Sample records for mfo peacekeeping pk

  1. African Peacekeepers in Africa

    Emmanuel, Nikolas G.


    behind African participation in United Nations (UN) peacekeeping operations in Africa. In doing so, this research focuses on US military aid and foreign troop training from 2002 to 2012, and its impact on African deployments into UN peacekeeping missions in Africa. As can be expected, such third...

  2. English for Global Peacekeeping

    Crossey, Mark


    In this article, I discuss the work of the British Council's Peacekeeping English Project: why the British Council is undertaking this work, why is it being sponsored, what exactly is being done and what are the key issues in English for peacekeeping and other security forces.

  3. PeaceKeeper

    Lanng, Henrik; Lykkegaard,, Anders; Thornholm, Søren


    . To address this challenge, we explore how to augment the awareness and communication of environmental noise among dorm residents through an ambient awareness system: PeaceKeeper. We describe the initial design, implementation and concept validation of PeaceKeeper with two students living in contiguous rooms......Noise pollution can be very problematic especially in shared-living facilities such as student dormitories. After conducting interviews with nine students, we found that students are usually not aware of the level of noise pollution they are producing as part of their everyday activities...... at the same dormitory. Based on our initial findings, we highlight how ambient awareness systems can provide opportunities to make students aware of their own level of noise to avoid disturbing their neighbours....

  4. Psychological aspects of peacekeeping operations

    M. S. V. K. Raju


    Full Text Available Peacekeeping operations are but one aspect of the systems of peace that have evolved over the past seven decades in a world that is riven with violence of all kinds. With the end of cold war in the late eighties of the last century we have come to see much intrastate violence, in addition to usual interstate hostilities and war, arising out of religious, political, ethnic and economic differences between people. In the changed scenario peacekeeping operations have become complex politico-military-humanitarian efforts. A soldier, trained for conventional military operations, is obliged to participate in the unconventional operations of waging peace in alien lands often in volatile and violent situations and in the process he stands to get exposed to widely variable demands for adjustment that have the potential to bring to the fore many maladaptive responses. Peacekeeping operations also have the potential to offer opportunities for growth and resilience. India is a major player in peacekeeping activities for well over sixty years all over the world. It is necessary for the commanders and mental health professionals to understand the multifarious factors that impinge on the peacekeeping soldier′s mind and the emerging patterns of responses thereof for effective management trained manpower and fulfillment of mission objectives

  5. What Makes a Good Peacekeeper?

    Bebbington, John; And Others


    Children can better understand the United Nations' role as a peacekeeper if they have some experience at it themselves. This activity for grades 4 to 6 demonstrates that the battles on the schoolground are not so different from those in the wider world. Includes a bingo gameboard and worksheet. (LZ)

  6. Mental Health of Chinese Peacekeepers in Liberia

    Xin-yang Sun


    Full Text Available Background and Objectives: As part of UN peacekeeping operations in Liberia, China has sent a dozen of batches of peacekeeping force to Liberia for medical, engineering and transporting purposes from 2003 to 2012. This study aimed to explore the mental health of Chinese peacekeepers under the influence of stressful and traumatic events in Liberia. Methods: A total of 440 Chinese peacekeepers were selected by cluster sampling and surveyed by Chinese Military Mental Health Scale (CMMHS before, during and after peacekeeping deployment. Results: The total CMMHS score (48.90 ± 21.15, depression factor (7.25 ± 3.43, interpersonal sensitivity (4.20 ± 2.15 of Chinese peacekeepers were significantly higher than the Chinese military norm (23.04 ± 14.70, 2.47 ± 2.46, 3.95 ± 2.97 respectively (p<0.01. The total score and anxiety, somatization factor score of the transporting group were significantly higher than those of the medical group (P <0.05; All CMMHS factors in the transporting group and the medical group were higher than those of the engineering group (p<0.01. CMMHS factors score of the peacekeepers positively correlated with the age, military service duration, years of eudcation and military rank (r = 0.107 ~ 0.523, p<0.05; stepwise linear regression analysis revealed that years of eudcation was the main influence factor for peacekeepers' mental health (t = 2.288 ~ 4.358, p<0.05 ~ 0.01. Conclusions: The mental health status of Chinese peacekeepers was worse than average Chinese servicemen. Peacekeepers of different mission groups had different degree of mental damage, and the years of education was the main influence factor for peacekeepers' mental health, whereas age, military service duration as well as military rank were the secondary influence factors.

  7. Gut microbiota: the brain peacekeeper


    Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota-gut-brain axis and the role of microbiota as a peacekeeper in the brain health. Here, we review recent discoveries on t...

  8. Suicide rate among former Swedish peacekeeping personnel.

    Michel, Per-Olof; Lundin, Tom; Larsson, Gerry


    Increased suicide rates for military personnel suffering from post-traumatic stress disorders have been reported in various countries. Although it is known that some peacekeepers are exposed to potentially traumatic events and are thus at risk of suffering from post-traumatic stress reactions, only a few studies have examined suicide rates in this group. Therefore, the aim of this study was to investigate the suicide rate among former Swedish peacekeeping personnel. We compared 39,768 former Swedish peacekeepers to the general population in the National General Population Registry and the Cause-of-Death Registry. A lower number of suicides was found among former Swedish peacekeepers than in the general population. In conclusion, Swedish personnel serving in international peace-keeping operations do not show a higher suicide rate than the general population. Unique problems associated with this research area are discussed.

  9. DNA-PK assay

    Anderson, Carl W.; Connelly, Margery A.


    The present invention provides a method for detecting DNA-activated protein kinase (DNA-PK) activity in a biological sample. The method includes contacting a biological sample with a detectably-labeled phosphate donor and a synthetic peptide substrate defined by the following features to provide specific recognition and phosphorylation by DNA-PK: (1) a phosphate-accepting amino acid pair which may include serine-glutamine (Ser-Gln) (SQ), threonine-glutamine (Thr-Gln) (TQ), glutamine-serine (Gln-Ser) (QS), or glutamine-threonine (Gln-Thr) (QT); (2) enhancer amino acids which may include glutamic acid or glutamine immediately adjacent at the amino- or carboxyl- side of the amino acid pair and forming an amino acid pair-enhancer unit; (3) a first spacer sequence at the amino terminus of the amino acid pair-enhancer unit; (4) a second spacer sequence at the carboxyl terminus of the amino acid pair-enhancer unit, which spacer sequences may include any combination of amino acids that does not provide a phosphorylation site consensus sequence motif; and, (5) a tag moiety, which may be an amino acid sequence or another chemical entity that permits separating the synthetic peptide from the phosphate donor. A compostion and a kit for the detection of DNA-PK activity are also provided. Methods for detecting DNA, protein phosphatases and substances that alter the activity of DNA-PK are also provided. The present invention also provides a method of monitoring protein kinase and DNA-PK activity in living cells. -A composition and a kit for monitoring protein kinase activity in vitro and a composition and a kit for monitoring DNA-PK activities in living cells are also provided. A method for identifying agents that alter protein kinase activity in vitro and a method for identifying agents that alter DNA-PK activity in living cells are also provided.



    Abstract. United Nations peacekeepers have been subject to allegations of serious sexual ... more innovative interventions to prevent and respond to SEA. The changing ... victims are infected with sexually transmitted diseases, including HIV.

  11. The United Nations Peacekeeping Current Challenges

    Yu P Spirin


    Full Text Available The article focuses on the problem of strengthening structures, potential and resources of the United Nations Secretariat forces, realizing peacekeeping activities of the Organization. The special attention is given to the «Brakhimi Group» as well as to the activities of the United Nations Security Council in the context of the search for effective peacekeeping activity of the Organization.

  12. Using GM (1,1 Optimized by MFO with Rolling Mechanism to Forecast the Electricity Consumption of Inner Mongolia

    Huiru Zhao


    Full Text Available Accurate and reliable forecasting on annual electricity consumption will be valuable for social projectors and power grid operators. With the acceleration of electricity market reformation and the development of smart grid and the energy Internet, the modern electric power system is becoming increasingly complex in terms of structure and function. Therefore, electricity consumption forecasting has become a more difficult and challenging task. In this paper, a new hybrid electricity consumption forecasting method, namely grey model (1,1 (GM (1,1, optimized by moth-flame optimization (MFO algorithm with rolling mechanism (Rolling-MFO-GM (1,1, was put forward. The parameters a and b of GM (1,1 were optimized by employing moth-flame optimization algorithm (MFO, which is the latest natured-inspired meta-heuristic algorithm proposed in 2015. Furthermore, the rolling mechanism was also introduced to improve the precision of prediction. The Inner Mongolia case discussion shows the superiority of proposed Rolling-MFO-GM (1,1 for annual electricity consumption prediction when compared with least square regression (LSR, GM (1,1, FOA (fruit fly optimization-GM (1,1, MFO-GM (1,1, Rolling-LSR, Rolling-GM (1,1 and Rolling-FOA-GM (1,1. The grey forecasting model optimized by MFO with rolling mechanism can improve the forecasting performance of annual electricity consumption significantly.

  13. Peacekeeper ICBM PBPS (Stage IV) Safing and Demilitarization Project

    Douglass, James L.


    Topics covered include: Overview of White Sands Test Facility (WSTF) and Capabilities. History of the Peacekeeper Intercontinental Ballistic Missile (ICBM) Program. Introduction to Safing & Demilitarization Project. Requirements for Safing Project. Approach Constellation Program. Need for Qualified Flight Hardware to Support Constellation. Ability to Use Peacekeeper Hardware to Support Constellation. Additional Uses for the Peacekeeper Post-Boost Propulsion System (PBPS) Hardware.

  14. Gut microbiota: the brain peacekeeper

    Chunlong eMu


    Full Text Available Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota-gut-brain axis and the role of microbiota as a peacekeeper in the brain health. Here, we review recent discoveries on the role of the gut microbiota in central nervous system (CNS-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gut microbiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders.

  15. Captures of MFO-resistant Cydia pomonella adults as affected by lure, crop management system and flight.

    Bosch, D; Rodríguez, M A; Avilla, J


    The main resistance mechanism of codling moth (Cydia pomonella) in the tree fruit area of Lleida (NE Spain) is multifunction oxidases (MFO). We studied the frequency of MFO-resistant adults captured by different lures, with and without pear ester, and flights in orchards under different crop management systems. The factor year affected codling moth MFO-resistance level, particularly in the untreated orchards, highlighting the great influence of codling moth migration on the spread of resistance in field populations. Chemical treatments and adult flight were also very important but mating disruption technique showed no influence. The second adult flight showed the highest frequency, followed by the first flight and the third flight. In untreated orchards, there were no significant differences in the frequency of MFO-resistant individuals attracted by Combo and BioLure. Red septa lures baited with pear ester (DA) captured sufficient insects only in the first generation of 2010, obtaining a significantly lower proportion of MFO-resistant adults than Combo and BioLure. In the chemically treated orchards, in 2009 BioLure caught a significantly lower proportion of MFO-resistant adults than Combo during the first and third flight, and also than DA during the first flight. No significant differences were found between the lures or flights in 2010. These results cannot support the idea of a higher attractiveness of the pear ester for MFO-resistant adults in the field but do suggest a high influence of the response to the attractant depending on the management of the orchard, particularly with regard to the use of chemical insecticides.

  16. Are UN peacekeepers at risk for suicide?

    Wong, A; Escobar, M; Lesage, A; Loyer, M; Vanier, C; Sakinofsky, I


    Media reports connecting UN peacekeeping duties by Canadian soldiers to their subsequent suicide prompted this study of peacekeeping as suicide risk. In a case-control design we retrospectively compared 66 suicides in the Canadian military between 1990 and 1995 with two control groups: (a) 2,601 controls randomly selected from the electronic military database and (b) 66 matched controls with complete personnel and medical data. We found no increased risk of suicide in peacekeepers except among a subgroup of air force personnel. Here confounding individual factors, isolation from supports, and possibly inadequate preparation for deployment elucidated their suicides. Theater of deployment (e.g., Bosnia) did not affect the suicide rate. Military suicides experienced psychosocial stresses and psychiatric illness more often than their matched controls. We conclude that although peacekeeping per se does not increase overall suicide risk, military life-styles may strain interpersonal relationships, encourage alcohol abuse, and contribute to psychiatric illness and suicide in a minority of vulnerable individuals irrespective of peacekeeping assignment. Careful selection, and preparatory military training that encourages intragroup bonding and mutual support, may protect against suicide risk.

  17. Friction and Inequality among Peacekeepers in Mali

    Cold-Ravnkilde, Signe Marie; Albrecht, Peter; Haugegaard, Rikke


    MINUSMA represents Europe’s return to peacekeeping, the largest troop contributors by a wide margin are African countries. Through exploring the task of securing mission convoys to the northern regions of the country, Signe Cold-Ravnkilde, Peter Albrecht and Rikke Haugegaard show how inequalities between...

  18. A Regime Legitimacy Explanation of African Peacekeeping


    Solutions are not Enough,” Ethics and International Affairs 22 (2008): 310; Jakkie Cilliers, “Peacekeeping, Africa and the Emerging Global Security...prominent political philosophers: Hobbes, Locke and Kant ; the Hobbesian culture is based on perpetual conflict, the Lockean on self-control and the...1998): 425– 439. Williams, Paul. “Keeping the Peace in Africa: Why ‘African’ Solutions are not Enough.” Ethics and International Affairs 22

  19. Friction and Inequality among Peacekeepers in Mali

    Cold-Ravnkilde, Signe Marie; Albrecht, Peter; Haugegaard, Rikke


    The United Nations Multidimensional Integrated Stabilization Mission in Mali (MINUSMA) was established in 2013 to support Mali’s peace process. It represents an emerging practice of deploying UN peacekeeping missions in asymmetrical conflict environments where there is no peace to keep. While...... European and African soldiers shape the distribution of death, danger and supplies in what has been named the world’s deadliest UN mission....

  20. Conceptualization of UN Peacekeeping as an International Regime

    Jana Urbanovská


    Full Text Available It is widely recognized that UN peacekeeping operations are an undertheorized topic. In this respect, scholars call to devote more attention to the incorporation of the study of UN peacekeeping operations into the framework of international relations theories. The article responds to these calls and suggests conceptualizing UN peacekeeping as an international regime. Some authors have already referred to UN peacekeeping as an international regime, however, the references have been rather fragmentary and there is no detailed identification of individual dimensions of this regime. The article uses the conception of Stephen Krasner who defines regimes as “principles, norms, rules, and decision-making procedures around which actors’ expectations converge in a given area of international relations” to carefully identify and characterize the dimensions of the UN peacekeeping regime. The conceptualization of UN peacekeeping as an international regime is understood as a first and necessary step to opening new ground to the theoretical study of UN peacekeeping operations within the regime analysis.

  1. Fatality trends in United Nations Peacekeeping Operations, 1948-1998.

    Seet, B; Burnham, G M


    The rising number of deaths among United Nations (UN) peacekeeping forces after the Cold War has made some troop-contributing countries hesitant to participate in peacekeeping operations. While the number and scale of missions have increased, no data have demonstrated a parallel increase in risks to peacekeepers. To determine the association of characteristics of UN peacekeeping operations with risks and mortality rates among UN peacekeeping forces in both the Cold War and post-Cold War periods. Descriptive analysis of 1559 personnel deaths during 49 UN peacekeeping missions from 1948-1998 based on the casualty database maintained by Department of Peacekeeping Operations, UN Headquarters. Number and percentage of deaths by circumstance, total crude death rate, and crude death rate and relative risk of death by circumstance (hostile acts, unintentional violence, and illness or other causes) and time period (Cold War vs post-Cold War), geographic region, and nature of peacekeeping response; and regression analysis of mission variables (strength, duration, and humanitarian mandate) associated with total number of deaths. More deaths have occurred among UN peacekeeping forces in the past decade alone than in the previous 40 years of UN peacekeeping (807 vs 752), but crude death rates did not differ significantly by time period (Cold War vs post-Cold War, 21.8 vs 21. 2 deaths per 10,000 person-years; P =.58), level of peacekeeping response, or for geographic regions other than East Europe and Central America, where rates were lower (PCold War (relative risk [RR] 1. 51; 95% confidence interval [CI], 1.22-1.88), while rates for deaths caused by unintentional violence decreased (RR, 0.79; 95% CI, 0.67-0. 94) but remain high, particularly in the Middle East and Asia (RR, 1. 39; 95% CI, 1.15-1.69). Regression analysis showed a significant association between number of deaths and the strength (PCold War rather than increased RR of death. Post-Cold War peacekeeping personnel

  2. Developmental peace missions: synergising peacekeeping and peacebuilding in transition periods

    Gueli, R


    Full Text Available Over the years, the functional gap between peacekeeping and peacebuilding (or 'post-conflict' reconstruction) has received a lot of attention because it remains a weakness in the policy framework of the United Nation (UN) conflict resolution...

  3. Denmark and UN peacekeeping: glorious past, dim future

    Jakobsen, Peter Viggo


    Denmark became a staunch supporter of UN peacekeeping during the cold war because it simultaneously served its interests and values and this winning combination meant that it relatively quickly became internalized as part of Denmark’s foreign policy identity. Denmark turned its back on UN peaceke...... a close relationship to NATO’s great powers make a major Danish return to UN peacekeeping unlikely....


    Ünsal Sigri; Giuseppe Caforio; Ufuk Basar


      This study aims to determine the role of the soft skills of adaptation, relations with locals, relations with other peacekeepers, stress management and cultural awareness, in accomplishing peacekeeping operations...

  5. DNA conformational transitions inferred from re-evaluation of m|Fo| - D|Fc| electron-density maps.

    Sunami, Tomoko; Chatake, Toshiyuki; Kono, Hidetoshi


    Conformational flexibility of DNA plays important roles in biological processes such as transcriptional regulation and DNA packaging etc. To understand the mechanisms of these processes, it is important to analyse when, where and how DNA shows conformational variations. Recent analyses have indicated that conventional refinement methods do not always provide accurate models of crystallographic heterogeneities and that some information on polymorphism has been overlooked in previous crystallographic studies. In the present study, the m|Fo| - D|Fc| electron-density maps of double-helical DNA crystal structures were calculated at a resolution equal to or better than 1.5 Å and potential conformational transitions were found in 27% of DNA phosphates. Detailed analyses of the m|Fo| - D|Fc| peaks indicated that some of these unassigned densities correspond to ZI ↔ ZII or A/B → BI conformational transitions. A relationship was also found between ZI/ZII transitions and metal coordination in Z-DNA from the detected peaks. The present study highlights that frequent transitions of phosphate backbones occur even in crystals and that some of these transitions are affected by the local molecular environment.

  6. Denmark and UN peacekeeping: glorious past, dim future

    Jakobsen, Peter Viggo


    Denmark became a staunch supporter of UN peacekeeping during the cold war because it simultaneously served its interests and values and this winning combination meant that it relatively quickly became internalized as part of Denmark’s foreign policy identity. Denmark turned its back on UN...... peacekeeping when NATO took over from the UN in Bosnia in 1995. Since then Denmark has prioritized NATO- and US-led operations. The Danish shift was driven by the interest in supporting the Western great powers as well as an altruistic desire to improve United Nations Protection Force’s (UNPROFOR) dismal...... a close relationship to NATO’s great powers make a major Danish return to UN peacekeeping unlikely....

  7. Challenges of the African Military in Peacekeeping Missions in Africa


    article is based on the authors’ book Peacekeeping in Africa: Capabilities and Culpabilities, Geneva, United Nations Institute for Disarmament Research...and the Institute of Security Studies, 2000, 572. http://www.peacepalacelibrary.nil/ ebooks /UNIDIR--pdf-art129.pdf. (accessed November 21, 2011). 14

  8. Meaning as a Mission: Making sense of war and peacekeeping

    Schok, M.L.


    The objective of this thesis was to examine the significance of meaning in a sample of veterans who were deployed during various war and peacekeeping operations. A cognitive perspective was chosen to explore how veterans make sense of their war zone experiences and find personal significance in thes

  9. Meaning as a Mission: Making sense of war and peacekeeping

    Schok, M.L.


    The objective of this thesis was to examine the significance of meaning in a sample of veterans who were deployed during various war and peacekeeping operations. A cognitive perspective was chosen to explore how veterans make sense of their war zone experiences and find personal significance in

  10. Blue sensors : technology and cooperative monitoring in UN peacekeeping.

    Dorn, A. Walter Dr. (Canadian Forces College, Toronto, Ontario)


    For over a half-century, the soldiers and civilians deployed to conflict areas in UN peacekeeping operations have monitored ceasefires and peace agreements of many types with varying degrees of effectiveness. Though there has been a significant evolution of peacekeeping, especially in the 1990s, with many new monitoring functions, the UN has yet to incorporate monitoring technologies into its operations in a systematic fashion. Rather, the level of technology depends largely on the contributing nations and the individual field commanders. In most missions, sensor technology has not been used at all. So the UN has not been able to fully benefit from the sensor technology revolution that has seen effectiveness greatly amplified and costs plummet. This paper argues that monitoring technologies need not replace the human factor, which is essential for confidence building in conflict areas, but they can make peacekeepers more effective, more knowledgeable and safer. Airborne, ground and underground sensors can allow peacekeepers to do better monitoring over larger areas, in rugged terrain, at night (when most infractions occur) and in adverse weather conditions. Technology also allows new ways to share gathered information with the parties to create confidence and, hence, better pre-conditions for peace. In the future sensors should become 'tools of the trade' to help the UN keep the peace in war-torn areas.

  11. Red blood cell PK deficiency: An update of PK-LR gene mutation database.

    Canu, Giulia; De Bonis, Maria; Minucci, Angelo; Capoluongo, Ettore


    Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Several reports have been published describing a large variety of genetic defects in PK-LR gene associated to CNSHA. Herein, we present a review of about 250 published mutations and six polymorphisms in PK-LR gene with the corresponding clinical and molecular data. We consulted the PubMed website for searching mutations and papers, along with two main databases: the Leiden Open Variation Database (LOVD, and Human Gene Mutation Database (HGMD, for selecting, reviewing and listing the annotated PK-LR gene mutations present in literature. This paper is aimed to provide useful information to clinicians and laboratory professionals regarding overall reported PK-LR gene mutations, also giving the opportunity to harmonize data regarding PK-deficient individuals.

  12. Simulating the Effect of Peacekeeping Operations 2010-2035

    Hegre, Håvard; Hultman, Lisa; Nygård, Håvard Mokleiv

    We simulate how a set of different UN policies for peace-keeping operations is likely to affect the global incidence of internal armed conflict. The simulation is based on a statistical model that estimates the efficacy of UN peacekeeping operations (PKOs) in preventing the onset, escalation, continuation, and recurrence of internal armed conflict. The model takes into account a set of important conflict predictors for which we have projections up to 2035 from the UN and the IIASA. The estimates are based on a 1970-2008 cross-sectional dataset of changes between conflict levels and new data on PKO budgets and mandates. The simulations show a strong effect of PKOs on the global incidence of major conflicts, although restricted to operations with robust mandates. Extensive use of 'transformational' PKOs can reduce the global incidence of the most lethal conflicts with 65%.

  13. Emerging applications for the Peacekeeper Post Boost Vehicle

    Blake, Jack


    The use of the Peacekeeper Post Boost Vehicle (PBV) is considered for applications beyond its original use as stage IV of the ICBM system. The PBV is described in the context of the Peacekeeper mission, and the axial engine and attitude-control engines are illustrated. The capability of the PBV is found to make the engine appropriate for use as a liquid-plume generator for the Space Pallet Satellite Experiment. The PBV could also be used as a system basis for transporting large payloads into LEO, and a PBV-based platform could remain in orbit to serve as an earth/payload communication link. The PBV offers technologies and capabilities required for such missions as a plume generator, space-experiment module, or as a transfer vehicle for Space Station logistics and resupply.

  14. Managing mistrust: an analysis of cooperation with UN peacekeeping in Africa

    Ruggeri, A.; Gizelis, T.I.; Dorussen, H.


    How many peacekeepers are needed to keep the peace? Under what conditions are local governments and rebel forces more willing to cooperate with an intervention force? From a theoretical perspective in which the main role of peacekeepers is to assist local actors in overcoming their commitment

  15. Digitaalisen markkinoinnin tehostaminen PK-sektorilla

    Viisteensaari, Keijo


    Opinnäytetyössä käsiteltiin digitaalista markkinointia. Työssä annetaan tietoa, miten PK-sektorin yrityksessä voidaan toteuttaa tuloksellista digitaalista markkinointia. Opinnäytetyö sisältää oppaan, jonka avulla PK-sektorin yrityksessä voidaan toteuttaa digitaalinen markkinointi. Työ ei paneudu teknisiin yksityiskohtiin vaan markkinoinnin näkökulmaan digitaalisen markkinoinnin toteuttamisessa. Aiheena digitaalinen markkinointi on ajankohtainen ja tärkeä, koska markkinointi on yhä enemmän sii...

  16. Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

    Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata Jr, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves


    To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

  17. Peacekeeping in Africa: Reflections on developments and trends

    Theo Neethling


    Full Text Available Africa is arguably the most important regional selling for United Nations peacekeeping challenges. Hence, Africa is the first continent where extensive efforts have recently been made between the United Nations and the Organisation of African Unity with the specific aim of enhancing the management of conflicts in the region. It is significant that the UN now seems prepared to form partnerships with willing regional organisations and alliances in Africa with regard to the conducting of peace-support operations. At the same time, the United States and certain European nations have begun to support the idea of an African response capability of some kind. Another significant development relates to the fact that sub-regional organisations in Africa have started to feature as important peacekeeping instruments in recent years as it has increasingly been accepted that there is a need for such institutions to take care of their own security requirements. In this regard, the “indigenous" intervention operations without UN endorsement or involvement in Sierra Leone, the Democratic Republic of the Congo and in Lesotho are of particular interest, as these would seem to represent a new dimension in the management of African peacekeeping requirements. What is needed in the African context is to establish an acceptable basis for involvement or intervention in intra-state conflicts that respects the dignity and independence of stales without sanctioning the misuse of sovereign rights to violate the security of people within a stale's borders. It would therefore be desirable that all the roleplayers in Africa and further afield should develop a set of broad principles to respond appropriately and speedily to situations where the security of people is imperilled.

  18. ‘Surrender’, peacekeeping and internal colonialism. A Malaysian instance

    Robert Knox Dentan


    Full Text Available A neglected episode in West Malaysia’s subaltern history illustrates how simplistic Western notions of peace—and consequently, of surrender and resistance—can be. In the case of Semai in the Semai heartland, what seems like submission to external pressures turns out to be an ambiguous and ambivalent way of keeping the peace between Malays and Semai in the guise of adding new tools to traditional Semai internal peacekeeping praxis. Semai “double consciousness” of both their own reality and how Malays conceive of it thus allows them to avoid the imposition of external authority by creating a simulacrum thereof. “Surrender” and resistance overlap.

  19. Number & operations drill sheets : grades PK-2

    Reed, Nat


    For grades PK-2, our Common Core State Standards-based resource meets the number & operations concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Each drill sheet contains warm-up and timed drill activities for the student to practice number & operations concepts.

  20. Algebra task sheets : grades pk-2

    Reed, Nat


    For grades PK-2, our Common Core State Standards-based resource meets the algebraic concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  1. Geometry task sheets : grades pk-2

    Rosenberg, Mary


    For grades PK-2, our Common Core State Standards-based resource meets the geometry concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Each task sheet is organized around a central problem taken from real-life experiences of the students.

  2. An analysis of personality traits of Chinese military medical peacekeepers in Lebanon

    Yu, Ke; Zhang, Yan; Li, Congyang; Wang, Qingsong; Tan, Yingjun; Shao, Yongcong


    In this study the Chinese version of the 16 Personality Factor Questionnaire (16PF; Cattell, Eber, & Tatsuoka, 1970; Dai & Zhu, 1988) was used to investigate the personality traits of 59 Chinese medical peacekeepers in Lebanon...

  3. Analysis of Serbian Military Riverine Units Capability for Participation in the United Nations Peacekeeping Operations

    Slobodan Radojevic


    Full Text Available This paper analyses required personnel, training capacities and equipment for participation in the United Nations peacekeeping operations with the riverine elements. In order to meet necessary capabilities for engagement in United Nations peacekeeping operations, Serbian military riverine units have to be compatible with the issued UN requirements. Serbian Armed Forces have the potential to reach such requirements with the River Flotilla as a pivot for the participation in UN missions. Serbian Military Academy adopted and developed educational and training program in accordance with the provisions and recommendations of the IMO conventions and IMO model courses. Serbian Military Academy has opportunities for education and training military riverine units for participation in the United Nations peacekeeping operations. Moreover, Serbia has Multinational Operations Training Center and Peacekeeping Operations Center certified to provide selection, training, equipping and preparations of individuals and units to the United Nations multinational operations.

  4. Transitioning from a U.N. Observer Mission to a Robust Peacekeeping Operation: Lessons from Sierra Leone


    U.N.CHAPTER VI OBSERVER MISSION TO A ROBUST PEACEKEEPING OPERATION: LESSONS FROM SIERRA LEONE 9. Personal Authors: Peter V. Londono, CIV 10.Type of...necessarily endorsed by the NWC or the Department of the Navy. 14. Ten key words that relate to your paper: Peacekeeping, U.N., Sierra Leone , UNOMSIL...UNAMSIL, RUF, Peace Enforcement, Operation Relief Focus, ECOWAS, ECOMOG 15.Abstract: U.N. peacekeeping operations in Sierra Leone have special

  5. An Upgradeable Agent-Based Model to Explore Non-Linearity and Intangibles in Peacekeeping Operations


    49 Figure 11. UML diagram of the BasicGoalManager, Goals, and Tickets.........................52 Figure 12. Generalized PRIZREN ...from reaching a certain area of a historic old town ( Prizren , Kosovo). Figure 1 shows the Graphical User Interface (GUI) in which the scenario the context of peacekeeping missions: The map exercise takes place in PRIZREN , KOSOVO. German peacekeeping forces have been deployed to PRIZREN

  6. The History of Peacekeeping in the Sinai Desert, 1956-2002


    Force (London: Stevens & Sons, New York: Frederick A. Praeger, 1960). The sponsors of the resolution were Lester Pearson the Canadian Foreign Minister and...Director General of the MFO was Leamon Hunt, a US diplomat. The first force commander was a Norwegian, LTG Frederic Bull-Hansen. Clearly, this

  7. Effects of sublethal dose of metaldehyde on the activities of AchE, GSTs and MFO in Pomacea canaliculata%四聚乙醛亚致死剂量对福寿螺AchE、GSTs 和MFO 活性的影响

    张文领; 牟希东; 韦慧; 杨叶欣; 徐猛; 罗渡; 胡隐昌


    为了解亚致死剂量四聚乙醛对福寿螺的主要靶标酶和解毒酶活性的影响,研究了0.50 mg/L 的四聚乙醛处理不同时间后福寿螺不同组织中乙酰胆碱酯酶(AchE)、谷胱甘肽 S-转移酶(GSTs)和多功能氧化酶(MFO)的活力变化。结果显示,四聚乙醛对福寿螺具有良好的杀灭效果,96 h LC50为3.856 mg/L,安全浓度为0.039 mg/L;在用0.50 mg/L 的四聚乙醛处理的24 h 内,福寿螺鳃和腹足内 AchE 酶活力分别升高到未处理时的1.565和1.481倍而后下降,肝和肠组织内AchE 酶活力分别下降为未处理时的0.132、0.282倍而后升高;不同组织中 GSTs 酶活力均呈现为“降低—升高—降低”的趋势;不同组织内 MFO 酶活力均为先下降后上升的趋势。研究表明0.50 mg/L 的四聚乙醛能诱导 AchE、MFO和 GST 活性不同程度的增加,解毒酶 MFO 和 GSTs 可能在四聚乙醛的代谢中起着一定作用。%To explore the sublethal effect of metaldehyde exposure on main target enzymes and detoxification en-zymes in Pomacea canaliculata ,the activity dynamics of AchE,GSTs and MFO were measured under sublethal concentrations of metaldehyde.The results showed that metaldehyde could significantly kill P .canaliculata ,and 96 h LC50 and the safe concentration were 3.856 mg/L and 0.039 mg/L,respectively.Under 0.50 mg/L metalde-hyde stress,AchE enzyme activity in gills and pleopod increased to 1.565 and 1.481 times as that of the control group,respectively,while the AchE activity in liver and intestine decreased to 0.132 and 0.282 times as that of the control group,respectively,but increased subsequently.GSTs activities were presented as a trend of “de-crease-increase-decrease”;MFO activities decreased at the beginning and then were induced to increase to differ-ent extents.The results indicated that the activities of AchE,MFO and GSTs were induced to enhance to some ex-tent during


    Azman Ismail


    Full Text Available The capability of service providers to plan and implement the quality components in executing daily job may have a significant impact on customer loyalty. However, the role of service quality as an important determinant has been given less attention in the workplace quality research literature. Therefore, this study was undertaken to measure the relationship between service quality and customer loyalty. A survey method was employed to collect data from Malaysian soldiers who involved in peacekeeping missions at Middle Eastern country. The outcomes of SmartPLS path model analysis demonstrate that the ability of organization to appropriately implement tangible, reliability, responsiveness, assurance and empathy in executing daily job has been important determinants of customer loyalty. Further, this study provides discussion, implications and conclusion.

  9. Skin disease in United Nations peacekeepers in Lebanon.

    Zhou, Zhou; Liu, T; Zhang, Z


    Skin disease is one of the major components of health problems for soldiers either during war or peacetime. Despite increased numbers and scale of military missions, dermatological survey is limited. The aim of this study was to outline the dermatological profile in international peacekeepers in Lebanon and to explore the features of disease pattern. The dermatological records of peacekeepers visiting a Chinese Level 2 hospital during a 7-year period were retrospectively assessed. Comparisons with previous reports of skin disease in military personnel were performed. A total of 1658 patients (91% men, with a mean age of 32 years) were included. More than half of them were Asian (62%). Dermatitis and eczema (27%) was the leading category. Tinea pedis (13%), lichen simplex chronicus (9%), unspecified dermatitis (8%), verruca vulgaris (7%) and alopecia areata (5%) were the top five complaints. Dermatitis and eczematous eruptions appeared to be the most common condition in troops deployed in the Middle East, whereas fungal infection was highly prevalent in tropical regions. Additionally, a remarkably high rate of alopecia areata was noted in two studies including ours. Environment, group living, occupational activities and work-related stress act as initiating and/or aggravating factors in the development and/or spread of some conditions. The knowledge of disease profile empowers doctors to enforce preventive measures and prepare for treatment modalities. In particular, the underlying psychological component in lichen simplex chronicus and alopecia areata should be addressed appropriately. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  10. Microsoft Office 365 Pk-yritysten tuottavuusratkaisuna

    Nyström, Taina


    Tuottavuus on tämän päivän trendi, sitä vaaditaan lähes joka taholta kiristyneessä kilpailutilanteessa ja digitalisoituneessa maailmassa. Opinnäytetyön tavoitteena oli selvittää Office 365 -pilvipalvelun soveltuvuutta Pk-yritysten tuottavuusratkaisuksi. Työn lähtökohtana oli ammatillinen mielenkiinto Office 365 -palveluita kohtaan. Tutkimuksessa selvitettiin Office 365 -palveluun siirtyneiden yritysten kokemia hyötyjä ja etuja. Tutkimustuloksilla selvitettiin, miten Office 365 -palvelu kulmin...

  11. Liikelahjat mikro- ja pk-yrityksissä

    Danhammer, Joni


    Liikelahjat ovat osa yrityksen menekinedistämistä ja kuuluvat tiiviisti yrityksen markkinointiviestintään. Kuitenkin yleinen talouden kiristynyt tilanne ja vuoden 2014 alussa voimaan astunut verouudistus liikelahjojen verovähennyksissä ovat asioita, jotka vaikuttavat liikelahjojen menekkiin ja niiden antamistapojen muuttumiseen mikro- ja pk-yrityksissä. Näin ollen yrityksillä tulisi tässä tilanteessa olla selkeä käsitys siitä, millaisia liikelahjoja yritys haluaa nykyisin henkilökunnalleen ja...

  12. Photoregulated expression of the PsPK3 and PsPK5 genes in pea seedlings.

    Khanna, R; Lin, X; Watson, J C


    The PsPK3 and PsPK5 genes of the garden pea encode protein-serine/threonine kinases whose catalytic domains are closely related to known signal transducing kinases from animals and fungi. The PsPK3 polypeptide is predicted to be located in the nucleus, whereas PsPK5 is a homologue of NPH1, the probable blue light receptor for phototropism from Arabidopsis. We found previously that when etiolated pea seedlings are illuminated with continuous white light, PsPK3 and PsPK5 transcript levels within apical buds decline substantially, reaching their minimum levels within one day of exposure to light. The role of light in regulating the expression of the PsPK3 and PsPK5 genes was investigated further. To gain insight into the rapidity with which expression changes, 6-day old, dark-grown pea seedlings were transferred to continuous white light, and PsPK3 and PsPK5 RNA levels monitored over the ensuing 24 h. While transcripts from the RbcS gene family increase, the PsPK3 and PsPK5 mRNAs decline rapidly to their minimum levels. PsPK5 mRNA declines 10-fold in ca. 2 h, whereas PsPK3 mRNA declines 4-fold in ca. 8 h. We used single pulses of light to elucidate which photoreceptor triggers the negative regulation of PsPK3 and PsPK5 gene expression. To assess phytochrome involvement, etiolated seedlings were treated with single pulses of red light, red followed by far-red light, or far-red light alone. RbcS induction by a red light pulse is reversible with a subsequent far-red light pulse, clearly showing that phytochrome mediates its induction. Likewise, RbcS expression is induced with a single pulse of blue light or a dichromatic pulse of red+blue light. However, none of these pulses trigger the PsPK3 and PsPK5 mRNA levels to decline. Given the lack of effectiveness of light pulses, etiolated seedlings were transferred to continuous light of three different qualities to determine the spectral sensitivity of PsPK3 and PsPK5 gene expression. Exposure to continuous red, continuous

  13. The Price of Peace? Peacekeeping with Impunity Harms Public Health in Haiti.

    Ivers, Louise C; Guillaume, Yodeline


    In April, 2017, the United Nations (UN) announced that it will withdraw peacekeeping soldiers from Haiti after 13 years there.(1) Known by its French acronym MINUSTAH, the mission has been controversial in security terms, but in terms of public health, it is not controversial to state that peacekeepers will be leaving a heavy mark on the health of Haitians. The UN has acknowledged that peacekeeping soldiers were responsible for both the introduction of cholera (which sparked a nationwide epidemic) and the sexual abuse and exploitation of Haitians, including minors. Despite these acknowledgments, there has been insufficient action to result in justice for either the victims of cholera or the victims of sexual abuse. On July 13, 2017, the UN General Assembly passed a resolution asking the UN member states to consider contributing $40 million in leftover funds from MINUSTAH to the control of cholera in the country, and the member states have 60 days to act.

  14. [PK/PD modeling of aminoglycoside nephrotoxicity].

    Rougier, F; Corvaisier, S; Ducher, M; Claude, D; Jelliffe, R W; Maire, P


    Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.

  15. PK-sensitive PrPSc is infectious and shares basic structural features with PK-resistant PrPSc

    One of the main characteristics of the transmissible isoform of the prion protein (PrPSc) is its partial resistance to proteinase K (PK) digestion. Diagnosis of prion disease typically relies upon immunodetection of PK-digested PrPSc following Western blot or ELISA. More recently, researchers determ...

  16. Perceived military organizational support and peacekeeper distress: a longitudinal investigation.

    Barnes, J Ben; Nickerson, Angela; Adler, Amy B; Litz, Brett T


    Many professions vital to the safety of society require workers to face high magnitude and potentially traumatizing events. Because this routine exposure can cause high levels of stress in workers, it is important to investigate factors that contribute to both risk of posttraumatic stress disorder (PTSD), and healthy responses to stress. Although some research has found social support to mitigate the effects of posttraumatic stress symptoms, scant research has investigated organizational support. The aim of the present study is to investigate the temporal relationship between stress symptoms and perceived organizational support in a sample of 1,039 service members deployed to the peacekeeping mission to Kosovo. Participants completed self-report measures of stress symptoms and perceived organizational support at 4 study time points. Bivariate latent difference score structural equation modeling was utilized to examine the temporal relationship among stress and perceived organizational support. In general, across the 4 time points, latent PCL scores evidenced a salient and negative relationship to subsequent POS latent difference scores. However, no significant relationship was found between latent POS variables and subsequent PCL latent difference scores. Findings suggest that prior stress symptoms are influencing service member's perceptions of the supportiveness of their organization such that increased prior stress is associated with worsening perceptions of support. These results illustrate that targeting stress directly may potentiate the positive influence of organizational support and that institutional support programs should be adapted to better account for the negative biases increased distress may encourage. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  17. From Crisis to Reform: Peacekeeping Strategies for the Protection of Civilians in the Democratic Republic of the Congo

    Boutellis, J. Arthur


    .... This article examines how lessons from early protection crises led the UN missions in the DRC to develop a series of innovative tools for a better peacekeeping response based on improved civil...

  18. RS-34 Phoenix (Peacekeeper Post Boost Propulsion System) Utilization Study

    Esther, Elizabeth A.; Kos, Larry; Burnside, Christopher G.; Bruno, Cy


    The Advanced Concepts Office (ACO) at the NASA Marshall Space Flight Center (MSFC) in conjunction with Pratt & Whitney Rocketdyne conducted a study to evaluate potential in-space applications for the Rocketdyne produced RS-34 propulsion system. The existing RS-34 propulsion system is a remaining asset from the de-commissioned United States Air Force Peacekeeper ICBM program, specifically the pressure-fed storable bipropellant Stage IV Post Boost Propulsion System, renamed Phoenix. MSFC gained experience with the RS-34 propulsion system on the successful Ares I-X flight test program flown in October 2009. RS-34 propulsion system components were harvested from stages supplied by the USAF and used on the Ares I-X Roll control system (RoCS). The heritage hardware proved extremely robust and reliable and sparked interest for further utilization on other potential in-space applications. MSFC is working closely with the USAF to obtain RS-34 stages for re-use opportunities. Prior to pursuit of securing the hardware, MSFC commissioned the Advanced Concepts Office to understand the capability and potential applications for the RS-34 Phoenix stage as it benefits NASA, DoD, and commercial industry. As originally designed, the RS-34 Phoenix provided in-space six-degrees-of freedom operational maneuvering to deploy multiple payloads at various orbital locations. The RS-34 Phoenix Utilization Study sought to understand how the unique capabilities of the RS-34 Phoenix and its application to six candidate missions: 1) small satellite delivery (SSD), 2) orbital debris removal (ODR), 3) ISS re-supply, 4) SLS kick stage, 5) manned GEO servicing precursor mission, and an Earth-Moon L-2 Waypoint mission. The small satellite delivery and orbital debris removal missions were found to closely mimic the heritage RS-34 mission. It is believed that this technology will enable a small, low-cost multiple satellite delivery to multiple orbital locations with a single boost. For both the small

  19. SU-E-T-529: Is MFO-IMPT Robust Enough for the Treatment of Head and Neck Tumors? A 2-Year Outcome Analysis Following Proton Therapy On the First 50 Oropharynx Patients at the MD Anderson Cancer Center

    Frank, S; Garden, A; Anderson, M; Rosenthal, D; Morrison, W; Gunn, B; Fuller, C; Phan, J; Zhang, X; Poenisch, F; Wu, R; Li, H; Gautam, A; Sahoo, N; Gillin, M; Zhu, X [MD Anderson Cancer Ctr., Houston, TX (United States)


    Purpose: Multi-field optimization intensity modulated proton therapy (MFO-IMPT) for oropharyngeal tumors has been established using robust planning, robust analysis, and robust optimization techniques. While there are inherent uncertainties in proton therapy treatment planning and delivery, outcome reporting are important to validate the proton treatment process. The purpose of this study is to report the first 50 oropharyngeal tumor patients treated de-novo at a single institution with MFO-IMPT. Methods: The data from the first 50 patients with squamous cell carcinoma of the oropharynx treated at MD Anderson Cancer Center from January 2011 to December 2014 on a prospective IRB approved protocol were analyzed. Outcomes were analyzed to include local, regional, and distant treatment failures. Acute and late toxicities were analyzed by CTCAE v4.0. Results: All patients were treated with definitive intent. The median follow-up time of the 50 patients was 25 months. Patients by gender were male (84%) and female (16%). The average age was 61 years. 50% of patients were never smokers and 4% were current smokers. Presentation by stage; I–1, II–0, III– 9, IVA–37 (74%), IVB–3. 88% of patients were HPV/p16+. Patients were treated to 66–70 CGE. One local failure was reported at 13 months following treatment. One neck failure was reported at 12 months. 94% of patients were alive with no evidence of disease. One patient died without evidence of disease. There were no Grade 4 or Grade 5 toxicities. Conclusion: MFO-IMPT for oropharyngeal tumors is robust and provides excellent outcomes 2 years after treatment. A randomized trial is underway to determine if proton therapy will reduce chronic late toxicities of IMRT.

  20. The Governors of Maryland and Education the Politics of Peacekeeper Rail Garrison


    members Bob Bell, Bob DeGrass, Terry Freeze, Jim Miller, and Bob Sherman ; Bob Einhorn from the Department of State; Steve Hildreth from the...Carlucci, 28 January 1988. ’ Frank C. Carlucci to Les Aspin, 2 February 1988. 141See, for example, Les Aspin, William L. Dickinson, Bill Chappell , Jr...Peacekeeper rail garrison "a 162Les Aspin and Bill Chappell , Jr. fo Frank C. Carlucci, 15 March 1988. 16Congress, House, Committee on Armed Services, National

  1. Peacekeeping in Mali: A Mismatch Between a Prejudiced Mandate and the Capacity of the Force


    security situation is challenging, but the Algerian Peace Accord offers some hope. Mali faces another civil war with Tuareg and Arab separatist groups...operations protect civilians in civil war ? Once again, a United Nations-mandated force is being challenged to protect civilians in the midst of civil...The data set covers civil wars from 1991 to 2008. In a follow-on article, Hultman et al again examine peacekeeping success in terms of capacity

  2. Friction and Inequality among Peacekeepers in Mali (genudgivet i tema artikelsamling)

    Haugegaard, Rikke


    Maintaining and restoring peace and security in fragile states remains a major global challenge. This virtual special issue of the RUSI Journal provides academics and practitioners with the latest research on peacekeeping, peacebuilding and community security. The collection covers a range......-prone countries? The articles in this issue answer these questions and, in turn, start an important discussion on the effectiveness of national and international responses to conflict prevention....

  3. State Responsibility in PeacekeepingThe effect of responsibility on future contributions

    Nina Mileva


    Full Text Available While the law on state responsibility is a well-developed field in international law, the potential for responsibility on the part of the state as a result of events taking place during peacekeeping missions is a fairly novel phenomenon. Internationally, claims in this field have been brought before the European Court of Human Rights and the International Court of Justice. National courts, on the other hand, have heard a total of six cases on the matter, in Belgium, the UK, and the Netherlands, all eventually apportioning responsibility to the state. This paper explores the effect that the potential for responsibility, as manifested in the outcomes of these recent cases, may have on state behaviour with respect to its future contributions to peacekeeping. The paper combines an exploration of the relevant adjudged cases with views collected from experts and academia in order to formulate three hypotheses on the effect of the potential for responsibility on future state behaviour. These hypotheses are then applied to the example of the Netherlands in the aftermath of a series of decisions finding it responsible for events taking place during its involvement in peacekeeping in Bosnia and Herzegovina in the 1990s. Due to the recent timing of the cases, the paper concludes with preliminary findings on each of the hypotheses, thereby opening the door to future research on the topic.

  4. A comparison of the structure of the PK-sensitive and PK-resistant forms of PrPSc(Abstract)

    Background/Introduction. One of the distinctive phenotypes of the infectious isoform of PrP(PrPSc)is its resistance to proteinase K (PK) digestion. The diagnosis of prion diseases is based on this phenotypic observation. More recently, researchers determined that there is a sizeable fraction of PrPS...

  5. n×k×m格图Pn×Pk×Pm的控制数%DOMINATION NUMBERS OF GRID GRAPHS Pn × Pk × Pm

    姜伟; 杨德林; 刘焕平


    n×k× m格图Pn×Pk×Pm是长为n的路与长为k的路与长为m的路的积,本文给出了Pn×Pk×Pm的控制数的一些结论.①当| n|≤3,|k|≤3,| m|≤3时的Pn×Pk×Pm格图的控制数.②当n∈N,k∈N,m∈N时,Pn×Pk×Pm的控制数的一个上界.③利用"隔空配凑"方法,生成Pn×Pk×Pm格图,并用其将Pn×Pk×Pm的控制数的上界加以优化.

  6. A group randomized trial of critical incident stress debriefing provided to U.S. peacekeepers.

    Adler, Amy B; Litz, Brett T; Castro, Carl Andrew; Suvak, Michael; Thomas, Jeffrey L; Burrell, Lolita; McGurk, Dennis; Wright, Kathleen M; Bliese, Paul D


    In a group randomized trial of critical incident stress debriefing (CISD) with platoons of 952 peacekeepers, CISD was compared with a stress management class (SMC) and survey-only (SO) condition. Multilevel growth curve modeling found that CISD did not differentially hasten recovery compared to the other two conditions. For those soldiers reporting the highest degree of exposure to mission stressors, CISD was minimally associated with lower reports of posttraumatic stress and aggression (vs. SMC), higher perceived organizational support (vs. SO), and more alcohol problems than SMC and SO. Soldiers reported that they liked CISD more than the SMC, and CISD did not cause undue distress.

  7. Peacekeeping, a New Challenge for Burkina Faso’s Armed Forces


    Wall, (accessed January 2, 2013.) 2 Francois Mitterand, “Le discours de la Baule », http...Specialized Requirements to Peacekeeping Operations” Peace operations: Trends,Progress and Prospects, p 80 5 Politique de Défense du Burkina Faso, p 5. 6...3462901.stm (accessed 13 February 2013). 24 Politique de Défense du Burkina Faso, p 12. 25

  8. Tumor Growth Model with PK Input for Neuroblastoma Drug Development


    9/2012 - 4/30/2017 2.40 calendar NCI Anticancer Drug Pharmacology in Very Young Children The proposed studies will use pharmacokinetic... anticancer drugs . DOD W81XWH-14-1-0103 CA130396 (Stewart) 9/1/2014 - 8/31/2016 .60 calendar DOD-DEPARTMENT OF THE ARMY Tumor Growth Model with PK... anticancer drugs . .60 calendar V Foundation Translational (Stewart) 11/1/2012-10/31/2015 THE V FDN FOR CA RES Identification & preclinical testing

  9. Five strands of math tasks big book : grades pk-2

    Reed, Nat; Forest, Chris


    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to learn and review the concepts in unique ways. Included are challenging problem-solving tasks which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  10. Five strands of math drills big book : grades PK-2

    Reed, Nat; Forest, Chris


    For grades PK-2, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Included are warm-up and timed drill activities which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  11. On the categorical nature of Korean /pk/ place assimilation

    Son, Minjung; Kochetov, Alexei


    Korean exhibits regressive place assimilation in /pk/ clusters, which has been described as gradient and rate dependent. However, this assumption has empirically only been tested on the basis of air pressure data [Jun, 1996] which does not provide a direct record of articulator movement. The present study examines articulator movement using EMMA. For three Seoul-dialect speakers, stimuli containing /pk/ clusters were elicited word-medially (for words and nonwords) and in a phrase-boundary condition; two rates were employed. Results show that the labial can indeed reduce word medially, rendering [kk]. However, contrary to previous claims, the data demonstrate that reduction in /pk/ is always categorical, although it is optional or stochastic in its occurrence. Substantial interspeaker variation is observed, with the frequency of reduction being higher at fast rate and ranging overall from 6 at both rates and is never gradient. The lack of reduction in nonsense words and in the phrase boundary condition shows that the process is sensitive to lexical properties. The observed tendency for more gestural overlap word medially compared to the phrase-boundary condition supports the hypothesis that gestural overlap plays a role in the origins of place assimilation. [Work supported by NIH.

  12. Correlation analysis of indicators of physical condition, health and physical fitness of soldiers involved in peacekeeping operations

    Fedak S.S.


    Full Text Available Purpose: to identify the main physical qualities, which positively influence the physical state, health and military - professional career peacekeepers when performing tasks in different climatic conditions. Material : the study involved 98 military service under the contract the first age group (men. Analyzed contingent divided into groups according to climatic conditions of service: in the highlands - 37 person, in hot climates - 35 person, in towns and areas with limited space - 26 person. A correlation analysis between the results of running 100 meters, pulling, running 3 kilometre and indicators of the health and physical condition of the soldiers. Results : It was determined that the participation in peacekeeping missions in mountainous areas and in areas with a hot climate is the quality of the underlying physical endurance. With the participation in peacekeeping missions in populated areas and in areas with limited space - this is the strength and speed. Conclusions : on improving these physical qualities should focus during lessons in physical training of peacekeepers in the centers of immediate preparation for missions.

  13. The prevalence of Blastocystis hominis and other protozoan parasites in soldiers returning from peacekeeping missions.

    Duda, Aleksandra; Kosik-Bogacka, Danuta; Lanocha-Arendarczyk, Natalia; Kołodziejczyk, Lidia; Lanocha, Aleksandra


    Blastocystis hominis is a common intestinal parasite found in humans living in poor sanitary conditions, living in tropical and subtropical climates, exposed to infected animals, or consuming contaminated food or water. The aim of this study was to determine the prevalence of B. hominis in Polish military personnel returning from peacekeeping missions in Iraq and Afghanistan. In total, 1,826 stool samples were examined. Gastrointestinal parasites were detected in 17% of the soldiers. The examined stool samples most frequently contained vacuolar forms of B. hominis (15.3%) and cysts of Entamoeba coli (1.0%) or Giardia lamblia (0.7%). In 97.1% of stool samples from infected soldiers, we observed less than five developmental forms of B. hominis in the field of view (40×). The parasite infections in soldiers were diagnosed in the autumn and the spring. There was no statistical correlation between age and B. hominis infection. Our results show that peacekeeping missions in countries with tropical or subtropical climates could be associated with risk for parasitic diseases, including blastocystosis.

  14. Cancer risk and all-cause mortality among Norwegian military United Nations peacekeepers deployed to Kosovo between 1999 and 2011.

    Strand, Leif Aage; Martinsen, Jan Ivar; Borud, Einar Kristian


    Media reports of leukaemia and other cancers among European United Nations (UN) peacekeepers who served in the Balkans, and a scientific finding of excess Hodgkin lymphoma among Italian UN peacekeepers who served in Bosnia, suggested a link between cancer incidence and depleted uranium (DU) exposure. This spurred several studies on cancer risk among UN peacekeepers who served in the Balkans. Although these studies turned out to be negative, the debate about possible cancers and other health risks caused by DU exposure continues. The aim of the present study was to investigate cancer incidence and all-cause mortality in a cohort of 6076 (4.4% women) Norwegian military UN peacekeepers deployed to Kosovo between 1999 and 2011. The cohort was followed for cancer incidence and mortality from 1999 to 2011. Standardised incidence ratios for cancer (SIR) and mortality ratios (SMR) were calculated from national rates. Sixty-nine cancer cases and 38 deaths were observed during follow-up. Cancer incidence in the cohort was similar to that in the general Norwegian population. No cancers in the overall cohort significantly exceeded incidence rates in the general Norwegian population, but there was an elevated SIR for melanoma of skin in men of 1.90 (95% confidence interval [CI] 0.95-3.40). A fivefold increased incidence of bladder cancer was observed among men who served in Kosovo for ≥ 1 year, based on 2 excess cases (SIR=5.27; 95% CI 1.09-15.4). All-cause mortality was half the expected rate (SMR=0.49; 95% CI 0.35-0.67). Our study did not support the suggestion that UN peacekeeping service in Kosovo is associated with increased cancer risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. ‘It’s Not a Gift When It Comes with Price’: A Qualitative Study of Transactional Sex between UN Peacekeepers and Haitian Citizens

    Athena Rebecca Kolbe


    Full Text Available Sexual exploitation of civilians by peacekeepers undermines the fragile stability established in post-conflict settings. Despite this, it continues to be an ongoing problem for peacekeeping missions worldwide. Efforts to respond to sexual exploitation and abuse (SEA have focused on the establishment of rules prohibiting this behavior, condom distribution, and the training of peacekeepers before and during deployment. In an effort to further our understanding of the dynamics that surround SEA by peacekeepers, 231 Haitian citizens who have engaged in transactional sex with peacekeepers were interviewed about their opinions and experiences. Themes which emerged from these interviews included the triggering events or situations which facilitated engagement in transactional sex, the individual’s understandings of their own experiences in relationship to cultural and social factors, sex as a strategy for filling unmet economic needs, and the differences between the relationships with peacekeepers and normal romantic relationships. Experiences with condom use, pregnancy, abuse, and barriers to reporting assault and harassment were also discussed.

  16. A Business Plan for PK Handbags Manufacturing Company

    Somchatvong, Laddaporn


    PK Co. Limited is a small family-business-owned company located in Thailand. Since established in 1998, the company’s business is manufacturing women’s fashion handbags for wholesale apparel trading company in Thailand. The company also produces and merchandises premium gifts for Kasikorn Bank, one of the largest banks in Thailand. Over the past ten years, the company has generated more than 200 million Baht in revenue or £ 3.6 million . The founders, Likit and Duangporn Somchatvong, have ...

  17. Monitoring VoIP Traffic Using OnePK Technology

    Spišiak, Matej


    Tato bakalářská práce se zabývá novou proprietární technologií od Cisco Systems zvanou OnePK (One Platform Kit). Soustřeďuje se na možnosti použití v oblasti zberu statistických dat o VoIP provozu. Používá DataPath service set, ktorý zabezpečuje sběr paketů ze síťových zařízení firmy Cisco. DataPath service set posílá pakety na vstup aplikace, která tvoří VoIP statistiku z příchozích SIP paketů. Tato aplikace a provedené testy na technologii OnePK jsou výsledky této práce. This bachelor's ...

  18. Invitation withdrawn: humanitarian action, United Nations peacekeeping, and state sovereignty in Chad.

    Karlsrud, John; Felix da Costa, Diana


    This paper looks at the three-way relationship between the Government of Chad, humanitarians, and the United Nations Mission in the Central African Republic and Chad (MINURCAT) from 2004 until June 2011. Chad was never comfortable with the international presence of either humanitarians or peacekeepers and asserted its sovereignty increasingly during this period. MINURCAT was deployed in 2008 to protect humanitarian workers and to facilitate the provision of humanitarian assistance in eastern Chad. This association between the UN mission and humanitarian agencies contributed to making the latter the target of repressive practices by the government, such as the imposition of armed escorts. Facing a steep learning curve, Chad and its state officials gradually appropriated the discourse of the humanitarian and international community and ultimately, in 2010, requested the departure of MINURCAT, claiming that they could meet the protection needs of vulnerable populations in eastern Chad on their own.

  19. Drug design tools--in silico, in vitro and in vivo ADME/PK prediction and interpretation: is PK in monkey an essential part of a good human PK prediction?

    Hosea, Natilie A


    Quantitative human pharmacokinetic (PK) predictions play a critical role in assessing the quality of potential drug candidates and in selecting a human starting dose for clinical evaluation, where the parameters of clearance, volume of distribution, and bioavailability as well as the plasma concentration time profiles are the desired endpoints. While there are numerous reports validating the use of different methods for predictions, it still remains an open question as to what animal species to include when extrapolating the animal PK to human. Given toxicological assessment is generally conducted in two species, a rodent and a non-rodent species, prior to evaluation in human subjects, rat, dog and/or monkey are typically the species ADME scientists employ to evaluate PK. However, the question is, can we achieve an adequate prediction without the use of larger species such as monkey? In the end, the data and tools utilized for human PK predictions will depend on a number of factors such as information from observed human PK for structurally related compounds; the primary mechanism of clearance, and the availability of in silico and in vitro tools applicable to the respective clearance mechanism. Despite these dependencies, for most situations, adequate predictions can be achieved without the use of monkey PK for predicting human.

  20. PK/DB: database for pharmacokinetic properties and predictive in silico ADME models.

    Moda, Tiago L; Torres, Leonardo G; Carrara, Alexandre E; Andricopulo, Adriano D


    The study of pharmacokinetic properties (PK) is of great importance in drug discovery and development. In the present work, PK/DB (a new freely available database for PK) was designed with the aim of creating robust databases for pharmacokinetic studies and in silico absorption, distribution, metabolism and excretion (ADME) prediction. Comprehensive, web-based and easy to access, PK/DB manages 1203 compounds which represent 2973 pharmacokinetic measurements, including five models for in silico ADME prediction (human intestinal absorption, human oral bioavailability, plasma protein binding, blood-brain barrier and water solubility).

  1. 联合国维和财政改革析论%On the UN Financial Reform for Peacekeeping Operation

    康焕华; 王晓静


    The UN financial reform for peacekeeping operation is the key to the sustainable development of UN peacekeeping operation. On the post cold war era, peaeekeeping operation is always in a situation of financial crisis. Therefore, on this background, the UN gradually pushes its financial reform for peacekeeping operation since 1990s and makes it a part of UN peacekeeping operation. During 20 years of reform, the finance of peacekeeping operation has been in a relative stable era under the circumstance of complex reasons and difficulties.%联合国维和财政是联合国维和行动可持续发展的关键。后冷战时代的联合国维和行动频现财政危机。在这一背景下,自20世纪90年代开始,联合国维和财政改革逐渐推进,成为改革联合国维持和平行动的一部分。经过二十多年维和财政改革,在改革动因错综复杂,改革面临诸多困难,改革方案众多的背景下,联合国维和行动的财政改革进入了相对稳定的时期。

  2. Native American Women Perceptions in Pk-12 Administrative Positions in North Dakota Public Schools

    DeCoteau, Lanelia Irene


    Historically Native American women have experienced barriers in their rise to Pk-12 educational leadership positions. There is limited research available on Native American women in educational leadership. Therefore, the purpose for this survey study was to discover what inspired current Pk-12 Native American women educational leaders to choose…

  3. Equidistribution speed towards the Green current for endomorphisms of P-k

    Taflin, Johan


    Let f be a non-invertible holomorphic endomorphism of P-k. For a hypersurface H of P-k, generic in the Zariski sense, we give an explicit speed of convergence of f(-n)(H) towards the dynamical Green (1, 1)-current of f. (C) 2011 Academie des sciences. Publie par Elsevier Masson SAS. Tous droits rese

  4. A physiologically based pharmacokinetic (PB-PK) model for ethylene dibromide; relevance of extrahepatic metabolism

    Hissink, A.M.; Wormhoudt, L.W.; Sherratt, P.J.; Hayes, J.D.; Commandeur, J.N.M.; Vermeulen, N.P.E.; Bladeren, van P.J.


    A physiologically-based pharmacokinetic (PB-PK) model was developed for ethylene dibromide (1,2-dibromoethane, EDB) for rats and humans, partly based on previously published in vitro data (Ploemen et al., 1997). In the present study, this PB-PK model has been validated for the rat. In addition, new

  5. Uptake of inflammatory cell marker [{sup 11}C]PK11195 into mouse atherosclerotic plaques

    Laitinen, Iina; Marjamaeki, Paeivi; Naagren, Kjell; Roivainen, Anne; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Laine, V.J.O. [Turku University Hospital, Department of Pathology, Turku (Finland); Wilson, Ian [GE Healthcare Biosciences, Medical Diagnostics, London (United Kingdom); Leppaenen, Pia; Ylae-Herttuala, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland)


    The ligand [{sup 11}C]PK11195 binds with high affinity and selectivity to peripheral benzodiazepine receptor, expressed in high amounts in macrophages. In humans, [{sup 11}C]PK11195 has been used successfully for the in vivo imaging of inflammatory processes of brain tissue. The purpose of this study was to explore the feasibility of [{sup 11}C]PK11195 in imaging inflammation in the atherosclerotic plaques. The presence of PK11195 binding sites in the atherosclerotic plaques was verified by examining the in vitro binding of [{sup 3}H]PK11195 onto mouse aortic sections. Uptake of intravenously administered [{sup 11}C]PK11195 was studied ex vivo in excised tissue samples and aortic sections of a LDLR/ApoB48 atherosclerotic mice. Accumulation of the tracer was compared between the atherosclerotic plaques and non-atherosclerotic arterial sites by autoradiography and histological analyses. The [{sup 3}H]PK11195 was found to bind to both the atherosclerotic plaques and the healthy wall. The autoradiography analysis revealed that the uptake of [{sup 11}C]PK11195 to inflamed regions in plaques was more prominent (p = 0.011) than to non-inflamed plaque regions, but overall it was not higher than the uptake to the healthy vessel wall. Also, the accumulation of {sup 11}C radioactivity into the aorta of the atherosclerotic mice was not increased compared to the healthy control mice. Our results indicate that the uptake of [{sup 11}C]PK11195 is higher in inflamed atherosclerotic plaques containing a large number of inflammatory cells than in the non-inflamed plaques. However, the tracer uptake to other structures of the artery wall was also prominent and may limit the use of [{sup 11}C]PK11195 in clinical imaging of atherosclerotic plaques. (orig.)

  6. UN Peacekeeping

    of civilians, Denmark’s contribution to the UN mission in Liberia, anti-piracy operations, and the prospective role of special forces in UN operations. The two forewords of the book have been written by Major General Hu Guangzheng from AMS and Rear Admiral Nils Christian Wang from the Royal Danish Defence...

  7. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

    Cynthia L. Hendrickson


    Full Text Available In mammalian cells, DNA double-strand breaks (DSBs are primarily repaired by nonhomologous end joining (NHEJ. The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, the presence of DNA-PKcs appears to inhibit DNA-PK-independent NHEJ, and in vitro analysis of DNA-PK-independent NHEJ in the presence of the DNA-PKcs protein remains problematic. We have developed an in vitro assay that is preferentially active for DNA-PK-independent DSB repair based solely on its reaction conditions, facilitating coincident differential biochemical analysis of the two pathways. The results indicate the biochemically distinct nature of the end-joining mechanisms represented by the DNA-PK-dependent and -independent NHEJ assays as well as functional differences between the two pathways.

  8. Expression pattern of the CsPK3 auxin-responsive protein kinase gene.

    Chono, M; Suzuki, Y; Nemoto, K; Yamane, H; Murofushi, N; Yamaguchi, I


    We have previously cloned a cDNA of a putative serine/threonine protein kinase gene named CsPK3 from cucumber, the mRNA level of which was up-regulated by auxin and down-regulated by light irradiation. To examine the CsPK3 gene expression in detail, we cloned a genomic DNA of CsPK3 gene and made transgenic tobacco (Nicotiana tabacum L. cv. Petit Havana SR1) plants containing the fused CsPK3 promoter-beta-glucuronidase gene. The beta-glucuronidase expression was detected in the shoot apex, vascular tissues, and the outermost layer of cortex. The histological distribution of CsPK3 mRNA in cucumber seedlings was supported by in situ hybridization, where the positive signals were observed in similar tissues as those observed by beta-glucuronidase staining. The responsiveness of the CsPK3 gene to auxin and light was also confirmed for beta-glucuronidase activity. The pattern of beta-glucuronidase staining changed during the development of the tobacco seedlings. The results of our experiment showed that CsPK3 was expressed in a wide variety of tissues and cells in which the developmental and growth controls by auxin are suggested.

  9. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

    Hendrickson, Cynthia L.; Purkayastha, Shubhadeep; Pastwa, Elzbieta; Neumann, Ronald D.; Winters, Thomas A.


    In mammalian cells, DNA double-strand breaks (DSBs) are primarily repaired by nonhomologous end joining (NHEJ). The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that mediate DSB end joining. However, recent studies show that additional DNA-PK-independent NHEJ pathways also exist. Unfortunately, the presence of DNA-PKcs appears to inhibit DNA-PK-independent NHEJ, and in vitro analysis of DNA-PK-independent NHEJ in the presence of the DNA-PKcs protein remains problematic. We have developed an in vitro assay that is preferentially active for DNA-PK-independent DSB repair based solely on its reaction conditions, facilitating coincident differential biochemical analysis of the two pathways. The results indicate the biochemically distinct nature of the end-joining mechanisms represented by the DNA-PK-dependent and -independent NHEJ assays as well as functional differences between the two pathways. PMID:20706599

  10. Service quality in peacekeeping mission as a determinant of customer’s perceived value: Empirical evidence

    Azman Bin Ismail


    Full Text Available Purpose: Previous studies have been employing SERVQUAL by Parasuraman et al. (1985, 1988 to measure service quality in various service sectors due to its generic nature. Understanding the relationship between service quality and customer’s perceived value in non-business organizational settings is equally important with business setting as positive perception leads to favorable outcome. Hence, the aim of this study is to examine the relationship between service quality and perceived value. Design/methodology/approach: The self-administered survey questionnaires were employed to gather data from Malaysian soldiers who involved in peacekeeping mission at a Middle Eastern country. The hypothesized model was analyzed using the SmartPLS 2.0. Findings: The outcomes of SmartPLS path model confirmed that that all service quality dimensions namely tangible, responsiveness, reliability, assurance, empathy did act as important determinants of customer’s perceived value in the organizational sample. Practical implications: The findings of this study may be used as guidelines by practitioners to formulate relevant and appropriate strategies in order to enhance quality of service delivery in agile organizations. Originality/value: The work deals with service quality in non-business setting. Although the scale has been widely used, some modifications are generally needed in order to reflect specific characteristics of service sectors under study. The findings confirmed that in general SERVQUAL five dimensions are important determinants to the various service sectors.

  11. Psychotrauma and effective treatment of post-traumatic stress disorder in soldiers and peacekeepers

    Quarcoo David


    Full Text Available Abstract Psychotrauma occurs as a result to a traumatic event, which may involve witnessing someone's actual death or personally experiencing serious physical injury, assault, rape and sexual abuse, being held as a hostage, or a threat to physical or psychological integrity. Post-traumatic stress disorder (PTSD is an anxiety disorder and was defined in the past as railway spine, traumatic war neurosis, stress syndrome, shell shock, battle fatigue, combat fatigue, or post-traumatic stress syndrome (PTSS. If untreated, post-traumatic stress disorder can impair relationships of those affected and strain their families and society. Deployed soldiers are especially at a high risk to be affected by PTSD but often receive inadequate treatment. Reviews to date have focused only on a single type of treatment or groups of soldiers from only one country. The aim of the current review was to evaluate characteristics of therapeutic methods used internationally to treat male soldiers' PTSD after peacekeeping operations in South Eastern Europe and the Gulf wars. This systematic literature review returned results pertaining to the symptoms, diagnosis, timing and effectiveness of treatment. Sample groups and controls were relatively small and, therefore, the results lack generalizability. Further research is needed to understand the influence and unique psychological requirements of each specific military operation on the internationally deployed soldiers.

  12. Synthesis of the enantiomers of [N-methyl-[sup 11]C]PK 11195 and comparison of their behaviours as radioligands for PK binding sites in rats

    Shah, Farah; Hume, S.P.; Pike, V.W.; Ashworth, S.; McDermott, J. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit)


    The enantiomers of [N-methyl-[sup 11]C]PK 11195, a radioligand for PET studies of PK (peripheral benzodiazepine) binding sites, have been prepared from the newly synthesized N-desmethyl-enantiomers by [sup 11]C-methylation with N.C.A. [[sup 11]C]iodomethane. The brain uptake and retention of each enantiomer was compared with that of the racemic radioligand after i.v. administration into normal rats and into rats with focal cortical lesions. The observed differences are consistent with the approximately 2-fold greater affinity of the R-enantiomer for PK binding sites reported in vitro and imply that the use of this entantiomer would have advantages over the use of the racemate currently used for PET studies. (author).




    In this paper, it is shown that a sufficient condition for the existence of a K1,pk-factorization of Km,n, whenever p is a prime number and k is a positive integer, is (1) m≤pkn,(2) n≤pkm,(3)pkn-m≡pkm- n≡0(mod(p2k - 1)) and (4)(pkn-m)(pkm- n)≡0(mod(pk - 1)pk×(p2k-1)(m+n)).

  14. Defining interactions between DNA-PK and ligase IV/XRCC4

    Hsu, Hsin-Ling; Yannone, Steven M.; Chen, David J.


    Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double-strand breaks in mammalian cells. DNA-dependent protein kinase (DNA-PK), ligase IV, and XRCC4 are all critical components of the NHEJ repair pathway. DNA-PK is composed of a heterodimeric DNA-binding component, Ku, and a large catalytic subunit, DNA-PKcs. Ligase IV and XRCC4 associate to form a multimeric complex that is also essential for NHEJ. DNA-PK and ligase IV/XRCC4 interact at DNA termini which results in stimulated ligase activity. Here we define interactions between the components of these two essential complexes, DNA-PK and ligase IV/XRCC4. We find that ligase IV/XRCC4 associates with DNA-PK in a DNA-independent manner. The specific protein-protein interactions that mediate the interaction between these two complexes are further identified. Direct physical interactions between ligase IV and Ku as well as between XRCC4 and DNA-PKcs are shown. No direct interactions are observed between ligase IV and DNA-PKcs or between XRCC4 and Ku. Our data defines the specific protein pairs involved in the association of DNA-PK and ligase IV/XRCC4, and suggests a molecular mechanism for coordinating the assembly of the DNA repair complex at DNA breaks.

  15. Deficiencies in the UN Peacekeeping Intelligence and Its Countermeasures%联合国维和情报保障缺陷与对策

    卢张哲; 段建炜; 孙维谦


    Purpose/Significance] Intelligence-ensured is the key factors to UN Peacekeeping. However, it is still marginalized effect zone, which lies in imperfect management mechanisms and obvious external influences. It affect Peacekeeping intelligence-ensured opera-tion. These factors have restricted the efficient functioning of UN Peacekeeping Intelligence. With the increasing complexity of UN Peace-keeping, How to optimize intelligence-ensured has become a focus problem. [ Method/Process] In this paepr, through the view of the historical and comparative analysis as well as the case study of the UN official documents and academic research, we analyze the flaws and problems of the UN Peacekeeping Intelligence. [ Result/Conclusion] At last,we put forward promoting legalization, unified management and multi-cooperation,which should be effective measures to optimize peacekeeping intelligence,these suggestions are expected beneficial to China's growing role in UN Peacekeeping.%[目的/意义]情报保障关乎联合国维和行动的成败,然而情报保障却一直被联合国置于边缘地带,加之管理不完善、受外部影响突出等问题,维和情报保障的运作被严重制约。当前联合国维和行动日趋复杂,如何优化情报保障已成为焦点问题。[方法/过程]通过查阅联合国官方文件和有关学者研究,采用历史分析法、个案研究法及比较分析法,深入剖析联合国维和情报保障的内在缺陷与问题。[结果/结论]指出推动维和情报法制化、实现管理一体化以及推动多方参与,是提升维和情报保障能力和维和行动实力的可行办法,对我国进一步参与联合国维和有一定的参考作用。

  16. The Promotion of Safety Awareness and Self - protection Capabilities of UN Peacekeeping Police%维和警察安全意识和自我防护能力刍议



    联合国维和任务日益复杂,维和警察在任务区面临的危险无法预知。从维和培训以及任务区执法着手,通过合理的安全教育,有助于不断提高维和警察的安全意识和白我防护能力。%The UN peacekeeping operations are becoming increasingly complex, which leads to many unpredictable risks for UN peacekeeping police officers. From the perspective of peacekeeping training and UN mission law enforcement and through appropriate safety awareness training, this paper focuses on the promotion of safety awareness and self - protection capabilities of UN peacekeeping police.

  17. International Conference CoMFoS15

    Kimura, Masato; Chalupecký, Vladimír; Ohtsuka, Kohji; Tagami, Daisuke; Takada, Akira


    This book focuses on mathematical theory and numerical simulation related to various aspects of continuum mechanics, such as fracture mechanics, elasticity, plasticity, pattern dynamics, inverse problems, optimal shape design, material design, and disaster estimation related to earthquakes. Because these problems have become more important in engineering and industry, further development of mathematical study of them is required for future applications. Leading researchers with profound knowledge of mathematical analysis from the fields of applied mathematics, physics, seismology, engineering, and industry provide the contents of this book. They help readers to understand that mathematical theory can be applied not only to different types of industry, but also to a broad range of industrial problems including materials, processes, and products.

  18. Simulation of the impact of rifampicin on darunavir/ritonavir PK and dose adjustment strategies in HIV-infected patients: a population PK approach

    Laura Dickinson


    Full Text Available Introduction: Treatment of HIV/TB co-infection is challenging due to high drug–drug interaction potential between antiretrovirals and rifamycins, such as rifampicin (RIF. The PK interaction between darunavir/ritonavir (DRV/RTV and RIF has not been studied. Utilizing other protease inhibitor data, population PK modelling and simulation was applied to assess the impact of RIF on DRV/RTV PK and generate alternative dosing strategies to aid future clinical trial design. Materials and Methods: A previously developed model describing DRV/RTV PK including data from three studies in HIV patients was used [n=51, 7 female, DRV/RTV 800/100 mg (n=32 or 900/100 mg once daily (qd; n=19 (1. The PK interaction between DRV/RTV and RIF was assumed to mimic that observed in HIV-infected, TB negative patients receiving lopinavir (LPV/RTV (n=21 (2. Simulations of DRV/RTV 800/100 mg qd (n=1000 were performed (-RIF. The model was adapted to increase the typical value of apparent oral clearance (CL/F by 71% and 36% and decrease relative bioavailability (F by 20% and 45% for DRV and RTV, respectively (2; 1000 simulations were generated (+RIF. Dose adjustments of DRV/RTV 1200/200 mg qd, 800/100 mg and 1200/150 mg twice daily (bid were simulated to overcome the interaction. DRV trough (Ctrough for each dosing scenario was compared to the reference (-RIF by GMR (90% CI. Results: DRV and RTV were described by a 1 and 2-compartment model, respectively. A maximum effect model, with RTV inhibiting DRV CL/F, best described the relationship between the drugs. Compared to the reference (-RIF, simulated DRV Ctrough was 70%, 46% and 20% lower for 800/100 mg qd, 1200/200 mg qd and 800/100 mg bid all +RIF, respectively. Ctrough was 38% higher with 1200/150 mg bid +RIF (Table 1. Conclusions: Modelling and simulation was used to investigate the theoretical impact of RIF on DRV/RTV PK. Based on simulations, 800/100 mg and 1200/150 mg both bid could largely overcome the impact of the

  19. Structure of Pseudoknot PK26 Shows 3D Domain Swapping in an RNA

    Lietzke, Susan E; Barnes, Cindy L.


    3D domain swapping provides a facile pathway for the evolution of oligomeric proteins and allosteric mechanisms and a means for using monomer-oligomer equilibria to regulate biological activity. The term "3D domain swapping" describes the exchange of identical domains between two protein monomers to create an oligomer. 3D domain swapping has, so far, only been recognized in proteins. In this study, the structure of the pseudoknot PK26 is reported and it is a clear example of 3D domain swapping in RNA. PK26 was chosen for study because RNA pseudoknots are required structures in several biological processes and they arise frequently in in vitro selection experiments directed against protein targets. PK26 specifically inhibits HIV-1 reverse transcriptase with nanomolar affinity. We have now determined the 3.1 A resolution crystal structure of PK26 and find that it forms a 3D domain swapped dimer. PK26 shows extensive base pairing between and within strands. Formation of the dimer requires the linker region between the pseudoknot folds to adopt a unique conformation that allows a base within a helical stem to skip one base in the stacking register. Rearrangement of the linker would permit a monomeric pseudoknot to form. This structure shows how RNA can use 3D domain swapping to build large scale oligomers like the putative hexamer in the packaging RNA of bacteriophage Phi29.

  20. D6PK AGCVIII kinases are required for auxin transport and phototropic hypocotyl bending in Arabidopsis.

    Willige, Björn C; Ahlers, Siv; Zourelidou, Melina; Barbosa, Inês C R; Demarsy, Emilie; Trevisan, Martine; Davis, Philip A; Roelfsema, M Rob G; Hangarter, Roger; Fankhauser, Christian; Schwechheimer, Claus


    Phototropic hypocotyl bending in response to blue light excitation is an important adaptive process that helps plants to optimize their exposure to light. In Arabidopsis thaliana, phototropic hypocotyl bending is initiated by the blue light receptors and protein kinases phototropin1 (phot1) and phot2. Phototropic responses also require auxin transport and were shown to be partially compromised in mutants of the PIN-FORMED (PIN) auxin efflux facilitators. We previously described the D6 PROTEIN KINASE (D6PK) subfamily of AGCVIII kinases, which we proposed to directly regulate PIN-mediated auxin transport. Here, we show that phototropic hypocotyl bending is strongly dependent on the activity of D6PKs and the PIN proteins PIN3, PIN4, and PIN7. While early blue light and phot-dependent signaling events are not affected by the loss of D6PKs, we detect a gradual loss of PIN3 phosphorylation in d6pk mutants of increasing complexity that is most severe in the d6pk d6pkl1 d6pkl2 d6pkl3 quadruple mutant. This is accompanied by a reduction of basipetal auxin transport in the hypocotyls of d6pk as well as in pin mutants. Based on our data, we propose that D6PK-dependent PIN regulation promotes auxin transport and that auxin transport in the hypocotyl is a prerequisite for phot1-dependent hypocotyl bending.

  1. Porcine circovirus-2 capsid protein induces cell death in PK15 cells

    Walia, Rupali; Dardari, Rkia, E-mail:; Chaiyakul, Mark; Czub, Markus


    Studies have shown that Porcine circovirus (PCV)-2 induces apoptosis in PK15 cells. Here we report that cell death is induced in PCV2b-infected PK15 cells that express Capsid (Cap) protein and this effect is enhanced in interferon gamma (IFN-γ)-treated cells. We further show that transient PCV2a and 2b-Cap protein expression induces cell death in PK15 cells at rate similar to PCV2 infection, regardless of Cap protein localization. These data suggest that Cap protein may have the capacity to trigger different signaling pathways involved in cell death. Although further investigation is needed to gain deeper insights into the nature of the pathways involved in Cap-induced cell death, this study provides evidence that PCV2-induced cell death in kidney epithelial PK15 cells can be mapped to the Cap protein and establishes the need for future research regarding the role of Cap-induced cell death in PCV2 pathogenesis. - Highlights: • IFN-γ enhances PCV2 replication that leads to cell death in PK15 cells. • IFN-γ enhances nuclear localization of the PCV2 Capsid protein. • Transient PCV2a and 2b-Capsid protein expression induces cell death. • Cell death is not dictated by specific Capsid protein sub-localization.

  2. [Proliferation characteristics of a PK-15 cell-adapted strain of porcine parvovirus].

    Wu, Yun-Fei; Zhu, Ling; Xu, Zhi-Wen; Fu, Meng-Jin; Chen, Lei; Yang, Ai-Guo; Guo, Wan-Zhu


    To study the proliferation characteristics of PPV in differently infected way and the variance of concentrations in different cells. A strain of porcine parvovirus(PPV) was adapted to PK-15 cells, and a Real-time fluorescent quantitative PCR (FQ-PCR) assay was developed based on the specific region of the NS1 gene of PPV to quantify the PPV. The FQ-PCR was used to measure the viral concentration of virus-infected cells by simultaneous or step by step inoculation and plot one-step growth curves. The proliferation characteristics of PPV strain in different cells lines (HeLa, MDBK, PK-15 ,ST, F81, BHK-21 and Marc-145) was also compared. The results showed the PK-15 cell -adapted strain of PPV produced CPE after 12 passages, and maintained stable CPE at the following 10 messages. The one-step growth curve showed that the virus concentration of simultaneous inoculation was higher than that of the step-by-step inoculation, and the proliferation cycle of step-by-step inoculation was shorter. The proliferation ability of PPV strain in different cells showed that CPE appeared first inPK-15, followed by ST, HeLa and MDBK, and the virus concentration was highest in ST, followed byPK-15, MDBK and HeLa. NO proliferation was observed in F81, BHK-21 and Marc-145 cells. These findings lay a material foundation for the basic researches on PPV and the development of vaccine.

  3. Sustained release ophthalmic dexamethasone: In vitro in vivo correlations derived from the PK-Eye.

    Awwad, Sahar; Day, Richard M; Khaw, Peng T; Brocchini, Steve; Fadda, Hala M


    Corticosteroids have long been used to treat intraocular inflammation by intravitreal injection. We describe dexamethasone loaded poly-DL-lactide-co-glycolide (PLGA) microparticles that were fabricated by thermally induced phase separation (TIPS). The dexamethasone loaded microparticles were evaluated using a two-compartment, in vitro aqueous outflow model of the eye (PK-Eye) that estimates drug clearance time from the back of the eye via aqueous outflow by the anterior route. A dexamethasone dose of 0.20±0.02mg in a 50μL volume of TIPS microparticles resulted in a clearance t1/2 of 9.6±0.3days using simulated vitreous in the PK-Eye. Since corticosteroids can also clear through the retina, it is necessary to account for clearance through the back of the eye. Retinal permeability data, published human ocular pharmacokinetics (PK) and the PK-Eye clearance times were then used to establish in vitro in vivo correlations (IVIVCs) for intraocular clearance times of corticosteroid formulations. A t1/2 of 48h was estimated for the dexamethasone-TIPS microparticles, which is almost 9 times longer than that reported for dexamethasone suspension in humans. The prediction of human clearance times of permeable molecules from the vitreous compartment can be determined by accounting for drug retinal permeation and determining the experimental clearance via the anterior aqueous outflow pathway using the PK-Eye. Copyright © 2017. Published by Elsevier B.V.

  4. Translational PK/PD modeling to increase probability of success in drug discovery and early development.

    Lavé, Thierry; Caruso, Antonello; Parrott, Neil; Walz, Antje

    In this review we present ways in which translational PK/PD modeling can address opportunities to enhance probability of success in drug discovery and early development. This is achieved by impacting efficacy and safety-driven attrition rates, through increased focus on the quantitative understanding and modeling of translational PK/PD. Application of the proposed principles early in the discovery and development phases is anticipated to bolster confidence of successfully evaluating proof of mechanism in humans and ultimately improve Phase II success. The present review is centered on the application of predictive modeling and simulation approaches during drug discovery and early development, and more specifically of mechanism-based PK/PD modeling. Case studies are presented, focused on the relevance of M&S contributions to real-world questions and the impact on decision making.

  5. The decay of $\\Lambda_b\\rightarrow p~K^-$ in QCD factorization approach

    Zhu, Jie; Wei, Zheng-Tao


    With only the tree level operator, the decay of $\\Lambda_b\\rightarrow pK$ is predicted to be one order smaller than the experimental data. The QCD penguin effects should be taken into account. In this paper, we explore the one-loop QCD corrections to the decay of $\\Lambda_b\\to pK$ within the framework of QCD factorization approach. For the baryon system, the diquark approximation is adopted. The transition hadronic matrix elements between $\\Lambda_b$ and $p$ are calculated in the light front quark model. The branching ratio of $\\Lambda_b\\rightarrow pK$ is predicted to be about $4.85\\times 10^{-6}$ which is consistent with experimental data $(4.9\\pm 0.9)\\times 10^{-6}$. The CP violation is about 5\\% in theory.

  6. Coincident In Vitro Analysis of DNA-PK-Dependent and -Independent Nonhomologous End Joining

    Hendrickson, Cynthia L.; Shubhadeep Purkayastha; Elzbieta Pastwa; Neumann, Ronald D.; Winters, Thomas A.


    In mammalian cells, DNA double-strand breaks (DSBs) are primarily repaired by nonhomologous end joining (NHEJ). The current model suggests that the Ku 70/80 heterodimer binds to DSB ends and recruits DNA-PKcs to form the active DNA-dependent protein kinase, DNA-PK. Subsequently, XRCC4, DNA ligase IV, XLF and most likely, other unidentified components participate in the final DSB ligation step. Therefore, DNA-PK plays a key role in NHEJ due to its structural and regulatory functions that media...

  7. Libéria 1993: o “não” das grandes potências militares do peacekeeping

    Pimenta, Catarina


    O artigo pretende aferir as razões que terão ditado a ausência das grandes potências geralmente envolvidas em peacekeeping na missão das Nações Unidas estabelecida em 1993 na Libéria (UNOMIL). Pelo recurso ao cruzamento de diferentes níveis de análise (sistémico, transnacional e estatal), tentar-se-á perceber por que motivos os Estados Unidos e o Canadá (e também Reino Unido, Itália e França, ainda que de forma menos central) não contribuíram militarmente para esta missão, marcando presença (...

  8. External-cause mortality among 21 609 Norwegian male military peacekeepers deployed to Lebanon between 1978 and 1998.

    Strand, Leif Aage; Martinsen, Jan Ivar; Fadum, Elin Anita; Borud, Einar Kristian


    To investigate external-cause mortality among 21 609 Norwegian male military peacekeepers deployed to Lebanon during 1978-1998. The cohort was followed from the 1st day of deployment through 2013, and mortality during deployment and post discharge was assessed using SMRs calculated from national rates in Norway. Poisson regression was used to see the effect of high-conflict versus low-conflict exposure. For the total cohort, external-cause mortality was within expected values during deployment (SMR=0.80) and post discharge (SMR=1.05). In the low-conflict exposure group, a lower mortality from all external causes (SMR=0.77), transport accidents (SMR=0.55) and accidental poisoning (SMR=0.53) was seen. The high-conflict exposure group showed an elevated mortality from all external causes (SMR=1.20), transport accidents (SMR=1.51) and suicide (SMR=1.30), but these risks were elevated only during the first 5 years after discharge. This group also showed elevated mortality from all external causes (rate ratio, RR=1.49), and for transport accidents (RR=3.30) when compared with the low-conflict exposure group. Overall external-cause mortality among our peacekeepers was equal to national rates during deployment and post discharge. High-conflict exposure was associated with elevated mortality from all external causes, transport accidents and suicide during the first 5 years after discharge from service. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Evaluation of a PK/PBAN Analog with an (E)-Alkene, trans-Pro Isostere Identifies the Pro Orientation for Activity in Four Diverse PK/PBAN Bioassays


    pentapeptide common to the PK/PBAN neuropeptide class retains activity in each of the disparate functions. The functional diversity of the PK/PBAN family...2008;29:268–75. [15] Matsumoto S, Kitamura A, Nagasawa H, Kataoka H, Orikasa C, Mitsui T, et al. Functional diversity of a neurohormone produced by the

  10. On Return from Peacekeeping: A review of current research on psychological well-being in military personnel returning from operational deployment

    Karen Brounéus


    Full Text Available The number and size of UN and Allied peacekeeping deployments[1] have increased dramatically since the end of the Cold War [1], as have the budgets that support them. The UN budgeted 7.23 billion USD for the 2012-2013 fiscal year for UN Peacekeeping operations.[2] An explanation for this increase is likely to be found in two global trends seen in armed conflict in recent years: first, that nearly all wars in the world today are fought within countries, and second, the unprecedented rise in peace agreements as a means to end conflict [2]. Both of these factors present new challenges for peace-building as former enemies must continue living side by side when the conflict has ended, in a continuous negotiation for peace. Research suggests that international peace support operations indeed have the potential to improve the chances for preventing further conflict. In the first global, quantitative analysis on the effect of peacekeeping operations (PKOs, Doyle and Sambanis found a significant and substantial effect of peacekeepers on peacebuilding two years post conflict [3]. This finding is similar to later studies. For example, Fortna demonstrated that the risk of further conflict drops by 75%–85% with the presence of a PKO [4, 5]. Other research has found that PKOs limit the temporal and spatial contagion of conflict [6], and can also have a preventive effect, reducing the risk of genocidal violence [7]. However, recent research has also found that peacekeeping operations in settings where there is not yet peace or stability, such as Afghanistan, may entail the risk of spurring violence against civilians by rebel groups if the deployment does not have an explicit mandate to protect civilians [8]. Similarly, when looking at other definitions of success aside from the prevention of further conflict, such as meeting the goals of the mandate, or establishing basic democracy and stability – a governance goal for most current deployments – the

  11. Traumatic events, other operational stressors and physical and mental health reported by Australian Defence Force personnel following peacekeeping and war-like deployments

    Waller Michael


    Full Text Available Abstract Background The association between stressful events on warlike deployments and subsequent mental health problems has been established. Less is known about the effects of stressful events on peacekeeping deployments. Methods Two cross sectional studies of the Australian Defence Force were used to contrast the prevalence of exposures reported by a group deployed on a peacekeeping operation (Bougainville, n = 1704 and those reported by a group deployed on operations which included warlike and non-warlike exposures (East Timor, n = 1333. A principal components analysis was used to identify groupings of non-traumatic exposures on deployment. Multiple regression models were used to assess the association between self-reported objective and subjective exposures, stressors on deployment and subsequent physical and mental health outcomes. Results The principal components analysis produced four groups of non-traumatic stressors which were consistent between the peacekeeping and more warlike deployments. These were labelled ‘separation’, ‘different culture’, ‘other people’ and ‘work frustration’. Higher levels of traumatic and non-traumatic exposures were reported by veterans of East Timor compared to Bougainville. Higher levels of subjective traumatic exposures were associated with increased rates of PTSD in East Timor veterans and more physical and psychological health symptoms in both deployed groups. In Bougainville and East Timor veterans some non-traumatic deployment stressors were also associated with worse health outcomes. Conclusion Strategies to best prepare, identify and treat those exposed to traumatic events and other stressors on deployment should be considered for Defence personnel deployed on both warlike and peacekeeping operations.

  12. The human DNA-activated protein kinase, DNA-PK: Substrate specificity

    Anderson, C.W.; Connelly, M.A.; Zhang, H.; Sipley, J.A. [Brookhaven National Lab., Upton, NY (United States). Biology Dept.; Lees-Miller, S.P.; Lintott, L.G. [Univ. of Calgary, Alberta (Canada). Dept. of Biological Sciences; Sakaguchi, Kazuyasu; Appella, E. [National Institutes of Health, Bethesda, MD (United States). Lab. of Cell Biology


    Although much has been learned about the structure and function of p53 and the probable sequence of subsequent events that lead to cell cycle arrest, little is known about how DNA damage is detected and the nature of the signal that is generated by DNA damage. Circumstantial evidence suggests that protein kinases may be involved. In vitro, human DNA-PK phosphorylates a variety of nuclear DNA-binding, regulatory proteins including the tumor suppressor protein p53, the single-stranded DNA binding protein RPA, the heat shock protein hsp90, the large tumor antigen (TAg) of simian virus 40, a variety of transcription factors including Fos, Jun, serum response factor (SRF), Myc, Sp1, Oct-1, TFIID, E2F, the estrogen receptor, and the large subunit of RNA polymerase II (reviewed in Anderson, 1993; Jackson et al., 1993). However, for most of these proteins, the sites that are phosphorylated by DNA-PK are not known. To determine if the sites that were phosphorylated in vitro also were phosphorylated in vivo and if DNA-PK recognized a preferred protein sequence, the authors identified the sites phosphorylated by DNA-PK in several substrates by direct protein sequence analysis. Each phosphorylated serine or threonine is followed immediately by glutamine in the polypeptide chain; at no other positions are the amino acid residues obviously constrained.

  13. The human DNA-activated protein kinase, DNA-PK: Substrate specificity

    Anderson, C.W.; Connelly, M.A.; Zhang, H.; Sipley, J.A. [Brookhaven National Lab., Upton, NY (United States). Biology Dept.; Lees-Miller, S.P.; Lintott, L.G. [Univ. of Calgary, Alberta (Canada). Dept. of Biological Sciences; Sakaguchi, Kazuyasu; Appella, E. [National Institutes of Health, Bethesda, MD (United States). Lab. of Cell Biology


    Although much has been learned about the structure and function of p53 and the probable sequence of subsequent events that lead to cell cycle arrest, little is known about how DNA damage is detected and the nature of the signal that is generated by DNA damage. Circumstantial evidence suggests that protein kinases may be involved. In vitro, human DNA-PK phosphorylates a variety of nuclear DNA-binding, regulatory proteins including the tumor suppressor protein p53, the single-stranded DNA binding protein RPA, the heat shock protein hsp90, the large tumor antigen (TAg) of simian virus 40, a variety of transcription factors including Fos, Jun, serum response factor (SRF), Myc, Sp1, Oct-1, TFIID, E2F, the estrogen receptor, and the large subunit of RNA polymerase II (reviewed in Anderson, 1993; Jackson et al., 1993). However, for most of these proteins, the sites that are phosphorylated by DNA-PK are not known. To determine if the sites that were phosphorylated in vitro also were phosphorylated in vivo and if DNA-PK recognized a preferred protein sequence, the authors identified the sites phosphorylated by DNA-PK in several substrates by direct protein sequence analysis. Each phosphorylated serine or threonine is followed immediately by glutamine in the polypeptide chain; at no other positions are the amino acid residues obviously constrained.

  14. Data of evolutionary structure change: 1ACMA-3E2PK [Confc[Archive


  15. Neuroinflammation in bipolar disorder : A [C-11]-(R)-PK11195 positron emission tomography study

    Haarman, Bartholomeus C.M.; Riemersma -van der Lek, Rixt; de Groot, Jan Cees; Ruhe, Eric; Klein, Hans C; Zandstra, Tjitske E; Burger, Huibert; Schoevers, Robert A.; de Vries, Erik F.J.; Drexhage, Hemmo A; Nolen, Willem A.; Doorduin, Janine


    Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential fo

  16. A Markov approach to characterising the PK-PD relationship of anti-migraine drugs

    Maas, Hugo J.


    The objective of the investigations described in this thesis was the development of novel PK-PD modelling for the characterisation and prediction of the effects of anti-migraine drugs in clinical investigations. The Markov approach has first been applied to migraine data by Hassani and Ebutt. They

  17. Construction of an integrated map of rose with AFLP, SSR, PK, RGA, SCAR and morphological markers

    Yan Zifu, Z.; Denneboom, C.; Hattendorf, A.; Dolstra, O.; Debener, T.; Stam, P.; Visser, P.B.


    A high-density genetic map with a number of anchor markers has been created to be used as a tool to dissect genetic variation in rose. Linkage maps for the diploid 94/1 population consisting of 88 individuals were constructed using a total of 520 molecular markers including AFLP, SSR, PK, RGA, RFLP,

  18. Derivation of adsorption parameters for nanofiltration membranes using a 1-pK Basic Stern model

    de Lint, W.B.S.; Benes, Nieck Edwin; Higler, A.P.; Verweij, H.


    The ion retention and flux of nanofiltration (NF) membranes are to a large extent determined by the membrane surface charge. This surface charge is in turn strongly influenced by adsorption of ions from the solution onto the membrane material. A 1-pK adsorption model with a Basic Stern electrostatic

  19. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Ijaz Ahmad


    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  20. Biostable beta-Amino Acid PK/PBAN Analogs: Agonist and Antagonist Properties


    peptide [1,11,29,30]. The functional diversity of the PK/PBAN family raises many questions regarding the mechanisms by which these neuropeptides operate and...46. [18] Matsumoto S. Functional diversity of a neurohormone produced by the subesophageal ganglion: molecular identity of melanization and reddish

  1. PK11195 effect on steroidogenesis is not mediated through the translocator protein (TSPO).

    Tu, Lan N; Zhao, Amy H; Stocco, Douglas M; Selvaraj, Vimal


    Translocator protein (TSPO) is a mitochondrial outer membrane protein of unknown function with high physiological expression in steroidogenic cells. Using TSPO gene-deleted mice, we recently demonstrated that TSPO function is not essential for steroidogenesis. The first link between TSPO and steroidogenesis was established in studies showing modest increases in progesterone production by adrenocortical and Leydig tumor cell lines after treatment with PK11195. To reconcile discrepancies between physiological and pharmacological interpretations of TSPO function, we generated TSPO-knockout MA-10 mouse Leydig tumor cells (MA-10:TspoΔ/Δ) and examined their steroidogenic potential after exposure to either dibutyryl-cAMP or PK11195. Progesterone production in MA-10:TspoΔ/Δ after dibutyryl-cAMP was not different from control MA-10:Tspo+/+ cells, confirming that TSPO function is not essential for steroidogenesis. Interestingly, when treated with increasing concentrations of PK11195, both control MA-10:Tspo+/+ cells and MA-10:TspoΔ/Δ cells responded in a similar dose-dependent manner showing increases in progesterone production. These results show that the pharmacological effect of PK11195 on steroidogenesis is not mediated through TSPO.

  2. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B


    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS...

  3. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance

    Euan A. Stronach


    Full Text Available Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinumresistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK, and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Re-sensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage–mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors.

  4. Quantification of (R)-[{sup 11}C]PK11195 binding in rheumatoid arthritis

    Kropholler, M.A.; Boellaard, R.; Kloet, R.W.; Lammertsma, A.A. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, PO Box 7057, Amsterdam (Netherlands); Elzinga, E.H.; Voskuyl, A.E. [VU University Medical Centre, Department of Rheumatology, Amsterdam (Netherlands); Laken, C.J. van der; Dijkmans, B.A.C. [VU University Medical Centre, Department of Rheumatology, Amsterdam (Netherlands); Jan van Breemen Instituut, Amsterdam (Netherlands); Maruyama, K. [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan)


    Rheumatoid arthritis (RA) involves migration of macrophages into inflamed areas. (R)-[{sup 11}C]PK11195 binds to peripheral benzodiazepine receptors, expressed on macrophages, and may be used to quantify inflammation using positron emission tomography (PET). This study evaluated methods for the quantification of (R)-[{sup 11}C]PK11195 binding in the knee joints of RA patients. Data from six patients with RA were analysed. Dynamic PET scans were acquired in 3-D mode following (R)-[{sup 11}C]PK11195 injection. During scanning arterial radioactivity concentrations were measured to determine the plasma (R)-[{sup 11}C]PK11195 concentrations. Data were analysed using irreversible and reversible one-tissue and two-tissue compartment models and input functions with various types of metabolite correction. Model preferences according to the Akaike information criterion (AIC) and correlations between measures were evaluated. Correlations between distribution volume (V{sub d}) and standardized uptake values (SUV) were evaluated. AIC indicated optimal performance for a one-tissue reversible compartment model including blood volume. High correlations were observed between V{sub d} obtained using different input functions (R {sup 2}=0.80-1.00) and between V{sub d} obtained with one- and two-tissue reversible compartment models (R {sup 2}=0.75-0.94). A high correlation was observed between optimal V{sub d} and SUV after injection (R {sup 2}=0.73). (R)-[{sup 11}C]PK11195 kinetics in the knee were best described by a reversible single-tissue compartment model including blood volume. Applying metabolite corrections did not increase sensitivity. Due to the high correlation with V{sub d}, SUV is a practical alternative for clinical use. (orig.)

  5. Exploration on Requirements for Specialties on Ideological and Political Competence of Peacekeeping Police%维和警察思想政治素质特殊性要求探讨


    维和警察代表国家执行联合国维和任务,我国的国家性质和人民警察的宗旨、维和警察担负的职责使命决定了对这一特殊群体思想政治素质的特殊要求。对于中国维和警察而言,加强维和能力建设首先就是要提高思想政治素质,确保维和警察永葆忠于党、忠于祖国、忠于人民、忠于法律的政治本色。%Peacekeeping police performing UN mission on behalf of our country, the national nature and the police tenet and the duty of peacekeeping police decided to the special requirements of ideological and political quality. For Chinese peacekeeping police, strengthen peacekeeping capacity building basically is to enhance ideological and political quality, ensure the peacekeeping police keep loyal to our party, to our motherland and loyalty to the people, loyal to the law of political character.

  6. Measurements of daily urinary uranium excretion in German peacekeeping personnel and residents of the Kosovo region to assess potential intakes of depleted uranium (DU)

    Oeh, U. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany)]. E-mail:; Priest, N.D. [Middlesex University, School of Health and Social Sciences, Queensway, Enfield, EN3 4SA (United Kingdom); Roth, P. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Ragnarsdottir, K.V. [University of Bristol, Department of Earth Sciences, Bristol, BS8 1RJ (United Kingdom); Li, W.B. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Hoellriegl, V. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Thirlwall, M.F. [Royal Holloway University of London, Department of Geology, Egham, TW20 0EX (United Kingdom); Michalke, B. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Giussani, A. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Universita degli Studi di Milano, Dipartimento di Fisica, and INFN, Sezione di Milano, 20133 Milan (Italy); Schramel, P. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany); Paretzke, H.G. [GSF-National Research Center for Environment and Health, Institute of Radiation Protection, 85764 Neuherberg (Germany)


    Following the end of the Kosovo conflict, in June 1999, a study was instigated to evaluate whether there was a cause for concern of health risk from depleted uranium (DU) to German peacekeeping personnel serving in the Balkans. In addition, the investigations were extended to residents of Kosovo and southern Serbia, who lived in areas where DU ammunitions were deployed. In order to assess a possible DU intake, both the urinary uranium excretion of volunteer residents and water samples were collected and analysed using inductively coupled plasma-mass spectrometry (ICP-MS). More than 1300 urine samples from peacekeeping personnel and unexposed controls of different genders and age were analysed to determine uranium excretion parameters. The urine measurements for 113 unexposed subjects revealed a daily uranium excretion rate with a geometric mean of 13.9 ng/d (geometric standard deviation (GSD) = 2.17). The analysis of 1228 urine samples from the peacekeeping personnel resulted in a geometric mean of 12.8 ng/d (GSD = 2.60). It follows that both unexposed controls and peacekeeping personnel excreted similar amounts of uranium. Inter-subject variation in uranium excretion was high and no significant age-specific differences were found. The second part of the study monitored 24 h urine samples provided by selected residents of Kosovo and adjacent regions of Serbia compared to controls from Munich, Germany. Total uranium and isotope ratios were measured in order to determine DU content. {sup 235}U/{sup 238}U ratios were within {+-} 0.3% of the natural value, and {sup 236}U/{sup 238}U was less than 2 x 10{sup -7}, indicating no significant DU in any of the urine samples provided, despite total uranium excretion being relatively high in some cases. Measurements of ground and tap water samples from regions where DU munitions were deployed did not show any contamination with DU, except in one sample. It is concluded that both peacekeeping personnel and residents serving or

  7. Total and unbound darunavir (DRV pharmacokinetics (PK in HIV-1-infected pregnant women

    C Zorrilla


    Full Text Available Antiretroviral (ARV therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission (MTCT. Physiologic changes during pregnancy can affect PK. We present the PK of total and unbound (pharmacologically active DRV in HIV-1-infected pregnant women receiving twice-daily (bid DRV/ritonavir (rtv. This Phase IIIb study enrolled HIV-1-infected pregnant women≥18 years old in the 2nd trimester of pregnancy receiving DRV/rtv 600/100 mg bid and other ARVs. DRV (total and unbound and rtv (total plasma concentrations were obtained predose and 1, 2, 3, 4, 6, 9 and 12 hours postdose during the 2nd and 3rd trimesters and postpartum. Total DRV and rtv plasma concentrations were determined using a previously validated HPLC-MS/MS assay (lower limit of quantification 5.00 ng/mL. Unbound DRV was determined by fortifying plasma samples with 14-C DRV and separating total and unbound DRV using ultrafiltration. Total and unbound 14-C DRV were measured using liquid scintillation counting. Total and unbound PK parameters were derived using a noncompartmental analysis. Safety and efficacy were investigated at each visit and summarized using descriptive statistics. Sixteen women (10 black, 4 Hispanic, 2 white were enrolled; 11 had evaluable PK data. Total DRV AUC12h was 24% and 17% lower during 2nd and 3rd trimesters, respectively, vs postpartum (Table. Unbound DRV AUC12h was unchanged during 2nd and 3rd trimesters vs postpartum. Total and unbound DRV Cmin increased by 43% and 10%, respectively, during 2nd trimester and by 86% and 14%, respectively, during 3rd trimester vs postpartum. Unbound DRV was above the EC50 (27.5 ng/mL for PI-resistant HIV in all patients. Albumin and α1-acid glycoprotein (AAG concentrations were 22%–29% lower during pregnancy vs postpartum. Viral load decreased and CD4+ count increased over time. One serious adverse event was reported (increased transaminase. Three of 12 infants were born prior to 37 weeks (30, 36 and

  8. Specific interaction of IP6 with human Ku70/80, the DNA-binding subunit of DNA-PK.

    Hanakahi, Les A; West, Stephen C


    In eukaryotic cells, DNA double-strand breaks can be repaired by non-homologous end-joining, a process dependent upon Ku70/80, XRCC4 and DNA ligase IV. In mammals, this process also requires DNA-PK(cs), the catalytic subunit of the DNA-dependent protein kinase DNA-PK. Previously, inositol hexakisphosphate (IP6) was shown to be bound by DNA-PK and to stimulate DNA-PK-dependent end-joining in vitro. Here, we localize IP6 binding to the Ku70/80 subunits of DNA- PK, and show that DNA-PK(cs) alone exhibits no detectable affinity for IP6. Moreover, proteolysis mapping of Ku70/80 in the presence and absence of IP6 indicates that binding alters the conformation of the Ku70/80 heterodimer. The yeast homologue of Ku70/80, yKu70/80, fails to bind IP6, indicating that the function of IP6 in non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian end-joining process.

  9. AMPD3-deficient mice exhibit increased erythrocyte ATP levels but anemia not improved due to PK deficiency.

    Cheng, Jidong; Morisaki, Hiroko; Toyama, Keiko; Ikawa, Masahito; Okabe, Masaru; Morisaki, Takayuki


    AMP deaminase (AMPD) catalyzes AMP to IMP and plays an important role in energy charge and nucleotide metabolism. Human AMPD3 deficiency is a type of erythrocyte-specific enzyme deficiency found in individuals without clinical symptoms, although an increased level of ATP in erythrocytes has been reported. To better understand the physiological and pathological roles of AMPD3 deficiency, we established a line of AMPD3-deficient [A3(-/-)] mice. No AMPD activity and a high level of ATP were observed in erythrocytes of these mice, similar to human RBC-AMPD3 deficiency, while other characteristics were unremarkable. Next, we created AMPD3 and pyruvate kinase (PK) double-deficient [PKA(-/-,-/-)] mice by mating A3(-/-) mice with CBA-Pk-1slc/Pk-1slc mice [PK(-/-)], a spontaneous PK-deficient strain showing hemolytic anemia. In PKA(-/-,-/-) mice, the level of ATP in red blood cells was increased 1.5 times as compared to PK(-/-) mice, although hemolytic anemia in those animals was not improved. In addition, we observed osmotic fragility of erythrocytes in A3(-/-) mice under fasting conditions. In contrast, the ATP level in erythrocytes was elevated in A3(-/-) mice as compared to the control. In conclusion, AMPD3 deficiency increases the level of ATP in erythrocytes, but does not improve anemia due to PK deficiency and leads to erythrocyte dysfunction.

  10. Nuclear imaging of neuroinflammation: a comprehensive review of [{sup 11}C]PK11195 challengers

    Chauveau, Fabien; Camp, Nadja van; Tavitian, Bertrand [Service Hospitalier Frederic Joliot, Laboratoire d' Imagerie Moleculaire Experimentale, CEA, Institut d' Imagerie BioMedicale, Orsay (France); INSERM, U803, Orsay (France); Boutin, Herve [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Dolle, Frederic [Service Hospitalier Frederic Joliot, Laboratoire d' Imagerie Moleculaire Experimentale, CEA, Institut d' Imagerie BioMedicale, Orsay (France)


    Neurodegenerative, inflammatory and neoplastic brain disorders involve neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful for diagnostic, drug development and therapy control of these frequent diseases. In vivo imaging can document the expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO) that is linked to microglial activation and considered a hallmark of neuroinflammation. The prototype positron emission tomography tracer for PBR, [{sup 11}C]PK11195, has shown limitations that until now have slowed the clinical applications of PBR imaging. In recent years, dozens of new PET and SPECT radioligands for the PBR have been radiolabelled, and several have been evaluated in imaging protocols. Here we review the new PBR ligands proposed as challengers of [{sup 11}C]PK11195, critically analyze preclinical imaging studies and discuss their potential as neuroinflammation imaging agents. (orig.)

  11. PaDEL-DDPredictor: open-source software for PD-PK-T prediction.

    He, Yuye; Liew, Chin Yee; Sharma, Nitin; Woo, Sze Kwang; Chau, Yi Ting; Yap, Chun Wei


    ADMET (absorption, distribution, metabolism, excretion, and toxicity)-related failure of drug candidates is a major issue for the pharmaceutical industry today. Prediction of PD-PK-T properties using in silico tools has become very important in pharmaceutical research to reduce cost and enhance efficiency. PaDEL-DDPredictor is an in silico tool for rapid prediction of PD-PK-T properties of compounds from their chemical structures. It is free and open-source software that, has both graphical user interface and command line interface, can work on all major platforms (Windows, Linux, and MacOS) and supports more than 90 different molecular file formats. The software can be downloaded from

  12. Construction of cytopathic PK-15 cell model of classical swine fever virus


    No cytopathic effect (CPE) can be observed on classical swine fever virus (CSFV) infected cell culture in vitro. This brings an obstacle to the researches on reciprocity between CSFV and host cells. Based on the construction of full-length genomic infectious Cdna clone of Chinese CSFV standard virulent Shimen strain, partial deletion is intro- duced into genomic Cdna to obtain a 7.5 kb subgenomic Cdna. A new subgenomic CSFV is derived from transfection with the subgenomic Cdna on PK-15 cells pre-infected by CSFV Shimen virus. Typical CPE induced by this subgenomic virus is observed on PK-15 cells. Coexistence of wild- type and subgenomic virus in cytopathic cell culture is dem- onstrated by RT-PCR detection in cytopathic cells. For conclusion, the construction of cytopathic cell model exploited a new way for researches on the molecular mechanism of CSFV pathogenesis.

  13. Effects of Patrol Operation on Hydration Status and Autonomic Modulation of Heart Rate of Brazilian Peacekeepers in Haiti.

    Duarte, Antonio F A; Morgado, Jairo J M


    The stress of operational missions may challenge the maintenance of body homeostasis, affecting soldiers' cardiac autonomic control, promoting dehydration, and compromising performance. Therefore, we aimed to determine the effects of peacekeeper patrol operation in Haiti on soldiers' hydration status and cardiac autonomic modulation, and to determine whether fluctuations in autonomic modulation were associated with changes in hydration status, energy expenditure (EE), and aerobic fitness (V[Combining Dot Above]O2max). A group of 20 soldiers (23.5 ± 4.7 years; V[Combining Dot Above]O2max 52.9 ± 4.5 ml·kg⁻¹·min⁻¹) completed an operational patrol mission with a mean duration of 160.6 ± 28.6 minutes. Before (Pre) and after (Post) the operation, the soldiers' body masses (BMs) were measured and 5-minute heart rate interbeat (R-R) intervals were recorded at rest to estimate heart rate variability (low-frequency [LF] and high-frequency [HF] power, and sympathovagal balance [LF/HF]). During the mission, EE was estimated using heart rate (HR) monitors. Changes from Pre to Post in BM (%BM loss) and LF/HF (ΔLF/HF) were used to evaluate the soldiers' dehydration levels and autonomic modulation, respectively. The mean EE was 711.0 ± 208.7 kcal. From pre to post, increases (p < 0.01) were noted in LF normalized units (n.u.) and LF/HF and decreases (p < 0.01) were noted in BM, R-R interval, and HF n.u. The variation in ΔLF/HF correlated with EE (r = 0.49; p = 0.02), V[Combining Dot Above]O2max (r = -0.42; p = 0.05), and %BM loss (r = 0.53; p = 0.02). The results demonstrated that an operational peacekeeper patrol with an approximate duration of 160 minutes promoted both dehydration and an imbalance in the autonomic modulation of soldiers' HR. The reduction in sympathovagal balance correlated with EE, dehydration, and aerobic conditioning.

  14. Integration of preclinical and clinical knowledge to predict intravenous PK in human: bilastine case study.

    Vozmediano, Valvanera; Ortega, Ignacio; Lukas, John C; Gonzalo, Ana; Rodriguez, Monica; Lucero, Maria Luisa


    Modern pharmacometrics can integrate and leverage all prior proprietary and public knowledge. Such methods can be used to scale across species or comparators, perform clinical trial simulation across alternative designs, confirm hypothesis and potentially reduce development burden, time and costs. Crucial yet typically lacking in integration is the pre-clinical stage. Prediction of PK in man, using in vitro and in vivo studies in different animal species, is increasingly well theorized but could still find wider application in drug development. The aim of the present work was to explore methods for bridging pharmacokinetic knowledge from animal species (i.v. and p.o.) and man (p.o.) into i.v. in man using the antihistamine drug bilastine as example. A model, predictive of i.v. PK in man, was developed on data from two pre-clinical species (rat and dog) and p.o. in man bilastine trials performed earlier. In the knowledge application stage, two different approaches were used to predict human plasma concentration after i.v. of bilastine: allometry (several scaling methods) and a semi-physiological method. Both approaches led to successful predictions of key i.v. PK parameters of bilastine in man. The predictive i.v. PK model was validated using later data from a clinical study of i.v. bilastine. Introduction of such knowledge in development permits proper leveraging of all emergent knowledge as well as quantification-based exploration of PK scenario, e.g. in special populations (pediatrics, renal insufficiency, comedication). In addition, the methods permit reduction or elimination and certainly optimization of learning trials, particularly those concerning alternative off-label administration routes.

  15. Responses of Bog Vegetation and CO2 Exchange to Experimental N and PK Addition

    Juutinen, S.; Bubier, J. L.; Shrestha, P.; Smith, R.; Moore, T.


    Atmospheric nitrogen (N) deposition has the potential to alter the structure and functioning of nutrient poor wetland ecosystems. It is important to quantify the effect of N input on ecosystem carbon (C) sequestration in these globally important C storages. We address this issue at the temperate Mer Bleue bog, ON, Canada. After 6 years of experimental fertilization, we saw that high N deposition can change mixed Sphagnum and dwarf shrub dominated communities to taller and denser dwarf shrub communities that are losing moss cover, and which might have even lower net C uptake. Now, after 8 years of fertilization and with new treatments we quantify the relationship between the plant community structure and ecosystem CO2 exchange. Three levels of N fertilization were applied with or without phosphorus and potassium (PK) into triplicate plots. We measured light saturated net ecosystem CO2 exchange (NEE), and its components ecosystem respiration and gross photosynthesis using clear and dark chambers (May-August). Vegetation characteristics were quantified by measuring foliage cover (LAI), amount of woody and foliar biomass, and abundance of moss species (point interception technique), moss growth (cranked wires) and green area of vascular leaves and moss. Addition of PK fertilizer did not alter NEE or its components relative to the control. The 8-year low N addition alone and with PK, and the 4-year fertilization with high N levels resulted in the highest net ecosystem CO2 uptake relative to the control. The ecosystem respiration increased with increasing N input rate. All levels of N fertilization resulted in higher gross photosynthesis than the control, but there was no increasing trend with increasing N input. Vascular foliage increased, while moss cover drastically decreased with increasing levels of N fertilization. At the highest level of N (and PK) addition woody biomass increased at the expense of leaf increment. Dependencies of ecosystem CO2 exchange on the

  16. A Population Pharmacokinetic (Pk- Pharmacodynamic (Pd Analysis Of Peginesatide India Lysis Patients With Chronic Kidney Disease

    Himanshu Naik


    Total bilirubin, body mass index, age, alkaline phosphatase, ethnicity, and serum creatinine (for non-dialysis subjects for PK and age and ESAD for PD were identified as statistically significant (p-value<0.005 covariates. None of these identified covariates were considered to be clinically relevant, based on their impact on simulated peginesatide exposure (<±30% and Hb (<0.2 g/dL levels.

  17. Arabidopsis D6PK is a lipid domain-dependent mediator of root epidermal planar polarity.

    Stanislas, Thomas; Hüser, Anke; Barbosa, Inês C R; Kiefer, Christian S; Brackmann, Klaus; Pietra, Stefano; Gustavsson, Anna; Zourelidou, Melina; Schwechheimer, Claus; Grebe, Markus


    Development of diverse multicellular organisms relies on coordination of single-cell polarities within the plane of the tissue layer (planar polarity). Cell polarity often involves plasma membrane heterogeneity generated by accumulation of specific lipids and proteins into membrane subdomains. Coordinated hair positioning along Arabidopsis root epidermal cells provides a planar polarity model in plants, but knowledge about the functions of proteo-lipid domains in planar polarity signalling remains limited. Here we show that Rho-of-plant (ROP) 2 and 6, phosphatidylinositol-4-phosphate 5-kinase 3 (PIP5K3), DYNAMIN-RELATED PROTEIN (DRP) 1A and DRP2B accumulate in a sterol-enriched, polar membrane domain during root hair initiation. DRP1A, DRP2B, PIP5K3 and sterols are required for planar polarity and the AGCVIII kinase D6 PROTEIN KINASE (D6PK) is a modulator of this process. D6PK undergoes phosphatidylinositol-4,5-bisphosphate- and sterol-dependent basal-to-planar polarity switching into the polar, lipid-enriched domain just before hair formation, unravelling lipid-dependent D6PK localization during late planar polarity signalling.

  18. PK-PD modeling of β-lactam antibiotics: in vitro or in vivo models?

    de Araujo, Bibiana Verlindo; Diniz, Andrea; Palma, Eduardo Célia; Buffé, Cândida; Dalla Costa, Teresa


    A modified E(max)-pharmacokinetic-pharmacodynamic (PK-PD) model was previously proposed in literature for describing the antimicrobial activity of β-lactam antibiotics based on in vitro experiments. However, bacteria behave differently in vitro and in vivo. Thus, the aims of this study were to model the killing effect of piperacillin (PIP) against Escherichia coli on immunocompromised infected rats using this model and to compare the parameters obtained in vitro and in vivo for the same bacteria/drug combination. The PK-PD parameters determined in vitro and in vivo were as follows: generation rate constant of 1.30 ± 0.10 and 0.76 ± 0.20 h(-1), maximum killing effect of 3.11 ± 0.27 and 1.38 ± 0.20 h(-1) and concentration to produce 50% of the maximum effect of 5.44 ± 0.03 and 1.31 ± 0.27 μg ml(-1), respectively. The comparison between the in vitro and in vivo parameters was not straightforward and had to take into consideration the intrinsic differences of the models involved. So far, the main application of the PK-PD model evaluated is for the comparison of different antimicrobial agent's potency and efficacy, under equivalent conditions.

  19. Molecular cloning of NHE3 from LLC-PK1 cells and localization in pig kidney.

    Shugrue, C A; Obermüller, N; Bachmann, S; Slayman, C W; Reilly, R F


    LLC-PK1 cells, an established line from pig kidney, express basolateral and apical Na+/H+ exchangers that can be distinguished by their differing sensitivities to the amiloride analog N-ethyl-N-isopropylamiloride (EIPA). It has been shown previously that the basolateral exchanger is encoded by NHE1. In the present study, a combination of reverse transcription-PCR, 5' RACE, and genomic library screening was used to clone the coding region of the porcine NHE3 gene. There was significant homology between the LLC-PK1 sequence and the previously reported rabbit and rat NHE3 genes, with nucleotide and deduced amino acid identities of 87 and 85% in rabbit, and 85 and 87% in rat, respectively. To study expression patterns, Northern analysis was carried out using an NHE3 cDNA to probe poly(A)+ RNA isolated from LLC-PK1 cells, and from pig kidney cortex. In all three cases, a major transcript of 6.1 kb was detected along with two minor transcripts of 4.7 and 3.8 kb. In situ hybridization with two different NHE3 probes gave intense labeling of the distal convoluted tubule in pig kidney but (unexpectedly) no detectable labeling of the proximal tubule. These studies suggest that there are marked species differences in NHE3 expression in the distal nephron.

  20. PK20, a new opioid-neurotensin hybrid peptide that exhibits central and peripheral antinociceptive effects

    Tsuda Yuko


    Full Text Available Abstract Background The clinical treatment of various types of pain relies upon the use of opioid analgesics. However most of them produce, in addition to the analgesic effect, several side effects such as the development of dependence and addiction as well as sedation, dysphoria, and constipation. One solution to these problems are chimeric compounds in which the opioid pharmacophore is hybridized with another type of compound to incease antinociceptive effects. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid elements may result in a potent synergistic antinociceptor. Results Using the known structure-activity relationships of neurotensin we have synthesized a new chimeric opioid-neurotensin compound PK20 which is characterized by a very strong antinociceptive potency. The observation that the opioid antagonist naltrexone did not completely reverse the antinociceptive effect, indicates the partial involvement of the nonopioid component in PK20 in the produced analgesia. Conclusions The opioid-neurotensin hybrid analogue PK20, in which opioid and neurotensin pharmacophores overlap partially, expresses high antinociceptive tail-flick effects after central as well as peripheral applications.

  1. Focus on English Training for UN Peacekeeping Police%维和警察英语培训的思考



    In 2011,the first police force of Liaoning province carried out civil peacekeeping mission in East Timor,who was trained in Liaoning Police and Justice Administrative College.As an English teacher for this training,I will introduce some conception,teaching method and contexts.Also,I would like to sum up some experience for the future job.%2011年,辽宁省公安厅组建警队赴东帝汶执行民事维和任务,省公安厅将此警队培训重任交付于辽宁公安司法管理干部学院,这是我省第一次单独组建警队执行维和任务。作为此次为何警察英语培训教师,特将此次英语培训思路、方法及内容作以介绍,并就相关内容进行思考,旨在总结此次英语培训任务,为进一步完成好积累维和警察培训工作积累经验。

  2. The combined influence of hardiness and cohesion on mental health in a military peacekeeping mission: A prospective study.

    Thomassen, Ådne G; Hystad, Sigurd W; Johnsen, Bjørn Helge; Johnsen, Grethe E; Laberg, Jon C; Eid, Jarle


    A large number of studies have shown that hardiness and cohesion are associated with mental health in a military context. However, most of them are presented without controlling for baseline mental health symptoms, which is their most significant source of error. The present study investigates the combined effect of hardiness and cohesion in a prospective design, controlling for baseline levels of symptoms among Norwegian personnel serving in a peacekeeping operation in Kosovo. Multivariate regression analyses were performed in which self-reported mental health complaints were regressed on our explanatory variables. Our findings suggest that both cohesion and hardiness contributed to increased stress resiliency, as measured by a lower level of reported mental health complaints. Our baseline measure of mental health accounted for a larger proportion of the variance than our other predictors. A significant interaction between cohesion and hardiness suggested a combined effect, over and above the individual contributions of the predictors. For individuals who scored high on hardiness, cohesion levels did not influence levels of mental health complaints. Individuals who scored low on hardiness, on the other hand, reported lower levels of mental health complaints when cohesion levels were high.

  3. A DNA-dependent stress response involving DNA-PK occurs in hypoxic cells and contributes to cellular adaptation to hypoxia.

    Bouquet, Fanny; Ousset, Marielle; Biard, Denis; Fallone, Frédérique; Dauvillier, Stéphanie; Frit, Philippe; Salles, Bernard; Muller, Catherine


    DNA-dependent protein kinase (DNA-PK) is involved in DNA double-strand break (DSB) signalling and repair. We report that DNA-PK is activated by mild hypoxia conditions (0.1-1% O₂) as shown by (1) its autophosphorylation on Ser2056, and (2) its mobilisation from a soluble nucleoplasmic compartment to a less extractable nuclear fraction. The recruitment of DNA-PK was not followed by activation and recruitment of the XRCC4-DNA-ligase-IV complex, suggesting that DSBs are not responsible for activation of DNA-PK. To unravel the mechanism of DNA-PK activation, we show that exposure of cells to trichostatin A, a histone deacetylase inhibitor, leads to DNA-PK autophosphorylation and relocalisation to DNA. Histone acetylation (mainly H3K14) is increased in hypoxic cells and treatment with anacardic acid, an inhibitor of histone acetyl transferase, prevented both histone modifications and DNA-PK activation in hypoxic conditions. Importantly, in using either silenced DNA-PK cells or cells exposed to a specific DNA-PK inhibitor (NU7026), we demonstrated that hypoxic DNA-PK activation positively regulates the key transcription factor HIF-1 and one subsequent target gene, GLUT1. Our results show that hypoxia initiates chromatin modification and consequently DNA-PK activation, which positively regulate cellular oxygen-sensing and oxygen-signalling pathways.

  4. Absence of mutations in the coding sequence of the potential tumor suppressor 3pK in metastatic melanoma

    Houben Roland


    Full Text Available Abstract Background Activation of Ras or Raf contributes to tumorigenesis of melanoma. However, constitutive Raf activation is also a characteristic of the majority of benign melanocytic nevi and high intensity signaling of either Ras or Raf was found to induce growth inhibition and senescence rather than transformation. Since the chromosome 3p kinase (3pK is a target of the Ras/Raf/Mek/Erk signaling pathway which antagonizes the function of the oncogene and anti-differentiation factor Bmi-1, 3pK may function as a tumor suppressor in tumors with constitutive Ras/Raf activation. Consequently, we tested whether inactivating 3pK mutations are present in melanoma. Methods 30 metastatic melanoma samples, which were positive for activating mutations of either BRaf or NRas, were analyzed for possible mutations in the 3pk gene. The 10 coding exons and their flanking intron sequences were amplified by PCR and direct sequencing of the PCR products was performed. Results This analysis revealed that besides the presence of some single nucleotide polymorphisms in the 3pk gene, we could not detect any possible loss of function mutation in any of these 30 metastatic melanoma samples selected for the presence of activating mutations within the Ras/Raf/Mek/Erk signaling pathway. Conclusion Hence, in melanoma with constitutively active Ras/Raf inactivating mutations within the 3pk gene do not contribute to the oncogenic phenotype of this highly malignant tumor.

  5. 维和医疗分队护理人员能力素质分析%Capability Analysis on the Nursing Personnel in Peacekeeping Medical Contingent

    苏嫦娥; 曾艳; 马岩; 张丹靖; 李丽娜


    Objective To discuss the essential capability and makings of the nursing Staff in the peacekeeping medical units. Methods By analyzing the characteristics of the working and living environment, correlated mission standard and demand, we combine with practical experience and suggest that the nurses have the capability and makings in order to fulfill peacekeeping tasks in higher standard. Results The nursing Staff should have solid professional skill, capability of independent working, perfect English, favorable communication and coordination , self - mental adjustment, the specialty of literature and athletics. Therefore we can be capable for Nursing Services under the difficult and perplexing circumstances. Conclusions It is substantial groundwork to accomplish the peacekeeping tasks well that the nurses have overall ability.%目的 探讨维和医疗分队护理人员应具备的相关能力与素质.方法 通过分析护理人员的工作、生活环境特点,相关任务标准及要求,结合实际工作经历,提出高标准完成上述工作任务应具备的能力与素质.结果 维和护理人员只有具备扎实的专业技术水平、独立工作的能力、较高的英语口语交流能力、良好的沟通协调能力、良好的外交礼仪风范、较高的自我心理调整能力、一定的文艺体育特长,才能胜任艰巨复杂的维和护理工作.结论 护理人员具备较高综合能力素质是完成好维和任务的坚实基础.

  6. Study on the Clinical Application Value of the tM2-PK in the colorectal cancer%tM2-PK 在结直肠癌的应用价值临床研究



    Objective To study the tumor pyruvate kinase (tM2-PK)expression and its relationship with clinico-pathological characteristics of colorectal cancer in patients with colorectal cancer.Methods 49 cases of colorectal cancer patients for the study,next to the immunohistochemistry cancer tissue and cancer tissue tM2-PK expression and cancer research organizations tM2-PK and serum tM2-PK levels in patients with correlation analysis tM2-PK colorectal cancer patients with pathological relationship.Results 49 cases of tissue tM2-PK positive rate of colorectal cancer in patients with cancer and adjacent tissues respectively 81.6%,42.9%,there was significant difference (P 0.05)at different ages,gender,and different degrees of differentiation on tM2-PK positive rate;40 cases of colorectal cancer cancer tissues tM2-PK-positive pa-tients,with an average score 7.53 ± 1.94,serum concentrations tM2-PK 26.59 ± 10.24,a positive correlation,r =0.876,P =0.0015,statistically significant (P <0.05).Conclusion tM2-PK in the early diagnosis of colorectal cancer, as well as assess the prognosis of the disease and has good prospects.%目的:研究肿瘤型丙酮酸激酶(tM2-PK)在结直肠癌患者表达情况及其与结直肠癌临床病理特征的关系。方法以49例结直肠癌患者为研究对象,免疫组化检测癌组织以及癌旁组织 tM2-PK 表达情况,并研究癌组织 tM2-PK 与患者血清 tM2-PK 水平相关性,分析 tM2-PK 与结直肠癌患者病理特征关系。结果49例结直肠癌患者癌组织与癌旁组织 tM2-PK 阳性率分别为81.6%、42.9%,两者存在统计学差异(P <0.05);结直肠癌组织最大Φ≥5 cm结直肠癌 tM2-PK 阳性率高于最大Φ<5 cm 结直肠癌,在 TNM 分期中Ⅲ+Ⅳ期 tM2-PK 阳性率高于Ⅰ+Ⅱ期,不同Duck 分期上 C+D 期 tM2-PK 阳性率高于 A+B 期;在不同年龄、性别以及不同分化程度上 tM2-PK 阳性率无统计学差异(P >0.05);40

  7. Isolation and characterization of DkPK genes associated with natural deastringency in C-PCNA persimmon

    Changfei eGuan


    Full Text Available Chinese pollination-constant nonastringent (C-PCNA persimmon (Diospyros kaki Thunb. is considered to be an important germplasm resource for the breeding of PCNA cultivars, though its molecular mechanisms of astringency removal remain to be elucidated. Previously, we showed that the abundance of pyruvate kinase gene (PK transcripts increased rapidly during astringency removal in C-PCNA persimmon fruit. Here, we report the full-length coding sequences (CDS of six novel DkPK genes from C-PCNA persimmon fruit isolated based on a complementary DNA (cDNA library and transcriptome data. The expression patterns of these six DkPK genes and correlations with the soluble proanthocyanidin (PA content were analyzed during various fruit development stages in different types of persimmon, with DkPK1 showing an expression pattern during the last stage in C-PCNA persimmon that was positively correlated with a decrease in soluble PAs. Phylogenetic analysis revealed that DkPK1 belongs to cytosolic-1 subgroup, and subcellular localization analysis confirmed that DkPK1 is located in the cytosol. Notably, tissue expression profiling revealed ubiquitous DkPK1 expression in different persimmon organs, with the highest expression in seeds. Furthermore, transient over-expression of DkPK1 in persimmon leaves resulted in a significant decrease in the content of soluble PAs but a significant increase in the transcript levels of pyruvate decarboxylase genes (DkPDC1, -3, -4, -5, which catalyze the conversion of pyruvate to acetaldehyde. Thus, we propose that an acetaldehyde-based coagulation effect reduces the content of soluble PAs. Taken together, our results suggest that DkPK1 might be involved in the natural removal of astringency at the last developmental stage in C-PCNA persimmon. This is the first report to identify several novel full-length DkPK genes as well as their potential roles in the natural loss of astringency in C-PCNA persimmon.

  8. [11C]-(R)-PK11195 positron emission tomography in patients with complex regional pain syndrome

    Jeon, So Yeon; Seo, Seongho; Lee, Jae Sung; Choi, Soo-Hee; Lee, Do-Hyeong; Jung, Ye-Ha; Song, Man-Kyu; Lee, Kyung-Jun; Kim, Yong Chul; Kwon, Hyun Woo; Im, Hyung-Jun; Lee, Dong Soo; Cheon, Gi Jeong; Kang, Do-Hyung


    Abstract Complex regional pain syndrome (CRPS) is characterized by severe and chronic pain, but the pathophysiology of this disease are not clearly understood. The primary aim of our case–control study was to explore neuroinflammation in patients with CRPS using positron emission tomography (PET), with an 18-kDa translocator protein specific radioligand [11C]-(R)-PK11195. [11C]-(R)-PK11195 PET scans were acquired for 11 patients with CRPS (30–55 years) and 12 control subjects (30–52 years). Parametric image of distribution volume ratio (DVR) for each participant was generated by applying a relative equilibrium-based graphical analysis. The DVR of [11C]-(R)-PK11195 in the caudate nucleus (t(21) = −3.209, P = 0.004), putamen (t(21) = −2.492, P = 0.022), nucleus accumbens (t(21) = −2.218, P = 0.040), and thalamus (t(21) = −2.395, P = 0.026) were significantly higher in CRPS patients than in healthy controls. Those of globus pallidus (t(21) = −2.045, P = 0.054) tended to be higher in CRPS patients than in healthy controls. In patients with CRPS, there was a positive correlation between the DVR of [11C]-(R)-PK11195 in the caudate nucleus and the pain score, the visual analog scale (r = 0.661, P = 0.026, R2 = 0.408) and affective subscales of McGill Pain Questionnaire (r = 0.604, P = 0.049, R2 = 0.364). We demonstrated that neuroinflammation of CRPS patients in basal ganglia. Our results suggest that microglial pathology can be an important pathophysiology of CRPS. Association between the level of caudate nucleus and pain severity indicated that neuroinflammation in this region might play a key role. These results may be essential for developing effective medical treatments. PMID:28072713

  9. A Comparison of Decision Methods for C pk When Data are Autocorrelated

    Lundkvist, Peder; Vannman, Kerstin; Kulahci, Murat


    In many industrial applications, autocorrelated data are becoming increasingly common due to, for example, on-line data collection systems with high-frequency sampling. Therefore, the basic assumption of independent observations for process capability analysis is not valid. The purpose...... of this article is to compare decision methods using the process capability index C-pk when data are autocorrelated. This is done through a case study followed by a simulation study. In the simulation study the actual significance level and power of the decision methods are investigated. The outcome...

  10. A PK-PD model of ketamine-induced high-frequency oscillations

    Flores, Francisco J.; Ching, ShiNung; Hartnack, Katharine; Fath, Amanda B.; Purdon, Patrick L.; Wilson, Matthew A.; Brown, Emery N.


    Objective. Ketamine is a widely used drug with clinical and research applications, and also known to be used as a recreational drug. Ketamine produces conspicuous changes in the electrocorticographic (ECoG) signals observed both in humans and rodents. In rodents, the intracranial ECoG displays a high-frequency oscillation (HFO) which power is modulated nonlinearly by ketamine dose. Despite the widespread use of ketamine there is no model description of the relationship between the pharmacokinetic-pharmacodynamics (PK-PDs) of ketamine and the observed HFO power. Approach. In the present study, we developed a PK-PD model based on estimated ketamine concentration, its known pharmacological actions, and observed ECoG effects. The main pharmacological action of ketamine is antagonism of the NMDA receptor (NMDAR), which in rodents is accompanied by an HFO observed in the ECoG. At high doses, however, ketamine also acts at non-NMDAR sites, produces loss of consciousness, and the transient disappearance of the HFO. We propose a two-compartment PK model that represents the concentration of ketamine, and a PD model based in opposing effects of the NMDAR and non-NMDAR actions on the HFO power. Main results. We recorded ECoG from the cortex of rats after two doses of ketamine, and extracted the HFO power from the ECoG spectrograms. We fit the PK-PD model to the time course of the HFO power, and showed that the model reproduces the dose-dependent profile of the HFO power. The model provides good fits even in the presence of high variability in HFO power across animals. As expected, the model does not provide good fits to the HFO power after dosing the pure NMDAR antagonist MK-801. Significance. Our study provides a simple model to relate the observed electrophysiological effects of ketamine to its actions at the molecular level at different concentrations. This will improve the study of ketamine and rodent models of schizophrenia to better understand the wide and divergent

  11. Human biodistribution and radiation dosimetry of {sup 11}C-(R)-PK11195, the prototypic PET ligand to image inflammation

    Hirvonen, Jussi; Roivainen, Anne; Virta, Jere; Helin, Semi; Naagren, Kjell; Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, P.O. Box 52, Turku (Finland)


    The positron emission tomography (PET) radiotracer {sup 11}C-(R)-PK11195 allows the in vivo imaging in humans of the translocator protein 18 kDa (TSPO), previously called peripheral benzodiazepine receptor (PBR), a marker of inflammation. Despite its widespread use, the radiation burden associated with {sup 11}C-(R)-PK11195 in humans is not known. To examine this, we performed dynamic whole-body imaging with PET and {sup 11}C-(R)-PK11195 in healthy humans. Five healthy male volunteers were scanned with PET and {sup 11}C-(R)-PK11195, using a dynamic whole-body imaging protocol. An organ-specific method was used to measure accumulated radioactivity in source organs, and residence times were calculated as areas under the curve of time-activity curves expressed as percentage of injected radioactivity. Residence times were used as input for OLINDA/EXM 1.0 software to model the equivalent organ doses and the effective dose for the 70-kg man. After intravenous injection of {sup 11}C-(R)-PK11195, radioactivity accumulated in organs rich in TSPO as well as routes of excretion: the hepatobiliary system and the urine. The mean effective dose was 4.8 {mu}Sv/MBq according to International Commission on Radiological Protection (ICRP) Publication 60 and 5.1 {mu}Sv/MBq according to ICRP Publication 103, and the highest equivalent organ doses were observed in the kidneys (14.0 {mu}Sv/MBq), spleen (12.5 {mu}Sv/MBq) and small intestine (12.2 {mu}Sv/MBq). Imaging of TSPO with PET using {sup 11}C-(R)-PK11195 is associated with modest radiation exposure, similar in magnitude to most other {sup 11}C-labelled PET tracers, suggesting feasibility of {sup 11}C-(R)-PK11195 imaging in clinical human studies involving multiple scans in the same subjects per year. (orig.)

  12. Doxycycline down-regulates DNA-PK and radiosensitizes tumor initiating cells: Implications for more effective radiation therapy.

    Lamb, Rebecca; Fiorillo, Marco; Chadwick, Amy; Ozsvari, Bela; Reeves, Kimberly J; Smith, Duncan L; Clarke, Robert B; Howell, Sacha J; Cappello, Anna Rita; Martinez-Outschoorn, Ubaldo E; Peiris-Pagès, Maria; Sotgia, Federica; Lisanti, Michael P


    DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline reduces DNA-PK protein expression by nearly 15-fold (> 90%). In accordance with these observations, we show that doxycycline functionally radio-sensitizes breast CSCs, by up to 4.5-fold. Moreover, we demonstrate that DNA-PK is highly over-expressed in both MCF7- and T47D-derived mammospheres. Interestingly, genetic or pharmacological inhibition of DNA-PK in MCF7 cells is sufficient to functionally block mammosphere formation. Thus, it appears that active DNA-repair is required for the clonal expansion of CSCs. Mechanistically, doxycycline treatment dramatically reduced the oxidative mitochondrial capacity and the glycolytic activity of cancer cells, consistent with previous studies linking DNA-PK expression to the proper maintenance of mitochondrial DNA integrity and copy number. Using a luciferase-based assay, we observed that doxycycline treatment quantitatively reduces the anti-oxidant response (NRF1/2) and effectively blocks signaling along multiple independent pathways normally associated with stem cells, including STAT1/3, Sonic Hedgehog (Shh), Notch, WNT and TGF-beta signaling. In conclusion, we propose that the efficacy of doxycycline as a DNA-PK inhibitor should be tested in Phase-II clinical trials, in combination with radio-therapy. Doxycycline has excellent

  13. DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA repair and suppresses sister chromatid exchange.

    Hungjiun Liaw

    Full Text Available Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8 has been used as a marker for activation of the DNA damage response. What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s are responsible for them, and what is the biological outcome of these phosphorylations, however, have not been fully investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks (DSBs and that the DNA-dependent protein kinase complex (DNA-PK is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to alanines, which prevent phosphorylations at these sites, caused increased mitotic entry with concomitant increases in RAD51 foci and homologous recombination. Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry. This pathway thus permits cells to repair DNA damage properly and increase cell viability.

  14. Challenges in application of bioanalytical method on different populations and effect of population on PK.

    Kale, Prashant; Shukla, Manoj; Soni, Gunjan; Patel, Ronak; Gupta, Shailendra


    Prashant Kale has 22 years of immense experience in the analytical and bioanalytical domain. He is Senior Vice President, Bioequivalence Operations of Lambda Therapeutic Research, India which includes Bioanalytical, Clinics, Clinical data management, Pharmacokinetics and Biostatistics, Protocol writing, Clinical lab and Quality Assurance departments. He has been with Lambda for over 14 years. By qualification he is a M.Sc. and an MBA. Mr. Kale is responsible for the management, technical and administrative functions of the BE unit located at Ahmedabad and Mumbai, India. He is also responsible for leading the process of integration between bioanalytical laboratories and services offered by Lambda at global locations (India and Canada). Mr. Kale has faced several regulatory audits and inspections from leading regulatory bodies including but not limited to DCGI, USFDA, ANVISA, Health Canada, UK MHRA, Turkey MoH, WHO. There are many challenges involved in the application of bioanalytical method on different populations. This includes difference in equipment, material and environment across laboratories, variations in the matrix characteristics in different populations, differences in techniques between analysts such as sample processing and handling and others. Additionally, there is variability in the PK of a drug in different populations. This article shows the effect of different populations on validated bioanalytical method and on the PK of a drug. Hence, the bioanalytical method developed and validated for a specific population may need required modification when applied to another population. Critical consideration of all such aspects is the key to successful implementation of a validated method on different populations.

  15. D6PK AGCVIII Kinases Are Required for Auxin Transport and Phototropic Hypocotyl Bending in Arabidopsis[C][W

    Willige, Björn C.; Ahlers, Siv; Zourelidou, Melina; Barbosa, Inês C.R.; Demarsy, Emilie; Trevisan, Martine; Davis, Philip A.; Roelfsema, M. Rob G.; Hangarter, Roger; Fankhauser, Christian; Schwechheimer, Claus


    Phototropic hypocotyl bending in response to blue light excitation is an important adaptive process that helps plants to optimize their exposure to light. In Arabidopsis thaliana, phototropic hypocotyl bending is initiated by the blue light receptors and protein kinases phototropin1 (phot1) and phot2. Phototropic responses also require auxin transport and were shown to be partially compromised in mutants of the PIN-FORMED (PIN) auxin efflux facilitators. We previously described the D6 PROTEIN KINASE (D6PK) subfamily of AGCVIII kinases, which we proposed to directly regulate PIN-mediated auxin transport. Here, we show that phototropic hypocotyl bending is strongly dependent on the activity of D6PKs and the PIN proteins PIN3, PIN4, and PIN7. While early blue light and phot-dependent signaling events are not affected by the loss of D6PKs, we detect a gradual loss of PIN3 phosphorylation in d6pk mutants of increasing complexity that is most severe in the d6pk d6pkl1 d6pkl2 d6pkl3 quadruple mutant. This is accompanied by a reduction of basipetal auxin transport in the hypocotyls of d6pk as well as in pin mutants. Based on our data, we propose that D6PK-dependent PIN regulation promotes auxin transport and that auxin transport in the hypocotyl is a prerequisite for phot1-dependent hypocotyl bending. PMID:23709629

  16. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.


    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma-radiation but at 0.25 Gy gamma

  17. Involvement of DNA-PK(sub cs) in DSB Repair Following Fe-56 Ion Irradiation

    O'Neill, Peter; Harper, Jane; Anderson, Jennifer a.; Cucinnota, Francis A.


    When cells are exposed to radiation, cellular lesions are induced in the DNA including double strand breaks (DSBs), single strand breaks and clustered DNA damage, which if not repaired with high fidelity may lead to detrimental biological consequences. Complex DSBs are induced by ionizing radiation and characterized by the presence of base lesions close to the break termini. They are believed to be one of the major causes of the biological effects of IR. The complexity of DSBs increases with the ionization density of the radiation and these complex DSBs are distinct from the damage induced by sparsely ionizing gamma-radiation. It has been hypothesized that complex DSBs produced by heavy ions in space pose problems to the DNA repair machinery. We have used imm uno-cyto-chemical staining of phosphorylated histone H2AX (gamma-H2AX) foci, as a marker of DSBs. We have investigated the formation and loss of gamma-H2AX foci and RAD51 foci (a protein involved in the homologous recombination pathway) in mammalian cells induced by low fluences of low-LET gamma-radiation and high-LET Fe-56 ions (1GeV/n, 151 keV/micron LET). M059J and M059K cells, which are deficient and proficient in DNA-PK(sub cs) activity respectively, were used to examine the role of DNA-PK(sub cs), a key protein in the non-homologous end joining (NHEJ) pathway of DSB repair, along with HF19 human fibroblasts. Followi ng irradiation with Fe-56 ions the rate of repair was slower in M059J cells compared with that in M059K, indicating a role for DNA-PK(sub cs) in the repair of DSB induced by Fe-56 ions. However a small percentage of DSBs induced are rejoined within 5 h although many DSBs still persist up to 24 h. When RAD51 was examined in M059J/K cells, RAD51 foci are visible 24 hours after irradiation in approximately 40% of M059J cells compared with DSB induced by 56Fe ions. Vanillin, an inhibitor of DNA-PK(sub cs), reduces significantly the rate of DSB repair in HF19 cells following 1 Gy gamma

  18. The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy; Le complexe de reparation de l'ADN DNA-PK, une cible pharmacologique en chimiotherapie et radiotherapie anticancereuse

    Salles, B.; Calsou, P.; Frit, P.; Muller, C. [Institut de Pharmacologie et Biologie Structurale (IPBS), UMR CNRS 5089, 31 - Toulouse (France)


    A line of investigation in the search for sensitizing tumor cells to chemotherapy or radiotherapy relies on the selection of DNA repair inhibitors. In the area of DNA repair mechanisms, DNA-dependent protein kinase (DNA-PK) represents a key complex. Indeed DNA-PK is involved in the non-homologous end joining (NHEJ) process that corresponds to the major activity responsible for cell survival after ionizing radiation or chemotherapeutic treatment producing DNA double strand breaks. DNA-PK belongs to the PI3-K related kinase family and specific inhibitors have been recently selected and evaluated as radio- and chemo-sensitizers. These drugs, along with other ways to inhibit the DSBs repair process, are presented and discussed. (authors)

  19. PK-SVD Filter for Impulse Noise Based on Non-noisy Pixel Reconstruction%基于非噪声像素重构的PK-SVD脉冲噪声滤波

    黄宴委; 祁冰露


    An improved K-SVD method based on non-noisy pixel reconstruction ( PK-SVD) is proposed to filter impulse noise. In the phase of image reconstruction, non-noisy pixels are applied in the construction of optimal function to obtain the reconstructed image and improve the filtering performance, and the optimal function is solved by integrating the hierarchical property into the OMP algorithm. In the phase of dictionary training, PK-SVD uses the iterant K-singular value decomposition to renovate both atoms and their coefficients rather than fixes the coefficients. The simulation results show that compared with the other three methods, PK-SVD obtains the sparsest dictionary and the clearest image with higher peak signal to noise ratio.%提出一种基于非噪声像素重构的K-SVD( Pixel K-SVD)脉冲噪声滤波方法。在图像重构阶段,以非噪声点像素值为优化目标,利用分层重构改进OMP算法求解优化函数,获得重构图像以提高恢复图像质量;在字典训练阶段,PK-SVD不再固定原子的系数,而是使用重复奇异值分解同时更新原子和系数。将PK-SVD与其他3种方法进行比较,实验结果表明,PK-SVD能得到最稀疏化的字典,较好地抑制脉冲噪声,使得滤波图像较清晰且具有较高的峰值信噪比。

  20. The ECMO PK Project: an incremental research approach to advance understanding of the pharmacokinetic alterations and improve patient outcomes during extracorporeal membrane oxygenation

    Shekar, Kiran; Roberts, Jason A; Smith, Maree T.; Fung, Yoke L.; Fraser, John F.


    Background Extracorporeal membrane oxygenation (ECMO) is a supportive therapy and its success depends on optimal drug therapy along with other supportive care. Emerging evidence suggests significant interactions between the drug and the device resulting in altered pharmacokinetics (PK) of vital drugs which may be further complicated by the PK changes that occur in the context of critical illness. Such PK alterations are complex and challenging to investigate in critically ill patients on ECMO...

  1. Rapid Determination of Ionization Constants (pK a) by UV Spectroscopy Using 96-Well Microtiter Plates.

    Martínez, Carlos H Ríos; Dardonville, Christophe


    We have developed a methodology that enables for the rapid measurement of ionization constants (pK a) of series of compounds by UV spectrophotometry. This protocol, which is straightforward to set up, takes advantage of the sensitivity of UV spectroscopy and the throughput enabled by the 96-well microplate (as opposed to the use of 1 cm quartz cuvette). The compounds, in stock solutions in DMSO, are dissolved in several aqueous buffer solutions directly in the microtiter plate, allowing the simultaneous determination of the UV spectra as a function of pH. Further treatment of the data provides the pK a values in a medium-throughput manner. The pK a values of 11 new antitrypanosomal dibasic compounds were determined using this methodology.

  2. DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells

    Urushihara, Yusuke [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Kobayashi, Junya [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Matsumoto, Yoshihisa [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Tokyo 152-8550 (Japan); Komatsu, Kenshi [Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan); Oda, Shoji [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Mitani, Hiroshi, E-mail: [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan)


    Highlights: Black-Right-Pointing-Pointer We investigated the effect of DNA-PK inhibition on DSB repair using fish cells. Black-Right-Pointing-Pointer A radiation sensitive mutant RIC1 strain showed a low level of DNA-PK activity. Black-Right-Pointing-Pointer DNA-PK dysfunction leads defects in HR repair and DNA-PKcs autophosphorylation. Black-Right-Pointing-Pointer DNA-PK dysfunction leads a slight increase in the number of 53BP1 foci after DSBs. Black-Right-Pointing-Pointer DNA-PK dysfunction leads an alternative NHEJ that depends on 53BP1. -- Abstract: Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK, a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ deficiency. However, in this study, we demonstrate that a wild-type cell line treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes). Previously, we reported that the radiation-sensitive mutant RIC1 strain has a defect in the Histone H2AX phosphorylation after {gamma}-irradiation. Here, we showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant reduction in the number of {gamma}H2AX foci after {gamma}-irradiation in wild-type cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells showed significantly lower levels of DNA-PK kinase activity compared with wild-type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild-type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency. These results indicated that aberrant DNA-PK causes the reduction in the number of {gamma}H2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated DNA-PKcs (Thr2609) and 53BP1 focus assay after {gamma}-irradiation. RIC1 cells showed significant reduction in the number of phosphorylated DNA-PKcs foci and no deference in the

  3. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald


    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  4. A Convenient Radiolabeling of [{sup 11}C](R)-PK11195 Using Loop Method in Automatic Synthesis Module

    Lee, Hak Jeong; Jeong, Jae Min; Lee, Yun Sang; Kim, Hyung Woo; Choi, Jae Yeon; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    ((R)-1-(2-chlorophenyl)-N-1-[[{sup 11}C]methyl-N-(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [[{sup 11}C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. (R)-NDesmethyl- PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [{sup 11}C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. The labeling efficiency of [[{sup 11}C](R)-PK11195 was 71.8{+-}8.5%. The specific activity was 11.8{+-}6.4 GBq/{mu}mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. By the one-step loop method with the [[{sup 11}C]CH3I automated synthesis module, [[{sup 11}C](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.

  5. PET study of carbon-11-PK 11195 binding to peripheral type benzodiazepine sites in glioblastoma: A case report

    Pappata, S.; Cornu, P.; Samson, Y.; Prenant, C.; Benavides, J.; Scatton, B.; Crouzel, C.; Hauw, J.J.; Syrota, A. (INSERM U. 334 Service Hospitalier Frederic Joliot, Paris (France))


    The utility of the peripheral type benzodiazepine site ligand 11C-PK 11195, for imaging human glioma in conjunction with Positron Emission Tomography, relies on a high specific binding of the tracer to tumoral peripheral type benzodiazepines sites. In a patient with glioblastoma, the authors found that 11C-PK 11195 binding was two-fold higher in the tumor than in normal gray matter and that 30% of tumoral binding could be displaced by a large excess of unlabeled drug. These findings suggest that tumoral retention of the ligand is due, in part, to specific binding.

  6. 非洲维和官兵适应性障碍及EPQ的相关研究%A Correlative Study of maladjustment and EPQ about African peacekeeping Soldiers with Suicide Ideation

    张理义; 王艳玲; 郭健; 林海; 陈春霞; 姚高峰


    目的 探讨有自杀意念的非洲维和官兵适应性障碍与人格特征的相关性.方法 采用随机整群抽样法,选取非洲维和官兵共270名,以艾森克人格问卷(EPQ)和军人适应不良自评量表(MMMS)进行测评,数据结果应用t检验,相关分析,多元逐步回归分析等进行统计学处理.结果 非洲维和官兵发生自杀意念率达21.85%,有自杀意念的非洲维和官兵中,个性内向情绪不稳定(抑郁质)12人,占20.0%,个性内向情绪稳定(粘液质)42人,占71.7%,个性外向情绪不稳定(胆汁质)2人,占3.3%,个性外向情绪稳定(多血质)3人,占5.0%;无自杀意念的维和官兵中,个性内向情绪不稳定(抑郁质)13人,占6.2%,个性内向情绪稳定(粘液质)149人,占70.6%,个性外向情绪不稳定(胆汁质)3人,占1.4%,个性外向情绪稳定(多血质)46人,占21.8%;有无自杀意念的非洲维和官兵的适应不良各因子分及总分均显著高于中国军人常模(P<0.05),但有无自杀意念的两组维和官兵适应不良各因子及总分无明显差异(P>0.05);有自杀意念维和官兵的EPQ-P,EPQ-N,EPQ-L得分显著升高(P<0.05);有自杀意念非洲维和官兵的EPQ-P与行为问题呈低度负相关(P<0.05)、与人际关系不良呈正相关(P<0.05).EPQ-N与环境适应呈显著负相关(P<0.05).另外,年龄、受教育年数、婚姻、职务与人际关系不良及适应不良总分关系密切,r在-0.188~0.153之间(P<0.05).结论 非洲维和官兵发生自杀意念率达21.85%,有自杀意念以个性内向情绪不稳定(抑郁质)型为多,更易出现适应性障碍,且有自杀意念维和官兵的适应性障碍与人格特征存在明显关系.%Objective To explore the correlation between psychological adaptation status and personality characteristics about Asian's peacekeeping soldiers. Methods Through random cluster sampling, 1343 peacekeeping soldiers by the Military Mental Maladjustment Scale

  7. Biochemical analysis of fruiting bodies of Volvariella volvacea strain Vv pk, grown on six different substrates

    Imran Ul Haq, Muhammad Aslam Khan, Sajid Aleem Khan


    Full Text Available A local strain of Volvariella volvacea Vv pk, locally known as Chinese mushroom was cultivated on six different agricultural wastes including paddy straw, cotton waste, banana leaves, corn stovers, sugarcane baggasse and pulses straw. The study was conducted to know that how much a substrate contributes in the nutritional value of the fruiting bodies of the mushroom harvested from such substrate and to recommend the best substrate for the commercial cultivation of the mushroom with high levels of protein, crude fibre and certain other elements. The biochemical analysis of the fruiting bodies harvested from the substrates was done to estimate the moisture percentage, crude fat, protein, fiber, and ash contents. Maximum protein (34.17%, ash (10.8 and crude fiber percentage (11.9% was observed in the fruiting bodies harvested from cotton waste. So, cotton waste is recommended as an effective substrate to grow Chinese mushroom on commercial scale.

  8. Prediction of PK-specific phosphorylation site based on information entropy


    Phosphorylation is a crucial way to control the activity of proteins in many eukaryotic organisms in vivo. Experimental methods to determine phosphorylation sites in substrates are usually restricted by the in vitro condition of enzymes and very intensive in time and labor. Although some in silico methods and web servers have been introduced for automatic detection of phosphorylation sites, sophisticated methods are still in urgent demand to further improve prediction performances. Protein primary se-quences can help predict phosphorylation sites catalyzed by different protein kinase and most com-putational approaches use a short local peptide to make prediction. However, the useful information may be lost if only the conservative residues that are not close to the phosphorylation site are consid-ered in prediction, which would hamper the prediction results. A novel prediction method named IEPP (Information-Entropy based Phosphorylation Prediction) is presented in this paper for automatic de-tection of potential phosphorylation sites. In prediction, the sites around the phosphorylation sites are selected or excluded by their entropy values. The algorithm was compared with other methods such as GSP and PPSP on the ABL, MAPK and PKA PK families. The superior prediction accuracies were ob-tained in various measurements such as sensitivity (Sn) and specificity (Sp). Furthermore, compared with some online prediction web servers on the new discovered phosphorylation sites, IEPP also yielded the best performance. IEPP is another useful computational resource for identification of PK-specific phosphorylation sites and it also has the advantages of simpleness, efficiency and con-venience.

  9. Valores, Creencias Y Objectivos: Base del programa de la Escuela Experimental P.K. Yonge. (Values, Beliefs and Objectives: The Basis of Experimental Schools P.K. Yonge's Program.)

    Florida Univ., Gainesville. Coll. of Education.

    The values, beliefs, and objectives that form the core of the program at the Experimental School P.K. Yonge in the University of Florida are presented in this paper which is written in Spanish. This experimental school serves approximately 900 students from grades one through twelve. The function of the school is to conduct research to solve…

  10. Proliferation Characteristics of a PK-15 Cell-adapted Strain of Porcine Parvovirus%猪细小病毒PK-15细胞适应株的培育及增殖特性

    吴云飞; 朱玲; 徐志文; 付梦瑾; 陈蕾; 阳爱国; 郭万柱


    To study the proliferation characteristics of PPV in differently infected way and the variance of concentrations in different cells.A strain of porcine parvovirus(PPV) was adapted to PK-15 cells,and a Real-time fluorescent quantitative PCR (FQ-PCR) assay was developed based on the specific region of the NS1 gene of PPV to quantify the PPV.The FQ-PCR was used to measure the viral concentration of virusinfected cells by simultaneous or step by step inoculation and plot one-step growth curves.The proliferation characteristics of PPV strain in different cells lines (HeLa,MDBK,PK-15,ST,F81,BHK-21 and Marc-145) was also compared.The results showed the PK-15 cell-adapted strain of PPV produced CPE after 12 passages,and maintained stable CPE at the following 10 messages.The one-step growth curve showed that the virus concentration of simultaneous inoculation was higher than that of the step-by-step inoculation,and the proliferation cycle of step-by-step inoculation was shorter.The proliferation ability of PPV strain in different ceils showed that CPE appeared first inPK-15,followed by ST,HeLa and MDBK,and the virus concentration was highest in ST,followed byPK-15,MDBK and HeLa.NO proliferation was observed in F81,BHK-21 and Marc-145 cells.These findings lay a material foundation for the basic researches on PPV and the development of vaccine.%为了研究猪细小病毒不同接毒方式的增殖规律及在不同细胞的病毒含量差异.本实验利用PK-15细胞对猪细小病毒(Porcine parvovirus,PPV)分离株进行适应性培养.针对PPV的NS1基因设计特异性引物,建立实时荧光定量PCR方法.利用该方法检测PPV分离株同步和分步接毒的病毒含量,绘制一步生长曲线;同时检测PPV在HeLa、MDBK、PK-15、ST、F81、BHK-21和Marc-145细胞上的增殖特性.结果显示,PPV分离株盲传至12代产生CPE,继续传代培养10代仍能产生稳定的细胞病变,成功培育出PK-15细胞适应株.一步生长曲线显示,

  11. A physiologically based pharmacokinetic (PB/PK) model for multiple exposure routes for soman in multiple species

    Sweeney, R.E.; Langenberg, J.P.; Maxwell, D.M.


    A physiologically based pharmacokinetic (PB/PK) model has been developed in advanced computer simulation language (ACSL) to describe blood and tissue concentration-time profiles of the C(±)P(-) stereoisomers of soman after inhalation, subcutaneous and intravenous exposures at low (0.8-1.0 × LD50), m

  12. The radiosynthesis of ( sup 18 F)PK 14105 as an alternative radioligand for peripheral type benzodiazepine binding sites

    Pascali, C.; Luthra, S.K.; Pike, V.W.; Price, G.W.; Ahier, R.G.; Hume, S.P.; Myers, R.; Manjil, L.; Cremer, J.E. (Hammersmith Hospital, London (UK). M.R.C. Cyclotron Unit)


    A method has been developed for labelling PK 14105 (N-methyl-N-(1-methyl-propyl)-1(2-fluoro-5-nitrophenyl)isoquinoline-3-carboxamide ), a ligand that has high affinity and selectivity for peripheral type benzodiazepine binding sites (PBBS), with NCA fluorine-18 (t{sub 1/2}=109.8 min, {beta}{sup +} = 96.9%). The method involves treating the 2-chloro-analogue with cyclotron-produced NCA ({sup 18}F)fluoride in dimethyl sulphoxide, with rubidium carbonate as base, at 140{sup 0}C for 20 min. Purification is achieved by separation on a reverse phase Sep-Pak followed by HPLC on a silica gel column, to give chemically and radiochemically pure product with a specific activity of ca 7.4 GBq/{mu}mol (200 mCi{mu}mol), decay-corrected to the end of radionuclide production (EOB). The radiosynthesis requires 210 min, giving a radiochemical yield of 10-20%, decay-corrected to EOB. ({sup 18}F)PK 14105 was found to bind avidly to sites associated with kainic acid-induced unilateral lesions of rat striata. Such binding was blocked by pre-dosing the rat with PK 11195, so providing evidence for specific binding to PBBS. These results suggest that ({sup 18}F)PK 14105 has potential for studying phenomena associated with PBBS in man by PET. (author).

  13. Comparison of the proteomes of three yeast wild type strains: CEN.PK2, FY1679 and W303

    Rogowska-Wrzesinska, A.; Mose Larsen, P.; Blomberg, A.


    Yeast deletion strains created during gene function analysis projects very often show drastic phenotypic differences depending on the genetic background used. These results indicate the existence of important molecular differences between the CEN.PK2, FY1679 and W303 wild type strains. To charact...

  14. The apparent positive cooperativity of in vivo [{sup 3}H]PK-11195 binding in mouse fibrosarcoma

    Momosaki, Sotaro [Course of Allied Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871 (Japan)]. E-mail:; Hosoi, Rie [Course of Allied Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871 (Japan); Takai, Nobuhiko [Heavy-Ion Radiobiology Research Group, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Gee, Antony [GlaxoSmithKline, Clinical Research Unit, ACCI, Addenbrookes Hospital, Cambridge CB2 2GC (United Kingdom); Inoue, Osamu [Course of Allied Health Sciences, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871 (Japan)


    To evaluate the binding properties of peripheral benzodiazepine receptor (PBR) in mouse fibrosarcoma, [{sup 3}H]PK-11195 binding, in vitro and in vivo, was investigated using either tissue dissection or autoradiographic method. The binding characteristics in fibrosarcoma were compared with those in the kidney. The results of an in vitro saturation study revealed that the maximal numbers of PBR binding sites (B {sub max}) in fibrosarcoma and in the kidney were almost the same (kidney: 5.2 pmol/mg protein; fibrosarcoma: 5.0 pmol/mg protein). On the other hand, the binding affinity (K {sub d}) in fibrosarcoma was lower than that in the kidney (kidney: 0.45 nM; fibrosarcoma: 1.34 nM). It is noteworthy that the in vivo binding of [{sup 3}H]PK-11195 in fibrosarcoma increased with increasing doses of [{sup 3}H]PK-11195 (in the dose range of 0.03-1 mg/kg), whereas that in the kidney decreased with competitive inhibition. The apparent positive cooperativity of [{sup 3}H]PK-11195 binding in fibrosarcoma was only observed under in vivo conditions and might be possibly related to the incoordination of PBR subunits.


    Muhammad Fauzan


    Full Text Available This research related to the implementation of good governance, free from corruption, collusion and nepotism. The approach used in this research is a descriptive qualitative approach. The Location of research conducted in the District of Pemalang. Based on the research results can presented that the District of Pemalang is committed and fully supports the government policy in eradicating corruption. District of Pemalang support to efforts to more information accelerate the eradication of corruption stated in the the Regional Action Plan to Accelerate the Eradication of Corruption (RAD-PK in 2011 -2016 which refers to the Medium Term Development Plan (RPJM District of Pemalang from 2011 to 2016 and the National Action Plan for Eradication of Corruption (RAN-PK and the President of Republic of Indonesia Instruction No. 5 Year 2004 on Accelerating the eradication of corruption. RAD-PK 2011-2016 District of Pemalang is a document that contains an action program that aims to accelerate the eradication of corruption. RAD-PK as a program of action containing concrete measures that have been agreed by the stakeholders in the area, so it has been a commitment of local governments prevention efforts corruption through the development of programs and activities aimed at improving public services and the application of the principles of good governance.

  16. Rapid and efficient radiosynthesis of [{sup 123}I]I-PK11195, a single photon emission computed tomography tracer for peripheral benzodiazepine receptors

    Pimlott, Sally L. [Department of Clinical Physics, West of Scotland Radionuclide Dispensary, Western Infirmary, G11 6NT Glasgow (United Kingdom)], E-mail:; Stevenson, Louise [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom); Wyper, David J. [Institute of Neurological Sciences, Southern General Hospital, G51 4TF Glasgow (United Kingdom); Sutherland, Andrew [Department of Chemistry, WestCHEM, University of Glasgow, G12 8QQ Glasgow (United Kingdom)


    Introduction: [{sup 123}I]I-PK11195 is a high-affinity single photon emission computed tomography radiotracer for peripheral benzodiazepine receptors that has previously been used to measure activated microglia and to assess neuroinflammation in the living human brain. This study investigates the radiosynthesis of [{sup 123}I]I-PK11195 in order to develop a rapid and efficient method that obtains [{sup 123}I]I-PK11195 with a high specific activity for in vivo animal and human imaging studies. Methods: The synthesis of [{sup 123}I]I-PK11195 was evaluated using a solid-state interhalogen exchange method and an electrophilic iododestannylation method, where bromine and trimethylstannyl derivatives were used as precursors, respectively. In the electrophilic iododestannylation method, the oxidants peracetic acid and chloramine-T were both investigated. Results: Electrophilic iododestannylation produced [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than achievable using the halogen exchange method investigated. Using chloramine-T as oxidant provided a rapid and efficient method of choice for the synthesis of [{sup 123}I]I-PK11195. Conclusions: [{sup 123}I]I-PK11195 has been successfully synthesized via a rapid and efficient electrophilic iododestannylation method, producing [{sup 123}I]I-PK11195 with a higher isolated radiochemical yield and a higher specific activity than previously achieved.

  17. The pkI gene encoding pyruvate kinase I links to the luxZ gene which enhances bioluminescence of the lux operon from Photobacterium leiognathi.

    Lin, J W; Lu, H C; Chen, H Y; Weng, S F


    Partial 3'-end nucleotide sequence of the pkI gene (GenBank accession No. AF019143) from Photobacterium leiognathi ATCC 25521 has been determined, and the encoded pyruvate kinase I is deduced. Pyruvate kinase I is the key enzyme of glycolysis, which converts phosphoenol pyruvate to pyruvate. Alignment and comparison of pyruvate kinase Is from P. leiognathi, E. coli and Salmonella typhimurium show that they are homologous. Nucleotide sequence reveals that the pkI gene is linked to the luxZ gene that enhances bioluminescence of the lux operon from P. leiognathi. The gene order of the pkI and luxZ genes is-pk1-ter-->-R&R"-luxZ-ter"-->, whereas ter is transcriptional terminator for the pkI and related genes, and R&R" is the regulatory region and ter" is transcriptional terminator for the luxZ gene. It clearly elicits that the pkI gene and luxZ gene are divided to two operons. Functional analysis confirms that the potential hairpin loop omega T is the transcriptional terminator for the pkI and related genes. It infers that the pkI and related genes are simply linked to the luxZ gene in P. leiognathi genome.

  18. On Basic Qualities of Peacekeeping Police%维和警察应具备的基本素质探析



    With the changing international situation, the complexity of peace - keeping work is also increasing. This demands peacekeeping police a higher level of basic qualities. Based on the special needs proposed, "One Must, Two Enhancement, Six Knowings, Six Understandings, Five Mastery" training requirements were suggested.%随着国际形势的不断变化,维和工作也日益复杂,对维和警察的基本素质提出更高的要求,在这种需求的基础上特提出了“一要、二增强、六懂、六会、五掌握”的训练要求。

  19. Post-cold war United Nations peacekeeping operations: a review of the case for a hybrid level 2+ medical treatment facility.

    Johnson, Ralph Jay


    Post-Cold War, UN peacekeeping operations (UN PKOs) have become larger, more mobile, multi-faceted and conducted over vast areas of remote, rugged, and harsh geography. They have been increasingly involved in dangerous areas with ill-defined boundaries, simmering internecine armed conflict, and disregard on the part of some local parties for peacekeepers' security and role. Yet progressively there have been expectations of financial restraint and austerity. Additionally, UN PKOs have become more "robust," that is, engaged in preemptive, assertive operations. A statistically positive and significant relationship exists between missions' size, complexity, remoteness, and aggressive tenor and a higher probability of trauma or death, especially as a result of hostile actions or disease. Therefore, in the interest of "force protection" and optimizing operations, a key component of UN PKOs is health care and medical treatment. The expectation is that UN PKO medical support must conform to the general intent and structure of current UN PKOs to become more streamlined, portable, mobile, compartmentalized, and specialized, but also more varied and complex to address the medical aspects of these missions cost-efficiently. This article contends that establishing a hybrid level 2-a level 2 with level 3 modules and components (i.e., level 2+)-is a viable course of action when considering trends in the medical aspects of Post-Cold War UN PKOs. A level 2 medical treatment facility has the potential to provide needed forward mobile medical treatment, especially trauma care, for extended, complex, large-scale, and comprehensive UN PKOs. This is particularly the case for missions that include humanitarian outreach, preventive medicine, and psychiatry. The level 2 treatment facility is flexible enough to expand into a hybrid level 2+ with augmentation of modules based on changes in mission requirements and variation in medical aspects.

  20. Molecular characterisation of cAMP-dependent protein kinase (PK-A) catalytic subunit isoforms in the male tick, Amblyomma hebraeum.

    Tabish, Mohammad; Clegg, Roger A; Turner, Philip C; Jonczy, Jan; Rees, Huw H; Fisher, Michael J


    The cAMP-dependent protein kinase (protein kinase A, PK-A) plays a central role in the regulation of diverse aspects of cellular activity. Specifically, PK-A appears to play a key controlling role in the maturation of spermatids. Using a PCR-based approach, with degenerate primers from the highly conserved regions of the PK-A catalytic (C) subunit in combination with 5' and 3' RACE, we have cloned three cDNAs for the PK-A C-subunit of the male tick, Amblyomma hebraeum. The three cDNAs have open reading frames of 1059, 1275 and 1404bp which encode proteins of 40.6, 48.2 and 52.5kDa, respectively. These transcripts appear to arise from 5' alternative splicing of RNA derived from a single gene for the PK-A C-subunit. One isoform (AH-PK-A C1), in common with PK-A C-subunits from a range of species, contains a consensus sequence for N-myristoylation. RT-PCR and Western blot experiments suggest that the three splice variants are expressed ubiquitously; however, expression of the myristoylatable AH-PK-A C1 isoform is predominant in all investigated tissues (accessory gland, midgut, Malpighian tubules, salivary gland, testis and immature spermatids). There is no evidence for a sperm-specific PK-A C-subunit (Cs) in tick sperm; however, tyrosine protein phosphorylation, previously shown to be modulated by PK-A activity during mammalian sperm maturation, was observed in tick sperm.

  1. Reasons and Management Strategy of Psychological Problems in Peacekeeping Medical Contingent%维和医疗分队心理问题产生原因及管理对策

    魏伟; 王滨; 吴成; 张亚斌


    The United Nations peacekeeping medical team suffer a lot of psychological problems,such as nervous, irritable. frustration, pain, guilt, loss of confidence because of the excessive pressures of the work, life and the security threats, target missing, different self - adjustment abilities and so on. During the different stages,the symptoms are significant differences. We can carry foresight collective methods and self adjusting to fit the UN peacekeeping missions.%本文对联合国维和医疗队员心理问题产生的原因进行分析,主要是因为工作、生活、安全压力过大,目标缺失、自我调适能力参差不齐等,针对不同临床表现提出集体和自我调适的心理管理策略.

  2. 维和医疗分队集训期心理干预效果评价%Effect Evaluation of Psychological Intervention for the Peacekeeping Medical Unit Servicemen During As-semble for Training

    王乃震; 牛晓棠; 韩兵


    目的:探讨心理干预对集训期维和医疗分队人员的影响效果。方法分别在官兵到达集训地后开始集训前一天和临集训结束前一天进行调查,采用症状自评量表( SCL-90)对来自不同部队的63名官兵进行调查。结果2次测试维和医疗分队官兵心理健康(SCL-90)状况较好。且集训结束时,SCL-90总分和部分因子分(躯体化、强迫、人际敏感、抑郁、焦虑和恐怖因子)显著低于集训前(P<0.01)。结论心理干预对集训期维和人员有良好的效果,可以使其保持良好的心理健康水平。%Objective To discuss the psychological intervention effect on the peacekeeping medical unit servicemen during assemble training.Methods Symptom Checklist ( SCL -90 ) were applied 63 peacekeeping medical unit servicemen the day before starting training and the day before the end of training.Results Mental health ( SCL-90) of two tests were good in peacekeeping medical unit servicemen, and the total score of SCL-90 and some factor scores(Somatization, Force, Interpersonal sensitivity, Depression, Anxiety and terror) were significantly lower than that before training(P<0.01).Conclusion The psychological intervention had a good effect on the peacekeeping medical unit servicemen during assemble for training, which can maintain good mental health.

  3. Physiologically based pharmacokinetic (PB-PK) modeling of indoor air pollutant degradation by houseplants

    Smith, E.K.; El-Masri, H.A.; Tessari, J.D.; Yang, R.S.H.; Reardon, K.F. [Colorado State Univ., Fort Collins, CO (United States)


    In the US, indoor air pollutant levels commonly exceed outdoor levels by a factor of 7 or more. Since people typically spend more than 90% percent of their time indoors, indoor air pollution has the potential for greater consequences on human health. A NASA researcher has reported that certain houseplants will reduce closed chamber concentrations of common indoor air pollutants by more than 75%. The authors are expanding this research; common houseplants and PB-PK modeling can be combined to predict the reduction rates of frequently detected indoor air pollutants, and be used as an environmental remediation approach. The approach to measuring plant gas uptake of indoor air pollutants provides a more quantitative and controlled approach than previous studies. Construction of the closed chamber system linked to a computerized gas chromatograph is complete. This system measures plant uptake of volatile organic chemicals. In experiments using initial concentrations of 21--2,100 ppm of the common indoor air pollutant trichloroethylene (TCE) with peace lily in soil, between 27--34% of TCE was removed during a 12-hour test period. In similar experiments, plants in abiotic potting media removed only 4--13% of TCE from the closed system, suggesting that microbial degradation or soil adsorption of TCE are significant factors.

  4. Standard systems for measurement of pK values and ionic mobilities: 2. Univalent weak bases.

    Slampová, Andrea; Krivánková, Ludmila; Gebauer, Petr; Bocek, Petr


    This paper contributes to the methodology of measuring pK values and ionic mobilities by capillary zone electrophoresis by introducing the principle of constant ionic strength and minimum interaction of analytes with counterionic components and presenting a standard system of cationic buffers for measurements of weak bases. The system is designed so that all buffers comprise the same concentration of Cl(-) present as the only counter anion. This minimizes problems caused by interactions between the counterion and the analytes which may otherwise bring biased values of obtained effective mobilities. Further, the buffer system provides constant and accurately known ionic strength for an entire set of measurements. When additionally all measurements are performed with constant Joule heating, one correction for ionic strength and temperature is then needed for the obtained set of experimental data. This considerably facilitates their evaluation and regression analysis as the corrections for ionic strength and Joule heating need not be implemented in the computation software and may be applied only once to the final regression results. An experimental example of the proposed methodology is presented and the reliability and the advantages of the proposed system are shown, where the known problematic groups of amines and pyridine were measured with high accuracy and without any notice of anomalous behavior.

  5. Cell cycle dependence of DNA-PK phosphorylation in response to DNAdouble strand breaks

    Chen, Benjamin P.C.; Chan, Doug W.; Kobayashi, Junya; Burma,Sandeep; Asaithamby, Aroumougame; Morotomi-Yano, Keiko; Quin, Jun; Chen,David J.


    DNA-dependent protein kinase (DNA-PK), consisting of Ku and DNA-PKcs subunits, is the key component of the non-homologous end joining (NHEJ) pathway of DNA double strand breaks (DSBs) repair. Though the kinase activity of DNA-PKcs is essential for NHEJ, thus far, no in vivo substrate has been conclusively identified except for an autophosphorylation site on DNA-PKcs itself (threonine 2609). Here we report the IR-induced autophosphorylation of DNA-PKcs at a novel site,serine 2056, and phosphorylation at this site is required for the repair of DSBs by NHEJ. Interestingly, IR-induced DNA-PKcs autophosphorylation is regulated in a cell cycle-dependent manner with attenuated phosphorylation in the S phase. In contrast, DNA replication-associated DSBs result in DNA-PKcs autophosphorylation and localization to DNA damage sites. These results indicate that, while IR-induced DNA-PKcs phosphorylation is attenuated in S phase, DNA-PKcs is preferentially activated by the physiologically relevant DNA replication-associated DSBs at the sites of DNA synthesis.

  6. Calcidiol and vitamin D binding protein uptake by LLC-PK/sub 1/ cells

    Keenan, M.J.; Holmes, R.P.


    The process by which target cells take up vitamin D and its metabolites is not known. The authors studied the uptake of both /sup 3/H-calcidiol and /sup 125/I-Vitamin D Binding Protein (DBP) by LLC-PK/sub 1/ cells. Uptake was directly related to their extracellular concentrations. In the presence of 55 serum in the growth media cells previously incubated with 10 nM calcitriol for 4 hr had a greater uptake of calcidiol than those cells not incubated with calcitriol. This effect of calcitriol on calcidiol uptake was absent when cells were grown in hormone-supplemented, serum-free media, despite these cells having a cytosolic calcitriol receptor. Equal uptake of calcidiol occurred when DBP was absent and when DBP was present in a one to one molar ratio to calcidiol. With a 1:1 ratio of DBP to calcidiol and a measured K/sub D/ of 2 x 10/sup -8/M, the uptake of calcidiol could not be accounted for by uptake of the free ligand alone. A large excess of DBP (100:1) in relation to calcidiol suppressed uptake of calcidiol by approx. 90%. The authors have not been able to identify a saturable, specific uptake of either calcidiol or DBP despite DBP appearing to facilitate calcidiol uptake.

  7. Ectopic TLX1 expression accelerates malignancies in mice deficient in DNA-PK.

    Konstantin Krutikov

    Full Text Available The noncluster homeobox gene HOX11/TLX1 (TLX1 is detected at the breakpoint of the t(10;14(q24;q11 chromosome translocation in patients with T cell acute lymphoblastic leukemia (T-ALL. This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHμ-TLX1(Tg mice which develop mature B cell lymphoma after a long latency period, suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHμ-TLX1(Tg mice with mice deficient in the DNA repair enzyme DNA-PK (Prkdc(Scid/Scid mice. IgHµ-TLX1(TgPrkdc(Scid/Scid mice developed T-ALL and acute myeloid leukemia (AML with reduced latency relative to control Prkdc(Scid/Scid mice. Further analysis of thymi from premalignant mice revealed greater thymic cellularity concomitant with increased thymocyte proliferation and decreased apoptotic index. Moreover, premalignant and malignant thymocytes exhibited impaired spindle checkpoint function, in association with aneuploid karyotypes. Gene expression profiling of premalignant IgHµ-TLX1(TgPrkdc(Scid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in double negative 2 (DN2 and DN3 stage thymocytes. Collectively, these findings reveal a novel synergy between TLX1 and impaired DNA repair pathway in leukemogenesis.

  8. The pK0Σ+ final state in proton-proton collisions

    Abdel-Bary, M.; Abdel-Samad, S.; Brinkmann, K.-Th.; Clement, H.; Dietrich, J.; Doroshkevich, E.; Dshemuchadse, S.; Ehrhardt, K.; Erhardt, A.; Eyrich, W.; Filippi, A.; Freiesleben, H.; Fritsch, M.; Gast, W.; Georgi, J.; Gillitzer, A.; Gottwald, J.; Hesselbarth, D.; Jäger, H.; Jakob, B.; Jäkel, R.; Karsch, L.; Kilian, K.; Koch, H.; Krapp, M.; Kreß, J.; Kuhlmann, E.; Lehmann, A.; Marcello, S.; Marwinski, S.; Mauro, S.; Meyer, W.; Michel, P.; Möller, K.; Morsch, H. P.; Mörtel, H.; Naumann, L.; Paul, N.; Pinna, L.; Pizzolotto, C.; Plettner, Ch.; Reimann, S.; Richter, M.; Ritman, J.; Roderburg, E.; Schamlott, A.; Schönmeier, P.; Schroeder, W.; Schulte-Wissermann, M.; Sefzick, T.; Stinzing, F.; Steinke, M.; Sun, G. Y.; Teufel, A.; Ullrich, W.; Wagner, G. J.; Wagner, M.; Wenzel, R.; Wilms, A.; Wintz, P.; Wirth, S.; Wüstner, P.; Zupranski, P.


    This paper reports results from a study of the reaction pp → pK0Σ+ at beam momenta of p beam = 2950, 3059, and 3200 MeV/ c (excess energies of ɛ = 126, 161, and 206 MeV. Total cross-sections were determined for all energies; a set of differential cross-sections (Dalitz plots; invariant-mass spectra of all two-body subsystems; angular distributions of all final-state particles; distributions in helicity and Jackson frames) are presented for ɛ = 161 MeV. The total cross-sections are proportional to the volume of available three-body phase space indicating that the transition matrix element does not change significantly in this range of excess energies. It is concluded from the differential data that the reaction proceeds dominantly via the N(1710) P 11- and/or N(1720) P 13-resonance(s); N(1650) S 11 and Δ(1600) P 33 could also contribute.

  9. Experimental Study on the Cryopreservation of LLC-PK1 Epithelial Cells with Hypoxic UW Solution

    WAN Chidan; WANG Chunyou; LIU Tao; WANG Hongbo; YANG Zhiyong


    The effects of oxygen partial pressure on cryopreservation of the cells with organ preservation solution were explored. Hypoxic UW solution was made by purging the UW solution with argon. The pig proximal tubule epithelial cells (LLC-PK1 cells) were cryopreserved in hypoxic UW solution (Ar-UW group) or standard UW solution (UW group) at 4℃ for 48 h. Trypan blue staining and LDH detection were performed to evaluate the injury of the cells. The results showed that the oxygen partial pressure in Ar-UW group was significantly declined from 242±6 mmHg to 83±10 mmHg. After cryopreservation at 4℃ for 48 h, LDH leakage rate and Trypan blue-stained rate in Ar-UW group were (11.3±3.4)% and (10.5±4.7)%, respectively, which were significantly lower than in UW group [(49.5±6.9)% and (47.6±9.3)% respectively, both P<0.01]. It was concluded that lower oxygen partial pressure of UW solution was more beneficial to the cryopreservation of LLC.

  10. Semi quantification study of [{sup 11}C]-(R)-PK11195 PET brain images in multiple sclerosis; Estudo da semiquantificacao de imagens PET cerebrais de [{sup 11}C]-(R)-PK11195 na esclerose multipla

    Narciso, Lucas D.L.; Schuck, Phelipi N.; Dartora, Caroline M.; Matushita, Cristina S.; Becker, Jefferson; Silva, Ana M. Marques da, E-mail: [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil)


    PET brain images with [{sup 11}C]-(R)-PK11195 are being widely used to visualize microglial activation in vivo in neuro degenerative diseases, such as multiple sclerosis (MS). The aim of this study is to investigate the uptake behavior in justacortical and periventricular regions of [{sup 11}C]-(R)-PK11195 PET brain images reformatted in different time intervals by applying three methods, seeking method and time interval that significantly differentiate MS patients from healthy controls. Semi-quantitative SUV and uptake relative to a reference region methods were applied to PET images from different time intervals acquired from 10 patients with MS and 5 healthy controls. The results show significant SUV values difference (p = 0.01, 40 to 60 min) in justacortical and periventricular regions between groups and using the normalization method in which the uptake is relative to the mean concentration activity in the white matter (p <0.01, 10 to 60 min). (author)

  11. The expression of one ankyrin pk2 allele of the WO prophage is correlated with the Wolbachia feminizing effect in isopods

    Pichon Samuel


    Full Text Available Abstract Background The maternally inherited α-Proteobacteria Wolbachia pipientis is an obligate endosymbiont of nematodes and arthropods, in which they induce a variety of reproductive alterations, including Cytoplasmic Incompatibility (CI and feminization. The genome of the feminizing wVulC Wolbachia strain harboured by the isopod Armadillidium vulgare has been sequenced and is now at the final assembly step. It contains an unusually high number of ankyrin motif-containing genes, two of which are homologous to the phage-related pk1 and pk2 genes thought to contribute to the CI phenotype in Culex pipiens. These genes encode putative bacterial effectors mediating Wolbachia-host protein-protein interactions via their ankyrin motifs. Results To test whether these Wolbachia homologs are potentially involved in altering terrestrial isopod reproduction, we determined the distribution and expression of both pk1 and pk2 genes in the 3 Wolbachia strains that induce CI and in 5 inducing feminization of their isopod hosts. Aside from the genes being highly conserved, we found a substantial copy number variation among strains, and that is linked to prophage diversity. Transcriptional analyses revealed expression of one pk2 allele (pk2b2 only in the feminizing Wolbachia strains of isopods. Conclusions These results reveal the need to investigate the functions of Wolbachia ankyrin gene products, in particular those of Pk2, and their host targets with respect to host sex manipulation.

  12. Synthesis and evaluation of sup 11 C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography

    Hashimoto, Kenji (Fukuyama Univ., Hiroshima (Japan). Faculty of Pharmacy and Pharmaceutical Sciences); Inoue, Osamu; Suzuki, Kazutoshi; Yamasaki, Toshiro; Kojima, Masaharu


    The biodistribution of {sup 3}H-PK 11195, an antagonist of the peripheral-type benzodiazepine receptors, was studied in mice. High accumulations of radioactivity in the heart, lung, spleen, kidney and adrenal were observed after intravenous injection of tracer amounts of {sup 3}H-PK 11195 into the mice. The radioactivity in the heart, lung, spleen, kidney and adrenal was significantly decreased by the coadministration of carrier PK 11195, which indicated that PK 11195 specifically binds to the receptors. No radioactive metabolites were observed in the heart, lung and brain 20 min after intravenous administration of {sup 3}H-PK 11195. The accumulation of {sup 3}H-PK 11195 in the lung was not affected by pretreatment with either {alpha}-methyl benzylamine or imipramine, suggesting that {sup 3}H-PK 11195 specifically binds to the receptors. The ratios of radioactivity of the kidney, adrenal and spleen to blood increased as a function of time, whereas that of the lung and heart rapidly reached to a steady state. {sup 11}C-PK 11195 was synthesized by the N-methylation of desmethyl precursor yielding more than 100 mCi with high specific activity (more than 1.4 Ci/{mu}mol). The lebeling and purification procedure was completed within 23 min after the end of bombardment (EOB). The {sup 11}C-PK 11195 solution for injection seems to have a high potential for the in vivo study of the peripheral-type benzodiazepine receptors in the living human by means of positron emission tomography (PET). (author).

  13. Application of PK/PD modeling and simulation to dosing regimen optimization of high-dose human regular U-500 insulin.

    de la Peña, Amparo; Ma, Xiaosu; Reddy, Shobha; Ovalle, Fernando; Bergenstal, Richard M; Jackson, Jeffrey A


    Pharmacokinetic/pharmacodynamic (PK/PD) studies of human regular U-500 insulin (U-500R) at high doses commonly used in clinical practice (>100 units) have not been performed. The current analysis applied PK/PD modeling/simulation to fit the data and simulate single-dose and steady-state PK/PD of U-500R high-dose regimens. Data from 3 single-dose euglycemic clamp studies in healthy obese and normal-weight patients, and normal-weight patients with type 1 diabetes were used to build the model. The model was sequential (PK inputs fed into PD component). PK was described using a 1-compartment model with first-order absorption and elimination. The model estimated separate absorption rate constants for U-500R and human regular U-100 insulin. The PD component used an effect compartment model, parameterized in terms of maximum pharmacologic effect (E(max)) and concentration to achieve 50% of E(max). The model described the data well. Steady-state PK for once-daily (QD), twice-daily (BID), or thrice-daily (TID) administration appeared to be reached 24 hours after the first dose. At steady-state, QD dosing showed the greatest fluctuations in PK/PD. BID dosing showed a gradual increase in insulin action with each dose and a fairly stable basal insulin effect. For TID dosing, activity was maintained throughout the dosing interval. PK/PD modeling/simulation of high U-500R doses supports BID or TID administration with an extended duration of activity relative to QD. TID dosing may provide slightly better full-day insulin effect. Additional PK/PD studies and randomized controlled trials of U-500R are needed to validate model predictions in patients with insulin-resistant diabetes requiring high-dose insulin.

  14. [Using CTS and PK-PD models to predict the effect of uncertainty about population parameters on clinical trial power].

    Zhu, Ling; Shi, Xinling; Liu, Yajie


    The traditional clinical trail designs always depend on expert opinions and lack statistical evaluations. In this article, we present a method and illustrate how population parameter uncertainty may be incorporated in the overall simulation model. Using the techniques of clinical trail simulation (CTS) and setting up predictions on the basis of pharmacokinetics-pharmacodynamics (PK-PD) models, we advance the modeling methods for simulation, for treatment effects, and for the clinical trail power under the given PK-PD conditions. Then we discuss the model of uncertainty, suggest an ANOVA-based method, add eta2 statistics for sensitivity analysis, and canvass the effect of uncertainty about population parameters on clinical trail power. The results from simulations and the indices derived from this type of sensitivity analysis may be used for grading the influence on the prediction quality of uncertainty about different population parameters. The experiment results are satisfactory and the approach presented has practical value in clinical trails.

  15. Integration of biostatistics and pharmacometrics computing platforms for efficient and reproducible PK/PD analysis: a case study.

    Ou, Ying C; Lo, Arthur; Lee, Brian; Liu, Phillip; Kimura, Karen; Eary, Charisse; Hopkins, Alan


    Results of pharmacometric analyses influence high-level decisions such as clinical trial design, drug approval, and labeling. Key challenges for timely delivery of pharmacometric analyses are the data assembly process and tracking and documenting the modeling process and results. Since clinical efficacy and safety data typically reside in the biostatistics computing area, an integrated computing platform for pharmacometric and biostatistical analyses would be ideal. A case study is presented integrating a pharmacometric modeling platform into an existing statistical computing environment (SCE). The feasibility and specific configurations of running common PK/PD programs such as NONMEM and R inside of the SCE are provided. The case study provides an example of an integrated repository that facilitates efficient data assembly for pharmacometrics analyses. The proposed platform encourages a good pharmacometrics working practice to maintain transparency, traceability, and reproducibility of PK/PD models and associated data in supporting drug development and regulatory decisions.

  16. Porcine parvovirus infection induces apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated pathway

    Zhang, Hongling; Huang, Yong; Du, Qian; Luo, Xiaomao; Zhang, Liang; Zhao, Xiaomin; Tong, Dewen, E-mail:


    Highlights: • PPV reduces PK-15 cells viability by inducing apoptosis. • PPV infection induces apoptosis through mitochondria-mediated pathway. • PPV infection activates p53 to regulate the mitochondria apoptotic signaling. - Abstract: Porcine parvovirus (PPV) infection has been reported to induce the cytopathic effects (CPE) in some special host cells and contribute the occurrence of porcine parvovirus disease, but the molecular mechanisms underlying PPV-induced CPE are not clear. In this study, we investigated the morphological and molecular changes of porcine kidney cell line (PK-15 cells) infected with PPV. The results showed that PPV infection inhibited the viability of PK-15 cells in a time and concentration dependent manner. PPV infection induced typical apoptotic features including chromatin condensation, apoptotic body formation, nuclear fragmentation, and Annexin V-binding activity. Further studies showed that Bax was increased and translocated to mitochondria, whereas Bcl-2 was decreased in PPV-infected cells, which caused mitochondrial outer-membrane permeabilization, resulting in the release of mitochondrial cytochrome c, followed by caspase-9 and caspase-3 activation. However, the expression of Fas and Fas ligand (FasL) did not appear significant changes in the process of PPV-induced apoptosis. Moreover, PPV infection activated p53 signaling, which was involved in the activation of apoptotic signaling induced by PPV infection via regulation of Bax and Bcl-2. Taken together, our results demonstrated that PPV infection induced apoptosis in PK-15 cells through activation of p53 and mitochondria-mediated apoptosis pathway. This study may contribute to shed light on the molecular pathogenesis of PPV infection.

  17. Investigation and analysis of asthenopia in units during their peacekeeping missions%某维和部队任务期内视疲劳调查分析

    潘学会; 李孙平; 彭琦; 邓太平; 张烈政


    目的 调查分析我驻黎维和二级医院和工兵营官兵视疲劳发生情况,为维和官兵的眼保健、视疲劳防护提供参考依据.方法 对在2011年3月1日~2011年10月20日任务期内的联合国驻黎巴嫩临时维和部队(UNIFIL)中国第七批维和医疗队及第八批维和工兵营官兵进行常规眼科体检及问卷调查,包括背景情况、眼病史、用眼习惯、上机(视频操作)习惯、体育运动、眼部视疲劳症状等,对调查结果进行统计分析.结果 本次参加调查的医护人员及官兵共计159人,年龄21~51岁,平均30岁;男性142人,占89.3%,女性17人,占10.7%.调查对象平均每天上机时间5.5 h,计算机视觉综合征(CVS)发生率高达72.3%.调查对象CVS自觉症状发生率依次为眼胀及眼眶酸痛、眼干、手/肩/足/腰部疲劳、眼痒、视物模糊、眼痛、眼红、眼部异物感、畏光流泪、头晕头痛、重影、恶心呕吐.结论 调查对象中CVS发生率高,症状表现多样化,其中屈光不正、眼与显示屏距离近、上机时间长等因素加重了CVS的发生.我驻黎维和部队应加强官兵的眼保护,降低视疲劳的发生,提高官兵的眼健康.%Objective To investigate and analyze the incidence of asthenopia among officers and soldiers of a level - two hospital and an engineering battalion in Lebanon during their peacekeeping missions, and to provide the reference for the eye care and prevention of asthenopia. Methods Conventional ophthalmologic examination and questionnaire were carried out among the officers and soldier of the seventh batch of peacekeeping medical corps and the eighth patch of peacekeeping engineering battalion during their peacekeeping missions in Lebanon from March 1, 2011 to October 20, 2011. The investigated situations included background information, the history of eye diseases, the habits of using eyes, the habits watching computer and video, sports, and asthenopia symptoms. The results were

  18. Modification of polyethylene glycol onto solid lipid nanoparticles encapsulating a novel chemotherapeutic agent (PK-L4 to enhance solubility for injection delivery

    Fang YP


    Full Text Available Yi-Ping Fang,1 Pao-Chu Wu,2 Yaw-Bin Huang,3 Cherng-Chyi Tzeng,4 Yeh-Long Chen,4 Yu-Han Hung,2 Ming-Jun Tsai,5,6 Yi-Hung Tsai31Department of Biotechnology, Yuanpei University, Hsinchu, Taiwan; 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; 4School of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 5Department of Neurology, China Medical University Hospital, Taichung, Taiwan; 6School of Medicine, Medical College, China Medical University, Taichung, TaiwanBackground: The synthetic potential chemotherapeutic agent 3-Chloro-4-[(4-methoxyphenylamino]furo[2,3-b]quinoline (PK-L4 is an analog of amsacrine. The half-life of PK-L4 is longer than that of amsacrine; however, PK-L4 is difficult to dissolve in aqueous media, which is problematic for administration by intravenous injection.Aims: To utilize solid lipid nanoparticles (SLNs modified with polyethylene glycol (PEG to improve the delivery of PK-L4 and investigate its biodistribution behavior after intravenous administration.Results: The particle size of the PK-L4-loaded SLNs was 47.3 nm and the size of the PEGylated form was smaller, at 28 nm. The entrapment efficiency (EE% of PK-L4 in SLNs with and without PEG showed a high capacity of approximately 100% encapsulation. Results also showed that the amount of PK-L4 released over a prolonged period from SLNs both with and without PEG was comparable to the non-formulated group, with 16.48% and 30.04%, respectively, of the drug being released, which fit a zero-order equation. The half-maximal inhibitory concentration values of PK-L4-loaded SLNs with and those without PEG were significantly reduced by 45%–64% in the human lung carcinoma cell line (A549, 99% in the human breast adenocarcinoma cell line with estrogen receptor (MCF7, and 95% in

  19. A pumpless multi-organ-on-a-chip (MOC) combined with a pharmacokinetic-pharmacodynamic (PK-PD) model.

    Lee, Hyuna; Kim, Dae Shik; Ha, Sang Keun; Choi, Inwook; Lee, Jong Min; Sung, Jong Hwan


    A multi-organ-on-a-chip (MOC), also known as a human-on-a-chip, aims to simulate whole body response to drugs by connecting microscale cell cultures of multiple tissue types via fluidic channels and reproducing the interaction between them. While several studies have demonstrated the usefulness of MOC at a proof-of-concept level, improvements are needed to enable wider acceptance of such systems; ease of use for general biological researchers, and a mathematical framework to design and interpret the MOC systems. Here, we introduce a pumpless, user-friendly MOC which can be easily assembled and operated, and demonstrate the use of a PK-PD model for interpreting drug's action inside the MOC. The metabolism-dependent anticancer activity of a flavonoid, luteolin, was evaluated in a two-compartment MOC containing the liver (HepG2) and the tumor (HeLa) cells, and the observed anticancer activity was significantly weaker than that anticipated from a well plate study. Simulation of a PK-PD model revealed that simultaneous metabolism and tumor-killing actions likely resulted in a decreased anti-cancer effect. Our work demonstrates that the combined platform of mathematical PK-PD model and an experimental MOC can be a useful tool for gaining an insight into the mechanism of action of drugs with interactions between multiple organs. Biotechnol. Bioeng. 2017;114: 432-443. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Ameliorative effect of adenosine on hypoxia-reoxygenation injury in LLC-PK1, a porcine kidney cell line.

    Yonehana, T; Gemba, M


    We studied the effects of adenosine on injury caused by hypoxia and reoxygenation in LLC-PK1 cells. Lactate dehydrogenase and gamma-glutamyltranspeptidase were released from cells exposed to hypoxia for 6 hr and then reoxygenation for 1 hr. The addition of adenosine at 100 microM to the medium before hypoxia began significantly decreased enzyme leakage into medium during both hypoxia and reoxygenation. The adenosine A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA), at the concentration of 100 microM, did not affect enzyme release, but the adenosine A2-receptor agonist 2-p-[2-car-boxyethyl]phenethyl-amino-5'-N-ethylcarboxamido-adenosi ne hydrochloride (CGS 21680) at the concentration of 100 nM, suppressed the injury caused by hypoxia and reoxygenation. There were decreases in cAMP contents and ATP levels in LLC-PK1 cells injured by hypoxia and reoxygenation. Adenosine (100 microM) restored ATP levels in the cells during reoxygenation. With adenosine, the intracellular cAMP level was increased prominently during reoxygenation. These results suggest that adenosine protects LLC-PK1 cells from injury caused by hypoxia and reoxygenation by increasing the intracellular cAMP level via adenosine A2 receptor.

  1. PK/PD modelling of comb-shaped PEGylated salmon calcitonin conjugates of differing molecular weights.

    Ryan, Sinéad M; Frías, Jesús M; Wang, Xuexuan; Sayers, Claire T; Haddleton, David M; Brayden, David J


    Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel comb-shaped end-functionalised (poly(PEG) methyl ether methacrylate) (sCT-P) polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E(max) and an EC(50) of 3.7nM. In vivo, while free sCT and the conjugates reduced serum [calcium] to a maximum of 15-30% over 240 min, the half-life (T(1/2)) was increased and the area under the curve (AUC) was extended in proportion to conjugate MW. Likewise, the polymer conferred protection on sCT against attack by trypsin, chymotrypsin, elastase, rat serum and liver homogenates, with the best protection afforded by sCT-P (40kDa). Mathematical modelling accurately predicted the MW relationships to in vitro efficacy, potency, in vivo PK and enzymatic stability. With a significant increase in T(1/2) for sCT, the 40kDa MW comb-shaped PEG conjugate of sCT may have potential as a long-acting injectable formulation.

  2. Denmark and UN peacekeeping

    Jakobsen, Peter Viggo


    humanitarian record in Bosnia. This belief was also generated by the positive lessons learned from Denmark’s pioneering use of tanks in UNPROFOR. This tank deployment and subsequent participation in NATO and US-led missions created a new warrior identity. This identity and the Danish interest in maintaining...

  3. African Peacekeepers in Mali

    Haugegaard, Rikke


    Dette fælles DIIS-FAK forskningsprojekt undersøger de interne dynamikker i FN’s stabiliseringsmission i Mali (MINUSMA). Studiet af interoperabilitet i missionen vægtes med fokus på afrikanske styrkers opfattelser og motivation for deltagelse i MINUSMA. De afrikanske styrkers bidrag til FN er et...

  4. Armed Peacekeepers in Bosnia


    on hold in 1994. Ground planning tapered off for several months but accelerated in November 1994 when Bosnian Serb military success and NATO sea...played volleyball with the local children, for example. They were allowed to frequent a restaurant, but in groups of four with at least one soldier...form of volleyball games or sharing meals. The result was both a calming community presence and a wealth of insight.98 Beyond that, like American SF

  5. Increased densities of binding sites for the peripheral-type benzodiazepine receptor ligand [3H]PK 11195 in congenital ornithine transcarbamylase-deficient sparse fur mouse.

    Rao, V L; Qureshi, I A; Butterworth, R F


    Peripheral-type (mitochondrial) benzodiazepine receptors (PTBR) were studied in the brain and peripheral organs (kidney, liver, and testis) of normal male mice (CD-1/Y) and the congenitally hyperammonemic sparse fur (spf/Y) mouse. Radioligand binding assays were performed with [3H]PK 11195, a ligand with high selectivity and affinity for PTBR. Densities (maximal number of binding sites) of [3H]PK 11195 binding sites were greatest in kidney, followed by liver, testis, and brain. Densities of [3H]PK 11195 binding sites were significantly increased in all tissues of spf mice compared with control animals. In view of the localization of PTBR on the outer mitochondrial membrane, changes in PTBR in spf mouse tissues may modulate the altered mitochondrial function and oxidative metabolism, in brain and peripheral tissues, in congenital OTC deficiency. The positron emission tomography ligand 11C-PK 11195 could find an application in the assessment of end organ dysfunction in this disorder.

  6. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas


    for the population PK/PD data analysis. A systematic population PK/PD model-building framework using stochastic differential equations was applied to the data to identify nonlinear dynamic dependencies and to deconvolve the functional feedback interactions of the HPG axis. Results In our final PK/PD model of the HPG......Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  7. Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

    Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling


    Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from

  8. Genetic diversity, haplotypes and allele groups of Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from Peninsular Malaysia.

    Fong, Mun-Yik; Lau, Yee-Ling; Chang, Phooi-Yee; Anthony, Claudia Nisha


    The monkey malaria parasite Plasmodium knowlesi is now recognized as the fifth species of Plasmodium that can cause human malaria. Like the region II of the Duffy binding protein of P. vivax (PvDBPII), the region II of the P. knowlesi Duffy binding protein (PkDBPαII) plays an essential role in the parasite's invasion into the host's erythrocyte. Numerous polymorphism studies have been carried out on PvDBPII, but none has been reported on PkDBPαII. In this study, the genetic diversity, haplotyes and allele groups of PkDBPαII of P. knowlesi clinical isolates from Peninsular Malaysia were investigated. Blood samples from 20 knowlesi malaria patients and 2 wild monkeys (Macaca fascicularis) were used. These samples were collected between 2010 and 2012. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and haplotypes of PkDBPαII were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Fifty-three PkDBPαII sequences from human infections and 6 from monkeys were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence showed 52 synonymous and 76 nonsynonymous mutations. Analysis on the rate of these mutations indicated that PkDBPαII was under purifying (negative) selection. At the amino acid level, 36 different PkDBPαII haplotypes were identified. Twelve of the 20 human and 1 monkey blood samples had mixed haplotype infections. These haplotypes were clustered into 2 distinct allele groups. The majority of the haplotypes clustered into the large dominant group. Our present study is the first to report the genetic diversity and natural selection of PkDBPαII. Hence, the haplotypes described in this report can be considered as novel. Although a high level of genetic diversity was observed, the PkDBPαII appeared to be under purifying selection. The distribution of the haplotypes was skewed, with one dominant major and one minor

  9. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK.

    Schneider, Joachim; Bitterlich, Norman; Schulze, Guntram


    The aim of this study was to improve diagnostic efficiency in the detection of gastro-intestinal cancers by using fuzzy logic modeling in combination with a tumor marker panel (CEA, CA72-4, CA19-9) including Tumor M2-PK. In this prospective study histologically confirmed colorectal (n=247), esophageal (n=86) and gastric cancer (n=122) patients were investigated and compared to control (n=53) persons without any malignant diseases. Tumor M2-PK was measured in plasma with an ELISA (ScheBoBiotech, Germany); all other markers were measured in sera (Roche, Germany). At 95% specificity, tumor detection was possible by the best single marker in colorectal cancer patients in 48% (Tumor M2-PK), in gastric cancers in 61% (CA72-4) and in esophageal cancers in 56% (Tumor M2-PK). A fuzzy logic rule-based system employing a tumor marker panel increased sensitivity significantly in colorectal cancers (pTumor M2-PK and CEA), in gastric cancers (pTumor M2-PK and CA 72-4) and in esophageal cancers (pTumor M2-PK and CA72-4). Adding a third marker further improved the sensitivity only marginally. Fuzzy logic analysis has proven to be more powerful than measurement of single markers alone or combinations using multiple logistic regression analysis of the markers. Therefore, with the fuzzy logic method and a tumor marker panel (including Tumor M2-PK), a new diagnostic tool for the detection of gastro-intestinal cancers is available.

  10. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M


    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  11. Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic/pharmacodynamic (PK/PD) simulation

    O. Asuphon; P. Montakantikul; J. Houngsaitong; Kiratisin, P.; P. Sonthisombat


    Objective: The purpose of the study was to determine the optimal dosing regimen of intravenous fosfomycin for the treatment of Pseudomonas aeruginosa (PA) based on PK/PD targets. Method: A total of 120 PA isolates were recovered from various clinical specimens at university hospital in Thailand. Minimum Inhibitory Concentrations (MICs) of all the isolates were determined by the E-test method. PK parameters were obtained from a published study. Monte Carlo simulation was performed to calcul...

  12. De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology.

    Nijkamp, Jurgen F; van den Broek, Marcel; Datema, Erwin; de Kok, Stefan; Bosman, Lizanne; Luttik, Marijke A; Daran-Lapujade, Pascale; Vongsangnak, Wanwipa; Nielsen, Jens; Heijne, Wilbert H M; Klaassen, Paul; Paddon, Chris J; Platt, Darren; Kötter, Peter; van Ham, Roeland C; Reinders, Marcel J T; Pronk, Jack T; de Ridder, Dick; Daran, Jean-Marc


    Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.

  13. The origin of multiply sigmoid curves of pH-dependence. The partitioning of groups among titration pK values.

    Dixon, H B; Clarke, S D; Smith, G A; Carne, T K


    An acid, HnA, with n ionizing groups is known to have the same titration curve as an equimolar mixture of n hypothetical monobasic acids, whose dissociation constants are known as the 'titration constants' of the real acid. We show that the pH-dependence of any property of HnA is also represented by the sum of one-site titration curves, characterized by these same titration constants. Since one such property is the degree of dissociation of one of the dissociating groups, a fraction of each group shows each of the various titration pK values, so that the group partitions among them. The n groups therefore share the same n titration pK values but differ in the fractions belonging to each. The one H+ ion per molecule that titrates with each pK is thus made up of the fractions, one from each group, that share this pK value. A group may possess a single pK value, in that it contributes virtually all of this pK and almost nothing to the others, only if either (1) in titrates in a different pH range from the other groups or (2) its affinity for H+ is unaffected by their ionization state.

  14. Analysis the causes of suspicious results for BECKMAN PK 7300 automatic blood inspection device%BECKM AN PK7300全自动血型检测系统可疑结果的原因分析

    刘淼; 王霞; 潘彤


    目的:探讨BECKMAN PK7300全自动血型检测系统在血站实验室用于血型筛查时出现结果可疑的原因以及应用中的注意事项。方法选取天津市血液中心2015年5月至2015年8月ABO及Rh血型经微板法鉴定后的无偿献血者的标本14417例,再由PK7300进行检测,统计分析ABO及Rh血型结果判读的正确率、错误率以及对可疑结果的原因进行分析。结果ABO血型结果一次性判读正确率为99.01%,失败率0.99%(其中正反定型不符0.48%),无错误判读;Rh(D)血型正确判读率100%。结论 BECKMAN PK7300全自动血型检测系统结果准确可靠,实现了血型检测的自动化、标准化,减少人为因素对实验的影响,反应图像可长期保存,保证结果的可溯性,节约成本,适用于血站实验室血型批量化检测需要。%Objective To investigate the causes of suspicious results for BECKMAN PK 7300 automatic blood inspection device on blood typing in blood station and the application notes .Methods A total of 11417 samples from unpaid blood donors were re‐cruited from Tianjin Blood Center between May 2015 and August 2015 .Microplate assay was applied in ABO and Rh(D)blood typ‐ing .All the samples were tested by BECKMAN PK7300 automatic blood inspection device .The accuracy and error rates were calcu‐lated for ABO and Rh(D)blood group and causes of suspicious results were analyzed .Results The accuracy and failure rate of ABO blood group were 99 .01% and 0 .99% (of which the inconsistent rate of positive and reverse ABO blood typing was 0 .48% )and there was no false reading .Its accuracy was 100% in Rh(D)blood grouping .Conclusion The results of BECKMAN PK7300 auto‐matic blood inspection device were accurate and reliable .The whole system achieved automation and standardization and reduced the artificial factors for experiments ,which images could be saved for a long period of time ,saving the cost .The

  15. Patch recordings from the electrocytes of Electrophorus electricus. Na currents and PNa/PK variability


    Sodium currents were recorded in cell-attached and inside-out patches from the innervated membrane of Electrophorus electrocytes. Electrocytes from Sachs and main electric organs were prepared as described by Pasquale et al. (1986. J. Membr. Biol. 93:195.). Maximal currents in the Sachs organ, measured with 1-2 microns diameter patch pipettes and at room temperature, were in the range of 20 to 300 pA (27 patches) and were obtained near +10 mV. This range of current corresponds to approximately 70 to 1,300 channels in a patch. Maximal current in main organ cells also occurred near +10 mV and were in the range of 100 to 400 pA. Delayed K current was observed in a few patches. The inactivation phase of the currents during maintained depolarizations appears to be a single-exponential relaxation. The time constant decreases from 1 ms near -55 mV to a minimum of 0.3 ms near 0 mV, and then gradually increases with stronger depolarization. The mean currents are half inactivated near -90 mV with an apparent voltage dependence of e-fold per 6 mV. No apparent differences were observed in the decay time course or steady-state inactivation of the currents in the same patch before and after excision. From ensemble fluctuation analysis the peak open probability was found to be approximately 0.5 at +25 mV and increased only gradually with larger depolarizations. The single channel conductances were approximately 20 pS with 200 mM Na outside and 200 mM K inside, and 40 pS in 400 mM solutions. Reversal potentials in the 200 Na parallel 200 K solutions ranged from +51 to +94 mV in multichannel patches, corresponding to selectivity ratios PNa/PK from 8 to 43. Large differences in reversal potentials were seen even among patches from the same cell. Several controls rule out obvious sources of error in the reversal potential measurements. It is concluded that there is heterogeneity in the selectivity properties of the Na channels. PMID:1650809

  16. Patch recordings from the electrocytes of Electrophorus electricus. Na currents and PNa/PK variability.

    Shenkel, S; Sigworth, F J


    Sodium currents were recorded in cell-attached and inside-out patches from the innervated membrane of Electrophorus electrocytes. Electrocytes from Sachs and main electric organs were prepared as described by Pasquale et al. (1986. J. Membr. Biol. 93:195.). Maximal currents in the Sachs organ, measured with 1-2 microns diameter patch pipettes and at room temperature, were in the range of 20 to 300 pA (27 patches) and were obtained near +10 mV. This range of current corresponds to approximately 70 to 1,300 channels in a patch. Maximal current in main organ cells also occurred near +10 mV and were in the range of 100 to 400 pA. Delayed K current was observed in a few patches. The inactivation phase of the currents during maintained depolarizations appears to be a single-exponential relaxation. The time constant decreases from 1 ms near -55 mV to a minimum of 0.3 ms near 0 mV, and then gradually increases with stronger depolarization. The mean currents are half inactivated near -90 mV with an apparent voltage dependence of e-fold per 6 mV. No apparent differences were observed in the decay time course or steady-state inactivation of the currents in the same patch before and after excision. From ensemble fluctuation analysis the peak open probability was found to be approximately 0.5 at +25 mV and increased only gradually with larger depolarizations. The single channel conductances were approximately 20 pS with 200 mM Na outside and 200 mM K inside, and 40 pS in 400 mM solutions. Reversal potentials in the 200 Na parallel 200 K solutions ranged from +51 to +94 mV in multichannel patches, corresponding to selectivity ratios PNa/PK from 8 to 43. Large differences in reversal potentials were seen even among patches from the same cell. Several controls rule out obvious sources of error in the reversal potential measurements. It is concluded that there is heterogeneity in the selectivity properties of the Na channels.

  17. Mental health in Japanese members of the United Nations peacekeeping contingent in the Golan Heights: effects of deployment and the Middle East situation.

    Sawamura, Takehito; Shimizu, Kunio; Masaki, Yoshinori; Kobayashi, Nobuhisa; Sugawara, Mariko; Tsunoda, Tomoya; Kikuchi, Akihito; Yamamoto, Taisuke; Toda, Hiroyuki; Nomura, Soichiro; Takahashi, Yoshitomo; Oryu, Takashi; Ogasawara, Tsuneyuki; Ogata, Katsuhiko


    This study evaluates the mental health of Japan Self-Defense Force (JSDF) members of the peacekeeping contingent in the Golan Heights before and since the Second Gulf War between 1998 and 2003. Before the war, the General Health Questionnaire 30 (GHQ30) scores during and after duty tended to be lower than those before duty; all scores were lower than those of adult Japanese men in general. After the war, GHQ30 scores did not significantly change between before, during, and after duty. Manifest Anxiety Scale (MAS) scores were not significantly different between groups. Stressors identified included problems with foreign language and familial matters at home. Post war stressors included work content and relationships with collaborating foreign army units. These findings suggest that the mental health of contingent members remained stable, with some variation in mental health conditions influenced by the situation in the Middle East. This study suggests that the stable mental condition of JSDF personnel during their deployment in the absence of combat, and that this could be enhanced by education about mental health issues and by providing counseling support to their families.

  18. A Review of Supplementary Medical Aspects of Post-Cold War UN Peacekeeping Operations: Trends, Lessons Learned, Courses of Action, and Recommendations.

    Johnson, Ralph J


    Post-Cold War United Nations Peace Keeping Operations (UN PKOs) have been increasingly involved in dangerous areas with ill-defined boundaries, harsh and remote geographies, simmering internecine armed conflict, and disregard on the part of some local parties for peacekeepers' security and role. In the interest of force protection and optimizing operations, a key component of UN PKOs is healthcare and medical treatment. The expectation is that UN PKO medical support will adjust to the general intent and structure of UN PKOs. To do so requires effective policies and planning informed by a review of all medical aspects of UN PKO operations, including those considered supplementary, that is, less crucial but contributing nonetheless. Medical aspects considered paramount and key to UN PKOs have received relatively thorough treatment elsewhere. The intent of this article is to report on ancillary and supplemental medical aspects practical to post-Cold War UN PKO operations assembled through an iterative inquiry of open-source articles. Recommendations are made about possible courses of action in terms of addressing trends found in such medical aspects of PKOs and relevance of US/NATO/European Union models and research.

  19. A qualitative content analysis of global health engagements in Peacekeeping and Stability Operations Institute's stability operations lessons learned and information management system.

    Nang, Roberto N; Monahan, Felicia; Diehl, Glendon B; French, Daniel


    Many institutions collect reports in databases to make important lessons-learned available to their members. The Uniformed Services University of the Health Sciences collaborated with the Peacekeeping and Stability Operations Institute to conduct a descriptive and qualitative analysis of global health engagements (GHEs) contained in the Stability Operations Lessons Learned and Information Management System (SOLLIMS). This study used a summative qualitative content analysis approach involving six steps: (1) a comprehensive search; (2) two-stage reading and screening process to identify first-hand, health-related records; (3) qualitative and quantitative data analysis using MAXQDA, a software program; (4) a word cloud to illustrate word frequencies and interrelationships; (5) coding of individual themes and validation of the coding scheme; and (6) identification of relationships in the data and overarching lessons-learned. The individual codes with the most number of text segments coded included: planning, personnel, interorganizational coordination, communication/information sharing, and resources/supplies. When compared to the Department of Defense's (DoD's) evolving GHE principles and capabilities, the SOLLIMS coding scheme appeared to align well with the list of GHE capabilities developed by the Department of Defense Global Health Working Group. The results of this study will inform practitioners of global health and encourage additional qualitative analysis of other lessons-learned databases.

  20. 维和警队思想政治工作地位与作用探析%A Tentative Study on the Role of Ideological and Political Work for Peacekeeping Police Force



    The ideological and political work is the lifeblood for peacekeeping police force, is fundamental to maintain the political life of the force. The important role that the ideological and political work plays for peacekeeping police force are as follows: it is the fundamental guarantee of a firm political direction for the peacekeeping police force; it is an important factor to enhance the combat effectiveness; it is an intrinsic moti- vation to solve various problems and to accomplish various tasks; it is the foundation to give full play to the temporary party organizations in combat; it is the inevitable requirement to fully develop the leadership and de- cision-making ability of the "squad leader".%内思想政治工作是维和警队的生命线,是维系维和警队政治生命的根本因素。思想政治工作对维和警队的地位和作用,体现在:思想政治工作是维和警队坚定政治方向的根本保证,是提升战斗力的重要因素;是解决各种问题、完成各项任务的内在动力;是充分发挥临时党组织战斗堡垒作用的基础;是全面培养“班长”的组织领导和决策能力的必然要求。

  1. Changes in the response of MCF-7 cells to ionizing radiation after the combination of ATM and DNA-PK inhibition.

    Ćmielová, Jana; Havelek, Radim; Vávrová, Jiřina; Řezáčová, Martina


    The aim of the present study is to evaluate the role of ATM (KU55933) and DNA-PK (NU7441) inhibitors in the repair of double-strand breaks and downstream signaling of DNA damage introduced by ionizing radiation. The irradiation of MCF-7 cells alone increased the proportion of cells in the G1 phase in comparison with mock-treated cells. After ATM inhibitor pretreatment, the cells were more accumulated in the G2 phase, whereas DNA-PK inhibitor application increased the percentage of cells in the G1 phase. ATM and DNA-PK inhibitor application alone increased the sensitivity of MCF-7 cells to ionizing radiation; however, combining both inhibitors together resulted in a further enhancement of cell death. Unexpectedly, combining both inhibitors decreased the percentage of senescent cells and increased G2 cell cycle arrest 3 days after treatment. After irradiation, the p21 protein was increased and Chk1 and Chk2 were activated. These proteins were not increased in cells pretreated with the ATM inhibitor prior to ionizing radiation exposure, albeit DNA-PK inhibitor application did not affect the amount of proteins detected. Formation of γH2AX was found to be ATM and DNA-PK dependent, application of the ATM inhibitor suppressed incidence of γH2AX, whereas DNA-PK caused persistence of γH2AX. Our results suggest that the further investigation of the ATM inhibitor in combination with the DNA-PK inhibitor as sensitizers preventing cell senescence and promoting cell death in breast carcinoma MCF-7 cells is warranted.

  2. Lesions inflammatory activity quantification in multiple sclerosis using [{sup 11}C]-(R)-PK11195 PET brain images; Quantificacao da atividade inflamatoria em lesoes na esclerose multipla usando imagens PET cerebrais com [{sup 11}C]-(R)-PK11195

    Schuck, Phelipi N.; Narciso, Lucas D.L.; Dartora, Caroline M.; Silva, Ana M. Marques da, E-mail: [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil). Nucleo de Pesquisa em Imagens Medicas


    The criteria for multiple sclerosis (MS) diagnosis include the presence of lesions in brain regions called black holes (BH), characterized by low signal on magnetic resonance imaging T1-weighted. Studies suggest that lesions in MS, if there is an inflammatory process, can be detected in PET imaging with [{sup 11}C]- (R)-PK11195. The aim of this study is to investigate the uptake of [{sup 11}C]-(R)-PK11195 in BH in PET images, searching for inflammation activity in lesions and neighborhoods. Semiquantitative methods of SUV and uptake normalization were applied to PET images, in different time intervals, acquired from 8 MS patients and 5 healthy controls. Higher uptake was identified in BH and its edges, when compared with health controls white matter, when the SUV method is applied (p < 0,01, 40 to 60 min). When uptake normalization method is applied, smaller uptake in black holes and its your edges is observed, when compared with white matter apparently healthy (p < 0,01, 0 to 60 min). (author)

  3. Increasing the reach of the PK-3R continuous Miner; Desarrollo y Ensayo de un Sistema para aumentar el alcance de la Pina de Rozado en un Minador PK-3R



    The objective of this project is the development and implementation of a system designed to increase the reach of the cutting head of a PK-3R continuous miner working in our coal operations. Justification for the project stems from our method of coal extraction, whereby once the sub-level gallery has been advanced to it`s limit, extraction of the coal is undertaken by retreat mining, using a room and pillar method. In this method the roof is blasted to allow greater coal recovery. Due to it`s short length, the original position of the cutting arm of the PK-3R miner did not permit the total recovery of the blasted coal piled up on the gallery floor. Therefore an increase in the reach of the arm is very beneficial, facilitating the recovery of coal that previously could not be recovered. The system also permits excavation for support methods to be undertaken more rapidly, and a better adaptation of the miner to the irregularities of the wall, thus permitting it to move up or down more quickly, reducing the movements required. The system has not caused significant breakdowns, and the availability of the miner is good. In addition, the substitution of the turret in the case of a breakdown is an easy task, as during the design stage, the ease of mounting and dismounting the turret was considered as a fundamental parameter. (Author)

  4. Cryo-EM Imaging of DNA-PK DNA Damage Repair Complexes

    Phoebe L. Stewart


    Exposure to low levels of ionizing radiation causes DNA double-strand breaks (DSBs) that must be repaired for cell survival. Higher eukaryotes respond to DSBs by arresting the cell cycle, presumably to repair the DNA lesions before cell division. In mammalian cells, the nonhomologous end-joining DSB repair pathway is mediated by the 470 kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs) together with the DNA-binding factors Ku70 and Ku80. Mouse knock-out models of these three proteins are all exquisitely sensitive to low doses of ionizing radiation. In the presence of DNA ends, Ku binds to the DNA and then recruits DNA-PKcs. After formation of the complex, the kinase activity associated with DNA-PKcs becomes activated. This kinase activity has been shown to be essential for repairing DNA DSBs in vivo since expression of a kinase-dead form of DNA-PKcs in a mammalian cell line that lacks DNA-PKcs fails to complement the radiosensitive phenotype. The immense size of DNA-PKcs suggests that it may also serve as a docking site for other DNA repair proteins. Since the assembly of the DNA-PK complex onto DNA is a prerequisite for DSB repair, it is critical to obtain structural information on the complex. Cryo-electron microscopy (cryo-EM) and single particle reconstruction methods provide a powerful way to image large macromolecular assemblies at near atomic (10-15 ?) resolution. We have already used cryo-EM methods to examine the structure of the isolated DNA-PKcs protein. This structure reveals numerous cavities throughout the protein that may allow passage of single or double-stranded DNA. Pseudo two-fold symmetry was found for the monomeric protein, suggesting that DNA-PKcs may interact with two DNA ends or two Ku heterodimers simultaneously. Here we propose to study the structure of the cross-linked DNA-PKcs/Ku/DNA complex. Difference imaging with our published DNA-PKcs structure will enable us to elucidate the architecture of the complex. A second

  5. A Research on the Psychological Stress of China Peacekeeping Police and Its Influencing Factors Analysis%中国维和警察心理压力及其影响因素研究



    To understand the China peacekeeping police' s psychological stress status and its influencing factors on their bodies and minds, the questionnaire edited on the basis of the Psychological Stress Questionnaire of Police ( edited by Yu Junjie) has been adopted to evaluate the China peacekeeping police' s psychology. The findings show that the psychological stress is normal as whole, and the two major causes are the mission stress and the potential dangers stress. The peacekeeping policemen' s stress is more serious than that from the policewomen. The stress of the married is more serious than unmarried. The newly selected peacekeeping police, who haven' t received any training yet, have the most serious psychological stress.%为了了解中国维和警察心理压力现状及其对维和警察身心健康的影响,在于俊杰主编的警察心理压力问卷的基础上,结合中国维和警察的特点编制了维和警察心理压力调查问卷,并对其进行了心理测评和影响因素分析。结果显示中国维和警察心理压力总体上处于中等水平,其中最重要的两种压力是任务区工作压力和潜在危险压力,男性维和警察压力高于女性维和警察,已婚维和警察压力高于未婚维和警察,刚刚从我国警察队伍中选拔出来且尚未接受培训的维和警察的心理压力高于其他维和警察。

  6. Population PK/PD model of homocysteine concentrations after high-dose methotrexate treatment in patients with acute lymphoblastic leukemia.

    Hauke Rühs

    Full Text Available Elevated homocysteine concentrations have been associated with methotrexate-induced neurotoxicity. Based on methotrexate and homocysteine plasma concentrations of 494 children with acute lymphoblastic leukemia treated with high-dose methotrexate in the TOTAL XV study, a pharmacokinetic/pharmacodynamic (PK/PD model was built with NONMEM. Several compartment and indirect response models were investigated. The pharmacokinetic disposition of methotrexate was best described by a two-compartment model. Homocysteine concentrations were included by an indirect response model where methotrexate inhibition of the homocysteine elimination rate was described by an E(max model. The homocysteine baseline level was found to be age-dependent. Simulations revealed that folinate rescue therapy does not affect peak concentrations of homocysteine but leads to a modestly reduced homocysteine exposure. In conclusion, our PK/PD model describes the increase of methotrexate-induced HCY concentrations with satisfactory precision and can be applied to assess the effect of folinate regimens on the HCY concentration-time course.

  7. Quantitative autoradiographic determination of binding sites for a peripheral benzodiazepine ligand ((/sup 3/H)PK 11195) in human iris

    Valtier, D.; Malgouris, C.; Uzan, A.


    Specific binding sites of peripheral-type benzodiazepines were investigated in human iris/ciliary body (8 eyes). Examination of color-coded prints and densitometric quantification of autoradiograms were performed on slides (20 labelled with (/sup 3/H)PK 11195 (1 nM) at 25 deg C. Nonspecific binding was determined with PK 11211 (5 or Ro 5-4864 (5 Binding sites were present on all the slides, with equivalent density in the 3 regions of the preparation (ciliary body, iris and pupil margin). The numbers of binding sites in ciliary body, iris, and pupil margin, respectively were: 42.7 +- 0.2, 30.1 +- 0.5 and 37.4 +- 0.4 femtomol/mg protein. Labelling on the pupil margin seemed to coincide with the iris sphincter muscle. The presence of peripheral benzodiazepine binding sites in iris muscular tissue, and particularly in the pupil margin, suggests that the iris preparation may be a valuable tool to detect putative physiological effects of peripheral benzodiazepines on muscular motility.

  8. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

    Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola


    The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; pholes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression.

  9. Tissue-specific alterations of binding sites for peripheral-type benzodiazepine receptor ligand [3H]PK11195 in rats following portacaval anastomosis.

    Rao, V L; Audet, R; Therrien, G; Butterworth, R F


    Kinetics of binding of [3H]PK11195, an antagonist ligand with high selectivity for the peripheral-type (mitochondrial) benzodiazepine receptor (PTBR), was studied in homogenates of cerebral cortex, kidney, heart, and testis of portacaval shunted rats and sham-operated controls. Portacaval anastomosis resulted in a significant two- to threefold increase in the number of [3H]PK11195 binding sites in cerebral cortex and kidney. A reduction in the number of [3H]PK11195 binding sites was observed in testis preparations, while the number of binding sites in the heart remained unaltered. These differences in the response of PTBRs to portacaval anastomosis, in different organs suggest that the physiological function of these receptors and the factors regulating them are modulated by distinct mechanisms. The finding of increased densities of [3H]PK11195 binding sites in brain and kidney following portacaval anastomosis parallels the cellular hypertrophy in these tissues and, together with previous observations of similar increases of these binding sites in brain and kidney in congenital hyperammonemia, suggest a pathophysiologic role for ammonia in these changes. In contrast, the significant loss of [3H]PK11195 binding sites in testicular preparations following portacaval anastomosis together with the known effects of steroid hormones on these sites suggests a role for PTBRs in the pathogenesis of testicular atrophy in chronic liver disease.

  10. PkMADS1 is a novel MADS box gene regulating adventitious shoot induction and vegetative shoot development in Paulownia kawakamii.

    Prakash, A Pavan; Kumar, Prakash P


    Direct regeneration of shoot buds in vitro is an important technique in plant genetic manipulation. We describe the isolation and functional characterization of a novel MADS box cDNA (PkMADS1) from Paulownia kawakamii leaf explants undergoing adventitious shoot regeneration. mRNA gel blot analysis confirmed the expression of PkMADS1 in the shoot-forming cultures, but no signal was observed in the callus-forming cultures. PkMADS1 transcripts were also detected in shoot apices, but not in root apices, initial leaf explants or the flower. In situ hybridization revealed that its expression was restricted to developing shoot primordia in the excised leaf cultures, suggesting a role for this gene in adventitious shoot formation. Transgenic Paulownia plants over-expressing the PkMADS1 gene showed some changes in phenotype, such as axillary shoot formation. In the antisense transformants, shoots were stunted and had altered phyllotaxy, and, in some lines, the shoot apical meristem appeared to have been used up early during shoot development. Leaf explants from the antisense transgenic plants showed a tenfold decrease in shoot regeneration compared with explants from sense transformants or wild-type. Our results show that PkMADS1 is a regulator of shoot morphogenesis.

  11. Protective effect of a protein kinase inhibitor on cellular injury induced by cephaloridine in the porcine kidney cell line LLC-PK(1).

    Kawai, Yoshiko; Kohda, Yuka; Kodawara, Takaaki; Gemba, Munekazu


    We investigated the effects of a protein kinase C inhibitor and a tyrosine kinase inhibitor on the cellular injury induced by cephaloridine in an established renal epithelial cell line, LLC-PK(1). Cephaloridine increased the leakage of lactate dehydrogenase (LDH) from LLC-PK(1) cells into the medium and also caused an increase in the level of lipid peroxide (index of oxidative stress) in the cells. Treatment of the cells with a hydroxyl radical scavenger, dimethylthiourea (DMTU), inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. A protein kinase C inhibitor, H-7, and tyrosine kinase inhibitors, genistein and lavendustinA, inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. These results suggest that a signaling pathway which involves protein kinase C and tyrosine kinase plays a role in the generation of reactive oxygen species in LLC-PK(1) cells damaged by cephaloridine.

  12. Biodistribution and dosimetry of [{sup 123}I]iodo-Pk 11195: a potential agent for SPET imaging of the peripheral benzodiazepine receptor

    Versijpt, J. [Groningen Univ. Hospital (Netherlands). Dept. of Biological Psychiatry; Div. of Nuclear Medicine, Ghent Univ. Hospital (Belgium); Dumont, F.; Vos, F. de; Slegers, G. [Dept. of Radiopharmacy, Ghent Univ. (Belgium); Thierens, H. [Dept. of Biomedical Physics and Radiation Protection, Ghent Univ. (Belgium); Jansen, H.; Dierckx, R.A. [Div. of Nuclear Medicine, Ghent Univ. Hospital (Belgium); Santens, P. [Dept. of Neurology, Ghent Univ. Hospital (Belgium); Korf, J. [Groningen Univ. Hospital (Netherlands). Dept. of Biological Psychiatry


    The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [{sup 123}I]iodo-PK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [{sup 123}I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [{sup 123}I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 {mu}Gy/MBq. All other organs investigated received doses of less than 50 {mu}Gy/MBq. The effective dose was 40.3 {mu}Sv/MBq. In conclusion, [{sup 123}I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [{sup 123}I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation. (orig.)

  13. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with ( sup 3 H)PK 11195 binding autoradiography

    Altar, C.A.; Baudry, M. (Genentech, Inc., South San Francisco, CA (USA))


    Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of (3H)PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in (3H)PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in (3H)PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of (3H)PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in (3H)PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of (3H)PK 11195 is a valuable tool to quantify the extent of neuronal degeneration.

  14. De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

    Nijkamp Jurgen F


    Full Text Available Abstract Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV, insertions/deletions (indels and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.

  15. A phenylalanine ammonia-lyase ortholog (PkPAL1) from Picrorhiza kurrooa Royle ex. Benth: molecular cloning, promoter analysis and response to biotic and abiotic elicitors.

    Bhat, Wajid Waheed; Razdan, Sumeer; Rana, Satiander; Dhar, Niha; Wani, Tariq Ahmad; Qazi, Parvaiz; Vishwakarma, Ram; Lattoo, Surrinder K


    Picrorhiza kurrooa Royle ex Benth. is a highly reputed medicinal herb utilised in the preparation of a number of herbal drug formulations, principally due to the presence of novel monoterpene iridoid glycosides kenned as picrosides. Phenylalanine ammonia-lyase catalyses an important rate-limiting step in phenylpropanoid pathway and supplies precursors like cinnamic acid, vanillic acid, ferulic acid, etc., to a variety of secondary metabolites including picrosides. The imperilled status of P. kurrooa coupled with lack of information regarding biogenesis of picrosides necessitates deciphering the biosynthetic pathway for picrosides. In the present study, a PAL gene, designated PkPAL1 was isolated from P. kurrooa. The cDNA is 2312 bp in length, consisting of an ORF of 2142 bp encoding for a 713 amino acid protein having a predicted molecular weight of 77.66 kDa and an isoelectric point of pH 6.82. qRT-PCR analysis of various tissues of P. kurrooa showed that PkPAL1 transcript levels were highest in the leaves, consistent with picroside accumulation pattern. Using Genome walking, a 718 bp promoter region was also isolated resulting in identification of distinct cis-regulatory elements including TGA-element, TGACG-motif, CGTCA-motif, etc. qRT-PCR indicated up-regulation of PkPAL1 by methyl jasmonate, salicylic acid, 2,4-dicholorophenoxy acetic acid and UV-B elicitations that corroborated positively with the identified cis-elements within the promoter region. Moreover, altitude was found to have a positive effect on the PkPAL1 transcript levels, driving the expression of PkPAL1 abundantly. Based on docking analysis, we identified eight residues as potentially essential for substrate binding in PkPAL1.

  16. {sup 18}F-GE-180: a novel TSPO radiotracer compared to {sup 11}C-R-PK11195 in a preclinical model of stroke

    Boutin, Herve; Gerhard, Alexander [University of Manchester, Faculty of Medical and Human Sciences, Manchester (United Kingdom); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Murray, Katie [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Pradillo, Jesus [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Universidad Complutense/Politecnica de Madrid, Madrid (Spain); Maroy, Renaud [SHFJ - CEA Orsay, Orsay (France); Smigova, Alison [University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Jones, Paul A.; Trigg, William [GE Healthcare Ltd., Amersham (United Kingdom)


    Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer {sup 11}C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer {sup 18}F-GE-180 in a rat model of stroke. Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with {sup 11}C-R-PK11195 and {sup 18}F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of {sup 18}F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP). {sup 18}F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of {sup 11}C-R-PK11195 uptake (1.5 ± 0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BP{sub ND} = 3.5 ± 0.4 and 2.4 ± 0.5 for {sup 18}F-GE-180 and {sup 11}C-R-PK11195, respectively, with R{sub 1} = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of {sup 18}F-GE-180 significantly displaced {sup 18}F-GE-180 (69 ± 5 % and 63 ± 4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry. The in vivo binding characteristics of {sup 18}F-GE-180 demonstrate a better signal to noise ratio than {sup 11}C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in

  17. The Effect of Psychological Intervention on Maladjustment of African peacekeepers and Related Factors%心理干预对非洲维和官兵适应不良的疗效

    王艳玲; 张理义; 郭健; 林海; 姚高峰; 陈春霞


    Objective To explore the effect of psychological interventions on maladjustment in Africa , Nigeria, Ghana, Namibia peacekeepers ,and analyze its relationship with social support and related factors .Methods The maladjustment and social support of Ni-gerian,Ghanaian,Namibian peacekeeping soldiers were investigated by the Military Mental Maladjustment Scale and the Social Support Scale,while mental interventions were undertaken on them .Results After mental intervention,Nigerian peacekeepers'total scores of Maladjustment Scale and its factor scores (except environmental adjustment ) were decreased significantly (t=4.62,5.38,5.01,6.31;P0.05).Age,recruited period,marital status selected into the regression function of African peacekeeper 'maladjust-ment(t=-2.177,3.091,2.727;P<0.05).Conclusion The Nigerian,Ghanaian and Namibian peacekeepers have high incidence of maladjustment ,and good social supports and effective interventions ,which can significantly reduce maladjustment occurs .%目的:探讨心理干预对非洲三国尼日利亚、加纳、纳米比亚维和官兵适应不良的疗效并分析其与社会支持及相关因素的关系。方法采用心理干预前、后观测军人适应不良量表和社会支持量表,并对以上人员进行相应的心理干预,对心理干预前、后适应不良各因子进行分析,并分析其与社会支持及相关因素的关系。结果心理干预后,尼日利亚维和官兵除环境适应因子分外,其适应不良总分及其它各因子分均显著降低(t=4.62,5.38,5.01,6.31;P<0.05);加纳维和官兵除行为问题和人际关系不良因子外,其适应不良总分及其它各因子分均显著降低(t=3.82,4.96,5.78;P<0.05)。尼日利亚、加纳、纳米比亚三国维和官兵的适应不良总分及各因子分均显著高于中国军人适应不良常模(t=3.87~7.86;P<0.05)。年龄、军龄、职别、教育

  18. Investigation on correlation between personality traits and mental health of officers and soldiers in Asian peacekeeping forces%亚洲维和官兵人格特征与心理健康状况的关系研究

    张理义; 唐开宏; 郭健; 林海; 陈春霞; 姚高峰


    目的 探讨亚洲三国维和官兵人格特征与心理健康状况的关系,为我国维和官兵的心理干预提供参考.方法 随机抽取2007年印度、巴基斯坦和孟加拉国赴利比里亚维和官兵380名作为研究对象,于到达维和任务区第7天和第120天采用《中国军人心理健康量表》(CMMHS)和《艾森克人格问卷》(EPQ)对其进行测评.结果 除焦虑因子分外,第120天时维和官兵CMMHS量表的总分及其他各因子分均显著低于第7天(P<0.05或0.01).单因素直线相关分析显示,维和官兵CMMHS总分及精神病性、神经衰弱因子分前后两次的差值与神经质分量表得分呈正相关(P<0.05或0.01),抑郁因子分前后两次的差值与内外向分量表呈负相关(P<0.01).多元逐步回归分析显示,内外向、神经质分别进入以抑郁、精神病性、神经衰弱及CMMHS总分差值为因变量的回归方程(P<0.05或0.01).结论 亚洲维和官兵的人格特征与心理健康状况关系密切,人格特征能明显影响个体的心理健康状况.%Objective To investigate the correlation between personality traits and mental health of officers and soldiers dispatched from three countries (India, Pakistan and Bangladesh) in Asian peacekeeping forces to provide reference for psychological interventions for Chinese peacekeepers. Methods A total of 380 peacekeepers dispatched by the three countries mentioned above to Liberia were selected by random sampling and were tested by Chinese Military Mental Health Scale (CMMHS) and Eysenck Personality Questionnaire (EPQ) on the 7th day and the 120th day after their arrival at the peacekeeping mission area. ResultS The total and each factor score of CMMHS (except anxiety) on the 7th day test and the 120th day test were significantly different (the farmer > the latter, P<0.05 or 0.01). Univariate correlation analysis showed that the total CMMHS score and difference value in psychosis score and neurasthenia score

  19. PkANN - II. A non-linear matter power spectrum interpolator developed using artificial neural networks

    Agarwal, Shankar; Feldman, Hume A; Lahav, Ofer; Thomas, Shaun A


    In this paper we introduce PkANN, a freely available software package for interpolating the non-linear matter power spectrum, constructed using Artificial Neural Networks (ANNs). Previously, using Halofit to calculate matter power spectrum, we demonstrated that ANNs can make extremely quick and accurate predictions of the power spectrum. Now, using a suite of 6380 N-body simulations spanning 580 cosmologies, we train ANNs to predict the power spectrum over the cosmological parameter space spanning $3\\sigma$ confidence level (CL) around the concordance cosmology. When presented with a set of cosmological parameters ($\\Omega_{\\rm m} h^2, \\Omega_{\\rm b} h^2, n_s, w, \\sigma_8, \\sum m_\

  20. Comparison of the anti-inflammatory actions of flunixin and ketoprofen in horses applying PK/PD modelling.

    Landoni, M F; Lees, P


    A comparative study in horses of the pharmacokinetics (PK) and pharmacodynamics (PD) of 2 extensively used nonsteroidal anti-inflammatory drugs (NSAIDs), flunixin (FXN) and ketoprofen (KTP), was carried out applying PK/PD modelling. To evaluate the anti-inflammatory properties of these drugs a model of acute inflammation, comprising surgically implanted subcutaneous tissue cages stimulated by intracaveal injection of carrageenan, was used. FXN elimination half-life (T1/2 beta) in plasma was 3.37 +/- 1.09 h. However, in exudate a much longer T1/2 beta was obtained (15.99 +/- 3.80 h). Apparent volume of distribution (Vdarea) for FXN was 0.317 +/- 0.126 l/kg and body clearance (ClB) was 0.058 +/- 0.004 l/kg/h. KTP displayed enantioselective pharmacokinetics, the S(+) enantiomer being predominant in plasma, exudate and transudate. T1/2 beta values for R(-) and S(+)KTP were, respectively, 1.09 +/- 0.19 h and 1.51 +/- 0.45 h (plasma) and 19.73 +/- 2.72 h and 22.64 +/- 4.34 h (exudate), respectively. R(-)KTP was cleared more rapidly than the S(+) enantiomer. ClB values were 0.277 +/- 0.035 l/kg/h and 0.202 +/- 0.022 l/kg/h, respectively. FXN and KTP pharmacodynamics was evaluated by determining their inhibitory effects on serum thromboxane (Tx)B2, exudate prostaglandin (PG)E2, leukotriene (LT)B4 and beta-glucuronidase (beta-glu) and intradermal bradykinin-induced swelling. Both drugs produced marked inhibition of serum TxB2 synthesis for up to 24 h, with no significant differences between the drugs. FXN was a more potent inhibitor of exudate PGE2, the EC50 for FXN being lower (P < 0.01) than that for KTP (0.019 +/- 0.010 microgram/ml and 0.057 +/- 0.009 microgram/ml, respectively). Neither drug had any effect on exudate LTB4 concentration. Differences between the 2 drugs were observed for the inhibition of beta-glu, the Emax for KTP being higher (P < 0.01) than for FXN. However, no differences were observed in other PD parameters. Both FXN and KTP inhibited bradykinin

  1. Feline and canine coronaviruses are released from the basolateral side of polarized epithelial LLC-PK1 cells expressing the recombinant feline aminopeptidase-N cDNA

    Rossen, J W; Kouame, J; Goedheer, A J; Vennema, H; Rottier, P J


    In this study feline (FECV and FIPV) and canine (CCoV) coronavirus entry into and release from polarized porcine epithelial LLC-PK1 cells, stably expressing the recombinant feline aminopeptidase-N cDNA, were investigated. Virus entry appeared to occur preferentially through the apical membrane, simi

  2. The distribution of radioactivity in brains of rats given (N-methyl- sup 11 C)PK 11195 in vivo after induction of a cortical ischaemic lesion

    Cremer, J.E.; Hume, S.P.; Cullen, B.M.; Myers, R.; Manjil, L.G.; Turton, D.R.; Luthra, S.K.; Bateman, D.M.; Pike, V.W. (Hammersmith Hospital, London (United Kingdom). M.R.C. Cyclotron Unit)


    PK 11195 is a selective ligand for the peripheral-type benzodiazepine bindings site (PTBBS). There are few sites in normal brain but their number increases in association with tissue necrosis. The time-course of appearance of PTBBS around a focally induced ischaemic lesion in frontal cortex of rat brain was established by autoradiography using (N-methyl-{sup 3} H )PK 11195. Using this information and the same experimental model of ischaemia, the distribution of radioactivity after injection of carbon-11 labelled PK 11195 was studied. The purpose was to synthesize (N-methyl-{sup 11}C)PK 11195 and to test its suitability as a tracer for depicting the presence of PTBB in ischaemic lesions. The time-profiles of distribution of radioactivity in brain regions after intravenous injection of tracer and the ratio of radioactivity in lesioned compared with unlesioned cortex were determined. Data for the temporal (days after lesion induction) and for the regional retention of radioactivity were consistent with independent evidence (autoradiographic and immunohistochemical) for the occurence of increased numbers of PTBBS, predominantly in association with macrophages, in areas undergoing necrosis. (Author).

  3. Assessment of neuroinflammation and microglial activation in Alzheimer's disease with radiolabelled PK11195 and single photon emission computed tomography - A Pilot Study

    Versijpt, JJ; Dumont, F; Van Laere, KJ; Decoo, D; Santens, P; Audenaert, K; Achten, E; Slegers, G; Dierckx, RA; Korf, J


    Objectives: Inflammation contributes to degeneration in Alzheimer's disease (AD), not simply as a secondary phenomenon, but primarily as a significant source of pathology. [I-123]iodo-PK11195 is a single photon emission computed tomography (SPECT) ligand for the peripheral benzodiazepine receptor, t

  4. Search for K-p→π0π0π0Λ from threshold to pK-=750 MeV/c

    Borgh, M.; Prakhov, S.; Nefkens, B. M.; Allgower, C. E.; Bekrenev, V.; Briscoe, W. J.; Clajus, M.; Comfort, J. R.; Craig, K.; Grosnick, D.; Isenhower, D.; Knecht, N.; Koetke, D.; Koulbardis, A.; Kozlenko, N.; Kruglov, S.; Lolos, G.; Lopatin, I.; Manley, D. M.; Manweiler, R.; Marušić, A.; McDonald, S.; Olmsted, J.; Papandreou, Z.; Peaslee, D.; Phaisangittisakul, N.; Price, J. W.; Ramirez, A. F.; Sadler, M.; Shafi, A.; Spinka, H.; Stanislaus, T. D.; Starostin, A.; Staudenmaier, H. M.; Supek, I.; Tippens, W. B.


    The results of a search for K-p→π0π0π0Λ (where the 3π0’s are not from η-meson decay) are presented. The data were obtained with the Crystal Ball spectrometer at eight beam momenta from 514 to 750 MeV/c. For the six beam momenta below pK-=714 MeV/c, no signal was found; the 90% C.L. upper limit obtained for the K-p→3π0Λ total cross section σt varies between 2 and 7 μb. This small upper limit is indicative that spontaneous π0 emission is insignificant, since the K-p→π0π0π0Λ threshold is at pK-=397 MeV/c. A signal was observed only at pK-=750 MeV/c, with σt=25±7 μb. These results can be explained only if triple π0 production goes predominantly by hyperon resonance deexcitation, K-p→Σ*→π0Λ*. There are several candidates for the Σ* but only one for the Λ*, namely, the Λ(1520)3/2-, as the threshold for K-p→π0Λ(1520) is at pK-=704 MeV/c.

  5. What We Stand "For", Not "Against": Presenting Our Teacher Education Colleagues with the Case for Social Foundations in PK-12 Teacher Preparation Programs

    Hartlep, Nicholas D.; Porfilio, Bradley J.; Otto, Stacy; O'Brien, Kathleen


    Social Foundations of Education (SFE) courses play a critical role in preparing professional, effective PK-12 teachers, yet, for reasons argued in this article and elsewhere, such courses remain under attack. In this article, by arguing what SFE "stands for" as opposed to what it "stands against," the authors intend to…

  6. Pharmacokinetic analysis of [11C]PBR28 in the rat model of herpes encephalitis: comparison with (R)-[11C]PK11195 for pre-clinical imaging

    Kopschina Feltes, Paula; Parente, Andrea; Vállez Garcia, David; Sijbesma, Jurgen; Moriguchi Jeckel, Cristina; Dierckx, Rudi; de Vries, Erik; Doorduin, Janine


    Aim: [11C]PBR28 is a second generation translocator protein (TSPO) ligand with supposedly better imaging characteristics than the most commonly used tracer [11C]PK11195. Surprisingly, only limited studies have evaluated the pharmacokinetic and binding profile of [11C]PBR28 in neuroinflammatory model

  7. Pharmacokinetic analysis of 11C-PBR28 in the rat model of herpes encephalitis (HSE): comparison with (R)-11C-PK11195

    Parente, Andrea; Kopschina Feltes, Paula; Vállez Garcia, David; Sijbesma, Jurgen; Moriguchi Jeckel, Cristina M; Dierckx, Rudi; de Vries, Erik F; Doorduin, Janine


    11C-PBR28 is a second generation TSPO tracer with supposedly superior characteristics than the most commonly used tracer for neuroinflammation, (R)-11C-PK11195. Despite its use in clinical research, no studies on the imaging properties and pharmacokinetic analysis of 11C-PBR28 in rodent models of ne

  8. De novo sequencing, assembly and analysis of the genome of the laboratory strain Saccharomyces cerevisiae CEN.PK113-7D, a model for modern industrial biotechnology

    Nijkamp, J.F.; Van den Broek, M.A.; Datema, E.; De Kok, S.; Bosman, L.; Luttik, M.A.H.; Daran-Lapujade, P.A.S.; Vongsangnak, W.; Nielsen, J.; Heijne. W.H.M.; Klaassen, P.; Paddon, C.J.; Platt, D.; Kötter, P.; Van Ham, R.C.; Reinders, M.J.T.; Pronk, J.T.; De Ridder, D.; Daran, J.M.


    Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization

  9. Concordant and opposite roles of DNA-PK and the "facilitator of chromatin transcription" (FACT in DNA repair, apoptosis and necrosis after cisplatin

    Calkins Anne S


    Full Text Available Abstract Background Platinum-containing chemotherapy produces specific DNA damage and is used to treat several human solid tumors. Tumors initially sensitive to platinum-based drugs frequently become resistant. Inhibition of DNA repair is a potential strategy to enhance cisplatin effectiveness. After cisplatin treatment, a balance between repair and apoptosis determines whether cancer cells proliferate or die. DNA-dependent protein kinase (DNA-PK binds to DNA double strand breaks (DSBs through its Ku subunits and initiates non-homologous end joining. Inhibition of DNA-PK sensitizes cancer cells to cisplatin killing. The goal of this study is to elucidate the mechanism underlying the effects of DNA-PK on cisplatin sensitivity. Results Silencing the expression of the catalytic subunit of DNA-PK (DNA-PKcs increased sensitivity to cisplatin and decreased the appearance of γH2AX after cisplatin treatment. We purified DNA-PK by its Ku86 subunit and identified interactors by tandem mass spectrometry before and after cisplatin treatment. The structure specific recognition protein 1 (SSRP1, Spt16 and γH2AX appeared in the Ku86 complex 5 hours after cisplatin treatment. SSRP1 and Spt16 form the facilitator of chromatin transcription (FACT. The cisplatin-induced association of FACT with Ku86 and γH2AX was abrogated by DNase treatment. In living cells, SSRP1 and Ku86 were recruited at sites of DSBs induced by laser beams. Silencing SSRP1 expression increased sensitivity to cisplatin and decreased γH2AX appearance. However, while silencing SSRP1 in cisplatin-treated cells increased both apoptosis and necrosis, DNA-PKcs silencing, in contrast, favored necrosis over apoptosis. Conclusions DNA-PK and FACT both play roles in DNA repair. Therefore both are putative targets for therapeutic inhibition. Since DNA-PK regulates apoptosis, silencing DNA-PKcs redirects cells treated with cisplatin toward necrosis. Silencing FACT however, allows both apoptosis and

  10. Purification and characterization of exonuclease-free Artemis: Implications for DNA-PK – dependent processing of DNA termini in NHEJ catalyzed DSB repair

    Pawelczak, Katherine S.; Turchi, John J.


    Artemis is a member of the β–CASP family of nucleases in the metallo-β-lactamase superfamily of hydrolases. Artemis has been demonstrated to be involved in V(D)J-recombination and in the NHEJ-catalyzed repair of DNA DSBs. In vitro, both DNA-PK independent 5’ to 3’ exonuclease activity and DNA-PK dependent endonuclease activity have been attributed to Artemis, though mutational analysis of the Artemis active site only disrupts endonuclease activity. This suggests that either the enzyme contains two different active sites, or the exonuclease activity is not intrinsic to the Artemis polypeptide. To distinguish between these possibilities, we sought to determine if it was possible to biochemically separate Artemis endonuclease activity from exonuclease activity. Recombinant [His]6–Artemis was expressed in a Baculovirus insect-cell expression system and isolated using a three-column purification methodology. Exonuclease and endonuclease activity, the ability to be phosphorylated by DNA-PK, and Artemis antibody reactivity was monitored throughout the purification and to characterize final pools of protein preparation. Results demonstrated the co-elution of exonuclease and endonuclease activity on a Ni-Agarose affinity column but separation of the two enzymatic activities upon fractionation on a hydroxyapatite column. An exonuclease free fraction of Artemis was obtained that retained DNA-PK dependent endonuclease activity, was phosphorylated by DNA-PK and reacted with an Artemis specific antibody. These data demonstrate that the exonuclease activity thought to be intrinsic to Artemis can be biochemically separated from the Artemis endonuclease. PMID:20347402

  11. Purification and characterization of exonuclease-free Artemis: Implications for DNA-PK-dependent processing of DNA termini in NHEJ-catalyzed DSB repair.

    Pawelczak, Katherine S; Turchi, John J


    Artemis is a member of the beta-CASP family of nucleases in the metallo-beta-lactamase superfamily of hydrolases. Artemis has been demonstrated to be involved in V(D)J-recombination and in the NHEJ-catalyzed repair of DNA DSBs. In vitro, both DNA-PK independent 5'-3' exonuclease activities and DNA-PK dependent endonuclease activity have been attributed to Artemis, though mutational analysis of the Artemis active site only disrupts endonuclease activity. This suggests that either the enzyme contains two different active sites, or the exonuclease activity is not intrinsic to the Artemis polypeptide. To distinguish between these possibilities, we sought to determine if it was possible to biochemically separate Artemis endonuclease activity from exonuclease activity. Recombinant [His](6)-Artemis was expressed in a Baculovirus insect-cell expression system and isolated using a three-column purification methodology. Exonuclease and endonuclease activities, the ability to be phosphorylated by DNA-PK, and Artemis antibody reactivity was monitored throughout the purification and to characterize final pools of protein preparation. Results demonstrated the co-elution of exonuclease and endonuclease activities on a Ni-agarose affinity column but separation of the two enzymatic activities upon fractionation on a hydroxyapatite column. An exonuclease-free fraction of Artemis was obtained that retained DNA-PK dependent endonuclease activity, was phosphorylated by DNA-PK and reacted with an Artemis specific antibody. These data demonstrate that the exonuclease activity thought to be intrinsic to Artemis can be biochemically separated from the Artemis endonuclease. Copyright 2010 Elsevier B.V. All rights reserved.

  12. Meropenem for treating KPC-producing Klebsiella pneumoniae bloodstream infections: Should we get to the PK/PD root of the paradox?

    Del Bono, Valerio; Giacobbe, Daniele Roberto; Marchese, Anna; Parisini, Andrea; Fucile, Carmen; Coppo, Erika; Marini, Valeria; Arena, Antonio; Molin, Alexandre; Martelli, Antonietta; Gratarola, Angelo; Viscoli, Claudio; Pelosi, Paolo; Mattioli, Francesca


    The objective of this study was to assess the achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets of meropenem (MEM) in critically-ill patients with bloodstream infections (BSI) due to Klebsiella pneumoniae-carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) with MEM minimum inhibitory concentrations (MICs) ≥16 mg/L. Nineteen critically-ill patients with KPC-Kp BSI were given combination therapy including MEM, tigecycline, plus colistin or gentamicin (according to susceptibility testing). MEM was administered as an extended 3-hour infusion of 2 g every 8 hours, or adjusted according to renal function. MEM plasma concentrations were determined by high-performance liquid chromatography. PK/PD targets for MEM were defined as T > 40% 1×MIC and T > 40% 4×MIC. Possible synergisms between MEM and coadministered agents were assessed by time-kill assays based on plasma levels for MEM and on fixed plasma concentrations for the other agents. In none of 19 patients MEM reached any PK/PD target. The actual MEM MICs were 256, 512, and 1024 mg/L in 1, 3, and 15 isolates, respectively. However, theoretically, the PK/PD target of T > 40% 1×MIC could have been achieved in 95%, 68%, 32% and 0% of the isolates for MIC equal to 8, 16, 32, and 64 mg/L, respectively. No synergisms were observed between MEM and coadministered agents. In conclusion, high-dose MEM failed to reach PK/PD targets in 19 patients with BSI due to KPC-Kp with very high MEM MICs. On a theoretical basis, our results suggest a possible usefulness of MEM against resistant blood isolates with MICs up to 32 mg/L.

  13. Cancer incidence and all-cause mortality in a cohort of 21,582 Norwegian military peacekeepers deployed to Lebanon during 1978-1998.

    Strand, Leif Aage; Martinsen, Jan Ivar; Borud, Einar Kristian


    We investigated cancer incidence and all-cause mortality among 21,582 Norwegian male military peacekeepers deployed to Lebanon during 1978-1998. We also looked at cancer risk according to duration of service in Lebanon, in the occupational groups of cooks and mechanics, and the risk of alcohol- and smoking-related cancers among those who served during high- or low-conflict periods. The cohort was followed for cancer incidence and all-cause mortality from 1978 through 2012. Standardised incidence ratios (SIR) for cancer and mortality ratios (SMR) were calculated from national rates for the total cohort. SIRs were calculated according to duration of service; among cooks and mechanics; and according to high- and low-conflict exposure. Poisson regression, expressed as rate ratio (RR), was used to see the effect of duration of service, and of conflict exposure. A decreased risk was found for cancer incidence overall (1050 cases, SIR=0.90, 95% confidence interval [CI] 0.84-0.95) and for cancers of the prostate (SIR=0.78) and skin (other than melanoma) (SIR=0.58). The incidence of rectal cancer was 73% higher in those who served for 1 year or more than in those with shorter-term service (RR=1.73, 95% CI 1.00-3.02). The cancer risk in cooks and mechanics was within expected values. The risk of lung cancer was higher in the high-conflict exposure group than in the low-conflict exposure group (RR=1.79; 95% CI 1.00-3.18). In the total cohort, all-cause mortality was lower than expected (SMR=0.83; 95% CI 0.78-0.88). We found a "healthy soldier effect" for overall cancer incidence and all-cause mortality. Service during high-conflict periods was associated with a higher risk of lung cancer than service during low-conflict periods, but this risk was in line with that of the reference population. Copyright © 2015. Published by Elsevier Ltd.

  14. Application of POCT dry biochemical analyzer in peacekeeping laboratory of UNIFIL%POCT干式生化分析仪在联合国驻黎巴嫩临时部队维和检验中的应用研究

    曾平; 谭映军; 刘媛; 吴丽娟


    Objective To investigate the difference of partial biochemical items between our military and foreign military in United Nations Interim Force in Lebanon(UNIFIL) peacekeepers and to explore application value of point of care testing(POCT) dry biochemical analyzer in peacekeeping medicine. Methods 167 peacekeepers from Chinese Kngineer Battalion were enrolled as control group. 115-303 peacekeepers from Spain, France, Indonesia, Malaysia and so on were enrolled as observation group. The biochemical test data was statistically analyzed by independent sample t test between the observation group and control group. Results The levels of ALB(n = 303) ,TBIL(n = 262) ,GPT(n = 242) ,GOT(n = 284) , LDH(n = 229) ,GLU(n = 147) and TCH(n = 168) in observation group were increased significantly than those in control group(n= 167,P0. 05). Conclusion There might exist statistical difference in some biochemical items between peacekeepers from China and other countries in UNIFIL. It could be suggested that different biochemical judgment standard should be established in clinical laboratory of Chinese Level II Hospital. Application value of POCT dry biochemical analyzer was great and obvious in peacekeeping laboratory medicine.%目的 研究联合国驻黎巴嫩临时部队(UNIFIL)我军和外军维和官兵部分生化指标的差异性,初步探讨POCT(point of care testing,POCT)干式生化分析仪在维和检验中的应用价值.方法 以UNIFIL外军维和官兵作为观察组(n=115~303),中国维和工兵营作为对照组(n=167),同时对两组生化检验数据均值行t检验分析其统计学差异性.结果 与167例中国赴黎维和工兵营官兵生化检测结果 相比较,赴黎维和外军官兵生化检测结果 中ALB、TBIL、GPT、GOT、LDH、GLU、TCH显著升高(P0.05).结论 UNIFIL外军和中国维和官兵部分生化指标存在统计学差异性,建议中国维和二级医院检验科应分别建立不同的判断标准;POCT干式生化分析仪在维

  15. Identification and analysis of differential miRNAs in PK-15 cells after foot-and-mouth disease virus infection.

    Ke-Shan Zhang

    Full Text Available The alterations of MicroRNAs(miRNAs in host cell after foot-and-mouth disease virus (FMDV infection is still obscure. To increase our understanding of the pathogenesis of FMDV at the post-transcriptional regulation level, Solexa high-throu MicroRNAs (miRNAs play an important role both in the post-transcriptional regulation of gene expression and host-virus interactions. Despite investigations of miRNA expression ghput sequencing and bioinformatic tools were used to identify differentially expressed miRNAs and analyze their functions during FMDV infection of PK-15 cells. Results indicated that 9,165,674 and 9,230,378 clean reads were obtained, with 172 known and 72 novel miRNAs differently expressed in infected and uninfected groups respectively. Some of differently expressed miRNAs were validated using stem-loop real-time quantitative RT-PCR. The GO annotation and KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in immune response and cell death pathways.

  16. Effects of rapid temperature changes on HK, PK and HSP70 of Litopenaeus vannamei in different seasons

    Guo, Biao; Wang, Fang; Dong, Shuanglin; Hou, Chunqiang


    Activities of hexokinase (HK), pyruvate kinase (PK) and levels of HSP70 were measured to evaluate the response of Litopenaeus vannamei to rapid temperature changes under controlled laboratory conditions. Shrimps were subjected to a quick temperature change from 27°C to 17°C for the summer case (Cold temperature treatment), or from 17°C to 27°C for the winter case (Warm temperature treatment). After 0.5, 1, 3, 6, 12, 24, 48, and 72 h of exposure time, shrimps were sampled and prepared for further analysis. The results showed that the effect of acute temperature changes on activities of HK was significant. Patterns of variations of the two glycolytic enzymes suggested that enzymes in the glycolysis cycle could adjust their activities to meet the acute temperature change. The HSP70 level increased in both cold and warm temperature treatments, suggesting that the rapid temperature changes activated the process of body’s self-protection. But the difference in expression peak of HSP70 might be related to the different body size and the higher thermal sensitivity to temperature increase than to temperature decrease of L. vannamei.

  17. Light energy conversion into H{sub 2} by Anabaena variabilis mutant PK84 dense cultures exposed to nitrogen limitations

    Liu, Jianguo [Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071 (China); Bukatin, Vyacheslav E.; Tsygankov, Anatoly A. [Institute of Basic Biological Problem, Russia Academy of Sciences, Pushchino, Moscow Region 142292 (Russian Federation)


    Concentrated cultures (25-86mgChl al{sup -1}) of Anabaena variabilis PK84 were incubated under 99% Ar+1% CO{sub 2} atmosphere in the photobioreactor made of coaxial cylinders. Under illumination equal to 353{mu}Em{sup -2}s{sup -1} they produced hydrogen with the rate more than 20mll{sup -1}h{sup -1} for several days. The efficiency of light energy conversion into H{sub 2} was approx. 1% and did not depend significantly on initial Chl a concentration. H{sub 2}/O{sub 2} ratio reached 41.5% of theoretical value for water photolysis. Data indicate that dense cultures might be used for outdoor systems under direct sun light. Supra-optimal temperatures 36{sup |}C were not harmful for cultures even for 2 days period. Short-term incubation of cultures under 36{sup |}C even increased H{sub 2} production rate and efficiency of light energy bioconversion by 1.25 times. (author)

  18. 赴利比里亚维和人员疟疾知识、行为及影响因素调查%Survey on knowledge and behaviors of malaria prevention and its influencing factors among the Chinese Peacekeepers to Liberia

    于卜一; 田睿; 袁园; 孙福军; 黄健华; 王康琳; 谢铮


    Objective To investigate the knowledge and behavior of Chinese Peacekeepers to Liberia on malaria prevention,and analyze influencing factors of people's knowledge on malaria and thus provide evidence for further health education to Chinese Peacekeepers.Methods A questionnaire survey was conducted to measure Peacekeepers' knowledge and behavior about malaria prevention.The Chinese Peacekeepers getting vaccination at Beijing International Travel Healthcare Center in 2013 took part in the survey.Results Most peacekeepers knew that mosquito were the major vector of malaria,while only 76.65% and 53.30% of them recognized the importance of emergency anti-malaria drugs and DEET repellents,respectively.Peacekeepers that had been to Africa have better knowledge of malaria prevention than those travelling to Africa for the first time.Most people (90.75%) chose long-lasting mosquito nets as first prevention abroad,while least people (62.56%) chose residual spraying of insecticides indoor.Conclusion The health education and training programs of malaria need to be strengthened among peacekeepers that go to Africa for the first time.More efforts should be put on the peacekeeping camp cleaning and various malaria prevention measures.%目的 调查北京出发赴利比里亚维和人员的疟疾相关知识及行为选择情况,分析疟疾知识知晓率的影响因素,为指导赴利维和人员的健康教育工作提供依据.方法 对2013年在北京国际旅行卫生保健中心接受预防接种的中国赴利维和人员的疟疾知识及防护措施选择情况进行问卷调查与分析.结果 90.53%的维和人员知晓疟疾主要由蚊子传播,对于紧急备用药品(76.65%)及含避蚊胺(DEET)的驱蚊霜(53.30%)作用的知晓率低.曾赴非人员疟疾知晓率较首次赴非人员高.出国后疟疾防护措施选择长效驱蚊蚊帐(90.75%)的人员最多,选择室内滞留喷洒杀虫剂(62.56%)的最少.结论 应加强对于首次赴

  19. Studying the effectiveness of using pneumoimpulsive technology for cleaning the platen surfaces of the PK-38 boiler at the Nazarovo district power station

    Agliulin, S. G.; Nikolaev, S. F.; Zvegintsev, V. I.; Yurkin, I. A.; Shabanov, I. I.; Palkin, V. F.; Sergienko, S. P.; Vlasov, S. M.


    A new pneumoimpulsive technology, central to which is an impact effect of air jet on ash deposits, was proposed for carrying out continuous preventive cleaning of the platens installed in the steam superheater primary and secondary paths of the PK-38 boiler at the Nazarovo district power station. The pneumoimpulsive cleaning system was mounted in the PK-38 boiler unit no. 6A, and the cleaning system tests were carried out during field operation of the boiler. Owing to the use of the proposed cleaning system, long-term (for no less than 3 months of observations) slag-free operation of the platen surfaces was achieved in the range of steam loads from 215 to 235 t/h with the average load equal to 225 t/h at furnace gas temperatures upstream of the platens equal to 1220-1250°C.

  20. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)


    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  1. PK/PD modelling of glucose-insulin-glucagon dynamics in healthy dogs after a subcutaneous bolus administration of native glucagon or a novel glucagon analogue

    Wendt, Sabrina Lyngbye; Møller, Jan Kloppenborg; Boye Knudsen, Carsten;

    Objective We aim to develop a simulation model of the complex glucose-insulin-glucagon dynamics based on physiology and data. Furthermore, we compare pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of marketed reconstituted glucagon with a stable liquid glucagon analogue invented...... satisfactorily for both glucagon and the analogue. Parameter estimates of the PD model were not significantly different between the two compounds. Conclusions The new PK/PD model enables simulations of the glucose-insulin-glucagon dynamics after a SC bolus of glucagon or glucagon analogue. The novel glucagon...... by Zealand Pharma A/S. Research Design and Methods We expanded a physiological model of endogenous glucose production with multiplicative effects of insulin and glucagon and combined it with the Hovorka glucoregulatory model. We used a Bayesian framework to perform multidimensional MAP estimation of model...

  2. Transcellular transport of 4-iodo-L-meta-tyrosine via system L across monolayers of kidney epithelial cell line LLC-PK{sub 1}

    Shikano, Naoto E-mail:; Kawai, Keiichi; Nakajima, Syuichi; Kubodera, Akiko; Kubota, Nobuo; Ishikawa, Nobuyoshi; Saji, Hideo


    The substance 4-[{sup 125}I]iodo-L-meta-tyrosin (4-[{sup 125}I]mTyr) is a radioiodinated amino acid that exhibits high in vivo stability and rapid renal elimination in vivo. We investigated transport of 4-[{sup 125}I]mTyr in LLC-PK{sub 1} (porcine kidney epithelial cell line) monolayers grown on collagen-coated, micro-porous membrane filters. We found that 4-[{sup 125}I]mTyr transport in LLC-PK{sub 1} cells was carrier-mediated and sodium-independent, and that 4-[{sup 125}I]mTyr transport was similar to that of L-Tyr and 3-iodo-{alpha}-methyl-L-tyrosine. The results of the inhibition experiments suggest that 4-[{sup 125}I]mTyr transport is predominantly mediated by a L-type amino acid transporter 1-like porcine homologue (a component of system L) in both basolateral and apical membrane.

  3. 有自杀意念的7国维和官兵心理健康与社会支持的相关性研究%A correlation study on mental health and social support of peacekeeping soldiers with suicidal ideation in seven countries

    张理义; 王艳玲; 郭健; 林海; 陈春霞; 姚高峰


    Objective To explore the correlation between mental health and social support of the seven countries peacekeeping soldiers,and provide theoretical guidance for the peacekeeping soldiers to improve the mental health status.Methods Through random cluster sampling,1143 peacekeeping soldiers were investigated with Chinese Military Mental Health Scale (CMMHS) and Social Support Scale (SSS).Results The total score of CMMHS and depression factor((61.06 ± 3.99),(10.11 ± 1.67)) of the suicidal ideation peacekeeping soldiers were significantly higher than the no-suicidal ideation peacekeeping soldiers ((59.97 ± 3.73),(8.97 ± 1.81))(P < 0.05),CMMHS total score and each factors of the seven countries peacekeeping soldiers were significantly higher than the Chinese soldiers norms (P < 0.05),and the total scores ((28.50 ± 1.69)) of the social support of the suicide idea peacekeeping soldiers was lower than the no-suicidal ideation peacekeeping soldiers ((28.92 ±1.78)) (P<0.05).The obsessive-compulsive factor,anxiety factor,depression factor,phobic anxiety factor,somatization factor,neurastheria factor and interpersonal sensitivity factor of CMMHS were the risk factors arise the mental diseases of the peacekeeping soldiers,especially the depression factor(OR =27.00,x2 =439.46,P < 0.05).The CMMHS total score and each factors had obvious negative correlation with social support scores(r =-0.199 ~0.434,P < 0.05).Analysis of multiple stepwise back displayed that the age,gender,education and social support were main factors of influencing mental health of the seven-country peacekeeping soldiers (age:t =2.428,educational level:t =-3.310,social support:t =1.990,P =0.047 ~ 0.01).Conclusion The suicidal ideation has close relationship with peacekeeping soldiers' psychological disease,and the mental health of the peacekeeping soldiers is influenced by the age,gender,education level,and especially by social support.%目的 探讨有自杀意念的7国维和官兵心理

  4. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies

    Boellaard, Ronald; Hinz, Rainer; Adriaan A. Lammertsma; Schuitemaker, Alie; Tomasi, Giampaolo; Turkheimer, Federico E.; van Berckel, Bart NM; Yaqub, Maqsood


    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[(11)C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were ana...

  5. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK.

    Costantini, Silvia; Woodbine, Lisa; Andreoli, Lucia; Jeggo, Penny A; Vindigni, Alessandro


    DNA non-homologous end-joining (NHEJ) is a major mechanism for repairing DNA double-stranded (ds) breaks in mammalian cells. Here, we characterize the interaction between two key components of the NHEJ machinery, the Ku heterodimer and the DNA ligase IV/Xrcc4 complex. Our results demonstrate that Ku interacts with DNA ligase IV via its tandem BRCT domain and that this interaction is enhanced in the presence of Xrcc4 and dsDNA. Moreover, residues 644-748 of DNA ligase IV encompassing the first BRCT motif are necessary for binding. We show that Ku needs to be in its heterodimeric form to bind DNA ligase IV and that the C-terminal tail of Ku80, which mediates binding to DNA-PKcs, is dispensable for DNA ligase IV recognition. Although the interaction between Ku and DNA ligase IV/Xrcc4 occurs in the absence of DNA-PKcs, the presence of the catalytic subunit of DNA-PK kinase enhances complex formation. Previous studies have shown that DNA-PK kinase activity causes disassembly of DNA-PKcs from Ku at the DNA end. Here, we show that DNA-PK kinase activity also results in disassembly of the Ku/DNA ligase IV/Xrcc4 complex. Collectively, our findings provide novel information on the protein-protein interactions that regulate NHEJ in cells.

  6. Study of pK values and effective dielectric constants of ionizable residues in pentapeptides and in staphylococcal nuclease (SNase) using a mean-field approach.

    Bossa, Guilherme Volpe; Fahr, Alfred; Pereira de Souza, Tereza


    The determination of pK values of amino acid residues as a function of temperature and ionic concentration is crucial to understanding the dynamics of various biological processes such as adsorption of peptides and their interactions with active sites of enzymes. In this study we developed a mean-field model to calculate the position-dependent dielectric constants of ionizable groups and the mean electrostatic potential on the surface. Such potential, which takes into account the contributions exerted by neighboring groups and ions in solution, is responsible for the fine-tuning of the pK value of each residue. The proposed model was applied to the amino acids Asp, Glu, Lys, His, Tyr, and Cys, and since the results were consistent with experimentally obtained values, the model was extended and applied to computation of pK values of Gly and Ala pentapeptides and of ionizable residues of the enzyme staphylococcal nuclease (SNase). In this latter case, we used an approach similar to a first-neighbors approximation, and the results turned out to be in good agreement with previously reported data when considering only the interactions of charged groups located at distances of maximally 20 Å. These considerations and the little computational cost involved turn the suggested approach into a promising tool for the modeling of force fields in computational simulations.

  7. High cell density culture with S. cerevisiae CEN.PK113-5D for IL-1β production: optimization, modeling, and physiological aspects.

    Landi, Carmine; Paciello, Lucia; de Alteriis, Elisabetta; Brambilla, Luca; Parascandola, Palma


    Saccharomyces cerevisiae CEN.PK113-5D, a strain auxotrophic for uracil belonging to the CEN.PK family of the yeast S. cerevisiae, was cultured in aerated fed-batch reactor as such and once transformed to express human interleukin-1β (IL-1β), aiming at obtaining high cell densities and optimizing IL-1β production. Three different exponentially increasing glucose feeding profiles were tested, all of them "in theory" promoting respiratory metabolism to obtain high biomass/product yield. A non-structured non-segregated model was developed to describe the performance of S. cerevisiae CEN.PK113-5D during the fed-batch process and, in particular, its capability to metabolize simultaneously glucose and ethanol which derived from the precedent batch growth. Our study showed that the proliferative capacity of the yeast population declined along the fed-batch run, as shown by the exponentially decreasing specific growth rates on glucose. Further, a shift towards fermentative metabolism occurred. This shift took place earlier the higher was the feed rate and was more pronounced in the case of the recombinant strain. Determination of some physiological markers (acetate production, intracellular ROS accumulation, catalase activity and cell viability) showed that neither poor oxygenation nor oxidative stress was responsible for the decreased specific growth rate, nor for the shift to fermentative metabolism.

  8. Measurement of $CP$ asymmetries in $\\Lambda_{b}^{0} \\to pK^{-}$ and $\\Lambda_{b}^{0} \\to p\\pi^-$ decays at LHCb

    Ferrari, F


    The LHCb experiment has been designed to perform precision measurements in the flavour physics sector at the Large Hadron Collider (LHC). The measurement of the CP-violating observable defined as ΔACP = ACP (Λ0b → pK − ) − ACP (Λ0b → pπ − ), where ACP (Λ0b → pK − ) and ACP (Λ0b → pπ − ) are the direct CP asymmetries in Λ0b → pK − and Λ0b → pπ − decays, is presented for the first time using LHCb data. Using the full 2011 and 2012 data sets of pp collisions collected with the LHCb detector, corresponding to an integrated luminosity of about 3 fb −1, the value ΔACP = (0.8 ± 2.1 ± 0.2)% is obtained. The first uncertainty is statistical and the second corresponds to one of the dominant systematic effects. As the result is compatible with zero, no evidence of CP violation is found. This is the most precise measurement of CP violation in the decays of baryons containing the b quark to date. Once the analysis will be completed with an exhaustive study of systematic uncertainti...

  9. Observation of narrow baryon resonance decaying into $pK^0_s$ in pA-interactions at $70 GeV/c$ with SVD-2 setup

    Aleev, A; Ardashev, E; Balandin, V; Basiladze, Sergei G; Berezhnev, S; Bogdanova, G A; Boguslavsky, M; Egorov, N; Ejov, V; Ermakov, G; Ermolov, P; Furmanec, N; Golovnia, S; Golubkov, S; Gorkov, A; Gorokhov, S; Gramenitsky, I; Grishin, N; Grishkevich, Ya; Karmanov, D; Kholodenko, A; Kiriakov, A; Kosarev, I; Kouzmine, N; Kozlov, V; Kozlov, Yu; Kokoulina, E; Korotkov, N V; Kramarenko, V; Kubarovsky, A; Kurchaninov, L L; Kuzmin, V; Kuznetsov, E; Lanshikov, G; Larichev, A; Leflat, A; Levitsky, M; Lyutov, S; Maiorov, S; Merkin, M; Minaenko, A A; Mitrofanov, G Ya; Moiseev, A; Murzin, V; Nikitin, V; Nomokonov, V P; Oleinik, A; Orfanitsky, S V; Parakhin, V; Petrov, V; Pilavova, L; Pleskach, A; Popov, V; Riadovikov, V; Rudenko, R; Rufanov, I; Senko, V; Shafranov, M; Shalanda, N A; Sidorov, A; Soldatov, M; Tikhonova, L A; Topuria, T; Tsyupa, Yu; Vasilev, M; Vischnevskaya, A; Volkov, V; Vorobev, A; Voronin, A; Yakimchuk, V; Yukaev, A I; Zakamsky, L; Zapolskii, V N; Zhidkov, N; Zmushko, V V; Zotkin, S A; Zotkin, D S; Zverev, E


    SVD-2 experiment data have been analyzed to search for an exotic baryon state, the $\\Theta^+$-baryon, in a $pK^0_s$ decay mode at $70 GeV/c$ on IHEP accelerator. The reaction $pA \\to pK^0_s+X$ with a limited multiplicity was used in the analysis. The $pK^0_s$ invariant mass spectrum shows a resonant structure with $M=1526\\pm3(stat.)\\pm 3(syst.) MeV/c^2$ and $\\Gamma < 24 MeV/c^2$. The statistical significance of this peak was estimated to be of $5.6 \\sigma$. The mass and width of the resonance is compatible with the recently reported $\\Theta^+$- baryon with positive strangeness which was predicted as an exotic pentaquark ($uudd\\bar{s}$) baryon state. The total cross section for $\\Theta^+$ production in pN-interactions for $X_F\\ge 0$ was estimated to be $(30\\div120) \\mu b$ and no essential deviation from A-dependence for inelastic events $(\\sim A^{0.7})$ was found.

  10. A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry).

    Cohen-Solal, M; Préhu, C; Wajcman, H; Poyart, C; Bardakdjian-Michau, J; Kister, J; Promé, D; Valentin, C; Bachir, D; Galactéros, F


    A Guinean woman, heterozygous for haemoglobin (Hb) S, was studied because of episodes of marked anaemia, repeated typical metaphyseal painful crises and haemosiderosis. Her sickling syndrome resulted from the association of Hb S trait with a severe pyruvate kinase deficiency leading to a 2,3-DPG concentration of twice normal levels. Sequence of the PK-R gene revealed an undescribed mutation in the homozygous or hemizygous state within exon 5 (nucleotide 2670 C-->A), leading to the interchange of Ser 130 into Tyr (PK Conakry). In addition, the patient carried a new haemoglobin variant, Hb Conakry [alpha80(F1) Leu-->Val], which seemed to have a mild effect. The high intraerythrocytic 2,3-DPG concentration induced by the PK deficiency resulted in a decreased oxygen affinity which favoured sickling to a level almost similar to that of Hb S/C compound heterozygous patients. This was confirmed by oxygen binding measurements of Hb A/Hb S erythrocytes in which 2,3-DPG content was modified in vitro. Hysteresis between deoxy- and reoxygenation curves, as well as increase in the n(max) value, demonstrated that the extent of HbS polymerization in the propositus was almost the same as that of RBCs from a homozygous sickle cell patient or those of an A/S heterozygous patient with an artificial in vitro increase of 2,3-DPG concentration.

  11. In-silico screening for DNA-dependent protein kinase (DNA-PK) inhibitors: Combined homology modeling, docking, molecular dynamic study followed by biological investigation.

    Tarazi, Hamadeh; Saleh, Ekram; El-Awady, Raafat


    DNA-dependent protein kinase (DNA-PK) is a key enzyme in non-homologous DNA end joining (NHEJ) repair pathway. The targeted inhibition of such enzyme would furnish a valuable option for cancer treatment. In this study we report the development of validation of enzyme homology model, and the subsequent use of this model to perform docking-based virtual screening against a database of FDA-approved drugs. The nominated highest ranking hits (Praziquantel and Dutasteride) were subjected to biological investigation. Additionally, molecular dynamic study was carried-out for binding mode exploration. Results of the biological evaluation revealed that both compounds inhibit the DNA-PK enzymatic activity at relatively high concentration levels with an IC50 of 17.3μM for praziquantel and >20μM for dutasteride. Furthermore, both agents enhanced the anti-proliferative effects of doxorubicin and cisplatin on breast cancer (MCF7) and lung cancer (A549) cell lines. This result indicates that these two hits are good candidate as DNA-PK inhibitors and worth further structural modifications to enhance their enzyme inhibitory effects. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Using Normal Form of Idempotent Matrices over Finite Local Ring Z/pkZ to Construct Cartesian Authentication Codes%利用有限局部环Z/pkZ上的幂等矩阵的标准型构作认证码

    赵辉芳; 南基洙


    In this paper, we determine the normal forms of idempotent matrices for similarity over finite local rings Z/pkZ, from which we construct a Cartesian authentication code and compute its size parameters and the probabilities of successful impersonation and substitution attack under the hypothesis that the cecoding rules are chosen according to a uniform probability distribution.

  13. Chronic high glucose inhibits albumin reabsorption by lysosomal alkalinization in cultured porcine proximal tubular epithelial cells (LLC-PK1).

    Ishibashi, Fukashi


    Lysosomal acidification is a key step of albumin reabsorption in proximal tubular epithelial cells (PTECs). This study was performed to examine the influence of chronic high glucose on lysosomal acidification in cultured PTECs. Porcine PTECs (LLC-PK(1) cells) were cultured in 16.7 mM (300 mg/dl) glucose (HG) alone or with 0.5 mM phlorizin for 24 weeks and subsequently for 12 weeks in 5.5 mM (100 mg/dl) glucose (NG). Chronic HG inhibited the fluorescein isothiocyanate (FITC)-albumin (A) uptake progressively, while phlorizin reversed the inhibition. NG for 12 weeks after HG normalized the uptake. The time-dependent uptake of FITC-A was inhibited by HG and bafilomycin A(1) (BafA(1)) after 15 min and by 4,4'-diisothiocyanato-2,2'-disulfonic acid (DIDS) and N-ethyl-N-isopropyl-amiloride (EIPA) after 3 min. Cellular ATP was depleted by HG and restored by NG. Lysosomal pH, assessed by an acidotropic fluorescent probe, was alkalinized (pH 4.5-7.8) with 5.5-27.8 mM glucose and normalized by subsequent NG. BafA(1) alkalinized lysosomes, and the concentration required to 50% change for the pH and 50% inhibition of FITC-A uptake was similar. EIPA inhibited FITC-A uptake, but did not influence lysosomal pH. DIDS inhibited FITC-A uptake, and unexpectedly lowered lysosomal pH. Real time PCR showed that HG reduced the mRNA level for vacuolar H(+)-ATPase, but did not alter those of chloride channel-5 and Na(+)-H(+)-exchanger-3. In conclusion, the chronic HG inhibits albumin reabsorption by lysosomal alkalinization in PTECs, probably due to ATP depletion and down-regulation of vacuolar H(+)-ATPase.

  14. 猪细小病毒感染PK-15细胞抗病毒相关因子转录变化的分析%The Analysis of Antiviral Cytokines Transcriptional Profiles of PK-15 Cell Cultures Following Infection with Porcine Parvovirus

    李厚伟; 魏战勇; 尹海燕; 陈红英; 李金磊; 韩志涛; 崔保安


    In order to survey the host inflammatory responses, particularly the antiviral cytokines responses of Porcine Parvovirus (PPV) infection, and to investigate the host-PPV interaction, Porcine Kidney-15 cells (PK-15) were infected by PPV. Then the viral DNA was measured and analyzed using real-time PCR. The transcript level of cytokines (IFN-β, IFN-y, IFNAR1, IF-NAR-2, MHC-I , MHC-Ⅱ , MX1, NOS, 2-5AS, Rnase L and IRF-3) were detected by realtime PCR too. The results showed that PPV proliferated rapidly in PK-15 cell 12 hours after infection, and reached peak 48 hours after infection; the transcription levels of IFN-β, IFN-y, IFNAR-1, IFNAR-2, MHC- I , MHC- Ⅱ , MX1, iNOS, 2-5AS, Rnase L and IRF-3 were increased obviously, and the transcription level of Mxl gene was increased 8 423 times at 24 hours after infection. The results revealed that the level of antiviral cytokines increased in PPV infected PK-15 cell.%为了解猪细小病毒(PPV)感染后引起干扰素及其相关细胞因子的反应,探讨宿主一病毒之间的作用关系,作者运用荧光定量PCR技术,测定和分析PPV感染PK-15细胞引起的病毒DNA量的变化和细胞因子IFN-β、IFN-γ、IFNAR-1、IFNAR 2、MHC-I、MHC一Ⅱ、MX1、iNOS、2-5AS、RNase L和IRF-3的转录水平.结果显示,PPV感染PK-15细胞12h病毒开始大量迅速增殖,48 h达到最高峰;PPV感染后可引起PK-15细胞中IFN-β、IFN-γ、IFNAR-1、IFNAR-2、MHC-I、MHC-Ⅱ、Mxl、iNOS、2-5AS、RNase I.和IRF-3的转录量显著增加,其中Mχ1基因在24 h转录量达到8 423倍.猪细小病毒感染可引起PK-15细胞抗病毒相关因子转录增加.

  15. [{sup 11}C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches

    Su, Zhangjie; Herholz, Karl; Gerhard, Alexander; Jackson, Alan; Hinz, Rainer [University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom); Roncaroli, Federico [Imperial College London, ' ' John Fulcher' ' Neuro-Oncology Lab, London (United Kingdom); Du Plessis, Daniel [Salford Royal NHS Foundation Trust, Neuropathology Unit, Salford (United Kingdom); Turkheimer, Federico [King' s College London, Centre for Neuroimaging, Institute of Psychiatry, London (United Kingdom)


    Translocator protein (TSPO) is a biomarker of neuroinflammation that can be imaged by PET using [{sup 11}C]-(R)PK11195. We sought to characterize the [{sup 11}C]-(R)PK11195 kinetics in gliomas of different histotypes and grades, and to compare two reference tissue input functions (supervised cluster analysis versus cerebellar grey matter) for the estimation of [{sup 11}C]-(R)PK11195 binding in gliomas and surrounding brain structures. Twenty-three glioma patients and ten age-matched controls underwent structural MRI and dynamic [{sup 11}C]-(R)PK11195 PET scans. Tissue time-activity curves (TACs) were extracted from tumour regions as well as grey matter (GM) and white matter (WM) of the brains. Parametric maps of binding potential (BP{sub ND}) were generated with the simplified reference tissue model using the two input functions, and were compared with each other. TSPO expression was assessed in tumour tissue sections by immunohistochemistry. Three types of regional kinetics were observed in individual tumour TACs: GM-like kinetics (n = 6, clearance of the tracer similar to that in cerebellar GM), WM-like kinetics (n = 8, clearance of the tracer similar to that in cerebral WM) and a form of mixed kinetics (n = 9, intermediate rate of clearance). Such kinetic patterns differed between low-grade astrocytomas (WM-like kinetics) and oligodendrogliomas (GM-like and mixed kinetics), but were independent of tumour grade. There was good agreement between parametric maps of BP{sub ND} derived from the two input functions in all controls and 10 of 23 glioma patients. In 13 of the 23 patients, BP{sub ND} values derived from the supervised cluster input were systematically smaller than those using the cerebellar input. Immunohistochemistry confirmed that TSPO expression increased with tumour grade. The three types of [{sup 11}C]-(R)PK11195 kinetics in gliomas are determined in part by tracer delivery, and indicated that kinetic analysis is a valuable tool in the study of

  16. In vivo imaging of ''neuroinflammation''. Principles and applications; In-vivo-Darstellung ''neuroinflammatorischer'' Veraenderungen mit [{sup 11}C] PK11195-PET. Grundlagen und Anwendung

    Gerhard, A.; Banati, R.B. [MRC Clinical Sciences Centre and Div. of Neuroscience, Faculty of Medicine, Imperial Coll., London (United Kingdom)


    Microglia are the brains' resident immunocompetent cells that can be activated by acute as well as chronic pathological stimuli. When activated they express the peripheral benzodiazepine binding site to which the isoquinolin PK11195 binds with high specificity. Labelled with [{sup 11}C], the R-enatiomer [{sup 11}C] PK1195 has been used for positron emission tomography (PET) studies to demonstrate neuroinflammatory changes in vivo. [{sup 11}C](R) PK11195-PET has been successfully used to show in vivo microglial activation in ischemic (stroke), inflammatory (multiple sclerosis) and degenerative (Alzheimer's and Parkinson's disease). Longitudinal studies are in progress to help to clarify the relationship between localisation and extent of microglial activation and the clinical presentations in these disorders. This will help to determine the role of [{sup 11}C](R) PK11195 PET as a diagnostic tool and a surrogate marker of ''neuroinflammation'' in therapeutic trials. (orig.) [German] Mikroglia sind residente immunkompetente Zellen des Gehirns, die durch akute, aber auch langsam voranschreitende, chronische Schaedigungprozesse aktiviert werden. Im aktivierten Zustand exprimieren sie den peripheren Benzodiazepinrezeptor, an den das Isoquinolin PK11195 spezifisch bindet. Radioaktiv markiert kann das R-Enantiomer [{sup 11}C] PK11195 als Ligand in der Positronenemissionstomographie (PET) genutzt werden und ermoeglicht so die In-vivo-Darstellung aktiver ''neuroinflammatorischer'', d.h. die Mikroglia aktivierender, Veraenderungen. Mit der [{sup 11}C](R) PK11195-PET konnte bisher In-vivo-Mikrogliaaktivierung bei ischaemischen (Schlaganfall), entzuendlichen (multiple Sklerose) und degenerativen (Morbus Alzheimer- und Parkinson-Erkrankung) demonstriert werden. Laufende longitudinale Studien werden dazu beitragen, die Beziehung zwischen Lokalisation und Ausmass der Mikrogliaaktivierung und klinischer Krankheitsauspraegung

  17. Application of a PK-PD Modeling and Simulation-Based Strategy for Clinical Translation of Antibody-Drug Conjugates: a Case Study with Trastuzumab Emtansine (T-DM1).

    Singh, Aman P; Shah, Dhaval K


    Successful clinical translation of antibody-drug conjugates (ADCs) can be challenging due to complex pharmacokinetics and differences between preclinical and clinical tumors. To facilitate this translation, we have developed a general pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation (M&S)-based strategy for ADCs. Here we present the validation of this strategy using T-DM1 as a case study. A previously developed preclinical tumor disposition model for T-DM1 (Singh and Shah, AAPSJ. 2015; 18(4):861-875) was used to develop a PK-PD model that can characterize in vivo efficacy of T-DM1 in preclinical tumor models. The preclinical data was used to estimate the efficacy parameters for T-DM1. Human PK of T-DM1 was a priori predicted using allometric scaling of monkey PK parameters. The predicted human PK, preclinically estimated efficacy parameters, and clinically observed volume and growth parameters for breast cancer were combined to develop a translated clinical PK-PD model for T-DM1. Clinical trial simulations were performed using the translated PK-PD model to predict progression-free survival (PFS) and objective response rates (ORRs) for T-DM1. The model simulated PFS rates for HER2 1+ and 3+ populations were comparable to the rates observed in three different clinical trials. The model predicted only a modest improvement in ORR with an increase in clinically approved dose of T-DM1. However, the model suggested that a fractionated dosing regimen (e.g., front loading) may provide an improvement in the efficacy. In general, the PK-PD M&S-based strategy presented here is capable of a priori predicting the clinical efficacy of ADCs, and this strategy has been now retrospectively validated for all clinically approved ADCs.

  18. 维和医疗分队官兵集训期心理弹性对心理健康的影响分析%Analysis on the Influence of Mental Resilience on Mental Health for the Peacekeeping Medical Unit Service-men during Assemble for Training

    闫玮娟; 袁阳; 韩兵; 王乃震


    目的:了解维和医疗分队官兵集训期间心理弹性及心理健康状况,考察心理弹性与心理健康之间的预测作用,为部队维和官兵的心理选拔和心理健康教育提供科学依据。方法抽取2014年赴南苏丹维和医疗分队官兵集训前一天(前测)和集训结束前一天(后测),采用 Connor Davidson 心理弹性问卷(CD -RISC)、症状自评量表(SCL -90)对来自不同单位的63名官兵进行调查。结果①维和医疗分队官兵心理弹性状况较好,两次测验的 CD 总分分别为(78.35±18.06)分和(81.05±17.93)分;②两次测试维和医疗分队官兵心理健康(SCL -90)状况较好。③心理弹性(前测)和心理健康(前测)呈显著负相关(P <0.01),心理弹性(后测)和心理健康(后测)也呈显著负相关(P <0.01)。结论集训期间维和医疗分队官兵心理弹性状况较好,维和官兵心理弹性对其心理健康具有较好的预测作用。%Objective To explore the resilience and mental health of peacekeeping medical unit service-men during training and to investigate mutual prediction of resilience and mental health and psychological stress to provide the scientific evidence for the mental health training and psychological selection of peacekeeping medical unit servicemen.Methods Connor -Davidson Resilience Questionnaire(CD -RISC),Symptom Checklist(SCL -90) were applied 63 peacekeeping medical unit servicemen the day before starting training and the day before the end of training.Results ①peacekeeping medical unit servicemen had a good resilience, and the CD scores of pre-test and post -test were (78.35 ±18.06)and (81.05 ±17.93) ②Mental health ( SCL -90) of two tests were good in peacekeeping medical unit servicemen③Resilience (pre -test) and mental health (pre -test) has signifi-cant negative correlation(P <0.01), Resilience (pro -test) and mental health (pro -test

  19. Reserve Component Soldiers as Peacekeepers.


    to discriminate between individuals (i.e., p values close to .50 from the pretest, high item-total correlations). For tasks that were tested by...Hepburn, 1980; Tajfel & Turner, 1986; Turner, 1984). Perceived inequity ("us" against "them") may also be experienced at the group level, and...Locksley, A., Ortiz, V., and Hepburn, C. (1980). Social categorization and discriminatory behavior: Extinguishing the minimal intergroup discrimination

  20. Gut Microbiota: The Brain Peacekeeper

    Mu, Chunlong; Yang, Yuxiang; Zhu, Weiyun


    Gut microbiota regulates intestinal and extraintestinal homeostasis. Accumulating evidence suggests that the gut microbiota may also regulate brain function and behavior. Results from animal models indicate that disturbances in the composition and functionality of some microbiota members are associated with neurophysiological disorders, strengthening the idea of a microbiota–gut–brain axis and the role of microbiota as a “peacekeeper” in the brain health. Here, we review recent discoveries on the role of the gut microbiota in central nervous system-related diseases. We also discuss the emerging concept of the bidirectional regulation by the circadian rhythm and gut microbiota, and the potential role of the epigenetic regulation in neuronal cell function. Microbiome studies are also highlighted as crucial in the development of targeted therapies for neurodevelopmental disorders. PMID:27014255

  1. Oxygen dependence of metabolic fluxes and energy generation of Saccharomyces cerevisiae CEN.PK113-1A

    Wiebe Marilyn


    Full Text Available Abstract Background The yeast Saccharomyces cerevisiae is able to adjust to external oxygen availability by utilizing both respirative and fermentative metabolic modes. Adjusting the metabolic mode involves alteration of the intracellular metabolic fluxes that are determined by the cell's multilevel regulatory network. Oxygen is a major determinant of the physiology of S. cerevisiae but understanding of the oxygen dependence of intracellular flux distributions is still scarce. Results Metabolic flux distributions of S. cerevisiae CEN.PK113-1A growing in glucose-limited chemostat cultures at a dilution rate of 0.1 h-1 with 20.9%, 2.8%, 1.0%, 0.5% or 0.0% O2 in the inlet gas were quantified by 13C-MFA. Metabolic flux ratios from fractional [U-13C]glucose labelling experiments were used to solve the underdetermined MFA system of central carbon metabolism of S. cerevisiae. While ethanol production was observed already in 2.8% oxygen, only minor differences in the flux distribution were observed, compared to fully aerobic conditions. However, in 1.0% and 0.5% oxygen the respiratory rate was severely restricted, resulting in progressively reduced fluxes through the TCA cycle and the direction of major fluxes to the fermentative pathway. A redistribution of fluxes was observed in all branching points of central carbon metabolism. Yet only when oxygen provision was reduced to 0.5%, was the biomass yield exceeded by the yields of ethanol and CO2. Respirative ATP generation provided 59% of the ATP demand in fully aerobic conditions and still a substantial 25% in 0.5% oxygenation. An extensive redistribution of fluxes was observed in anaerobic conditions compared to all the aerobic conditions. Positive correlation between the transcriptional levels of metabolic enzymes and the corresponding fluxes in the different oxygenation conditions was found only in the respirative pathway. Conclusion 13C-constrained MFA enabled quantitative determination of

  2. Practice in Deal ing with Refugees Cirs is of Peacekeeping Level ⅡHospital%维和二级医院应对难民潮危机的做法

    张立新; 郭春亮; 李金起


    赴南苏丹维和二级医院执行维和任务期间,驻地突然发生部族武装冲突,大量难民涌入UN城。难民成份复杂,秩序混乱,缺少食物,卫生条件极差,二级医院营区紧邻难民点,防卫力量薄弱,安全形势严峻。二级医院迅速启动应急预案,加强情报收集,提高防卫能力,从严管控部队,做好食物储备,积极开展国际人道主义援助,有效化解危机,确保维和部队人员、财物安全。确保信息渠道通畅、科学制定预案、加强队员心理疏导、超前做好物资储备是应对危机的有效措施。%During the period of participating the operations of Peacekeeping level II hospital in south Su-dan, an armed conflict happened suddenly between local tribes .A large number of refugees fled to the UN city . Refugees came from different tribes , of confusion order , lack of food, poor sanitary conditions .Level II hospital was close to the refugee camp , the defense force was weak , and the security situation was grim .So we rapidly star-ted the emergency plan , strengthened the collection of information , to improve the defense capability ,strictly con-trolled team, completed the food reserves , actively carried out international humanitarian aid , and effectively re-solved the crisis , to ensured that the peacekeeping personnel and property safety .The author pointed out that ensu-ring information channel unobstructed , of scientific plan , strengthening the psychological counseling , reserving ma-terials in advanced are the effective measures to cope with the crisis .

  3. Occupational Protection in Peacekeeping Level Ⅱ Hospital Based on Standard Precautions%基于“标准预防”的维和二级医院职业防护

    崔忠; 岳宝玲; 牛艳萍


    目的 研究维和二级医院职业防护管理方法.方法 建立感染控制管理组织.实施手卫生学防护管理、执业个人防护要求、医疗锐器防护要求、伤员隔离要求、医疗环境与物品管理要求、医疗垃圾和废弃物处置的“标准预防”职业防护管理制度.明确维和职业暴露发生后的处置预案,实施规范的预防职业暴露培训计划.结果 任务期43名队员未发生任何职业暴露,实现院内感染“零记录”、医疗队员疟疾“零感染”,两次圆满通过联合国核查.结论 在感染控制组织领导下,实施“标准预防”管理,对维和医疗队执业暴露感染控制发挥重要的作用,为今后我军海外医疗任务保障提供研究平台.%Objective To study the management methods of standard precautions in Peacekeeping Level ]I hospital. Methods Establishing the following regulations: hand hygiene protection management, practicing personal protection requirements, medical sharp appliance protection requirements, wounded segregation requirements, medical environment and materials management requirements, the standard precautions of medical waste and garbage treatment. Explicit dealing with the peace -keeping occupational exposure, Implementing the standardized training programs for the prevention of occupational exposure. Result 43 team members did not have any occupational exposure during the task. The hospital achieved the hospital infection "zero record" , finishing die U-nited Nations verification twice successfully. Conclusions Under the direction of the infection control organization , implement " standard precautions" management, it has played an important role in peacekeeping medical team infection control, provided a research platform for the future protection of our military overseas medical task.

  4. Eficiência e efeito residual de biofertilizantes de rochas com PK e enxofre com Acidithiobacillus em alface Efficiency and residual effect of PK rock biofertilizers with sulfur and Acidithiobacillus on lettuce

    Rita de Cássia Matias de Lima


    PB2 and KB2 and 150% the recommended level PB3 and KB3 for SSP and KCl and a control treatment with no P and K (P0K0. The experimental design was a factorial 5² in the randomized block, with four replicates. There was similar performance of the PK rock biofertilizers compared to the mineral fertilizers, especially when the level BP2BK3 was applied. The consecutive crop showed residual effect on lettuce yield (fresh shoot biomass, height, number of leaves, commercial evaluation, and P and K accumulation on shoot dry biomass. The results suggest that P and K rock biofertilizers may be used as an alternative in mineral fertilization.

  5. Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

    E.A. Pessoa


    Full Text Available Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU. After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3% and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1% and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 µg/mg protein and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

  6. 分组“PK”教学法的设计与实践%Design and practice of group PK teaching

    刘长利; 蔡少青


    The author designed and practiced group PK teaching model in Pharmaceutical Botany combined with the ideas of educational skill training program in Peking university aiming at promoting students' learning initiative and enthusiasm as well as collective and teamwork sense.The paper discussed the concept of group PK teaching,requirements for teaching design and problems which should be noted in practice from the aspects of introduction,design and practice of the method as well as teaching effect evaluation and teaching method reflection.Survey questionnaire was used to evaluate the preliminary teaching effect of the new teaching method and to explore its teaching thought and educational idea.In practice,group PK teaching model improved students' self-learning awareness and ability,communication skills,collective and teamwork sense.%设计“分组PK教学法”,并在《药用植物学》课程教学中实施.从该教学法的提出、设计、教学实践应用、教学效果分析以及教学方法思考等方面,阐述新教学法的概念、教学设计要求、在教学实践应用中需注意的问题.采用调查问卷初步评价教学效果,探讨新教学法实施的教学思想与育人理念.新教学法的提出并实施,对于强化大学生的主动求知意识和团队合作意识、提高其自主学习能力、表达交流能力具有促进作用.

  7. Quantitative longitudinal imaging of activated microglia as a marker of inflammation in the pilocarpine rat model of epilepsy using [(11)C]-( R)-PK11195 PET and MRI.

    Yankam Njiwa, J; Costes, N; Bouillot, C; Bouvard, S; Fieux, S; Becker, G; Levigoureux, E; Kocevar, G; Stamile, C; Langlois, J B; Bolbos, R; Bonnet, C; Bezin, L; Zimmer, L; Hammers, A


    Inflammation may play a role in the development of epilepsy after brain insults. [(11)C]-( R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [(11)C]-( R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 + 6, D0 + 35, D0 = SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/CT. On D0 + 35, femoral arterial blood was sampled for rat-specific metabolite-corrected arterial plasma input functions (AIFs). In multiple MR-derived ROIs, we assessed four kinetic models (two with AIFs; two using a reference region), standard uptake values (SUVs), and a model with a mean AIF. All models showed large (up to two-fold) and significant TSPO binding increases in regions expected to be affected, and comparatively little change in the brainstem, at D0 + 6. Some individuals showed increases at D0 + 35. AIF models yielded more consistent increases at D0 + 6. FA values were decreased at D0 + 6 and had recovered by D0 + 35. MD was increased at D0 + 6 and more so at D0 + 35. [(11)C]-( R)-PK11195 PET binding and MR biomarker changes could be detected with only nine rats, highlighting the potential of longitudinal imaging studies.

  8. Cadmium chloride induced cell injury through oxidative stress%镉通过氧化应激机制诱导LLC-PK1细胞损伤

    方鑫; 李海玲; 安彩艳


    目的:探讨镉诱导猪肾近曲小管上皮细胞(LLC-PK1)毒性及氧化应激在其中的作用。方法用不同浓度的氯化镉刺激细胞9h和25μmol/L的氯化镉刺激细胞不同时间,采用Formazan 分析细胞存活率反映镉对细胞的损伤程度;以还原型谷胱甘肽(GSH)为靶点,影响GSH浓度的两个试剂BSO和NAC,观察镉诱导细胞损伤中氧化应激的作用。结果随着氯化镉染毒时间延长,细胞存活率下降,同样,随着剂量的增加,细胞的存活率逐渐也下降。同时BSO加重镉诱导的细胞损伤,NAC完全抑制镉诱导的细胞损伤。结论氯化镉对LLC- PK1细胞具有明显的毒性,细胞损伤是通过氧化应激介导,且与细胞内的谷胱甘肽的水平有着密切关系。%Objective To investigate the possible mechanisms of cadmium chloride-induced LLC-PK1 cell toxicity and the role of oxidative stress during the progress. Methods LLC-PK1 cells were treated with different concentrations of cadmium chloride for 9h,and different times at the same dose of cadmium chloride (25μmol/L), respectively.Formazan was used to analyze the cells viability.GSH was taken as a target,and the role of oxidative stress in the progress of cadmium chloride-induced cell injury was assessed by BSO and NAC. Results With the increasing of treatment time and cadmium concentration,Cadmium-induced cell toxicity became more serious and the viability of cells decreased.The cell susceptibility to cadmium chloride could be substantially altered by glutathione (GSH)-modulating agents.Depletion of GSH with BSO increased, whereas supply of cells with NAC decreased subsequent cell injury. Conclusion Cadmium chloride induced cell injury through oxidative stress,which was closely associated with the expression level of intracellular GSH.

  9. Organization and Implementation of Peace-keeping Medical and Health Equipment's Transfer%维和二级医院医疗卫生装备交接的组织与实施



    结合中国第九批刚果(金)维和医疗分队二级医院医疗卫生装备交接实践,分析了维和任务区环境条件对交接工作的影响,论述了医疗分队轮换中卫生装备交接的前期准备及交接组织和实施方法,总结了交接中的注意事项,以期为今后维和医疗分队顺利交接提供借鉴.%The influence of peace -keeping environmental conditions on transfer combined with medical and health equipment's transfer practice in China's ninth batch to Congo peace -keeping unit level II hospital is analyzed. The preparation of handover, transfer organization and implementation methods in the medical team rotation are discussed, which provides useful experience and notes for the future peace-keeping medical team.[Chinese Medical Equipment Journal, 2011,33(3) :94-95,100

  10. Partial wave analysis of the reaction p (3.5 GeV) + p → pK+ Λ to search for the " ppK-" bound state

    Agakishiev, G.; Arnold, O.; Belver, D.; Belyaev, A.; Berger-Chen, J. C.; Blanco, A.; Böhmer, M.; Boyard, J. L.; Cabanelas, P.; Chernenko, S.; Dybczak, A.; Epple, E.; Fabbietti, L.; Fateev, O.; Finocchiaro, P.; Fonte, P.; Friese, J.; Fröhlich, I.; Galatyuk, T.; Garzón, J. A.; Gernhäuser, R.; Göbel, K.; Golubeva, M.; González-Díaz, D.; Guber, F.; Gumberidze, M.; Heinz, T.; Hennino, T.; Holzmann, R.; Ierusalimov, A.; Iori, I.; Ivashkin, A.; Jurkovic, M.; Kämpfer, B.; Karavicheva, T.; Koenig, I.; Koenig, W.; Kolb, B. W.; Kornakov, G.; Kotte, R.; Krása, A.; Krizek, F.; Krücken, R.; Kuc, H.; Kühn, W.; Kugler, A.; Kunz, T.; Kurepin, A.; Ladygin, V.; Lalik, R.; Lapidus, K.; Lebedev, A.; Lopes, L.; Lorenz, M.; Maier, L.; Mangiarotti, A.; Markert, J.; Metag, V.; Michel, J.; Müntz, C.; Münzer, R.; Naumann, L.; Pachmayer, Y. C.; Palka, M.; Parpottas, Y.; Pechenov, V.; Pechenova, O.; Pietraszko, J.; Przygoda, W.; Ramstein, B.; Reshetin, A.; Rustamov, A.; Sadovsky, A.; Salabura, P.; Schmah, A.; Schwab, E.; Siebenson, J.; Sobolev, Yu. G.; Spataro, S.; Spruck, B.; Ströbele, H.; Stroth, J.; Sturm, C.; Tarantola, A.; Teilab, K.; Tlusty, P.; Traxler, M.; Tsertos, H.; Vasiliev, T.; Wagner, V.; Weber, M.; Wendisch, C.; Wüstenfeld, J.; Yurevich, S.; Zanevsky, Y.; Sarantsev, A. V.


    Employing the Bonn-Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction p (3.5 GeV) + p → pK+ Λ. This reaction might contain information about the kaonic cluster " ppK-" (with quantum numbers JP =0- and total isospin I = 1 / 2) via its decay into pΛ. Due to interference effects in our coherent description of the data, a hypothetical K ‾ NN (or, specifically " ppK-") cluster signal need not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectrum like pΛ. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a K ‾ NN cluster. At a confidence level of CLs = 95% such a cluster cannot contribute more than 2-12% to the total cross section with a pK+ Λ final state, which translates into a production cross-section between 0.7 μb and 4.2 μb, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.

  11. Influences of surface treatments with abrasive paper and sand-blasting on surface morphology, hydrophilicity, mineralization and osteoblasts behaviors of n-CS/PK composite.

    Tang, Xiaoming; Huang, Kai; Dai, Jian; Wu, Zhaoying; Cai, Liang; Yang, Lili; Wei, Jie; Sun, Hailang


    The surfaces of nano-calcium silicate (n-CS)/polyetheretherketone (PK) composites were treated with abrasive paper and sand-blasting, and the surfaces performances of the as-treated composites were studied. The results showed that the surface roughness, hydrophilicity and mineralization of the simulated body fluid (SBF) of the composites surfaces were significantly improved, and the properties of the composites treated by with sand-blasting were better than those treated with abrasive paper. Moreover, the treated composites significantly promoted osteoblasts responses, such as cell attachment, spreading, proliferation and alkaline phosphatase (ALP) activity, compared to un-treated composites, and the cellular responses to the composites treated with sand-blasting were better than those treated with abrasive paper. The results suggested that surface treatment with sand-blasting was an effective method to greatly improve the surface bioperformances of the n-CS/PK composite, and this treated composite with improved bioactivity and cytocompatibility might be a promising implant material for orthopedic applications.

  12. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies.

    Yaqub, Maqsood; van Berckel, Bart N M; Schuitemaker, Alie; Hinz, Rainer; Turkheimer, Federico E; Tomasi, Giampaolo; Lammertsma, Adriaan A; Boellaard, Ronald


    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[(11)C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMV(b)). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (V(b)) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of V(b) in RPM improved both parametric images and binding potential contrast between groups. Incorporation of V(b) within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[(11)C]PK11195 neurodegeneration studies.

  13. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[11C]PK11195 brain PET studies

    Yaqub, Maqsood; van Berckel, Bart NM; Schuitemaker, Alie; Hinz, Rainer; Turkheimer, Federico E; Tomasi, Giampaolo; Lammertsma, Adriaan A; Boellaard, Ronald


    Performance of two supervised cluster analysis (SVCA) algorithms for extracting reference tissue curves was evaluated to improve quantification of dynamic (R)-[11C]PK11195 brain positron emission tomography (PET) studies. Reference tissues were extracted from images using both a manually defined cerebellum and SVCA algorithms based on either four (SVCA4) or six (SVCA6) kinetic classes. Data from controls, mild cognitive impairment patients, and patients with Alzheimer's disease were analyzed using various kinetic models including plasma input, the simplified reference tissue model (RPM) and RPM with vascular correction (RPMVb). In all subject groups, SVCA-based reference tissue curves showed lower blood volume fractions (Vb) and volume of distributions than those based on cerebellum time-activity curve. Probably resulting from the presence of specific signal from the vessel walls that contains in normal condition a significant concentration of the 18 kDa translocation protein. Best contrast between subject groups was seen using SVCA4-based reference tissues as the result of a lower number of kinetic classes and the prior removal of extracerebral tissues. In addition, incorporation of Vb in RPM improved both parametric images and binding potential contrast between groups. Incorporation of Vb within RPM, together with SVCA4, appears to be the method of choice for analyzing cerebral (R)-[11C]PK11195 neurodegeneration studies. PMID:22588187

  14. New analysis on narrow baryon resonance decaying into $pK^0_s$ in $pA$-interactions at $70 GeV/c$ with SVD-2 setup

    Aleev, A; Balandin, V; Basiladze, S; Berezhnev, S; Bogdanova, G; Boguslavsky, I; Bychkov, V; Ejov, V; Ermakov, G; Ermolov, P; Furmanec, N; Golovkin, V; Golovnia, S; Gorokhov, S; Gramenitsky, I; Grishin, N; Grishkevich, Ya; Karmanov, D; Kholodenko, A; Kiriakov, A; Kouzmine, N; Kozlov, V; Kokoulina, E; Kramarenko, V; Kubarovsky, A; Kudryashov, I; Kuzmin, V; Kuznetsov, E; Lanshikov, G; Larichev, A; Leflat, A; Levitsky, M; Lyutov, S; Merkin, M; Minaenko, A; Mitrofanov, G; Nikitin, V; Orfanitsky, S; Parakhin, V; Petrov, V; Peshekhonov, V; Pleskach, A; Popov, V; Riadovikov, V; Ronjin, V; Rufanov, I; Savrina, D; Senko, V; Shalanda, N; Soldatov, M; Tikhonova, L; Topuria, T; Tsyupa, Yu; Uzbyakova, A; Vasilev, M; Vishnevskaya, A; Viriasov, K; Volkov, V; Vorobiev, A; Voronin, A; Yakimchuk, V; Yukaev, A; Zakamsky, L; Zapolsky, V; Zhidkov, N; Zotkin, D; Zotkin, S; Zverev, E


    The inclusive reaction $p A \\to pK^0_s + X$ was studied at IHEP accelerator with $70 GeV/c$ proton beam using SVD-2 detector. Two different samples of $K^0_s$, statistically independent and belonging to different phase space regions, were used in the analyses and a narrow baryon resonance with the mass $M=1523\\pm 2(stat.)\\pm 3(syst.) MeV/c^2$ was observed in both samples of the data. The combined statistical significance was estimated to be of 8.0 (392 signal over 1990 background events). Using the part of events reconstructed with better accuracy the width of resonance was constrained to $\\Gamma \\approx 0.1$}, that qualitatively agrees to a Regge-based model predictions. A new cross section estimate of $\\sigma \\cdot BR(\\Theta^+ \\to pK^0) = 4.9 \\pm 1.0(stat.) \\pm 1.5(syst.) \\mu b/nucleon$ for $x_F > 0$ was obtained.

  15. Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC

    Perrone, Francesco; Baldassarre, Gustavo; Indraccolo, Stefano; Signoriello, Simona; Chiappetta, Gennaro; Esposito, Franca; Ferrandina, Gabriella; Franco, Renato; Mezzanzanica, Delia; Sonego, Maura; Zulato, Elisabetta; Zannoni, Gian F.; Canzonieri, Vincenzo; Scambia, Giovanni; Sorio, Roberto; Savarese, Antonella; Breda, Enrico; Scollo, Paolo; Ferro, Antonella; Tamberi, Stefano; Febbraro, Antonio; Natale, Donato; Maio, Massimo Di; Califano, Daniela; Scognamiglio, Giosuè; Lorusso, Domenica; Canevari, Silvana; Losito, Simona; Gallo, Ciro; Pignata, Sandro


    Background No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m², every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m², every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. Results After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. Conclusion These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted. PMID:27655643

  16. Characterization of preclinical in vitro and in vivo ADME properties and prediction of human PK using a physiologically based pharmacokinetic model for YQA-14, a new dopamine D3 receptor antagonist candidate for treatment of drug addiction.

    Liu, Fei; Zhuang, Xiaomei; Yang, Cuiping; Li, Zheng; Xiong, Shan; Zhang, Zhiwei; Li, Jin; Lu, Chuang; Zhang, Zhenqing


    YQA-14 is a novel and selective dopamine D3 receptor antagonist, with potential for the treatment of drug addiction. However, earlier compounds in its structural class tend to have poor oral bioavailability. The objectives of this study were to characterize the preclinical absorption, distribution, metabolism and excretion (ADME) properties and pharmacokinetics (PK) of YQA-14, then to simulate the clinical PK of YQA-14 using a physiologically based pharmacokinetics (PBPK) model to assess the likelihood of developing YQA-14 as a clinical candidate. For human PK prediction, PBPK models were first built in preclinical species, rats and dogs, for validation purposes. The model was then modified by input of human in vitro ADME data obtained from in vitro studies. The study data showed that YQA-14 is a basic lipophilic compound, with rapid absorption (Tmax ~ 1 h) in both rats and dogs. Liver microsomal clearances and in vivo clearances were moderate in rats and dogs consistent with the moderate bioavailability observed in both species. The PBPK models built for rats and dogs simulated the observed PK data well in both species. The PBPK model refined with human data predicted that YQA-14 would have a clearance of 8.0 ml/min/kg, a volume distribution of 1.7 l/kg and a bioavailability of 16.9%. These acceptable PK properties make YQA-14 an improved candidate for further research and development as a potential dopamine D3R antagonism for the treatment of drug addiction in the clinic.

  17. PK-15细胞α干扰素效应因子qPCR检测方法的建立及其初步应用%The Establishment of qPCR Detecting Method for αIFN Effector of PK-15 Cells and Its Preliminary Application

    邹榕凯; 李俊; 时建立; 柳晓; 丛晓燕; 孙文博; 杜以军; 吴家强; 王金宝


    为建立一种用SYBR Green Ⅰ荧光染料检测PK-15细胞α干扰素(α-IFN)效应因子Mx1、OAS的mRNA表达水平的qPCR检测方法,通过在猪圆环病毒2型(Porcine Circovirus Type 2,PCV2)抑制α-IFN发挥效应的信号通路中进行初步应用.根据GenBank中目的基因的序列,利用分子生物学软件Premier 5.0在其保守区设计并合成相应的特异性引物.利用TRIzol法提取总RNA,经Oligo d(T) 15进行反转录,利用PCR扩增各段目的基因,并克隆至pMD 18-T载体,转化大肠杆菌DH 5α,经鉴定为阳性的重组质粒作为标准品模板建立SYBR Green I qPCR标准曲线和溶解曲线,并进行灵敏性、特异性和重复性试验.根据建立的实时qPCR方法,检测PCV2对α-IFN效应因子的抑制效果.对建立的PK-15细胞α-IFN效应因子SYBR Green I qPCR方法进行分析,结果表明Mx1、OAS和内参β-actin基因的Ct值与标准品稀释度在1×10(1)~1×10(8) copies/μL的范围分别呈良好的线性关系.PK-15细胞在接种PCV2,并受到α-IFN刺激后Mx1、OAS的相对表达量较未接种PCV2明显降低.本试验建立了PK-15细胞α-IFN效应因子的qPCR检测方法,为在mRNA水平上对PK-15细胞α-IFN效应因子的定量分析奠定了基础,并成功地初步应用于PCV2抑制α-IFN发挥效应的信号通路研究中.

  18. PCV-2感染对PK-15细胞IL mRNA转录水平的影响%Analysis of the transcriptional profiles of inflammatory related cytokines of PK-15 cell cultures following Porcine circovirus type 2 infection

    商艳红; 刘欣辛; 李金磊; 王淑娟; 魏静; 赵岩; 崔保安; 魏战勇


    【Objective】The study was conducted to investigate the effect of Porcine circovirus type 2(PCV-2) on the expression of inflammatory cytokines in PK-15 cells(PK-15),and to explore the host and PCV-2 interaction and the mechanism for cellular inflammatory responses.【Method】PCV-2 was used to infect PK-15 cells,then the viral DNA and the transcript level of inflammatory cytokines(IL-6,IL-8,IL-12p35,IL-12p40,IL-13,IL-17 and IL-18) were detected and analyzed in different post-infectious time using real-time PCR,respectively.【Result】The results showed that the mRNA transcript levels of IL-6,IL-13,IL-17,IL-18 significantly decreased on 12 h postinoculation(p.i.),however,the mRNA transcript levels notably increased on 24 h p.i.The mRNA transcript levels of IL-8 were 2.5 times the control group within 48 h p.i,and notably increased on 24 h p.i;The mRNA transcript levels of IL-12p35,IL-12p40 were significantly lower than the control with time.【Conclusion】The mRNA transcript levels of IL-6,IL-8,IL-13,IL-17,IL-18 cytokines increased,and the level of IL-12 decreased when PCV-2 infected PK-15 cells.The results suggested that the inflammatory responses of PK-15 cells induced by PCV-2 infection were associated with the changes of inflammatory related cytokines.%【目的】观察猪圆环病毒2型(PCV-2)感染对猪肾传代细胞(PK-15细胞)炎性细胞因子白细胞介素(IL)mRNA转录水平的影响,探讨宿主与病毒之间的作用关系及细胞炎性反应机制。【方法】以未感染PCV-2的PK-15细胞为对照组,运用相对定量PCR技术,测定和分析PCV-2感染PK-15细胞后,PCV-2DNA相对含量的变化,以及炎性细胞因子IL-6、IL-8、IL-12p35、IL-12p40、IL-13、IL-17、IL-18mRNA转录水平在1,6,12,24,48,和72h的变化。【结果】PCV-2感染后,PK-15细胞的IL-6、IL-13、IL-17、IL-18的mRNA转录水平在12h显著增加,24h后mRNA转录水平下降;IL-8的mRNA转录水平在48h

  19. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production.

    Meng, Qiao; Hagemeier, Stacy R; Fingeroth, Joyce D; Gershburg, Edward; Pagano, Joseph S; Kenney, Shannon C


    Ganciclovir (GCV) and acyclovir (ACV) are guanine nucleoside analogues that inhibit lytic herpesvirus replication. GCV and ACV must be monophosphorylated by virally encoded enzymes to be converted into nucleotides and incorporated into viral DNA. However, whether GCV and/or ACV phosphorylation in Epstein-Barr virus (EBV)-infected cells is mediated primarily by the EBV-encoded protein kinase (EBV-PK), the EBV-encoded thymidine kinase (EBV-TK), or both is controversial. To examine this question, we constructed EBV mutants containing stop codons in either the EBV-PK or EBV-TK open reading frame and selected for stable 293T clones latently infected with wild-type EBV or each of the mutant viruses. Cells were induced to the lytic form of viral replication with a BZLF1 expression vector in the presence and absence of various doses of GCV and ACV, and infectious viral titers were determined by a green Raji cell assay. As expected, virus production in wild-type EBV-infected 293T cells was inhibited by both GCV (50% inhibitory concentration [IC(50)] = 1.5 microM) and ACV (IC(50) = 4.1 microM). However, the EBV-PK mutant (which replicates as well as the wild-type (WT) virus in 293T cells) was resistant to both GCV (IC(50) = 19.6 microM) and ACV (IC(50) = 36.4 microM). Expression of the EBV-PK protein in trans restored GCV and ACV sensitivity in cells infected with the PK mutant virus. In contrast, in 293T cells infected with the TK mutant virus, viral replication remained sensitive to both GCV (IC(50) = 1.2 microM) and ACV (IC(50) = 2.8 microM), although susceptibility to the thymine nucleoside analogue, bromodeoxyuridine, was reduced. Thus, EBV-PK but not EBV-TK mediates ACV and GCV susceptibilities.

  20. Drug Distribution to Human Tissues: Prediction and Examination of the Basic Assumption in In Vivo Pharmacokinetics-Pharmacodynamics (PK/PD) Research.

    Poulin, Patrick


    The tissue:plasma partition coefficients (Kp ) are good indicators of the extent of tissue distribution. Therefore, advanced tissue composition-based models were used to predict the Kp values of drugs under in vivo conditions on the basis of in vitro and physiological input data. These models, however, focus on animal tissues and do not challenge the predictions with human tissues for drugs. The first objective of this study was to predict the experimentally determined Kp values of seven human tissues for 26 drugs. In all, 95% of the predicted Kp values are within 2.5-fold error of the observed values in humans. Accordingly, these results suggest that the tissue composition-based model used in this study is able to provide accurate estimates of drug partitioning in the studied human tissues. Furthermore, as the Kp equals to the ratio of total concentration between tissue and plasma, or the ratio of unbound fraction between plasma (fup ) and tissue (fut ), this parameter Kp would deviate from the unity. Therefore, the second objective was to examine the corresponding relationships between fup and fut values experimentally determined in humans for several drugs. The results also indicate that fup may significantly deviate to fut ; the discrepancies are governed by the dissimilarities in the binding and ionization on both sides of the membrane, which were captured by the tissue composition-based model. Hence, this violated the basic assumption in in vivo pharmacokinetics-pharmacodynamics (PK/PD) research, since the free drug concentration in tissue and plasma was not equal particularly for the ionizable drugs due to the pH gradient effect on the fraction of unionized drug in plasma (fuip ) and tissue (fuit ) (i.e., fup × fuip × total plasma concentration = fut × fuit × total tissue concentration, and, hence, the free drug concentration in plasma and tissue differed by fuip/fuit). Therefore, this assumption should be adjusted for the ionized drugs, and, hence, a


    ZHONG Ping-ping; HE Yu-xiang; XIA Yun-fei; YAN Shan-shan


    Objective: Radiosensitivity is mainly determined by the number of DNA double-strand breaks (DSBs) induced by ionizing radiation and the extent of its repair. The DNA-PK complex formation is one of the major pathways by which the mammalian cells respond to DSBs repairing. Our previous study suggested that CNE1 is more radioresistant than CNE2. This study was designed to answer whether the radiosensitive difference of Nasopharyngeal Carcinoma cell lines CNE 1/CNE2 was related to the expression and localization of Ku70/Ku80/DNA-PKcs. Methods: Immunohistochemistry was performed to detect the subcellular localization of Ku70/Ku80/DNA-PKcs in NPC cells lines CNE1 and CNE2. Western-blot was used to determine the expression of Ku protein in total extract of CNE1 and CNE2 and semi-quantitative assay of protein expression was performed to estimate the optic density (OD) value of each band using automatic image analysis system. Results:Ku70/Ku80/DNA-PKcs primarily located in the nuclei. A part of nucleolus in CNE1 and CNE2 showed positive dyeing of DNA-PKcs. Protein expression of Ku70/Ku80/DNA-PKcs was detected in CNE1 and CNE2, and the integral optical density (IOD) of Ku70 protein was 22.03 ± 7.56 and 19.98 ± 6.04 respectively (t=0.021, P>0.05), while the IODs of Ku80 protein in the two cell lines were 33.44 ± 12.87 and 28.98 ± 9.24 respectively (t=0.24, P>0.05), and the IODs of DNA-PKcs protein were 45.03 ± 1.77 and 40.87 ± 4.19 (t=1.58, P>0.05). The above results suggested that the basic expression of Ku70/Ku80/DNA-PKcs had no statistic difference between the different radiosensitive NPC cell lines CNE1 and CNE2.Conclusion: The variation of radiosensitivity in NPC cell lines CNE1 and CNE2 has no obviously correlation with the subcellular localization and basic expression of DNA-PK protein. So we presumed that the difference of radiosensitivity between CNE1 and CNE2 may be on account of some other factors than subcellular localization and basic expression of

  2. Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of the hypothalamic-pituitary-gonadal axis following treatment with GnRH analogues

    Tornøe, Christoffer Wenzel; Agersø, Henrik; Senderovitz, Thomas;


    Aims To develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of the hypothalamic-pituitary-gonadal (HPG) axis describing the changes in luteinizing hormone (LH) and testosterone concentrations following treatment with the gonadotropin-releasing hormone (GnRH) agonist triptorelin...... and the GnRH receptor blocker degarelix. Methods Fifty-eight healthy subjects received single subcutaneous or intramuscular injections of 3.75 mg of triptorelin and 170 prostate cancer patients received multiple subcutaneous doses of degarelix of between 120 and 320 mg. All subjects were pooled...... for the different dynamic responses observed after administration of both GnRH agonists and GnRH receptor blockers, suggesting that the model adequately characterizes the underlying physiology of the endocrine system....

  3. Optimization of Novel Aza-benzimidazolone mGluR2 PAMs with Respect to LLE and PK Properties and Mitigation of CYP TDI.

    Pero, Joseph E; Rossi, Michael A; Kelly, Michael J; Lehman, Hannah D G F; Layton, Mark E; Garbaccio, Robert M; O'Brien, Julie A; Magliaro, Brian C; Uslaner, Jason M; Huszar, Sarah L; Fillgrove, Kerry L; Tang, Cuyue; Kuo, Yuhsin; Joyce, Leo A; Sherer, Edward C; Jacobson, Marlene A


    Investigation of a novel amino-aza-benzimidazolone structural class of positive allosteric modulators (PAMs) of metabotropic glutamate receptor 2 (mGluR2) identified [2.2.2]-bicyclic amine 12 as an intriguing lead structure due to its promising physicochemical properties and lipophilic ligand efficiency (LLE). Further optimization led to chiral amide 18, which exhibited strong in vitro activity and attractive pharmacokinetic (PK) properties. Hypothesis-driven target design identified compound 21 as a potent, highly selective, orally bioavailable mGluR2 PAM, which addressed a CYP time-dependent inhibition (TDI) liability of 18, while maintaining excellent drug-like properties with robust in vivo activity in a clinically validated model of antipsychotic potential.

  4. Incorporation of mineral phosphorus and potassium on leather waste (collagen): A new N{sub collagen}PK-fertilizer with slow liberation

    Nogueira, Francisco G.E.; Prado, Nayara T. do [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Oliveira, Luiz C.A., E-mail: [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Bastos, Ana R.R. [Departamento de Quimica, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil); Lopes, Joao H. [Departamento de Quimica, UNICAMP, CEP 13083-970, Campinas-SP (Brazil); Carvalho, Janice G. de [Departamento de Ciencia do Solo, Universidade Federal de Lavras, Caixa Postal 3037, CEP 37200-000, Lavras-MG (Brazil)


    The feasibility of using a solid waste (rich in nitrogen) from the leather industry, after chromium extraction, as adsorbent for P and K, for possible utilization as NPK fertilizer was evaluated. The materials, with and without the addition of P and K, were characterized by chemical analyses, infrared spectroscopy, EDS (energy dispersive X-ray spectrometry) and SEM (scanning electronic microscopy). Langmuir and Freundlich equations were used for analyzing the experimental data, which showed a better fit to the Freundlich model, thus suggesting a multilayer adsorption process on the surface of the adsorbent. A preliminary test in greenhouse demonstrates that the P and K incorporation on the matrix rich in nitrogen (collagen) is a interesting alternative to use such material as NPK fertilizer. The application of N{sub collagen}PK formulations, as a source of nutrients for the growth of rice plants, showed promising agronomic results.

  5. Search for a narrow baryonic state decaying to ${pK^0_S}$ and ${\\overline{p}K^0_S}$ in deep inelastic scattering at HERA

    Abramowicz, H.; Adamczyk, L.; Adamus, M.; Antonelli, S.; Aushev, V.; Behnke, O.; Behrens, U.; Bertolin, A.; Bhadra, S.; Bloch, I.; Boos, E.G.; Brock, I.; Brook, N.H.; Brugnera, R.; Bruni, A.; Bussey, P.J.; Caldwell, A.; Capua, M.; Catterall, C.D.; Chwastowski, J.; Ciborowski, J.; Ciesielski, R.; Cooper-Sarkar, A.M.; Corradi, M.; Dementiev, R.K.; Devenish, RCE; Dusini, S.; Foster, B.; Gach, G; Gallo, E.; Garfagnini, A.; Geiser, A.; Gizhko, A.; Gladilin, L.K.; Golubkov, Yu.A.; Grzelak, G.; Guzik, M.; Gwenlan, C.; Hain, W.; Hlushchenko, O.; Hochman, D.; Hori, R.; Ibrahim, Z.A.; Iga, Y.; Ishitsuka, M.; Januschek, F.; Jomhari, N.Z.; Kadenko, I.; Kananov, S.; Karshon, U.; Kaur, P.; Kisielewska, D.; Klanner, R.; Klein, U.; Korzhavina, I.A.; Kotański, A.; Kötz, U.; Kovalchuk, N.; Kowalski, H.; Krupa, B.; Kuprash, O.; Kuze, M; Levchenko, B.B.; Levy, A.; Limentani, S.; Lisovyi, M.; Lobodzinska, E.; Löhr, B.; Lohrmann, E.; Longhin, A.; Lontkovskyi, D.; Lukina, O.Yu.; Makarenko, I.; Malka, J.; Mastroberardino, A.; Mohamad Idris, F.; Mohammad Nasir, N; Myronenko, V.; Nagano, K.; Nobe, T.; Nowak, R.J.; Onishchuk, Yu.; Paul, E.; Perlański, W.; Pokrovskiy, N.S.; Polini, A.; Przybycien, M.; Roloff, P.; Ruspa, M.; Saxon, D.H.; Schioppa, M.; Schneekloth, U.; Schörner-Sadenius, T.; Shcheglova, L.M.; Shevchenko, R.; Shkola, O.; Shyrma, Yu.; Singh, I.; Skillicorn, I.O.; Słomiński, W.; Solano, A.; Stanco, L.; Stefaniuk, N.; Stern, A.; Stopa, P.; Sztuk-Dambietz, J.; Tassi, E.; Tokushuku, K.; Tomaszewska, J.; Tsurugai, T.; Turcato, M.; Turkot, O.; Tymieniecka, T.; Verbytskyi, A.; Wan Abdullah, W.A.T.; Wichmann, K.; Wing, M.; Yamada, S.; Yamazaki, Y.; Zakharchuk, N.; Żarnecki, A.F.; Zawiejski, L.; Zenaiev, O.; Zhautykov, B.O.; Zotkin, D.S.; Mastroberardino, A


    A search for a narrow baryonic state in the $pK^0_S$ and $\\overline{p}K^0_S$ system has been performed in $ep$ collisions at HERA with the ZEUS detector using an integrated luminosity of 358 pb$^{-1}$ taken in 2003-2007. The search was performed with deep inelastic scattering events at an $ep$ centre-of-mass energy of 318 GeV for exchanged photon virtuality, $Q^2$, between 20 and 100 $\\rm{} GeV^{2}$. Contrary to evidence presented for such a state around 1.52 GeV in a previous ZEUS analysis using a sample of 121 pb$^{-1}$ taken in 1996-2000, no resonance peak was found in the $p(\\overline{p})K^0_S$ invariant-mass distribution in the range 1.45-1.7 GeV. Upper limits on the production cross section are set.

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

    Shamim H Rahman


    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.

  7. DNA-PK triggers histone ubiquitination and signaling in response to DNA double-strand breaks produced during the repair of transcription-blocking topoisomerase I lesions.

    Cristini, Agnese; Park, Joon-Hyung; Capranico, Giovanni; Legube, Gaëlle; Favre, Gilles; Sordet, Olivier


    Although defective repair of DNA double-strand breaks (DSBs) leads to neurodegenerative diseases, the processes underlying their production and signaling in non-replicating cells are largely unknown. Stabilized topoisomerase I cleavage complexes (Top1cc) by natural compounds or common DNA alterations are transcription-blocking lesions whose repair depends primarily on Top1 proteolysis and excision by tyrosyl-DNA phosphodiesterase-1 (TDP1). We previously reported that stabilized Top1cc produce transcription-dependent DSBs that activate ATM in neurons. Here, we use camptothecin (CPT)-treated serum-starved quiescent cells to induce transcription-blocking Top1cc and show that those DSBs are generated during Top1cc repair from Top1 peptide-linked DNA single-strand breaks generated after Top1 proteolysis and before excision by TDP1. Following DSB induction, ATM activates DNA-PK whose inhibition suppresses H2AX and H2A ubiquitination and the later assembly of activated ATM into nuclear foci. Inhibition of DNA-PK also reduces Top1 ubiquitination and proteolysis as well as resumption of RNA synthesis suggesting that DSB signaling further enhances Top1cc repair. Finally, we show that co-transcriptional DSBs kill quiescent cells. Together, these new findings reveal that DSB production and signaling by transcription-blocking Top1 lesions impact on non-replicating cell fate and provide insights on the molecular pathogenesis of neurodegenerative diseases such as SCAN1 and AT syndromes, which are caused by TDP1 and ATM deficiency, respectively.

  8. Erythropoietin suppresses epithelial to mesenchymal transition and intercepts Smad signal transduction through a MEK-dependent mechanism in pig kidney (LLC-PK1) cell lines

    Chen, Chien-Liang; Chou, Kang-Ju; Lee, Po-Tsang [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Chen, Ying-Shou; Chang, Tsu-Yuan; Hsu, Chih-Yang; Huang, Wei-Chieh [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Chung, Hsiao-Min [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Fang, Hua-Chang, E-mail: [Division of Nephrology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (China); Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)


    Purpose: Tumor growth factor-{beta}1 (TGF-{beta}1) plays a pivotal role in processes like kidney epithelial-mesenchymal transition (EMT) and interstitial fibrosis, which correlate well with progression of renal disease. Little is known about underlying mechanisms that regulate EMT. Based on the anatomical relationship between erythropoietin (EPO)-producing interstitial fibroblasts and adjacent tubular cells, we investigated the role of EPO in TGF-{beta}1-mediated EMT and fibrosis in kidney injury. Methods: We examined apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells in the presence or absence of EPO. We examined the effect of EPO on TGF-{beta}1-mediated Smad signaling. Apoptosis and cell proliferation were assessed with flow cytometry and hemocytometry. We used Western blotting and indirect immunofluorescence to evaluate expression levels of TGF-{beta}1 signal pathway proteins and EMT markers. Results: We demonstrated that ZVAD-FMK (a caspase inhibitor) inhibited TGF-{beta}1-induced apoptosis but did not inhibit EMT. In contrast, EPO reversed TGF-{beta}1-mediated apoptosis and also partially inhibited TGF-{beta}1-mediated EMT. We showed that EPO treatment suppressed TGF-{beta}1-mediated signaling by inhibiting the phosphorylation and nuclear translocation of Smad 3. Inhibition of mitogen-activated protein kinase kinase 1 (MEK 1) either directly with PD98059 or with MEK 1 siRNA resulted in inhibition of EPO-mediated suppression of EMT and Smad signal transduction in TGF-{beta}1-treated cells. Conclusions: EPO inhibited apoptosis and EMT in TGF-{beta}1-treated LLC-PK1 cells. This effect of EPO was partially mediated by a mitogen-activated protein kinase-dependent inhibition of Smad signal transduction.

  9. (R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: evaluation in a rat epilepsy model.

    Bogdanović, Renée Marie; Syvänen, Stina; Michler, Christina; Russmann, Vera; Eriksson, Jonas; Windhorst, Albert D; Lammertsma, Adriaan A; de Lange, Elisabeth C; Voskuyl, Rob A; Potschka, Heidrun


    Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.

  10. Solution structures of the prototypical 18 kDa translocator protein ligand, PK 11195, elucidated with 1H/13C NMR spectroscopy and quantum chemistry.

    Lee, Yong-Sok; Siméon, Fabrice G; Briard, Emmanuelle; Pike, Victor W


    Eighteen kilodalton translocator protein (TSPO) is an important target for drug discovery and for clinical molecular imaging of brain and peripheral inflammatory processes. PK 11195 [1a; 1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoquinoline carboxamide] is the major prototypical high-affinity ligand for TSPO. Elucidation of the solution structure of 1a is of interest for understanding small-molecule ligand interactions with the lipophilic binding site of TSPO. Dynamic (1)H/(13)C NMR spectroscopy of 1a revealed four quite stable but interconverting rotamers, due to amide bond and 2-chlorophenyl group rotation. These rotamers have been neglected in previous descriptions of the structure of 1a and of the binding of 1a to TSPO. Here, we used quantum chemistry at the level of B3LYP/6-311+G(2d,p) to calculate (13)C and (1)H chemical shifts for the rotamers of 1a and for the very weak TSPO ligand, N-desmethyl-PK 11195 (1b). These data, plus experimental NMR data, were then used to characterize the structures of rotamers of 1a and 1b in organic solution. Energy barriers for both the amide bond and 2'-chlorophenyl group rotation of 1a were determined from dynamic (1)H NMR to be similar (ca.17 to 18 kcal/mol), and they compared well with those calculated at the level of B3LYP/6-31G*. Furthermore, the computed barrier for Z to E rotation is considerably lower in 1a(18.7 kcal/mol) than in 1b (25.4 kcal/mol). NMR (NOE) unequivocally demonstrated that the E rotamer of 1a is the more stable in solution by about 0.4 kcal/mol. These detailed structural findings will aid future TSPO ligand design and support the notion that TSPO prefers to bind ligands as amide E-rotamers.

  11. Omega 3 (peripheral type benzodiazepine binding) site distribution in the rat immune system: an autoradiographic study with the photoaffinity ligand (/sup 3/H)PK 14105

    Benavides, J.; Dubois, A.; Dennis, T.; Hamel, E.; Scatton, B.


    The anatomical distribution of omega 3 (peripheral type benzodiazepine binding) sites in the immune system organs of the rat has been studied autoradiographically at both macroscopic and microscopic levels of resolution using either reversible or irreversible (UV irradiation) labeling with (/sup 3/H)PK 14105. In thymus sections, (/sup 3/H)PK 14105 labeled with high affinity (Kd, derived from saturation experiments = 10.8 nM) a single population of sites which possessed the pharmacological characteristics of omega 3 sites. In the thymus gland, higher omega 3 site densities were detected in the cortex than in the medulla; in these subregions, silver grains were associated to small (10-18 microns diameter) cells. In the spleen, omega 3 sites were more abundant in the white than in the red pulp. In the white pulp, silver grains were denser in the marginal zone than in the vicinity of the central artery and labeling was, as in the thymus, associated to small cytoplasm-poor cells. In the red pulp, omega 3 site associated silver grains were observed mainly in the Bilroth cords. In the lymph nodes, the medullary region showed a higher labeling than the surrounding follicles and paracortex. A significant accumulation of silver grains was observed in the lymph node medullary cords. In the intestine, Peyer patches were particularly enriched in omega 3 sites (especially in the periphery of the follicles). The distribution of omega 3 sites in the immune system organs suggests a preferential labeling of cells of T and monocytic lineages. This is consistent with the proposed immunoregulatory properties of some omega 3 site ligands.

  12. Arecoline-induced pro-fibrotic proteins in LLC-PK1 cells are dependent on c-Jun N-terminal kinase.

    Lin, Sheng-Hsuan; Chiou, Shean-Jaw; Ho, Wan-Ting; Chuang, Chao-Tang; Chuang, Lea-Yea; Guh, Jinn-Yuh


    Areca nut (AN) chewing is associated with chronic kidney disease (CKD). However, the molecular mechanisms of AN-induced CKD are not known. Thus, we studied the effects of arecoline, a major alkaloid of AN, on proximal tubule (LLC-PK1) cells in terms of cytotoxicity, fibrosis, transforming growth factor-β (TGF-β) and c-Jun N-terminal kinase (JNK). We found that arecoline dose (0.1-0.5mM) and time (24-72h)-dependently induced cytotoxicity without causing cell death. Arecoline (0.25 mM) also time-dependently (24-72h) increased fibronectin and plasminogen activator inhibitor-1 (PAI1) protein expressions. Arecoline (0.25 mM) time-dependently (24-72h) increased TGF-β gene transcriptional activity and supernatant levels of active TGF-β1. Moreover, arecoline (0.25 mM) activated JNK while SP600125 (a JNK inhibitor) attenuated arecoline-induced TGF-β gene transcriptional activity. SP600125, but not SB431542 (a TGF-β receptor type I kinase inhibitor), attenuated arecoline-induced fibronectin and PAI1 protein expressions. Finally, tubulointerstitial fibrosis occurred and renal cortical expressions of fibronectin and PAI1 proteins increased in arecoline-fed mice at 24 weeks. We concluded that arecoline induced tubulointerstitial fibrosis in mice while arecoline-induced TGF-β and pro-fibrotic proteins (fibronectin, PAI1) are dependent on JNK in LLC-PK1 cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. tM2-PK蛋白在结直肠癌中的表达及临床意义%The expression and clinical signification of tM2-PK in colorectal cancer

    喻鑫; 刘弋


    Objective To investigate the expression and clinical signification of tumor M2 pyruvate kinase in pa-tients with CRC, and to try to find a reliable and atraumatic method to predict the progress and pronosis in the CRC. Methods ELISA method was used to determine the serum levels of tM2-PK in 68 patients with CRC,40 pa-tients with colorectal polyps and 40 cases of normal subjects; immunohistochemistry ( IHC ) methods were respec-tively used to detect the expression of tM2-PK in tissues. Results ① The level of serum tM2-PK in patients with CRC was significantly higher than the group of patients with polyps and the normal subjects ( P<0.05 ) . The serum tM2-PK levels was closely correlated to tumor size and Duke stage.②The positive rate of tissue tM2-PK was signif-icantly higher in CRC than in colorectal polyps and normal subjects ( P<0.05 ) . Tissue tM2-PK levels was closely correlated to tumor size,Duke stage and differentiation grade. ③Serum tM2-PK levels was correlated to tissue tM2-PK levels (r=0.357,P=0.003). Conclusion Combined detection of expression of tM2-PK can provide the basis theory for the diagnosis and prognosis evaluation of CRC.%目的研究肿瘤型丙酮酸激酶( tM2-PK)在结直肠癌( CRC)患者中的表达及相关性,为CRC的早期诊断、预后判断和治疗后随访,寻求一种简便可靠、无创的检测方法。方法分别应用免疫组化( IHC )法和酶联免疫吸附( ELISA )法检测68例CRC患者癌组织和术前血清tM2-PK水平,并与40例结直肠息肉患者和40例健康体检者作比较。结果① CRC组血清tM2-PK水平明显高于结直肠息肉组、正常组(P<0.05),其表达与肿瘤大小、Duke分期均显著相关;②CRC组织中tM2-PK阳性表达率明显高于结直肠息肉组织和癌旁正常组织(P<0.05),其表达与肿瘤大小、分化程度、Duke分期均显著相关;③血清与癌组织的tM2-PK水平密切相关(r =0.357,P =0.003)。结论摇血清和癌组织tM2-PK 测定对CRC 诊

  14. Linezolid pharmacokinetics/pharmacodynamics and the development of dosage regimen design optimization%利奈唑胺的PK/PD与给药方案优化设计研究进展

    金砚杰; 张晶; 卢克鹏; 刘倩; 林立敏; 宋洪涛


    To provide reference for clinical reasonable application by introducing linezolid pharmacokinetics and pharmacodynamics characteristics in different diseases.The data from CNKI,PUBMED were analyzed.On the basis of PK/PD parameters,the dosage regimen was optimized,which could better improve the curative effect of antimicrobial drugs,and reduce the incidence of adverse reactions,drug resistance and the patients' economic burden.Linezolid had strong antibacterial effect against gram-positive bacteria.It is meaningful to study on the optimum dosage regimen and promote the rational drug use due to the different pathological physiological factors instead of PK/PD characteristics.%通过CNKI、PUBMED等文献库查阅相关文献进行分析,介绍利奈唑胺在不同疾病中PK/PD特点,从而为临床合理应用提供参考.以PK/PD参数为依据,对给药方案进行优化,可以更好地发挥抗菌药物的临床治疗效果,降低不良反应和耐药性的发生率,减轻患者经济负担.利奈唑胺具有强大的抗革兰阳性菌活性,由于不同病理生理因素与其PK/PD特点,研究优化给药方案、促进合理用药具有重大意义.

  15. The study of the relationship among personality,coping style and mental health of Chinese medical force of peacekeeping in Lebanon%赴黎巴嫩维和卫勤保障人员个性、应对与心理健康的相关性研究

    李学成; 胡光涛; 宋航; 赵雯婧; 刘卉; 陆地


    Objective To explore the correlation between personality,coping style and mental health on Chinese peacekeeping medical soldiers in Lebanon,for providing basis of rational developing education programs of mental health.Methods 54 Chinese peacekeeping medical soldiers in Lebanon taking medical support were assessed by Cattell the sixteen personality factor test (16PF),coping style questionnaire,symptom checklist-90(SCL-90) and the questionnaire of the related factors.Results (l)The total score of SCL-90 and the factor scores of somatization,compulsion,interpersonal relationships,anxiety,hostility,psychosis of peacekeeping force taking medical support were significantly lower than the norm of Chinese soldiers(P0.05).(2)The total score and factor scores of SCL-90 of medical support staff had a significant positive correlation with immature and mixed coping style (self-blame,fantasy,avoidance,rationalization) ,while had no significant correlation with the factor scores of help;In addition to the psychosis factor,the total score and other factor scores of SCL-90 showed a significant negative correlation with the factor scores of problem-solving;the total score of SCL-90 showed a significant negative correlation with gregariousness,excitement and sensitivity,while the anxiety,psychosis,and tension was significantly positively correlated (P<0.05).Conclusion Chinese peacekeeping medical soldiers in Lebanon performed well in mental health integratedly and possessed the personality to accomplish peacekeeping mission,the problem-solving and remorse were their main coping style in peacekeeping.As a result,less immature coping are advantage of raising the level of mental health in peacekeeping force for medical support.%目的 探讨中国赴黎巴嫩维和卫勤保障人员个性特征、应对方式与心理健康状况的关系,为合理制订维和人员心理健康教育方案提供依据.方法 应用卡特尔16项个性因素测定(16PF)、应对方式

  16. Phenotypes of PK2/PKR2 heterozygosis mutant mice%前动力蛋白2/前动力蛋白受体2基因杂合突变小鼠表型特征

    肖玲; 周闻白; 周群勇; 胡仁明


    目的 观察前动力蛋白(PK2)、前动力蛋白受体2(PKR2)基因单拷贝丢失后小鼠生长发育及生殖系统发育情况.方法 对比观察PK2+/-、PKR2+/-、以及PK2+/-∶PKR2+/-复合杂合突变小鼠与野生型小鼠体重增长、外生殖器发育情况;免疫荧光染色法观察四组小鼠颅内促性腺激素释放激素(GnRH)神经元分布;阴道冲洗细胞涂片评估法观察小鼠动情周期. 结果 三组杂合突变小鼠体重增长、外生殖器发育及颅内GnRH神经元分布与野生型小鼠相比均无显著差异,但杂合突变小鼠动情周期延长、无规律,双基因杂合突变小鼠表现最明显. 结论 PK2、PKR2基因单拷贝丢失后虽不影响小鼠生殖系统和GnRH神经元发育,但雌鼠表现出动情周期紊乱.因此PK2/PKR2通路对生殖系统功能有调节作用.%Objective; To observe the phenotype changes including weight growth and reproductive system development in PK2/PKR2 heterozygosis mutant mice. Methods; The weight gain and external genitalia development were compared between the three heterozygosis mutant mice groups and the wild type group. GnRH neurons distribution was observed by fluorescent staining method in four groups. The stage of estrus cycle was determined by cytologic evaluation of vaginal smears. The vaginal exfoliate cells were smeared on glass slides, and the cytologic features were evaluated under microscopy Results; There were no changes in weight growth, external genitalia development and the GnRH neurons distribution in brain between the three mutant mice groups and the wild type mice group. The length of estrus cycle was extended in heterogeneous mice, especially in PK2/PKR2 heterogeneous mutation mice. Conclusions: Loss of one copy of PK2 or PKR2 gene did not change reproductive system and GnRH neurons development except estrous cycle. So PK2/PKR2 pathway may play roles in the regulation of reproductive system function.

  17. Studies of renal injury. II. Activation of the glucose transporter 1 (GLUT1) gene and glycolysis in LLC-PK1 cells under Ca2+ stress.

    Dominguez, J H; Song, B; Liu-Chen, S; Qulali, M; Howard, R; Lee, C H; McAteer, J


    Injury to the renal proximal tubule is common and may be followed by either recovery or cell death. The survival of injured cells is supported by a transient change in cellular metabolism that maintains life even when oxygen tension is reduced. This adaptive process involves the activation of the gene encoding the glucose transporter GLUT1, which is essential to maintain the high rates of glucose influx demanded by glycolysis. We hypothesized that after cell injury increases of cell Ca2+ (Ca2+i) initiate the flow of information that culminates with the upregulation of the stress response gene GLUT1. We found that elevations of Ca2+i caused by the calcium ionophore A23187 activated the expression of the GLUT1 gene in LLC-PK1 cells. The stimulatory effect of Ca2+i on GLUT1 gene expression was, at least in part, transcriptional and resulted in higher levels of GLUT1 mRNA, cognate protein, cellular hexose transport activity, glucose consumption, and lactate production. This response was vital to the renal cells, as its interruption severely increased Ca2+-induced cytotoxicity and cell mortality. We propose that increases of Ca2+i initiate stress responses, represented in part by activation of the GLUT1 gene, and that disruption to the flow of information originating from Ca2+-induced stress, or to the coordinated expression of the stress response, prevents cell recovery after injury and may be an important cause of permanent renal cell injury and cell death. PMID:8755650

  18. Pre-Service Teachers Enhance Climate Literacy Through Writing Children's Books on Climate Literacy Concepts and Implementing Related Activities in the PK-12 Classroom

    Walton-Jaggers, L. J.


    Grambling State University faculty participated in NICE workshops during 2011, 2012, and 2013 that were designed to help pre-service teachers increase their knowledge about global climate change through the use of NASA Earth observation sets. The faculty members were encouraged to infuse climate education projects and activities into their courses from information and resources provided during the workshops. As a result, pre-service teacher candidates in the Department of Curriculum and Instruction of the College of Education at Grambling State University have written Children's Literature that specifically focused on different climate change concepts. This project has served as the culminating Climate Change Signature Project that was designed to promote increased opportunities for PK-12 students to expand their knowledge and understanding of climate literacy concepts while enhancing Reading/Literacy skills. The pre-service teacher candidates completed several sequential steps in preparing for the culminating project. This paper will include the presentation ofseveral formal and informal assessments that were used to determine the impact of the project on the teacher candidates and their students.

  19. Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets.

    Davda, Jasmine P; Hansen, Ryan J


    Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are explored, and situations are described when deviations from the basic assumptions may be necessary. This model is most useful for in vivo situations where both antibody and ligand levels are available following drug administration. For a given antibody exposure, the extent and duration of suppression of free ligand is impacted by the apparent affinity of the interaction, as well as by the rate of ligand turnover. The applicability of the general equilibrium model of in vivo antibody-ligand interaction is demonstrated with an anti-Aß antibody.

  20. The MLH1 c.1852_1853delinsGC (p.K618A variant in colorectal cancer: genetic association study in 18,723 individuals.

    Anna Abulí

    Full Text Available Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance", being the c.1852_1853delinsGC (p.K618A variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

  1. Update on the GRB universal scaling E$_{\\rm{X,iso}}$-E$_{\\rm{\\gamma,iso}}$-E$_{\\rm{pk}}$ with ten years of $Swift$ data

    Zaninoni, Elena; Margutti, Raffaella; Amati, Lorenzo


    From a comprehensive statistical analysis of $Swift$ X-ray light-curves of gamma-ray bursts (GRBs) collected from December 2004 to the end of 2010, we found a three-parameter correlation between the isotropic energy emitted in the rest frame 1-10$^4$ keV energy band during the prompt emission (E$_{\\rm{\\gamma,iso}}$), the rest frame peak of the prompt emission energy spectrum (E$_{\\rm{pk}}$), and the X-ray energy emitted in the rest frame 0.3-30 keV observed energy band (E$_{\\rm{X,iso}}$), computed excluding the contribution of the flares. In this paper, we update this correlation with the data collected until June 2014, expanding the sample size with $\\sim$35% more objects, where the number of short GRBs doubled. With this larger sample we confirm the existence of a universal correlation that connects the prompt and afterglow properties of long and short GRBs. We show that this correlation does not depend on the X-ray light-curve morphology and that further analysis is necessary to firmly exclude possible bia...

  2. H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations.

    Anandakrishnan, Ramu; Aguilar, Boris; Onufriev, Alexey V


    The accuracy of atomistic biomolecular modeling and simulation studies depend on the accuracy of the input structures. Preparing these structures for an atomistic modeling task, such as molecular dynamics (MD) simulation, can involve the use of a variety of different tools for: correcting errors, adding missing atoms, filling valences with hydrogens, predicting pK values for titratable amino acids, assigning predefined partial charges and radii to all atoms, and generating force field parameter/topology files for MD. Identifying, installing and effectively using the appropriate tools for each of these tasks can be difficult for novice and time-consuming for experienced users. H++ ( is a free open-source web server that automates the above key steps in the preparation of biomolecular structures for molecular modeling and simulations. H++ also performs extensive error and consistency checking, providing error/warning messages together with the suggested corrections. In addition to numerous minor improvements, the latest version of H++ includes several new capabilities and options: fix erroneous (flipped) side chain conformations for HIS, GLN and ASN, include a ligand in the input structure, process nucleic acid structures and generate a solvent box with specified number of common ions for explicit solvent MD.

  3. Addition of ash and PK with or without N on a peatland in southern Sweden. Effects on tree growth and needle element concentrate; Tillfoersel av aska och PK med eller utan N paa en torvmark i soedra Sverige. Effekter paa traedtillvaext och aemneshalter i barr

    Sikstroem, Ulf (Forestry Research Inst. of Sweden, Uppsala (Sweden))


    In Sweden, about 1.3 million tonnes of ash are produced annually. Out of that amount, 150 000 - 300 000 tonnes have been estimated to originate from forest fuels, i.e. ashes that potentially can be brought back to the forest. Apart from being a compensatory measure after intensive forest harvest (e.g. including tops and branches), the ash may be used to increase the tree growth on peat soils (ash fertilization). On peat soils, tree growth is generally increased after addition of ash or phosphorous (P) and potassium (K) fertilizers. However, in some cases also nitrogen (N) addition is required. On sparsely stocked mires, fertilization may promote the regeneration as well as increase the growth of the trees. Sufficient drainage and supply of plant-available N are some prerequisites for increasing tree growth by PK-addition. In 1982, Skogforsk established a field experiment (168 Perstorp) located in the province of Scania in a sparsely stocked Pinus Sylvestris (L.) sapling stand on a ditched mire where different nutrient regimes were tested. The experiment had a randomized block design including four blocks and seven treatments. Ash and different dozes of P (raw phosphate) and K (potassium chloride), with or without simultaneous N addition, were included as well as un untreated control. The aim of the present study was to evaluate the effects on tree growth and needle elemental concentrations 26 years after treatment. The addition of similar dozes of P (approx. 40 kg P/ha), as ash (2.5 tonnes/ha) or as PK-fertilizer rendered similar growth responses. The increase in stem-wood growth was in the order of 1,6 - 1,9 m3/ha/yr during the 26-year period. The N-addition had no additional effect. On the control plots, the growth was more or less negligible (approx. 0,04 m3sk/ha/yr). On average, the high dozes of raw-phosphate and potassium chloride (40 kg P/ha and 80 kg K/ha) gave a higher growth increase than the low dozes (20 kg P/ha and 40 kg K/ha), although this effect was

  4. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk;

    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  5. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    Nielsen, Ole Lerberg; Afzelius, Pia; Bender, Dirk;


    The aim of this study was to compare (111)In-labeled leukocyte single-photon emission computed tomography (SPECT) and (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose (11)C-methionine, (11......)C-PK11195 and (68)Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using...... a sequential scan protocol with (18)F-FDG, (68)Ga-citrate, (11)C-methionine, (11)C-PK11195, (99m)Tc-Nanocoll and (111)In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis...

  6. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    Nielsen, Ole Lehberg; Afzelius, Pia; Bender, Dirk;


    The aim of this study was to compare 111In-labeled leukocyte single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to PET with tracers that potentially could improve detection of osteomyelitis. We chose 11C-methionine, 11C-PK11195...... and 68Ga-citrate and validated their diagnostic utility in a porcine haematogenous osteomyelitis model. Four juvenile 14-15 weeks old female pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of Staphylococcus aureus using a sequential scan...... protocol with 18F-FDG, 68Ga-citrate, 11C-methionine, 11C-PK11195, 99mTc-Nanocoll and 111In-labelled autologous leukocytes. This was followed by necropsy of the pigs and gross pathology, histopathology and microbial examination. The pigs developed a total of five osteomyelitis lesions, five lesions...

  7. Optimizing an online SPE-HPLC method for analysis of (R)-[{sup 11}C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)- 3-isoquinolinecarboxamide [(R)-[{sup 11}C]PK11195] and its metabolites in humans

    Greuter, Henri N.J.M. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands)]. E-mail:; van Ophemert, Patricia L.B. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Luurtsema, Gert [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); van Berckel, Bart N.M. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Franssen, Eric J.F. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Windhorst, Bert D. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands); Lammertsma, Adriaan A. [Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam (Netherlands)


    (R)-[{sup 11}C]PK11195 is used as a positron emission tomography tracer for activated microglia in several neurological disorders. Quantification of specific binding requires a metabolite-corrected plasma input function. In this study, a high-performance liquid chromatography (HPLC) procedure with online solid phase extraction was modified for analyzing (R)-[{sup 11}C]PK11195 plasma samples, yielding total sample recoveries of more than 98%. When applied to human studies, the use of two HPLC systems enabled analysis of up to seven plasma samples under regular conditions. Online radioactivity detection was compared with offline sample measurements of HPLC profiles. Offline measurements provided the most reliable results especially for late plasma samples. In 10 patients, an average decrease of parent compound from 94.6% at 2.5 min to 45.2% at 1 h after administration was observed.

  8. 胃癌组织中ENO1、M2-PK蛋白表达及其临床意义%Expressions and Clinical Significances of ENO1 and M2-PK in Gastric Cancer

    倪田根; 祝秉东; 周欣; 王娜; 曾峰; 关泉林


    目的:探讨胃癌组织中烯醇化酶-α(enolase-α,ENO1)、肿瘤型丙酮酸激酶(tumor M2 pyruvate kinase,M2-PK)的表达、相互关系及临床病理学意义.方法:应用免疫组织化学SP染色方法分别对55例胃癌组织和23例胃良性病变组织切片染色,观察胃癌组织和良性病变组织ENO1、M2-PK的表达情况及分析两者临床病理关系.结果:胃癌组织中ENO1阳性表达率为67.3% (37/55),明显高于胃良性病变组30.4%(7/23)(P<0.01),其表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期均显著相关(均P<0.05).M2-PK在胃癌组织中的阳性表达率为78.2%(43/55),明显高于胃良性病变组织39.1%(9/23) (P<0.01),其表达与胃癌分化程度、浸润深度均显著相关(均P<0.05).胃癌组织中ENO1与M2-PK的表达呈正相关(r=0.5729,P<0.05).结论:ENO1和M2-PK的表达上调与胃癌的发生、发展可能有关,联合检测两种蛋白在肿瘤组织中的表达,对临床判断胃癌的预后有一定的指导意义.%Objective: To investigate the expression and clinicopathotogical significance of enolase-a (ENO1) and tumor M2 pyruvate kinase (M2-PK) in gastric cancer. Methods: The expression of ENO1 and M2-PK in 55 paraffin-embedded specimens of gastric cancer and 23 paraffin-embedded specimens of benign gastric tissue was detected by S-P immunohistochemistry. The correlation of ENO1 expression to M2-PK. Expression, and their correlations to the clinicophathologic features of gastric cancer were analyzed. Results: The positive rate of ENO1 was significantly higher in gastric cancer than in benign gastric tissue (67.3% vs . 30.4%, P<0.01) , and closely related to differentiation grade ( P<0.01) , depth of invasion (P<0.01), lymph node metastasis (P<0.05) and TNM staging( P<0. 05),The positive rate of M2-PK. Was significantly higher in gastric cancer than in benign gastric tissue (78.2%vs . 39,1%, P<0.01) , and closely related to differentiation grade ( P0

  9. In vivo imaging of neuroinflammation: a comparative study between [{sup 18}F]PBR111, [{sup 11}C]CLINME and [{sup 11}C]PK11195 in an acute rodent model

    Van Camp, Nadja [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); University of Antwerp, Bio-Imaging Lab, Antwerp (Belgium); Boisgard, Raphael; Theze, Benoit; Viel, Thomas; Tavitian, Bertrand [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); Kuhnast, Bertrand; Dolle, Frederic [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); Gregoire, Marie-Claude; Katsifis, Andrew [ANSTO, Radiopharmaceutical Research Institute, Lucas Heights (Australia); Chauveau, Fabien [CEA, I2BM, SHFJ, Laboratoire d' Imagerie Moleculaire Experimentale (LIME), Orsay (France); INSERM U803, Orsay (France); CREATIS-LRMN, CNRS, UMR 5220, Lyon (France); INSERM U630, Lyon (France); Boutin, Herve [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom)


    The key role of neuroinflammation in acute and chronic neurological disorders has stimulated the search for specific radiotracers targeting the peripheral benzodiazepine receptor (PBR)/18 kDa translocator protein (TSPO), a hallmark of neuroinflammation. Here we evaluate the new radiotracer for positron emission tomography (PET) [{sup 18}F]PBR111 in a rodent model of acute inflammation and compare it with [{sup 11}C]CLINME, an {sup 11}C-labelled tracer of the same chemical family, and with the isoquinolinic carboxamide [{sup 11}C]PK11195. We studied radiometabolites by HPLC, in vitro binding by autoradiography and in vivo brain kinetics as well as in vivo specificity of binding using PET imaging. We show that this radiotracer has a high in vitro specificity for PBR/TSPO versus central benzodiazepine receptors, as reflected by the drastic reduction of its binding to target tissue by addition of PK11195 or PBR111, while addition of flumazenil does not affect binding. Only intact [{sup 18}F]PBR111 is detected in brain up to 60 min after i.v. injection, and PET imaging shows an increased uptake in the lesion as compared to the contralateral side as early as 6 min after injection. Administration of an excess of PK11195 and PBR111, 20 min after [{sup 18}F]PBR111 administration, induces a rapid and complete displacement of [{sup 18}F]PBR111 binding from the lesion. Modelling of the PET data using the simplified reference tissue model showed increased binding potential (BP) in comparison to [{sup 11}C]PK11195. [{sup 18}F]PBR111 is a metabolically stable tracer with a high specific in vitro and in vivo binding to TSPO. In addition, considering the longer half-life of {sup 18}F over {sup 11}C, these results support [{sup 18}F]PBR111 as a promising PET tracer of the PBR/TSPO for neuroinflammation imaging. (orig.)

  10. Study of the production of A(b)(0) and (B)over-bar(0) hadrons in pp collisions and first measurement of the A(b)(0)-> J/psi pK(-) branching fraction

    Aaij, R.; Adeva, B.; Adinoffi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; d'Argent, P.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baldini, W.; Barlow, R. J.; Barsche, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediagal, I.; Be, L. J.; Bellee, V.; Belloli, N.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Bettler, M-O; Van Beuzekom, M.; Bien, A.; Bifani, S.; Billoir, P.; Bird, T.; Birnkraut, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britschl, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Buchanan, E.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Gomez, M. Calvo; Campana, P.; Perez, D. Campora; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch.; Cavallero, G.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S. -F.; Chiapolini, N.; Chrzaszcz, M.; Vida, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collazuo, G.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Torres, M. Cruz; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dall'Occo, E.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Simone, P.; Dean, C. -T.; Decamp', D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Demmer, M.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Ruscio, F.; Dijkstra, H.; Donleavy, S.; Dordeill, F.; Dorigo, M.; Suarez, A. Dosil; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farber, C.; Farley, N.; Farry, S.; Fay, R.; Ferguson, D.; Albor, V. Fernandez; Ferrari, F.; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Foh, K.; Fo, P.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Torreira, A. Gallas; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Pardinas, J. Garcia; Tico, J. Garra; Garrido, L.; Gascon, D.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeckil, E.; Gersabeck, M.; Gershon, T.; Chez, Ph.; Giani, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gligorov, V. V.; Gobel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Gandara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Grauges, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grunberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hal, S.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Humair, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jane, E.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Keckell, M.; Kelsey, M.; Kenyon, I. R.; Kenzie, M.; Kete, T.; Khanji, B.; Khurewathanaku, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg', P.; Kozeiha, M.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lail, A.; Lambert, D.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Van Leerdam, J.


    The product of the A(b)(0) ((B) over bar (0)) differential production cross-section and the branching fraction of the decay A(b)(0)-> J/psi pK(-) ((B) over bar (0)-> J/psi p (K) over bar*(892)(0)) is measured as a function of the beauty hadron transverse momentum, p(T), and rapidity, y. The kinemati

  11. Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3-dicyclohexylurea in rats: Preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery

    Chiang, Po-Chang; Ran, Yingqing; Chou, Kang-Jye; Cui, Yong; Wong, Harvey


    1,3-Dicyclohexylurea (DCU), a potent soluble epoxide hydrolase (sEH) inhibitor has been reported to lower systemic blood pressure in spontaneously hypertensive rats. One limitation of continual administration of DCU for in vivo studies is the compound's poor oral bioavailability. This phenomenon is mainly attributed to its poor dissolution rate and low aqueous solubility. Previously, wet-milled DCU nanosuspension has been reported to enhance the bioavailability of DCU. However, the prosperities and limitations of wet-milled nanosuspension have not been fully evaluated. Furthermore, the oral pharmacokinetics of DCU in rodent are such that the use of DCU to understand PK/PD relationships of sEH inhibitors in preclinical efficacy model is less than ideal. In this study, the limitation of orally delivered DCU nanosuspension was assessed by a surface area sensitive absorption model and pharmacokinetic modeling. It was found that dosing DCU nanosuspension did not provide the desired plasma profile needed for PK/PD investigation. Based on the model and in vivo data, a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK/PD studies.

  12. Investigation of utilization of nanosuspension formulation to enhance exposure of 1,3-dicyclohexylurea in rats: Preparation for PK/PD study via subcutaneous route of nanosuspension drug delivery

    Chiang Po-Chang


    Full Text Available Abstract 1,3-Dicyclohexylurea (DCU, a potent soluble epoxide hydrolase (sEH inhibitor has been reported to lower systemic blood pressure in spontaneously hypertensive rats. One limitation of continual administration of DCU for in vivo studies is the compound's poor oral bioavailability. This phenomenon is mainly attributed to its poor dissolution rate and low aqueous solubility. Previously, wet-milled DCU nanosuspension has been reported to enhance the bioavailability of DCU. However, the prosperities and limitations of wet-milled nanosuspension have not been fully evaluated. Furthermore, the oral pharmacokinetics of DCU in rodent are such that the use of DCU to understand PK/PD relationships of sEH inhibitors in preclinical efficacy model is less than ideal. In this study, the limitation of orally delivered DCU nanosuspension was assessed by a surface area sensitive absorption model and pharmacokinetic modeling. It was found that dosing DCU nanosuspension did not provide the desired plasma profile needed for PK/PD investigation. Based on the model and in vivo data, a subcutaneous route of delivery of nanosuspension of DCU was evaluated and demonstrated to be appropriate for future PK/PD studies.

  13. Study of the production of $\\Lambda_b^0$ and $\\overline{B}^0$ hadrons in $pp$ collisions and first measurement of the $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ branching fraction

    Aaij, R.; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Buchanan, Emma; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fohl, Klaus; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Ninci, Daniele; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zucchelli, Stefano


    The product of the $\\Lambda_b^0$ ($\\overline{B}^0$) differential production cross-section and the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ ($\\overline{B}^0\\rightarrow J/\\psi\\overline{K}^*(892)^0$) is measured as a function of the beauty hadron transverse momentum, $p_{\\rm T}$, and rapidity, $y$. The kinematic region of the measurements is $p_{\\rm T}<20~{\\rm GeV}/c$ and $2.0 < y < 4.5$. The measurements use a data sample corresponding to an integrated luminosity of $3~{\\rm fb}^{-1}$ collected by the LHCb detector in $pp$ collisions at centre-of-mass energies $\\sqrt{s}=7~{\\rm TeV}$ in 2011 and $\\sqrt{s}=8~{\\rm TeV}$ in 2012. Based on previous LHCb results of the fragmentation fraction ratio, $f_{\\Lambda_B^0}/f_d$, the branching fraction of the decay $\\Lambda_b^0\\rightarrow J/\\psi pK^-$ is measured to be \\begin{equation*} \\mathcal{B}(\\Lambda_b^0\\rightarrow J/\\psi pK^-)= (3.04\\pm0.04\\pm0.06\\pm0.33^{+0.43}_{-0.27})\\times10^{-4}, \\end{equation*} where the first uncertainty is st...

  14. Correlative analysis on personality characteristics and mental health of PLA the eighth peacekeeping troops stationed in Wau Sudan%赴苏丹瓦乌维和官兵人格特征和心理健康状况相关分析

    陈合钦; 王玲; 吴青华; 唐时荣; 吕爱娟; 胡百奇; 刘学周


    目的 分析中国第八批赴苏丹瓦乌地区,运输、医疗两个分队的维和官兵初期心理健康状况及人格特征的相关性,为针对性的心理教育提供依据.方法 使用症状自评量表(SCL-90)和艾森克个性问卷(EPQ)对运输分队和医疗分队共160名维和官兵进行集中测试.结果 (1)维和官兵在执行任务初期SCL-90除躯体化因子高于军人常模(P<0.01)外,其他各因子分均低于中国军人常模(P<0.01).(2)维和官兵心理健康状况与人格特征相关.EPQ内外向维度与SCL-90强迫、抑郁、恐怖、偏执、精神病性因子呈负相关(P<0.05,P<0.01),与人际关系、焦虑、敌对因子呈正相关(P<0.05,P<0.01);神经质维度与SCL-90各因子呈正相关(P<0.05,P<0.01),除躯体化、强迫因子外,精神质维度与SCL-90其余各因子呈正相关(P<0.05,P<0.01);掩饰性维度与抑郁、焦虑因子呈正相关(P<0.05,P<0.01).(3)运输分队的强迫、抑郁、焦虑及恐怖因子分显著高于医疗分队(P<0.05).结论 赴苏丹瓦乌地区初期,维和官兵心理健康状况良好;维和官兵心理健康状况与自身的人格特征相关;医疗分队相对运输分队心理健康状况要好.%Objective To analyze the correlation of mental health and personality characteristics of transport and medical units of Chinese peace-keepers stationed in Wau Sudan in the initialstage and provide the basis for the targeted psychological education. Methods Using the symptom checklist (SCL-90) and the Eysenck Personality Questionnaire (EPQ) for testing a total of 160 peacekeeping soldiers in the transport and medical units. Results ( 1) Of the peacekeepers on duty, in addition to the initial SCL-90 somatization factor is higher than the military norm ( P < 0.01) , the other factors were lower than the norm of Chinese soldiers (P < 0. 01 ) . (2) Peacekeepers' mental health was related to personality traits. Internal and external dimensions of

  15. First observation of γγ-> p$\\bar{p}$K+K- and search for exotic baryons in pK systems

    Shen, C. P.; Yuan, C. Z.; Adachi, I.; Aihara, H.; Asner, David M.; Aulchenko, V.; Aushev, T.; Ayad, R.; Babu, V.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Behera, P.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bonvicini, Giovanni; Bozek, A.; Bracko, Marko; Browder, Thomas E.; Cervenkov, D.; Chang, P.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Chistov, R.; Cho, K.; Chobanova, V.; Choi, S-K.; Choi, Y.; Cinabro, David A.; Dalseno, J.; Danilov, M.; Dash, N.; Dolezal, Z.; Drasal, Z.; Dutta, D.; Eidelman, S.; Fang, Wenzheng; Fast, James E.; Ferber, T.; Fulsom, Bryan G.; Gaur, Vipin; Gabyshev, N.; Garmash, A.; Gillard, R.; Glattauer, R.; Goldenzweig, P.; Grzymkowska, O.; Haba, J.; Hayasaka, K.; Hayashii, H.; Hou, W. S.; Iijima, T.; Inami, K.; Inguglia, G.; Ishikawa, A.; Itoh, R.; Iwasaki, Y.; Jaegle, Igal; Jeon, H. B.; Joo, K. K.; Julius, T.; Kang, K. H.; Kato, E.; Kiesling, C.; Kim, D. Y.; Kim, J. B.; Kim, K. T.; Kim, S. H.; Kim, Y. J.; Kodys, P.; Korpar, S.; Kotchetkov, Dmitri V.; Krizan, P.; Krokovny, Pavel; Kuzmin, A.; Kwon, Y. J.; Lange, J. S.; Li, C. H.; Li, H.; Li, Y.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matsuda, T.; Matvienko, D.; Miyabayashi, K.; Miyata, H.; Mizuk, R.; Mohanty, G. B.; Mohanty, Subhashree; Moll, A.; Moon, H K.; Mussa, R.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K.; Natkaniec, Z.; Nishida, S.; Ogawa, S.; Olsen, Stephen L.; Ostrowicz, W.; Pakhlov, P.; Pakhlova, G.; Pal, Bilas K.; Park, C. S.; Park, H.; Pesantez, L.; Pestotnik, R.; Petric, M.; Piilonen, Leo E.; Pulvermacher, C.; Rauch, J.; Ritter, M.; Sakai, Y.; Sandilya, Saurabh; Santelj, L.; Sanuki, T.; Savinov, Vladimir; Schluter, T.; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Semmler, D.; Senyo, K.; Seong, Ilsoo; Sevior, ME; Shibata, T. A.; Shiu, Jing-Ge; Shwartz, B.; Simon, F.; Sokolov, A.; Solovieva, E.; Stanic, S.; Staric, M.; Strube, Jan F.; Stypula, J.; Sumihama, M.; Sumiyoshi, T.; Takizawa, M.; Tamponi, Umberto; Tanida, K.; Tenchini, F.; Trabelsi, K.; Uchida, M.; Uehara, S.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Wang, C. H.; Wang, M. Z.; Wang, P.; Watanabe, M.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamaoka, Jared AK; Yelton, John; Yook, Youngmin; Yusa, Y.; Zhang, C. C.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.


    The process γγ→p$\\bar{p}$K+K- and its intermediate processes are measured for the first time using a 980 fb-1 data sample collected with the Belle detector at the KEKB asymmetric-energy e+e- collider. The production of p$\\bar{p}$K+K- and a Λ(1520)0 ($\\bar{Λ}$(1520)0) signal in the pK- ($\\bar{p}$K+) invariant mass spectrum are clearly observed. However, no evidence for an exotic baryon near 1540 MeV/c2, denoted as Θ(1540)0 ($\\bar{Θ}$(1540)0) or Θ(1540)++ (Θ(1540)--), is seen in the pK- ($\\bar{p}$K+) or pK+ ($\\bar{p}$K-) invariant mass spectra. Cross sections for γγ→p$\\bar{p}$K+K-, Λ(1520)0$\\bar{p}$K++c.c. and the products σ(γγ→Θ(1540)0$\\bar{p}$K++c.c.)B(Θ(1540)0→pK-) and σ(γγ→Θ(1540)++$\\bar{p}$K-+c.c.)B(Θ(1540)++→pK+) are measured. We also determine upper limits on the products of the χc0 and χc2 two-photon decay widths and their branching fractions to p$\\bar{p}$K+K- at the 90% credibility level.

  16. Biochemical and Spectroscopic Characterization of the Non-Heme Fe(II)- and 2-Oxoglutarate-Dependent Ethylene-Forming Enzyme from Pseudomonas syringae pv. phaseolicola PK2.

    Martinez, Salette; Hausinger, Robert P


    The ethylene-forming enzyme (EFE) from Pseudomonas syringae pv. phaseolicola PK2 is a member of the mononuclear non-heme Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenase superfamily. This enzyme is reported to simultaneously catalyze the conversion of 2OG into ethylene and three CO2 molecules and the Cδ hydroxylation of l-arginine (l-Arg) while oxidatively decarboxylating 2OG to form succinate and carbon dioxide. A new plasmid construct for expression in recombinant Escherichia coli cells allowed for the purification of large amounts of EFE with activity greater than that previously recorded. A variety of assays were used to quantify and confirm the identity of the proposed products, including the first experimental demonstration of l-Δ(1)-pyrroline-5-carboxylate and guanidine derived from 5-hydroxyarginine. Selected l-Arg derivatives could induce ethylene formation without undergoing hydroxylation, demonstrating that ethylene production and l-Arg hydroxylation activities are not linked. Similarly, EFE utilizes the alternative α-keto acid 2-oxoadipate as a cosubstrate (forming glutaric acid) during the hydroxylation of l-Arg, with this reaction unlinked from ethylene formation. Kinetic constants were determined for both ethylene formation and l-Arg hydroxylation reactions. Anaerobic UV-visible difference spectra were used to monitor the binding of Fe(II) and substrates to the enzyme. On the basis of our results and what is generally known about EFE and Fe(II)- and 2OG-dependent oxygenases, an updated model for the reaction mechanism is presented.

  17. The result of PK-rich biological organic fertilizer on cucumber production%富磷钾矿物有机肥在黄瓜生产上的肥效研究

    占昕; 陈明智; 张仙梅; 何振全; 盖国胜; 杨玉芬


    富磷钾矿物有机肥是一种新研制的生物有机肥,本实验采用田间试验和室内分析相结合的方法,研究了施用富磷钾矿物有机肥对黄瓜土壤养分和黄瓜产量、品质的影响,研究结果如下:(1)富磷钾矿物有机肥和普通化肥处理NPK相比,磷肥利用率提高了21%,钾肥利用率提高了18%。(2)施用富磷钾矿物有机肥的黄瓜较NPK处理总酸度提高14%,维生素C含量分别提高12%。在黄瓜果实长度增加13%,黄瓜直径增加14%。(3)施用富磷钾矿物有机肥相较不施肥的CK处理增产103%,达到5%显著性差异。相对普通化肥NPK处理增产13%,相对缺素处理NP、NK分别增产30%、13%。说明施用富磷钾矿物有机肥对黄瓜有增产趋势。%PK-rich biological organic fertilizer is a new development of biological organic fertilizer, this experiment used the methods involve field trials and indoor analysis to find the PK-rich biological organic fertilizer has a great influence on cucumber soil nutrient and cucumber production, and quality of effects, the results are as follows:PK-rich biological organic fertilizer, which different to NPK test region in such accepts:(1) An utilization of P and K increase 21%,and 18%;(2) The total acidity increase 14%, and the vitamin c content increased by 12%;and 13%improve on length of cucumber fruit, 14%on diameter as well. (3) PK-rich biological organic fertilizer add up 103%of production in CK test region and which from 5%significant difference;raising the 13%of production than NPK test region, which compare to NP, NK yield is 30%and 13%respectively. The experiment shows that the PK-rich biological organic fertilizer has a beneficial influence on cucumber yield so that the production is trend to be increasing.

  18. WDR-PK-AK-018

    Hollister, R


    Method - CES SOP-HW-P556 'Field and Bulk Gamma Analysis'. Detector - High-purity germanium, 40% relative efficiency. Calibration - The detector was calibrated on February 8, 2006 using a NIST-traceable sealed source, and the calibration was verified using an independent sealed source. Count Time and Geometry - The sample was counted for 20 minutes at 72 inches from the detector. A lead collimator was used to limit the field-of-view to the region of the sample. The drum was rotated 180 degrees halfway through the count time. Date and Location of Scans - June 1,2006 in Building 235 Room 1136. Spectral Analysis Spectra were analyzed with ORTEC GammaVision software. Matrix and geometry corrections were calculated using OR TEC Isotopic software. A background spectrum was measured at the counting location. No man-made radioactivity was observed in the background. Results were determined from the sample spectra without background subtraction. Minimum detectable activities were calculated by the Nureg 4.16 method. Results - Detected Pu-238, Pu-239, Am-241 and Am-243.

  19. Clinical features of malaria and the other diseases in Chinese peace-keeping task region in Liberia%利比里亚维和任务区疟疾和其他疾病的临床特点

    孙逊; 左卉川; 安亮恩


    respiratory tract and intestinal infection and the other diseases in Chinese peace-keeping task region in Zwedru, Liberia. Methods Analyzing retrospectively the data of 39 malaria (group A) and 29 no-malaria (group B) outpatients and inpatients in the Chinese Level- Ⅱ hospital in the Liberia, which is organized by thirteenth peace-keeping medical contingent from Beijing military district. Results A total of 25 patients from group A had a fever accompany the other symptoms or not, and among them 19 ones showed positive result of rapid diagnosis test (RDT) to plasmodium. 14 patients from group A had precursory symptom such as headache, muscular soreness, lassitude or diarrhea, et al, but had no fever, among them positive RDT had two ones. All 18 negative RDT ones from group A turned to positive results after 3 days, group A included 36 falciparum malaria and 3 mixed malaria patients, and 17 ones were founded plasmodium in the thick/thin blood smear, and 5 inpatients were all ardent fever, positive RDT. Negative RDT patients at first visit were diagnosed acute upper respiratory infection, chordapsus, et al, who were given anti-infection and aim at signs' treatments. Misdiagnosis proportion was 46.2%( 18/39) at first visit. 39 malaria ones were all clinical recovery after anti-malaria treatments. A total of 29 patients from group B were negative RDT at first visit, which were diagnosed acute upper respiratory infection, amygdalitis, enteritis, et al, respectively. Their RDT to plasmodium were all negative repeatedly during next 5 days, but 3 ones among them turned to positive RDT when they felt fever again after 2 weeks. The 3 patients recovered after anti-malaria treatment. Conclusion All patients should be doubted malaria extremely when they appear fever or their respiratory tract or intestinal tract unwell in hyperendemic malaria of west Afric, but it's not suitable to be given anti-malaria cure immediately when their RDT to plasmodium are negative. It should be rechecked

  20. Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on PK/PD of telmisartan in Chinese patients with mild to moderate essential hypertension

    Pei, Qi; Yang, Liu; Tan, Hong-Yi; Liu, Shi-Kun; Liu, Yang; Huang, Lu; Li, Rong-Hui; Wan, Qian; Huang, Jie; Guo, Cheng-Xian; Zuo, Xiao-Cong; Li, Jingle; Yang, Guo-Ping


    This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood pressure) of telmisartan in Chinese patients. 58 Han Chinese patients (aged 45 - 72 years) with mild to moderate essential hypertension were included and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry, respectively. Multivariable linear analysis was used to examine the relationships between PK/PD and genetic variants. Females showed a significantly higher AUClast than males (n = 22, 4,879.48 ± 3,449.33 h×ng/mL vs. n = 36, 2,715.59 ± 2,223.77 h×ng/mL, p = 0.047). Amongst all genetic variants investigated, the patients with UGT1A1 rs4124874 AA (n = 11, 1,730.51 ± 1,325.79 h×ng/mL) had a significantly lower AUClast compared with patients with UGT1A1 rs4124874 CC+AC (n = 19 + 28, 4,177.44 ± 3,222.11 h×ng/mL and 3,810.82 ± 2,960.43 h×ng/mL, p = 0.027). None of the SNPs investigated was associated with the PD responses to telmisartan. Variation of UGT1A1 (rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value of genetic testing in precision medicine as the telmisartan dose could be adjusted based on UGT1A1 genetic variations.

  1. Enhanced PK-resistance of the Cu2+-induced recombinant prion protein treated by ADAM10%ADAM10处理增强铜离子诱导的重组朊蛋白的蛋白酶抗性

    陈操; 吕燕; 石琦; 董小平


    目的 分析ADAM10对铜离子诱导后的PrP蛋白的剪切特点.方法 常规方法表达、纯化人PrP全长蛋白(aa 23-230),利用氯化铜对纯化后的PrP蛋白进行诱导.用不同浓度的ADAM10对PrP蛋白进行处理,检测诱导后全长蛋白及剪切片段的PK抗性.结果 重组人PrP蛋白经Cu2诱导后具有部分抵抗PK消化的特点.Cu2+诱导后的PrP蛋白可被ADAM10剪切,具有剂量依赖性.ADAM10对Cu2+诱导的PrP蛋白处理后抵抗PK消化的能力明显加强.结论 ADAM10可以剪切Cu2+诱导的PrP蛋白,同时增加了处理后PrP蛋白的PK抗性.%Objective To analyze the characteristics of the ADAM10 cleavage on the Cu2+-induced recombinant prion protein.Methods Recombinant human prion protein (PrP,aa 23-230) was expressed and purified by routine methods.The purified human PrP was induced by copper chloride.Subsequently,the Cu2+-induced recombinant human PrP was treated with various concentrations of ADAM10 and its PK-resistance was assessed by PrP-specific Western Blot after incubating with various concentrations of proteinase K.Results The Cu2 +-induced purified recombinant prion protein has the characteristic of partial PK-resistance.ADAM10 can cleavage the Cu2+-induced purified recombinant prion protein,with a dosedependent manner.The PK-resistance ability of ADAM10-treated Cu2+-induced purified recombinant prion protein is higher than that of ADAM10-untreated one.Conclusions ADAM10 can cleavage the Cu2+ induced purified recombinant prion protein and enhance the PK-resistance ability of the treated prion protein.

  2. Textural and structural features, composition and formation conditions of arenaceous rocks in PK1 horizon, Pokursk suite in south-eastern Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory)

    Nedolivko, N.; Perevertailo, T.; Barkalova, A.; Dolgaya, T.


    Terrigenous deposits of the productive PK1 horizon in Pokursk suite of Pur-Tazovsk area (Yamalo-Nenets Autonomous Territory) were studied to specify the structure and identify the formation features. Complex horizon structure of sequential silt, mudrock interbedding and alternation has been identified. Littoral-marine type of sedimentation (occurring during the total marine transgression increase) by the help of genetic rock features identified during the core sampling and by the granulometry and X-ray-phase results analysis has been determined.

  3. Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD)

    Isla, Arantxazu; Canut, Andrés; Rodríguez-Gascón, Alicia; Planells del Pozo, Paloma; Beltri Orta, Paola; Salmerón-Escobar, José Ignacio; Labora, Alicia; Pedraz, José Luis


    El objetivo de este estudio es evaluar la eficacia de los tratamientos más utilizados en infecciones odontogénicas en niños y adolescentes aplicando criterios farmacocinéticos/farmacodinámicos (PK/PD). Se han simulado las curvas de concentración plasmática libre-tiempo a partir de parámetros farmacocinéticos medios de amoxicilina, amoxicilina-ácido clavulánico, cefuroxima axetilo, espiramicina, clindamicina, azitromicina y metronidazol. Para los antibióticos con actividad dependiente del tiem...

  4. International Organization and Peacekeeping. Teacher's Guide.

    Freeman, Robert E.

    The teaching guide for secondary students focuses on the structure, authority, and decision making procedures of international organizations and their ability to keep peace. Students participate in an exercise for predicting how present organizations can handle peace-threatening situations and how they can be designed to improve their peacekeeping…

  5. the consequences of humanitarian peacekeeping in africa


    continent was plagued by 16 armed conflicts in 1999 alone (Docking 2001:1). Seven of these armed ... since SA should also protect itself from the spill-over effects of regional conflicts. ..... remembered for the children conceived and left behind.

  6. Faction Liaison Teams: A Peacekeeping Multiplier


    Bihac Capt (UK) Driver (UK) Local Interpreter VRS/ 1st Corps/ Banja Luka Capt (UK) Driver (UK) Local Interpreter VRS/ 2nd Corps/Prijedor Capt (UK) Driver...DLO to the 1st Krajina Corps in Banja Luka . 67 Both of these, frequency and reputation, are regarded as key ingredients by Robert Axelrod in his

  7. Peace-keeping Forces: YA War Books.

    Crowe Chris


    Argues that good young adult books about war can help teenagers appreciate the blessings of peace and the horrors of war, and perhaps may inspire them to do what they can to preserve peace. Describes briefly 71 young adult war books worth reading. (SR)

  8. High-strength concrete for Peacekeeper facilities

    Saucier, K. L.


    An investigation is described which was conducted to determine the processes and techniques required to produce portland-cement concrete with a compressive strength of 15,000 psi or greater using conventional concreting methods and equipment, and to develop physical property data on the mixtures. It was permitted that special materials and admixtures be used, but a requirement was set that the aggregates and cements be selected from those available in the Cheyenne, Wyoming, area. Results indicated that it is feasible to achieve the 15,000-psi compressive strengths but that workability may decrease over a 2-hour period, and this latter development should be studied under job conditions. It is recommended that: (1) all materials and procedures to be used on a specific project be tested in the laboratory for basic property information, and (2) selected mixtures be tested in the field under expected environmental conditions prior to actual job use.

  9. Military Implications of United Nations Peacekeeping Operations


    maintenance of law and order, protecting the delivery of humanitarian assistance, the denial of an air space and the guarantee of rights of passage . In...involve the coordinated presence of warships and combat aircraft in the disputed region. Operations to guarantee rights of passage may be mounted to ensure

  10. Prostředí pro monitorování přístupu ke zdrojům v síti s využitím technologie OnePK

    Kollát, Samuel


    V tejto práci je popísaný návrh, architektúra a implementácia systému, ktorý slúži k monitorovaniu služieb a súborov v počítačovej sieti. Monitorovací systém je založený na princípu softvérovo definovaných sietí. Prvá časť práce sa zameriava na popis princípov SDN a platformy OnePK, ktorá je využitá na návrh monitorovacieho systému. Samotné jadro práce sa zameriava na využitie platformy OnePK, návrh, dekompozíciu a výslednú implementáciu spojenú s testovaním monitorovacieho systému. This r...

  11. 非致命性武器在联合国维和警察防暴行动中的应用及发展趋势%The Application of Non -Lethal Weapons in the Anti -riot Operations of Peacekeeping Police and It' s Developmental Trend

    钱晋军; 张太果


    With the rapid development oi modem teennology, ul~ ~u more important. This paper summarizes the related concepts of non - lethal weapons and peaeekeeping anti - riot op- erations, sums up the application status of the non - lethal weapons in peacekeeping anti - riot operations and forecasts the future development trend of non - lethal weapons. It points out that riot police should utilize the incapacitating weapons which will make the combatants lose their fighting capacities.%随着现代科学技术的迅猛发展,非致命性武器在联合国维和防暴行动中的作用越来越重要。鉴于非致命性武器在维和防暴行动中的应用现状,展望了非致命性武器在未来的发展趋势,并提出在今后的维和防暴行动中应着重使用使人员丧失战斗力的失能性武器。

  12. 赴利比里亚维和部队轮换期间埃博拉防控的实践与思考%Practice and Reflection on Preventing and Controlling the Ebolavirus for Chinese Peacekeeping Forces to Liberia during Cyclic Permutation Period

    朱焱华; 邴峰; 琴明贤; 鄢雷


    本文介绍了利比里亚地区埃博拉疫情和第16和第17批赴利比里亚维和部队轮换期间埃博拉疫情防控的主要措施,提出了坚持联动及时的疫情应对、明确层次分明的防控责任、理顺军地协同的工作关系、严格轮换期间的生活管理、加强全程伴随的心理保障等方面的体会思考.%Ebola epidemic situation in Liberia region and main prevention and control measures for the ebolavirus in the 16 th and 17 th detachments of Chinese peacekeeping forces to Liberia during cyclic permutation period were intro-duced in this paper. Experiences have been summarized in this study, such as keeping combined action timely for epi-demic outbreak, clarifying the responsibilities of prevention and control, coordinating the working relationship between the military and the local government, strictly managing the life regulation during cyclic permutation period and enhancing the psychological security during the whole mission.

  13. Comparative Evaluation of the Translocator Protein Radioligands {sup 11}C-DPA-713, {sup 18}F-DPA- 714, and {sup 11}C-PK11195 in a Rat Model of Acute Neuro-inflammation

    Chauveau, F.; Van Camp, N.; Dolle, F.; Kuhnast, B.; Hinnen, F.; Damont, A.; Boutin, H.; Tavitian, B. [CEA, DSV, I2BM, LIME, Orsay (France); Chauveau, F.; Van Camp, N.; Boutin, H; Tavitian, B. [INSERM, U803, Orsay (France); Chauveau, F. [CREATIS-LRMN, CNRS, UMR 5220, and INSERM, U630, Bron (France); Boutin, H. [Faculty of Life Sciences, AV Hill Building, University of Manchester, Manchester (GB); James, M. [Brain and Mind Research Institute, University of Sydney, Sydney, New South Wales (Australia); Kassiou, M. [Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New SouthWales (Australia); Kassiou, M. [School of Chemistry, University of Sydney, Sydney, New SouthWales (Australia)


    Overexpression of the translocator protein, TSPO (18 kDa), formerly known as the peripheral benzodiazepine receptor, is a hallmark of activation of cells of monocytic lineage (micro-glia and macrophages) during neuro-inflammation. Radiolabeling of TSPO ligands enables the detection of neuro-inflammatory lesions by PET. Two new radioligands, {sup 11}C-labeled N, N-diethyl-2-[2-(4- methoxy-phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl] acetamide (DPA-713) and {sup 18}F-labeled N, N-diethyl-2-(2-(4-(2- fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl) acetamide (DPA-714), both belonging to the pyrazolopyrimidine class, were compared in vivo and in vitro using a rodent model of neuro-inflammation. Methods: {sup 11}C-DPA-713 and {sup 18}F-DPA-714, as well as the classic radioligand {sup 11}C-labeled (R)-N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide (PK11195), were used in the same rat model, in which intra-striatal injection of (R, S)-a-amino-3-hydroxy-5-methyl-4-isoxazolopropionique gave rise to a strong neuro-inflammatory response. Comparative endpoints included in vitro autoradiography and in vivo imaging on a dedicated small-animal PET scanner under identical conditions. Results: {sup 11}C-DPA-713 and {sup 18}F-DPA-714 could specifically localize the neuro-inflammatory site with a similar signal-to-noise ratio in vitro. In vivo, {sup 18}F-DPA-714 performed better than {sup 11}C-DPA-713 and {sup 11}C-PK11195, with the highest ratio of ipsilateral to contralateral uptake and the highest binding potential. Conclusion: {sup 18}F-DPA-714 appears to be an attractive alternative to {sup 11}C-PK11195 because of its increased bioavailability in brain tissue and its reduced nonspecific binding. Moreover, its labeling with {sup 18}F, the preferred PET isotope for radiopharmaceutical chemistry, favors its dissemination and wide clinical use. {sup 18}F-DPA-714 will be further evaluated in longitudinal studies of neuro

  14. Biodistribution of the radionuclides (18)F-FDG, (11)C-methionine, (11)C-PK11195, and (68)Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    Afzelius, Pia Maria Tullia; Nielsen, Ole L; Alstrup, Aage Ko


    with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with (18)F-FDG, (11)C-methionine, (11)C-PK11195 and (68)Ga......-methionine and particularly (11)C-PK11195 and (68)Ga-citrate accumulated to a lesser extent in infectious foci. (18)F-FDG-uptake was seen in the areas of inflammatory cells and to a much lesser extent in reparative infiltration surrounding necrotic regions....

  15. Estudio para la redacción de un proyecto básico de acondicionamiento de la carretera CV-941 entre los P.K. 2+000 y 7+712, entre los municipios de San Miguel de Salinas y Dehesa de Campoamor (Alicante). Diseño geométrico y del firme.


    [EN] The purpose of this study is the analysis of the problems that exists in the CV-941 road between PK 2+000 and PK 7+712, in order to propose an alternative that, according to the rules and several criteria to meet comfort and driver expectations, resolve any problems identified. This will make it possible to improve the safety and comfort of road users. To do this, there has been an analysis of existing path, checking compliance with criteria and limitations imposed by the ¿Instrucció...

  16. Effect analysis on drug prevention and comprehensive prevention and control for malaria of peacekeeping forces in Nan Sudan%南苏丹维和部队疟疾药物预防及综合防制效果分析

    付留杰; 朱涛; 倪志杨; 余黎明; 岳荣喜; 何伟华


    目的 分析南苏丹维和部队疟疾药物预防及综合防制效果.方法 采取综合防制措施,制定三种药物预防方案,普查疟原虫感染.结果 三次普查疟原虫感染率逐渐降低,分别为9.2%、6.2%、4.8%.采取同样的综合防制措施,科泰复预防效果好于科泰新,科泰复与甲氟喹预防效果无差异.甲氟喹精神系统症状比科泰复明显,科泰复消化系统症状突出.结论 综合防制措施和药物相结合预防疟疾,效果明显.%Objective To analyze the effects of drug prevention and comprehensive prevention and control for malaria of peacekeeping forces in Nan Sudan.Methods Plasmodium infection was investigated after taking comprehensive prevention and control measures.3 drug programs were formulated to prevent malaria.Results The infection rate of plasmodium decreased gradually,which were 9.2%,6.2%,4.8% respectively in three times investigation.Under the same comprehensive prevention and control measures,the preventive effects of Duo-cotecxin were better than cotecxin,but there was no difference between the Duo-cotecxin and Mefloquine.The psychiatric symptoms of Mefloquine was more serious than that of Duo-cotecxin,while the digestive system symptoms were the main side effect of Duo-cotecxin.Conclusions Comprehensive prevention measures combined with drugs can prevent malaria and the effects were obvious.

  17. Pharmacokinetics and pharmacodynamics of sulfamethoxazole and trimethoprim in swimming crabs (Portunus trituberculatus) and in vitro antibacterial activity against Vibrio: PK/PD of SMZ-TMP in crabs and antibacterial activity against Vibrio.

    Fu, Guihong; Peng, Jiahong; Wang, Yuan; Zhao, Shu; Fang, Wenhong; Hu, Kun; Shen, Jinyu; Yao, Jiayun


    Serious bacterial pathogens have recently become a major cause of massive mortality in swimming crabs (Portunus trituberculatus). In this study, the antibacterial activity against Vibrio and the pharmacokinetics (PK) of sulfamethoxazole (SMZ)-trimethoprim (TMP) in crabs were estimated to explore the pharmacokinetics/pharmacodynamics (PK/PD) properties of the SMZ-TMP combination. The in vitro bacteriostatic activity and the anti-Vibrio infection activity of the SMZ-TMP combination at various ratios in crabs were studied. A degree of synergism was observed in the SMZ-TMP combination at ratios ranging from 50:1 to 1:5. The results showed that the MIC50 and MIC90 values for different SMZ-TMP combinations were in the ranges of 0.62-5 and 0.62-10μg/mL, respectively. The distribution of the MIC values of the SMZ-TMP combination at ratios of 1:1 and 5:1 were 0.31-5 and 0.31-10μg/mL, respectively. Crabs were then fed the SMZ-TMP combination (at ratios of 5:1 and 1:1) six successive times and then challenged with Vibrio parahaemolyticus at 1×10(5), 1×10(6), and 5×10(6) colony forming units (cfu) per crab. The results showed that the number of surviving crabs administered SMZ-TMP at a ratio of 1:1 was greater than that of the crabs given SMZ-TMP at a ratio of 5:1. In addition, the tissue distribution and absorption of SMZ-TMP (ratios of 5:1 and 1:1) in crabs were studied through high-performance liquid chromatography (HPLC). In the crabs fed SMZ-TMP at a ratio of 5:1, the CmaxSMZ/TMP values in the hemolymph, hepatopancreas, muscle and gill were 104:1. 0.57:1, 19:1 and 6:1, respectively. In contrast, the corresponding CmaxSMZ/TMP values in these tissues in the crabs fed SMZ-TMP at a ratio of 1:1 were 34:1, 0.14:1, 4:1 and 3:1, respectively. The results showed that TMP was better absorbed and eliminated in the crabs fed SMZ-TMP at a ratio of 1:1 than in the crabs fed this combination at a ratio of 5:1. In addition, TMP was absorbed and eliminated more rapidly in the

  18. Continuous Passaging of a Recombinant C-Strain Virus in PK-15 Cells Selects Culture-Adapted Variants that Showed Enhanced Replication but Failed to Induce Fever in Rabbits.

    Tong, Chao; Chen, Ning; Liao, Xun; Yuan, Xuemei; Sun, Mengjiao; Li, Xiaoliang; Fang, Weihuan


    Classical swine fever virus (CSFV) is the etiologic agent of classical swine fever, a highly contagious disease that causes significant economic losses to the swine industry. The lapinized C-strain, a widely used vaccine strain against CSFV, has low growth efficiency in cell culture, which limits the productivity in the vaccine industry. In this study, a recombinant virus derived from C-strain was constructed and subjected to continuous passaging in PK-15 cells with the goal of acquiring a high progeny virus yield. A cell-adapted virus variant, RecCpp80, had nearly 1,000-fold higher titer than its parent C-strain but lost the ability to induce fever in rabbits. Sequence analysis of cell-adapted RecC variants indicated that at least six nucleotide changes were fixed in RecCpp80. Further adaption of RecCpp80 variant in swine testicle cells led to a higher virus yield without additional mutations. Introduction of each of these residues into the wild-type RecC backbone showed that one mutation, M979R (T3310G), located in the C-terminal region of E2 might be closely related to the cell-adapted phenotype. Rabbit inoculation revealed that RecCpp80+10 failed to induce fever in rabbits, whereas RecCpp40+10 caused a fever response similar to the commercial C-strain vaccine. In conclusion, the C-strain can be adapted to cell culture by introducing specific mutations in its E2 protein. The mutations in RecCpp80 that led to the loss of fever response in rabbits require further investigation. Continuous passaging of the C-strain-based recombinant viruses in PK-15 cells could enhance its in vitro adaption. The non-synonymous mutations at 3310 and 3531 might play major roles in the enhanced capacity of general virus reproduction. Such findings may help design a modified C-strain for improved productivity of commercial vaccines at reduced production cost.

  19. Study on the relationship between pharmacokinetics and pharmacodynamics for statins in hyperlipidemia model in rats%他汀类药物在高脂血症大鼠体内的PK-PD关系研究

    李静远; 蔡家利; 戴仁科; 谢水林; 邓继锋; 卢沛枫; 李认书; 孙鹤; 刘延淮


    AIM: To explore the relationship between exposure level (such as pharmacokinet-ics parameters) and pharmacodynamics for statins in hyperlipidemia model in rats. METHODS; The hyper- lipidemia rat model was established with the method of diet-induced, and the rats were given different does of statins to treat. The pharmacokinetics and pharmacodynamics parameters were determined, and the value of PK/PD were calculated, and their correlations were analyzed. RESULTS: TG-AUC showed a good linear relationship at the range of 0-10. 96 folds, Y=0. 01036X-7. 6445 (γ = 0. 9599), theintermediate data such as CHOL-AUC, LDL-C-AUC, HDL-C-AUC were on the low side, which resulted large deviation, so there was an extremely weak linear correlation in these groups. CONCLUSION: There was a good linear relationship between TG and AUC in the range of AUC (0 - 10.96 folds), it could be efficaciously used to predicted the pharmacodynamics upon the related datas for AUC.%目的:探讨他汀类药物在高脂血症大鼠体内暴露水平(药代动力学参数AUC)与药效之间的关系.方法:建立大鼠高脂血症模型,给予不同剂量的他汀类药物干预治疗,进行药代动力学和药效学测定,计算药代动力学/药效学(PK/PD)值,并进行相关分析.结果:TG-AUC在药代动力学(AUC)变化范围内(0~10.96倍)线性关系良好,Y=0.01036X-7.6445(γ=0.9599).胆固醇(CHOL)-AUC、低密度脂蛋白胆固醇(LDL-C)-AUC、高密度脂蛋白胆固醇(HDL-C)-AUC由于中间数据偏低,与预测样本数据偏差太大,线性关系不明显.结论:TG-AUC在药代动力学(AUC)变化范围内(0~10.96倍)线性关系良好,可以在知道药代动力学的相关数据基础上对药效进行预测.

  20. Pharmacokinetics and pharmacodynamics in HIV prevention; current status and future directions: a summary of the DAIDS and BMGF sponsored think tank on pharmacokinetics (PK)/pharmacodynamics (PD) in HIV prevention.

    Romano, Joseph; Kashuba, Angela; Becker, Stephen; Cummins, James; Turpin, Jim; Veronese, Fulvia


    Thirty years after its beginning, the HIV/AIDS epidemic is still raging around the world. According to UNAIDS, in 2011 alone 1.7M deaths were attributable to AIDS, and 2.5M people were newly infected by the virus. Despite the success in treating HIV-infected people with potent antiretroviral drugs, preventing HIV infection is the key to ending the epidemic. Recently, the efficacy of topical and systemic antiviral chemoprophylaxis (i.e., preexposure prophylaxis or "PrEP"), using the same drugs used for HIV treatment, has been demonstrated in a number of clinical trials. However, results from other trials have been inconsistent, especially those evaluating PrEP in women. These inconsistencies may result from our incomplete understanding of pharmacokinetics (PK)/pharmacodynamics (PD) at the mucosal sites of sexual transmission: the male and female gastrointestinal and reproductive tracts. The drug concentrations used in these trials were derived from those used for treatment; however, we still do not know the relationship between the therapeutic and the preventive dose. This article presents the first comprehensive review of the available data in the HIV pharmacology field from animal models to human studies, and outlines gaps, challenges, and future directions. Addressing these pharmacological gaps and challenges will be critical in selecting and advancing future PrEP candidates and strategies with the greatest impact on the HIV epidemic.

  1. Protective effect and mechanism of action of saponins isolated from the seeds of gac (Momordica cochinchinensis Spreng.) against cisplatin-induced damage in LLC-PK1 kidney cells.

    Jung, Kiwon; Lee, Dahae; Yu, Jae Sik; Namgung, Hojin; Kang, Ki Sung; Kim, Ki Hyun


    This study was performed to investigate the renoprotective effect and mechanism of Momordicae Semen, gac seeds, against the cisplatin-induced damage in LLC-PK1 kidney cells. In order to identify the active components, three major saponins were isolated from extract of the gac seed, gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (1), quillaic acid 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (2), and momordica saponin I (3). Compounds 1 and 2 ameliorated cisplatin-induced nephrotoxicity up to 80% of the control value at both 5 and 25μM. Phosphorylation of MAPKs was decreased along cisplatin treatment after treatment with compounds 1 and 2. These results show that blocking the MAPKs signaling cascade plays a critical role in mediating the renoprotective effect of Momordicae Semen extract and compounds 1 and 2. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Application of PK/PD parameters in selection of antibiotic regimes for patients with multi-drug resistant bacterial infection%PK/PD 在多重耐药菌感染抗菌药物治疗方案优化中的应用

    李昕; 张菁; 施毅


    抗菌药物的广泛应用使细菌耐药问题日益严重,多重耐药菌感染已成为重症感染者主要死亡原因之一。将药物在体内的药代动力学(Pharmacokinetics,PK)参数与体外药效学(Pharmacodynamics,PD)参数结合起来的 PK/PD 在提高抗菌药物疗效、阻断细菌耐药性产生等方面均具有重要意义。本文根据抗菌药物的 PK/PD 特点,就其在多重耐药菌感染的药物选择和应用等方面作一综述。%With the wide use of antibiotics,the problems of drug-resistance are increasing seriously.Multi-drug resistant bacteria have become one of the major causes of death in patients with severe infections.The PK/PD parameters that combine pharmacokinetics parameters (PK ) in vivo with pharmacodynamic parameters (PD)in vitro play an important role in improving antimicrobial efficacy and suppressing antimicrobial resistance.This article reviews the selection of antibiotic regime based on the characteristics of PK/PD parameters and its application for patients with multidrug resistant bacterial infections.

  3. Insulin-mediated oxidative stress and DNA damage in LLC-PK1 pig kidney cell line, female rat primary kidney cells, and male ZDF rat kidneys in vivo.

    Othman, Eman Maher; Kreissl, Michael C; Kaiser, Franz R; Arias-Loza, Paula-Anahi; Stopper, Helga


    Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.

  4. Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells.

    Rasmussen, Rune Nørgaard; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd


    The aim of the present study was to investigate if basic GABA-mimetics interact with the taurine transporter (TauT, Slc6a6), and to find a suitable cell based model that is robust towards extracellular changes in osmolality during uptake studies. Taurine uptake was measured in human Caco-2 cells, porcine LLC-PK1 cells, and rat SKPT cells using radiolabelled taurine. Hyperosmotic conditions were obtained by incubation with raffinose (final osmolality of 500mOsm) for 24h prior to the uptake experiments. Expression of the taurine transporter, TauT, was investigated at the mRNA level by real-time PCR. Uptake of the GABA-mimetics gaboxadol and vigabatrin was investigated in SKPT cells, and quantified by liquid scintillation or HPLC-MS/MS analysis, respectively. The uptake rate of [(3)H]-taurine was Na(+) and Cl(-) and concentration dependent with taurine with an apparent Vmax of 6.3±1.6pmolcm(-2)min(-1) and a Km of 24.9±15.0μM. β-alanine, nipecotic acid, gaboxadol, GABA, vigabatrin, δ-ALA and guvacine inhibited the taurine uptake rate in a concentration dependent manner. The order of affinity for TauT was β-alanine>GABA>nipecotic acid>guvacine>δ-ALA>vigabatrin>gaboxadol with IC50-values of 0.04, 1.07, 2.02, 4.19, 4.94, 31.4 and 39.9mM, respectively. In conclusion, GABA mimetics inhibited taurine uptake in hyperosmotic rat renal SKPT cells. SKPT cells, which seem to be a useful model for investigating taurine transport in the short-term presence of high concentrations of osmolytes. Furthermore, analogues of β-alanine appear to have higher affinities for TauT than GABA-analogues.

  5. Troglitazone induced cytosolic acidification via extracellular signal-response kinase activation and mitochondrial depolarization: complex I proton pumping regulates ammoniagenesis in proximal tubule-like LLC-PK1 cells.

    Oliver, Robert; Friday, Ellen; Turturro, Francesco; Welbourne, Tomas


    To determined the mechanism(s) through which troglitazone induces cytosolic acidification and glutamine-dependent ammoniagenesis in pig kidney derived LLC-PK1 cells. Acute experiments measured acid extrusion, acid production and simultaneous Extracellular Signal-Regulated Kinase activation. TRO-enhanced acid production was correlated with mitochondrial membrane potential and rotenone and 5-(N-ethyl-N-isopropyl) amiloride, were employed to test specifically the role of Complex I proton pumping. Chronic experiments correlated inhibitors of Complex I with prevention of TRO-increased ammoniagenesis and affects on glutamine metabolism. Exposure to TRO acutely activated Extracellular Signal-Regulated Kinase in a dose dependent manner associated with a fall in spontaneous cytosolic pH. Cytosolic acidosis was associated with both an increase in acid production and inhibition of sodium/hydrogen ion exchanger -mediated acid extrusion. Preventing TRO-induced Extracellular Signal-Regulated Kinase activation with Mitogen Activated Protein Kinase Kinase inhibitors blocked the increase in acid production, restored sodium/hydrogen ion exchanger-activity and prevented cytosolic acidification. Mechanistically, increased acid production was associated with a rapid mitochondrial depolarization and Complex I proton pumping. Blocking Extracellular Signal-Regulated Kinase activation prevented both the fall in Psim and the increased acid production suggesting that the former underlies the accelerated mitochondrial 'acid production'. Mitochondrial Complex I inhibitors EIPA and rotenone prevented increased acid production despite Extracellular Response Kinase activation and reduced sodium/hydrogen ion activity. Inhibition of Complex I prevented TRO's effects on glutamine metabolism. TRO induces cellular acidosis through Extracellular Signal-Regulated Kinase activation-associated acid production and impaired acid extrusion. Acutely, increased acid production reflects mitochondrial Complex I

  6. Expression and Antiviral Effects of Sus Scrofa Mx1 and Bos taurus Mx1 on PRV%猪Mx1和牛Mx1蛋白在PK-15细胞中的表达及其对伪狂犬病病毒的抑制

    王鹏; 郑兆鑫; 刘明秋


    目的:研究猪Mx1和牛Mx1蛋白在PK-15细胞中的表达并检测其是否对伪狂犬病病毒(PRV)具有抑制作用.方法:从IBRS-2细胞和MDBK细胞中分别调取猪Mx1和牛Mx1基因,并克隆到pcDNA3.1/myc-His(-)B,构建得到真核重组表达质粒,以脂质体转染的方法将其分别导入到PK-15细胞,从mRNA水平和蛋白质水平鉴定重组质粒在细胞内的表达情况,然后用细胞毒性试剂盒检测这两种蛋白是否对PK-15细胞具有毒性.之后,通过荧光定量PCR检测猪Mx1和牛Mx1在攻毒后不同时间、不同攻毒剂量的条件下对PRV的抑制情况,并观察100TCID5o病毒攻击细胞72h后的病变程度.结果:成功克隆了猪Mx1和牛Mx1基因,经mRNA水平和蛋白质水平证实,两种重组质粒在PK-15细胞内能够正常表达.从荧光定量PCR和细胞病变的角度来看,细胞内表达的Mx1蛋白对PRV具有显著性的抑制(P <0.001).结论:猪Mx1和牛Mx1基因在PK-15细胞中表达的Mx1蛋白能够抑制PRV在胞内的复制.

  7. 轻装出行UMPC大PK




  8. Respostas do feijoeiro à aplicação de diversos tipos de matéria orgânica não decomposta, na presença de adubações minerais com P, PK, NPou NPK Responses of dry beans to applications of some undecomposed organic materials in the presence of mineral fertilizers containing, P, PK, NP or NPK

    Shiro Miyasaka


    Full Text Available Experiências conduzidas em Campinas (solo Latosol Roxo e Pindorama (solo Podzolizado de Lins e Marília, variação Marília, para estudar os efeitos de diversos tipos de matéria orgânica não decomposta, na presença de adubações minerais com P, PK, NP ou NPK, mostraram que, dos adubos minerais, sòmente o nitrogênio aumentou substancialmente a produção do feijoeiro. Dos adubos orgânicos comparados - ramas de soja perene, capim-gordura, fôlhas de café e serapilheira - o primeiro foi o mais eficiente. Em Campinas, as ramas de soja aumentaram a produção, tanto na ausência como na presença do nitrogênio mineral, quer aplicadas em sulcos laterais aos destinados às sementes de feijão, quer em cobertura, após a emergência das plantas. Em Pindorama, porém, só atuaram favoravelmente quando empregadas em sulcos laterais, na ausência do nitrogênio mineral.Experiments were conducted at Campinas and Pindorama, State of São Paulo, to study the effects of the indicated treatments on dry beans (Phaseolus vulgarisL. Of the mineral fertilizers, only nitrogen increased the yields in both localities. Of the organic materials - Glycine javanica, Melinis minutiflora, coffee tree leaves and forest litter - the first mentioned was the most effective. In the Campinas experiment, G. javanica induced considerable yield increases, either when side placed or top dressed in the absence or in the presence of mineral nitrogen. At Pindorama, however, it was effective only when side placed in the absence of mineral nitrogen.

  9. Efeitos sõbre a produção do feijoeiro, da aplicação de diversos tipos de matéria orgânica, não decomposta, na presença de adubação mineral com P, NP, PK Responses of dry beans to the application of several undecomposed organic materials in the presence of mineral fertilizers with P, NP and PK

    Shiro Miyasaka


    Full Text Available Numa experiência em que se estudou, na cultura do feijoeiro, o comportamento de diversos tipos de matéria orgânica, não decomposta, na presença de adubações minerais com P, NP ou PK, o nitrogênio foi o elemento que controlou a produção. Nas parcelas adubadas exclusivamente com P, os adubos orgânicos, aplicados em sulcos laterais aos destinados às sementes, aumentaram consideràvelmente a produção, crescendo os aumentos na seguinte ordem: bagaço de cana, capim-gordura, soja perene, fôlhas de cafeeiro, cascas de café e cascas de amendoim. Nas parcelas com NP, as produções foram geralmente maiores, e dos adubos orgânicos sòmente as cascas de amendoim, o capim-gordura e a dose dupla de fôlhas de café proporcionaram pequenos aumentos.Nitrogen was the element that limited the yield of dry beans. In the plots with P alone, the responses to the side-placed organic materials were very good and increased in the order: sugar cane thrash, Melinis minutiflora hay, Glycine javanica hay, coffee tree leaves, coffee fruit hulls and peanut hulls. In the NP plots, the yields were generally higher but only peanut hulls, M. minutiflora hay and the double dose of coffee tree leaves induced small increases.

  10. [Analysis on the sensitivity to beta-lactam antibiotics of respiratory-infectious isolates on the second survey on the sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007--concerning the aspect of PK/PD break points].

    Niki, Yoshihito; Kohno, Shigeru; Watanabe, Akira; Aoki, Nobuki


    Sensitivity to beta-lactam antibiotics of isolates clinically obtained from respiratory infection sites in adults on the second survey on sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007 was investigated according to the classification of the "Guideline for treatment for adult nosocomial pneumonia in 2008". Among the primary antibacterial drugs for mild (A) and moderate (B) nosocomial pneumonia in adults, beta-lactam antibiotics; ceftriaxone (CTRX), sulbactam/ampicillin (SBT/ABPC), panipenem/betamipron (PAPM/BP), tazobactam/piperacillin (TAZ/PIPC), imipenem/cilastatin (IPM/CS), meropenem (MEPM), doripenem (DRPM), biapenem (BIPM) were studied to evaluate their clinical efficacy. The covering rate was analyzed using the minimal inhibitory concentration (MIC) and break point of pharmacokinetics/pharmacodynamics (PK/PD). Consequently, the results with methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae revealed the MIC90 of all antibacterial drugs to be at low levels, while almost 100% of isolates were within the range of PK/PD break points except BIPM and SBT/ABPC to H. influenzae, and SBT/ABPC to K. pneumoniae. However, the analysis of P. aeruginosa didn't reach 100% for the covering rates of isolates, indicating that these drugs did not have a complete inhibitory action to restrict bacterial proliferation. The analysis of all 5 carbapenem drugs showed superiority to TAZ/PIPC in MIC90 while covering rates of isolates at PK/PD break points showed inferiority to TAZ/PIPC. This tendency was found to be more significant in covering the rates of isolates on the regular dose with maximal bactericidal action and on the maximum dose. This is because the maximum dose approved in Japan is as low as half that in IPM/CS and 1/3 that in MEPM in Western countries.

  11. Research progress of optimizing vancomycin individual administration with the PK/PD model%结合药代动力学/药效学模式优化儿童万古霉素个体给药方案研究进展

    邹心(综述); 罗征秀(审校)


    万古霉素是从链霉菌中分离得到的糖肽类抗生素,至今仍是治疗耐甲氧西林葡萄球菌的首选药物。万古霉素代谢个体差异显著,仅通过药物说明书和医师经验性用药,对于重症及复杂感染患儿很难使血药浓度达到目标范围(15~20 mg/L),必须借助万古霉素血药浓度监测(TDM),利用群体药代动力学/药效学(PK/PD)模式,通过贝叶斯(Bayes)反馈获得个体PK/PD参数来实施精细调控。文章从万古霉素当前临床用药指南拓展到最新研究理论,充分显示肾功能、体质量、年龄、疾病状态是影响儿童万古霉素代谢效应的主要参数;且血药浓度-时间曲线下面积/最小抑菌浓度(AUC/MIC)≥400为更佳的监测效应值。%e: Vancomycin is a glycopeptide antibiotic separated from streptomycete, having been used as the ifrst choice to treat methicillin-resistant Staphylococcus aureus infection so far. The studies show that because of the individual difference in the metabolism of vancomycin, it is dififcult to get the trough concentration of pediatric patients severely ill or complicatedly in-fected to reach the target range (15—20 mg/L). However, with the help of therapeutic drug monitoring (TDM) of vancomycin and the pharmacokinetic/pharmacodynamic parameter (PK/PD) mode, the PK/PD parameters to achieve the precise control can be acquired by using the Bayes feedback. By a stretched review from clinical medication guide of vancomycin to the latest evidence from research, this paper fully demonstrates that renal function, weight, age, and disease state are the principal parameters to impact pediatric patient’s vancomycin metabolism and that the area under the concentration-time curve divided by the minimum inhibitory concentration (AUC/MIC)≥400 is the better cut-off value to determine vancomycin efifcacy and toxicity.

  12. 基于多靶点PK-PD模型评价丹酚酸A对缺血性心衰的保护作用%Evaluation of the protective effect of salvianolic acid A on ischemic heart failure by a multi-target pharmacokinetic-pharmacodynamic model

    张雪; 王玉浩; 郑运思; 何华; 柳晓泉


    基于代谢平衡模型,建立多靶点药代动力学-药效学(PK-PD)结合模型,从整体角度评价丹酚酸A(Sal A)对缺血性心衰的保护作用.大鼠随机分为3组,分别为假手术组、缺血性心衰组和SalA给药组,结扎后立即给药,连续给药4周,分别于给药前和给药后1、2、3、4周采集血样,测定血浆中脑钠肽(BNP)、血管紧张素Ⅱ(AngⅡ)、丙二醛(MDA)、不对称二甲基精氨酸(ADMA)含量以及谷胱甘肽过氧化物酶(GSH-Px)酶活力,基于上述标志物建立代谢平衡模型,选用代谢失衡动力学参数k从整体角度量化机体状态,并以参数k的变化率作为替代药效指标建立多靶点PK-PD模型,用以考察SalA对缺血性心衰的保护作用.结果显示,SalA对各标志物均有一定的改善作用,参数k与表征心功能的指标左心室射血分数相关性良好,模型可以很好地拟合Sal A的血浆药物浓度-曲线下面积(AUC)和药物对参数k的改善程度Ⅰ之间的关系.基于代谢平衡模型建立的多靶点PK-PD模型能够很好地评估Sal A对缺血性心衰的保护作用,为多靶点中药PK-PD模型的建立提供了新的思路.

  13. Study on therapeutic effect of anti-TB drugs and regimens for tuberculosis meningitis and PK /PD of these drugs%抗结核药物及方案对结核性脑炎治疗作用及药物的药代动力学/药效学研究

    赵伟杰; 付雷; 李破; 王彬; 徐建


    Objective To determinte the concentrations of three anti -TB drugs are increased in the brain tissue of health and TB meningitis( MTB) model mice , study the pharmacokinetics/pharmacodynamics ( PK/PD) parameters of them in plasma and brain tissue using healthy and MTB model mice , evaluate the activities of these drugs respectively and combinations of them , provide information for the treatment of MTB based on their activities and parameters . Methods MTB mice model was developed through injecting H 37Rv into the tail vein of mice. After administrated RFP . Lfx. Mfx for 5 days , the plasma and brain tissue of healthy and MTB mice were gotten at different time points and the concentrations of these drugs were determined by HPLC , and then obtain the PK and PK/PD parameters.The mice were given Lfx. Mfx and other drugs usually used to therapy TB alone or combination , CFU in lungs and brain tissues were obtained after treatment for 8 weeks and these data together with the PK and PK/PD parameters were analyzed to evaluate the efficiency of treating pulmonaiy TB and MTB. Results The AUC0-24 of RFP, Lfx, Mfx were increased by 56. 0% , 148. 5% , 80. 4% , AUC0-24/MIC were 445. 0, 16. 5, 7. 4 respectively ; after treatment for 8 weeks, except PZA , Lfx that the CFU were decreased more . For MTB , every groups except Lfx were effective and INH , RHPto, RHLfx, RHMfx were more effective. Conclusions The amounts of drugs entering into the brain tissue increase while the hrain was infected by H 37Rv when compared with that of healthy mice ; RHPto, RHLfx, RHMfx are effective combinations to therapy MTB , so all of them can be choosed as therapeutic remedy for different patients.%目的 测定三种抗结核药在健康和结核性脑膜炎小鼠脑组织中的浓度,评价几种单药和联合方案抗肺结核和结核性脑膜炎的活性;评价其药代动力学/药效学(PK/PD)参数.方法 通过小鼠静脉感染H37Rv 建立结核性脑膜炎模型,健康和结核

  14. Die Checkliste PK "Professionelles ärztliches Kommunikationsverhalten" in Unterricht und Evaluation kommunikativer Fertigkeiten im Medizinstudium [Checklist "Professional Communication in Medicine" in teaching and assessing of anamnesis and communication skills in medical education

    Pucher-Matzner, Ingeborg


    Full Text Available [english] Objectives: The checklist „Professional Communication in Medicine“ serves as a tool for teaching and training medical students in communication skills, it has also been developed in order to evaluate the students’ performance at the end of their second year at the Medical University of Vienna. The checklist consists of three parts: 26 items referring to the contents of the interview according to George Engel’s ten step model of anamnesis, 10 items referring to the style of communication and 12 items deal with the relationship established. Methods: Teachers of communication skills in medicine were asked to check the list for objectivity (interrater- reliability. In a first step (learning, after they got to know how to handle the list, they were trained in applying this checklist with the help of videos – each presenting a complete anamnesis. The testing that followed looked at the items in terms of their level of consensus. Results: On the whole it can be said that a good level of consensus – in around 75 percent of all items - was reached in assessing all three parts, i.e. style of communication, contents and relationship. The highest levels of consensus were observed in part B: style of communication, the lowest in section C: relationship. Conclusion: Results have turned out satisfactorily as far as they provide consistent forms of assessment for the major part of items. However, improvements need to be made in areas dealing with question-building, psychosocial aspects but also personal development. All in all, the checklist can be seen as an essential contribution to quality assurance in medical communication, involving both, students and teachers. [german] Zielsetzungen: Die Checkliste PK „Professionelles ärztliches Kommunikationsverhalten“ ist als Unterrichtsmittel, für gezieltes Training und die Evaluation kommunikativer Fertigkeiten, im medizinischen Unterricht an der Medizinischen Universität Wien (MUW

  15. Environmental Impact Statement: Peacekeeper Missile System Deactivation and Dismantlement


    goldenrod (Solidago sp.), and death camus (Zygadenus elegans). Shrub species occur on rocky slopes at higher elevations within the deployment area...Federal Lands Highway Projects Office, Lakewood, CO. November. Thuman, Albert and Richard Miller, 1976. Secrets of Noise Control. 2nd ed. Atlanta

  16. Japan: Asian Peacekeeper of the 21st Century?


    what if every nation acted that way? There will be no more international order. [Ref. 189] MP Nakasone states that by clinging stubbornly to its egoism ... case . In fact, they have a bureaucratically guided conomy, one where industry cooperates closely with government, but few Japanese realize this. [i...Japan’s defense, ASDF aircraft and MSDF ships could engage those enemy aircraft. This was an actual test case put before the government in 1983. [Ref. 241

  17. Dysfunction Junction: Intelligence, Peacekeeping, and the United Nations


    government’s formulating and implementing policy to further its national security interests and to deal with threats to those interests from actual or...their internal affairs to be the focus of a UN collection effort.68 Martha Finnemore documented a shift in the consideration of international...Chesterman, 154. 69 Martha Finnemore , “Changing Norms of Humanitarian Intervention,” in The Purpose of Intervention: Changing Beliefs about the Use of Force

  18. working towards an african peacekeeping capability: key issues ...


    Scientia Militaria, South African Journal of Military Studies, Vol 34, Nr 2, ..... disciplinary standby capabilities at the AU and sub-regional level which would be ..... Charter. A great deal of the practical challenges and responsibility for developing.

  19. Environmental Impact Statement. Peacekeeper Rail Garrison Program. Volume 1


    leucocephalus migrant Barn owl Tyto alba - E Occurs onbase as migrant Black-tailed Lepus californicus - R Occurs onbase jackrabbit Cooper’s hawk...Millsap (Austin, Texas) Honorable Billy Montgomery (Haughton, Louisiana) Honorable Alejandro Moreno , Jr. (Edinburg, Texas) Honorable Anna Mowery (Fort

  20. President Reagan’s commitment of Peacekeepers in Lebanon, 1983


    over the spoils of office.”26 Lebanon also enjoyed a peaceful transitions of power and civic empowerment as shown when President Bishara Khoury was...the Reagan administration looked at while mentally conflating the Lebanese anti-aircraft missile crisis in 1981 with the larger U.S. – Soviet...misgivings about the mission in a memorandum to CJCS Vessey on August 9, 1982. Among his concerns were the “vague and ill -defined mission” that did not

  1. Environmental Impact Statement. Peacekeeper Rail Garrison Program. Executive Summary


    inmigration would increase the population in the Cheyenne area by 7.5 percent above baseline projections during construction (1995) and approximately...transportation. Socioeconomic impacts would be low because program-induced inmigration would increase the population in the Great Falls area by 1.3...socioeconomic impacts would be high because inmigration would increase the population in the Great Falls area by 13 percent above baseline projections

  2. Draft Environmental Impact Statement: Peacekeeper Rail Garrison Program


    advanced culture characterized by an extensive trade network and a series of traits such as ceremonial architecture and maize (corn) agriculture...Statement, Pantex Plant Site, Amarillo , Texas (U.S. Department of Energy 1983), which covers nuclear weapons assembly, stockpile monitoring, maintenance...1983 Final Environmental Impact Statement, Pantex Plant Site, Amarillo ,_ Texas (DOE/EIS-0098). National Technical Information Service, Washington

  3. Turkey’s Soft Power Assets in Peacekeeping Operations


    range in different areas such as education, transportation, health, water and sanitation, communication, energy projects, trade and tourism . In these...175 Ibid. 54 Ghazi Camp situated at Kabul as well.176 In addition, TAF supports the military hospital with medical staff and provides health

  4. The Challenges and Opportunities of UN Peacekeeping in Darfur


    sense to cover all types of peace operations. 6 Lawrence. Ziring, Robert Riggs, and Jack Plano, The United Nations (Belmont, CA: Malloy Incorporated...15. 20 Adam Roberts , ”The So-Called ‘Right’ of Humanitarian Intervention,” Yearbook of International Humanitarian Law 2000, Vol.3(The Hague: T.M.C

  5. Preparation of Leaders to Make Decisions in Peacekeeping Operations

    Pappal, Michael


    .... Areas investigated include personal confidence in decision-making of various types, amount of training and education received in peace operations, and assessments of Army preparations of leaders...

  6. international peace-keeping operation: a breach of international law ...


    peaceable relations by civil and military means. .... Rwandan Genocide, described the problems posed by the companion to more ... R. Dallaire, Shake Hands with the Devil, Cambridge University press, USA: 2004 .... India subcontinent.27.

  7. Peacekeeper Quantity-Distance Verification Program and Addendum.


    Early Time Break Up 6-1 6.2 Surface Spallation 6-3 6.3 Fragment Launch Characteristics 6-9 6.4 Test Predictions 6-14 7.0 FRAGMENT SCALING METHODOLOGY 7-1...backfill, the lower portion of the 6-inch diameter columns was drilled into the native soil and backfilled with colored sand. Two-foot-long sections of...structural break up, attention was focused on three major areas: * early time break up response, surface spallation phenomena and fragment launch

  8. The United Nations in Peacekeeping Operations of the Future


    Humanitarian assistance including protection to relief agencies for the delivery of humanitarian aid. (j) Guarantee of rights of passage . (k) Sanctions...using force only as a last resort and in self-defense where duties such as the guarantee of rights of passage , etc are involved. In this context it

  9. United Nations Secretary General’s Peacekeeping Proposals


    have undertaken to make available to the Security Council, on its call, " armed forces, assistance and facilities, and rights of passage , necessary...readiness and general locations and the nature of facilities and assistance, including rights of passage , to be made available to the Security

  10. Peacekeeping in the Congo, 1999-2001: Success or Failure?


    toolkit provides a framework for more effective conflict resolution. The framework contains two critical concepts that are extremely useful in...recommends that a proper assessment of the fighting forces can help create the potential for more effective resolution of a conflict. The assessment...War. President Nelson Mandela was the chairman of the South African Development Community (SADC) in the summer of 1998 when the war broke out in the

  11. Magistrate, Peacekeeper, Politician, Administrator - Insights from Four Leading Women Lawyers

    Nicola Roxon


    Full Text Available The Honourable Nicola Roxon, during Law Week 2014, chaired a panel of experts discussing the role of women in the field of law and legal studies: Dr Helen Durham, Director of International Law and Strategy, Australian Red Cross; Clare Francis, State Coordinator, Children’s Court of Victoria; and Jelena Popovic, Deputy Chief Magistrate, Magistrates’ Court Victoria.

  12. Temporal changes in glial fibrillary acidic protein messenger RNA and [{sup 3}H]PK11195 binding in relation to imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding in the hippocampus following transient global forebrain ischaemia in the rat

    Craven, J.A.; Gundlach, A.L.; Conway, E.L. [The University of Melbourne, Clinical Pharmacology and Therapeutics Unit (Australia); Department of Medicine, Austin and Repatriation Medical Centre (Australia)


    Immunohistochemical studies have demonstrated that following global forebrain ischaemia the selective neuronal loss that occurs in the CA1 pyramidal cell layer of the hippocampus is accompanied by a reactive astrocytosis, characterized by increases in glial fibrillary acidic protein, and activation of microglia. In this study the spatial changes in glial fibrillary acidic protein messenger RNA levels in the hippocampus have been mapped four, eight, 12, 16 and 20 days following 10 min of global forebrain ischaemia in the rat and related to changes in [{sup 3}H]PK11195 binding to peripheral benzodiazepine receptors, a putative marker of activated microglia. Recent studies have suggested that the imidazoline-I{sub 2}-receptor, one of a class of non-adrenergic receptors related to, but structurally and functionally distinct from {alpha}{sub 2}-adrenoceptors, may have a functional role in controlling the expression of glial fibrillary acidic protein. To explore this possibility further we have also mapped changes in imidazoline-I{sub 2}-receptor and {alpha}{sub 2}-adrenoceptor binding sites. Following transient ischaemia there was a marked, biphasic increase in glial fibrillary acidic protein messenger RNA levels throughout the vulnerable CA1 region of the hippocampus, peaking four days after ischaemia and then increasing gradually during the remainder of the study period. There was also a sustained increase in [{sup 3}H]PK11195 binding, however, in contrast to the initial increase in glial fibrillary acidic protein messenger RNA levels that peaked four days after ischaemia the density of [{sup 3}H]PK11195 binding increased rapidly in all strata of the CA1 region over the first eight days and then increased more slowly throughout days 12 to 20. Despite the marked increase in glial fibrillary acidic protein messenger RNA levels there was no concomitant alteration in imidazoline-I{sub 2}-receptor binding sites detected using the specific radioligand, [{sup 3}H]2

  13. Synthesis of 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)-substituted pyrazolo[3,4-d]pyrimidin-4-amines via click chemistry: potential inhibitors of the Plasmodium falciparum PfPK7 protein kinase.

    Klein, Michael; Dinér, Peter; Dorin-Semblat, Dominique; Doerig, Christian; Grøtli, Morten


    Efficient routes to 3-(1,2,3-triazol-1-yl)- and 3-(1,2,3-triazol-4-yl)pyrazolo[3,4-d]pyrimidin-4-amines using a one-pot two-step reaction are presented. The two routes give easy access to two different isomers of 1,4-disubstituted triazoles and the target compounds are obtained from a variety of readily available aromatic and aliphatic halides without isolation of potentially unstable organic azide intermediates. Two compounds show activity towards the PfPK7 kinase (IC(50) 10-20 microM) of P. falciparum, the organism responsible for the most virulent form of malaria, and can be regarded as hits useful for further development into lead compounds.

  14. 基于PK-PD研究确定头孢曲松舒巴坦Ⅱ期临床给药方案%Use of preclinical and phase Ⅰ data for determining a phase Ⅱ dose for ceftriaxone/sulbactam injection

    李苌清; 陈昭丽; 王广基; 王霆


    目的:基于临床前药效学(PD)和Ⅰ期临床药动学(PK)资料,进行给药方案的Monte Carlo模拟,确定头孢曲松钠舒巴坦钠(2:1)Ⅱ期临床试验的给药方案.方法:整理临床前的药敏实验、后抑效应和Ⅰ期临床药动学等PK-PD相关研究资料.以静脉滴注0.5~2.5 g/次(以头孢曲松量计),每日1次(Qd)、2次(Bid)、3次(Tid)等多种给药方案,治疗常见产ESBLs致病菌感染进行Monte Carlo模拟,将获得的累积反应分数(CFR)做给药方案的比较.结果:以CFR>~90%的给药方案为最佳给药方案.按Qd、Bid和Tid等不同频率给药,治疗常见产ESBLs致病菌感染所需的每次最低给药剂量分别为2.2 g、1.3 g和1.1 g.结论:从药物安全性、药代动力学同步性、以及成本效益角度考虑,头孢曲松钠舒巴坦钠(2:1)Ⅱ期临床试验的最佳给药方案是1.3 g Bid.

  15. Pharmacokinetic-pharmacodynamic(PK-PD) modeling of salvianolic acid A on the plasma homocysteine in rats%丹酚酸A对大鼠血浆中同型半胱氨酸调节作用的药动学-药效学结合模型

    任欣怡; 陈渊成; 王琰; 肖媛媛; 柳晓泉


    同型半胱氨酸(Hcy)是独立的心血管危险因子,降低Hcy水平有利于减少心血管疾病风险.以大鼠急性蛋氨酸(Met)负荷作为药理模型,就丹参水溶性物质主要活性成分丹酚酸A(salA)对大鼠血浆中Hcy调节作用进行了药动学和药效学研究,发现1,2.5,5 mg/kg 3个剂量的SalA对Met负荷引起的血浆中总同型半胱氨酸(tHcy)升高有降低作用,并且存在一定的剂量依赖性.本文建立了基于SalA对Hcy调节作用机制的药动学-药效学结合(PK-PD)模型,较好的拟合了药动学和药效学的实验结果,并与丹参素(DSS)对Hcy调节作用的PK-PD模型结果进行比较,定量揭示了SalA对tHcy升高促进作用以及转硫途径消除作用与DSS的差异:SalA对于tHcy上升促进作用弱于DSS,但是对于tHcy转硫途径消除的作用强于DSS.

  16. Framtidens hållbara elbilskoncept : En jämförande LCA-studie mellan en elbil och en bränslecellsbil

    Ulin, Sofia; Wiebert, Julia


    Transportsektorn så som den ser ut i dagens samhälle är inte hållbar då den står för ungefär 30 % av Sveriges totala utsläpp av koldioxid. Detta beror framför allt på att fossila bränslen utgör det främsta drivmedlet inom transportsektorn, och alternativa lösningar måste därför undersökas. Två sådana alternativ är elbilar och bränslecellsbilar. För att ta reda på vilket av dessa elbilskoncept som har störst möjlighet att skapa en utsläppsfri transportsektor har liv...

  17. Quantitative determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol and its active phosphorylated metabolite in rat blood by LC-MS/MS and application to PK/PD analysis.

    Zhao, Manman; Mi, Jiaqi; Li, Dan; Liu, Xin; Yang, Shuang; Wang, Baolian; Sheng, Li; Wang, Xiaojian; Jin, Jing; Hu, Jinping; Li, Yan


    A sensitive and specific LC-MS/MS method was developed and validated for simultaneous determination of 2-amino-2-(2-(4'-(2-propyloxazol-4-yl)-[1,1'-biphenyl]-4-yl)ethyl)propane-1,3-diol (SYL930) and its active phosphate metabolite (SYL930-P) in rat blood using SYL927, an analogue of SYL930 as the internal standard. Blood samples were prepared by a simple protein precipitation with acetonitrile. The chromatographic separation was performed on a ZorbaxSB-C18 column (3.5 μm, 2.1 × 100 mm) with a gradient mobile phase of methanol/water containing 0.1 % formic acid (v/v) at a flow rate of 0.2 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization (ESI) in multiple reactions monitoring mode (MRM). The monitored transitions were 381.2 → 364.2 for SYL930, 461.2 → 334.2 for SYL930-P, and 367.1 → 350.4 for the internal standard, respectively. Good linearity was obtained for the analytes over the range of 0.2-100 ng/mL for SYL930 and 0.5-100 ng/mL for SYL930-P. The lower limits of quantitation (LLOQs) for SYL930 and SYL930-P were 0.2 and 0.5 ng/mL, respectively. The intra-day and inter-day precisions (RSD, %) of analytes were within 9.87 %, and the accuracy (RE, %) ranged from -7.04 to 13.15 %. The mean recoveries for two compounds in rat blood were 87.9-109 %. The analytes were proved to be stable during all sample storage, preparation, and analytic procedures. The validated method was successfully applied to pharmacokinetic and PK/PD studies of SYL930 and SYL930-P in rats after oral administration of SYL930. Graphical Abstract Quantitative determination of SYL930 and its active phosphorylated metabolite in rat blood by LCMS/MS and application to PK/PD analysis.

  18. Rahoitusselvitys aloittelevalle pk-yritykselle : Case: Pets Cooler

    Uotinen, Emmi


    Tarkoituksena oli selvittää erilaisia rahoitusvaihtoehtoja aloittelevalle pienelle ja keskisuurelle yritykselle. Opinnäytetyön tavoite oli helpottaa toimeksiantajayrityksen Pets Cooler rahoituslähteiden valintaa. Yritystoiminnan on tarkoitus käynnistyä mahdollisimman nopeasti, ja selvitys on tukena aloituksessa. Toimeksiantaja halusi käsiteltävän myös kansainvälisen liiketoiminnan rahoitusta. Vienti ja mahdollisesti myös ulkomailla tapahtuva tuotanto on yrityksen haaveena tulevaisuudessa. ...

  19. Google与 Yahoo企业文化之间的PK



    @@ 在美国硅谷Yahoo公司办公室的墙上贴着一些获得了专利的古怪发明的草图,比如说便携式的鸟笼.其用意就是告诉Yahoo的员工:只要花些心思,我们一定能够创造出一些更大的发明来.

  20. PK-12 Public Educational Facilities Master Plan Evaluation Guide

    21st Century School Fund, 2011


    Proper planning of school facilities is critical for all school districts no matter how large or small, whether major construction is in the works or the district is managing enrollment declines. When school districts properly plan for their school facilities they have better schools, more public use and higher value for public spending. This…

  1. Isospin odd @pK scattering length [rapid communication

    Schweizer, J.


    We make use of the chiral two-loop representation of the πK scattering amplitude [J. Bijnens, P. Dhonte, P. Talavera, JHEP 0405 (2004) 036] to investigate the isospin odd scattering length at next-to-next-to-leading order in the SU (3) expansion. This scattering length is protected against contributions of ms in the chiral expansion, in the sense that the corrections to the current algebra result are of order Mπ2. In view of the planned lifetime measurement on πK atoms at CERN it is important to understand the size of these corrections.

  2. PK-PD integration and modeling of marbofloxacin in sheep.

    Sidhu, P K; Landoni, M F; Aliabadi, F S; Lees, P


    The fluoroquinolone antimicrobial drug, marbofloxacin, was administered intravenously (IV) and intramuscularly (IM) to sheep at a dose rate of 2 mg kg(-1) in a 2-period cross-over study. Using a tissue cage model of inflammation, the pharmacokinetic properties of marbofloxacin were established for serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). For serum, after IV dosing, mean values for pharmacokinetic parameters were: clearance 0.48 L kg(-1) h(-1); elimination half-life 3.96 h and volumes of distribution 2.77 and 1.96 L kg(-1), respectively, for V(darea) and V(ss). After IM dosing mean values for pharmacokinetic variables were: absorption half-time 0.112 h, time of maximum concentration 0.57 h, terminal half-life (T(1/2)el) 3.65 h and bioavailability 106%. For exudate, mean T(1/2)el values were 12.38 and 13.25 h, respectively, after IV and IM dosing and for transudate means were 13.39 h (IV) and 12.55 h (IM). The in vitro minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and ex vivo time-kill curves for marbofloxacin in serum, exudate and transudate were established against a pathogenic strain of Mannheimia haemolytica. Integration of in vivo pharmacokinetic data with MIC determined in vitro provided mean values of area under curve (AUC)/MIC ratio for serum, exudate and transudate of 120.2, 156.0 and 156.6 h after IV dosing and 135.5, 165.3 and 146.2 h after IM dosing, respectively. After IM administration maximum concentration (C(max))/MIC ratios were 21.1, 6.76 and 5.91, respectively, for serum, exudate and transudate. The ex vivo growth inhibition data after IM administration were fitted to the sigmoid E(max) (Hill) equation to provide values for serum of AUC(24h)/MIC producing, bactericidal activity (22.51 h) and virtual eradication of bacteria (35.31 h). It is proposed that these findings might be used with MIC(50) or MIC(90) data to provide a rational approach to the design of dosage schedules which optimise efficacy in respect of bacteriological as well as clinical cures.

  3. Sähköinen markkinointikampanja PK-yritykselle

    Vuorinen, Marika


    Tämä opinnäytetyö käsittelee sähköistä markkinointia ja sen erilaisia keinoja painottuen sosiaaliseen mediaan. Opinnäytetyössä on tilaajana sisustukseen keskittynyt yritys, jonka nimeä ei kuitenkaan mainita liiketoiminnallisista syistä. Teoriaosuudessa käydään läpi suosituimpia sosiaalisia medioita tällä hetkellä ja pohditaan mitä kaikkea on huomioitava kampanjaa tehdessä. Ennen kun kampanjaa voidaan lähteä suunnittelemaan, on tehtävä yritysanalyysi ja tarkasteltava toimintaa useista näkö...

  4. On the use of fractional order PK-PD models

    Ionescu, Clara; Copot, Dana


    Quantifying and controlling depth of anesthesia is a challenging process due to lack of measurement technology for direct effects of drug supply into the body. Efforts are being made to develop new sensor techniques and new horizons are explored for modeling this intricate process. This paper introduces emerging tools available on the ‘engineering market’ imported from the area of fractional calculus. A novel interpretation of the classical drug-effect curve is given, enabling linear control. This enables broadening the horizon of signal processing and control techniques and suggests future research lines.

  5. 以原核表达的非洲猪瘟病毒pK205R蛋白为包被抗原的间接ELISA抗体检测方法的建立%Development of an indirect ELISA for detection of antibody against African swine fever virus (ASFV) with prokaryotic expressed ASFV pK205R protein as the coating antigen

    邬旭龙; 彭彬; 姜睿姣; 肖璐; 王印; 姚学萍; 杨泽晓; 张鹏飞; 张博


    为建立快速检测非洲猪瘟病毒(ASFV)的血清学方法,本研究原核表达ASFV pK205R重组蛋白,并以其为包被抗原,通过反应条件优化,建立了一种快速的ASFV间接ELISA检测方法.结果显示,原核表达的ASFV pK205R蛋白约为44 ku,western blot证实表达蛋白具有良好的反应原性;以其作为包被抗原建立的ASFV抗体间接ELISA方法仅对ASFV血清检测为阳性,与猪瘟病毒、猪伪狂犬病毒、猪繁殖与呼吸综合症病毒、副猪嗜血杆菌及猪大肠杆菌阳性血清均无交叉反应,具有良好的特异性;该方法检测灵敏度为1:2 560;批内和批间重复性试验的变异系数均小于10%;利用该方法对临床样品检测的结果与国外商品化试剂盒检测结果符合率为100%.本研究建立的ASFV抗体间接ELISA方法为防止该病传入我国以及ASFV的实时监测提供技术储备.

  6. Solvability of the Diophantine equations xp + 22m y4 = pk z2 and xp + y2 = pk z4


    We study the solvability of two classes of Diophantine equations by using some new methods and new results in this paper.Letp be an odd prime and Bn denote nth Bernoulli number.We prove that ifp ≡ 1(mod 4)andp |B(p-1)/2,then the equationxp +22mn4 = pky2,m,n,k ∈ N ,k > 1,gcd(x,py)= 1,and the equationxp +y2 =pkz4,k ∈ N,gcd(x,y)= 1,k > 1,21 y have no integral solutions respectively.

  7. 逐饮Ⅰ号对恶性胸水大鼠模型血清TUM2-PK含量和胸膜组织bFGF表达的影响%Effect on TUM2 - PK in Serum of MPE Rat Model and bFGF in Its Membrana Pleuralis Treated by Zhu Yin Ⅰ

    刘建秋; 李竹英; 蒋鹏娜



  8. Preparing for the Inevitable: Examining Future U.S. Peacekeeping in Israel and the Occupied Territories Through the Lens of the Sinai and Lebanon Peacekeeping Missions


    lost military sales due to Israeli objections or competition 22 USAID West Bank and Gaza. “Program Overview .” Washington D.C., 16 December 2003. 8...25 U.S Department of State, Patterns of Global Terrorism 2001, Middle East Overview , 5 26 USA Today. “Sharon: Syria Peace Means Golan...the West Bank.52 Other Jewish extremist groups are Gush Emunim, who plotted to destroy the Al Aqsa mosque on the Temple Mount in the 1980’s, and

  9. Tezkire-i Buğra Han’ın Çağatayca Yazılmış Bir Nüshası Metin- Dil İncelemesi- Tıpkıbasım A Manuscript Of Tazkira-i Bughra Khan Written In Chagatay Turkısh Texte- Grammar Notes- Facsimile



    ındaki bilgiler oldukça sınırlıdır. Bu dönem hakkındaki bilinmezliklerin benzeri, İslamiyet’in Türkler arasında yayılmasında büyük bir yeri bulunan ve efsanevi özellikler taşıyan Satuk Buğra Han için de geçerlidir.Bu makale, Türklerin İslamiyeti kitle hâlinde kabul edişlerini ve ilk Müslüman Türk hükümdarının efsanevi hayatını anlatan Tezkire-i Buğra Han kitabının 19. yüzyılda Çağatayca olarak kaleme alınmış bir nüshasının çeviri yazı ve dil incelemesini içermektedir.Çalışmamıza konu olan eser, Klasik Çağataycanın dil özelliklerini taşımakla beraber, Özbekçe ve Çağdaş Uygurcanın ses ve şekil bilgisi özelliklerini de barındırmaktadır. Tezkire-i Buğra Han kitabı gerek ses gerekse şekil bilgisi bakımından Çağatayca öncesi arkaik örnekleri de içermektedir. Eser bu özellikleriyle, hem Çağataycadan çağdaş Türk lehçelerine geçişi yansıtmakta hem de içerdiği arkaik yapılarla dikkat çekmektedir.Yazmanın Çağatayca dışında en çok Çağdaş Uygurcanın dil özelliklerini barındırdığı görülmektedir. Kitabın ilk sayfasındaki karışık bir hâlde yazılmış ifadelerin içinden tespit edebildiğimiz tārįħķa bir min g iki yüz yėtmiş1 ….. inal aķsuluķ taĥrįri āħir boldı cümlesi eserin Çağdaş Uygurcayla olan bağını da açıklar niteliktedir.Bu makalede söz konusu yazma eserin bütünü hakkında, yazarı, yazıldığı yüzyıl, diğer nüshaları vb. özellikleri bakımından bilgi verilmiş olup yalnızca Satuk Buğra Han menkabesinin geçtiği kısmın çeviri yazılı metni sunulmuştur. Ayrıca incelenen kısmın tıpkıbasımı da makalenin sonuna eklenmiştir.Bu yazıda, British Library’deki Or. 8161 numaralı metnin 83a-102b varakları arasındaki Satuk Buğra Han menkabesini esas almakla birlikte, dil incelemesinde gerek duyuldukça yazmanın bütünü göz önünde bulundurularak açıklamalar yapılmıştır.

  10. United Nations Peacekeeping Participation and Civil-Military Relations in Troop Contributing Countries


    unrest, King Birendra conducted a plebiscite in 1980 that offered a choice between a multiparty democratic system and a "reformed Panchayat system...political parties whose approaches were anti-monarchist since King Mahendra dismantled the first democratic system in the 1960’s. The was taught to be loyal to the king and the country rather than to the people and the democratic system . At the end of the Panchayat, the gap

  11. The German Debate Over Military Peacekeeping Missions: The First Step Toward an Eventual Combat Role


    by Hussein’s forces and the fear that Germany would be pulled into an unwanted war. Former Chancellor Willy Brandt of the SPD party and Germany’s...use of military force in the Gulf crisis was passed and war seemed inevitable, Defense Minister Gerhard Stoltenberg (CDU), at a special Bundestag...positions within two months of each other. Gerhard Stoltenberg, Minister of Defense (MOD) since 1989, stepped down on 31 March 1992 in the midst of an

  12. Environmental Impact Statement. Peacekeeper Rail Garrison Program. Volume 2. Public Comments


    Cheyenne, Wyoming) 426 17 Adora Lindsley Palma (Cheyenne, Wyoming) 452 18 Sally Palmer (Laramie, Wyoming) 388 19 Bernard Phelan (Cheyenne, Wyoming) 229...the Governor (T.C. Adams) (Austin, Texas) 514, 519 5 Washington Department of Ecology (M.F. Palko) 511 (Olympia, Washington) Individuals 1 D. L. Blank...those ecological messes? RESPONSE: See response to Document 50, Comment 30. 270 22 ISSUE: What would happen if 1 of the 10 bombs within the MX missile

  13. Outsourcing Human Security: The Pros and Cons of Private Security Companies in Peacekeeping


    on United Nations Peace Operations204 When we had need of skilled soldiers to separate fighters from refugees in the Rwandan refugee camps in Goma ...refugees in the Rwandan refugee camps in Goma ,” but concluded that, “the world may not be ready to privatize peace.” Faite, “Involvement of Private

  14. The Role of Fire Support in Peacekeeping and Peace Enforcement Operations.


    Between Peace and War: Comprehending Low Intensity Conflict, (National Security Discussion Paper Series 88-02: Harvard, National Security Fellows, 1986...Richard Williams, Between Peace and War: Comprehending Low Intensity Conflict, National Security Discussion Paper Series 88-02: Harvard, National Security

  15. The Norwegian media image of the war in Afghanistan: Peacekeeping or aggression?

    Rune Ottosen


    Full Text Available This article analyzes the framing of Norwegian media coverage of the war against terror in Afghanistan with special emphasis of the coverage of the Norwegian military presence in Afghanistan. Norwegian forces became involved in a military intervention for the first time since the Second World War when ex-Yugoslavia was attacked in April 1999. At that time, Norway provided military support for the invasion and placed fighter planes and Norwegian pilots at the disposal of NATO. The war in Afghanistan represented an additional dimension, with Norwegian ground forces taking part in the hunt for al-Qaida fighters in the mountains of Afghanistan. The purpose of this article is to give a picture of Norwegian media coverage of the war in Afghanistan, with a special emphasis on the coverage of Norway's role in the conflict. As a small country with traditionally close relations to US, Norway had to balance, like many other small countries, between the need uphold its traditional policy of complying with international law, and the desire to avoid provoking the USA with criticism and actions that could be regarded as disloyal and thus harm the bilateral relationship. This dilemma must also be seen as a problem for the mainstream media, which traditionally has been loyal to Norwegian security policy. Two main issues are discussed: 1. How was the start of the war covered in the media in October 2001? 2. In what context was the Norwegian military presence covered? The two newspapers analyzed are Aftenposten and VG. The choice of these two newspapers was made to include Norway's largest and potentially most influential morning paper (Aftenposten and its largest tabloid, as well as largest newspaper (VG. Quantitative as well as qualitative methods are used to analyze the coverage. Both Aftenposten's and VG's coverage on the first day of the war in Afghanistan are dominated by pro-US framing and the use of Western sources. The pro-US framing is more obvious in Aftenposten than in VG. The editorial in VG was more unconditionally supportive than the editorial in Aftenposten. VG is also much clearer in its framing of Norway as a potential victim of future acts of terror. Norway's role as a potential military actor in the region is at this stage virtually absent in both newspapers. The legal aspects are mentioned in the two newspapers, though in a very superficial manner. Neither of the newspapers focuses on potential "hidden agendas" in their news coverage. No issue is made of the USA's potential global interests or the issue of controlling oil flows from the region. Aftenposten, in its coverage of an attack on a wedding party, treats this incident as "collateral damage" and in no way links it to Norway's military presence. Norway is simply a "loyal ally" receiving praise from the US for doing a "good job".

  16. The Economic Impact of Peacekeeping in Burkina Faso: A Motivation to Contribute


    and regular feedback allowed me to deliver a better product. I also want to express my gratitude to the staff of the Combined Arms Research has two head organizations: the UN and the AU. ‡ Laafi means Peace in Moore, the most largely spoken language in Burkina Faso. 5 two infantry

  17. Privatization of Peacekeeping: UN’s Institutional Capacity to Control Private Military and Security Companies


    League’s Covenant, which was incorporated to the Versailles treaty . Thus, League did not entitle the Axis powers the right to join. 1. Legal and...International Armed Conflicts (Protocol I), 8 June 1977, International Humanitarian Law - Treaties & Documents, International Committee of the Red Cross...Libreville, July 3, 1977, International Humanitarian Law - Treaties & Documents, International Committee of the Red Cross,

  18. Peacekeeping and the Armed Forces of the Southern Cone: Current Trends and Future Prospects


    en Operaciones de Mantenimiento de Paz,” Pagina Web del Ejercito de Chile; available from; Internet...Pittsburgh: University of Pittsburgh Press, 1998), 134. 66 “Operaciones de Mantenimiento de Paz,” Pagina Web de la Mision de Chile Ante las Naciones...69 “Operaciones de Mantenimiento de Paz,” Pagina Web de la Mision de Chile Ante las Naciones Unidas; available from http

  19. From Guerillas to Peacekeepers: The Evolution of the Rwandan Defense Forces


    JSTOR [ database online]. Available from MCRC (accessed October 25,2007), 177. 20. Major Ndore Rurinda, RDF. Interview by author. Personal. Kigali...72 (1996): 162-194. fu JSTOR [ database online]. Available from MCRC (accessed October 25,2007). Gourevitch, Philip. We Wish to Inform You That...In Proquest[ database online]. Available from MCRC (accessed October 15, 2007). Richardson, R., D. Verweij, and D. Winslow. "Moral Fitness for Peace

  20. Agent-Based Model and System Dynamics Model for Peace-Keeping Operations


    himself/herself, or to bring about change for the benefit of the society as a whole. Durkheim explained Anomie Theory as a process whereby some members of...lessens social control Durkheim Anomie (gap between goals and means) creates deviance Merton Differential social opportunity Cloward and Ohlin Lower...Mannheim): low expectancy that satisfactory predic- tions about future outcomes of behavior can be made • Normlessness ( Durkheim -Merton): high

  1. Lessons Learned from the Srebrenica Massacre : From UN Peacekeeping Reform to Legal Responsibility

    Ryngaert, C.M.J.; Schrijver, Nico


    This article introduces the special issue on Srebrenica by reflecting on how the fall of Srebrenica has served as a trigger for proposals to fundamentally transform international law, especially the law relating to international crimes, responsibility, and legal remedies for victims. It also

  2. Peacekeeper Ballistic Missile System Fiscal Impact Analysis of Deployment in Wyoming and Nebraska


    REGION ON INFLUENCE JOBS, LOCAL AND REGIONAL HIRES, AND INMIGRATION 1991 1984 1985 1986 1987 1988 1989 1990 and on Total Additional 250 2,400 2,650 2,550...0 Weekly Commuters Average Annual 75 425 950 1,100 925 1,000 425 360 Inmigrant Workers Unsuccessful 30 185 180 150 165 110 70 0 Job-Seekers Inmigrant ...1 275 1,475 2,875 3,200 3,025 2,875 1,200 925 Population Note: 1 Includes inmigrant workers and unsuccessful job-seekers and accompanying dependents

  3. Final Environmental Impact Statement, Peacekeeper in Minuteman Silos, F.E. Warren AFB, Wyoming. Volume 1.


    Scottsbluff Chapter Richard Deyo Herman Noe Betty Jean Dower Garry Oliver G. J. Edwards Lee A. Otto Joel Engelhardt Nellie Red Owl Mayor Don Erickson ...Russell Dale Doremis Sam Sang William Edwards Anne Saunders Darren Erickson Beverly Schwieger J. Erickson Paul Schwieger Seath Fanir M. Shaw Mauriel Frank...Stout Alice M. Iverson Gary Thorson Lama Johnson John Turnr ’ Julia Judson Bob Unruh .r Mrs. Rodney Kirtbride Ed Usui . Edmond Levering Richard Vose

  4. Colonial Roots, Conflict and Peacekeeping in Africa: Defining the Need for an African Airlift Consortium


    35 Cowan, The Dilemmas of African Independence, 1.  36 Arthur Lewin , “Independence Years and Dates of African Countries,” Indigenous People 2 (April, 1983): 95-108. 25 Gene Schackman, “Brief Review of Trends in Political Change: Freedom and Conflict,” The Global Social Change...University Press, 1999. Lewin , Arthur. "Independence Years and Dates of African Countries." Indigenous People of Africa and America Magazine

  5. The DTIC Review. Volume 3, Number 1, Terrorism, Peacekeeping, and Operations Other Than War


    fighting overpopulation , AIDS, drug smuggling and envi- endanger our citizens, ronmental degradation, ensure that future generations of 3 Americans will...the long run. Despite recent setbacks in Colombia , narcotics traffickers show no signs of scaling down their level of activity. Their use of payoffs...production in Afghanistan hasskyrocketed since 1990 and Colombia has surpassed Mexico asthe largest producer of opium in the Western Hemisphere

  6. Brazilian Peacekeeping: Challenges and Potentials in Turbulent Landscapes at Home and Internationally

    Cezne, Eric Miro; Hamann, Eduarda


    Over the last decade, Brazil has taken a more substantial role in international peace and security, and has become increasingly involved in UN peace operations. Particularly through its participation in Haiti, leading the military component of the UN Stabilization Mission in Haiti (MINUSTAH), Brazil

  7. Peacekeeping on the Golan Heights in the Event of an Israeli-Syrian Peace Accord.


    Fried Chicken branch in Damascus. Mobil is currently considering investing in oil exploration in Syria. These investments are a just prelude to the...private companies to invest in fertilizer projects and on the 16 May 1998 American franchising was introduced to Syria with the opening of a Kentucky

  8. U.N. Peacekeeping in Yugoslavia: Background, Analysis, and Lessons Learned


    headquarters in Sarajevo, sub-offices in Belgrade and Zagreb, and a logistics-base in Banja Luka (a town of Bosnia-Herzegovina). Fifth and perhaps most...Canadian battalion, which has arrived in Daruvar in Sector West, have not been able to carry out any reconnaissance in the Banja Luka area, as the missions out of the Bosnian Serbs’ main air force base at Banja Luka northwest of Sarajevo. There are also unconfirmed intelligence reports that

  9. A Longitudinal Analysis of PTSD Symptom Course: Delayed-Onset PTSD in Somalia Peacekeepers

    Gray, Matt J.; Bolton, Elisa E.; Litz, Brett T.


    Posttraumatic stress disorder (PTSD) typically follows an acute to chronic course. However, some trauma victims do not report significant symptoms until a period of time has elapsed after the event. Although originally dismissed as an artifact of retrospective methodologies, recent prospective studies document apparent instances of delayed-onset…

  10. Danish Peacekeepers in the Republic of Serbian Krajina (Croatia), 1992-1995. Abridged Version

    Brink Rasmussen, Jakob


    This article is an abridged version of my dissertation “Den danske FN-bataljon i den ikke-anerkendte stat Republika Srpska Krajina, 1992-1995”, that was originally published in the Danish language journal “Fra Krig og Fred” (2014/2)” This article examines how the existence of the unrecognized state......, “Republika Srpska Krajina” (RSK), influenced a Danish infantry battalion during its deployment in Croatia between March 1992 and August 1995. Being a part of United Nations Protection Force (UNPROFOR), and later United Nations Confidence Restoration Force in Croatia (UNCRO), the battalion was to protect...

  11. Rapid Reaction Peacekeeping Under a Blue Flag: A Viable Response to Today’s Global Environment


    withdrawal , the US rejected an indefinite troop commitment to Somalia. Therefore the US urged a follow on UN led mission. The UN led force arrived...3. 26 is reinforced by the animosity of the conflict, which further degrade the political, social, and economic dynamics in a spiral of incivility ...move forward, unable to stay put taking casualties for no purpose, and unable to withdraw without repercussions for national foreign policies and UN

  12. Factors Affecting the Role and Employment of Peacekeeping Forces in Africa South of the Sahara.


    reinforcing. Although abstract, the w concept is similar to that used by Emile Durkheim in his discussion of social solidarity. I rhe concept of...I Forces Involved: Support for Congolese air power: Ethiopia provided Emil a jet fighter and possibly pilots; Ghana, seven pilots and two air traffic...problems Durkheim 3 ’ encountered when he attempted to measure social solidarity. His earlier efforts to social solidarity directly through an

  13. Brazilian Peacekeeping : Challenges and Potentials in Turbulent Landscapes at Home and Internationally

    Cezne, Eric Miro; Hamann, Eduarda


    Over the last decade, Brazil has taken a more substantial role in international peace and security, and has become increasingly involved in UN peace operations. Particularly through its participation in Haiti, leading the military component of the UN Stabilization Mission in Haiti (MINUSTAH), Brazil

  14. 在海地维和的日子%In the Peacekeeping Days in Haiti




  15. Discussion on Human Dignity and Human Rights Protection from the Perspective of Peacekeeping



    From an academic point of view,human dignity is the source of human fights,and has a orofound academic history.Since the end of World War Ⅱ,the issue of human fights has received great attention from the international community.So,human right theories,for which human dignity is the basic consideration,have developed continuously.In this era of advocating rights,human dignity and human fights protection are universal values and concepts,which were emphasized once again after World War Ⅱ.Moreover,human dignity was clearly identified as the basis of human rights at the system level.This paper begins by describing the relationship between human dignity and human rights.

  16. Supporting Australian Defence Force Peacekeepers and Their Families: The Case of East Timor


    difficulties in children, developmental disorders such as autism , language disorders, osteoarthritis, speech disorders, chronic fatigue syndrome, chronic pain...married with children. So very little was pitched toward single, female, owns own home has a dog . So there was pretty well. There wasn’t much room if you...basically said if you don’t call off your dog , I’ll have you discharged. Which is probably not very professional but yeah, I could see where he was

  17. The Uruguayan Armed Forces and the Challenge of 21st Century Peacekeeping Operations


    criticized for its 46 Miguel Angel Campόdonico, Antes del Silencio , Bordaberry, Memorias de un...Lula’s Zero Hunger Program,” (accessed August 15, 2005). Campόdonico, Miguel Angel. Antes del Silencio

  18. The Republic of Croatia’s National Interest in Peacekeeping Operations


    important peace support operation, the Croatian Armed Forces also participates in the following NATO-led operations: Kosovo Force ( KFOR ), Kosovo ...the transfer of the UN Mission in Kosovo (UNMIK). Croatia sent a line unit for the first time In 2008, a company of 95 soldiers to participate as...Rule of Law Mission) - Kosovo . Members of the Croatia Armed Forces are also involved in the EU battle group. “The Battlegroup Concept consists of

  19. The Use of Force in International Peacekeeping : with the Cases of MONUC and KFOR


    本論は、国際平和維持活動における伝統的な課題である武力行使について論じる。平和維持活動、とりわけ平和執行部隊における武力行使は、国際連合(国連)や地域機構を代表とする非国連におけるミッション双方によって積極的に推進された経緯があり、それと同時にケース・スタディーとして多く論文等においてミッションの武力行使について論じられてきた。本論では、中でもコンゴ民主共和国における国連ミッションであるMONUCとコソボにおけるNATO のミッションであるKFOR の2 つの平和執行部隊の武力行使に関する効果について調査をした。その結果、武力行使においては兵力の規模や軍備の精度は過大評価されるべきではないという結論に至った。本論では、平和活動における武力行使や派遣国のあり方は国際的に規定されるべきであり、さらに派遣されるタイミングや、それに至る準備やPKO 要員の意識の高さ、さらには強健な政治的な意志も重要な要因であると結論付けている。...

  20. PeaceKeeper: Augmenting the Awareness and Communication of Noise Pollution in Student Dormitories

    Lanng, Henrik; Lykkegaard,, Anders; Thornholm, Søren;

    Noise pollution can be very problematic especially in shared-living facilities such as student dormitories. After conducting interviews with nine students, we found that students are usually not aware of the level of noise pollution they are producing as part of their everyday activities. To addr......Noise pollution can be very problematic especially in shared-living facilities such as student dormitories. After conducting interviews with nine students, we found that students are usually not aware of the level of noise pollution they are producing as part of their everyday activities...... at the same dormitory. Based on our initial findings, we highlight how ambient awareness systems can provide opportunities to make students aware of their own level of noise to avoid disturbing their neighbours....

  1. Civilian Protection in the Eastern DRC: Evaluation of the MONUSCO Peacekeeping Operation


    1996–2003),” in Reseau des Femmes pour un Developpement Associatif (RFDA), International Alert, 2005. 123 Woudenberg, “You Will Be Punished,” 52...Violence Against Women and Girls During the War in the Democratic Republic of Congo, South Kivu (1996–2003).” Reseau des Femmes pour un

  2. 印楝素作用下小菜蛾体内MFO和JHE活力的变化%Changes of JHE and MFO Activity in Body of Plutella xylostella under Neem Treating

    王娟; 戴华国; 李洪山



  3. Schools Of Up to A Dozen Animal Skeletons, Each In Form of the Ellipitcal Letter "O", Ranging in Height From 4 Inches to Over 1 Ft. and Body Thickness of 1/2-3/4 Inches, Have Been Found Embedded in Top 1 of Only 2 Extruded Limestone Streambeds That Run Across West Face of Grandeur Pk., Wasatch Range and Then Turn East, Going Upstream, to Church Fork (or Park), Millcreek Canyon, Remaining Separated. Lower Streambed Was Not Examined Beyond West Face. Various Other Skeletal Structures Exist and Strata of Seashells Have Previously Been Shown(1), Esp. in Antitributary Streams.

    McDonald, Keith L.; McDonald, Russell T.


    Walking s. along dirt road that lies above residential area at about Lake Bonneville shoreline (5,200 ft.) and viewing e. at the 8,299 ft. Gradeur Pk., we count e-w running subridges from Parleys Canyon and recognize that 4th such ridge is that which descends from Grandeur Pk. About 300 ft. below the peak (no surveyor's instruments are employed), the upper limestone streambed passes thru 4th subridge, where the streambed reaches its highest elevation on w. face, running due n. and then this white limestone streambed to its present main ravine, turns 90 degrees to w., down towards Salt Lake Valley and remains, closely, the former main drainage ravine. Intersection of this 4th subridge with upper limestone streambed locates about 1 dozen "0"-shaped skeletons. However, it is clear that at some period, upper stream turned 90 degrees to w. at this intersection, running down present 4th ridgecrest and then turned to n.w., 50-100 ft. later to travel a few hundred meters to intercept the former main revine. Some seashells and "0" skeletons are located in this 50-100 ft. distance but immed. beyond, on 4th subridge, we could find no evidence of streamflow, altho observations were too hasty and we could have gone further w. We Rocky Mts. were formed this 1st and smallest n.w. streambed was forced out of ground and is very appar. when viewed from S. L. Valley, but small. The lower extruded streambed, above, is probably younger than the above highest one, which is more rich in limestone over w. face of Grandeur Pk. and lies perhaps 300 ft below 1st streambed and connects to 4th subridge high up on it's s. side, near ridge crest, in a broad and spread out manner. It probably supplied all water for the extruded large 2nd, smaller 3rd, large 4th, n.w. oriented streambeds that each make a 45 degree angle with 4th subridge and terminate in above drainage ravine. These skeletal forms demonstrate early life that existed 1/4 - 1/3 billion years ago (permocarboniferous ice age) and


    Saring Marsudi


    Full Text Available The general objective of this community service activity is facilitating the theoretical and practical BK services in Muhammadiyah Elementary School of Special Program in Surakarta and MIM Kartasura in implementing Permendikbud No. 111 of 2014 in an effort to improve the professionalism of teachers. In particular, the purpose of the community service is to facilitate the understanding the partner schools in Counselling services in the areas of personal, social, learning, and career. The service activities include socialization Permendikbud No. 111 of 2014 concerning guidance and counseling services in primary school, a discussion on the basic concept of guidance and counseling, and workshops on the implementation of guidance and counseling in Muhammadiyah Elementary School of Special Program in Surakarta and MIM Kartasura. Community service activities have received positive responses namely the formation of a formal institution Institute of Guidance and Counseling in each school. These institutions equipped with the personnel in charge, coordinator and teacher who oversees areas: personal, social, learning, and career.

  5. Search for a new baryonic state decaying to $pK^0_S$

    Bussey, P J


    We report on a new ZEUS search for a narrow state decaying into $p(\\bar{p})K^0_S$, which was previously claimed by the ZEUS collaboration. In the present search, which uses much increased statistics, no evidence for this state is found. Limits on the cross section for such a state are given.

  6. Assessing circadian rhythms in propofol PK and PD during prolonged infusion in ICU patients.

    Bienert, Agnieszka; Kusza, Krzysztof; Wawrzyniak, Katarzyna; Grześkowiak, Edmund; Kokot, Zenon J; Matysiak, Jan; Grabowski, Tomasz; Wolc, Anna; Wiczling, Paweł; Regulski, Miłosz


    This study evaluates possible circadian rhythms during prolonged propofol infusion in patients in the intensive care unit. Eleven patients were sedated with a constant propofol infusion. The blood samples for the propofol assay were collected every hour during the second day, the third day, and after the termination of the propofol infusion. Values of electroencephalographic bispectral index (BIS), arterial blood pressure, heart rate, blood oxygen saturation and body temperature were recorded every hour at the blood collection time points. A two-compartment model was used to describe propofol pharmacokinetics. Typical values of the central and peripheral volume of distribution and inter-compartmental clearance were V(C) = 27.7 l, V(T) = 801 l, and CL(D) = 2.73 l/min. The systolic blood pressure (SBP) was found to influence the propofol metabolic clearance according to Cl (l/min) = 2.65 x (1-0.00714 x (SBP-135)). There was no significant circadian rhythm detected with respect to propofol pharmacokinetics. The BIS score was assessed as a direct effect model with EC(50) equal 1.98 mg/l. There was no significant circadian rhythm detected within the BIS scores. We concluded that the light-dark cycle did not influence propofol pharmacokinetics and pharmacodynamics in intensive care units patients. The lack of night-day differences was also noted for systolic blood pressure, diastolic blood pressure and blood oxygenation. Circadian rhythms were detected for heart rate and body temperature, however they were severely disturbed from the pattern of healthy patients.

  7. PK-PD modelling of the interaction of propofol and midazolam : implementation and future perspectives

    Lichtenbelt, Bart Jan


    This thesis describes the day to day interaction between propofol and midazolam as encountered in every day practice. The direct interaction of premedication given to patients before surgery has profound implications. The propofol induction dose can be decreased with respect to the target BIS.

  8. PK-PD Modeling of Fluoroquinolones and ABC Transporters in Poultry

    Haritova, A.M.


    In the first part of this thesis advance pharmacokinetic models, based on an integration of pharmacokinetic and pharmacodynamic data for selected fluotoquinolones, are presented. The comparative investigations with danofloxacin mesylate and marbofloxacin indicated that with both fluoroquinolones a

  9. Microsoft Office 365 palvelun käyttöönotto PK-yrityksissä

    Matrone, Gianluca


    Opinnäytetyön aiheena oli Office 365 -palvelun käyttöönotto pienissä ja keskisuurissa yrityksissä. Tässä työssä sain toimeksiannoksi projektin selvittää, kuinka Microsoft Office 365 -palvelu otetaan käyttöön pienissä ja keskisuurissa yrityksissä käyttäen Microsoft kumppani tiliä. Työssä olen keskittynyt vain pienille ja keskisuurille yrityksille tarkoitettuihin palveluihin ja ratkaisuihin. Opinnäytetyön teoriaosuudessa kerrotaan yleisesti pilvipalveluista ja niiden toimintamalleista,...

  10. Revisiting Beta-lactams - PK/PD improves dosing of old antibiotics.

    MacGowan, Alasdair


    Pre-clinical pharmacokinetic-pharmacodynamic assessments indicate Beta-lactam antibiotics have time-dependent killing, variable persistent antibiotic effects and that free drug T>MIC is the dominant pharmacodynamic index. Prolonged or continuous infusion therapy has improved microbiological responses in pathogens with MICs at or 2-4 fold higher than existing EUCAST clinical breakpoints in pre-clinical studies. Human population pharmacokinetic modelling combined with Monte Carlo Simulation indicates improved pharmacodynamic target attainment rates and hence predicts improved clinical responses for those pathogens with raised MICs. However, the majority of human clinical trials comparing prolonged or continuous infusion to intermittent injection have failed to show superior clinical cures and for the most part microbiological successes. The exception being in various subgroup analyses. Future clinical trials need to focus on defining the T>MIC sizes associated with clinical or microbiological cure in man, on those subgroups of patients where continuous, or prolonged infusion, is likely to be of greatest benefit, seek to reduce pharmacokinetic variability by the use of therapeutic drug monitoring and include measurement of the risks of emergence of resistance in target pathogens At present, the clinical evidence base for prolonged or continuous infusion therapy is insufficiently strong to support widespread use.

  11. PkANN I: Non-Linear Matter Power Spectrum Estimation through Artificial Neural Networks

    Agarwal, Shankar; Feldman, Hume A; Lahav, Ofer; Thomas, Shaun A


    We investigate a new approach to confront small-scale non-linearities in the power spectrum of matter fluctuations. This ever-present and pernicious uncertainty is often the Achilles' heel in cosmological studies and must be reduced if we are to see the advent of precision cosmology in the late-time Universe. We show that an optimally trained Artificial Neural Network (ANN), when presented with a set of cosmological parameters ($\\Omega_{\\rm m} h^2, \\Omega_{\\rm b} h^2, n_s, w_0, \\sigma_8, \\sum m_\

  12. Nuclear imaging of neuroinflammation : a comprehensive review of [C-11]PK11195 challengers

    Chauveau, Fabien; Boutin, Herve; Van Camp, Nadja; Dolle, Frederic; Tavitian, Bertrand


    Neurodegenerative, inflammatory and neoplastic brain disorders involve neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful for diagnostic, drug development and therapy control of these frequent diseases. In vivo imaging can document the expression of the peripheral benz

  13. Strategic Planning for Educational Technology Initiatives in PK-12 Lutheran Schools

    Muth, Nicole


    Technology rich learning environments provide the potential for engaging, relevant, and personalized curricula that prepare students for 21st century careers. However, a lack of strategic planning by educators results in available technology not being used to its fullest potential. Several educational organizations have published guidelines for…

  14. CompTIA Project+ Study Guide: Exam PK0-003

    Heldman, Kim


    Prepare for CompTIA's newly updated Project+ certification exam. CompTIA is offering the first major update to its Project+ certification in six years, and this in-depth study guide from project management industry experts Kim and William Heldman is the perfect preparation for the new exam. You'll find complete coverage of all exam objectives, including key topics such as project planning, execution, delivery, closure, and others.: CompTIA's Project+ is the foundation-level professional exam in the complex world of project management; certified project managers often choose to go on and obtain

  15. Toward a poetics of dislocation: Elizabeth Bishop and PK Page writing "Brazil"

    McNeilly, Kevin


    ...."), what she and her fellow tourists actually come to possess as place are their seats on an unstable boat. [Lorrie Goldensohn] contends that [Brett C. Elizabeth Bishop]'s "new poems [of the mid-1950s...

  16. PK-PD modelling of the interaction of propofol and midazolam : implementation and future perspectives

    Lichtenbelt, Bart Jan


    This thesis describes the day to day interaction between propofol and midazolam as encountered in every day practice. The direct interaction of premedication given to patients before surgery has profound implications. The propofol induction dose can be decreased with respect to the target BIS. Besid

  17. Neutron experiments on nuclear order in silver at pK temperatures

    Nummila, K.K.; Tuoriniemi, J.T.; Vuorinen, R.T.


    Spontaneous long range antiferromagnetic order in the spin-1/2 s ystem of silver nuclei has been observed by neutron diffraction on a single crystal of Ag The observed antiferromagnetic state had a simple 1-k structure and no field induced phase transitions within the ordered state could be inden...

  18. PK-12 Virtual Schools: The Challenges and Roles of School Leaders

    Abrego, Jesus, Jr.; Pankake, Anita


    Building and sustaining a school and district culture that has a technology "growth mindset" and the implementation of processes that support a technology-specific culture in which, "the role of the leader is to ensure that the organization develops relationships that help produce desirable results," would ensure that teachers and principals…

  19. Vaatetusalan pk-yrityksen visuaalinen ilme ja viestintäcase Erja Raittinen Oy /

    Jäntti, Sohvi.


    Yrityksen visuaalinen viestintä on yksi tärkeimmistä tekijöistä pyrittäessä yrityksen oman erikoislaadun esiintuomiseen ja kilpailijoista erottumiseen. Onnistunut markkinointimateriaali on hyvä väline tunnettuuden lisäämisessä ja kohderyhmän tavoittamisessa. Erityisen tärkeäksi vaatetusalan pienille ja keskisuurille yrityksille visuaalisen ilmeen suunnittelun tekee alalla vallitseva kova kilpailu ja suuri tarjonta. Tutkimus pyrki selvittämään erottumisen ja oman erikoisosaamisen esi...

  20. Rational Daily Administration Times of Yinchenhao Decoction in Rats with Jaundice Based on PD/PK

    LV Jun-lan; JIN Shi-ying; YUAN Hai-long; HAN Jin; FU Shan-shan; JIN Shi-xiao; GUO Jing-jing; XIAO Xiao-he


    Objective To study the rational daily administration times of Yinchenhao Decoction (YCHD) when it was used to treat experimental jaundice in rats based on pharmacodynamics/pharmacokinetics model.Methods Rats were modeled by 4% 1-naphthylisothiocyanate (75 mg/kg) for 48 h,then YCHD was drenched with doses of 0.324 g/kg (extract,calculated with the clinical dosage) once,0.162 g/kg twice,and 0.108 g/kg thrice a day,respectively.The total bile and the flow rate of bile were observed after the first administration; Blood samples collected from the orbital sinus at different intervals were used to investigate the levels of liver enzymes (ALT and AST) and bilimbins (TBIL and DBIL),and determine the concentration of 6,7-dimethoxycoumarin (DME) in the plasma using UPLC at the same time,then we obtained the time-effect and time-dose curves.The rational daily administration times of YCHD when treating experimental jaundice were determined based on the comprehensive analysis of time-effect and time-concentration relationships.Results Within 10 h the total bile of rats which were administered once daily (G1) was I.65 and 1.33 times higher than that of twice and thrice (G2 and G3) a day,respectively,and the four biochemical indexes (TBIL,ALT,DBIL,and AST) of Gl decreased faster than those of G2 and G3 (P < 0.05).On the other hand,the blood drug level of DME when administrated once daily could maintain at a higher level for a longer time,and its Cmax and AUC0→t were higher than those of G2 and G3,which might be the main reason why its effect was the most significant.Conclusion It is more appropriate to administrate once daily when YCHD is used to treat jaundice.

  1. Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

    Auler Jr. J.O.


    Full Text Available Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB, 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m2 body surface area (BSA, and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m2 BSA (mean ± SD. Sodium diclofenac (1 mg/kg, im Voltaren 75® twice a day was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX were: 25% VAS (CPB vs 10% VAS (control, P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences

  2. The pK0\\Sigma+ final state in proton-proton collisions

    Abdel-Bary, M; Brinkmann, K-Th; Clement, H; Dietrich, J; Doroshkevich, E; Dshemuchadse, S; Ehrhardt, K; Erhardt, A; Eyrich, W; Filippi, A; Freiesleben, H; Fritsch, M; Gast, W; Georgi, J; Gillitzer, A; Gottwald, J; Hesselbarth, D; Jäger, H; Jakob, B; Jäkel, R; Karsch, L; Kilian, K; Koch, H; Krapp, M; Kreß, J; Kuhlmann, E; Lehmann, A; Marcello, S; Marwinski, S; Mauro, S; Meyer, W; Michel, P; Möller, K; Morsch, H P; Mörtel, H; Naumann, L; Paul, N; Pinna, L; Pizzolotto, C; Plettner, Ch; Reimann, S; Richter, M; Ritman, J; Roderburg, E; Schamlott, A; Schönmeier, P; Schroeder, W; Schulte-Wissermann, M; Sefzick, T; Stinzing, F; Steinke, M; Sun, G Y; Teufel, A; Ullrich, W; Wagner, G J; Wagner, M; Wenzel, R; Wilms, A; Wintz, P; Wirthand, S; Wüstner, P; Zupranski, P


    This paper reports results from a study of the reaction pp->pK0\\Sigma+ at beam momenta of p_{beam} = 2950, 3059, and 3200 MeV/c (excess energies of \\epsilon= 126, 161, and 206 MeV). Total cross sections were determined for all energies; a set of differential cross sections (Dalitz plots; invariant mass spectra of all two-body subsystems; angular distributions of all final state particles; distributions in helicity and Jackson frames) are presented for \\epsilon= 161 MeV. The total cross sections are proportional to the volume of available three-body phase-space indicating that the transition matrix element does not change significantly in this range of excess energies. It is concluded from the differential data that the reaction proceeds dominantly via the N(1710)P_{11} and/or N(1720)P_{13} resonance(s); N(1650)S_{11} and \\Delta(1600)P_{33} could also contribute.

  3. The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

    E. Reiling (Erwin); M.E.T. Dollé (Martijn); A.R. Youssef; M. Lee (Moonsook); B. Nagarajah (Bhawani); M. Roodbergen (Marianne); P. de With (Piet); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); J. Vijg (Jan); H. van Steeg (Harry); P. Hasty (Paul)


    textabstractKu80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based

  4. Experience of attaining high labor productivity in a stoping face using mechanized complex 110PK-70

    Reshetnikov, M.N.


    In 1979 when the first 1 million T of coal was produced at the mine ''Zyryanovskaya'' high volumes of coal extraction were attained in individual months: in January 102,300 T, in July 122,200 T. In 1980, high results were also attained. In January 106,000 T were extracted and in November 108,500 T of coal. The brigade has accumulated experience for introducing scientific organization of labor and improving labor productivity. In 1977 labor productivity of the workers in the stoping face was 31.5 T per shift, in 1978 variable productivity was elevated to 48.2 T. In 1979 labor productivity reached 67.3 T per shift. The best results for productivity was reached in June 1979, 90 T at the outlet, in February 1980--81.1 T per shift. The success of the brigade is formed of many factors, technical, organizational, economic. The basis for high labor productivity of the workers is timely preparation of new longwalls, normal production conditions for fulfillment of plans and the adopted socialist commitments. An important factor in the work of the extraction brigade is the type and condition of mining equipment. The level of work organization as a whole depends on the brigade, directly on the miners and the section leaders themselves. High conscientiousness of all the brigade members also is important for improving labor productivity. The majority of workers in the brigade (about 70%) are members of the party. Mass technical creativity of all the brigade members is also a great reserve for improving labor efficiency. The brigade has 24 efficiency experts who annually introduce 20-30 suggestions each aimed at improving work efficiency.

  5. A PK-PD model-based assessment of sugammadex effects on coagulation parameters.

    Bosch, Rolien; van Lierop, Marie-José; de Kam, Pieter-Jan; Kruithof, Annelieke C; Burggraaf, Jacobus; de Greef, Rik; Visser, Sandra A G; Johnson-Levonas, Amy O; Kleijn, Huub-Jan


    Exposure-response analyses of sugammadex on activated partial thromboplastin time (APTT) and prothrombin time international normalized ratio (PT(INR)) were performed using data from two clinical trials in which subjects were co-treated with anti-coagulants, providing a framework to predict these responses in surgical patients on thromboprophylactic doses of low molecular weight or unfractionated heparin. Sugammadex-mediated increases in APTT and PT(INR) were described with a direct effect model, and this relationship was similar in the presence or absence of anti-coagulant therapy in either healthy volunteers or surgical patients. In surgical patients on thromboprophylactic therapy, model-based predictions showed 13.1% and 22.3% increases in respectively APTT and PT(INR) within 30min after administration of 16mg/kg sugammadex. These increases remain below thresholds seen following treatment with standard anti-coagulant therapy and were predicted to be short-lived paralleling the rapid decline in sugammadex plasma concentrations. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. PK-12 Virtual Schools: The Challenges and Roles of School Leaders

    Abrego, Jesus, Jr.; Pankake, Anita


    Building and sustaining a school and district culture that has a technology "growth mindset" and the implementation of processes that support a technology-specific culture in which, "the role of the leader is to ensure that the organization develops relationships that help produce desirable results," would ensure that teachers and principals…

  7. A Descriptive Study of Wisconsin PK-12 Virtual Public School Program Operations and Management

    Banker, Margaret M.


    E-Learning as it pertains to public education is in its infancy in America. There is limited research on what operational design, development, and management attributes of virtual school programs foster student achievement. The Wisconsin Department of Instruction has not developed or adopted program standards for E-Learning programs. The purpose…

  8. PK-PD Modeling of Fluoroquinolones and ABC Transporters in Poultry

    Haritova, A.M.


    In the first part of this thesis advance pharmacokinetic models, based on an integration of pharmacokinetic and pharmacodynamic data for selected fluotoquinolones, are presented. The comparative investigations with danofloxacin mesylate and marbofloxacin indicated that with both fluoroquinolones a c

  9. PK-PD Modeling of Fluoroquinolones and ABC Transporters in Poultry

    Haritova, A.M.


    In the first part of this thesis advance pharmacokinetic models, based on an integration of pharmacokinetic and pharmacodynamic data for selected fluotoquinolones, are presented. The comparative investigations with danofloxacin mesylate and marbofloxacin indicated that with both fluoroquinolones a c

  10. Search for the kaonic bound state ppK- in pp→ pK

    Münzer, Robert; Epple, Eliane; Fabbietti, Laura


    The investigation of the kaon-nucleon interaction has been intensified in the last years due to new measurements of the Λ(1405) resonance and indications on the existence of the ppK- bound state. Such results are heavily discussed, since they can lead to new knowledge about the -Nucleon interaction. In the last years, the reaction p+p →p+ K+ + Λ has been measured at the GSI Helmholtzcentre in Darmstadt with the FOPI and the HADES spectrometers at beam energies of 3.1 GeV and 3.5 GeV, respectively. New analyses methods have been developed to understand quantitatively all the processes contributing to the pK+Λ final state. At the FOPI experiment a set of around 1.000 events and in the HADES experiment around 22.000 events of the exclusive reaction p+p →p+ K+ + Λ could be extracted. These reconstructed exclusive events were analyzed within the Bonn Gatchina Partial Wave Analysis (BG-PWA) framework, which provides a coherent description of the data including several resonant and non-resonant production channels. The results have shown that the inclusion of interferences between different channels has to be considered in the analysis. Based on the description of the data with the Partial Wave Analysis an upper limit on the cross-section for the production of the ppK- could be determined.

  11. The Fungal Metabolite, Pyrrocidine A, induces Apoptosis in HEPG2 Hepatocytes and PK15 Renal Cells

    Pyrrocidines are polyketide-amino acid-derived antibiotics produced by Acremonium zeae, a prevalent seed-borne endophyte of corn. Pyrrocidines exhibit potent activity against Gram-positive bacteria, including drug resistant strains, and display significant activity against Candida albicans, as well...

  12. Reflections upon UNPOL Peacekeeping English Training%关于维和警察英语培训的思考




  13. Russian-United States Guide for Tactics, Techniques and Procedures of Peacekeeping Forces during the Conduct of Exercises


    relations become too familia -. There are two major disadvantages: first, the -ontingent may not have enough time to acquire a working knowledge of the...ACT. DEPENDENT ALWAYS UPON THE CIRCUM4STANCES, THE FOLLOWING ARE SOME EXAMPLES OF SUCE ACTS: (1) FIRING OR BEING ABOUT TO FIRE A WEAPON. (2) PLANTING

  14. Environmental Assessment, Minuteman III and Peacekeeper Silo Elimination, Malmstrom AFB, Montana; F. E. Warren AFB, Wyoming; and Vandenberg AFB, California


    so small watersheds can receive heavy rainfall for short durations, and localized flooding can occur. However, because of the nature of the...and topography of the air basin, and the prevailing meteorological conditions. The significance of a pollutant concentration is determined by...Demographic information from the U.S. Bureau of the Census was used to extract data on minority, low-income, and child populations within Montana and

  15. Final Environmental Impact Statement, Peacekeeper in Minuteman Silos, F. E. Warren AFB, Wyoming. Volume 2. Public Comments.


    thoE91- OlaOlnueatoot toets 82011. OR aula 1-tO. 4 t008t88h 3. - 011.0. CA- St. IItaahba tt00ta.’Wa.o~ttppoijd~atto10I Qo 1062 12 IRI 7-t0. omeal...otte s , sort t,t of accidents are virtually iared in the 910. mis cosiuenenhsntscts.firq 1t."oetttn U’ nsvtngusi agn-tdmo httats’c serou ’wsic t...betdenioq 5 "the Imlt detrec that we despetely 0"to 6 ef foot, aux land bmed syste arm virtually Ineffective 6 adres them two proble that I Mak. of, .a

  16. Warriors and peacekeepers: testing a biosocial implicit leadership hypothesis of intergroup relations using masculine and feminine faces.

    Brian R Spisak

    Full Text Available This paper examines the impact of facial cues on leadership emergence. Using evolutionary social psychology, we expand upon implicit and contingent theories of leadership and propose that different types of intergroup relations elicit different implicit cognitive leadership prototypes. It is argued that a biologically based hormonal connection between behavior and corresponding facial characteristics interacts with evolutionarily consistent social dynamics to influence leadership emergence. We predict that masculine-looking leaders are selected during intergroup conflict (war and feminine-looking leaders during intergroup cooperation (peace. Across two experiments we show that a general categorization of leader versus nonleader is an initial implicit requirement for emergence, and at a context-specific level facial cues of masculinity and femininity contingently affect war versus peace leadership emergence in the predicted direction. In addition, we replicate our findings in Experiment 1 across culture using Western and East Asian samples. In Experiment 2, we also show that masculine-feminine facial cues are better predictors of leadership than male-female cues. Collectively, our results indicate a multi-level classification of context-specific leadership based on visual cues imbedded in the human face and challenge traditional distinctions of male and female leadership.

  17. Affecting Reform: Explaining the Kingdom of Cambodia’s Contributions to United Nations Peacekeeping Operations in Comparative Context


    Yudhoyono was a principal architect of the New Paradigm ( Paradigma Baru), the formal military doctrine that replaced [Dual Function] dwi-fungsa.”164 Under... Paradigma Baru, and in stark contrast to the RCAF in Cambodia, “the TNI has withdrawn, as an institution, from day-to-day political activities.”165

  18. African Sub-Regional Organizations in Peacekeeping and Peacemaking: The Economic Community of West African State (ECOWAS)


    West Africa.18 At the advent of the Liberian crisis ECOWAS attempted to move quickly from dealing with economic to security 17 Confort Ero and> (8 February 2005). Confort Ero and A, Ndinga-Muvumba, "Small Arms, Light Weapons", in Adekeye Adebajo and Ismail Rashid, West

  19. 76 FR 71332 - Notice of Intent (Noi) To Prepare an Environmental Assessment for Minuteman III and Peacekeeper...


    ... Great Falls, Shelby, Choteau, and Conrad, Montana; and Cheyenne, Torrington, and Chugwater, Wyoming. The... Conrad, MT 6:30-8:30 p.m. December 7, 2011 Great Falls, MT 6:30-8:30 p.m. December 8, 2011 Shelby, MT...

  20. Draft Environmental Impact Statement. Peacekeeper in Minuteman Silos, 90th Strategic MIssile Wing, F. E. Warren Air Force Base


    m ~ ’. - C\\.J > LL L o- r-. LA) CD\\ M0 m ’f0 C\\J a)0 2- LUC 0 C) 1-- J -J ’ n 1.U-- 00 U-) C) ’.0 C:) 0 00 a)- ko0 . C) C.) (f)a)’ Lfl (Ř (’.4 _JC...Strand Nancy Williams Thomas Williams John Winkel Jim Woodward CHEYENNE CENTRAL HIGH SCHOOL June 28, 1983 - 1:00 PM SCOPING MEETING ATTENDANCE LIST...Virgil Slough Mark Winkel Joan Snow Rizzo Zars Jean Stout PINE BLUFFS HIGH SCHOOL June 28, 1983 - 7:00 PM SCOPING MEETING ATTENDANCE LIST Theron Anderson

  1. Female Participation in Formed Police Units: A Report on the Integration of Women in Formed Police Units of Peacekeeping Operations

    2012-09-01 women- femmes /resolution1325_04.aspx?lang=eng&view=d 61 127. Gary W. Cordner and Ann Marie Cordner , “Stuck on a Plateau...Security Council Resolution 1325 on women, peace and secu- rity,” July 2004, women- femmes

  2. A single-field integrated boost treatment planning technique for spot scanning proton therapy

    Zhu, Xiaorong Ronald; Poenisch, Falk; LI, Heng; Zhang, Xiaodong; Sahoo, Narayan; Richard Y. Wu; Li, Xiaoqiang; Lee, Andrew K.; Chang, Eric L.; Choi, Seungtaek; Pugh, Thomas; Steven J. Frank; Gillin, Michael T.; Mahajan, Anita; Grosshans, David R.


    Purpose Intensity modulated proton therapy (IMPT) plans are normally generated utilizing multiple field optimization (MFO) techniques. Similar to photon based IMRT, MFO allows for the utilization of a simultaneous integrated boost in which multiple target volumes are treated to discrete doses simultaneously, potentially improving plan quality and streamlining quality assurance and treatment delivery. However, MFO may render plans more sensitive to the physical uncertainties inherent to partic...

  3. Estudio de trazado de la variante de la carretera CV-700 a su paso por el municipio de Vall de Gallinera del PK 42+300 al PK 45+200 (provincia de Alicante).



    [EN] This basic project consists in a bypass design of the Valencian regional road CV-700 as it passes the urban villages of Benialí, Benissivà and Benitaia, belonging to municipality of La Vall de Gallinera in Alicante province. The project is based on improving layout of road, avoiding to pass through villages. Becuase nowadays the road passes with a lot of curves. The final result is a 1696 metres bypass, a conventional road C-40 single carriageway and a 3 metres lanes with 0.5 metres shou...

  4. EFECTO DEL MEDIO DE CULTIVO EN EL DESARROLLO DE Suillus granulatus (L. Roussel y S. brevipes (Pk. Kuntze

    Dulce Ma. Murrieta-Hernández


    Full Text Available La tasa de crecimiento micelial de los hongos ectomicorrícicos Suillus granulatus y S. brevipes, se evaluó en tres medios de cultivo (PDA, BAF y MNM con dos valores de pH (4.8 y 5.8, con el fin de seleccionar el mejor medio de cultivo. Las cepas se aislaron de esporomas colectados en el bosque de Pinus hartwegii del Parque Nacional Cofre de Perote, Veracruz, México. Se encontraron diferencias significativas (Tukey, P ≤ 0.05 en el área de crecimiento de ambas especies; los valores más altos se registraron en el medio PDA. Respecto a los valores de pH evaluados, no hubo diferencias significativas. Cada uno de los medios evaluados se puede utilizar para el cultivo de las cepas S. granulatus y S. brevipes dependiendo de los objetivos. El medio PDA fue el mejor sustrato para el crecimiento de las cepas. Se sugiere utilizar el medio BAF para la producción masiva de micelio para inóculo y el medio MNM se recomienda ya sea para el mantenimiento de las cepas o para pruebas de micorrización.

  5. Practical experience of using human microdosing with AMS analysis to obtain early human drug metabolism and PK data.

    Garner, R Colin


    The background to human microdosing or Phase 0 studies is reviewed, focusing particularly on the information that such studies can provide in the context of exploratory clinical development. Examples are provided of the microdose-validation studies known as the Consortium for Resourcing and Evaluating AMS Microdosing trial and EU Microdosing AMS Partnership Programme, which demonstrated that there was good dose proportionality between microdose and pharmacological dose pharmacokinetics. When microdosing was applied to ten development drugs, it was found that all ten molecules showed dose proportionality between the microdose and the pharmacological dose. The majority of microdose studies have used accelerator mass spectrometry (AMS) analysis and only these studies that are considered here; AMS provides information on all metabolites, even if these are minor. There is now sufficient scientific data to justify microdose studies being routinely conducted as part of the drug-development process.

  6. Recurrent and founder mutations in the Netherlands : mutation p.K217del in troponin T2, causing dilated cardiomyopathy

    Otten, E.; Deprez, R. H. Lekanne Dit; Weiss, M. M.; van Slegtenhorst, M.; Joosten, M.; van der Smagt, J. J.; Kerstjens-Frederikse, W. S.; Roofthooft, M. T. R.; Balk, A. H. M. M.; van den Berg, M. P.; van Tintelen, J. P.; Ruiter, J.S.; de Jonge, N.


    Background. About 30% of dilated cardiomyopathy (DCM) cases are familial. Mutations are mostly found in the genes encoding lanain A/C, beta-myosin heavy chain and the sarcomeric protein cardiac troponin-T (TNNT2). Mutations in TNNT2 are reported in approximately 3% of DCM patients. The overall pheno

  7. Acid-base titrations for polyacids: Significance of the pK sub a and parameters in the Kern equation

    Meites, L.


    A new method is suggested for calculating the dissociation constants of polyvalent acids, especially polymeric acids. In qualitative form the most significant characteristics of the titration curves are demonstrated and identified which are obtained when titrating the solutions of such acids with a standard base potentiometrically.

  8. Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

    Bodenlenz, Manfred; Höfferer, Christian; Magnes, Christoph;


    patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps. METHODS: Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple d......OFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis. RESULTS: dOFM was well tolerated...... and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1. CONCLUSIONS: Novel membrane-free probes and wearable multi...

  9. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Mahmoud Ameri


    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  10. A Physiologically Based Pharmacokinetic (PB/PK) Model for Multiple Exposure Routes of Soman in Multiple Species


    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing...Although the beagle is extensively used susceptible to the neurotoxicity induced by ivermectin , a in the safety assessment studies of new drug candidates...tissueainto CYP isozyme polymorphism in dogs. Recently, a single ivermectin not to be extruded from the brain tissue into nucleotide polymorphism

  11. [PK/PD Modeling as a Tool for Predicting Bacterial Resistance to Antibiotics: Alternative Analyses of Experimental Data].

    Golikova, M V; Strukova, E N; Portnoy, Y A; Firsov, A A


    Postexposure number of mutants (NM) is a conventional endpoint in bacterial resistance studies using in vitro dynamic models that simulate antibiotic pharmacokinetics. To compare NM with a recently introduced integral parameter AUBC(M), the area under the time course of resistance mutants, the enrichment of resistant Staphylococcus aureus was studied in vitro by simulation of mono(daptomycin, doxycycline) and combined treatments (daptomycin + rifampicin, rifampicin + linezolid). Differences in the time courses of resistant S. aureus could be reflected by AUBC(M) but not N(M). Moreover, unlike AUBC(M), N(M) did not reflect the pronounced differences in the time courses of S. aureus mutants resistant to 2x, 4x, 8x and 16xMIC of doxycycline and rifampicin. The findings suggested that AUBC(M) was a more appropriate endpoint of the amplification of resistant mutants than N(M).

  12. Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells

    Hye Lim Lee


    Conclusion: These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.

  13. Transgender and Gender-Creative Students in PK-12 Schools: What We Can Learn from Their Teachers

    Meyer, Elizabeth J.; Tilland-Stafford, Anika; Airton, Lee


    Context: A growing body of work reflects the ways in which gender-creative and transgender students are ill-served by current social climates in the vast majority of public schools. Few studies have explored this topic from an educator's perspective. Purpose: This study was designed to develop a conception of the barriers and supports that exist…

  14. Self-assembly of 2D sandwich-structured MnFe{sub 2}O{sub 4}/graphene composites for high-performance lithium storage

    Li, Songmei, E-mail:; Wang, Bo; Li, Bin; Liu, Jianhua; Yu, Mei; Wu, Xiaoyu


    Highlights: • MFO/GN composites were synthesized by a facile in situ solvothermal approach. • The MFO microspheres are sandwiched between the graphene layers. • Each MFO microsphere is an interstitial cluster of nanoparticles. • The MFO/GN electrode exhibits an enhanced cyclability for Li-ion batteries anodes. - Abstract: In this study, two-dimensional (2D) sandwich-structured MnFe{sub 2}O{sub 4}/graphene (MFO/GN) composites are synthesized by a facile in situ solvothermal approach, using cetyltrimethylammonium bromide (CTAB) as cationic surfactant. As a consequence, the nanocomposites of MFO/GN self-assembled into a 2D sandwich structure, in which the interstitial cluster structure of microsphere-type MnFe{sub 2}O{sub 4} is sandwiched between the graphene layers. This special structure of the MFO/GN composites used as anodes for lithium-ion batteries will be favorable for the maximum accessible surface of electroactive materials, fast diffusion of lithium ions and migration of electron, and elastomeric space to accommodate volume changes during the discharge–charge processes. The as-synthesized MFO/GN composites deliver a high specific reversible capacity of 987.95 mA h g{sup −1} at a current density of 200 mA g{sup −1}, a good capacity retention of 69.27% after 80 cycles and excellent rate performance for lithium storage.

  15. 中国维和警察培训课程资源探析%On Construction of Curriculum Resources of China Peacekeeping Police Training




  16. Probe into the Basic Knowledge System of Peacekeeping Discipline%试论维和学的基本知识体系




  17. 中国维和警察:十年征战,捍卫和平%China's Peacekeeping Police: Decade of Expedition for Safeguarding Peace



    @@ 2010年是中国警察参加联合国民事维和行动10周年.然而不幸的是,1月13日,在海地发生的里氏7.3级强烈地震中,正在海地执行维和任务的朱晓平等8位中国维和警察殉职.在8位英烈极尽哀荣的悼念活动中,中国维和警察群体引起了亿万国人和国际社会的普遍关注.

  18. 维和警察的心理压力及其调控%On the stress management of Chinese peacekeeping CIVPOL




  19. 中国维和警察学科理论体系基本框架构想%Basic Conception Framework on China Peacekeeping Police Science




  20. An Analysis of Australia' s Peacekeeping Police Institution%澳大利亚维和警察新体制解析