, technologically, to attain each competency, and have a rigorous measure of the current level of effectiveness of various technologies. NIST is working with partner organizations to measure the performance of robotic USAR competencies and technologies. In this paper, we describe the reference test arenas for USAR robots, assess the current challenges within the field, and discuss experiences thus far in the testing effort.

  7. Designing Intelligent Robots for Human-Robot Teaming in Urban Search & Rescue

    OpenAIRE

    Kruijff, Geert; Colas, Francis; Svoboda, Tomáš; Van Diggelen, Jurriaan; Balmer, Patrick; Pirri, Fiora; Worst, Rainer

    2012-01-01

    The paper describes ongoing integrated research on designing intelligent robots that can assist humans in making a situation assessment during Urban Search & Rescue (USAR) missions. These robots (rover, microcopter) are deployed during the early phases of an emergency response. The aim is to explore those areas of the disaster hotzone which are too dangerous or too difficult for a human to enter at that point. This requires the robots to be " intelligent " in the sense of being capable of var...

  8. Identity through photography: identity construction and rescue of the Community Novo Aarão Reis

    OpenAIRE

    Laís de Paula Fiuza Costa; Rodrigo Viana de Ávila

    2011-01-01

    This article reports an innovative experience of mounting a traveling exhibition of photographs, which was held at the Community Health Center of Novo Aarão Reis, Municipality of Belo Horizonte, in Minas Gerais. It aims to present a form of construction, rescue, and maintenance of memory, history, and identity of the community residents, as it transforms the perception of residents about themselves and the world around them. Furthermore, it exposes these residents to others from elsewhere in ...

  9. Rescue treatment with terlipressin in children with refractory septic shock: a clinical study

    OpenAIRE

    Rodríguez-Núñez, Antonio; López-Herce, Jesús; Gil-Antón, Javier; Hernández, Arturo; Rey, Corsino; ,

    2006-01-01

    Introduction Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock. Methods We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive ca...

  10. Low-cost MultiTerrainRescuing 4-Legged Bot Prototype

    OpenAIRE

    Deep Dwivedi; Yokesh Babu Sundaresan; Kumaresan, P

    2013-01-01

    in modern day disaster recovery mission has become one of the top priorities in any natural disaster management regime. Smart autonomous robots may play a significant role in such missions,including search for life under earth quake hit rubbles, Tsunami hit islands, de-mining in war affected areas and many other such situations. This paper presents a way to build a low cost rescuing 4-legged bot prototype based on Arduino with multiple features like obstacle avoidance , wireless communication...

  11. Rescue Living-donor Liver Transplantation for Liver Failure Following Hepatectomy for Hepatocellular Carcinoma

    OpenAIRE

    Chan, See Ching; Sharr, William Wei; Chan, Albert Chi Yan; Chok, Kenneth Siu Ho; Lo, Chung Mau

    2013-01-01

    Liver failure following major hepatectomy for hepatocellular carcinoma is a known but uncommon mode of early treatment failure. When post-hepatectomy liver failure becomes progressive, the only effective treatment for rescuing the patient is liver transplantation. Deceased-donor liver transplantation in this situation is often not feasible because of the shortage of deceased-donor liver grafts. Proceeding with living-donor liver transplantation is an ethical challenge because of the possibili...

  12. Supporting Urban Search and Rescue with digital assessments of structures and requests of response resources

    OpenAIRE

    Chen, Albert Y.; Peña Mora, Feniosky; Plans Pujolràs, Albert; Mehta, Saumil J.; Aziz, Zeeshan

    2013-01-01

    First responders, including structural engineers and firefighters, inspect buildings and identify the structural integrity of buildings within a disaster affected area. The performance of their inspection and dissemination of the assessment information are critical to Urban Search and Rescue (US&R) operations. This paper presents an innovative approach for structural assessment and resource requests through an application – Supporting Urban Preparedness and Emergency Response usin...

  13. Evaluation of the Effects of Standard Rescue Procedure on Severe Trauma Treatment in China

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yin; Tian-Bing Wang; Pei-Xun Zhang; Yu-Hui Kou; Dian-Ying Zhang; Kai Yu; De-Cheng Lyu

    2015-01-01

    Background:This study aimed to evaluate the effects of standard rescue procedure (SRP) in improving severe trauma treatments in China.Methods:This study was conducted in 12 hospitals located in geographically and industrially different cities in China.A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment.A regional network (system) efficiently integrating prehospital rescue,emergency room treatments,and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments.Treatment outcomes were compared between before and I year after the implementation of the SRP.Results:The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP.Implementation of the SRP led to efficient cooperation and information sharing of different treatment services.The emergency response time,prehospital transit time,emergency rescue time,consultation call time,and mortality rate of patients were 24.24 ± 4.32 min,45.69 ± 3.89 min,6.38 ± 1.05 min,17.53 ± 0.72 min,and 33.82% ± 3.87% (n =441),respectively,before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min,22.39 ± 4.32 min,3.26 ± 0.89 min,3.45 ± 0.45 min,and 20.49% ± 3.11%,separately (n =495,P < 0.05) after that.Conclusions:Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.

  14. INTEGRATION OF MULTIPLE UNMANNED SYSTEMS IN AN URBAN SEARCH AND RESCUE ENVIRONMENT

    OpenAIRE

    Chua, Boon Heng

    2013-01-01

    In view of the local, regional and global security trends over the past decade, the threats of disaster to the populace inhabiting urbanized areas are real and there is a need for increased vigilance. There can be multiple causes for urban disaster natural disasters, terrorist attack and urban warfare are all viable. This thesis focused on the event in which an urban search and rescue operation is required due to the aftermath of a terrorist activity. Systems engineering techniques were utili...

  15. Modelling Lost Person Behaviour and Intelligent Unmanned Aerial Vehicles in a Wilderness Search and Rescue Scenario

    OpenAIRE

    DeRiggi, John

    2013-01-01

    Search and rescue cases studies offer interesting insights into the thought process of a lost person. There is evidence that the behavior of a lost person is inextricably linked to how they perceive the problem of being lost. If panic presides, then behavior could be irrational, repetitive, and counter-intuitive. If a calm, disciplined, and problem-solving mindset takes reign, then the patterns of motion are predictable and are often the product of a careful evaluation of options. Regardless ...

  16. DESIGN OF UNMANNED AIR SYSTEMS FOR USE IN SEARCH AND RESCUE IN THE NORTH ATLANTIC

    OpenAIRE

    Melin, Tomas

    2012-01-01

    A comparison of aircraft performance and program costs involved with unmanned air vehicle (UAV) projects has been performed. The assessment has been taken from a systems engineering point of view when designing a new unmanned air system for a search and rescue case study. Two different design strategies were investigated, one being a traditional aircraft system with servicing and maintenance intervals and the other being a single use aircraft system. The design paradigm is design-to-objective...

  17. Worsening of Cardiomyopathy Using Deflazacort in an Animal Model Rescued by Gene Therapy

    OpenAIRE

    Ida Luisa Rotundo; Stefania Faraso; Elvira De Leonibus; Gerardo Nigro; Carmen Vitiello; Alessio Lancioni; Daniele Di Napoli; Sigismondo Castaldo; Vincenzo Russo; Fabio Russo; Giulio Piluso; Alberto Auricchio; Vincenzo Nigro

    2011-01-01

    We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection in...

  18. Genomic sweep and potential genetic rescue during limiting environmental conditions in an isolated wolf population

    OpenAIRE

    Adams, Jennifer R.; Vucetich, Leah M.; Hedrick, Philip W.; Rolf O Peterson; Vucetich, John A.

    2011-01-01

    Genetic rescue, in which the introduction of one or more unrelated individuals into an inbred population results in the reduction of detrimental genetic effects and an increase in one or more vital rates, is a potentially important management tool for mitigating adverse effects of inbreeding. We used molecular techniques to document the consequences of a male wolf (Canis lupus) that immigrated, on its own, across Lake Superior ice to the small, inbred wolf population in Isle Royale National P...

  19. Genetic Analysis and Rescue of a Triple-reassortant H3N2 Influenza A Virus Isolated From Swine in Eastern China

    Institute of Scientific and Technical Information of China (English)

    Xian QI; Yong-jun JIAO; Hao PAN; Lun-biao CUI; Wei-xing FAN; Bao-xu HUANG; Zhi-yang SHI; Hua WANG

    2009-01-01

    One influenza H3N2 virus, A/swine/Shandong/3/2005 (Sw/SD/3/2005), was isolated from pigs with respiratory disease on a farm in eastern China. Genetic analysis revealed that Sw/SD/3/2005 was a triple-reassortant virus with a PB2 gene from human-like HIN1, NS from classical swine H1NI, and the remaining genes from human-like H3N2 virus. These findings further support the concept that swine can serve as reservoir or mixing vessels of influenza virus strains and maintain genetic and antigenic stability of viruses. Furthermore, we have successfully established a reverse genetics system based on eight plasmids and rescued Sw/SD/3/2005 through cell transfection. HI tests and RT-PCR confirmed that the rescued virus maintained the biological properties of the wild type Sw/SD/3/2005. The successful establishment of the reverse genetics system of Sw/SD/3/2005 will enable us to conduct extensive studies of the molecular evolution of H3N2 influenza viruses in swine.

  20. [Rescue of bovine Asia 1 serotype foot-and-mouth disease virus from a full-length cDNA clone].

    Science.gov (United States)

    Li, Shuang; Zhang, Runxiang; Song, Ge; Gao, Mingchun; Liu, Xiangtao; Wang, Junwei

    2009-11-01

    After sequencing the Asia 1 foot-and-mouth disease virus (FMDV) (As01 strain), we amplified the two fragments covering the whole genome by overlapping PCR and long PCR. The 5' fragment was 1.8 kb in length including 15Cs, and the 3' fragment was 6.7 kb in length. The two fragments were cloned into the pBluescript SK vector to construct recombinant plasmid pBSAs carrying the full-length cDNA of FMDV As01 strain. The RNA transcript was synthesized in vitro using T7 polymerase and transfected into BHK-21 cells. We observed the typical CPE caused by rescued FMDV. The harvested virus was confirmed to be Asia 1 FMDV by RT-PCR, indirect immunofluorescence assay (IFA) and electron microscope observation. The rescued virus showed a similar pathogenicity in suckling mouse (LD50) compared to its wild-type virus. The infectious cDNA clone of the FMDV As01 strain laid a new ground for further investigation of FMDV virulence determinants and development of novel vaccines against FMD. PMID:20222458

  1. Blueprint for Implementing New Processes in Acute Care: Rescuing Adult Patients With Intraosseous Access.

    Science.gov (United States)

    Chreiman, Kristen M; Kim, Patrick K; Garbovsky, Lyudmila A; Schweickert, William D

    2015-01-01

    The intraosseous (IO) access initiative at an urban university adult level 1 trauma center began from the need for a more expeditious vascular access route to rescue patients in extremis. The goal of this project was a multidisciplinary approach to problem solving to increase access of IO catheters to rescue patients in all care areas. The initiative became a collaborative effort between nursing, physicians, and pharmacy to embark on an acute care endeavor to standardize IO access. This is a descriptive analysis of processes to effectively develop collaborative strategies to navigate hospital systems and successfully implement multilayered initiatives. Administration should empower nurse to advance their practice to include IO for patient rescue. Intraosseous access may expedite resuscitative efforts in patients in extremis who lack venous access or where additional venous access is required for life-saving therapies. Limiting IO dwell time may facilitate timely definitive venous access. Continued education and training by offering IO skill laboratory refreshers and annual e-learning didactic is optimal for maintaining proficiency and knowledge. More research opportunities exist to determine medication safety and efficacy in adult patients in the acute care setting. PMID:26352658

  2. Hematologic and serum biochemical parameters of apparently healthy rescued formosan pangolins (Manis pentadactyla pentadactyla).

    Science.gov (United States)

    Chin, Shih-chien; Lien, Chen-yah; Chan, Yating; Chen, Chun-lin; Yang, Yi- ching; Yeh, Lih-seng

    2015-03-01

    Natural habitats of pangolins are rapidly deteriorating because of extensive farming, logging, and human construction activities. In addition, the illegal trading of pangolins substantially accelerated the decline of the pangolins' population in southeastern Asia. The maintenance of confiscated pangolins in rescue centers is currently a daunting task for veterinarians and conservation biologists. There is limited information in the literature about the reference values regarding the physiology of pangolins. The purpose of this study is to establish reliable hematologic and serum biochemical reference values for the Formosan pangolin (Manis pentadactyla pentadactyla). Blood samples were collected from 51 apparently healthy pangolins from a population of 117 rescued pangolins at the Taipei Zoo. Sex-related differences were observed in platelet count, alanine aminotransferase level, mean corpuscular hemoglobin concentration, and total protein level. Age-related differences were also noted; juveniles have significantly higher platelet counts and alkaline phosphatase levels than their adult counter parts. The hematologic and serum biochemical reference values for the Formosan pangolin presented in this study can be applied in the medical care of this important species during rescue attempts. It is the first systematic report of blood parameters of apparently healthy pangolins and provides a basis for future investigation of this species. The reference values reported in this study may also be applicable to other pangolin species in the genus Manis. PMID:25831578

  3. Worsening of cardiomyopathy using deflazacort in an animal model rescued by gene therapy.

    Directory of Open Access Journals (Sweden)

    Ida Luisa Rotundo

    Full Text Available We have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF. However, the EF value declined (52±14% with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients.

  4. Pharmacological rescue of hERG currents carried out by G604S and wide type hERG co-expression.

    Science.gov (United States)

    Huo, Jianhua; Zhang, Aifeng; Guo, Xueyan; Qiang, Hua; Liu, Ping; Bai, Ling; Ma, Aiqun

    2016-09-01

    Mutations in human ether-a-go-go-related gene (hERG) can lead to type 2 long-QT syndrome (LQT2). The authors previously identified the hERG mutation G604S results in a loss of function and obviously decreased current amplitude and impaired channel protein trafficking when co-expressed with WT-hERG. The present study further investigates the biological and electrophysiological consequences of pharmacologic chaperones in HEK293 cells expressing G604S-hERG or co-expressing G604S-hERG and WT-hERG. It was found that a low temperature (27°C), thapsigargin, NS1643 and E-4031 fail to rescue the G604S mutation. Interestingly, only E-4031 treatment resulted in a significant increase in hERG currents in cells co-expressing G604S-hERG and WT-hERG, correspondingly more mature protein band at 155 kDa by Western blotting and an increased membrane staining by confocal microscopy. In addition, E-4031 treatment shifted the steady-state half maximal activation voltage (V1/2 ) of the inactivation curve by +8 mV in cells co-expressing G604S-hERG and WT-hERG. The present experimental results suggest that a G604S mutation is resistant to pharmacological rescue. E-4031 treatment resulted in a significant increase in hERG currents by promoting the hERG channel processing and trafficking in cells co-expressing G604S-hERG and WT-hERG. PMID:27199074

  5. Use of Recombination-Mediated Genetic Engineering for Construction of Rescue Human Cytomegalovirus Bacterial Artificial Chromosome Clones

    Directory of Open Access Journals (Sweden)

    Kalpana Dulal

    2012-01-01

    Full Text Available Bacterial artificial chromosome (BAC technology has contributed immensely to manipulation of larger genomes in many organisms including large DNA viruses like human cytomegalovirus (HCMV. The HCMV BAC clone propagated and maintained inside E. coli allows for accurate recombinant virus generation. Using this system, we have generated a panel of HCMV deletion mutants and their rescue clones. In this paper, we describe the construction of HCMV BAC mutants using a homologous recombination system. A gene capture method, or gap repair cloning, to seize large fragments of DNA from the virus BAC in order to generate rescue viruses, is described in detail. Construction of rescue clones using gap repair cloning is highly efficient and provides a novel use of the homologous recombination-based method in E. coli for molecular cloning, known colloquially as recombineering, when rescuing large BAC deletions. This method of excising large fragments of DNA provides important prospects for in vitro homologous recombination for genetic cloning.

  6. Refuge Management Program Part 3 : Search and Rescue Plan : Horicon National Wildlife Refuge, Fox River National Wildlife Refuge, Wilderness Islands

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — An effective search and rescue plan is required for Horicon NWR due to the diversity of activities open to the general public, the large expanse of isolated...

  7. ADMINISTRATIVE CIRCULAR No. 25 (REV. 3) - Special provisions for the fire and rescue service governing working and rest time

    CERN Multimedia

    2012-01-01

    Administrative Circular No. 25 (Rev. 3) entitled “Special provisions for the Fire and Rescue Service governing working and rest time”, approved by the Director-General following discussion at the Standing Concertation Committee meeting of 28 September 2012 and entering into force in October 2012, is available on the intranet site of the Human Resources Department: http://cern.ch/hr-docs/admincirc/admincirc.asp This Circular is applicable to staff members of the Fire and Rescue Service It cancels and replaces Administrative Circular No. 25 (Rev. 2) entitled “Shift work – Special provisions for the Fire and Rescue Service” of April 2003. This new version takes into account the new organisation of the Fire and Rescue Service, members of which will henceforth not exclusively perform their functions in the context of shift work, but also during reference working hours and during stand-by duty. Additionally, applicable limits regarding working and rest times an...

  8. Replicon rescue: a novel strategy to clone the genomic DNA flanking insertions of integrating shuttle vector DNA.

    OpenAIRE

    McMahon, T L; Wilczynska, Z.; Barth, C.; Fraser, D. J.; Pontes, L; Fisher, P R

    1996-01-01

    A novel cloning strategy, replicon rescue, was developed for cloning genes disrupted by plasmid insertions. After ligation to a tetracycline resistance cassette, fragments containing a bacterial origin of replication from the insertion are recovered in Escherichia coli because they replicate autonomously. Restriction enzymes for cloning are so chosen that the only legitimate two fragment ligation yielding TetR clones involves a fragment spanning the boundary of the insertion. Replicon rescue ...

  9. R.ox.an.e: An Embedded System for Search and Rescue of Trapped in the Ruins of an Earthquake

    Directory of Open Access Journals (Sweden)

    A. Pantelis

    2010-01-01

    Full Text Available R.ox.an.e is an embedded system for search and rescue of trapped victims in the ruins of an earthquake. A rescue team coulduse such kind of digital assistants in order to have quick and safe information about the disaster. The proposed system is asmall size vehicle, with microcontroller based hardware and is wirelessly controlled. The operator has full control of thevehicle and is able to capture real time image of the accident place and various sensors measurements.

  10. Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit.

    OpenAIRE

    Lem, J.; Flannery, J. G.; Li, T; Applebury, M L; Farber, D B; Simon, M. I.

    1992-01-01

    The beta subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE beta subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photorecept...

  11. Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit

    OpenAIRE

    Lem, Janis; Flannery, John G.; Li, Tiansen; Applebury, Meredithe L.; Farber, Debora B.; Simon, Melvin I.

    1992-01-01

    The ß subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE ß subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photoreceptors in...

  12. Peritraumatic Distress, Watching Television, and Posttraumatic Stress Symptoms among Rescue Workers after the Great East Japan Earthquake

    OpenAIRE

    Daisuke Nishi; Yuichi Koido; Naoki Nakaya; Toshimasa Sone; Hiroko Noguchi; Kei Hamazaki; Tomohito Hamazaki; Yutaka Matsuoka

    2012-01-01

    BACKGROUND: The Great East Japan Earthquake of March 11, 2001 left around 20,000 dead or missing. Previous studies showed that rescue workers, as well as survivors, of disasters are at high risk for posttraumatic stress disorder (PTSD). This study examined the predictive usefulness of the Peritraumatic Distress Inventory (PDI) among rescue workers of Disaster Medical Assistance Teams (DMATs) deployed during the acute disaster phase of the Great East Japan Earthquake. METHODOLOGY/PRINCIPAL FIN...

  13. Minocycline and risperidone prevent microglia activation and rescue behavioral deficits induced by neonatal intrahippocampal injection of lipopolysaccharide in rats.

    Directory of Open Access Journals (Sweden)

    Furong Zhu

    Full Text Available BACKGROUND: Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia. METHODS: Neonatal intrahippocampal injection of lipopolysaccharide (LPS, an activator of microglia, was performed in rats at postnatal day 7 (P7, and they were separately given saline, risperidone (0.5 mg/kg, minocycline (40 mg/kg or a combination of both of them at P42 for consecutive 14 days. Behavioral changes (locomotion activity, social interaction, novel object recognition and prepulse inhibition were examined and the number of microglia was assessed by using immunohistochemistry in adulthood. RESULTS: The adult rats in LPS-injected group showed obvious behavioral alteration (e. g. deficits in social interaction, novel object recognition and prepulse inhibition and a dramatic increase of number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, application of either minocycline, risperidone or both of them significantly rescued behavioral deficits and attenuated microglia activation. CONCLUSION: Our results suggest that inhibition of microglia activation may be one of mechanisms underlying the antipsychotic effect of minocycline and risperidone.

  14. Minocycline and Risperidone Prevent Microglia Activation and Rescue Behavioral Deficits Induced by Neonatal Intrahippocampal Injection of Lipopolysaccharide in Rats

    Science.gov (United States)

    Ding, Yu-qiang; Liu, Yong; Zhang, Xianghui; Wu, Renrong; Guo, Xiaofeng; Zhao, Jingping

    2014-01-01

    Background Various signs of activation of microglia have been reported in schizophrenia, and it is hypothesized that microglia activation is closely associated with the neuropathology of schizophrenia. Methods Neonatal intrahippocampal injection of lipopolysaccharide (LPS), an activator of microglia, was performed in rats at postnatal day 7 (P7), and they were separately given saline, risperidone (0.5 mg/kg), minocycline (40 mg/kg) or a combination of both of them at P42 for consecutive 14 days. Behavioral changes (locomotion activity, social interaction, novel object recognition and prepulse inhibition) were examined and the number of microglia was assessed by using immunohistochemistry in adulthood. Results The adult rats in LPS-injected group showed obvious behavioral alteration (e. g. deficits in social interaction, novel object recognition and prepulse inhibition) and a dramatic increase of number of activated microglial cells in the hippocampus and other brain regions such as cerebral cortex and thalamus compared to those in saline-injected group. Interestingly, application of either minocycline, risperidone or both of them significantly rescued behavioral deficits and attenuated microglia activation. Conclusion Our results suggest that inhibition of microglia activation may be one of mechanisms underlying the antipsychotic effect of minocycline and risperidone. PMID:24705495

  15. Clinical polyomavirus BK variants with agnogene deletion are non-functional but rescued by trans-complementation

    International Nuclear Information System (INIS)

    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 infectious 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.

  16. Sera from children with autism induce autistic features which can be rescued with a CNTF small peptide mimetic in rats.

    Directory of Open Access Journals (Sweden)

    Syed Faraz Kazim

    Full Text Available Autism is a neurodevelopmental disorder characterized clinically by impairments in social interaction and verbal and non-verbal communication skills as well as restricted interests and repetitive behavior. It has been hypothesized that altered brain environment including an imbalance in neurotrophic support during early development contributes to the pathophysiology of autism. Here we report that sera from children with autism which exhibited abnormal levels of various neurotrophic factors induced cell death and oxidative stress in mouse primary cultured cortical neurons. The effects of sera from autistic children were rescued by pre-treatment with a ciliary neurotrophic factor (CNTF small peptide mimetic, Peptide 6 (P6, which was previously shown to exert its neuroprotective effect by modulating CNTF/JAK/STAT pathway and LIF signaling and by enhancing brain derived neurotrophic factor (BDNF expression. Similar neurotoxic effects and neuroinflammation were observed in young Wistar rats injected intracerebroventricularly with autism sera within hours after birth. The autism sera injected rats demonstrated developmental delay and deficits in social communication, interaction, and novelty. Both the neurobiological changes and the behavioral autistic phenotype were ameliorated by P6 treatment. These findings implicate the involvement of neurotrophic imbalance during early brain development in the pathophysiology of autism and a proof of principle of P6 as a potential therapeutic strategy for autism.

  17. Adeno-associated viral-mediated LARGE gene therapy rescues the muscular dystrophic phenotype in mouse models of dystroglycanopathy.

    Science.gov (United States)

    Yu, Miao; He, Yonglin; Wang, Kejian; Zhang, Peng; Zhang, Shengle; Hu, Huaiyu

    2013-03-01

    Dystroglycanopathies are a group of congenital muscular dystrophies (CMD) often caused by mutations in genes encoding glycosyltransferases that lead to hypoglycosylation of α-dystroglycan (α-DG) and reduce its extracellular matrix-binding activity. Overexpressing LARGE (formerly known as like-glycosyltransferase) generates an extracellular matrix-binding carbohydrate epitope in cells with CMD-causing mutations in not only LARGE but also other glycosyltransferases, including POMT1, POMGnT1, and fukutin, creating the possibilities of a one-for-all gene therapy. To determine the feasibility of LARGE gene therapy, a serotype 9 adeno-associated viral vector for overexpressing LARGE (AAV9-LARGE) was injected intracardially into newborns of two mouse models of CMD: the natural LARGE mutant Large(myd) mice and protein O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1) knockout mice. AAV9-LARGE virus treatment yielded partial restoration of α-DG glycosylation and ligand-binding activity. The muscular dystrophy phenotype in skeletal muscles was ameliorated as revealed by significantly reduced fibrosis, necrosis, and numbers of centrally located nuclei with improved motor function. These results indicate that LARGE overexpression in vivo by AAV9-mediated gene therapy is effective at restoring functional glycosylation of α-DG and rescuing the muscular dystrophy phenotype in deficiency of not only LARGE but also POMGnT1, providing evidence that in vivo LARGE gene therapy may be broadly useful in dystroglycanopathies. PMID:23379513

  18. The future for the Global Sea Level Observing System (GLOSS) Sea Level Data Rescue

    Science.gov (United States)

    Bradshaw, Elizabeth; Matthews, Andrew; Rickards, Lesley; Aarup, Thorkild

    2016-04-01

    Historical sea level data are rare and unrepeatable measurements with a number of applications in climate studies (sea level rise), oceanography (ocean currents, tides, surges), geodesy (national datum), geophysics and geology (coastal land movements) and other disciplines. However, long-term time series are concentrated in the northern hemisphere and there are no records at the Permanent Service for Mean Sea Level (PSMSL) global data bank longer than 100 years in the Arctic, Africa, South America or Antarctica. Data archaeology activities will help fill in the gaps in the global dataset and improve global sea level reconstruction. The Global Sea Level Observing System (GLOSS) is an international programme conducted under the auspices of the WMO-IOC Joint Technical Commission for Oceanography and Marine Meteorology. It was set up in 1985 to collect long-term tide gauge observations and to develop systems and standards "for ocean monitoring and flood warning purposes". At the GLOSS-GE-XIV Meeting in 2015, GLOSS agreed on a number of action items to be developed in the next two years. These were: 1. To explore mareogram digitisation applications, including NUNIEAU (more information available at: http://www.mediterranee.cerema.fr/logiciel-de-numerisation-des-enregistrements-r57.html) and other recent developments in scanning/digitisation software, such as IEDRO's Weather Wizards program, to see if they could be used via a browser. 2. To publicise sea level data archaeology and rescue by: • maintaining and regularly updating the Sea Level Data Archaeology page on the GLOSS website • strengthening links to the GLOSS data centres and data rescue organisations e.g. linking to IEDRO, ACRE, RDA • restarting the sea level data rescue blog with monthly posts. 3. Investigate sources of funding for data archaeology and rescue projects. 4. Propose "Guidelines" for rescuing sea level data. These action items will aid the discovery, scanning, digitising and quality control

  19. The testicular form of hormone-sensitive lipase HSLtes confers rescue of male infertility in HSL-deficient mice.

    Science.gov (United States)

    Vallet-Erdtmann, Virginie; Tavernier, Geneviève; Contreras, Juan Antonio; Mairal, Aline; Rieu, Cécile; Touzalin, Anne-Marie; Holm, Cecilia; Jégou, Bernard; Langin, Dominique

    2004-10-01

    Inactivation of the hormone-sensitive lipase gene (HSL) confers male sterility with a major defect in spermatogenesis. Several forms of HSL are expressed in testis. HSLtes mRNA and protein are found in early and elongated spermatids, respectively. The other forms are expressed in diploid germ cells and interstitial cells of the testis. To determine whether the absence of the testis-specific form of HSL, HSLtes, was responsible for the infertility in HSL-null mice, we generated transgenic mice expressing HSLtes under the control of its own promoter. The transgenic animals were crossed with HSL-null mice to produce mice deficient in HSL in nongonadal tissues but expressing HSLtes in haploid germ cells. Cholesteryl ester hydrolase activity was almost completely blunted in HSL-deficient testis. Mice with one allele of the transgene showed an increase in enzymatic activity and a small elevation in the production of spermatozoa. The few fertile hemizygous male mice produced litters of very small to small size. The presence of the two alleles led to a doubling in cholesteryl ester hydrolase activity, which represented 25% of the wild type values associated with a qualitatively normal spermatogenesis and a partial restoration of sperm reserves. The fertility of these mice was totally restored with normal litter sizes. In line with the importance of the esterase activity, HSLtes transgene expression reversed the cholesteryl ester accumulation observed in HSL-null mice. Therefore, expression of HSLtes and cognate cholesteryl ester hydrolase activity leads to a rescue of the infertility observed in HSL-deficient male mice. PMID:15292223

  20. Intraovarian Transplantation of Female Germline Stem Cells Rescue Ovarian Function in Chemotherapy-Injured Ovaries

    OpenAIRE

    Xiong, Jiaqiang; Lu, Zhiyong; Wu, Meng; Zhang, Jinjin; Cheng, Jing; Luo, Aiyue; Shen, Wei; Fang, Li; Zhou, Su; Wang, Shixuan

    2015-01-01

    Early menopause and infertility often occur in female cancer patients after chemotherapy (CTx). For these patients, oocyte/embryo cryopreservation or ovarian tissue cryopreservation is the current modality for fertility preservation. However, the above methods are limited in the long-term protection of ovarian function, especially for fertility preservation (very few females with cancer have achieved pregnancy with cryopreserved ovarian tissue or eggs until now). In addition, the above method...

  1. Rescue procedures in the major trauma of upper extremities – The role of the polish medical air rescue in the therapeutic process

    Directory of Open Access Journals (Sweden)

    Robert Gałązkowski

    2014-12-01

    Full Text Available Background: Due to the growing use of various types of industrial and agricultural machinery, occupational accidents are among the most serious ones and quite frequently result in the permanent posttraumatic disability of the injured person. In Poland, a replantation service has been operating since 2010. Each day, one out of six centres provides emergency replantation service accepting amputation calls from across the country. Patients qualified for replantation often need to be transported from places located even several hundred kilometres from the target hospital. Material and Methods: The analysis covered 174 Helicopter Emergency Medical Service (HEMS missions and 112 interhospital transports. The data were obtained as a result of a retrospective analysis of the air and medical documentation of 23 460 missions carried out by the Polish Medical Air Rescue (Samodzielny Publiczny Zakład Opieki Zdrowotnej Lotnicze Pogotowie Ratunkowe – SP ZOZ LPR aircrafts in the years 2011–2013. Results: In the period under study, the Polish Medical Air Rescue helicopters dressed 135 patients with upper extremity amputations at the scene and transported them to hospitals as part of HEMS missions. At the same time, SP ZOZ LPR aircrafts made 102 interhospital transports. Ninety patients were qualified for treatment in replantation service centres. The average air transport time was 76 min, while the total transport time was 172.3 min. With transport exceeding 300 km, the average time advantage over the ground transport was approximately 1.5 h. Conclusions: In justified cases, the use of helicopters and airplanes is an optimal method of transporting patients with the major trauma to upper extremities. Med. Pr. 2014;65(6:765–776

  2. Rescuing Epistemology

    OpenAIRE

    Nunes, João Arriscado

    2009-01-01

    Over the last three decades, the whole project of epistemology has been subjected to criticism and change. This process has been marked, successively, by the transfer of epistemic sovereignty to the “social” domain, by the rediscovery of ontology and by attention to constitutive normativity and the political implications of knowledge. Some have even suggested that epistemology should be abandoned altogether as a philosophical project. However, this process has been offset by a proposal for a ...

  3. Rescue in vitro maturation (IVM) of immature oocytes in stimulated cycles in women with low functional ovarian reserve (LFOR).

    Science.gov (United States)

    Lee, Ho-Joon; Barad, David H; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni-Tealdi, Emanuela; Wu, Yan-Guang; Gleicher, Norbert

    2016-04-01

    Rescue in vitro maturation (IVM) is currently not a routine procedure in association with in vitro fertilization (IVF). We compared in a prospectively cohort study of 10 patients with normal functional ovarian reserve (NFOR) and of 25 with low functional ovarian reserve (LFOR), defined by abnormally high FSH and/or abnormally low AMH levels), IVM dynamics of immature oocytes. Following controlled ovarian hyperstimulation in IVF cycles, only immature oocytes underwent rescue IVM (for up to 48 h). Oocyte maturation dynamics, fertilization rates, embryo development, and pregnancy rates were then compared between NFOR and LFOR patients. Though proportion of MI and GV oocytes reaching MII stages within 48 h and rate of maturation of MI oocytes did not differ, in women with LFOR significantly more GV oocytes reached MII stage within 24 h (30.4 vs. 66.9 %; P = 0.013), while fertilization rates and embryo generation numbers were similar between both groups. Rescue IVM, thus, produced 1.5 additional embryos for transfer in women with LFOR and 1.6 in patients with NFOR, a highly significant difference in relative improvement in available embryo numbers for LFOR (+60.0 %) and NFOR women (+16.5 %). Rescue IVM, thus, not only demonstrates different time dynamics between women with LFOR and NFOR but also disproportionate efficacy in improving available embryo numbers for transfer in favor of LFOR patients. 1/7 patients, who reached embryo transfer with only embryos produced via rescue IVF conceived and delivered, proving that rescue IVF in women with LFOR also improves pregnancy and delivery chances. Because of the small number of embryos LFOR patients produce, every additional embryo is of considerable potential clinical significance for them, suggesting that rescue IVM in women with LFOR should become routine practice. PMID:26419849

  4. The habitus of 'rescue' and its significance for implementation of rapid response systems in acute health care.

    Science.gov (United States)

    Mackintosh, Nicola; Humphrey, Charlotte; Sandall, Jane

    2014-11-01

    The need to focus on patient safety and improve the quality and consistency of medical care in acute hospital settings has been highlighted in a number of UK and international reports. When patients on a hospital ward become acutely unwell there is often a window of opportunity for staff, patients and relatives to contribute to the 'rescue' process by intervening in the trajectory of clinical deterioration. This paper explores the social and institutional processes associated with the practice of rescue, and implications for the implementation and effectiveness of rapid response systems (RRSs) within acute health care. An ethnographic case study was conducted in 2009 in two UK hospitals (focussing on the medical directorates in each organisation). Data collection involved 180 h of observation, 35 staff interviews (doctors, nurses, health care assistants and managers) and documentary review. Analysis was informed by Bourdieu's logic of practice and his relational concept of the 'field' of the general medical ward. Three themes illustrated the nature of rescue work within the field and collective rules which guided associated occupational distinction practices: (1) the 'dirty work' of vital sign recording and its distinction from diagnostic (higher order) interpretive work; (2) the moral order of legitimacy claims for additional help; and (3) professional deference and the selective managerial control of rescue work. The discourse of rescue provided a means of exercising greater control over clinical uncertainty. The acquisition of 'rescue capital' enabled the social positioning of health care assistants, nurses and doctors, and shaped use of the RRS on the wards. Boundary work, professional legitimation and jurisdictional claims defined the social practice of rescue, as clinical staff had to balance safety, professional and organisational concerns within the field. This paper offers a nuanced understanding of patient safety on the front-line, challenging notions of

  5. Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy

    International Nuclear Information System (INIS)

    total clinical response rate of 75.0%. None achieved a complete pathological response. MDR1 mRNA expression detected by RT-PCR was associated with the presence of invaded axillary nodes at surgery in 18/22 cases (81.8%), compared with 13/24 (54.2%) in the group with undetectable MDR1 expression. This difference was statistically significant (P < 0.05). LRP expression in more than 20% of tumor cells before any treatment was associated with axillary nodal metastasis after chemotherapy and rescue mastectomy in 17/23 cases, compared with 3/8 in nonexpressors. Again, this difference was highly significant (P < 0.01). LRP expression before treatment and MDR1 mRNA expression after treatment were significantly interrelated (P < 0.001), which might reflect the presence of chemoresistant clones liable to metastasize to the regional nodes. Persistence of previously detected MDR1-positivity after treatment (7/9 compared with 0/2 cases) was significantly associated with axillary node metastasis (P < 0.05). Finally, in a logistic regression multivariate model, histology other than ductal, a Ki67 labeling index of at least 20% and the combination of LRP and MDR1 positivity emerged as independent predictors of axillary node invasion at the time of rescue mastectomy. The expression of different genes involved in resistance to chemotherapy, both before and after treatment with neoadjuvant, is associated with the presence of axillary node invasion at rescue surgery in locally advanced breast cancer. This might reflect the presence of intrinsically resistant clones before any form of therapy, which persist after it, and could be helpful both for prognosis and for the choice of individual treatment

  6. Virulence in pigs of vPader10 rescued from an infectious cDNA clone of the CSFV strain Paderborn

    DEFF Research Database (Denmark)

    Friis, Martin Barfred; Nielsen, Jens; Uttenthal, Åse;

    The BAC clone, pBeloPader10, contains a complete cDNA of the CSFV strain Paderborn. Virus, named vPader10, was rescued from this construct by electroporation of RNA transcripts into porcine PK15 cells. To further study the characteristics of vPader10, we evaluated the virulence of this virus in...... vivo in pigs. An animal experiment was performed where three pigs were inoculated with vPader10 and housed in-contact with two non-inoculated pigs for 5 weeks. Following inoculation with vPader10, two out of three pigs displayed severe clinical signs of CSF from PID 14 that progressed until death of...

  7. Mortality in free range rescued wild animals of Shivalik Hills in Himachal Pradesh, India

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2012-02-01

    Full Text Available The present study was conducted on 143 free range wild animals of 12 different species rescued from different locations in Shivalik Hills since Jan 2004 to June 2011. Mortality was reported in 79.02% (113 of rescued wild animals. Mortality in Herbivores, Carnivores, Pheasants and Omnivores was 84.74% (50, 79.06% (34 72.72% (24 and 62.50% (05 respectively. Post mortem was conducted at field level to determine causes of mortality in all the 113 died wild animals. Necropsy findings revealed musculoskeletal injuries 68.14% (77, more specifically fractures 37.16% (42 and fatal trauma 30.97% (35 as most common cause of mortality in all the animals. On the other hand Cardiovascular and haemorrhagic shock constituted 11.50% (13 while septicemia were noted in 8.84% (10 of all the recorded causes of mortality in rescued animals. Mortality with other causes noticed in 11.50% cases is attributable to diagnosed causes including froathy bloat, tympany, intussusceptions, senility with associated lesions and unknown causes like infectious diseases or toxicosis without a clear symptomatology. The highest mortality was found in male herbivores 28.31% (32 followed by female carnivores 16.81% (19 and male pheasants 13.27% (15. Only 39.82% (45 mortality was observed in adult animals compared to juveniles 51.32% (58. Mortality in winter season 52.21 % (59 was higher than summer 33.62% (38 and rainy season 14.15% (16.

  8. Organization and implementation of medical rescue of mass casualties during earthquake

    Directory of Open Access Journals (Sweden)

    Yan-ling ZHANG

    2012-01-01

    Full Text Available Over the past century, there were more than 40 earthquakes greater than 7 magnitude occurred worldwide, 10 of which in China, which killed 600 thousand people accounting for 53% of global earthquake deaths. On May 12, 2008, an 8.0-magnitude earthquake occurred in Wenchuan, Sichuan Province, causing 69000 deaths, 18000 missings, and 370000 injuries. Among 10 thousand severe injuries, most were traumatic injuries, 74% of which were fracture. On April 14, 2010, a 7.1-magnitude earthquake occurred in Yushu, Qinghai Province. There were 2698 deaths, 270 missings and 11000 injuries. Among 3100 severe injuries, fracture accounted for 58.4%. After each earthquake, the Chinese Army Medical Services took actions and made quick response according to the law. They sent out elites with efficient command and scientific organization, fully participating in the medical rescue operations. After Wenchuan earthquake, 397 mobile medical service units and 7061 health workers were sent out. A total of 69000 people were treated, and 22000 cases of surgeries were performed. After Yushu earthquake, a total of 25 mobile medical service units and 2025 health workers were sent. They performed 1635 cases of surgeries with a miracle of "zero death" in mass earthquake casualties and altitude diseases in cold highlands. After each earthquake, injuries cured within 1 week accounted for 60% of the total, and patients evacuated accounted for 80% of the total, which owed to the effective first aid in site of Chinese Army Medical Service. They effectively played the role as the main force, making significant contributions for the final victory of earthquake relief. From the practice of medical rescue revelation after the two earthquakes, what Chinese Army Medical Services Services learned are: firstly, the theory of medical relief should be innovated; secondly, military and civilian organizations should be coordinated; thirdly, professional rescue force should be strengthened

  9. Dense 3D Map Construction for Indoor Search and Rescue

    DEFF Research Database (Denmark)

    Ellekilde, Lars-Peter; Huang, Shoudong; Miró, Jaime Valls;

    2007-01-01

    The main contribution of this paper is a new simultaneous localization and mapping  SLAM algorithm for building dense three-dimensional maps using information ac- quired from a range imager and a conventional camera, for robotic search and rescue in unstructured indoor environments. A key challenge...... in this scenario is that the robot moves in 6D and no odometry information is available. An extended information ?lter  EIF is used to estimate the state vector containing the sequence of camera poses and some selected 3D point features in the environment. Data association is performed using a...

  10. Based on A* and Q-Learning Search and Rescue Robot Navigation

    OpenAIRE

    Ruiyuan Fan; Xiaogang Ruan; Tao Pang; Ershen Wang

    2012-01-01

    For the search and rescue robot navigation in unknown environment, a bionic self-learning algorithm based on A* and Q-Learning is put forward. The algorithm utilizes the Growing Self-organizing Map (GSOM) to build the environment topology cognitive map. The heuristic search A* algorithm is used the global path planning. When the local environment changes, Q-Learning is used the local path planning. Thereby the robot can obtain the self-learning skill by studying and training like human or ani...

  11. An application of the MEMbrain training module: Pre-hospital rescue operation

    DEFF Research Database (Denmark)

    Andersen, V.

    1998-01-01

    A system for training in pre-hospital emergency management is being developed and the first version of a prototype has been completed. The training system fulfils the demands from the domain of hospital emergency planning centres and medical attendants concerning increased efficiency of rescue...... efforts. This includes enhanced first aid on site and improved overall co-ordination amongst the organisations involved in coping with emergency situations. The training system is based on the Multi-User System for Training Emergency Response (MUSTER) concept which is used for the training module in the...

  12. Heat Shock Protein 90AB1 and Hyperthermia Rescue Infectivity of HIV with Defective Cores

    OpenAIRE

    Joshi, Pheroze; Sloan, Barbara; Torbett, Bruce E.; Stoddart, Cheryl A.

    2012-01-01

    We previously showed that reduced infectivity of HIV with incompletely processed capsid-spacer protein 1 (CA-SP1) is rescued by cellular activation or increased expression of HSP90AB1, a member of the cytosolic heat shock protein 90 family. Here we show that HSP90AB1 is present in HIV virions and that HSP90AB1, but not nonfunctional mutated HSP90AB1E42A+D88A, restores infectivity to HIV with mutations in CA that alter core stability. Further, the CA mutants were hypersensitive to pharmacologi...

  13. In vitro maintenance, under slow-growth conditions, of oil palm germplasm obtained by embryo rescue

    Directory of Open Access Journals (Sweden)

    Julcéia Camillo

    2015-05-01

    Full Text Available The objective of this work was to evaluate the in vitro maintenance of oil palm (Elaeis guineensis and E. oleifera accessions under slow-growth conditions. Plants produced by embryo rescue were subject to 1/2MS culture medium supplemented with the carbohydrates sucrose, mannitol, and sorbitol at 1, 2, and 3% under 20 and 25±2ºC. After 12 months, the temperature of 20°C reduced plant growth. Sucrose is the most appropriate carbohydrate for maintaining the quality of the plants, whereas mannitol and sorbitol result in a reduced plant survival.

  14. Rescue of placental phenotype in a mechanistic model of Beckwith-Wiedemann syndrome

    Directory of Open Access Journals (Sweden)

    Higgins Michael J

    2010-05-01

    Full Text Available Abstract Background Several imprinted genes have been implicated in the process of placentation. The distal region of mouse chromosome 7 (Chr 7 contains at least ten imprinted genes, several of which are expressed from the maternal homologue in the placenta. The corresponding paternal alleles of these genes are silenced in cis by an incompletely understood mechanism involving the formation of a repressive nuclear compartment mediated by the long non-coding RNA Kcnq1ot1 initiated from imprinting centre 2 (IC2. However, it is unknown whether some maternally expressed genes are silenced on the paternal homologue via a Kcnq1ot1-independent mechanism. We have previously reported that maternal inheritance of a large truncation of Chr7 encompassing the entire IC2-regulated domain (DelTel7 allele leads to embryonic lethality at mid-gestation accompanied by severe placental abnormalities. Kcnq1ot1 expression can be abolished on the paternal chromosome by deleting IC2 (IC2KO allele. When the IC2KO mutation is paternally inherited, epigenetic silencing is lost in the region and the DelTel7 lethality is rescued in compound heterozygotes, leading to viable DelTel7/IC2KO mice. Results Considering the important functions of several IC2-regulated genes in placentation, we set out to determine whether these DelTel7/IC2KO rescued conceptuses develop normal placentae. We report no abnormalities with respect to the architecture and vasculature of the DelTel7/IC2KO rescued placentae. Imprinted expression of several of the IC2-regulated genes critical to placentation is also faithfully recapitulated in DelTel7/IC2KO placentae. Conclusion Taken together, our results demonstrate that all the distal chromosome 7 imprinted genes implicated in placental function are silenced by IC2 and Kcnq1ot1 on the paternal allele. Furthermore, our results demonstrate that the methylated maternal IC2 is not required for the regulation of nearby genes. The results show the potential for

  15. The Airtraq as a rescue airway device following failed direct laryngoscopy: a case series.

    LENUS (Irish Health Repository)

    Maharaj, C H

    2007-06-01

    We report the successful use of the Airtraq as a rescue device following failed direct laryngoscopy, in patients deemed at increased risk for difficult tracheal intubation. In a series of seven patients, repeated attempts at direct laryngoscopy with the Macintosh blade, and the use of manoeuvres to aid intubation, such as the gum elastic bougie placement, were unsuccessful. In contrast, with the Airtraq device, each patient\\'s trachea was successfully intubated on the first attempt. This report underlines the utility of the Airtraq device in these patients.

  16. Research of Tourism Rescue System based on Social-Local-Mobile

    Directory of Open Access Journals (Sweden)

    SHI Beiqi

    2013-08-01

    Full Text Available Tourism Rescue System(TRSis a key issue to ensure the success of tourism service.The development of our country′s TRS showed that tourists are usually in a moving state with the geographical position information during travel accident process.So it is necessary to construct TRS using Social-Local-Mobile technology.The paper has presented the detail of Social-Local-Mobile technology,and has analyzed the motivation and practical strategy of building TRS.

  17. Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1-/- phenotype and forms complexes with wildtype PS1 and nicastrin.

    Science.gov (United States)

    Brautigam, Hannah; Moreno, Cesar L; Steele, John W; Bogush, Alexey; Dickstein, Dara L; Kwok, John B J; Schofield, Peter R; Thinakaran, Gopal; Mathews, Paul M; Hof, Patrick R; Gandy, Sam; Ehrlich, Michelle E

    2015-01-01

    The presenilin 1 (PSEN1) L271V mutation causes early-onset familial Alzheimer's disease by disrupting the alternative splicing of the PSEN1 gene, producing some transcripts harboring the L271V point mutation and other transcripts lacking exon 8 (PS1(∆exon8)). We previously reported that PS1 L271V increased amyloid beta (Aβ) 42/40 ratios, while PS1(∆exon8) reduced Aβ42/40 ratios, indicating that the former and not the exon 8 deletion transcript is amyloidogenic. Also, PS1(∆exon8) did not rescue Aβ generation in PS1/2 double knockout cells indicating its identity as a severe loss-of-function splice form. PS1(∆exon8) is generated physiologically raising the possibility that we had identified the first physiological inactive PS1 isoform. We studied PS1(∆exon8) in vivo by crossing PS1(∆exon8) transgenics with either PS1-null or Dutch APP(E693Q) mice. As a control, we crossed APP(E693Q) with mice expressing a deletion in an adjacent exon (PS1(∆exon9)). PS1(∆exon8) did not rescue embryonic lethality or Notch-deficient phenotypes of PS1-null mice displaying severe loss of function in vivo. We also demonstrate that this splice form can interact with wildtype PS1 using cultured cells and co-immunoprecipitation (co-IP)/bimolecular fluorescence complementation. Further co-IP demonstrates that PS1(∆exon8) interacts with nicastrin, participating in the γ-secretase complex formation. These data support that catalytically inactive PS1(∆exon8) is generated physiologically and participates in protein-protein interactions. PMID:26608390

  18. Physiologically generated presenilin 1 lacking exon 8 fails to rescue brain PS1−/− phenotype and forms complexes with wildtype PS1 and nicastrin

    Science.gov (United States)

    Brautigam, Hannah; Moreno, Cesar L.; Steele, John W.; Bogush, Alexey; Dickstein, Dara L.; Kwok, John B.J.; Schofield, Peter R.; Thinakaran, Gopal; Mathews, Paul M.; Hof, Patrick R.; Gandy, Sam; Ehrlich, Michelle E.

    2015-01-01

    The presenilin 1 (PSEN1) L271V mutation causes early-onset familial Alzheimer’s disease by disrupting the alternative splicing of the PSEN1 gene, producing some transcripts harboring the L271V point mutation and other transcripts lacking exon 8 (PS1∆exon8). We previously reported that PS1 L271V increased amyloid beta (Aβ) 42/40 ratios, while PS1∆exon8 reduced Aβ42/40 ratios, indicating that the former and not the exon 8 deletion transcript is amyloidogenic. Also, PS1∆exon8 did not rescue Aβ generation in PS1/2 double knockout cells indicating its identity as a severe loss-of-function splice form. PS1∆exon8 is generated physiologically raising the possibility that we had identified the first physiological inactive PS1 isoform. We studied PS1∆exon8 in vivo by crossing PS1∆exon8 transgenics with either PS1-null or Dutch APPE693Q mice. As a control, we crossed APPE693Q with mice expressing a deletion in an adjacent exon (PS1∆exon9). PS1∆exon8 did not rescue embryonic lethality or Notch-deficient phenotypes of PS1-null mice displaying severe loss of function in vivo. We also demonstrate that this splice form can interact with wildtype PS1 using cultured cells and co-immunoprecipitation (co-IP)/bimolecular fluorescence complementation. Further co-IP demonstrates that PS1∆exon8 interacts with nicastrin, participating in the γ–secretase complex formation. These data support that catalytically inactive PS1∆exon8 is generated physiologically and participates in protein-protein interactions. PMID:26608390

  19. Impact of Job Stress on Consumer Satisfaction with Role of Mediating Variables (Employee Satisfaction and Employee Performance): A Study of Punjab Emergency Service (Rescue 1122) Sahiwal, Pakistan

    OpenAIRE

    Raja Irfan Sabir; Naeem Akhtar; Usman Zakir; Iram Nadeem; Asad Ur Rehman

    2014-01-01

    Rescue 1122 is playing a vital role in rescue services in Punjab. Rescue services basically upon employee?s efficiency. Low wages, extra working hours, fake and irrelevant phone calls are the causes of stress on employees and resultantly employee?s satisfaction impact on customer?s satisfaction. This study will investigate the impact of stress on employees and its impact on customer?s satisfaction and dissatisfaction. The researcher will use explanatory research and describe the phenomena of ...

  20. Development of a Search and Rescue Simulation to Study the Effects of Prolonged Isolation on Team Decision Making

    Science.gov (United States)

    Entin, Elliot E.; Kerrigan, Caroline; Serfaty, Daniel; Young, Philip

    1998-01-01

    The goals of this project were to identify and investigate aspects of team and individual decision-making and risk-taking behaviors hypothesized to be most affected by prolonged isolation. A key premise driving our research approach is that effects of stressors that impact individual and team cognitive processes in an isolated, confined, and hazardous environment will be projected onto the performance of a simulation task. To elicit and investigate these team behaviors we developed a search and rescue task concept as a scenario domain that would be relevant for isolated crews. We modified the Distributed Dynamic Decision-making (DDD) simulator, a platform that has been extensively used for empirical research in team processes and taskwork performance, to portray the features of a search and rescue scenario and present the task components incorporated into that scenario. The resulting software is called DD-Search and Rescue (Version 1.0). To support the use of the DDD-Search and Rescue simulator in isolated experiment settings, we wrote a player's manual for teaching team members to operate the simulator and play the scenario. We then developed a research design and experiment plan that would allow quantitative measures of individual and team decision making skills using the DDD-Search and Rescue simulator as the experiment platform. A description of these activities and the associated materials that were produced under this contract are contained in this report.

  1. Stereotypical Behaviors in Chimpanzees Rescued from the African Bushmeat and Pet Trade

    Directory of Open Access Journals (Sweden)

    Ashlynn Dube

    2012-12-01

    Full Text Available Many orphaned chimpanzees whose mothers are illegally killed for their meat (bushmeat in Africa are sold as pets or kept caged at hotels and businesses to attract tourists. As a result of being separated from their mothers and other chimpanzees at an early age, and spending years in impoverished captive conditions, some of these individuals engage in abnormal behaviors, including stereotypically scratching at their flesh and repetitively rocking back and forth. This paper presents case studies of Poco and Safari, two chimpanzees who were rescued by sanctuaries after living alone on display for humans at businesses for the first 7 to 8 years of their lives. Decades after their rescue, they still engage in stereotypical behaviors as a result of the psychological and physical trauma they endured early on. This paper combines data from in depth interviews with caregivers and direct observations of abnormal behaviors to assess psychological distress in captive-living chimpanzees. Our results highlight some lesser known harms of the bushmeat trade and the detrimental life-long consequences that keeping chimpanzees as “pets” can have on their mental health.

  2. Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Rana, Anil; Seinen, Erwin; Siudeja, Katarzyna; Muntendam, Remco; Srinivasan, Balaji; van der Want, Johannes J; Hayflick, Susan; Reijngoud, Dirk-Jan; Kayser, Oliver; Sibon, Ody C M

    2010-04-13

    Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. PMID:20351285

  3. Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

    Science.gov (United States)

    Rana, Anil; Seinen, Erwin; Siudeja, Katarzyna; Muntendam, Remco; Srinivasan, Balaji; van der Want, Johannes J.; Hayflick, Susan; Reijngoud, Dirk-Jan; Kayser, Oliver; Sibon, Ody C. M.

    2010-01-01

    Pantothenate kinase–associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. PMID:20351285

  4. An Operational Search and Rescue Model for the Norwegian Sea and the North Sea

    CERN Document Server

    Breivik, Øyvind; 10.1016/j.jmarsys.2007.02.010

    2011-01-01

    A new operational, ensemble-based search and rescue model for the Norwegian Sea and the North Sea is presented. The stochastic trajectory model computes the net motion of a range of search and rescue objects. A new, robust formulation for the relation between the wind and the motion of the drifting object (termed the leeway of the object) is employed. Empirically derived coefficients for 63 categories of search objects compiled by the US Coast Guard are ingested to estimate the leeway of the drifting objects. A Monte Carlo technique is employed to generate an ensemble that accounts for the uncertainties in forcing fields (wind and current), leeway drift properties, and the initial position of the search object. The ensemble yields an estimate of the time-evolving probability density function of the location of the search object, and its envelope defines the search area. Forcing fields from the operational oceanic and atmospheric forecast system of The Norwegian Meteorological Institute are used as input to th...

  5. Cardiovascular Automatic Feedback Control Instrument for Rescuing Critical Patients With Abnormal Blood Pressure

    Institute of Scientific and Technical Information of China (English)

    Ge Yuzhi; Wu Zhiting; Sheng Guotai; Li Gang

    2006-01-01

    Objectives Most medical instruments are designed for diagnosis purpose but very few for clinical treatment. Our research aim is to design and develop a cardiovascular automatic feedback control instrument (CAFCI) for rescuing the critical patients with abnormal blood pressure.Methods The CAFCI was designed on the basis of abundant clinical experiences and on successful mathematic modeling of our experimental data. The blood pressure, pulmonary capillary wedge pressure,and rates of heart beat were measured and inputted into a computer and drugs were chosen by a doctor through a user-friendly interface with the computer.The responses to medication were rapidly acquired and feed back to the computer by automatic detection system in a close-loop system. The data were refreshed every 7.5 sec in order to regulate the speed and dosage of the medications that were given. Results The experimental results with ten dogs showed that the CAFCI system took samples promptly and accurately so that the targeted blood pressure could be reached reliably based on our input parameters and our designing requirements. Conclusions Since the dependability and accuracy of the CAFCI system are much superior to that of the traditional method, its clinical application to rescue the critical patient warrants evaluation in the future.

  6. Ventilator Strategies and Rescue Therapies for Management of Acute Respiratory Failure in the Emergency Department.

    Science.gov (United States)

    Mosier, Jarrod M; Hypes, Cameron; Joshi, Raj; Whitmore, Sage; Parthasarathy, Sairam; Cairns, Charles B

    2015-11-01

    Acute respiratory failure is commonly encountered in the emergency department (ED), and early treatment can have effects on long-term outcome. Noninvasive ventilation is commonly used for patients with respiratory failure and has been demonstrated to improve outcomes in acute exacerbations of chronic obstructive lung disease and congestive heart failure, but should be used carefully, if at all, in the management of asthma, pneumonia, and acute respiratory distress syndrome. Lung-protective tidal volumes should be used for all patients receiving mechanical ventilation, and FiO2 should be reduced after intubation to achieve a goal of less than 60%. For refractory hypoxemia, new rescue therapies have emerged to help improve the oxygenation, and in some cases mortality, and should be considered in ED patients when necessary, as deferring until ICU admission may be deleterious. This review article summarizes the pathophysiology of acute respiratory failure, management options, and rescue therapies including airway pressure release ventilation, continuous neuromuscular blockade, inhaled nitric oxide, and extracorporeal membrane oxygenation. PMID:26014437

  7. Portable mixed abrasive water jet equipment for rescue in high gas mine shaft

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui; DU Chang-long; XU Rui; ZHAO Jing

    2011-01-01

    In order to rescue a trapped miner and clean out roadways quickly in a high gas mine shaft after a mining mishap, a special portable cold-cutting equipment is needed, the main technology parameters were calculated according to the advanced cold-cutting technology of high pressure abrasive water jet and the portable mixed abrasive water jet equipment (PAWE) was designed to meet the needs of emergency rescue in high gas mine shafts. Tested the PAWE in a high gas environment, and the result shows that the maximum cutting depth of solid iron pipe is 18 mm and the recoilforce of the sprayer is 28.9 N under the conditions that actual cutting pressure is 29 MPa, starting target distance is 10 mm, cutting speed is 180 mm/min and concentration of abrasive is 32%. The course of the experiment in the high gas environment was smooth and continuous, without any explosion. The PAWE is easy to move and operate, but the nozzle which was worn badly in the sprayer should be changed every 8 minutes.

  8. Pain, health perception and sleep: impact on the quality of life of firefighters/rescue professionals

    Directory of Open Access Journals (Sweden)

    Rafael Silva Marconato

    2015-12-01

    Full Text Available Objective: to evaluate the quality of life of firefighters and rescue professionals, and characterize their socio-demographic, health, work and lifestyle profile. Methods: cross-sectional study that used a socio-demographic, lifestyle, health, work data questionnaire and the WHOQOL-BREF quality of life aspects, in Fire Department bases, Civil Air Patrol Group of the Military Police and Rescue Group of Emergency Services. Results: ninety professionals participated in this study - 71 firefighters, 9 nurses, 7 doctors and 3 flight crew members. The average age of the group was 36.4 ± 7.8 years; they worked about 63.7 hours per week; 20.2% reported pain in the last week and 72.7% had body mass index above 25 kg/m2. The average of the WHOQOL-BREF domains was: physical (74.6, psychological (75.2, social (76.5 and environmental (58.7. Significant association was found (Mann-Whitney test and Spearman correlation between the WHOQOL-BREF domains and pain in the past six months, in the last week, health perception, job satisfaction, hours of sleep, domestic tasks and study. Conclusion: the main factors related to quality of life were presence of pain, health perception, sleep and domestic activity.

  9. FTY720, a new immunosuppressant,as rescue therapy in mouse cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    WANGMing-Hui; VitaliyMILEKHIN; ZHANGHua; HUANGHong-Zheng

    2003-01-01

    AIM: FTY720 is a new synthetic immunosuppressive agent which has a unique mechanism of action and induceslong-term graft acceptance in rat and dog allotransplantation as prophylactic administration. The present studyinvestigated whether FTY720 was able to rescue ongoing acute rejection of solid organ transplants in a mouseheterotopic cardiac transplantation model. METHODS: BALB/c hearts were heterotopically grafted in C57BL/6mice. FTY720, at the doses of 0.5, 1, and 5 mg.kg-l.d-1 or vehicle was administered to recipients once daily by oralgavage from d 3 to d 7 after transplantation. Histological changes of grafts, and the lymphocyte number in theperipheral blood and the peripheral lymph nodes were determined on d 5 after transplantation. RESULTS: FTY720prolonged the median graft survival time dose-dependently and significantly. Histological evaluation revealed lesslymphocytic infiltration in cardiac allografts treated with FTY720. Moreover, FTY720 remarkably lowered thenumber of peripheral blood lymphocytes but significantly increased the lymphocyte number in the mesentericlymph nodes and the peripheral lymph nodes. CONCLUSION: FTY720 used orally as rescue therapy significantlyextended allograft survival in mouse heterotopic cardiac transplantation.

  10. A retrspective study of rescuing severe open craniocerebral injuries caused by traffic accidents

    Institute of Scientific and Technical Information of China (English)

    陈长才; 宁可; 等

    1999-01-01

    Objective:To investigate the rescuing principles of severe open craniocerebral injuries caused by traffic accidents.Methods:A retrospective study was performed for 36 patients admitted to our hospital from January 1986 to December 1995,who suffered from severe open craniocerebral injuries in traffic accidents.Results:These 36 cases occupied 52.10% of all the severe open craniocerebral injuries during the same period.The clinical features included confusion of consciousness, extensive cerebral contusion and laceration,severe contamination of the wound,high incidence of intracranial hematoma and multiple system injuries.Nineteen patients.(63.34%)ecovered normal neurological function,7 were (23.33%)mild disabled,4(13.33%)severe disabled,2(5.56%) vegetative survival,and 4(11.11%)dead.Conclusions:The main principles of salvage should emphasize the importance of emergent prehospital rescue,and be transfered to a specialized hospital as soon as possible.Postoperative complications included severe brain edema,intracerebral infection,and pneumonia,Debriding thoroughly at early stage and treating complications effectively would lower the rate of mortality and disability.

  11. La Serra d'Almos (Tarragona): an example of phenological data rescue and preservation in Catalonia

    Science.gov (United States)

    Busto, Montserrat; Cunillera, Jordi; de Yzaguirre, Xavi; Borrell, Josep

    2016-04-01

    The interruption of important phenological series and the progressive disappearance of phenological observations in Catalonia led the Meteorological Service of Catalonia (SMC) to design and impulse a new phenological network promoted by the Climate Change Unit of this Met Service. The "Fenocat" network was born in March 2013, and currently has around fifty observers distributed throughout Catalonia that observe plants, birds and butterflies. We are providing data from different plant phenophases to PEP725 database. Besides this new phenological network (Fenocat), one of the aims of SMC is to rescue and preserve historical data from different observation points in Catalonia. We show in this poster the example of rescue and preservation of phenological data from la Serra d'Almos (in Tivissa, near Tarragona, Catalonia, NE Iberian Peninsula), an observation series that began in 1973. After digitalization process and quality control tasks, we show preliminary results of this phenological series, and we compare them with those of similar European series. We show the evolution trends for different observed species, such as almond tree (Prunus dulcis), hazel (Corylus avellana), plum (Prunus domestica), olive tree (Olea europea), apple tree (Malus domestica) or vineyard (Vitis vinifera).

  12. The theoretical research on localization using improved particle filter for mine rescue robot in unknown underground space

    Institute of Scientific and Technical Information of China (English)

    MA Hong-wei; LI Xiao-peng

    2008-01-01

    The localization for mine rescue robot in unknown space of coal mine emer-gency was researched, basing on the requirement of mine rescue robot localization whichenters the scene of the coal mine accident, unknown circumstance, the unstructured,non-Gaussian and nonlinear work-space for robot works. The localization using particlefilter was proposed to which is applied in mine rescue robot in unknown under-groundspace. Meanwhile, focusing on severe particle sample degeneracy in the primary particlefilter, an improved particle filter was proposed to reinforce the stability of particle filter. Be-ing compared with localization using extended Kalman filter through simulation experiment, the localization using particle filter is proved to have more locating accuracy in unknownunderground space and better computational real-time ability, which solves the pre-local-ization problem of robot underground.

  13. EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair

    Science.gov (United States)

    Wu, Yuehan; Lee, Suk-Hee; Williamson, Elizabeth A.; Reinert, Brian L.; Cho, Ju Hwan; Xia, Fen; Jaiswal, Aruna Shanker; Srinivasan, Gayathri; Patel, Bhavita; Brantley, Alexis; Zhou, Daohong; Shao, Lijian; Pathak, Rupak; Hauer-Jensen, Martin; Singh, Sudha; Kong, Kimi; Wu, Xaiohua; Kim, Hyun-Suk; Beissbarth, Timothy; Gaedcke, Jochen; Burma, Sandeep; Nickoloff, Jac A.; Hromas, Robert A.

    2015-01-01

    Replication fork stalling and collapse is a major source of genome instability leading to neoplastic transformation or cell death. Such stressed replication forks can be conservatively repaired and restarted using homologous recombination (HR) or non-conservatively repaired using micro-homology mediated end joining (MMEJ). HR repair of stressed forks is initiated by 5’ end resection near the fork junction, which permits 3’ single strand invasion of a homologous template for fork restart. This 5’ end resection also prevents classical non-homologous end-joining (cNHEJ), a competing pathway for DNA double-strand break (DSB) repair. Unopposed NHEJ can cause genome instability during replication stress by abnormally fusing free double strand ends that occur as unstable replication fork repair intermediates. We show here that the previously uncharacterized Exonuclease/Endonuclease/Phosphatase Domain-1 (EEPD1) protein is required for initiating repair and restart of stalled forks. EEPD1 is recruited to stalled forks, enhances 5’ DNA end resection, and promotes restart of stalled forks. Interestingly, EEPD1 directs DSB repair away from cNHEJ, and also away from MMEJ, which requires limited end resection for initiation. EEPD1 is also required for proper ATR and CHK1 phosphorylation, and formation of gamma-H2AX, RAD51 and phospho-RPA32 foci. Consistent with a direct role in stalled replication fork cleavage, EEPD1 is a 5’ overhang nuclease in an obligate complex with the end resection nuclease Exo1 and BLM. EEPD1 depletion causes nuclear and cytogenetic defects, which are made worse by replication stress. Depleting 53BP1, which slows cNHEJ, fully rescues the nuclear and cytogenetic abnormalities seen with EEPD1 depletion. These data demonstrate that genome stability during replication stress is maintained by EEPD1, which initiates HR and inhibits cNHEJ and MMEJ. PMID:26684013

  14. Analysis of dose-incidence relationships for marrow failure in different species, in terms of radiosensitivity of tissue-rescuing units

    International Nuclear Information System (INIS)

    The analysis of 68 published sets of dose-incidence data for marrow failure in different species, using a double-log mortality function, indicates: (a) There is more heterogeneity, i.e. greater sums-of-squares per degree of freedom, within the data sets for mouse than for larger species (monkey, dog, sheep, goat, pig). (b) For mice the curves for acute doses are characterized by a D0 of about 100 cGy for tissue-rescuing units (or target cells), which are depleted at most to about 3 x 10(-4) at LD50. (c) Larger species are much less tolerant to target-cell depletion, the corresponding level being consistently in the range of 10(-2)-10(-3) at LD50. Also, the D0 is often lower (approximately 55 cGy), which is compatible in the dog with such a value for hemopoietic progenitor cells. (d) With larger species there is an unexpected reduction in heterogeneity when the dose rate is lower, which gives a D0 lower than expected and a higher extrapolate. It is concluded that the position and slope of the dose-incidence curves are compatible with interpretations based primarily on target-cell number and survival characteristics, modified by additional heterogeneity factors

  15. Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats.

    Science.gov (United States)

    Liao, S-J; Gong, Q; Chen, X-R; Ye, L-X; Ding, Q; Zeng, J-S; Yu, J

    2013-02-12

    Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the

  16. Intergenomic arms races: detection of a nuclear rescue gene of male-killing in a ladybird.

    Directory of Open Access Journals (Sweden)

    Tamsin M O Majerus

    Full Text Available Many species of arthropod are infected by deleterious inherited micro-organisms. Typically these micro-organisms are inherited maternally. Consequently, some, particularly bacteria of the genus Wolbachia, employ a variety of strategies that favour female over male hosts. These strategies include feminisation, induction of parthenogenesis and male-killing. These strategies result in female biased sex ratios in host populations, which lead to selection for host factors that promote male production. In addition, the intra-genomic conflict produced by the difference in transmission of these cytoplasmic endosymbionts and nuclear factors will impose a pressure favouring nuclear factors that suppress the effects of the symbiont. During investigations of the diversity of male-killing bacteria in ladybirds (Coccinellidae, unexpected patterns of vertical transmission of a newly discovered male-killing taxon were observed in the ladybird Cheilomenes sexmaculata. Initial analysis suggested that the expression of the bacterial male-killing trait varies according to the male(s a female has mated with. By swapping males between females, a male influence on the expression of the male-killing trait was confirmed. Experiments were then performed to determine the nature of the interaction. These studies showed that a single dominant allele, which rescues male progeny of infected females from the pathological effect of the male-killer, exists in this species. The gene shows typical Mendelian autosomal inheritance and is expressed irrespective of the parent from which it is inherited. Presence of the rescue gene in either parent does not significantly affect the inheritance of the symbiont. We conclude that C. sexmaculata is host to a male-killing gamma-proteobacterium. Further, this beetle is polymorphic for a nuclear gene, the dominant allele of which rescues infected males from the pathogenic effects of the male-killing agent. These findings represent the first

  17. A simulated avalanche search and rescue mission induces temporary physiological and behavioural changes in military dogs.

    Science.gov (United States)

    Diverio, Silvana; Barbato, Olimpia; Cavallina, Roberta; Guelfi, Gabriella; Iaboni, Martina; Zasso, Renato; Di Mari, Walter; Santoro, Michele Matteo; Knowles, Toby G

    2016-09-01

    Saving human lives is of paramount importance in avalanche rescue missions. Avalanche military dogs represent an invaluable resource in these operations. However, their performance can be influenced by several environmental, social and transport challenges. If too severe, these are likely to activate a range of responses to stress, which might put at risk the dogs' welfare. The aim of this study was to assess the physiological and behavioural responses of a group of military dogs to a Simulated Avalanche Search and Rescue mission (SASR). Seventeen avalanche dogs from the Italian Military Force Guardia di Finanza (SAGF dogs) were monitored during a simulated search for a buried operator in an artificial avalanche area (SASR). Heart rate (HR), body temperature (RBT) and blood samples were collected at rest the day before the trial (T0), immediately after helicopter transport at the onset of the SASR (T1), after the discovery of the buried operator (T2) and 2h later (T3). Heart rate (HR), rectal body temperature (RBT), cortisol, aspartate aminotransferase (AST), creatine kinase (CK), non-esterified fatty acids (NEFA) and lactate dehydrogenase (LDH) were measured. During the search mission the behaviour of each SAGF dog was measured by focal animal sampling and qualitatively assessed by its handler and two observers. Inter-rater agreement was evaluated. Snow and environmental variables were also measured. All dogs successfully completed their search for the buried, simulated victim within 10min. The SASR was shown to exert significant increases on RBT, NEFA and cortisol (Pstress probably induced by the addition of factors such as helicopter transport, disembarking, and the search and rescue exercise. However, changes were moderate and limited over time, progressively decreasing with complete recovery at T3 except for sera cortisol that showed a slightly slower decline. More time walking within the search was related to lower RBT, conversely to walking. Standing still

  18. Opioid Education and Nasal Naloxone Rescue Kits in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Dwyer, Kristin

    2015-05-01

    Full Text Available Introduction: Emergency departments (EDs may be high-yield venues to address opioid deaths with education on both overdose prevention and appropriate actions in a witnessed overdose. In addition, the ED has the potential to equip patients with nasal naloxone kits as part of this effort. We evaluated the feasibility of an ED-based overdose prevention program and described the overdose risk knowledge, opioid use, overdoses, and overdose responses among participants who received overdose education and naloxone rescue kits (OEN and participants who received overdose education only (OE. Methods: Program participants were surveyed by telephone after their ED visit about their substance use, overdose risk knowledge, history of witnessed and personal overdoses, and actions in a witnessed overdose including use of naloxone. Results: A total of 415 ED patients received OE or OEN between January 1, 2011 and February 28, 2012. Among those, 51 (12% completed the survey; 37 (73% of those received a naloxone kit, and 14 (27% received OE only. Past 30-day opioid use was reported by 35% OEN and 36% OE, and an overdose was reported by 19% OEN and 29% OE. Among 53% (27/51 of participants who witnessed another individual experiencing an overdose, 95% OEN and 88% OE stayed with victim, 74% OEN and 38% OE called 911, 26% OEN and 25% OE performed rescue breathing, and 32% OEN (n=6 used a naloxone kit to reverse the overdose. We did not detect statistically significant differences between OEN and OE-only groups in opioid use, overdose or response to a witnessed overdose. Conclusion: This is the first study to demonstrate the feasibility of ED-based opioid overdose prevention education and naloxone distribution to trained laypersons, patients and their social network. The program reached a high-risk population that commonly witnessed overdoses and that called for help and used naloxone, when available, to rescue people. While the study was retrospective with a low

  19. Stem cell transplantation for neuroblastoma

    OpenAIRE

    Fish, JD; Grupp, SA

    2007-01-01

    High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to...

  20. SITE EVALUATION OF SOIL AMENDMENT TECHNOLOGIES AT THE CROOKSVILLE/ROSEVILLE POTTERY AREA OF CONCERN - STAR ORGANICS SOIL RESCUE INNOVATIVE TECHNOLOGY EVALUATION REPORT (ITER)

    Science.gov (United States)

    Star Organics, L.L.C., of Dallas, Texas (Star Organics) has developed Soil Rescue to treat soil contaminated with metals. Star Organics claims that Soil Rescue forms metal complexes that immobilize toxic metals, thereby reducing the risk to human health and the environment. The ...

  1. 面向紧急救援的搜救装备产品设计人性化考量%Considerations of Search and Rescue Equipment Product Humanized Design for Emergency Rescue

    Institute of Scientific and Technical Information of China (English)

    钱洪伟

    2015-01-01

    In this paper, the humanized product design preliminary definition of the concept, design, product design, humanization and search and rescue equipment product design humanization, etc.; Architecture of the search and rescue equipment product design problem: the logic of human interpretation interpretation of search and rescue equipment product design humanized nature, characteristics and functions; Based on dynamicexpounds “technology” , build the implementing mechanism of search and rescue equipment humanized product design; And proved by actual case. Studies have shown that the emergency rescue equipment in the product design process is integrated into the human factors, such as efficiency, security, risk factors, directly affect the rescue equipment when using relief effect; Product design if you don ’t consider modularity, removable, etc, in the event of accident, how to product of involved has been put into use forcible entry directly affect the relief progress; This study has important theoretical significance for deepening the research on design philosophy, to guide the search and rescue equipment humanized product design has strong practical significance.%本文对产品设计人性化的相关概念进行了初步的界定:设计、产品设计、人性化以及搜救装备产品设计人性化等;架构了搜救装备产品设计人性化的逻辑阐释问题:诠释了搜救装备产品设计人性化的本质;基于“技术动态过程论“思想,构建了搜救装备产品设计人性化的实现机制。研究表明:应急搜救装备在产品设计环节是否融入人性化因素,如工效、安全风险因素,直接影响救援装备使用时的救灾效果;产品设计时如果不考虑模块化、可拆卸等功能,一旦发生事故,如何对所涉已投入使用的产品进行破拆都直接影响救灾进度。本研究对于深化设计哲学研究具有重要的理论意义,对于引导搜救装备产品设

  2. Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

    International Nuclear Information System (INIS)

    Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy

  3. Isolation, Genome Phylogenetic Analysis and In vitro Rescue of a Newly Emerging Porcine Circovirus Type 2

    Directory of Open Access Journals (Sweden)

    Weijuan Zhu and Xiaofeng Ren*

    2012-05-01

    Full Text Available Porcine circovirus type 2 (PCV2 is the major causative agent of post-weaning multisystemic wasting syndrome (PMWS. Infection by PCV2 may cause heavy losses in pig industry. In this study, we report the isolation of a newly emerging PCV2 from northeastern China. The complete genome of the PCV2 isolate named PCV2-LJR contains 1766 nucleotides and was compared with reference sequences published in GenBank followed by topology analysis of the resulting phylogenetic tree. The data indicated that the prevalent PCV2 isolates in the northeastern China had close relationship, although various genotypes of PCV2 existed. In addition, by gene recombination and transfection techniques, the PCV2 infectious clone was achieved and was able to rescue virus in vitro determined by indirect immunofluorescence assay and PCR. The obtained biological materials may be used for biological characterization of PCV2.

  4. Based on A* and Q-Learning Search and Rescue Robot Navigation

    Directory of Open Access Journals (Sweden)

    Ruiyuan Fan

    2012-11-01

    Full Text Available For the search and rescue robot navigation in unknown environment, a bionic self-learning algorithm based on A* and Q-Learning is put forward. The algorithm utilizes the Growing Self-organizing Map (GSOM to build the environment topology cognitive map. The heuristic search A* algorithm is used the global path planning. When the local environment changes, Q-Learning is used the local path planning. Thereby the robot can obtain the self-learning skill by studying and training like human or animal, and looks for a free path from the initial state to the target state in unknown environment. The theory proves the validity of the method. The simulation result shows the robot obtains the navigation capability.

  5. Research on Centroid Position for Stairs Climbing Stability of Search and Rescue Robot

    Directory of Open Access Journals (Sweden)

    Yan Guo

    2011-01-01

    Full Text Available This paper represents the relationship between the stability of stairs climbing and the centroid position of the search and rescue robot. The robot system is considered as a mass point-plane model and the kinematics features are analyzed to find the relationship between centroid position and the maximal pitch angle of stairs the robot could climb up. A computable function about this relationship is given in this paper. During the stairs climbing, there is a maximal stability-keeping angle depends on the centroid position and the pitch angle of stairs, and the numerical formula is developed about the relationship between the maximal stability-keeping angle and the centroid position and pitch angle of stairs. The experiment demonstrates the trustworthy and correction of the method in the paper.

  6. Cracking the humanitarian logistic coordination challenge: lessons from the urban search and rescue community.

    Science.gov (United States)

    Tatham, Peter; Spens, Karen

    2016-04-01

    The challenges of achieving successful inter-agency logistic coordination in preparing for and responding to natural disasters and complex emergencies are both well understood and well documented. However, although many of these challenges remain unresolved, the literature reveals that the organisations that form the urban search and rescue (USAR) community have attained a high level of coherence and interoperability that results in a highly efficient and effective response. Therefore, this paper uses the idea of 'borrowing' from other fields as it explores how the processes and procedures used by the USAR community might be applied to improve humanitarian logistic operations. The paper analyses the USAR model and explores how the resultant challenges might be addressed in a humanitarian logistic context. The paper recommends that further research be undertaken in order to develop a modified USAR model that could be operationalised by the international community of humanitarian logisticians. PMID:26283578

  7. A Multirobot Path-Planning Strategy for Autonomous Wilderness Search and Rescue.

    Science.gov (United States)

    Macwan, Ashish; Vilela, Julio; Nejat, Goldie; Benhabib, Beno

    2015-09-01

    This paper presents a novel strategy for the on-line planning of optimal motion-paths for a team of autonomous ground robots engaged in wilderness search and rescue (WiSAR). The proposed strategy, which forms part of an overall multirobot coordination (MRC) methodology, addresses the dynamic nature of WiSAR by: 1) planning initial, time-optimal, and piecewise polynomial paths for all robots; 2) implementing and regularly evaluating the optimality of the paths through a set of checks that gauge feasibility of path-completion within the available time; and 3) replanning paths, on-line, whenever deemed necessary. The fundamental principle of maintaining the optimal deployment of the robots throughout the search guides the MRC methodology. The proposed path-planning strategy is illustrated through a simulated realistic WiSAR example, and compared to an alternative, nonprobabilistic approach. PMID:25376050

  8. Encoded packet-Assisted Rescue Approach to Reliable Unicast in Wireless Networks

    CERN Document Server

    Zhou, Zhiheng; Wang, Xing; Tan, Yuanquan

    2010-01-01

    Recently, there has been a growing interest of using network coding to support reliable unicast over an error-prone channel. However, previous network coding schemes focused only on native packets and ignored the role of encoded packets. In this paper, we develop an efficient retransmission approach with network coding method, namely Encoded packet-Assisted Rescue (EAR), which is able to overcome this limitation. Using the proposed network coding approach, clients store the overheard encoded packets and report to the sender. And then, when the sender makes coding decisions, it not only considers native packets, but also takes account of encoded packets. In this way, more coding opportunities are emerged, i.e. more packets can be mixed together, resulting in improving the retransmission efficiency. Moreover, theoretical analysis and simulation results show that comparing with the existing schemes, our schemes can greatly reduce the total number of retransmissions.

  9. FIRE, FLOOD AND ICE: SEARCH AND RESCUE MISSIONS OF THE SOUTH AFRICAN AIR FORCE

    Directory of Open Access Journals (Sweden)

    Lindelwa Simphiwe Mnyandu

    2012-02-01

    Full Text Available Between the end of 1999 and the early months of the year 2000, the south western parts of South Africa (SA were subjected to raging infernos that saw a lot of commercial wine farms as well as tourist spots almost irreparably ravaged. With volunteers and rescue personnel still gasping for fresh breath another disaster, in the form of torrential rains, struck the impoverished country of Mozambique and the north western parts of SA. The attendant floods did not only cripple agriculture but also drowned people and livestock alike. With them, also came the first "treebirth" in this new millennium (if not in the history of mankind. In both catastrophes, the men and women of the South African Air Force (SAAF, as well as thousands of other volunteers, worked tirelessly and unselfishly in efforts to save endangered lives and property and to bring a sense of normality in otherwise tragic circumstances.

  10. Defects and rescue of the minor salivary glands in Eda pathway mutants.

    Science.gov (United States)

    Wells, K L; Mou, C; Headon, D J; Tucker, A S

    2011-01-15

    Despite their importance to oral health, the mechanisms of minor salivary gland (SG) development are largely unexplored. Here we present in vivo and in vitro analyses of developing minor SGs in wild type and mutant mice. Eda, Shh and Fgf signalling pathway genes are expressed in these glands from an early stage of development. Developing minor SGs are absent in Eda pathway mutant embryos, and these mice exhibit a dysplastic circumvallate papilla with disrupted Shh expression. Supplementation of Eda pathway mutant minor SG explants with recombinant EDA rescues minor SG induction. Supplementation with Fgf8 or Shh, previously reported targets of Eda signalling, leads to induction of gland like structures in a few cases, but these fail to develop into minor SGs. PMID:20969842

  11. Thermal requirements for surviving a mass rescue incident in the Arctic: project update

    Energy Technology Data Exchange (ETDEWEB)

    Boileau, Renee [National Research Council Canada: Institute for Ocean Technology, St. John' s, Newfoundland and Labrador (Canada)], email: renee.boileau@nrc-cnrc.gc.ca; DuCharme, Michel B. [Defence Research and Development Canada, Quebec, Quebec (Canada)], email: michel.ducharme@drdc-rddc.gc.ca.gc.ca; Cheung, Stephen [Brock University Department of Physical Education and Kinesiology, St. Catherines, Ontario (Canada)], email: stephen.cheung@brocku.ca; Mak, Lawrence [National Research Council Canada: Institute for Ocean Technology St. John' s, Newfoundland and Labrador (Canada)], email: lawrence.mak@nrc-cnrc.gc.ca

    2010-07-01

    Recently the number of tourists travelling though the Arctic has risen to over 1.5 million per year, increasing the risk of accidents in these extreme conditions. With such harsh conditions, it could take several days for the rescue to arrive on site; however there are no standards specifying the thermal insulation properties that equipment should have. The aim of this paper is to assess the thermal protection afforded by the equipment available and to assess human endurance. A 3 year study was carried out with experiments being performed in simulated Arctic conditions. This study is intended to assess the likelihood of survival for victims in the Arctic with the use of equipment currently available and to identify the principal risks. Subsequent to this assessment, survival prediction tools are expected to be improved based upon the knowledge gained in this study and recommendations made for better equipment to improve the likelihood of survival in accidents in the Arctic Seas.

  12. A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

    Science.gov (United States)

    Tosco, A; De Gregorio, F; Esposito, S; De Stefano, D; Sana, I; Ferrari, E; Sepe, A; Salvadori, L; Buonpensiero, P; Di Pasqua, A; Grassia, R; Leone, C A; Guido, S; De Rosa, G; Lusa, S; Bona, G; Stoll, G; Maiuri, M C; Mehta, A; Kroemer, G; Maiuri, L; Raia, V

    2016-08-01

    We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (Ptreatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment. PMID:27035618

  13. Spontaneous tumor development in bone marrow-rescued DNA-PKcs(3A/3A) mice due to dysfunction of telomere leading strand deprotection.

    Science.gov (United States)

    Zhang, S; Matsunaga, S; Lin, Y-F; Sishc, B; Shang, Z; Sui, J; Shih, H-Y; Zhao, Y; Foreman, O; Story, M D; Chen, D J; Chen, B P C

    2016-07-28

    Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at the Thr2609 cluster is essential for its complete function in DNA repair and tissue stem cell homeostasis. This phenomenon is demonstrated by congenital bone marrow failure occurring in DNA-PKcs(3A/3A) mutant mice, which require bone marrow transplantation (BMT) to prevent early mortality. Surprisingly, an increased incidence of spontaneous tumors, especially skin cancer, was observed in adult BMT-rescued DNA-PKcs(3A/3A) mice. Upon further investigation, we found that spontaneous γH2AX foci occurred in DNA-PKcs(3A/3A) skin biopsies and primary keratinocytes and that these foci overlapped with telomeres during mitosis, indicating impairment of telomere replication and maturation. Consistently, we observed significantly elevated frequencies of telomere fusion events in DNA-PKcs(3A/3A) cells as compared with wild-type and DNA-PKcs-knockout cells. In addition, a previously identified DNA-PKcs Thr2609Pro mutation, found in breast cancer, also induces a similar impairment of telomere leading-end maturation. Taken together, our current analyses indicate that the functional DNA-PKcs T2609 cluster is required to facilitate telomere leading strand maturation and prevention of genomic instability and cancer development. PMID:26616856

  14. Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and life span defects in the tafazzin mutant: implications for Barth syndrome.

    Science.gov (United States)

    Ye, Cunqi; Lou, Wenjia; Li, Yiran; Chatzispyrou, Iliana A; Hüttemann, Maik; Lee, Icksoo; Houtkooper, Riekelt H; Vaz, Frédéric M; Chen, Shuliang; Greenberg, Miriam L

    2014-02-01

    Cardiolipin (CL) that is synthesized de novo is deacylated to monolysocardiolipin (MLCL), which is reacylated by tafazzin. Remodeled CL contains mostly unsaturated fatty acids. In eukaryotes, loss of tafazzin leads to growth and respiration defects, and in humans, this results in the life-threatening disorder Barth syndrome. Tafazzin deficiency causes a decrease in the CL/MLCL ratio and decreased unsaturated CL species. Which of these biochemical outcomes contributes to the physiological defects is not known. Yeast cells have a single CL-specific phospholipase, Cld1, that can be exploited to distinguish between these outcomes. The cld1Δ mutant has decreased unsaturated CL, but the CL/MLCL ratio is similar to that of wild type cells. We show that cld1Δ rescues growth, life span, and respiratory defects of the taz1Δ mutant. This suggests that defective growth and respiration in tafazzin-deficient cells are caused by the decreased CL/MLCL ratio and not by a deficiency in unsaturated CL. CLD1 expression is increased during respiratory growth and regulated by the heme activator protein transcriptional activation complex. Overexpression of CLD1 leads to decreased mitochondrial respiration and growth and instability of mitochondrial DNA. However, ATP concentrations are maintained by increasing glycolysis. We conclude that transcriptional regulation of Cld1-mediated deacylation of CL influences energy metabolism by modulating the relative contribution of glycolysis and respiration. PMID:24318983

  15. A smart phone-based pocket fall accident detection, positioning, and rescue system.

    Science.gov (United States)

    Kau, Lih-Jen; Chen, Chih-Sheng

    2015-01-01

    We propose in this paper a novel algorithm as well as architecture for the fall accident detection and corresponding wide area rescue system based on a smart phone and the third generation (3G) networks. To realize the fall detection algorithm, the angles acquired by the electronic compass (ecompass) and the waveform sequence of the triaxial accelerometer on the smart phone are used as the system inputs. The acquired signals are then used to generate an ordered feature sequence and then examined in a sequential manner by the proposed cascade classifier for recognition purpose. Once the corresponding feature is verified by the classifier at current state, it can proceed to next state; otherwise, the system will reset to the initial state and wait for the appearance of another feature sequence. Once a fall accident event is detected, the user's position can be acquired by the global positioning system (GPS) or the assisted GPS, and sent to the rescue center via the 3G communication network so that the user can get medical help immediately. With the proposed cascaded classification architecture, the computational burden and power consumption issue on the smart phone system can be alleviated. Moreover, as we will see in the experiment that a distinguished fall accident detection accuracy up to 92% on the sensitivity and 99.75% on the specificity can be obtained when a set of 450 test actions in nine different kinds of activities are estimated by using the proposed cascaded classifier, which justifies the superiority of the proposed algorithm. PMID:25486656

  16. A 2-week Nitazoxanide-based quadruple treatment as a rescue therapy for Helicobacter pylori eradication

    Science.gov (United States)

    Abd-Elsalam, Sherief; Kobtan, Abdelrahman; El-kalla, Ferial; Elkhalawany, Walaa; Nawasany, Sally El; Saif, Sabry Abou; Yousef, Mohamed; Ali, Lobna Abo; Soliman, Samah; Mansour, Loai; Habba, Eslam; Soliman, Hanan; Rizk, Fatma; Shehata, Mona AH

    2016-01-01

    Abstract As there are increasing reports of fluoroquinolone resistance on use as a first- or second-line treatment for Helicobacter pylori (H pylori), we aimed at evaluation of the efficacy and safety of nitazoxanide-based regimen as a rescue regimen in Egyptian patients whose previous traditional treatment for H pylori infection failed.In total, 100 patients from the outpatient clinic of the Tropical medicine department, Tanta University hospital in whom the standard triple therapy (clarithromycin-based triple therapy) failed were enrolled in the study. Nitazoxanide (500 mg bid), levofloxacin (500 mg once daily), omeprazole (40 mg bid), and doxycyclin (100 mg twice daily) were prescribed for 14 days. Eradication was confirmed by stool antigen for H pylori 6 weeks after the end of treatment. Among the patients enrolled in the study, 44% of patients were men and the mean age for the participants in the study was 46.41 ± 8.05, 13% of patients were smokers, and 4% of patients had a previous history of upper gastro-intestinal bleeding. A total of 94 patients (94%) completed the study with excellent compliance. Only 1 patient (1%) discontinued treatment due to intolerable side effects and 5 patients (5%) did not achieve good compliance or were lost during follow up. However, 83 patients had successful eradication of H pylori with total eradication rates 83% (95 % CI 75.7–90.3%) and 88.30% (95 % CI 81.8–94.8%) according to an intention-to-treat and per-protocol analysis, respectively. Adverse events were reported in 21% of patients: abdominal pain (6%), nausea (9%) and constipation (12%), (2%) headache, and (1%) dizziness. A 2-week nitazoxanide-based regimen is an effective and safe rescue therapy in Egyptian patients whose previous standard triple therapy has failed. PMID:27310977

  17. Concern over radiation exposure and psychological distress among rescue workers following the Great East Japan Earthquake

    Directory of Open Access Journals (Sweden)

    Matsuoka Yutaka

    2012-05-01

    Full Text Available Abstract Background On March 11, 2011, the Great East Japan Earthquake and tsunami that followed caused severe damage along Japans northeastern coastline and to the Fukushima Daiichi nuclear power plant. To date, there are few reports specifically examining psychological distress in rescue workers in Japan. Moreover, it is unclear to what extent concern over radiation exposure has caused psychological distress to such workers deployed in the disaster area. Methods One month after the disaster, 424 of 1816 (24% disaster medical assistance team workers deployed to the disaster area were assessed. Concern over radiation exposure was evaluated by a single self-reported question. General psychological distress was assessed with the Kessler 6 scale (K6, depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D, fear and sense of helplessness with the Peritraumatic Distress Inventory (PDI, and posttraumatic stress symptoms with the Impact of Event Scale-Revised (IES-R. Results Radiation exposure was a concern for 39 (9.2% respondents. Concern over radiation exposure was significantly associated with higher scores on the K6, CES-D, PDI, and IES-R. After controlling for age, occupation, disaster operation experience, duration of time spent watching earthquake news, and past history of psychiatric illness, these associations remained significant in men, but did not remain significant in women for the CES-D and PDI scores. Conclusion The findings suggest that concern over radiation exposure was strongly associated with psychological distress. Reliable, accurate information on radiation exposure might reduce deployment-related distress in disaster rescue workers.

  18. Factors impacting the success of post-mortem sperm rescue in the rhinoceros.

    Science.gov (United States)

    Roth, T L; Stoops, M A; Robeck, T R; O'Brien, J K

    2016-04-01

    The goal of this study was to identify factors that influenced the ability to successfully rescue sperm post-mortem from rhinoceroses maintained in North American zoos. Factors considered included procedural technicalities, individual rhinoceros characteristics and timing. Gross testicular pathology was noted in 17.4% of males (4/23) but did not impact sperm recovery except in one case of azoospermia (4.3%). Of the males in which sperm recovery was attempted (n=21), 62% yielded quality samples considered adequate for cryopreservation (≥30% motility with ≥2.0 forward progressive status). A high percentage of males (70.6%; 12/17) from which reproductive tissue was removed and cooled ≤4h after death yielded quality sperm samples, whereas only 25% (1/4) of males from which tissue was removed>4h after death yielded quality samples. Quality samples were recovered 1-51h post-mortem from rhinoceroses 8 to 36 years old. Neither type of illness (prolonged or acute), or method of death (euthanasia or natural) affected the ability to harvest quality samples (P>0.05). The Indian rhinoceros yielded significantly more sperm on average (40×10(9)) than the African black rhinoceros (3.6×10(9); Ppost-thaw sperm motility (41%), was only 15% less than pre-freeze motility (56%) and only decreased to 22% during the 6h post-thaw assessment period. Rhinoceros sperm rescue post-mortem is relatively successful across a wide range of variables, especially when tissues are removed and cooled promptly after death, and should be considered standard practice among zoos. PMID:26879096

  19. Furazolidone,amoxicillin,bismuth and rabeprazole quadruple rescue therapy for the eradication of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Hong Cheng; Fu-Lian Hu

    2009-01-01

    AIM:To compare the efficacy and side effect profiles of three furazolidone and amoxicillin-based quadruple rescue therapies for the eradication of Helicobacter pylori ( H pylori).METHODS: Patients who failed in the H pylori eradication therapy for at least one course were randomly allocated into three groups. Group A received rebaprazole 10 mg + amoxicillin 1 g + furazolidone 100 mg, and bismuth subcitrate 220 mg, twice daily for 1 wk; group B received the same regimen of group A but for 2 wk; and group C received the same regimen of group B, but furazolidone was replaced by furazolidone 100 mg three times daily. To record the side effect profiles at the end of the treatment, H pylori eradication was assessed with 13C-urea breath test 4 wk after therapy. RESULTS: Sixty patients were enrolled including 28 males, and 20 patients in each group. The average age of the patients was 49.2 years, ranging from 18 to 84 years. H pylori eradication rates with per-protocol analysis were 82%, 89% and 90% in the three groups, respectively. Side effects were found in 11 patients, including mild dizziness, nausea, diarrhea and increased bowel movement. None of the 11 patients needed treatment for their side effects. CONCLUSION: One- or two-week furazolidone and amoxicillin-based quadruple rescue therapy with a low dose furazolidone (100 mg bid) for the eradication of H pylori is effective. Extending the antibiotic course to 14 d could improve the eradication rates. 2009 The WJG Press and Baishideng. All rights reserved.

  20. SALVEREMO, an automatic system for the search and rescue in the wilderness and mountain areas

    Science.gov (United States)

    Penna, Roberto; Allasia, Walter; Bianchi, Luca; Licata, Enrico; Duranti, Pierluigi; Molino, Andrea; Bagalini, Enea; Sagliocco, Sergio; Scarafia, Simone; Prinetto, Paolo; Airofarulla, Giuseppe; Carelli, Alberto

    2016-04-01

    SALVEREMO project aims at designing and prototyping an innovative system for searching and rescuing individuals (especially hikers and mountaineers) who got lost or in peril in wilderness or mountain areas. It makes use of Remotely Piloted Aircraft System (RPAS) equipped with a sensor suite specifically selected according to the requirements identified involving alpine rescuers and government officials. The peculiarity of the proposed solution is the exploitation and integration of the special skill and expertise coming from different competence fields. It will dramatically decrease the searching time in the wilderness and remote areas off the beaten tracks, providing rescuers and operators with a decision support system increasing successful results and reducing rescue missions costs. The system benefits from the adoption of a scaled-down Base Transceiver Station (BTS) embarked in the payload sensor suite of a small RPAS that can be carried in a back pack of rescuers. A Software Defined Radio (SDR) board implementing the BTS protocol stack has been integrated in a complex sensor suite made up of open processing boards and camera devices. Moreover computer vision (CV) algorithms for real time pattern detection and image enhancements have been investigated for assisting the rescuers during the searching operations. An easy-to-use ground station application has been developed for speeding up the overall mission accomplishment. Aknowledgement SALVEREMO project is a research project co-funded by Regione Piemonte according to the call for proposal POR F.E.S.R. 2007/2013, "Linea di attività I.1.3-Innovazione e PMI - Polo della Meccatronica e dei Sistemi Avanzati di Produzione". The authors want to thank "Il Soccorso Alpino Italiano" for the invaluable support for establishing operative requirements.