How leukemia stem cells gained resistance to radiation and chemotheraphy is poorly defined, yet critically determines how leukemia cells tolerate conventional leukemia therapy. Normal hematopoietic stem cells and leukemia initiating cells are known to share many functional properties. Therefore, they are supposed to utilize many common mechanistic pathways for their survival and migration. Using genetically engineered mice we demonstrated the functional roles of P2Y14 in preserving regenerative capacity by constraining senescence induction and molecular events governing it. Since P2Y14 is highly expressed in differentiation-resistant leukemia cells, P2Y14 expression in leukemia cells may also function in modulating the resistance to conventional cancer treatment. We believe these data define for the first time in mammals the identity and impact of a receptor modulating stem/progenitor tolerance of stress. By providing a mechanistic insight for the roles of P2Y14 in the stress-induced injury, our preliminary results are expected to provide the foundation for an effective treatment to destroy therapy resistant leukemia cells. In addition, we identified a nucleotide sugar, UDP-Glc, as a novel mobilizer of long-term repopulating HSPCs. This finding may also have important clinical implications in designing new mobilization strategies to improve the efficiency and outcome of autologous and allogeneic peripheral blood stem cell (PBSC) transplantation.

关键词：白血病;干细胞;老化(生理学);血液细胞,癌症;化疗;造血细胞

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Studies indicate that Posttraumatic Stress Disorder (PTSD) is not uncommon among medical personnel serving in the military and that its prevention remains a significant challenge. While extensive PTSD research findings exist that are generalizable to the military dedicated research specific to its at-risk population of medical workers is less common. The purpose of this review is to perform a systematic search for the most effective strategies in the prevention of PTSD and consider their applicability to the military healthcare provider. Comprehensive electronic search was performed utilizing MEDLINE, Cochrane Database PubMed, CINAHL (EBSCO), Health and Wellness Resource Center, Nursing and Allied Health Source, Applied Social Sciences Index (CSA), PsycARTICLES (APA), and PAIS International (CSA). Significant variation exists among PTSD preventive strategies in effectiveness and in applicability to military healthcare workers. Strategies such as multiple early interventions, psychological debriefing, pre-deployment training and psychoeducation lack current evidence for efficacy in the prevention of PTSD. PTSD preventive strategies should favor therapy that identifies the traumatic event, with long-term outpatient therapy more effective than short-term inpatient. Vigorous physical exercise and unit cohesion are significantly associated with decreased odds of PTSD symptom development among military personnel. Awareness of significant risk factors may improve preventive outcomes by enabling earlier intervention, and insights on resiliency may further optimize effective PTSD preventive strategies. Modified Prolonged Exposure (PE) therapy may be an effective and practical early intervention with expanded applicability to military operation settings.

关键词：健康;医务人员;精神障碍,创伤后应激障碍

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The hydrostatic hyperbaric chamber (HHC) represents the merger of several technologies in development for NASA aerospace applications, harnessed to directly benefit global health. NASA has significant experience developing composite hyperbaric chambers for a variety of applications. NASA also has researched the application of water-filled vessels to increase tolerance of acceleration forces. The combination of these two applications has resulted in the hydrostatic chamber, which has been conceived as a safe, affordable means of making hyperbaric oxygen therapy (HBOT) available in the developing world for the treatment of a variety of medical conditions. Specifically, HBOT is highly-desired as a possibly curative treatment for Buruli Ulcer, an infectious condition that afflicts children in sub-Saharan Africa. HBOT is simply too expensive and too dangerous to implement in the developing world using standard equipment. The HHC technology changes the paradigm. The HHC differs from standard hyperbaric chambers in that the majority of its volume is filled with water which is pressurized by oxygen being supplied in the portion of the chamber containing the patient s head. This greatly reduces the amount of oxygen required to sustain a hyperbaric atmosphere, thereby making the system more safe and economical to operate. An effort was taken to develop an HHC system to apply HBOT to children that is simple and robust enough to support transport, assembly, maintenance and operation in developing countries. This paper details the concept for an HHC ventilation and pressurization system to provide controlled pressurization and adequate washout of carbon dioxide while the subject is enclosed in the confined space during the administration of the medical treatment. The concept took into consideration operational complexity, safety to the patient and operating personnel, and physiological considerations. The simple schematic, comprised of easily acquired commercial hardware, supports sustainability.

关键词：高压室；流体静力学；航空航天工程

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Almost 50of all ER+ breast tumors will not respond to endocrine therapy. Resistance to endocrine therapy remains a significant clinical problem and advanced ER+ breast cancer is largely an incurable disease. Endocrine manipulation in sensitive cells can result in the induction of cell death through autophagy and/or apoptosis. We have recently obtained data implicating the unfolded protein response (UPR) as induced by the splicing of X-box binding protein-1 (XBP1) in the regulation of endocrine responsiveness in breast cancer cells. UPR is a key component of the endoplasmic reticulum stress response and has not previously been implicated in endocrine responsiveness. We hypothesize that XBP1(S) is a key regulator of breast cancer cell fate, acting through its regulation of UPR, BCL2, and BCL2:BECN1 heterodimers, and their subsequent effects on autophagy and apoptosis. We will determine how XBP1(S) affects cell fate, evaluating the role of an induction of UPR that activates a prosurvival autophagy. In endocrine sensitive cells, autophagy should persist and become a cell death mechanism that can also initiate apoptosis. In resistant cells, basal autophagy should represent a survival mechanism to deal with the loss of autocrine and other growth factor signaling that accompanies endocrine therapy. We will explore the mechanistic role of XBP1(S) and its integrated signaling through UPR and BCL2 to regulate cell fate in both endocrine sensitive and resistant cells.

关键词：乳腺癌;内分泌腺体;蛋白质;灵敏度;细胞(生物学)

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The goal of this work is to increase the availability of critical mouse models of human muscular dystrophy (MD) for both hypothesis testing and preclinical therapy development. Our multi-disciplinary team from The Jackson Laboratory (JAX) and the Children s National Medical Center (CNMC) has expertise in MD, repository management, mouse models, and preclinical testing. At JAX, Drs. Lutz and Cox have established the MD Repository (Aim1) to leverage JAX s considerable expertise and infrastructure to maintain and distribute MD mouse and information resources to the scientific community. In Aim 2 we are developing novel DMD transgenic mice, which model patients receiving successful exon-skipping therapies. We propose to address the fundamental, but often overlooked question related to the functionality of resulting Dystrophin molecules containing in-frame deletions that are expected to arise by successful treatment of patient mutations. Our transgenic experiments will model the best-case-scenario outcome for AO-mediated therapy in which one assumes that a particular compound is capable of 100effective exon-skipping to restore the reading frame. In Aim 3, we are generating congenic mdx mice to better model the symptoms of the human disease and to identify genetic modifiers that can alter disease onset and severity. In Aim 4, Dr. Nagaraju at CNMC is carrying out preclinical studies with three promising therapeutic compounds (GW501516, AICAR and Dantrolene) using key models developed at JAX. Overall, this program will greatly expand the accessibility and availability of mouse model resources for MD translational research and therapeutic development.

关键词：临床医学;医疗服务;症状和体征

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In space, the absence of gravity alone causes unique physiological stress. Significant biomedical changes, across multiple organ systems, such as body fluid redistribution, diminished musculoskeletal strength, changes in cardiac function and sensorimotor control have been reported. The time course of development of these disorders and severity of symptoms experienced by individuals varies widely. Space motion sickness (SMS) is an example of maladaptation to microgravity, which occurs early in the mission and can have profound effects on physical health and crew performance. Disturbances in sleep quality, perception, emotional equilibrium and mood have also been reported, with impact to health and performance varying widely across individuals. And lastly, post-flight orthostatic intolerance, low blood pressure experienced after returning to Earth, is also of serious concern. Both the Russian and American space programs have a varied list of human errors and mistakes, which adversely impacted mission goals. Continued probability of human exposure to microgravity for extended time periods provides a rationale for the study of the effects of stress. The primary focus of this research group is directed toward examining individual differences in: (a) prediction of susceptibility to these disorders, (b) assessment of symptom severity, (c) evaluation of the effectiveness of countermeasures, and (d) developing and testing a physiological training method, Autogenic-Feedback Training Exercise (AFTE) as a countermeasure with multiple applications. The present paper reports on the results of a series of human flight experiments with AFTE aboard the Space Shuttle and Mir Space Station, and during emergency flight scenarios on Earth.

关键词：航空航天医学杂志；心理生理学；生理效应；生物医学

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A technology which enables us to share haptic information between remote several systems is required. Multilateral control system is an effective system which can implement the technology. However, haptic information tends to deteriorate under communication delay because haptic information is bilateral. Since multilateral control connects all subsystems to share information, the information is greatly affected by time delay. Selecting the communication link is one way of the solving the problem, however there were no means to know the strength of the link. Therefore, two things are proposed in this paper. Firstly, the index which is named "information volume" to quantify the amount of information that each subsystem has is proposed. This index can be applied to a system which has time delay in communication links. Using the index, the importance of each communication link which includes delay time can be quantified. Secondly, the algorithm to select the communication links is proposed based on the information volume. The target relationship regarding the information volumes is set and the links which are unnecessary are to be removed. The validity of the proposal is confirmed by experiments, and the results show that the degradation of haptic sensation under communication delay is prevented.

关键词：多边控制系统;邻接矩阵图;最大特征值;系统连接;通信延迟

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Until ~2010, the only astronaut data available to researchers was de-identified or grouped data archived within the Life Sciences Data Archive (LSDA).

关键词：生命科学；国际空间站；航天医学；生物医学数据

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This paper addresses the problem of finding several different solutions with the same optimum performance in single objective real-world engineering problems. In this paper a parallel robot design is proposed. Thereby, this paper presents a genetic algorithm to optimize uni-objective problems with an infinite number of optimal solutions. The algorithm uses the maximin concept and e-dominance to promote diversity over the admissible space. The performance of the proposed algorithm is analyzed with three well-known test functions and a function obtained from practical real-world engineering optimization problems. A spreading analysis is performed showing that the solutions drawn by the algorithm are well dispersed.

关键词：算法；机器人；函数；性能

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This paper addresses the tracking problem for the dynamic model of a unicycle mobile robot. A novel optimization method inspired on the chemical reactions is applied to solve this motion problem by integrating a kinematic and a torque controller based on fuzzy logic theory. Computer simulations are presented confirming that this optimization paradigm is able to outperform other optimization techniques applied to this particular robot application.

关键词：机器人；模糊逻辑理论；仿真；动力学

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