Regenerative Medicine: Creating the Future for Military Medicine
2009-08-01
research institutes, and/or small/large businesses by identifying and facilitating appropriate partnerships as well as recommending more targeted...cells without the need for prolonged culture periods to expand the cell populations. In addition, the researchers have found a method that will induce...Regenerative Medicine CREATING THE FUTURE FOR MILITARY MEDICINE U.S. ARMY MEDICAL RESEARCH & MATERIEL COMMAND (USAMRMC) TELEMEDICINE & ADVANCED
Multi-target drugs: the trend of drug research and development.
Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao
2012-01-01
Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.
Religious bias among religiously conscious black christians in the United States.
Van Camp, Debbie; Sloan, Lloyd Ren; Elbassiouny, Amanda
2014-01-01
Research with White participants has demonstrated religious intergroup bias; however, religious identity may be different for Black Americans. Only religiously conscious Black Christians demonstrated a preference for Christian targets over Muslim and Atheist targets. Future research should consider what factors result in a person becoming conscious of other's religion.
Drug target inference through pathway analysis of genomics data
Ma, Haisu; Zhao, Hongyu
2013-01-01
Statistical modeling coupled with bioinformatics is commonly used for drug discovery. Although there exist many approaches for single target based drug design and target inference, recent years have seen a paradigm shift to system-level pharmacological research. Pathway analysis of genomics data represents one promising direction for computational inference of drug targets. This article aims at providing a comprehensive review on the evolving issues is this field, covering methodological developments, their pros and cons, as well as future research directions. PMID:23369829
Double-shell target fabrication workshop-2016 report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Y. Morris; Oertel, John; Farrell, Michael
On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activitiesmore » at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.« less
Guidance, Navigation, and Control Technology Assessment for Future Planetary Science Missions
NASA Technical Reports Server (NTRS)
Beauchamp, Pat; Cutts, James; Quadrelli, Marco B.; Wood, Lincoln J.; Riedel, Joseph E.; McHenry, Mike; Aung, MiMi; Cangahuala, Laureano A.; Volpe, Rich
2013-01-01
Future planetary explorations envisioned by the National Research Council's (NRC's) report titled Vision and Voyages for Planetary Science in the Decade 2013-2022, developed for NASA Science Mission Directorate (SMD) Planetary Science Division (PSD), seek to reach targets of broad scientific interest across the solar system. This goal requires new capabilities such as innovative interplanetary trajectories, precision landing, operation in close proximity to targets, precision pointing, multiple collaborating spacecraft, multiple target tours, and advanced robotic surface exploration. Advancements in Guidance, Navigation, and Control (GN&C) and Mission Design in the areas of software, algorithm development and sensors will be necessary to accomplish these future missions. This paper summarizes the key GN&C and mission design capabilities and technologies needed for future missions pursuing SMD PSD's scientific goals.
Language Teachers' Target Language Project: Language for Specific Purposes of Language Teaching
ERIC Educational Resources Information Center
Korenev, Alexey; Westbrook, Carolyn; Merry, Yvonne; Ershova, Tatiana
2016-01-01
The Language Teachers' Target Language project (LTTL) aims to describe language teachers' target language use domain (Bachman & Palmer 2010) and to develop a language test for future teachers of English. The team comprises four researchers from Moscow State University (MSU) and Southampton Solent University.
Incorporating additional targets into learning trials for individuals with autism spectrum disorder.
Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany M
2015-01-01
Recently, researchers have investigated the effectiveness and efficiency of presenting secondary targets during learning trials for individuals with autism spectrum disorder (ASD). This instructional method may be more efficient than typical methods used with learners with ASD, because learners may acquire secondary targets without additional instruction. This review will discuss the recent literature on providing secondary targets during teaching trials for individuals with ASD, identify common aspects and results among these studies, and identify areas for future research. © Society for the Experimental Analysis of Behavior.
Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang
2016-01-01
The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397
Time Critical Targeting: Predictive Vs Reactionary Methods An Analysis For The Future
2002-06-01
critical targets. To conduct the analysis, a four-step process is used. First, research is conducted to determine which future aircraft, spacecraft , and...the most promising aircraft, spacecraft , and weapons are determined , they are categorized for use in either the reactive or preemptive method. For...no significant delays, 292; Alan Vick et al., 17. 33 Ibid. 12 sensors are Electro-optical (EO) sensors, thermal imagers , and signal intelligence
2001 Gordon Research Conference on MYOGENESIS
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wold, Barbara
2001-05-04
The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.
Wilson, Nathan J; Cordier, Reinie; Doma, Kenji; Misan, Gary; Vaz, Sharmila
2015-08-01
The Men's Shed movement supports a range of men's health promotion initiatives. This paper examines whether a Men's Shed typology could inform future research and enable more efficient and targeted health promotion activities through Men's Sheds. The International Men's Shed Survey consisted of a cross-sectional exploration of sheds, their members, and health and social activities. Survey data about shed 'function' and 'philosophy' were analysed using descriptive and inferential statistics. A framework of Men's Sheds based on function and philosophy demonstrated that most sheds serve a primary utility function, a secondary social function, but most importantly a primary social opportunity philosophy. Sheds with a primary health philosophy participated in fewer health promotion activities when compared with sheds without a primary health philosophy. In addition to the uniform health promotion resources distributed by the Men's Shed associations, specific health promotion activities, such as prostate education, are being initiated from an individual shed level. This framework can potentially be used to enable future research and health promotion activities to be more efficiently and effectively targeted. SO WHAT? Men experience poorer health and well being outcomes than women. This framework offers a novel approach to providing targeted health promotion activities to men in an environment where it is okay to talk about men's health.
NASA Astrophysics Data System (ADS)
Olson, C. L.; Cuneo, M. E.; Desjarlais, M. P.; Filuk, A. B.; Greenly, J. B.; Hanson, D. L.; Hinshelwood, D. D.; Hubbard, R. F.; Lampe, M.; Lockner, T. R.
Present Light Ion Fusion (LIF) target experiments on PBFA 2 use a barrel diode in which the total transport length from the anode to the target is less than or equal to 15 cm. Future LIF development includes high yield applications (LMF) and energy production (ETF and LIBRA power plants) that require standoff - the generation of extracted ion beams and transport of these beams over distances of several meters. Standoff research includes the development of high efficiency extraction diodes (single stage and two-stage), improvements in beam quality (divergence, purity, uniformity, etc.), and the efficient transport and focusing of these beams over distances of several meters to a fusion target. Progress in all of these areas is discussed, as well as a strategy to reduce the divergence from the present 17 mrad for 5 MeV protons on SABRE to the required mrad for 35 MeV Li ions for LMF. The status of experiments is summarized, and future directions are indicated.
Future vaccination strategies against tuberculosis: thinking outside the box.
Kaufmann, Stefan H E
2010-10-29
With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.
Focus on flaviviruses: current and future drug targets.
Geiss, Brian J; Stahla, Hillary; Hannah, Amanda M; Gari, Amanda M; Keenan, Susan M
2009-05-01
Infection by mosquito-borne flaviviruses (family Flaviviridae) is increasing in prevalence worldwide. The vast global, social and economic impact due to the morbidity and mortality associated with the diseases caused by these viruses necessitates therapeutic intervention. There is currently no effective clinical treatment for any flaviviral infection. Therefore, there is a great need for the identification of novel inhibitors to target the virus life cycle. In this article, we discuss structural and nonstructural viral proteins that are the focus of current target validation and drug discovery efforts. Both inhibition of essential enzymatic activities and disruption of necessary protein–protein interactions are considered. In addition, we address promising new targets for future research. As our molecular and biochemical understanding of the flavivirus life cycle increases, the number of targets for antiviral therapeutic discovery grows and the possibility for novel drug discovery continues to strengthen.
Exploration-Related Research on ISS: Connecting Science Results to Future Missions
NASA Technical Reports Server (NTRS)
Rhatigan, Jennifer L.; Robinson, Julie A.; Sawin, Charles F.
2005-01-01
In January, 2004, the U.S. President announced The Vision for Space Exploration, and charged the National Aeronautics and Space Administration (NASA) with using the International Space Station (ISS) for research and technology targeted at supporting U.S. space exploration goals. This paper describes: What we have learned from the first four years of research on ISS relative to the exploration mission; The on-going research being conducted in this regard; and Our current understanding of the major exploration mission risks that the ISS can be used to address. Specifically, we discuss research carried out on the ISS to determine the mechanisms by which human health is affected on long-duration missions, and to develop countermeasures to protect humans from the space environment. These bioastronautics experiments are key enablers of future long duration human exploration missions. We also discuss how targeted technological developments can enable mission design trade studies. We discuss the relationship between the ultimate number of human test subjects available on the ISS to the quality and quantity of scientific insight that can be used to reduce health risks to future explorers. We discuss the results of NASA's efforts over the past year to realign the ISS research programs to support a product-driven portfolio that is directed towards reducing the major risks of exploration missions. The fundamental challenge to science on ISS is completing experiments that answer key questions in time to shape design decisions for future exploration. In this context, exploration relevant research must do more than be conceptually connected to design decisions - it must become a part of the mission design process.
CAPSAICIN: ITS BIOLOGICAL ACTIVITIES AND IN SILICO TARGET FISHING.
Akhtar, Fahad; Muhammad Sharif, Hajra; Arshad Mallick, Muhammad; Zahoor, Fareeha; Abdulmalik, Attiya; Baig, Warda; Shujaat, Nodia; Gul, Sundas; Bibi, Gulfam; Ramzan, Rahdia; Murtaza, Ghulam
2017-03-01
Capsicum annuum L. is a rich source of capsaicin, an alkaloid, which is a very pungent compound. Due to ever growing need of capsaicin, an extensive research on its efficient cultivation as well as chemical synthesis is underway. Owing to the pungent nature of capsaicin, its analogous molecules without pungent effect are being explored. The objective of this descriptive review is to comprehensively present the updates on the bioactivities of capsaicin. Additionally, the in silico target fishing approach has been used to identify the possible protein targets of capsaicin. This article will definitely provide future perspectives of research on capsaicin.
The Estimation of Future Pump Capacity for the Urban Drainage System under Climate Change
NASA Astrophysics Data System (ADS)
Kang, Narae; Noh, Huiseong; Kim, Yonsoo; Lee, Jongso; Kim, Hungsoo
2013-04-01
In the recent years, flash flood and local heavy rainfall have been frequently occurred in Korea and this may be due to the climate change. Korea Meteorological Administration(KMA) and IPCC AR5 reported new greenhouse gas scenario called RCPs(Representative concentration pathways) which are becoming an interesting subject in the field of water resources. These days, the urban areas in the Korean Peninsula have been suffered from the floods, almost every year, by the localized heavy rainfall and this abnormal rainfall may be due to the climate change. Also, the runoff in the urban area has increased due to the rapid urbanization and so the current design rainfall could not be proper any more for accommodating the abnormal runoff capacity. When we determine the frequency of drainage facilities, the maximum flood discharge from the recorded rainfall intensity is used as the design capacity of the facilities. However, there is a need to examine the future rainfall tendency for the re-establishment of the design criteria of the facilities under the climate change, since the recorded rainfall intensity does not reflect the trend of the abnormal rainfall which can be occurred. This study tries to analyze the variability and trend of future rainfall using RCP scenarios and estimate the future capacity at existing pumping station for the urban drainage system. The future projection periods are set to the next 90 years(2011-2100) and are divided into three cases; Target I : 2011~2040 yrs, Target II : 2041~2070 yrs, and Target III : 2071~2100 yrs. The study area is Incheon-city, Korea which has 9 pumping stations. According to the RCP 8.5 scenario which is the worst scenario of RCPs, the Target I design rainfall is increased by 20%, Target II increased by 33%, and Target III increased by 74% compared with the reference period(1970-2010). When considering the impact of climate change, 3 of 9 pumping stations are expected to have no difficulty in the future rainfall. But, the capacities of 6 pumping stations will not be sufficient for the future rainfall and runoff. Therefore, it is expected to construct more pumping stations allowable 6 times of existing pump capacity especially for Target III(2071-2100). ACKNOWLEDGMENT This research was supported by a grant 'The development of disaster risk assessment technique for flood prevention facilities considering the multi risk factors' [NEMA-NH-2010-33] from the Natural Hazard Mitigation Research Group, National Emergency Management Agency of Korea.
Thomas, Neil; Hayward, Mark; Peters, Emmanuelle; van der Gaag, Mark; Bentall, Richard P.; Jenner, Jack; Strauss, Clara; Sommer, Iris E.; Johns, Louise C.; Varese, Filippo; García-Montes, José Manuel; Waters, Flavie; Dodgson, Guy; McCarthy-Jones, Simon
2014-01-01
This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. Recent developments include the application of acceptance- and mindfulness-based approaches, and consolidation of methods for working with connections between voices and views of self, others, relationships and personal history. In this article, we discuss the development of therapies for voices and review the empirical findings. This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation. PMID:24936081
Cadogan, Cathal A; Ryan, Cristín; Hughes, Carmel
2016-01-01
There is a growing emphasis on behavior change in intervention development programmes aimed at improving public health and healthcare professionals' practice. A number of frameworks and methodological tools have been established to assist researchers in developing interventions seeking to change healthcare professionals' behaviors. The key features of behavior change intervention design involve specifying the target group (i.e. healthcare professional or patient cohort), the target behavior and identifying mediators (i.e. barriers and facilitators) of behavior change. Once the target behavior is clearly specified and understood, specific behavior change techniques can then be used as the basis of the intervention to target identified mediators of behavior change. This commentary outlines the challenges for pharmacy practice-based researchers in targeting dispensing as a behavior when developing behavior change interventions aimed at pharmacists and proposes a definition of dispensing to consider in future research. Copyright © 2016 Elsevier Inc. All rights reserved.
Notes on Inventive Methodologies and Affirmative Critiques of an Affective Edu-Future
ERIC Educational Resources Information Center
Staunaes, Dorthe
2016-01-01
What are the possible futures for educational research? The essay concerns two intertwined agendas. The first agenda is empirical and concerns how educational policy and leadership constitute, circulate, transform and modify feelings, moods and affects. Especially, motivation, engagement and the desire for learning are targets for policy and…
Technology, Learning Communities and Young People: The Future Something Project
ERIC Educational Resources Information Center
Herne, Steve; Adams, Jeff; Atkinson, Dennis; Dash, Paul; Jessel, John
2013-01-01
The "Future Something Project" ("FSP"), a two-year action research project, was devised to nurture the creative and technological talent of small groups of young people at risk by creating a structured network, mentored and driven by creative professionals exploring innovative ways for the two distinct target groups to work…
Future orientation: a construct with implications for adolescent health and wellbeing.
Johnson, Sarah R Lindstrom; Blum, Robert W; Cheng, Tina L
2014-01-01
Multidisciplinary research has supported a relationship between adolescent future orientation (the ability to set future goals and plans) and positive adolescent health and development outcomes. Many preventive strategies - for example, contracepting, exercising - are based on taking actions in the present to avoid unwanted or negative future consequences. However, research has been hampered by unclear and often divergent conceptualizations of the future orientation construct. The present paper aims to integrate previous conceptual and operational definitions into a conceptual framework that can inform programs and services for youth and efforts to evaluate future orientation as a target for intervention. Recommendations focus on furthering the study of the construct through measurement synthesis as well as studies of the normative development of future orientation. Also suggested is the need to pair environmental intervention strategies with individual level efforts to improve future orientation in order to maximize benefits.
Future Orientation: A Construct with Implications for Adolescent Health and Wellbeing
Lindstrom Johnson, Sarah; Blum, Robert W; Cheng, Tina L.
2016-01-01
Multi-disciplinary research has supported a relationship between adolescent future orientation (the ability to set future goals and plans) and positive adolescent health and development outcomes. Many preventive strategies—for example contracepting, exercising—are based on taking actions in the present to avoid unwanted or negative future consequences. However, research has been hampered by unclear and often divergent conceptualizations of the future orientation construct. The present paper aims to integrate previous conceptual and operational definitions into a conceptual framework that can inform programs and services for youth and efforts to evaluate future orientation as a target for intervention. Recommendations focus on furthering the study of the construct through measurement synthesis as well as studies of the normative development of future orientation. Also suggested is the need to pair environmental intervention strategies with individual level efforts to improve future orientation in order to maximize benefits. PMID:24523304
A new prospect in cancer therapy: targeting cancer stem cells to eradicate cancer.
Chen, Li-Sha; Wang, An-Xin; Dong, Bing; Pu, Ke-Feng; Yuan, Li-Hua; Zhu, Yi-Min
2012-12-01
According to the cancer stem cell theory, cancers can be initiated by cancer stem cells. This makes cancer stem cells prime targets for therapeutic intervention. Eradicating cancer stem cells by efficient targeting agents may have the potential to cure cancer. In this review, we summarize recent breakthroughs that have improved our understanding of cancer stem cells, and we discuss the therapeutic strategy of targeting cancer stem cells, a promising future direction for cancer stem cell research.
Thomas, Neil; Hayward, Mark; Peters, Emmanuelle; van der Gaag, Mark; Bentall, Richard P; Jenner, Jack; Strauss, Clara; Sommer, Iris E; Johns, Louise C; Varese, Filippo; García-Montes, José Manuel; Waters, Flavie; Dodgson, Guy; McCarthy-Jones, Simon
2014-07-01
This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. Recent developments include the application of acceptance- and mindfulness-based approaches, and consolidation of methods for working with connections between voices and views of self, others, relationships and personal history. In this article, we discuss the development of therapies for voices and review the empirical findings. This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
Preventing Rapid Repeat Births Among Latina Adolescents: The Role of Parents
Guilamo-Ramos, Vincent; Cherry, Kevin; Dittus, Patricia; Michael, Shannon; Gloppen, Kari
2012-01-01
Latina adolescent parents are at increased risk for rapid repeat births (second birth ≤ 24 months after the first), sexually transmitted infections, and negative educational and social outcomes. Although several effective parent-based interventions have been developed to prevent Latino youths’ sexual risk taking, little research has explored the development of interventions to prevent repeat births that involve the parents of these adolescents. Existing preventative interventions involving parents suffer from important methodological limitations. Additional research is needed to advance theories of behavior, identify the causal pathways of parental influence, and specify appropriate behavioral targets. Future parent-based interventions to prevent repeat births should target pregnancy intentions, age of partners, contraceptive use, integrated prevention of pregnancies and sexually transmitted infections, educational attainment, and future orientations. PMID:22897524
Radar Resource Management in a Dense Target Environment
2014-03-01
problem faced by networked MFRs . While relaxing our assumptions concerning information gain presents numerous challenges worth exploring, future research...linear programming MFR multifunction phased array radar MILP mixed integer linear programming NATO North Atlantic Treaty Organization PDF probability...1: INTRODUCTION Multifunction phased array radars ( MFRs ) are capable of performing various tasks in rapid succession. The performance of target search
ERIC Educational Resources Information Center
Kanwit, Matthew
2017-01-01
This study aimed to advance research on first and second language future-time expression in Spanish and to demonstrate the strengths of combining functionalist, concept-oriented approaches (e.g., Andersen, 1984; Bardovi-Harlig, 2000; Shirai, 1995; von Stutterheim & Klein, 1987) with variationist approaches. The study targeted 140 participants…
Persuasive technology for health and wellness: State-of-the-art and emerging trends.
Orji, Rita; Moffatt, Karyn
2018-03-01
The evolving field of persuasive and behavior change technology is increasingly targeted at influencing behavior in the area of health and wellness. This paper provides an empirical review of 16 years (85 papers) of literature on persuasive technology for health and wellness to: (1.) answer important questions regarding the effectiveness of persuasive technology for health and wellness, (2.) summarize and highlight trends in the technology design, research methods, motivational strategies, theories, and health behaviors targeted by research to date, (3.) uncover pitfalls of existing persuasive technological interventions for health and wellness, and (4.) suggest directions for future research.
O’Carroll Bantum, Erin; Owen, Jason; Bakken, Suzanne; Elhadad, Noémie
2017-01-01
Objectives: The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. Target audience: The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. Scope: The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. PMID:27402140
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-30
... study examines quantitative and qualitative information obtained from community-based initiatives... future research initiatives targeting childhood obesity. Frequency of Response: One time. Affected Public...
[HPV-associated head and neck cancer. The basics of molecular and translational research].
Wittekindt, C; Wagner, S; Klussmann, J P
2011-09-01
Translational research refers to the interfaces between preclinical research and targeted short- and medium-term developments through to clinical standards. There are two distinct groups of oropharyngeal malignancies: those caused by tobacco and alcohol abuse and those caused by HPV infection. Although the prognosis of patients in the latter group is significantly better, this is not taken into consideration in the choice of treatment. However, less intensive use of radiotherapy, chemotherapy, or surgery, as well as targeted multimodal therapeutic approaches, is under research. This article summarizes the main events in the HPV life cycle, with emphasis on carcinogenic mechanisms and potential new molecular targets. Identifying distinct tumor entities of the oropharynx enables the design and development of new preventive and therapeutic strategies to reduce the incidence and mortality of HPV-associated oropharyngeal cancers in the near future.
Achondroplasia: pathogenesis and implications for future treatment.
Laederich, Melanie B; Horton, William A
2010-08-01
Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.
Secondary light-ion transport from intermediate-energy hadron experiments
NASA Astrophysics Data System (ADS)
Srikrishna, Ashwin P.; Castellanos, Luis A.; McGirl, Natalie A.; Heilbronn, Lawrence H.; Tessas, Chiara La; Rusek, Adam; Sivertz, Michael; Blattnig, Steve; Clowdsley, Martha; Slaba, Tony; Zeitlin, Cary
2017-09-01
The aim of this research is to produce double differential thick target yields, angular distributions and integrated yields for the inclusive production of neutrons, protons, deuterons, tritons, 3He, and 4He from intermediate heavy-ion interactions on thick targets of aluminium, polyethylene and other targets of interest to the radiation shielding program as specified by the National Aeronautics and Space Administration (NASA). In tandem with the experimental research, transport model calculations of these thick target yields were also performed. The first such experimental run was conducted in May 2015, with the expectation of improved experimental results at a following March 2016 run at the NASA Space Radiation Laboratory (NSRL) on the campus of Brookhaven National Laboratory (BNL). The May 2015 commissioning run served to test the electronics of the experimental setup, as well as the various detectors and other equipment under the conditions in which the following measurements will be run. The series of future accelerator-based experiments will rely on the inclusion of two separate upstream and downstream targets. Analysis of the data from both sets of detectors - liquid scintillator and sodium iodide - using both pulse height and time-of-flight methods will allow NASA to perform uncertainty quantification and sensitivity analysis on their transport codes and future shielding studies.
Student research with 400keV beams: {sup 13}N radioisotope production target development
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fru, L. Che; Clymer, J.; Compton, N.
2013-04-19
The AN400 Van de Graaff accelerator at the Minnesota State University, Mankato, Applied Nuclear Science Lab has demonstrated utility as an accessible and versatile platform for student research. Despite the limits of low energy, the research team successfully developed projects with applications to the wider radioisotope production community. A target system has been developed for producing and extracting {sup 13}N by the {sup 12}C(d,n){sup 13}N reaction below 400keV. The system is both reusable and robust, with future applications to higher energy machines producing this important radioisotope for physiological imaging studies with Positron Emission Tomography. Up to 36({+-}1)% of the {supmore » 13}N was extracted from the graphite matrix when 35 A current was externally applied to the graphite target while simultaneously flushing the target chamber with CO{sub 2} gas.« less
Zavala, Egbert
2017-05-01
This study analyzed data from the Police Stress and Domestic Violence in Police Families in Baltimore, Maryland, 1997-1999 ( N = 753) to examine propositions derived from target congruence theory in the context of intimate partner violence (IPV) victimization experienced by police officers. Specifically, this study tested the influence of target vulnerability, target gratifiability, and target antagonism on IPV victimization. Results from logistic regression models showed that all three theoretical constructs positively and significantly predicted IPV victimization. Results, as well as the study's limitations and directions for future research, are discussed.
Geller, Alan C; Dickerman, Barbra A; Taber, Jennifer M; Dwyer, Laura A; Hartman, Anne M; Perna, Frank M
2018-06-01
While the general efficacy of skin cancer interventions have been reviewed, employing the cancer control continuum would be useful to identify research gaps at specific cancer control points. We characterized the intervention evidence base for specific behavioral targets (e.g., tanning, sun protection, screening) and clinically related targets (e.g., sunburn, skin exams, cancers) at each point in the cancer control continuum. The review included articles published from 1/1/2000-6/30/15 that had an experimental design and targeted behavioral intervention in skin cancer (e.g., specific behaviors or clinically related targets). The search yielded 86 articles, including seven dissemination studies. Of the 79 non-dissemination studies, 57 exclusively targeted primary prevention behaviors, five exclusively targeted screening, 10 targeted both detection and prevention, and eight addressed cancer survivorship. Among prevention studies (n=67), 29 (43%) targeted children and 38 (57%) targeted adults. Of the 15 screening studies, nine targeted high-risk groups (e.g., men aged ≥50 years) and six targeted the general population. Although research has focused on skin cancer prevention, empirically validated interventions are still needed for youth engaged in indoor tanning and for behavioral interventions to pursue change in clinically relevant targets. Research must also address detection among those at highest risk for skin cancer, amelioration of emotional distress attendant to diagnosis and treatment, and survivorship concerns. We discuss essential qualities and opportunities for intervention development and translational research to inform the field. Copyright © 2018 Elsevier Inc. All rights reserved.
ERIC Educational Resources Information Center
Chittleborough, Gail
2014-01-01
The Australian Government initiative, Teaching Teachers for the Future (TTF), was a targeted response to improve the preparation of future teachers with integrating technology into their practice. This paper reports on TTF research involving 28 preservice teachers undertaking a chemistry curriculum studies unit that adopted a technological focus.…
Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework
Huang, Bin; Pendley, Jennifer Shroff; Delamater, Alan; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis
2015-01-01
Objectives This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). Methods This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. Results Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. Conclusions Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. PMID:26152400
Identification of Direct Protein Targets of Small Molecules
2010-01-01
Small-molecule target identification is a vital and daunting task for the chemical biology community as well as for researchers interested in applying the power of chemical genetics to impact biology and medicine. To overcome this “target ID” bottleneck, new technologies are being developed that analyze protein–drug interactions, such as drug affinity responsive target stability (DARTS), which aims to discover the direct binding targets (and off targets) of small molecules on a proteome scale without requiring chemical modification of the compound. Here, we review the DARTS method, discuss why it works, and provide new perspectives for future development in this area. PMID:21077692
McMahon, Camilla M; Lerner, Matthew D; Britton, Noah
2013-01-01
In this paper, we synthesize the current literature on group-based social skills interventions (GSSIs) for adolescents (ages 10–20 years) with higher-functioning autism spectrum disorder and identify key concepts that should be addressed in future research on GSSIs. We consider the research participants, the intervention, the assessment of the intervention, and the research methodology and results to be integral and interconnected components of the GSSI literature, and we review each of these components respectively. Participant characteristics (eg, age, IQ, sex) and intervention characteristics (eg, targeted social skills, teaching strategies, duration and intensity) vary considerably across GSSIs; future research should evaluate whether participant and intervention characteristics mediate/moderate intervention efficacy. Multiple assessments (eg, parent-report, child-report, social cognitive assessments) are used to evaluate the efficacy of GSSIs; future research should be aware of the limitations of current measurement approaches and employ more accurate, sensitive, and comprehensive measurement approaches. Results of GSSIs are largely inconclusive, with few consistent findings across studies (eg, high parent and child satisfaction with the intervention); future research should employ more rigorous methodological standards for evaluating efficacy. A better understanding of these components in the current GSSI literature and a more sophisticated and rigorous analysis of these components in future research will lend clarity to key questions regarding the efficacy of GSSIs for individuals with autism spectrum disorder. PMID:23956616
Airborne ladar man-in-the-loop operations in tactical environments
NASA Astrophysics Data System (ADS)
Grobmyer, Joseph E., Jr.; Lum, Tommy; Morris, Robert E.; Hard, Sarah J.; Pratt, H. L.; Florence, Tom; Peddycoart, Ed
2004-09-01
The U.S. Army Research, Development and Engineering Command (RDECOM) is developing approaches and processes that will exploit the characteristics of current and future Laser Radar (LADAR) sensor systems for critical man-in-the-loop tactical processes. The importance of timely and accurate target detection, classification, identification, and engagement for future combat systems has been documented and is viewed as a critical enabling factor for FCS survivability and lethality. Recent work has demonstrated the feasibility of using low cost but relatively capable personal computer class systems to exploit the information available in Ladar sensor frames to present the war fighter or analyst with compelling and usable imagery for use in the target identification and engagement processes in near real time. The advantages of LADAR imagery are significant in environments presenting cover for targets and the associated difficulty for automated target recognition (ATR) technologies.
Adamo, Kristi B; Shen, Garry X; Mottola, Michelle; Nascimento, Simony; Jean-Philippe, Sonia; Ferraro, Zachary M; Nerenberg, Kara; Smith, Graeme; Chari, Radha; Gaudet, Laura; Piccinini-Vallis, Helena; McDonald, Sarah; Atkinson, Stephanie; Godbout, Ariane; Robitaille, Julie; Davidge, Sandra T; Gruslin, Andrée; Prud’homme, Denis; Stacey, Dawn; Rossiter, Melissa; Goldfield, Gary S; Dodd, Jodie
2014-01-01
This report summarizes a meeting, Obesity Prevention from Conception, held in Ottawa in 2012. This planning workshop was funded by the Canadian Institutes of Health Research (CIHR) to bring together researchers with expertise in the area of maternal obesity (OB) and weight gain in pregnancy and pregnancy-related disease to attend a one-day workshop and symposium to discuss the development of a cross-Canada lifestyle intervention trial for targeting pregnant women. This future intervention will aim to reduce downstream OB in children through encouraging appropriate weight gain during the mother’s pregnancy. The workshop served to (i) inform the development of a lifestyle intervention for women with a high pre-pregnancy body mass index (BMI), (ii) identify site investigators across Canada, and (iii) guide the development of a grant proposal focusing on the health of mom and baby. A brief summary of the presentations as well as the focus groups is presented for use in planning future research.
Pharmacogenomic strategies against microbial resistance: from bright to bleak to innovative.
Dandekar, Thomas; Dandekar, Gudrun
2010-09-01
The last decade saw an alarming increase in antibiotic resistance in infections, with more than 13 million deaths per year from infections. Counter strategies include hygiene, antibiotic restriction and new antibiotics such as quinupristin, linezolid, tigecycline, daptomycin and dalbavancin. Presently, pharmacogenomics with basic research is revealing new antimicrobial peptides and is applying old drugs in new ways to break resistance. New approaches with host-directed drug targeting emerge to circumvent resistance. A future systems perspective from large-scale molecular techniques and bioinformatic modeling allows pharmacogenomics to reveal new intervention angles. This includes the fight against resistance and its transmission, improved vaccines, disarmament of microbes and antibiotic options from novel molecular targets (lipids, RNA and carbohydrates). Such a system perspective is also essential for improved diagnostics and individualized medicine. However, an increase in public awareness and closer cooperation of industry and basic research are essential to turn research into powerful new drugs that will enable us to treat new arising infections in the future.
Bartlett, John M S
2010-11-01
The phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathway regulates a broad spectrum of physiologic and pathologic processes. In breast cancer mutation, amplification, deletion, methylation, and posttranslational modifications lead to significant dysregulation of this pathway leading to more aggressive and potentially drug-resistant disease. Multiple novel agents, targeting different nodes within the pathway are currently under development by both commercial and academic partners. The key to the successful validation of these markers is selection of the appropriate patient groups using biomarkers. This article reviews current progress in this area, highlighting the key molecular alterations described in genes within the PI3K/Akt/mTOR pathway that may have an effect on response to current and future therapeutic interventions. Herein, gaps in current knowledge are highlighted and suggestions for future research directions given that may facilitate biomarker development in partnership with current drug development.
Strategy of Daiichi Sankyo discovery research in oncology.
Akahane, Kouichi; Hirokawa, Kazunori
2014-02-01
We would like to introduce Daiichi Sankyo's approach to developing cancer targeted medicines with special reference to the drug discovery strategy, global discovery activities and external research collaboration leading to generation of innovative drugs for cancer patients. We are developing 14 clinical projects for cancer treatment and three of them have been previously approved. These are mostly targeted for growth and survival signals of cancer cells. To overcome the drug resistance mechanism derived from the heterogeneous nature of cancer, we are developing selective inhibitors in three major clusters of signal pathways which may allow future rational combinations of oncology products. In addition to the main research facility in Japan, research sites in the EU and the USA provide us with different technical expertise and diversified ideas of drug discovery. To access novel drug targets, we are facilitating research collaboration with leading academia and successful cancer research scientists. In conclusion, we intend to focus more on developing innovative personalized medicines for better treatment of cancer.
Oral Health Disparities and the Future Face of America.
Ebersole, J L; D'Souza, R; Gordon, S; Fox, C H
2012-11-01
The 4th Annual AADR Fall Focused Symposium (FFS), "Oral Health Disparities Research and the Future Face of America", took place on November 3-4, 2011 in Washington, DC. The FFS strategy was developed by the AADR to help provide additional opportunities for members to engage in research discussions during the year by identifying specific research topics of interest among the 21 Scientific Groups and 4 Networks of the IADR and targeting a focused topic area for the FFS. The conference attracted an international group of approximately 120 registrants, including participants from Canada, India, Mexico, and China; 4 oral sessions and 32 poster presentations were offered.
Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.
Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning
2016-05-01
Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.
ERIC Educational Resources Information Center
Laguilles, Jerold S.
2013-01-01
As colleges and universities seek to increase the enrollment of low-income students through targeted financial aid strategies, such as no-loans policies, little research has looked into how engaged these future alumni would be as volunteers or donors. Using data from administrative databases at a single institution, this study focused on three…
On Target Localization Using Combined RSS and AoA Measurements
Beko, Marko; Dinis, Rui
2018-01-01
This work revises existing solutions for a problem of target localization in wireless sensor networks (WSNs), utilizing integrated measurements, namely received signal strength (RSS) and angle of arrival (AoA). The problem of RSS/AoA-based target localization became very popular in the research community recently, owing to its great applicability potential and relatively low implementation cost. Therefore, here, a comprehensive study of the state-of-the-art (SoA) solutions and their detailed analysis is presented. The beginning of this work starts by considering the SoA approaches based on convex relaxation techniques (more computationally complex in general), and it goes through other (less computationally complex) approaches, as well, such as the ones based on the generalized trust region sub-problems framework and linear least squares. Furthermore, a detailed analysis of the computational complexity of each solution is reviewed. Furthermore, an extensive set of simulation results is presented. Finally, the main conclusions are summarized, and a set of future aspects and trends that might be interesting for future research in this area is identified. PMID:29671832
Walter, Ebile Akoh; Jerome, Ateudjieu; Marceline, Djuidje Ngounoue; Yakum, Martin Ndinakie; Pierre, Watcho
2017-11-21
Over the last decade, there has been a rapid increase in biomedical research in Cameroon. However, the question of whether these research projects target major health priorities, vulnerable populations and geographic locations at risk remains to be answered. The aim of this paper is to describe the state of biomedical research in Cameroon which is a key determinant that would guide future health care policies and promote equitable access to healthcare. A documentary review of all approved protocols (proposals) of biomedical research projects, from 1997 through 2012, at the Cameroon National Ethics Committee. Protocols were reviewed systematically by independent reviewers and data were extracted on a grid. Data were analyzed by calculating proportions at 95% confidence interval, chi-square test (chi2) and p-values. Two thousand one hundred seventy two protocols were reviewed for data extraction. One thousand three hundred ninety-five (64.7%) were student projects, 369 (17.0%) projects had international sponsors, and 1528 (72.4%) were hospital-based studies. The most targeted domain was the fight against diseases 1323 (61.3%); mostly HIV 342 (25.8%) and Malaria 136 (10.3%). Over half of the studies were concentrated in the Centre region 1242 (57.2%), with the least projects conducted in the Northern region 15 (0.7%). There was strong evidence that international and local sponsors would influence the research site (p-value = 0.01) and population targets (p-value = 0.00). Although biomedical research targets some important diseases that pose a great burden to Cameroonians, the most vulnerable populations are excluded from research. Biomedical research scarcely addresses other components of the health system and emerging diseases of vital public health importance. We recommend that the government should play a central role, between researchers from academic institutions, sponsors, NGOs and research institutions, to ensure that biomedical research addresses the health priorities of Cameroonians. It should include vulnerable populations, and address other components of the health system for a balance. These recommendations are critical to ensuring that future research informed health policies reflect the health needs of the populations and promote equity in healthcare access.
Two decades of ART: improving on success through further research
HOLMGREN, Christopher J.; FIGUEREDO, Márcia Cançado
2009-01-01
ABSTRACT Since the introduction of the Atraumatic Restorative Treatment (ART) approach over twenty years ago, more than 190 research publications have appeared. The last research agenda defining research priorities for ART was published in 1999. The objective of the present work was to review existing research in the context of future research priorities for ART. Material and Methods: An internet survey was conducted amongst those who had published on ART or were known to be working on the ART approach, to solicit their views as to areas of future ART research. Three broad categories were defined, namely: 1. Basic and laboratory research; 2. Clinical research, and, 3. Community, Public Health, Health Services Research. Results: A 31% response rate was achieved. The study identified a number of new areas of research as well as areas where additional research is required. These are expressed as recommendations for future ART research. Conclusions: The ART approach is based on a robust, reliable and ever-growing evidence base concerning its clinical applications which indicates that it is a reliable and quality treatment approach. In common with all other oral health care procedures, targeted applied research is required to improve the oral health care offered. PMID:21499666
Early life programming as a target for prevention of child and adolescent mental disorders
2014-01-01
This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477
Female serial murderers: directions for future research on a hidden population.
Gurian, Elizabeth A
2011-02-01
This comprehensive overview on a sample of 65 cases (134 total offenders, including some partnered teams of more than 2 offenders) provides information on female serial murderers who either work in a mixed-sex offending group or alone. These female serial homicide offenders have a distinct set of offender-victim characteristics, including specific victim preferences, methods, and motivations: Partnered serial homicide offenders are more likely to target adult strangers and dispatch them using a combination of methods, whereas solo female serial murderers are most likely to target adult family members and murder them with poison. These patterns have the potential to add to our understanding of the possible similarities and differences of serial homicide cases by building on established offender characteristics. Convictions and sentences for the offenders are included and areas of future research and implications for treatment with this sample are also explored.
Knipe, David M; Whelan, Sean P
2015-08-01
Harvard Medical School convened a meeting of biomedical and clinical experts on 5 March 2015 on the topic of "Rethinking the Response to Emerging Microbes: Vaccines and Therapeutics in the Ebola Era," with the goals of discussing the lessons from the recent Ebola outbreak and using those lessons as a case study to aid preparations for future emerging infections. The speakers and audience discussed the special challenges in combatting an infectious agent that causes sporadic outbreaks in resource-poor countries. The meeting led to a call for improved basic medical care for all and continued support of basic discovery research to provide the foundation for preparedness for future outbreaks in addition to the targeted emergency response to outbreaks and targeted research programs against Ebola virus and other specific emerging pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Acero, Francisco Javier Fernández; Carbú, María; El-Akhal, Mohamed Rabie; Garrido, Carlos; González-Rodríguez, Victoria E.; Cantoral, Jesús M.
2011-01-01
Proteomics has become one of the most relevant high-throughput technologies. Several approaches have been used for studying, for example, tumor development, biomarker discovery, or microbiology. In this “post-genomic” era, the relevance of these studies has been highlighted as the phenotypes determined by the proteins and not by the genotypes encoding them that is responsible for the final phenotypes. One of the most interesting outcomes of these technologies is the design of new drugs, due to the discovery of new disease factors that may be candidates for new therapeutic targets. To our knowledge, no commercial fungicides have been developed from targeted molecular research, this review will shed some light on future prospects. We will summarize previous research efforts and discuss future innovations, focused on the fight against one of the main agents causing a devastating crops disease, fungal phytopathogens. PMID:21340014
The application of antitumor drug-targeting models on liver cancer.
Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke
2016-06-01
Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.
a Plutonium Ceramic Target for Masha
NASA Astrophysics Data System (ADS)
Wilk, P. A.; Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Patin, J. B.; Lougheed, R. W.; Ebbinghaus, B. B.; Landingham, R. L.; Oganessian, Yu. Ts.; Yeremin, A. V.; Dmitriev, S. N.
2005-09-01
We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 °C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied.
Black sexuality, social construction, and research targeting 'The Down Low' ('The DL').
Ford, Chandra L; Whetten, Kathryn D; Hall, Susan A; Kaufman, Jay S; Thrasher, Angela D
2007-03-01
The purpose of this commentary is to explain how social constructions of black sexuality are relevant to research targeting black sexual behavior and the ostensibly new and race-specific phenomenon known as "the Down Low" (the DL). The term "the DL" is widely used to refer to black men publicly presenting as heterosexual while secretly having sex with other men and presumably spreading human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) to unsuspecting women. We briefly review lay and public health literature from 1998 to 2004 about the DL, describe existing social constructions of black sexuality, discuss two implications for epidemiologic research, and offer recommendations to guide future research. The lifestyle referenced by the term the DL is neither new nor limited to blacks, and sufficient data linking it to HIV/AIDS disparities currently are lacking. Common perceptions about the DL reflect social constructions of black sexuality as generally excessive, deviant, diseased, and predatory. Research targeting black sexual behavior that ignores these constructions may unwittingly reinforce them. Unaddressed social constructions of black sexuality have implications for epidemiologic research targeting black sexual behavior. Explicit examination of these concerns is necessary to eliminate fundamental causes of health disparities.
Transparent Conducting Oxides: Status and Opportunities in Basic Research
DOE Office of Scientific and Technical Information (OSTI.GOV)
Coutts, T. J.; Perkins, J. D.; Ginley, D.S.
1999-08-01
In this paper, we begin by discussing the historical background of transparent conducting oxides and then make some general remarks about their typical properties. This is followed by a short discussion of the desired properties for future applications (particularly photovoltaic devices). These are ambitious objectives but they provide targets for future basic research and development. Although it may be possible to obtain these properties in the laboratory, it is vital to ensure that account is taken of industrial perceptions to the development of the next generation of materials. Hence, we spend some time discussing industrial criteria. Next, we discuss keymore » physical properties that determine the macroscopic physical properties that, in turn, affect the performance of devices. Finally, we select several key topics that ought to be included in future basic research programs.« less
FSA future directions: FSA technology activities in FY86
NASA Technical Reports Server (NTRS)
Leipold, M. H.
1985-01-01
The silicon material, advanced silicon sheet, device research, and process research activities are explained. There will be no new initiatives. Many activities are targeted for completion and the emphasis will then be on technology transfer. Industrial development of the fluidized-bed reactor (FBR) deposition technology is proceeding. Technology transfer and industry funding of sheet development are continuing.
Kahl, Brad S; Dreyling, Martin; Gordon, Leo I; Quintanilla-Martinez, Leticia; Sotomayor, Eduardo M
2017-07-01
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically associated with the t(11;14) chromosomal translocation, resulting in overexpression of cyclin D1. Although MCL is associated with clinical heterogeneity, outcomes are generally poor and no standard treatment has been established. However, the recent approval of ibrutinib provides a new therapeutic option. Moreover, recent clinical trials have provided new perspectives on the relative efficacy and safety of various approaches for both transplant-eligible and transplant-ineligible patients. Multiple novel strategies are being evaluated in the treatment of MCL, including both targeted agents and cellular immunotherapies. At the Lymphoma Research Foundation's 12th MCL Workshop, researchers gathered to discuss research findings, clinical trial results, and future directions related to MCL, its biology, and its treatment. This manuscript, which includes a summary of each presentation, aims to review recent findings in MCL research and highlight potential areas for future study.
Targeted therapy for non-small cell lung cancer: current standards and the promise of the future
Chan, Bryan A.
2015-01-01
In recent years, there has been a major paradigm shift in the management of non-small cell lung cancer (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes of oncogenic drivers behind NSCLC as well as the development of targeted agents available to treat them both now and in the foreseeable future. PMID:25806345
Development of advanced entry, descent, and landing technologies for future Mars Missions
NASA Technical Reports Server (NTRS)
Chu, Cheng-Chih (Chester)
2006-01-01
Future Mars missions may need the capability to land much closer to a desired target and/or advanced methods of detecting, avoiding, or tolerating landing hazards. Therefore, technologies that enable 'pinpoint landing' (within tens of meters to 1 km of a target site) will be crucial to meet future mission requirements. As part of NASA Research Announcement, NRA 03-OSS-01, NASA solicited proposals for technology development needs of missions to be launched to Mars during or after the 2009 launch opportunity. Six technology areas were identified as of high priority including advanced entry, descent, and landing (EDL) technologies. In May 2004, 11 proposals with PIs from universities, industries, and NASA centers, were awarded in the area of advanced EDL by NASA for further study and development. This paper presents an overview of these developing technologies.
Tabachnick, Walter J
2016-09-28
Research on mosquitoes and mosquito-borne diseases has contributed to improvements in providing effective, efficient, and environmentally proper mosquito control. Florida has benefitted from several research accomplishments that have increased the state's mosquito control capabilities. Research with Florida's mosquitoes has resulted in the development of ecologically sound management of mosquito impoundments on Florida's east coast. This strategy, called Rotational Impoundment Management (RIM), has improved the ability to target the delivery of pesticides and has helped to reduce non-target effects and environmental damage. Research has led to the development of an arbovirus surveillance system which includes sentinel chicken surveillance, real time use of environmental contributing factors like meteorology and hydrology to target mosquito control, as well as public health efforts to mitigate disease outbreaks to areas with risk of disease. These research driven improvements have provided substantial benefits to all of Florida. More research is needed to meet the future challenges to reduce emerging pathogens like Zika virus and the consequences of environmental changes like global climate change that are likely to influence the effects of mosquito-borne pathogens on human health and well-being.
Personalized targeted therapy for esophageal squamous cell carcinoma
Kang, Xiaozheng; Chen, Keneng; Li, Yicheng; Li, Jianying; D'Amico, Thomas A; Chen, Xiaoxin
2015-01-01
Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial. PMID:26167067
Federal Register 2010, 2011, 2012, 2013, 2014
2011-06-17
... age range of children is 3-15 years upon entry into the study. The study examines quantitative and... scientific journals and will be used for the development of future research initiatives targeting childhood...
Members of FOX family could be drug targets of cancers.
Wang, Jinhua; Li, Wan; Zhao, Ying; Kang, De; Fu, Weiqi; Zheng, Xiangjin; Pang, Xiaocong; Du, Guanhua
2018-01-01
FOX families play important roles in biological processes, including metabolism, development, differentiation, proliferation, apoptosis, migration, invasion and longevity. Here we are focusing on roles of FOX members in cancers, FOX members and drug resistance, FOX members and stem cells. Finally, FOX members as drug targets of cancer treatment were discussed. Future perspectives of FOXC1 research were described in the end. Copyright © 2017 Elsevier Inc. All rights reserved.
Alwan, Wisam; Nestle, Frank O
2015-01-01
Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.
Stereotypes, prejudice and discrimination of women with anorexia nervosa.
Stewart, Maria-Christina; Schiavo, R Steven; Herzog, David B; Franko, Debra L
2008-07-01
Limited research indicates that public attitudes toward individuals with eating disorders are moderately negative. The present study examined specific forms of stigmatisation attributed to individuals with anorexia nervosa (AN). Eighty female participants recruited from an undergraduate institution completed questionnaires assessing stereotypes, prejudice and discrimination of four target individuals: a woman with AN, depression, schizophrenia and mononucleosis. AN was considered to result more from lack of social support and biological factors than poor living habits. Characteristics attributed to targets were less positive for AN than the targets with schizophrenia and mononucleosis; participants reported greater discomfort interacting with the target with AN compared to the targets with depression and mononucleosis. Having actual contact with an individual with AN related to a positive predicted outcome of and comfort in interacting with the target with AN. Findings support the existence of stigma toward individuals with AN. Future research should examine means of reducing stigma. Copyright 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
Research on Information Sharing Method for Future C2 in Network Centric Environment
2011-06-01
subscription (or search) request. Then, some of the information service nodes for future C2 deal with these users’ requests, locate, federated search the... federated search server is responsible for resolving the search requests sending out from the users, and executing the federated search . The information... federated search server, information filtering model, or information subscription matching algorithm (such as users subscribe the target information at two
Predicting Health Resilience in Pediatric Type 1 Diabetes: A Test of the Resilience Model Framework.
Rohan, Jennifer M; Huang, Bin; Pendley, Jennifer Shroff; Delamater, Alan; Dolan, Lawrence; Reeves, Grafton; Drotar, Dennis
2015-10-01
This research examined whether individual and family-level factors during the transition from late childhood to early adolescence protected individuals from an increased risk of poor glycemic control across time, which is a predictor of future diabetes-related complications (i.e., health resilience). This longitudinal, multisite study included 239 patients with type 1 diabetes and their caregivers. Glycemic control was based on hemoglobin A1c. Individual and family-level factors included: demographic variables, youth behavioral regulation, adherence (frequency of blood glucose monitoring), diabetes self-management, level of parental support for diabetes autonomy, level of youth mastery and responsibility for diabetes management, and diabetes-related family conflict. Longitudinal mixed-effects logistic regression indicated that testing blood glucose more frequently, better self-management, and less diabetes-related family conflict were indicators of health resilience. Multiple individual and family-level factors predicted risk for future health complications. Future research should develop interventions targeting specific individual and family-level factors to sustain glycemic control within recommended targets, which reduces the risk of developing future health complications during the transition to adolescence and adulthood. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Targeting the Cerebellum by Noninvasive Neurostimulation: a Review.
van Dun, Kim; Bodranghien, Florian; Manto, Mario; Mariën, Peter
2017-06-01
Transcranial magnetic and electric stimulation of the brain are novel and highly promising techniques currently employed in both research and clinical practice. Improving or rehabilitating brain functions by modulating excitability with these noninvasive tools is an exciting new area in neuroscience. Since the cerebellum is closely connected with the cerebral regions subserving motor, associative, and affective functions, the cerebello-thalamo-cortical pathways are an interesting target for these new techniques. Targeting the cerebellum represents a novel way to modulate the excitability of remote cortical regions and their functions. This review brings together the studies that have applied cerebellar stimulation, magnetic and electric, and presents an overview of the current knowledge and unsolved issues. Some recommendations for future research are implemented as well.
The prospect of gene therapy for prostate cancer: update on theory and status.
Koeneman, K S; Hsieh, J T
2001-09-01
Molecularly based novel therapeutic agents are needed to address the problem of locally recurrent, or metastatic, advanced hormone-refractory prostate cancer. Recent basic science advances in mechanisms of gene expression, vector delivery, and targeting have rendered clinically relevant gene therapy to the prostatic fossa and distant sites feasible in the near future. Current research and clinical investigative efforts involving methods for more effective vector delivery and targeting, with enhanced gene expression to selected (specific) sites, are reviewed. These areas of research involve tissue-specific promoters, transgene exploration, vector design and delivery, and selective vector targeting. The 'vectorology' involved mainly addresses selective tissue homing with ligands, mechanisms of innate immune system evasion for durable transgene expression, and the possibility of repeat administration.
Evidence base and future research directions in the management of low back pain.
Abbott, Allan
2016-03-18
Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care.
NASA Astrophysics Data System (ADS)
Tahir, N. A.; Weick, H.; Iwase, H.; Geissel, H.; Hoffmann, D. H. H.; Kindler, B.; Lommel, B.; Radon, T.; Münzenberg, G.; Shutov, A.; Sümmerer, K.; Winkler, M.
2005-06-01
A superconducting fragment separator (Super-FRS) is being designed for the production and separation of radioactive isotopes at the future FAIR (Facility for Antiprotons and Ion Research) facility at Darmstadt. This paper discusses various aspects and requirements for the high-power production target that will be used in the Super-FRS experiments. The production target must survive over an extended period of time as it will be used during the course of many experiments. The specific power deposited by the high intensity beam that will be generated at the future FAIR facility will be high enough to destroy the target in most of the cases as a result of a single shot from the new heavy ion synchrotrons SIS100/300. By using an appropriate beam intensity and focal spot parameters, the target would survive after being irradiated once. However, the heat should be dissipated efficiently before the same target area is irradiated again. We have considered a wheel shaped solid carbon target that rotates around its axis so that different areas of the target are irradiated successively. This allows for cooling of the beam heated region by thermal conduction before the same part of the target is irradiated a second time. Another attractive option is to use a liquid jet target at the Super-FRS. First calculations of a possible liquid lithium target are also presented in this paper. One of the advantages of using lithium as a target is that it will survive even if one uses a smaller focal spot, which has half the area of that used for a solid carbon target. This will significantly improve the isotope resolution. A similar problem associated with these experiments will be safe deposition of the beam energy in a beamdump after its interaction with the production target. We also present calculations to study the suitability of a proposed beamdump.
Metzinger, Thomas
2013-01-01
This metatheoretical paper develops a list of new research targets by exploring particularly promising interdisciplinary contact points between empirical dream research and philosophy of mind. The central example is the MPS-problem. It is constituted by the epistemic goal of conceptually isolating and empirically grounding the phenomenal property of “minimal phenomenal selfhood,” which refers to the simplest form of self-consciousness. In order to precisely describe MPS, one must focus on those conditions that are not only causally enabling, but strictly necessary to bring it into existence. This contribution argues that research on bodiless dreams, asomatic out-of-body experiences, and full-body illusions has the potential to make decisive future contributions. Further items on the proposed list of novel research targets include differentiating the concept of a “first-person perspective” on the subcognitive level; investigating relevant phenomenological and neurofunctional commonalities between mind-wandering and dreaming; comparing the functional depth of embodiment across dream and wake states; and demonstrating that the conceptual consequences of cognitive corruption and systematic rationality deficits in the dream state are much more serious for philosophical epistemology (and, perhaps, the methodology of dream research itself) than commonly assumed. The paper closes by specifying a list of potentially innovative research goals that could serve to establish a stronger connection between dream research and philosophy of mind. PMID:24198793
Metzinger, Thomas
2013-01-01
This metatheoretical paper develops a list of new research targets by exploring particularly promising interdisciplinary contact points between empirical dream research and philosophy of mind. The central example is the MPS-problem. It is constituted by the epistemic goal of conceptually isolating and empirically grounding the phenomenal property of "minimal phenomenal selfhood," which refers to the simplest form of self-consciousness. In order to precisely describe MPS, one must focus on those conditions that are not only causally enabling, but strictly necessary to bring it into existence. This contribution argues that research on bodiless dreams, asomatic out-of-body experiences, and full-body illusions has the potential to make decisive future contributions. Further items on the proposed list of novel research targets include differentiating the concept of a "first-person perspective" on the subcognitive level; investigating relevant phenomenological and neurofunctional commonalities between mind-wandering and dreaming; comparing the functional depth of embodiment across dream and wake states; and demonstrating that the conceptual consequences of cognitive corruption and systematic rationality deficits in the dream state are much more serious for philosophical epistemology (and, perhaps, the methodology of dream research itself) than commonly assumed. The paper closes by specifying a list of potentially innovative research goals that could serve to establish a stronger connection between dream research and philosophy of mind.
Verstappen, Wim; Gaal, Sander; Bowie, Paul; Parker, Diane; Lainer, Miriam; Valderas, Jose M; Wensing, Michel; Esmail, Aneez
2015-09-01
Healthcare can cause avoidable serious harm to patients. Primary care is not an exception, and the relative lack of research in this area lends urgency to a better understanding of patient safety, the future research agenda and the development of primary care oriented safety programmes. To outline a research agenda for patient safety improvement in primary care in Europe and beyond. The LINNEAUS collaboration partners analysed existing research on epidemiology and classification of errors, diagnostic and medication errors, safety culture, and learning for and improving patient safety. We discussed ideas for future research in several meetings, workshops and congresses with LINNEAUS collaboration partners, practising GPs, researchers in this field, and policy makers. This paper summarizes and integrates the outcomes of the LINNEAUS collaboration on patient safety in primary care. It proposes a research agenda on improvement strategies for patient safety in primary care. In addition, it provides background information to help to connect research in this field with practicing GPs and other healthcare workers in primary care. Future research studies should target specific primary care domains, using prospective methods and innovative methods such as patient involvement.
Verstappen, Wim; Gaal, Sander; Bowie, Paul; Parker, Diane; Lainer, Miriam; Valderas, Jose M.; Wensing, Michel; Esmail, Aneez
2015-01-01
ABSTRACT Background: Healthcare can cause avoidable serious harm to patients. Primary care is not an exception, and the relative lack of research in this area lends urgency to a better understanding of patient safety, the future research agenda and the development of primary care oriented safety programmes. Objective: To outline a research agenda for patient safety improvement in primary care in Europe and beyond. Methods: The LINNEAUS collaboration partners analysed existing research on epidemiology and classification of errors, diagnostic and medication errors, safety culture, and learning for and improving patient safety. We discussed ideas for future research in several meetings, workshops and congresses with LINNEAUS collaboration partners, practising GPs, researchers in this field, and policy makers. Results: This paper summarizes and integrates the outcomes of the LINNEAUS collaboration on patient safety in primary care. It proposes a research agenda on improvement strategies for patient safety in primary care. In addition, it provides background information to help to connect research in this field with practicing GPs and other healthcare workers in primary care. Conclusion: Future research studies should target specific primary care domains, using prospective methods and innovative methods such as patient involvement. PMID:26339841
Quant, Eudocia C; Wen, Patrick Y
2010-08-01
The prognosis for glioblastoma is poor despite optimal therapy with surgery, radiation, and chemotherapy. New therapies that improve survival and quality of life are needed. Research has increased our understanding of the molecular pathways important for gliomagenesis and disease progression. Novel agents have been developed against these targets, including receptor tyrosine kinases, intracellular signaling molecules, epigenetic abnormalities, and tumor vasculature and microenvironment. This article reviews novel therapies for glioblastoma, with an emphasis on targeted agents. Copyright 2010 Elsevier Inc. All rights reserved.
Minimum reporting standards for clinical research on groin pain in athletes
Delahunt, Eamonn; Thorborg, Kristian; Khan, Karim M; Robinson, Philip; Hölmich, Per; Weir, Adam
2015-01-01
Groin pain in athletes is a priority area for sports physiotherapy and sports medicine research. Heterogeneous studies with low methodological quality dominate research related to groin pain in athletes. Low-quality studies undermine the external validity of research findings and limit the ability to generalise findings to the target patient population. Minimum reporting standards for research on groin pain in athletes are overdue. We propose a set of minimum reporting standards based on best available evidence to be utilised in future research on groin pain in athletes. Minimum reporting standards are provided in relation to: (1) study methodology, (2) study participants and injury history, (3) clinical examination, (4) clinical assessment and (5) radiology. Adherence to these minimum reporting standards will strengthen the quality and transparency of research conducted on groin pain in athletes. This will allow an easier comparison of outcomes across studies in the future. PMID:26031644
Schultze-Lutter, F
2016-12-01
The early detection of psychoses has become increasingly relevant in research and clinic. Next to the ultra-high risk (UHR) approach that targets an immediate risk of developing frank psychosis, the basic symptom approach that targets the earliest possible detection of the developing disorder is being increasingly used worldwide. The present review gives an introduction to the development and basic assumptions of the basic symptom concept, summarizes the results of studies on the specificity of basic symptoms for psychoses in different age groups as well as on studies of their psychosis-predictive value, and gives an outlook on future results. Moreover, a brief introduction to first recent imaging studies is given that supports one of the main assumptions of the basic symptom concept, i. e., that basic symptoms are the most immediate phenomenological expression of the cerebral aberrations underlying the development of psychosis. From this, it is concluded that basic symptoms might be able to provide important information on future neurobiological research on the etiopathology of psychoses. © Georg Thieme Verlag KG Stuttgart · New York.
A Plutonium Ceramic Target for MASHA
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wilk, P A; Shaughnessy, D A; Moody, K J
2004-07-06
We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments wheremore » the chemical properties of the heaviest elements are studied.« less
Abdelhafiz, Ahmed Samir; Fouda, Merhan Ahmed; El-Jaafary, Shaimaa Ibrahim; Farghly, Maysa Ibrahim; Salem, Mazen; Tammam, Ahmed; Gabr, Hala
2017-08-01
Biobanking is a relatively new concept in the Arab region. Targeting different stakeholders to introduce the concept of biobanking and develop an acceptance of it among them is important for the growth of biobanking in the region. Undergraduate students of life sciences represent an important segment of stakeholders, since they constitute potential future biobank customers. Limited funding, lack of awareness of the existence of the term "biobanking" itself among these students, and questions regarding best marketing strategies presented challenges to planning for the most effective message delivery to this target group. A specific course was designed for undergraduate students of life sciences, which was conducted at the Faculty of Medicine, Cairo University, Egypt. The course was conducted twice in 2016 and included lectures covering biobanking, quality, ethics, information technology, and translational research. Facebook and word-of-mouth were used for marketing and advertising. A total number of 125 participants attended both courses cumulatively. Facebook appeared to have been an effective marketing outlet, especially when paid advertisements were used. Evaluation of knowledge, measured using a pretest and posttest, demonstrated some improvement in knowledge of participants. Evaluation forms filled after the course showed positive attitude toward content and message delivery by a majority of participants. Facebook was also used as an evaluation method through analysis of engagement with posts created after course completion. Biobanking education can be carried out effectively with limited resources. Understanding the needs of the target group and using appropriate methods of communication are essential prerequisites to a well-tailored curriculum and effective message delivery. Using Facebook appears to be an effective and affordable method of communication and advertising. Targeting undergraduate students of life sciences interested in research is a good investment and can be very effective in increasing awareness about biobanking inside the research community.
Development of Water Target for Radioisotope Production
NASA Astrophysics Data System (ADS)
Tripp, Nathan
2011-10-01
Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.
NASA Astrophysics Data System (ADS)
Klim, Adam; Morrison, J. T.; Orban, C.; Feister, S.; Ngirmang, G. K.; Smith, J.; Frische, K.; Peterson, A. C.; Chowdhury, E. A.; Freeman, R. R.; Roquemore, W. M.
2016-10-01
The success of laser-accelerated ion experiments depends crucially on a number of factors including how thin the targets can be created. We present experimental results demonstrating extremely thin (under 200 nm) water sheet targets that can be used for ultra-intense laser-accelerated ion experiments conducted at the Air Force Research Laboratory at Wright-Patterson Air Force Base. Importantly, these experiments operate at a kHz repetition rate and the recovery time of the liquid targets is fast enough to allow the laser to interact with a refreshed, thin target on every shot. We present results from liquid water targets which are useful for proton acceleration experiments via the mechanism of Target Normal Sheath Acceleration (TNSA). In future work, we will create thin sheets from deuterated water in order to perform laser-accelerated deuteron experiments. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the AFOSR, under the management of Dr. Enrique Parra, and support from the DOD HPCMP Internship Program.
Johns, Margaret A; Meyerkord-Belton, Cheryl L; Du, Yuhong; Fu, Haian
2014-03-01
The Emory Chemical Biology Discovery Center (ECBDC) aims to accelerate high throughput biology and translation of biomedical research discoveries into therapeutic targets and future medicines by providing high throughput research platforms to scientific collaborators worldwide. ECBDC research is focused at the interface of chemistry and biology, seeking to fundamentally advance understanding of disease-related biology with its HTS/HCS platforms and chemical tools, ultimately supporting drug discovery. Established HTS/HCS capabilities, university setting, and expertise in diverse assay formats, including protein-protein interaction interrogation, have enabled the ECBDC to contribute to national chemical biology efforts, empower translational research, and serve as a training ground for young scientists. With these resources, the ECBDC is poised to leverage academic innovation to advance biology and therapeutic discovery.
Targeted therapy in esophageal cancer.
Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming
2016-01-01
An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.
Summary results of the Industry Conference on the Commercial Use of Space
NASA Technical Reports Server (NTRS)
REUSE; Thuerbach, R. P.
1985-01-01
The future intentions of the Federal Republic of Germany in the area of the commercialization of space are presented. It is shown that significant advances in microgravity research, particulary in the areas of materials science, composite materials, physical chemistry, crystal growth, biology, and process engineering will have an effect on future plans for establishing sponsoring organizations to guide commercial interests in German space research. An organizational and functional outline of a proposed sponsoring organization to promote space commercialization under German supervision, including the objectives, the target group to be served, and the administrative structure, is presented. The role of the DFVLR (German Aerospace Research Establishment) and the BMFT (German Ministry for Research and Technology) as sponsoring organizations representing the interests of the German government is shown.
Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.
Rahman, Wahida; Dickenson, Anthony H
2015-06-01
Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.
Targeted radiotherapy with gold nanoparticles: current status and future perspectives
Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A; Berbeco, Ross; Makrigiorgos, G Mike
2014-01-01
Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed. PMID:24978464
Ma, Nylanda; Roberts, Rachel; Winefield, Helen; Furber, Gareth
2015-02-01
While the importance of looking at the entire family system in the context of child and adolescent mental health is well recognised, siblings of children with mental health problems (MHPs) are often overlooked. The existing literature on the mental health of these siblings needs to be reviewed. A systematic search located publications from 1990 to 2011 in four electronic databases. Thirty-nine relevant studies reported data on the prevalence of psychopathology in siblings of target children with MHPs. Siblings of target children had higher rates of at least one type of psychopathology than comparison children. Risk of psychopathology varied across the type of MHP in the target child. Other covariates included sibling age and gender and parental psychopathology. Significant variations and limitations in methodology were found in the existing literature. Methodological guidelines for future studies are outlined. Implications for clinicians, parents, and for future research are discussed.
Bartsch, R; Frings, S; Marty, M; Awada, A; Berghoff, A S; Conte, P; Dickin, S; Enzmann, H; Gnant, M; Hasmann, M; Hendriks, H R; Llombart, A; Massacesi, C; von Minckwitz, G; Penault-Llorca, F; Scaltriti, M; Yarden, Y; Zwierzina, H; Zielinski, C C
2014-04-01
Insights into tumour biology of breast cancer have led the path towards the introduction of targeted treatment approaches; still, breast cancer-related mortality remains relatively high. Efforts in the field of basic research revealed new druggable targets which now await validation within the context of clinical trials. Therefore, questions concerning the optimal design of future studies are becoming even more pertinent. Aspects such as the ideal end point, availability of predictive markers to identify the optimal cohort for drug testing, or potential mechanisms of resistance need to be resolved. An expert panel representing the academic community, the pharmaceutical industry, as well as European Regulatory Authorities met in Vienna, Austria, in November 2012, in order to discuss breast cancer biology, identification of novel biological targets and optimal drug development with the aim of treatment individualization. This article summarizes statements and perspectives provided by the meeting participants.
Gold-manganese nanoparticles for targeted diagnostic and imaging
DOE Office of Scientific and Technical Information (OSTI.GOV)
Murph, Simona Hunyadi
Imagine the possibility of non-invasive, non-radiation based Magnetic resonance imaging (MRI) in combating cardiac disease. Researchers at the Savannah River National Laboratory (SRNL) are developing a process that would use nanotechnology in a novel, targeted approach that would allow MRIs to be more descriptive and brighter, and to target specific organs. Researchers at SRNL have discovered a way to use multifunctional metallic gold-manganese nanoparticles to create a unique, targeted positive contrast agent. SRNL Senior Scientist Dr. Simona Hunyadi Murph says she first thought of using the nanoparticles for cardiac disease applications after learning that people who survive an infarct exhibitmore » up to 15 times higher rate of developing chronic heart failure, arrhythmias and/or sudden death compared to the general population. Without question, nanotechnology will revolutionize the future of technology. The development of functional nanomaterials with multi-detection modalities opens up new avenues for creating multi-purpose technologies for biomedical applications.« less
Creating targeted initial populations for genetic product searches in heterogeneous markets
NASA Astrophysics Data System (ADS)
Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph
2014-12-01
Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.
The physical basis and future of radiation therapy.
Bortfeld, T; Jeraj, R
2011-06-01
The remarkable progress in radiation therapy over the last century has been largely due to our ability to more effectively focus and deliver radiation to the tumour target volume. Physics discoveries and technology inventions have been an important driving force behind this progress. However, there is still plenty of room left for future improvements through physics, for example image guidance and four-dimensional motion management and particle therapy, as well as increased efficiency of more compact and cheaper technologies. Bigger challenges lie ahead of physicists in radiation therapy beyond the dose localisation problem, for example in the areas of biological target definition, improved modelling for normal tissues and tumours, advanced multicriteria and robust optimisation, and continuous incorporation of advanced technologies such as molecular imaging. The success of physics in radiation therapy has been based on the continued "fuelling" of the field with new discoveries and inventions from physics research. A key to the success has been the application of the rigorous scientific method. In spite of the importance of physics research for radiation therapy, too few physicists are currently involved in cutting-edge research. The increased emphasis on more "professionalism" in medical physics will tip the situation even more off balance. To prevent this from happening, we argue that medical physics needs more research positions, and more and better academic programmes. Only with more emphasis on medical physics research will the future of radiation therapy and other physics-related medical specialties look as bright as the past, and medical physics will maintain a status as one of the most exciting fields of applied physics.
The physical basis and future of radiation therapy
Bortfeld, T; Jeraj, R
2011-01-01
The remarkable progress in radiation therapy over the last century has been largely due to our ability to more effectively focus and deliver radiation to the tumour target volume. Physics discoveries and technology inventions have been an important driving force behind this progress. However, there is still plenty of room left for future improvements through physics, for example image guidance and four-dimensional motion management and particle therapy, as well as increased efficiency of more compact and cheaper technologies. Bigger challenges lie ahead of physicists in radiation therapy beyond the dose localisation problem, for example in the areas of biological target definition, improved modelling for normal tissues and tumours, advanced multicriteria and robust optimisation, and continuous incorporation of advanced technologies such as molecular imaging. The success of physics in radiation therapy has been based on the continued “fuelling” of the field with new discoveries and inventions from physics research. A key to the success has been the application of the rigorous scientific method. In spite of the importance of physics research for radiation therapy, too few physicists are currently involved in cutting-edge research. The increased emphasis on more “professionalism” in medical physics will tip the situation even more off balance. To prevent this from happening, we argue that medical physics needs more research positions, and more and better academic programmes. Only with more emphasis on medical physics research will the future of radiation therapy and other physics-related medical specialties look as bright as the past, and medical physics will maintain a status as one of the most exciting fields of applied physics. PMID:21606068
Mattei, Tobias A; Rehman, Azeem A
2015-01-01
The term "nanotechnology" refers to the development of materials and devices that have been designed with specific properties at the nanometer scale (10(-9) m), usually being less than 100 nm in size. Recent advances in nanotechnology have promised to enable visualization and intervention at the subcellular level, and its incorporation to future medical therapeutics is expected to bring new avenues for molecular imaging, targeted drug delivery, and personalized interventions. Although the central nervous system presents unique challenges to the implementation of new therapeutic strategies involving nanotechnology (such as the heterogeneous molecular environment of different CNS regions, the existence of multiple processing centers with different cytoarchitecture, and the presence of the blood-brain barrier), numerous studies have demonstrated that the incorporation of nanotechnology resources into the armamentarium of neurosurgery may lead to breakthrough advances in the near future. In this article, the authors present a critical review on the current 'state-of-the-art' of basic research in nanotechnology with special attention to those issues which present the greatest potential to generate major therapeutic progresses in the neurosurgical field, including nanoelectromechanical systems, nano-scaffolds for neural regeneration, sutureless anastomosis, molecular imaging, targeted drug delivery, and theranostic strategies.
The assessment of commitment: advantages of a unidimensional, target-free approach.
Klein, Howard J; Cooper, Joseph T; Molloy, Janice C; Swanson, Jacqueline A
2014-03-01
This study presents a new approach to assessing commitment reflecting the Klein, Molloy, and Brinsfield (2012) reconceptualization. Klein et al. recast the construct to address issues hindering commitment scholarship, but their claims cannot be tested with existing measures. This paper presents a 4-item measure consistent with the Klein et al. conceptual definition, a measure intended to be unidimensional and applicable across all workplace targets. Our purpose is to present the development of and provide initial validity evidence for this new commitment measure and to compare it to existing alternative measures. Hypotheses around these objectives were tested with data gathered across 5 samples yielding 2,487 participants representing a wide range of jobs, organizations, and industries. Each sample examined a unique set of variables and targets that together provide a comprehensive test of this new measure relative to 8 different targets, several constructs within the nomological network, and 4 prior commitment measures. Results support our hypotheses regarding (a) the measure's properties and structure, (b) convergence and divergence with prior measures of commitment and other constructs in the nomological network, and (c) advantages over prior measures. These findings support the validity of this new approach to assessing commitment, laying the foundation for future research to address critiques of the commitment construct; better examine the multiple commitments individuals simultaneously hold; and bring consistency, synergy, and integration to commitment scholarship across workplace targets. The conceptual, methodological, and practical benefits of the measure are discussed, along with study limitations and future research opportunities.
PTSD: from neurobiology to pharmacological treatments
Kelmendi, Benjamin; Adams, Thomas G.; Yarnell, Stephanie; Southwick, Steven; Abdallah, Chadi G.; Krystal, John H.
2016-01-01
Posttraumatic stress disorder (PTSD) is a chronic debilitating psychiatric disorder characterized by symptoms of re-experience, avoidance, and hyperarousal that can arise immediately or many years after exposure to a traumatic event and injury. Although extensive research has been done over the past 30 years, the etiology of PTSD remains largely unknown. Several neurobiological systems have been implicated in the pathophysiology and vulnerability for developing PTSD; however, first-line pharmacotherapies are limited. Less than 30% achieve full remission, and even then, approved pharmacological treatments often take weeks for therapeutic effect. This article aims to review the pathophysiology of PTSD within multiple neurobiological systems and how these mechanisms are used as pharmacologic targets of treatment, as well as their potential for future targets of intervention. Highlights of the article We reviewed the neurobiological abnormalities in PTSD as they relate to well-established, preliminary, and future targets for pharmacological interventions. Abnormalities across different neurotransmitter systems have been implicated in the pathophysiology of PTSD but none of these systems function uniformly among all patients with PTSD First-line pharmacotherapy for PTSD provides a suboptimal response rates. Future pharmacological targets for PTSD include the cannabinoid and oxytocin systems, as well glutamatergic modulating agents. Drug development for PTSD should specifically address various dimensions of PTSD symptomatology. PMID:27837583
Internet interventions for mental health and addictions: current findings and future directions.
Cunningham, John A; Gulliver, Amelia; Farrer, Lou; Bennett, Kylie; Carron-Arthur, Bradley
2014-12-01
Over the last several years, there has been a substantial increase in the number of publications reporting on Internet interventions for mental health and addictions. This paper provides a summary of the recent research on Internet interventions for the most common mental health and addictions concerns-depression, anxiety, alcohol and smoking. There is considerable evidence for the effectiveness of Internet-based interventions targeting depression, anxiety disorders, alcohol use and smoking. Small to moderate effect sizes have been reported for interventions targeting depression, anxiety and alcohol use, and smoking interventions have shown large effects. The addition of human support to depression and anxiety interventions has generally resulted in larger treatments effects, but this trend has not been observed in trials of interventions targeting alcohol use. There is some evidence that online interventions can be as effective as face-to-face therapies, at least for anxiety disorders. Despite a proliferation of research activity in this area, gaps in knowledge remain. Future research should focus on the development and evaluation of interventions for different platforms (e.g. smartphone applications), examining the long-term impacts of these interventions, determining active intervention components and identifying methods for enhancing tailoring and engagement. Careful consideration should be given to the ongoing technical and clinical expertise required to ensure that Internet interventions are delivered safely and professionally in a rapidly changing technology environment.
LeNoue, Sean R; Riggs, Paula D
2016-04-01
Substance use disorders account for approximately 6% of deaths worldwide and cost about $700 billion in the United States. Approximately 80% of drug users begin using during adolescence, underscoring the public health importance of effective substance prevention programs for youth and families. Prevention science designates 3 intervention categories: (1) universal prevention, targeting all individuals in the population, (2) selective interventions, targeting high-risk groups, and (3) indicated prevention interventions for youth with risk-taking behaviors. School-based and non-school-based interventions are reviewed, as well as the limitations of existing research, gaps in access and availability, and directions for future research and development. Copyright © 2016 Elsevier Inc. All rights reserved.
Ball, Jennifer Gerard; Manika, Danae; Stout, Patricia
2011-10-01
Direct-to-consumer pharmaceutical advertising (DTCA) studies have typically focused on older adults or a general population of adults. However, college students are viable targets for DTCA and are receiving more research attention in this area. In this article, we compare college students with two adult age segments. Our findings indicate all age groups had relatively high awareness of DTCA and similar attitudes and behavioral responses to the ads. However, there were significant differences in media use and health characteristics as well as the factors predicting DTCA ad trust, attitudes, and behavioral intentions. Implications and future research suggestions are discussed.
ERIC Educational Resources Information Center
Foreman, Jennifer; Renzulli, Joseph
2012-01-01
Dr. Persson's (2012a) target article addresses a number of key points that will greatly impact the study of giftedness, gifted education, and talent development in the "flat" world of the 21st century and beyond. Research in these areas needs to continually reflect upon changes in the social world outside its narrow purview to validate its…
Hocking, Matthew C.; McCurdy, Mark; Turner, Elise; Kazak, Anne E.; Noll, Robert B.; Phillips, Peter; Barakat, Lamia P.
2014-01-01
Pediatric brain tumor (BT) survivors are at risk for psychosocial late effects across many domains of functioning, including neurocognitive and social. The literature on the social competence of pediatric BT survivors is still developing and future research is needed that integrates developmental and cognitive neuroscience research methodologies to identify predictors of survivor social adjustment and interventions to ameliorate problems. This review discusses the current literature on survivor social functioning through a model of social competence in childhood brain disorder and suggests future directions based on this model. Interventions pursuing change in survivor social adjustment should consider targeting social ecological factors. PMID:25382825
Evidence base and future research directions in the management of low back pain
Abbott, Allan
2016-01-01
Low back pain (LBP) is a prevalent and costly condition. Awareness of valid and reliable patient history taking, physical examination and clinical testing is important for diagnostic accuracy. Stratified care which targets treatment to patient subgroups based on key characteristics is reliant upon accurate diagnostics. Models of stratified care that can potentially improve treatment effects include prognostic risk profiling for persistent LBP, likely response to specific treatment based on clinical prediction models or suspected underlying causal mechanisms. The focus of this editorial is to highlight current research status and future directions for LBP diagnostics and stratified care. PMID:27004162
NASA Technical Reports Server (NTRS)
Didion, Jeffrey R.
2018-01-01
Electrically Driven Thermal Management is an active research and technology development initiative incorporating ISS technology flight demonstrations (STP-H5), development of Microgravity Science Glovebox (MSG) flight experiment, and laboratory-based investigations of electrically based thermal management techniques. The program targets integrated thermal management for future generations of RF electronics and power electronic devices. This presentation reviews four program elements: i.) results from the Electrohydrodynamic (EHD) Long Term Flight Demonstration launched in February 2017 ii.) development of the Electrically Driven Liquid Film Boiling Experiment iii.) two University based research efforts iv.) development of Oscillating Heat Pipe evaluation at Goddard Space Flight Center.
Microbial Source Tracking of Avian Sources
What Have We Learned After 10 Years of MST Research: Its Importance in the Developments of New Markers and Future Directions. Feces Production in the U.S.: Human - 07%; Chickens - 22%; Pigs - 20%; Dairy - 10%; and Beef Cattle 44%. Evaluation of Swine Assays - PF163 targeting...
A brief randomized controlled intervention targeting parents improves grades during middle school.
Destin, Mesmin; Svoboda, Ryan C
2017-04-01
Despite a growing number of brief, psychosocial interventions that improve academic achievement, little research investigates how to leverage parents during such efforts. We designed and tested a randomized controlled intervention targeting parents to influence important discussions about the future and responses to academic difficulty experienced by their adolescent during eighth grade in the United States. We recruited experienced parents to convey the main messages of the intervention in a parent panel format. As expected, current parents who were randomly assigned to observe the parent panel subsequently planned to talk with their adolescents sooner about future opportunities and to respond more positively to experiences of academic difficulty than parents who were randomly assigned to a control group. The intervention also led to a significant increase in student grades, which was mediated by parents' responses to academic difficulty. We suggest an increase in experimental research that utilizes parents to influence student achievement. Copyright © 2017 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.
The future of quantum dots in drug discovery.
Lin, Guimiao; Yin, Feng; Yong, Ken-Tye
2014-09-01
The rapid development of drug discovery today is inseparable from the interaction of advanced particle technologies and new drug synthesis protocols. Quantum dots (QDs) are regarded as a unique class of fluorescent labels, with unique optical properties such as high brightness and long-term colloidal and optical stability; these are suitable for optical imaging, drug delivery and optical tracking, fluorescence immunoassay and other medicinal applications. More importantly, QD possesses a rich surface chemistry property that is useful for incorporating various drug molecules, targeting ligands, and additional contrast agents (e.g., MRI, PET, etc.) onto the nanoparticle surface for achieving targeted and traceable drug delivery therapy at both cellular and systemic levels. In recent times, the advancement of QD technology has promoted the use of functionalized nanocrystals for in vivo applications. Such research is paving the way for drug discovery using various bioconjugated QD formulations. In this editorial, the authors highlight the current research progress and future applications of QDs in drug discovery.
Tabachnick, Walter J.
2016-01-01
Research on mosquitoes and mosquito-borne diseases has contributed to improvements in providing effective, efficient, and environmentally proper mosquito control. Florida has benefitted from several research accomplishments that have increased the state’s mosquito control capabilities. Research with Florida’s mosquitoes has resulted in the development of ecologically sound management of mosquito impoundments on Florida’s east coast. This strategy, called Rotational Impoundment Management (RIM), has improved the ability to target the delivery of pesticides and has helped to reduce non-target effects and environmental damage. Research has led to the development of an arbovirus surveillance system which includes sentinel chicken surveillance, real time use of environmental contributing factors like meteorology and hydrology to target mosquito control, as well as public health efforts to mitigate disease outbreaks to areas with risk of disease. These research driven improvements have provided substantial benefits to all of Florida. More research is needed to meet the future challenges to reduce emerging pathogens like Zika virus and the consequences of environmental changes like global climate change that are likely to influence the effects of mosquito-borne pathogens on human health and well-being. PMID:27690112
A Combinatorial Geometry Computer Description of the XR311 Vehicle
1978-04-01
cards or magnetic tape. The shot line output of the GRID subroutine of the GIFT code is also stored on magnetic tape for future vulnera- bility...descriptions as processed by the Geometric Information For Targets ( GIFT )2 computer code. This report documents the COM-GEOM target description for all...72, March 1974. ’L.W. Bains and M.J. Reisinger, "The GIFT Code User Manual, VOL 1, Introduction and Input Requirements, " Ballistic Research
CNS drug development: part III: future directions.
Preskorn, Sheldon H
2011-01-01
This column, the third in a series on central nervous system (CNS) drug development, discusses advances during the first decade of the 21st century and directions the field may take in the next 10 years. By identifying many possible new drug targets, the human genome project has created the potential to develop novel central nervous system (CNS) drugs with new mechanisms of action. At the same time, this proliferation of possible new targets has complicated the drug development process, since research has not yet provided guidance as to which targets may be most fruitful. This and other factors (eg, increasing regulatory requirements) have increased the cost and complexity of the drug development process. In addition, as more is learned about the biology of psychiatric illnesses, syndromes may be subdivided into more specific entities that are better understood from a pathophysiological and pathoetiological perspective. This is likely to lead to development of more targeted treatments focused on underlying causes of illness as well as prevention. The development of drugs for Alzheimer's disease is discussed as a possible model for future CNS drug development. We are at the beginning of an era when it is likely that the way in which CNS drugs are developed will need to be rethought, which will call for flexibility and creativity on the part of both drug developers and clinical researchers.
Li, Hongxiang; Sun, Xiaoyuan; Yu, Fan; Xu, Lijia; Miu, Jianhua; Xiao, Peigen
2018-05-10
Based on compelling experimental and clinical evidence, Ginkgo biloba L. exerts a beneficial effect in ameliorating mild to moderate dementia in patients with Alzheimer’s disease (AD) and other neurological disorders, although the pharmacological mechanisms remain unknown. In the present study, compounds, their putative target proteins identified using an inverse docking approach, and clinically tested AD-related target proteins were systematically integrated together with applicable bioinformatics methods in silico . The results suggested that the beneficial effects of G. biloba on AD may be contributed by the regulation of hormone sensitivity, improvements in endocrine homeostasis, maintenance of endothelial microvascular integrity, and proteolysis of tau proteins, particularly prior to amyloid β-protein (Aβ) plaque formation. Moreover, we identified six putative protein targets that are significantly related to AD, but have not been researched or have had only preliminary studies conducted on the anti-AD effects of G. biloba . These mechanisms and protein targets are very significant for future scientific research. In addition, the existing mechanisms were also verified, such as the reduction of oxidative stress, anti-apoptotic effects, and protective effects against amyloidogenesis and Aβ aggregation. The discoveries summarized here may provide a macroscopic perspective that will improve our understanding of the molecular mechanism of medicinal plants or dietary supplements, as well as new clues for the future development of therapeutic strategies for AD.
NASA Astrophysics Data System (ADS)
Klim, Adam; Morrison, J.; Orban, C.; Chowdhury, E.; Frische, K.; Feister, S.; Roquemore, M.
2017-10-01
The success of laser-accelerated ion experiments depends crucially on a number of factors including how thin the targets can be created. We present experimental results demonstrating extremely thin (under 200 nm) glycol sheet targets that can be used for ultra-intense laser-accelerated ion experiments conducted at the Air Force Research Laboratory at Wright-Patterson Air Force Base. Importantly, these experiments operate at a kHz repetition rate and the recovery time of the liquid targets is fast enough to allow the laser to interact with a refreshed, thin target on every shot. These thin targets can be used to produce energetic electrons, light ions, and neutrons as well as x-rays, we present results from liquid glycol targets which are useful for proton acceleration experiments via the mechanism of Target Normal Sheath Acceleration (TNSA). In future work, we will create thin sheets from deuterated water in order to perform laser-accelerated deuteron experiments. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the AFOSR, under the management of Dr. Enrique Parra, and support from the DOD HPCMP Internship Program.
Corner, Emily; Gill, Paul; Schouten, Ronald; Farnham, Frank
2018-06-06
This article aims to move away from intuitive appeals that link mental disorder with violence such as terrorism, mass murder, and other targeted violence. The article synthesizes the existing evidence base regarding the relationship between mental disorders and personality traits and (a) attitudinal affinities with violent causes, and (b) a number of violent behaviors (including mass murder and terrorism). The evidence base is mixed and the research focus changed across time: from simple and unempirical assertions of causation to an almost complete rejection of their presence to a finer grained and disaggregated understanding. Empirical research examining mental disorder in crime and violence highlights that the commission of such events is a complex synthesis of psychopathology, personal circumstance, and environment. The article concludes with several suggestions regarding future research and practice.
White, Mathew P; Eiser, J Richard; Harris, Peter R; Pahl, Sabine
2007-06-01
Although the issue of risk target (e.g., self, others, children) is widely acknowledged in risk perception research, its importance appears underappreciated. To date, most research has been satisfied with demonstrating comparative optimism, i.e., lower perceived risk for the self than others, and exploring its moderators, such as perceived controllability and personal exposure. Much less research has investigated how the issue of target may affect benefit perceptions or key outcomes such as stated preferences for hazard regulation. The current research investigated these issues using data from a public survey of attitudes toward mobile phone technology (N= 1,320). First, results demonstrated comparative optimism for this hazard, and also found moderating effects of both controllability and personal exposure. Second, there was evidence of comparative utility, i.e., users believed that the benefits from mobile phone technology are greater for the self than others. Third, and most important for policy, preferences for handset regulation were best predicted by perceptions of the risks to others but perceived benefits for the self. Results suggest a closer awareness of target can improve prediction of stated preferences for hazard regulation and that it would be profitable for future research to pay more attention to the issue of target for both risk and benefit perceptions.
Satellite remote sensing, biodiversity research and conservation of the future
Pettorelli, Nathalie; Safi, Kamran; Turner, Woody
2014-01-01
Assessing and predicting ecosystem responses to global environmental change and its impacts on human well-being are high priority targets for the scientific community. The potential for synergies between remote sensing science and ecology, especially satellite remote sensing and conservation biology, has been highlighted by many in the past. Yet, the two research communities have only recently begun to coordinate their agendas. Such synchronization is the key to improving the potential for satellite data effectively to support future environmental management decision-making processes. With this themed issue, we aim to illustrate how integrating remote sensing into ecological research promotes a better understanding of the mechanisms shaping current changes in biodiversity patterns and improves conservation efforts. Added benefits include fostering innovation, generating new research directions in both disciplines and the development of new satellite remote sensing products. PMID:24733945
Genetics, obesity, age, and lifestyle are major susceptibility factors in the induction of asthma and can interact with environmental exposures either synergistically or antagonistically. Different environmental exposures that increase or decrease the likelihood of developing as...
Technical Challenges and Solutions in Representing Lakes when using WRF in Downscaling Applications
The Weather Research and Forecasting (WRF) model is commonly used to make high resolution future projections of regional climate by downscaling global climate model (GCM) outputs. Because the GCM fields are typically at a much coarser spatial resolution than the target regional ...
Modeling Human Visual Perception for Target Detection in Military Simulations
2009-06-01
incorrectly, is a subject for future research. Possibly, one could exploit the Recognition-by-Components theory of Biederman (1987) and decompose the...Psychophysiscs, 55, 485-496. Biederman , I. (1987). Recognition-by-components: A theory of human image understand- ing. Psychological Review, 94, 115-147
Development of the Los Alamos National Laboratory Cryogenic Pressure Loader
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ebey, Peter S.; Dole, James M.; Hoffer, James K.
2003-05-15
Targets for inertial fusion research and ignition at OMEGA, the National Ignition Facility, LMJ, and future facilities rely on beta-radiation-driven layering of spherical cryogenic DT ice layers contained within plastic or metal shells. Plastic shells will be permeation filled at room temperature then cooled to cryogenic temperatures before removal of the overpressure. The cryogenic pressure loader (CPL) was recently developed at Los Alamos National Laboratory as a testbed for studying the filling and layering of plastic target shells with DT. A technical description of the CPL is provided. The CPL consists of a cryostat, which contains a high-pressure permeation cell,more » and has optical access for investigating beta layering. The cryostat is housed within a tritium glovebox that contains manifolds for supplying high-pressure DT. The CPL shares some design elements with the cryogenic target handling system at the OMEGA facility to allow testing of tritium issues related to that system. The CPL has the capability to fill plastic targets by permeation to pressures up to 100 MPa and to cool them to 15 K. The CPL will accommodate a range of targets and may be modified for future experiments.« less
Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S
2018-02-01
The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.
Development of CRISPR/Cas9 mediated virus resistance in agriculturally important crops.
Khatodia, Surender; Bhatotia, Kirti; Tuteja, Narendra
2017-05-04
Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR associated nuclease 9 (Cas9) system of targeted genome editing has already revolutionized the plant science research. This is a RNA guided programmable endonuclease based system composed of 2 components, the Cas9 nuclease and an engineered guide RNA targeting any DNA sequence of the form N20-NGG for novel genome editing applications. The CRISPR/Cas9 technology of targeted genome editing has been recently applied for imparting virus resistance in plants. The robustness, wide adaptability, and easy engineering of this system has proved its potential as an antiviral tool for plants. Novel DNA free genome editing by using the preassembled Cas9/gRNA ribonucleoprotein complex for development of virus resistance in any plant species have been prospected for the future. Also, in this review we have discussed the reports of CRISPR/Cas9 mediated virus resistance strategy against geminiviruses by targeting the viral genome and transgene free strategy against RNA viruses by targeting the host plant factors. In conclusion, CRISPR/Cas9 technology will provide a more durable and broad spectrum viral resistance in agriculturally important crops which will eventually lead to public acceptance and commercialization in the near future.
TARGETED CAPTURE IN EVOLUTIONARY AND ECOLOGICAL GENOMICS
Jones, Matthew R.; Good, Jeffrey M.
2016-01-01
The rapid expansion of next-generation sequencing has yielded a powerful array of tools to address fundamental biological questions at a scale that was inconceivable just a few years ago. Various genome partitioning strategies to sequence select subsets of the genome have emerged as powerful alternatives to whole genome sequencing in ecological and evolutionary genomic studies. High throughput targeted capture is one such strategy that involves the parallel enrichment of pre-selected genomic regions of interest. The growing use of targeted capture demonstrates its potential power to address a range of research questions, yet these approaches have yet to expand broadly across labs focused on evolutionary and ecological genomics. In part, the use of targeted capture has been hindered by the logistics of capture design and implementation in species without established reference genomes. Here we aim to 1) increase the accessibility of targeted capture to researchers working in non-model taxa by discussing capture methods that circumvent the need of a reference genome, 2) highlight the evolutionary and ecological applications where this approach is emerging as a powerful sequencing strategy, and 3) discuss the future of targeted capture and other genome partitioning approaches in light of the increasing accessibility of whole genome sequencing. Given the practical advantages and increasing feasibility of high-throughput targeted capture, we anticipate an ongoing expansion of capture-based approaches in evolutionary and ecological research, synergistic with an expansion of whole genome sequencing. PMID:26137993
Burke, Meghan; Arnold, Catherine; Owen, Aleksa
2018-04-01
Although individuals with intellectual and developmental disabilities (IDD) are living longer lives, fewer than half of parents of individuals with IDD conduct future planning. The correlates and barriers to future planning must be identified to develop targeted interventions to facilitate future planning. In this study, 388 parents of individuals with IDD responded to a national, web-based survey. Participants who were older, more educated, attended more parent training and support activities, and had children with fewer functional abilities, were more likely to engage in future planning. Reported barriers to future planning included: (a) lack of available services, (b) financial challenges, (c) reluctance of family members, (d) lack of time, (e) the emotional nature of future planning, (f) inertia, and (g) a lack of family members to be caregivers. Implications for policy, practice, and future research are discussed.
Zhang, Shaodian; O'Carroll Bantum, Erin; Owen, Jason; Bakken, Suzanne; Elhadad, Noémie
2017-03-01
The Internet and social media are revolutionizing how social support is exchanged and perceived, making online health communities (OHCs) one of the most exciting research areas in health informatics. This paper aims to provide a framework for organizing research of OHCs and help identify questions to explore for future informatics research. Based on the framework, we conceptualize OHCs from a social support standpoint and identify variables of interest in characterizing community members. For the sake of this tutorial, we focus our review on online cancer communities. The primary target audience is informaticists interested in understanding ways to characterize OHCs, their members, and the impact of participation, and in creating tools to facilitate outcome research of OHCs. OHC designers and moderators are also among the target audience for this tutorial. The tutorial provides an informatics point of view of online cancer communities, with social support as their leading element. We conceptualize OHCs according to 3 major variables: type of support, source of support, and setting in which the support is exchanged. We summarize current research and synthesize the findings for 2 primary research questions on online cancer communities: (1) the impact of using online social support on an individual's health, and (2) the characteristics of the community, its members, and their interactions. We discuss ways in which future research in informatics in social support and OHCs can ultimately benefit patients. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association.
Male contraception: past, present and future.
Payne, Christopher; Goldberg, Erwin
2014-01-01
Current contraceptive options available to men include withdrawal, condoms, and vasectomy, each of which has its own drawbacks. In this chapter we will describe the pros and cons for each, as well as methodological and product updates. Statistics from the U.S. Centers for Disease Control on acceptance and satisfaction will be included. Advances in vasectomy and reversal will be presented. Methods to develop new contraceptive technologies fall into two categories: hormonal and non-hormonal. Many targets and strategies have been proposed for non-hormonal male contraception within the testis. Targets include structural components in the testis, as well as enzymes, ion channels and other proteins specific to spermatozoa. Here we provide an overview of the spermatogenic mechanisms and proteins that have received research interest to date. We also discuss potential novel targets, such as ubiquitin specific proteases, that warrant greater research emphasis.
Using Social Media to Target Cancer Prevention in Young Adults: Viewpoint.
Sarkar, Urmimala; Le, Gem M; Lyles, Courtney R; Ramo, Danielle; Linos, Eleni; Bibbins-Domingo, Kirsten
2018-06-05
Focusing on primary cancer prevention can reduce its incidence. Changing health behaviors is critical to cancer prevention. Modifiable cancer risk factors include lifestyle behaviors related to vaccination, physical activity, weight control and maintenance, alcohol consumption, and tobacco use. These health habits are often formed in young adulthood, a life stage which currently intersects with the growing population of digital natives whose childhood occurred in the internet era. Social media is a critical communication medium to reach this population of digital natives. Using a life course perspective, the purpose of this viewpoint paper is to describe the current landscape of nascent research using social media to target cancer prevention efforts in young adults and propose future directions to strengthen the scientific knowledge supporting social media strategies to promote cancer prevention behaviors. Leveraging social media as a health promotion tool is a promising strategy to impact modifiable behavioral risk factors for cancer and warrants further research on developing effective communication strategies in young adults to prevent cancer in the future generations. ©Urmimala Sarkar, Gem M Le, Courtney R Lyles, Danielle Ramo, Eleni Linos, Kirsten Bibbins-Domingo. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.06.2018.
Eating disorders: Insights from imaging and behavioral approaches to treatment.
Stice, Eric; Shaw, Heather
2017-11-01
Understanding factors that contribute to eating disorders, which affect 13% of females, is critical to developing effective prevention and treatment programs. In this paper, we summarize results from prospective studies that identified factors predicting onset and persistence of eating disorders and core symptom dimensions. Next, implications for intervention targets for prevention, and treatment interventions from the risk- and maintenance-factor findings are discussed. Third, given that evidence suggests eating disorders are highly heritable, implying biological risk and maintenance factors for eating disorders, we offer working hypotheses about biological factors that might contribute to eating disorders, based on extant risk factor findings, theory, and cross-sectional studies. Finally, potentially fruitful directions for future research are presented. We suggest that it would be useful for experimental therapeutics trials to evaluate the effects of reducing the risk factors on future onset of eating pathology and on reducing maintenance factors on the risk for persistence of eating pathology, and encourage researchers to utilize prospective high-risk studies so that knowledge regarding potential intervention targets for prevention and treatment interventions for eating disorders can be advanced. Using the most rigorous research designs should help improve the efficacy of prevention and treatment interventions for eating disorders.
Katz, Carmit; Hamama, Liat
2016-07-20
Siblings share a common and unique bond. It is one of the most enduring relationships during an individual's life span. Thus, the impact of child maltreatment on sibling relationships is an important area of research to explore. The current article carries out a scoping review targeted at determining the existing knowledge and then identifying research priorities within the field of sibling relationship in the context of child maltreatment. The method elaborates on the various stages that were taken to perform the scoping review, and later, the article provides three results for the readers: The first result is a detailed mapping of the existing literature in the area of sibling relationship in the context of maltreatment. The second result is a thorough thematic analysis that was carried out on this literature that focused on several relevant domains: sibling exposure to intimate partner violence, sibling relationship and experiences in the context of child maltreatment, risk assessment for siblings following maltreatment, and sibling relationships and out-of-home placement. The third result is a set of conclusions targeted mainly at recommending future directions to researchers. © The Author(s) 2016.
Kaplan, Deanna M; Palitsky, Roman; Carey, Angela L; Crane, Tracy E; Havens, Cody M; Medrano, Michael R; Reznik, Samantha J; Sbarra, David A; O'Connor, Mary-Frances
2018-07-01
Maladaptive repetitive thought (RT), the frequent and repetitive revisiting of thoughts or internal experiences, is associated with a range of psychopathological processes and disorders. We present a synthesis of prior research on maladaptive RT and develop a framework for elucidating and distinguishing between five forms of maladaptive RT. In addition to the previously studied maladaptive RT (worry, rumination, and obsession), this framework is used to identify two additional forms of maladaptive RT (yearning and interoceptive RT). We then present a review of extant psychotherapy intervention research targeting maladaptive RT, focusing both on specific empirically based treatment strategies, and also constructs within treatments that impact maladaptive RT. The paper concludes with recommendations for future basic and intervention research on maladaptive RT and related psychopathologies. © 2018 Wiley Periodicals, Inc.
ERIC Educational Resources Information Center
Hyde, Joan; Perez, Rosa; Forester, Brent
2007-01-01
Purpose: This article presents an overview of what is known about dementia services in assisted living settings and suggests areas for future research. Design and Methods: We undertook a search of Medline, the "Journals of Gerontology," and "The Gerontologist." We then organized publications dealing with the target subject into 10 topic areas and…
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-27
... community programs and policies and their relationship to childhood obesity. The HCS is an observational... reduce childhood obesity. Furthermore, HCS results will be published in scientific journals and will be used for the development of future research initiatives targeting childhood obesity. Frequency of...
The Reliability of Environmental Measures of the College Alcohol Environment.
ERIC Educational Resources Information Center
Clapp, John D.; Whitney, Mike; Shillington, Audrey M.
2002-01-01
Assesses the inter-rater reliability of two environmental scanning tools designed to identify alcohol-related advertisements targeting college students. Inter-rater reliability for these forms varied across different rating categories and ranged from poor to excellent. Suggestions for future research are addressed. (Contains 26 references and 6…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ammigan, K.; Hurh, P.
The Radiation Damage In Accelerator Target Environments (RaDIATE) collaboration was founded in 2012 and currently consists of over 50 participants and 11 institutions globally. Due to the increasing power of future proton accelerator sources in target facilities, there is a critical need to further understand the physical and thermo-mechanical radiation response of target facility materials. Thus, the primary objective of the RaDIATE collaboration is to draw on existing expertise in the nuclear materials and accelerator targets fields to generate new and useful materials data for application within the accelerator and fission/fusion communities. Current research activities of the collaboration include postmore » irradiation examination (PIE) of decommissioned components from existing beamlines such as the NuMI beryllium beam window and graphite NT-02 target material. PIE of these components includes advanced microstructural analyses (SEM/TEM, EBSD, EDS) and micro-mechanics technique such as nano-indentation, to help characterize any microstructural radiation damage incurred during operation. New irradiation campaigns of various candidate materials at both low and high energy beam facilities are also being pursued. Beryllium helium implantation studies at the University of Surrey as well as high energy proton irradiation of various materials at Brookhaven National Laboratory’s BLIP facility have been initiated. The program also extends to beam-induced thermal shock experiments using high intensity beam pulses at CERN’s HiRadMat facility, followed by advanced PIE activities to evaluate thermal shock resistance of the materials. Preliminary results from ongoing research activities, as well as the future plans of the RaDIATE collaboration R&D program will be discussed.« less
Targeted therapies in gastric cancer and future perspectives.
Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan
2016-01-14
Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.
Dara, Ajay; Sangamwar, Abhay T
2014-08-01
This review discusses the various drug therapeutic targets and latest technologies of anticancer patents from 10 Indian public-funded research organizations covering more than 150 esteemed institutes. We have identified and reported the leading assignee and inventors along with their collaboration network and, thereby, have analyzed the various patent trends, geographical distributions, citation maps, Derwent World Patents Index, international patent classification analysis and the like. This article provides the insights of 1905 patent documents from 191 families and discusses in-depth anticancer technology through categorization studies at the level of drug discovery, drug development and treatment and diagnosis. In addition, various cancer targets were correlated with recent technologies so as to identify the white spaces for upcoming technologies. Over a period of 13 years (1990 - 2013) the main focus of Indian cancer research was in the field of synthetic chemistry and natural extracts followed by the pharmaceutical compositions and combinations, whereas, the white spaces for future cancer remedy were identified from research in the areas of cancer stem cell lines, vaccines, gene therapy, nano formulations with targeted drug delivery systems as core and latest technologies.
Temporal reasoning over clinical text: the state of the art
Sun, Weiyi; Rumshisky, Anna; Uzuner, Ozlem
2013-01-01
Objectives To provide an overview of the problem of temporal reasoning over clinical text and to summarize the state of the art in clinical natural language processing for this task. Target audience This overview targets medical informatics researchers who are unfamiliar with the problems and applications of temporal reasoning over clinical text. Scope We review the major applications of text-based temporal reasoning, describe the challenges for software systems handling temporal information in clinical text, and give an overview of the state of the art. Finally, we present some perspectives on future research directions that emerged during the recent community-wide challenge on text-based temporal reasoning in the clinical domain. PMID:23676245
Inhibiting the HIV Integration Process: Past, Present, and the Future
2013-01-01
HIV integrase (IN) catalyzes the insertion into the genome of the infected human cell of viral DNA produced by the retrotranscription process. The discovery of raltegravir validated the existence of the IN, which is a new target in the field of anti-HIV drug research. The mechanism of catalysis of IN is depicted, and the characteristics of the inhibitors of the catalytic site of this viral enzyme are reported. The role played by the resistance is elucidated, as well as the possibility of bypassing this problem. New approaches to block the integration process are depicted as future perspectives, such as development of allosteric IN inhibitors, dual inhibitors targeting both IN and other enzymes, inhibitors of enzymes that activate IN, activators of IN activity, as well as a gene therapy approach. PMID:24025027
Torchalla, Iris; Strehlau, Verena
2018-03-01
The purpose of this study was to summarize the evidence base for interventions targeting individuals with work-related posttraumatic stress disorder (PTSD), to make recommendations for clinicians and administrative decision makers involved in their rehabilitation, and to guide future research in this area. Particular attention was given to studies that were conducted in naturalistic clinical settings or in a workers' compensation claim context. Electronic searches of Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, PsycINFO, CINAHL, PILOTS, and EMBASE identified 11 articles. Study populations included railroad personnel, police officers, disaster workers, and individuals with industrial injuries. Interventions included trauma-focused cognitive-behavioral therapy and eye movement desensitization and reprocessing. Several studies specifically targeted workers who had failed to return to work (RTW) after standard PTSD treatment. The results suggest that psychotherapy interventions are beneficial for helping clients recover from PTSD symptoms and RTW. In studies that reported on work status, RTW rates increased over time and generally lay between 58% and 80% across follow-up time points. Narrative impressions were supplemented by calculation of Risk Differences for individuals working at pretreatment versus posttreatment. Clinical consideration, methodological issues limiting the current body of work, and recommendations for future research are discussed.
Contests versus Norms: Implications of Contest-Based and Norm-Based Intervention Techniques
Bergquist, Magnus; Nilsson, Andreas; Hansla, André
2017-01-01
Interventions using either contests or norms can promote environmental behavioral change. Yet research on the implications of contest-based and norm-based interventions is lacking. Based on Goal-framing theory, we suggest that a contest-based intervention frames a gain goal promoting intensive but instrumental behavioral engagement. In contrast, the norm-based intervention was expected to frame a normative goal activating normative obligations for targeted and non-targeted behavior and motivation to engage in pro-environmental behaviors in the future. In two studies participants (n = 347) were randomly assigned to either a contest- or a norm-based intervention technique. Participants in the contest showed more intensive engagement in both studies. Participants in the norm-based intervention tended to report higher intentions for future energy conservation (Study 1) and higher personal norms for non-targeted pro-environmental behaviors (Study 2). These findings suggest that contest-based intervention technique frames a gain goal, while norm-based intervention frames a normative goal. PMID:29218026
Contests versus Norms: Implications of Contest-Based and Norm-Based Intervention Techniques.
Bergquist, Magnus; Nilsson, Andreas; Hansla, André
2017-01-01
Interventions using either contests or norms can promote environmental behavioral change. Yet research on the implications of contest-based and norm-based interventions is lacking. Based on Goal-framing theory, we suggest that a contest-based intervention frames a gain goal promoting intensive but instrumental behavioral engagement. In contrast, the norm-based intervention was expected to frame a normative goal activating normative obligations for targeted and non-targeted behavior and motivation to engage in pro-environmental behaviors in the future. In two studies participants ( n = 347) were randomly assigned to either a contest- or a norm-based intervention technique. Participants in the contest showed more intensive engagement in both studies. Participants in the norm-based intervention tended to report higher intentions for future energy conservation (Study 1) and higher personal norms for non-targeted pro-environmental behaviors (Study 2). These findings suggest that contest-based intervention technique frames a gain goal, while norm-based intervention frames a normative goal.
Houben, R.; Cohen, T.; Pai, M.; Cobelens, F.; Vassall, A.; Menzies, N. A.; Gomez, G. B.; Langley, I.; Squire, S. B.; White, R.
2014-01-01
SUMMARY The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert® MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research. PMID:25189546
Ronda, Elena; López-Jacob, M José; Paredes-Carbonell, Joan J; López, Pilar; Boix, Pere; García, Ana M
2014-01-01
This article describes the experience of knowledge translation between researchers of the ITSAL (immigration, work and health) project and representatives of organizations working with immigrants to discuss the results obtained in the project and future research lines. A meeting was held, attended by three researchers and 18 representatives from 11 institutions. Following a presentation of the methodology and results of the project, the participants discussed the results presented and research areas of interest, thus confirming matches between the two sides and obtaining proposals of interest for the ITSAL project. We understand the process described as an approach to social validation of some of the main results of this project. This experience has allowed us to open a channel of communication with the target population of the study, in line with the necessary two-way interaction between researchers and users. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.
Jack, Leonard; Toston, Tyra; Jack, Nkenge H; Sims, Mario
2010-03-01
Blacks have traditionally experienced a disproportionate burden of diabetes in the United States. Research published from 1980 to 2008 revealed a paucity of diabetes education and management research targeting Black men. There is a paucity of published research that takes into consideration attributes of "being male," such as masculinity, and how its attributes influence diabetes self-management behaviors. This article discusses three important factors that may help explain diabetes-related disparities among Black men.These factors include absence of consistent sources of health care, lack of health insurance, and the absence of a masculinity perspective in diabetes education and management research. This article offers a gender-centered ecological framework that examines pathways between demographic factors, family functioning, knowledge and psychological health, biological health, behavioral health and medical compliance, masculinity, and diabetes-related outcomes. Recommendations for future research that consider how aspects of masculinity might lead to the identification of gender-based risk factors are presented.
Friendship Satisfaction in Children with Autism Spectrum Disorder and Nominated Friends.
Petrina, Neysa; Carter, Mark; Stephenson, Jennifer; Sweller, Naomi
2017-02-01
The current study examined the level of friendship satisfaction of children with autism spectrum disorder (ASD) and their nominated friends (with and without diagnosis of ASD). A total of 77 target children with ASD and friends from 49 nominated friendships participated in the study. Relatively high levels of friendship satisfaction were reported by both target children and their nominated friends with no overall difference between dyads involving typically developing friends and friends with ASD. Analysis at the individual dyad level showed a high level of agreement on the reported level of satisfaction across the target participants and their friends. Limitations and directions for future research are presented.
Photoelectrochemical enzymatic biosensors.
Zhao, Wei-Wei; Xu, Jing-Juan; Chen, Hong-Yuan
2017-06-15
Enzymatic biosensors have been valuable bioanalytical devices for analysis of diverse targets in disease diagnosis, biological and biomedical research, etc. Photoelectrochemical (PEC) bioanalysis is a recently emerged method that promptly becoming a subject of new research interests due to its attractive potential for future bioanalysis with high sensitivity and specificity. PEC enzymatic biosensors integrate the inherent sensitivities of PEC bioanalysis and the selectivity of enzymes and thus share their both advantages. Currently, PEC enzymatic biosensors have become a hot topic of significant research and the recent impetus has grown rapidly as demonstrated by increased research papers. Given the pace of advances in this area, this review will make a thorough discussion and survey on the fundamentals, sensing strategies, applications and the state of the art in PEC enzymatic biosensors, followed by future prospects based on our own opinions. We hope this work could provide an accessible introduction to PEC enzymatic biosensors for any scientist. Copyright © 2016 Elsevier B.V. All rights reserved.
Online recognition of Chinese characters: the state-of-the-art.
Liu, Cheng-Lin; Jaeger, Stefan; Nakagawa, Masaki
2004-02-01
Online handwriting recognition is gaining renewed interest owing to the increase of pen computing applications and new pen input devices. The recognition of Chinese characters is different from western handwriting recognition and poses a special challenge. To provide an overview of the technical status and inspire future research, this paper reviews the advances in online Chinese character recognition (OLCCR), with emphasis on the research works from the 1990s. Compared to the research in the 1980s, the research efforts in the 1990s aimed to further relax the constraints of handwriting, namely, the adherence to standard stroke orders and stroke numbers and the restriction of recognition to isolated characters only. The target of recognition has shifted from regular script to fluent script in order to better meet the requirements of practical applications. The research works are reviewed in terms of pattern representation, character classification, learning/adaptation, and contextual processing. We compare important results and discuss possible directions of future research.
Path forward: emerging issues and challenges.
Gillen, Matt; Gittleman, Janie L
2010-06-01
The NIOSH Construction Program worked with industry stakeholders to develop a National Occupational Safety and Health Construction Agenda to target future research and activities. The Program and its partners are also cognizant that new developments can emerge over time and that research can play an important role in helping to understand and address these emerging issues. Examples of emerging issues relevant to construction safety and health are described. These include: (a) climate change and energy considerations; (b) green construction developments and opportunities; (c) new materials; (d) changes in industry structure and practice; (e) workforce developments and disparities; (f) injury underreporting and cost and risk shifting; and (g) increased interest in addressing root causes. Responding to emerging issues while maintaining a focus on fundamental longstanding issues represents an ongoing challenge for researchers and industry organizations. Additional research to understand the diffusion and adoption of research by the industry is also needed. Research accomplished to date provides a strong foundation for addressing future industry needs and trends. (c) 2010 Elsevier Ltd. All rights reserved.
Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.
2014-01-01
Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957
Proteomics and Systems Biology: Current and Future Applications in the Nutritional Sciences1
Moore, J. Bernadette; Weeks, Mark E.
2011-01-01
In the last decade, advances in genomics, proteomics, and metabolomics have yielded large-scale datasets that have driven an interest in global analyses, with the objective of understanding biological systems as a whole. Systems biology integrates computational modeling and experimental biology to predict and characterize the dynamic properties of biological systems, which are viewed as complex signaling networks. Whereas the systems analysis of disease-perturbed networks holds promise for identification of drug targets for therapy, equally the identified critical network nodes may be targeted through nutritional intervention in either a preventative or therapeutic fashion. As such, in the context of the nutritional sciences, it is envisioned that systems analysis of normal and nutrient-perturbed signaling networks in combination with knowledge of underlying genetic polymorphisms will lead to a future in which the health of individuals will be improved through predictive and preventative nutrition. Although high-throughput transcriptomic microarray data were initially most readily available and amenable to systems analysis, recent technological and methodological advances in MS have contributed to a linear increase in proteomic investigations. It is now commonplace for combined proteomic technologies to generate complex, multi-faceted datasets, and these will be the keystone of future systems biology research. This review will define systems biology, outline current proteomic methodologies, highlight successful applications of proteomics in nutrition research, and discuss the challenges for future applications of systems biology approaches in the nutritional sciences. PMID:22332076
Determination of Flood Reduction Alternatives for Climate Change Adaptation in Gyeongancheon basin
NASA Astrophysics Data System (ADS)
Han, D.; Joo, H. J.; Jung, J.; Kim, H. S.
2017-12-01
Recently, the frequency of extreme rainfall event has increased due to the climate change and the impermeable area in an urban watershed has also increased due to the rapid urbanization. Therefore, the flood risk is increasing and we ought to prepare countermeasures for flood damage reduction. For the determination of appropriate measures or alternatives, firstly, this study estimated the frequency based rainfall considering the climate change according to the each target period(reference : 1971˜2010, Target period Ⅰ : 2011˜2040, Target period Ⅱ : 2041˜2070, Target period Ⅲ : 2071˜2100). Then the future flood discharge was computed by using HEC-HMS model. We set 5 sizes of drainage pumps and detention ponds respectively as the flood reduction alternatives and the flood level in the river was obtained by each alternative through HEC-RAS model. The flood inundation map was constructed using topographical data and flood water level in the river and the economic analysis was conducted for the flood damage reduction studies using Multi Dimensional Flood Damage Analysis (MD-FDA) tool. As a result of the effectiveness analysis of the flood reduction alternatives, the flood level by drainage pump was reduced by 0.06m up to 0.44m while it was reduced by 0.01m up to 1.86m in the case of the detention pond. The flooded area was shrunk by up to 32.64% from 0.3% and inundation depth was also dropped. As a result of a comparison of the Benefit/Cost ratio estimated by the economic analysis, a detention pond E in the target period Ⅰ and the pump D in the periods Ⅱ and Ⅲ were considered as the appropriate alternatives for the flood damage reduction under the climate change. AcknowledgementsThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2017R1A2B3005695)
Biosafety research for non-target organism risk assessment of RNAi-based GE plants
Roberts, Andrew F.; Devos, Yann; Lemgo, Godwin N. Y.; Zhou, Xuguo
2015-01-01
RNA interference, or RNAi, refers to a set of biological processes that make use of conserved cellular machinery to silence genes. Although there are several variations in the source and mechanism, they are all triggered by double stranded RNA (dsRNA) which is processed by a protein complex into small, single stranded RNA, referred to as small interfering RNAs (siRNA) with complementarity to sequences in genes targeted for silencing. The use of the RNAi mechanism to develop new traits in plants has fueled a discussion about the environmental safety of the technology for these applications, and this was the subject of a symposium session at the 13th ISBGMO in Cape Town, South Africa. This paper continues that discussion by proposing research areas that may be beneficial for future environmental risk assessments of RNAi-based genetically modified plants, with a particular focus on non-target organism assessment. PMID:26594220
Kinase inhibitors for CNS diseases: an analysis of the recent patent literature.
Amigoni, Federica; Legnaghi, Elena; Pevarello, Paolo
2012-05-01
Protein kinases (PKs), as members of an important target class in current pharmaceutical research, have been mostly exploited so far in therapeutic areas such as oncology and inflammation. However, basic research on some PKs as key components of molecular mechanisms underlying neurodegeneration and neuroprotection may translate into new medicines for CNS diseases in the next few years. This review is an account of recent patents dealing with kinase inhibitors primarily designed for CNS indications. CNS-directed patents on kinase modulators published after 2008 were surveyed using SciFinder(®) and public patent search engines. Some PK targets, such as GSK-3β, CDK5, ROCK and p38α MAPK, continue to attract interest even though a clinical proof-of-concept is yet to be attained in a CNS setting. Less established PKs such as LRRK2, MLK, PAK and DAPK-1 hold promise as valuable targets of the future.
Jump start: a targeted substance abuse prevention program.
Harrington, N G; Donohew, L
1997-10-01
A substance abuse prevention and life skills program for economically disadvantaged, high sensation seeking African American teens was developed and tested in Cincinnati, Ohio. Formative research was conducted to determine program content and format. Over two implementations, 289 individuals in the target population were recruited as participants for the field test of the program. For the first implementation, participants were randomly selected from the city's summer youth employment program. For the second, a media campaign was designed to recruit participants. Process evaluation indicated that participants evaluated the program extremely positively. Outcome evaluation indicated that significant pretest differences between high and low sensation seekers were neutralized for liquor and marijuana in both years of the program and for attitude toward drugs in the first year of the program. These results suggest that sensation seeking is a useful message design and audience-targeting variable for substance abuse prevention program design. Implications and recommendations for future research are discussed.
Sequential Stereotype Priming: A Meta-Analysis.
Kidder, Ciara K; White, Katherine R; Hinojos, Michelle R; Sandoval, Mayra; Crites, Stephen L
2017-08-01
Psychological interest in stereotype measurement has spanned nearly a century, with researchers adopting implicit measures in the 1980s to complement explicit measures. One of the most frequently used implicit measures of stereotypes is the sequential priming paradigm. The current meta-analysis examines stereotype priming, focusing specifically on this paradigm. To contribute to ongoing discussions regarding methodological rigor in social psychology, one primary goal was to identify methodological moderators of the stereotype priming effect-whether priming is due to a relation between the prime and target stimuli, the prime and target response, participant task, stereotype dimension, stimulus onset asynchrony (SOA), and stimuli type. Data from 39 studies yielded 87 individual effect sizes from 5,497 participants. Analyses revealed that stereotype priming is significantly moderated by the presence of prime-response relations, participant task, stereotype dimension, target stimulus type, SOA, and prime repetition. These results carry both practical and theoretical implications for future research on stereotype priming.
Emerging drugs for the treatment of wound healing.
Zielins, Elizabeth R; Brett, Elizabeth A; Luan, Anna; Hu, Michael S; Walmsley, Graham G; Paik, Kevin; Senarath-Yapa, Kshemendra; Atashroo, David A; Wearda, Taylor; Lorenz, H Peter; Wan, Derrick C; Longaker, Michael T
2015-06-01
Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process. A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed. The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.
Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.
Philip, Philip A; Lutz, Manfred P
2015-10-01
Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.
Quality-of-care research in mental health: responding to the challenge.
McGlynn, E A; Norquist, G S; Wells, K B; Sullivan, G; Liberman, R P
1988-01-01
Quality-of-care research in mental health is in the developmental stages, which affords an opportunity to take an integrative approach, building on principles from efficacy, effectiveness, quality assessment, and quality assurance research. We propose an analytic strategy for designing research on the quality of mental health services using an adaptation of the structure, process, and outcome classification scheme. As a concrete illustration of our approach, we discuss research on a particular target population-patients with chronic schizophrenia. Future research should focus on developing models of treatment, establishing criteria and standards for outcomes and processes, and gathering data on community practices.
Behavioral Health and Disasters: Looking to the Future
Palinkas, Lawrence A.
2014-01-01
Along with other manmade and natural disasters, oil spills produce profound and long-term impacts on the behavioral health of their survivors. While previous and ongoing research has focused on producing evidence of the breadth and depth of these impacts, future efforts must begin to translate this evidence into developing and implementing policies, programs and practices that effectively contribute to their prevention and mitigation. Drawing upon a conceptual framework of the behavioral health impacts of oil spills developed from data collected in the aftermath of the Exxon Valdez oil spill in 1989, this paper examines potential interventions designed to prevent or mitigate biopsychosocial, interpersonal and intrapersonal impacts on behavioral health. Future efforts to translate behavioral health research into effective practice will require the formation and maintenance of academic-community partnerships for the purpose of building resilience to these impacts and providing targeted services to those most vulnerable to their long-term consequences. PMID:24443145
Recent Advancements in the Global Understanding of what Drives Heatwaves
NASA Astrophysics Data System (ADS)
Perkins-Kirkpatrick, S.
2016-12-01
Heatwaves, defined as prolonged periods of extreme heat, are disastrous events that impact human, natural and industrial systems all over the world. In recent years, the global research effort has greatly increased our understanding on quantifying heatwaves and how they have changed, what drives them, and their future projections. This talk will summarize critical developments made in this field, with particular emphasis on the physical driving mechanisms and the role of internal climate variability. Case studies from various global regions will illustrate both similarities and differences in the physical set-ups of these fascinating events. Future projections of heatwaves and the human contribution behind specific observed heatwave events will be briefly discussed. The talk will conclude by highlighting research priorities such that future investigation is targeted, and closes existing knowledge gaps on what drives heatwaves as effectively as possible. Such developments will ultimately aid in the predictability of heatwaves, thus aiding in reducing their devastating impacts.
Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes
2018-09-01
Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.
Do Financial Education Programs Work? Working Paper 08-03
ERIC Educational Resources Information Center
Hathaway, Ian; Khatiwada, Sameer
2008-01-01
In this paper we provide a comprehensive critical analysis of research that has investigated the impact of financial education programs on consumer financial behavior. In light of the evidence, we recommend that future programs be highly targeted towards a specific audience and area of financial activity (e.g. home-ownership or credit card…
ERIC Educational Resources Information Center
Laursen, Sandra L.; Hassi, Marja-Liisa; Hough, Sarah
2016-01-01
This mixed-methods study describes classroom characteristics and student outcomes from university mathematics courses that are based in mathematics departments, targeted to future pre-tertiary teachers, and taught with inquiry-based learning (IBL) approaches. The study focused on three two-term sequences taught at two research universities,…
The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project
NASA Astrophysics Data System (ADS)
Edwards, Mark
2008-04-01
The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing many operational needs of the future Canadian Army's Surveillance and Reconnaissance forces. Using the surveillance system of the Coyote reconnaissance vehicle as an experimental platform, the ALERT TD project aims to significantly enhance situational awareness by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. The project is exploiting important advances made in computer processing capability, displays technology, digital communications, and sensor technology since the design of the original surveillance system. As the major research area within the project, concepts are discussed for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as from beyond line-of-sight systems such as mini-UAVs and unattended ground sensors. Video-rate image processing has been developed to assist the operator to detect poorly visible targets. As a second major area of research, automatic target cueing capabilities have been added to the system. These include scene change detection, automatic target detection and aided target recognition algorithms processing both IR and visible-band images to draw the operator's attention to possible targets. The merits of incorporating scene change detection algorithms are also discussed. In the area of multi-sensor data fusion, up to Joint Defence Labs level 2 has been demonstrated. The human factors engineering aspects of the user interface in this complex environment are presented, drawing upon multiple user group sessions with military surveillance system operators. The paper concludes with Lessons Learned from the project. The ALERT system has been used in a number of C4ISR field trials, most recently at Exercise Empire Challenge in China Lake CA, and at Trial Quest in Norway. Those exercises provided further opportunities to investigate operator interactions. The paper concludes with recommendations for future work in operator interface design.
Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma
Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang
2016-01-01
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520
A Literature Synthesis of Health Promotion Research in Salons and Barbershops
Linnan, Laura A.; D’Angelo, Heather; Harrington, Cherise B.
2015-01-01
Context Barbershops and beauty salons are located in all communities and frequented by diverse groups of people, making them key settings for addressing health disparities. No studies have reviewed the growing body of literature describing studies promoting health in these settings. This review summarized the literature related to promoting health within barbershops and beauty salons to inform future approaches that target diverse populations in similar settings. Evidence Acquisition We identified and reviewed published research articles describing formative research, recruitment, and health-related interventions set in beauty salons and barbershops. PubMed and other secondary search engines were searched in 2010 and again in 2013 for English-language papers indexed from 1990 through August 2013. The search yielded 110 articles, 68 of which were formerly reviewed, and 54 were eligible for inclusion. Evidence Synthesis Included articles were categorized as formative research (n=27), recruitment (n=7), or intervention (n=20). Formative research studies showed that owners, barbers/stylists, and their customers were willing participants, clarifying the feasibility of promoting health in these settings. Recruitment studies demonstrated that salon/shop owners will join research studies and can enroll customers. Among intervention studies, level of stylist/barber involvement was categorized. More than 73.3% of intervention studies demonstrated statistically significant results, targeting mostly racial/ethnic minority groups and focusing on a variety of health topics. Conclusions Barbershops and beauty salons are promising settings for reaching populations most at risk for health disparities. Although these results are encouraging, more rigorous research and evaluation of future salon- and barbershop-based interventions are needed. PMID:24768037
Sivaramalingam, Bhairavi; Young, Ian; Pham, Mai T; Waddell, Lisa; Greig, Judy; Mascarenhas, Mariola; Papadopoulos, Andrew
2015-07-01
Improper food handling by consumers at home is a major cause of foodborne illness. Therefore, effective education strategies are essential to change consumers' food safety attitudes and behaviors. The purpose of this scoping review was to identify and characterize primary literature examining the effectiveness of consumer food-safety education interventions. Ten bibliographic databases were searched using a comprehensive search strategy. Citations were identified; two reviewers screened them for relevance and characterized relevant articles. To ensure results would be applicable to end users, stakeholders were engaged to provide input on the review scope, methods, and results. We identified 246 relevant articles, of which 150 were quantitative, 66 qualitative, and 30 mixed-method research studies. Most studies (64.2%) were published in the United States, using an uncontrolled before-and-after study design (31.3%), and investigated the effectiveness of community-based training sessions and workshops (52.0%). Research gaps were found in the number of randomized controlled studies conducted, academic- and school-based courses and curricula investigated, and interventions targeting high-risk populations (e.g., pregnant women, those who are immunocompromised) and using new media channels (e.g., social media). Key opportunities to enhance the utility of future primary research investigating consumer food-safety interventions include the following: using studies based on behavior-change theories and formative research; engaging the target population in the research; using validated instruments to measures outcomes; and reporting intervention characteristics and outcomes completely. Results of this review can be used to prioritize future primary research and decision-making in this area.
Bauer, Sebastian; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Rosenow, Felix
2017-11-01
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. This Part II includes the experimental and translational approaches and a discussion of the future perspectives, while the diagnostic methods, EEG network analysis, biomarkers, and personalized treatment approaches were addressed in Part I [1]. Copyright © 2017. Published by Elsevier Inc.
Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A
2015-12-01
Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets. Copyright © 2015 Elsevier Ltd. All rights reserved.
Advancing Translational Research through Facility Design in Non-AMC Hospitals.
Pati, Debajyoti; Pietrzak, Michael P; Harvey, Thomas E; Armstrong, Walter B; Clarke, Robert; Weissman, Neil J; Rapp, Paul E; Smith, Mark S; Fairbanks, Rollin J; Collins, Jeffreyg M
2013-01-01
This article aims to explore the future of translational research and its physical design implications for community hospitals and hospitals not attached to large centralized research platforms. With a shift in medical services delivery focus to community wellness, continuum of care, and comparative effectiveness research, healthcare research will witness increasing pressure to include community-based practitioners. The roundtable discussion group, comprising 14 invited experts from 10 institutions representing the fields of biomedical research, research administration, facility planning and design, facility management, finance, and environmental design research, examined the issue in a structured manner. The discussion was conducted at the Washington Hospital Center, MedStar Health, Washington, D.C. Institutions outside the AMCs will be increasingly targeted for future research. Three factors are crucial for successful research in non-AMC hospitals: operational culture, financial culture, and information culture. An operating culture geared towards creation, preservation, and protection of spaces needed for research; creative management of spaces for financial accountability; and a flexible information infrastructure at the system level that enables complete link of key programmatic areas to academic IT research infrastructure are critical to success of research endeavors. Hospital, interdisciplinary, leadership, planning, work environment.
The Future of Healthcare–Information Based Medicine
Borangiu, T; Purcărea, V
2008-01-01
The paper discusses how information based medicine has become an increasingly important model of healthcare. Today's patients are better informed and therefore play a more active role in their own healthcare, fuelling the drive towards personalized medicine. Information Based Medicine enables researchers to design targeted therapeutics and rapidly develop best practices guidelines to enable healthcare providers to deliver the most complete individualized healthcare solutions. Information based medicine is realized thanks to growth in four key areas–Clinical Genomics, Medical Imaging, Targeted Pharmaceuticals, and Information Systems. Also discussed, is how technological advances throughout this decade are changing the discovery, development and delivery of new treatments–with healthcare becoming increasingly personalized as a result. A glimpse into the future of personalised healthcare is presented, highlighting scenarios in development today along with the challenges and perspectives which lie ahead. PMID:20108471
Future communications satellite applications
NASA Technical Reports Server (NTRS)
Bagwell, James W.
1992-01-01
The point of view of the research is made through the use of viewgraphs. It is suggested that future communications satellite applications will be made through switched point to point narrowband communications. Some characteristics of which are as follows: small/low cost terminals; single hop communications; voice compatible; full mesh networking; ISDN compatible; and possible limited use of full motion video. Some target applications are as follows: voice/data networks between plants and offices in a corporation; data base networking for commercial and science users; and cellular radio internodal voice/data networking.
Drug targets for resistant malaria: Historic to future perspectives.
Kumar, Sahil; Bhardwaj, T R; Prasad, D N; Singh, Rajesh K
2018-05-11
New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Advanced Materials for Exploration Task Research Results
NASA Technical Reports Server (NTRS)
Cook, M. B. (Compiler); Murphy, K. L.; Schneider, T.
2008-01-01
The Advanced Materials for Exploration (AME) Activity in Marshall Space Flight Center s (MSFC s) Exploration Science and Technology Directorate coordinated activities from 2001 to 2006 to support in-space propulsion technologies for future missions. Working together, materials scientists and mission planners identified materials shortfalls that are limiting the performance of long-term missions. The goal of the AME project was to deliver improved materials in targeted areas to meet technology development milestones of NASA s exploration-dedicated activities. Materials research tasks were targeted in five areas: (1) Thermal management materials, (2) propulsion materials, (3) materials characterization, (4) vehicle health monitoring materials, and (5) structural materials. Selected tasks were scheduled for completion such that these new materials could be incorporated into customer development plans.
The four key characteristics of interpersonal emotion regulation.
Niven, Karen
2017-10-01
Emotion researchers are increasingly interested in processes by which people influence others' feelings. Although one such process, interpersonal emotion regulation, has received particular attention in recent years, there remains confusion about exactly how to define this process. The present article aims to distinguish interpersonal emotion regulation from other, related processes by outlining its four key characteristics. Specifically, interpersonal emotion regulation is presented as a process of (i) regulation, that (ii) has an affective target, (iii) is deliberate, and (iv) has a social target. Considering these characteristics raises questions for future research concerning factors that may influence the process of interpersonal emotion regulation, why interpersonal emotion regulation sometimes fails, and whether interventions can improve people's use of interpersonal emotion regulation. Copyright © 2017 Elsevier Ltd. All rights reserved.
Infrared spectroscopy of exoplanets: observational constraints
Encrenaz, Thérèse
2014-01-01
The exploration of transiting extrasolar planets is an exploding research area in astronomy. With more than 400 transiting exoplanets identified so far, these discoveries have made possible the development of a new research field, the spectroscopic characterization of exoplanets' atmospheres, using both primary and secondary transits. However, these observations have been so far limited to a small number of targets. In this paper, we first review the advantages and limitations of both primary and secondary transit methods. Then, we analyse what kind of infrared spectra can be expected for different types of planets and discuss how to optimize the spectral range and the resolving power of the observations. Finally, we propose a list of favourable targets for present and future ground-based observations. PMID:24664918
Infrared spectroscopy of exoplanets: observational constraints.
Encrenaz, Thérèse
2014-04-28
The exploration of transiting extrasolar planets is an exploding research area in astronomy. With more than 400 transiting exoplanets identified so far, these discoveries have made possible the development of a new research field, the spectroscopic characterization of exoplanets' atmospheres, using both primary and secondary transits. However, these observations have been so far limited to a small number of targets. In this paper, we first review the advantages and limitations of both primary and secondary transit methods. Then, we analyse what kind of infrared spectra can be expected for different types of planets and discuss how to optimize the spectral range and the resolving power of the observations. Finally, we propose a list of favourable targets for present and future ground-based observations.
2014-01-01
This review aims to highlight the recent advances and methodological improvements in instrumental techniques applied for the analysis of different brominated flame retardants (BFRs). The literature search strategy was based on the recent analytical reviews published on BFRs. The main selection criteria involved the successful development and application of analytical methods for determination of the target compounds in various environmental matrices. Different factors affecting chromatographic separation and mass spectrometric detection of brominated analytes were evaluated and discussed. Techniques using advanced instrumentation to achieve outstanding results in quantification of different BFRs and their metabolites/degradation products were highlighted. Finally, research gaps in the field of BFR analysis were identified and recommendations for future research were proposed. PMID:27433482
An overview of juveniles and school violence.
Murakami, Saori; Rappaport, Nancy; Penn, Joseph V
2006-09-01
Despite the relative rarity of school shootings, targeted violence, and school-associated violent deaths, any youth who presents with words, gestures, or actions of a threatening or violent nature in a school setting should be assessed and referred for further evaluation by a mental health professional and, if clinically indicated, a forensic evaluator.The request for a juvenile risk assessment for future dangerousness requires careful delineation of role and agency; confidentiality issues; a comprehensive diagnostic evaluation of the youth; and a detailed assessment of the youth's perceived threat or problematic behavior. Various protective and risk factors and consideration of other individual, family, school/peer, and situational factors should also be explored.There is still much information that is unknown when considering school violence or targeted school violence. There is clearly a need for additional research on the identification of at-risk youths, the contributions and significance of various protective and risk factors, the impact of peer relationships, and perceived rejection, socioeconomic status, subtypes of aggression, and developmental stages. Examples of future research direction might include difference by gender, presence of affective or psychotic disorders, substance abuse, emerging characterologic disturbances, and physiologic markers, such as cortisol or serotonin. Additional research regarding best practices and the development of clinical guidelines or practice parameters is also needed.
Miller-Kleinhenz, Jasmine M.; Bozeman, Erica N.
2015-01-01
Effective treatment of triple negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and non-invasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise towards the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug-resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention (EPR) effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor associated endothelial cells, stromal fibroblasts and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as others and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. PMID:25966677
Workaholism: An overview and current status of the research
Andreassen, Cecilie Schou
2014-01-01
Aims: This article addresses the stable tendency of excessive and compulsive working (i.e., workaholism). The main aim is to provide an updated oversight of the research area related to definition, prevalence, assessment, causes, outcomes, intervention as well as proposed future research directions. The target-population is both researchers and clinicians. Methods: The findings are identified by narratively reviewing the literature. Results: Research into workaholism has expanded over the last two decades. Several screening instruments to identify workaholics have been developed. The vast majority of these are based on seemingly atheoretical foundations, lacking convergent validity with each other and with related constructs. Research generally shows that workaholism is related to impaired health and well-being as well as to conflicts between work and family life. Workaholism is probably caused and maintained by a range of factors, although solid empirical underpinnings for suggested antecedents are currently sparse. So far no well-evaluated interventions for workaholism exist. Conclusions: At present, workaholism as a construct lacks conceptual and empirical clarity. Future research efforts should prioritize longitudinal studies as well as studies incorporating unbiased, firm parameters of both health and behavior. PMID:25215209
43 CFR 418.22 - Future adjustments to Lahontan Reservoir storage targets.
Code of Federal Regulations, 2010 CFR
2010-10-01
... RECLAMATION PROJECT, NEVADA Operations and Management § 418.22 Future adjustments to Lahontan Reservoir storage targets. (a) The Lahontan Reservoir storage targets must be adjusted to accommodate changes in... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Future adjustments to Lahontan Reservoir...
43 CFR 418.22 - Future adjustments to Lahontan Reservoir storage targets.
Code of Federal Regulations, 2011 CFR
2011-10-01
... RECLAMATION PROJECT, NEVADA Operations and Management § 418.22 Future adjustments to Lahontan Reservoir storage targets. (a) The Lahontan Reservoir storage targets must be adjusted to accommodate changes in... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Future adjustments to Lahontan Reservoir...
Brochu, Paula M; Morrison, Melanie A
2007-12-01
The authors examined prejudice toward overweight men and women. Participants (N = 76) indicated their perceptions, attitudes, behavioral intentions, and implicit associations toward an average-weight or overweight man or woman. Results indicated the presence of explicit and implicit antifat prejudice, with male participants showing greater negativity toward overweight targets. Analyses of covariance indicated that overweight targets received greater derogation than did their average-weight counterparts, regardless, for the most part, of the target's gender. With one exception, no significant relations emerged between explicit and implicit measures of weight bias. The authors discuss limitations of the study and implications for future research.
Foodservice employees benefit from interventions targeting barriers to food safety.
York, Valerie K; Brannon, Laura A; Shanklin, Carol W; Roberts, Kevin R; Howells, Amber D; Barrett, Elizabeth B
2009-09-01
The number of foodborne illnesses traced to improper food handling in restaurants indicates a need for research to improve food safety in these establishments. Therefore, this 2-year longitudinal study investigated the effectiveness of traditional ServSafe (National Restaurant Association Educational Foundation, Chicago, IL) food-safety training and a Theory of Planned Behavior intervention program targeting employees' perceived barriers and attitudes toward important food-safety behaviors. The effectiveness of the training and intervention was measured by knowledge scores and observed behavioral compliance rates related to food-safety practices. Employees were observed for handwashing, thermometer usage, and proper handling of work surfaces at baseline, after receiving ServSafe training, and again after exposure to the intervention targeting barriers and negative attitudes about food-safety practices. Repeated-measures analyses of variance indicated training improved handwashing knowledge, but the intervention was necessary to improve overall behavioral compliance and handwashing compliance. Results suggest that registered dietitians; dietetic technicians, registered; and foodservice managers should implement a combination of training and intervention to improve knowledge and compliance with food-safety behaviors, rather than relying on training alone. Challenges encountered while conducting this research are discussed, and recommendations are provided for researchers interested in conducting this type of research in the future.
Cardioprotective role of G-Protein Coupled Estrogen Receptor 1 (GPER1).
Koganti, Sivaramakrishna
2015-01-01
G-Protein Coupled Estrogen Receptor 1 (GPER1), also known as G-Protein Coupled Receptor 30 (GPR30) and initially considered an orphan receptor, has become one of the most important pharmacological targets in cardiovascular research. Since the gene encoding this putative receptor was cloned nearly 20 years ago, researchers have addressed its role in various aspects of physiology, including cardioprotection. Although extensive research has been carried out to understand the role of GPER1 as a pharmacological target to treat cardiovascular diseases, there are few current reviews addressing the overall cardioprotective benefits of this receptor and the signaling intermediates involved. This review considers the origins of GPER1, its cell biology, its physiological and pharmacological roles as a therapeutic target in cardiovascular disease, and what future research on GPER1 might entail. More specifically, the review focuses on GPER1 regulation of Angiotensin Type I Receptor (AT1R) and the role of estrogen receptors, epidermal growth factor receptor (EGFR) and matrix metalloproteinases (MMPs) in bringing about the cardioprotective effects of GPER1. Areas where improved knowledge of GPER1 biology is still needed to better understand the receptor's cardioprotective effects are also discussed.
A community perspective on the role of fathers during pregnancy: a qualitative study
2013-01-01
Background Defining male involvement during pregnancy is essential for the development of future research and appropriate interventions to optimize services aiming to improve birth outcomes. Study Aim: To define male involvement during pregnancy and obtain community-based recommendations for interventions to improve male involvement during pregnancy. Methods We conducted focus groups with mothers and fathers from the National Healthy Start Association program in order to obtain detailed descriptions of male involvement activities, benefits, barriers, and proposed solutions for increasing male involvement during pregnancy. The majority of participants were African American parents. Results The involved “male” was identified as either the biological father, or, the current male partner of the pregnant woman. Both men and women described the ideal, involved father or male partner as present, accessible, available, understanding, willing to learn about the pregnancy process and eager to provide emotional, physical and financial support to the woman carrying the child. Women emphasized a sense of “togetherness” during the pregnancy. Suggestions included creating male-targeted prenatal programs, enhancing current interventions targeting females, and increasing healthcare providers’ awareness of the importance of men’s involvement during pregnancy. Conclusions Individual, family, community, societal and policy factors play a role in barring or diminishing the involvement of fathers during pregnancy. Future research and interventions should target these factors and their interaction in order to increase fathers’ involvement and thereby improve pregnancy outcomes. PMID:23497131
ERIC Educational Resources Information Center
Glisan, Eileen W.; Swender, Elvira; Surface, Eric A.
2013-01-01
The renewed national focus on teacher quality and effectiveness has resulted in more rigorous standards that describe the knowledge and skills required of teacher candidates across all disciplines. In the area of foreign languages, three sets of professional standards address the oral proficiency of teachers in the target languages they teach…
Reading the Past to Inform the Future: 25 Years of "The Reading Teacher"
ERIC Educational Resources Information Center
Mohr, Kathleen A. J.; Ding, Guoqin; Strong, Ashley; Branum, Lezlie; Watson, Nanette; Priestley, K. Lea; Juth, Stephanie; Carpenter, Neil; Lundstrom, Kacy
2017-01-01
This analysis examines articles from the past 25 years of "The Reading Teacher" to better understand the journal's content and trends influencing literacy instruction. A research team coded and analyzed the frequency of topics and grade levels targeted, then compared results with those of a similar analysis published in 1992. The Web of…
Research and Development Project Summaries, October 1991
1991-10-01
delivery methods, training cost reduction, demonstration of technology’ effectiveness, and the reduction of acquisition risk . The majority of the work...demonstrations, risk reduction developments, and cost-effectiveness investigations in simulator and training technologzv. This advanced development program is a...systems. The program is organized around specific demonstration tasks that target critical technical risks that confront future weapons system
Rape Treatment Outcome Research: Empirical Findings and State of the Literature
Vickerman, Katrina A.; Margolin, Gayla
2009-01-01
This article reviews empirical support for treatments targeting women sexually assaulted during adolescence or adulthood. Thirty-two articles were located using data from 20 separate samples. Of the 20 samples, 12 targeted victims with chronic symptoms, three focused on the acute period post-assault, two included women with chronic and acute symptoms, and three were secondary prevention programs. The majority of studies focus on posttraumatic stress disorder (PTSD), depression, and/or anxiety as treatment targets. Cognitive Processing Therapy and Prolonged Exposure have garnered the most support with this population. Stress Inoculation Training and Eye Movement Desensitization and Reprocessing also show some efficacy. Of the four studies that compared active treatments, few differences were found. Overall, cognitive behavioral interventions lead to better PTSD outcomes than supportive counseling does. However, even in the strongest treatments more than one-third of women retain a PTSD diagnosis at post-treatment or drop out of treatment. Discussion highlights the paucity of research in this area, methodological limitations of examined studies, generalizability of findings, and important directions for future research at various stages of trauma recovery. PMID:19442425
Schumacher, I; Zechmeister, I
2012-04-01
In Austria research in Health Technology Assessment (HTA) has been conducted since the 1990s. Research in HTA aims at supporting an adequate and efficient use of health care resources in order to sustain a publicly financed and solidary health care system. Ultimately, HTA research should result in better health of the population. Research results should provide independent information for decision makers. For legitimizing further research resources and for prioritizing future HTA research and guaranteeing the value of future research, HTA research needs itself to undergo evaluation. Aim of the study is to design a conceptual framework for evaluating the impact of HTA research in Austria on the basis of the existing literature. An already existing review which presents methods and concepts how to evaluate HTA-impact was updated by a systematic research including literature of the years 2004-January 2010. Results were analysed in regard to 4 categories: definition of the term impact, target groups and system levels, operationalisation of indicators and evaluation methods. Overall, 19 publications were included. Referring to the 4 categories, an explanation of impact has to take into account HTAs multidisciplinary setting and needs a context related definition. Target groups, system levels, indicators and methods depend on the impact defined. Studies investigated direct and indirect impact and were focused on different target groups like physicians, nurses and decision makers on the micro-, and meso level, as well as politicians and reimbursement institutions on the macro level. Except for one reference all studies applied already known and mostly qualitative methods for measuring the impact of HTA research. Thus, an appropriate pool of instruments seems to be available. There is a lack of information about validity of applied methods and indicators. By adapting adequate methods and concepts a conceptual framework for the Austrian HTA-Impact evaluation has been designed. The paper presents an overview of existing methods for the evaluation of the HTA research. This has been used to identify useful approaches for measuring the HTA-impact in Austria. By providing a context sensitive framework for impact evaluation in Austria the Austrian HTA-research contributes to the international trend of impact-evaluation. © Georg Thieme Verlag KG Stuttgart · New York.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burpee, Heather; Loveland, Joel; Helmers, Aaron
2015-09-02
This research, Targeting 100!, provides a conceptual framework and decision-making structure at a schematic design level of precision for hospital owners, architects and engineers to radically reduce energy use in hospitals. Following the goals of Architecture 2030 and The 2030 Challenge, it offers access to design strategies and the cost implications of those strategies for new hospitals to utilize 60% less energy. The name, Targeting 100!, comes from the 2030 Challenge energy reduction goal for hospitals; a 60% energy use reduction from typical acute care hospital targets approximately 100 KBtu/SF Year, thus the name “Targeting 100!”. Targeting 100! was developedmore » through funding partnerships with the US Department of Energy and the Northwest Energy Efficiency’s BetterBricks Initiative. The technical team was led by the University of Washington Integrated Design Lab supported by deep collaboration with Solarc Architecture and Engineering, TBD Cost Consultants, and NBBJ Architecture. Through extensive research and design development, Targeting 100! provides a framework for developing high performance healthcare projects today and into the future. An online tool houses a Targeting 100! knowlegebase and roadmap. It can be accessed at: www.idlseattle.com/t100. The webtool is structured from high-level overview materials to detailed library with modeling inputs and outputs, providing a comprehensive report of the background, data, and outcomes from the project.« less
Ecott, Cheryl L; Critchfield, Thomas S
2004-01-01
Basic researchers, but not most applied researchers, have assumed that the behavior-decelerating effects of noncontingent reinforcement result at least partly from adventitious reinforcement of competing behaviors. The literature contains only sketchy evidence of these effects because few noncontingent reinforcement studies measure alternative behaviors. A laboratory model is presented in which concurrent schedules of contingent reinforcement were used to establish a "target" and an "alternative" behavior. Imposing noncontingent reinforcement decreased target behavior rates and increased alternative behavior rates, outcomes that were well described by the standard quantitative account of alternative reinforcement, the generalized matching law. These results suggest that adventitious reinforcement of alternative behaviors can occur during noncontingent reinforcement interventions, although the range of conditions under which this occurs remains to be determined in future studies. As an adjunct to applied studies, laboratory models permit easy measurement of alternative behaviors and parametric manipulations needed to answer many research questions. PMID:15529885
Di Meglio, Paola; Villanova, Federica; Nestle, Frank O
2014-08-01
Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.
Sensor Technology for Integrated Vehicle Health Management of Aerospace Vehicles
NASA Technical Reports Server (NTRS)
Prosser, W. H.; Brown, T. L.; Woodard, S. E.; Fleming, G. A.; Cooper, E. G.
2002-01-01
NASA is focusing considerable efforts on technology development for Integrated Vehicle Health Management systems. The research in this area is targeted toward increasing aerospace vehicle safety and reliability, while reducing vehicle operating and maintenance costs. Onboard, real-time sensing technologies that can provide detailed information on structural integrity are central to such a health management system. This paper describes a number of sensor technologies currently under development for integrated vehicle health management. The capabilities, current limitations, and future research needs of these technologies are addressed.
Moran, Jonathan A; Clarke, Charles M
2010-06-01
Nepenthes is the largest genus of pitcher plants, with its centre of diversity in SE Asia. The plants grow in substrates that are deficient in N and offset this deficiency by trapping animal prey, primarily arthropods. Recent research has provided new insights into the function of the pitchers, particularly with regard to prey tapping and retention. Species examined to date use combinations of wettable peristomes, wax layers and viscoelastic fluid to trap and retain prey. In many respects, this has redefined our understanding of the functioning of Nepenthes pitchers. In addition, recent research has shown that several Nepenthes species target specific groups of prey animals, or are even evolving away from a strictly carnivorous mode of operation. Future research into nutrient sequestration strategies and mechanisms of prey attraction would no doubt further enhance our knowledge of the ecology of this remarkable genus.
Knopf, Antje; Bert, Christoph; Heath, Emily; Nill, Simeon; Kraus, Kim; Richter, Daniel; Hug, Eugen; Pedroni, Eros; Safai, Sairos; Albertini, Francesca; Zenklusen, Silvan; Boye, Dirk; Söhn, Matthias; Soukup, Martin; Sobotta, Benjamin; Lomax, Antony
2010-09-01
This article reports on a 4D-treatment planning workshop (4DTPW), held on 7-8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D-treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state-of-the-art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.
Ajie, Whitney N; Chapman-Novakofski, Karen M
2014-06-01
The purpose of this systematic review was to evaluate recent research regarding the use of computer-based nutrition education interventions targeting adolescent overweight and obesity. Online databases were systematically searched using key words, and bibliographies of related articles were manually searched. Inclusion/exclusion criteria were applied and included studies evaluated for their ability to achieve their objectives and for quality using the Nutrition Evidence Library appraisal guidelines for research design and implementation. Of the 15 studies included, 10 were randomized controlled trials. Two studies targeted weight loss, 2 targeted weight maintenance, and 11 targeted dietary improvement with or without physical activity. At least half of in-school (60%) and nonschool interventions (80%) exhibited significantly positive effects on nutrition- or obesity-related variables. Small changes in diet, physical activity, knowledge, and self-efficacy were shown; however, few results were sustained long term. Recommendations included application of health behavior theory and computer tailoring for feedback messages. Future research should include thorough description of intervention content (messages, theory, multimedia, etc.), application of rigorous methodology, as well as consideration of covariates such as parental involvement and gender. With further research and evidentiary support, this approach to obesity-related nutrition education has the potential to be successful. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Radar signature generation for feature-aided tracking research
NASA Astrophysics Data System (ADS)
Piatt, Teri L.; Sherwood, John U.; Musick, Stanton H.
2005-05-01
Accurately associating sensor kinematic reports to known tracks, new tracks, or clutter is one of the greatest obstacles to effective track estimation. Feature-aiding is one technology that is emerging to address this problem, and it is expected that adding target features will aid report association by enhancing track accuracy and lengthening track life. The Sensor's Directorate of the Air Force Research Laboratory is sponsoring a challenge problem called Feature-Aided Tracking of Stop-move Objects (FATSO). The long-range goal of this research is to provide a full suite of public data and software to encourage researchers from government, industry, and academia to participate in radar-based feature-aided tracking research. The FATSO program is currently releasing a vehicle database coupled to a radar signature generator. The completed FATSO system will incorporate this database/generator into a Monte Carlo simulation environment for evaluating multiplatform/multitarget tracking scenarios. The currently released data and software contains the following: eight target models, including a tank, ammo hauler, and self-propelled artillery vehicles; and a radar signature generator capable of producing SAR and HRR signatures of all eight modeled targets in almost any configuration or articulation. In addition, the signature generator creates Z-buffer data, label map data, and radar cross-section prediction and allows the user to add noise to an image while varying sensor-target geometry (roll, pitch, yaw, squint). Future capabilities of this signature generator, such as scene models and EO signatures as well as details of the complete FATSO testbed, are outlined.
2010-01-01
Subtraction technique has been broadly applied for target gene discovery. However, most current protocols apply relative differential subtraction and result in great amount clone mixtures of unique and differentially expressed genes. This makes it more difficult to identify unique or target-orientated expressed genes. In this study, we developed a novel method for subtraction at mRNA level by integrating magnetic particle technology into driver preparation and tester–driver hybridization to facilitate uniquely expressed gene discovery between peanut immature pod and leaf through a single round subtraction. The resulting target clones were further validated through polymerase chain reaction screening using peanut immature pod and leaf cDNA libraries as templates. This study has resulted in identifying several genes expressed uniquely in immature peanut pod. These target genes can be used for future peanut functional genome and genetic engineering research. PMID:21406066
Assessing the Effects of Momentary Priming on Memory Retention During an Interference Task
NASA Technical Reports Server (NTRS)
Schutte, Paul C.
2007-01-01
A memory aid, that used brief (33ms) presentations of previously learned information (target words), was assessed on its ability to reinforce memory for target words while the subject was performing an interference task. The interference task required subjects to learn new words and thus interfered with their memory of the target words. The brief presentation (momentary memory priming) was hypothesized to refresh the subjects memory of the target words. 143 subjects, in a within subject design, were given a 33ms presentation of the target memory words during the interference task in a treatment condition and a blank 33ms presentation in the control condition. The primary dependent measure, memory loss over the interference trial, was not significantly different between the two conditions. The memory prime did not appear to hinder the subjects performance on the interference task. This paper describes the experiment and the results along with suggestions for future research.
Batman, Angela M.; Miles, Michael F.
2015-01-01
Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of streamlining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD. PMID:26259085
Translating Alcohol Research: Opportunities and Challenges.
Batman, Angela M; Miles, Michael F
2015-01-01
Alcohol use disorder (AUD) and its sequelae impose a major burden on the public health of the United States, and adequate long-term control of this disorder has not been achieved. Molecular and behavioral basic science research findings are providing the groundwork for understanding the mechanisms underlying AUD and have identified multiple candidate targets for ongoing clinical trials. However, the translation of basic research or clinical findings into improved therapeutic approaches for AUD must become more efficient. Translational research is a multistage process of stream-lining the movement of basic biomedical research findings into clinical research and then to the clinical target populations. This process demands efficient bidirectional communication across basic, applied, and clinical science as well as with clinical practitioners. Ongoing work suggests rapid progress is being made with an evolving translational framework within the alcohol research field. This is helped by multiple interdisciplinary collaborative research structures that have been developed to advance translational work on AUD. Moreover, the integration of systems biology approaches with collaborative clinical studies may yield novel insights for future translational success. Finally, appreciation of genetic variation in pharmacological or behavioral treatment responses and optimal communication from bench to bedside and back may strengthen the success of translational research applications to AUD.
The effects of workplace physical activity interventions in men: a systematic review.
Wong, Jason Y L; Gilson, Nicholas D; van Uffelen, Jannique G Z; Brown, Wendy J
2012-07-01
The workplace is cited as a promising setting for physical activity (PA) promotion, but workplace PA interventions tend not to specifically target men. The aim of this article was to review the literature on workplace PA interventions for men and to identify key issues for future intervention development. Articles targeting PA at the workplace were located through a structured database search. Information on intervention strategies and PA outcomes were extracted. Only 13 studies (10.5%) reviewed focused on men, of which 5 showed significant increases in PA. These studies used generic, multicomponent, health promotion strategies with a variety of timeframes, self-report PA measures, and PA outcomes. The systematic review identified that evidence on the effectiveness of workplace PA interventions for men is equivocal and highlighted methodological concerns. Future research should use reliable and valid measures of PA and interventions that focus specifically on men's needs and PA preferences.
miRNAs as potential therapeutic targets for age-related macular degeneration.
Wang, Shusheng; Koster, Kyle M; He, Yuguang; Zhou, Qinbo
2012-03-01
Since their recent discovery, miRNAs have been shown to play critical roles in a variety of pathophysiological processes. Such processes include pathological angiogenesis, the oxidative stress response, immune response and inflammation, all of which have been shown to have important and interdependent roles in the pathogenesis and progression of age-related macular degeneration (AMD). Here we present a brief review of the pathological processes involved in AMD and review miRNAs and other noncoding RNAs involved in regulating these processes. Specifically, we discuss several candidate miRNAs that show promise as AMD therapeutic targets due to their direct involvement in choroidal neovascularization or retinal pigment epithelium atrophy. We discuss potential miRNA-based therapeutics and delivery methods for AMD and provide future directions for the field of miRNA research with respect to AMD. We believe the future of miRNAs in AMD therapy is promising.
Progress in Life Marker Chip Technology for Detection of Life on Mars
NASA Astrophysics Data System (ADS)
Sims, M. R.; Cullen, D. C.; Laan, E.; Borst, G.; Prak, A.; Richter, L.; Gaubert, F.; Steele, A.; Parnell, J.; Sephton, M.
2007-12-01
Detection of Life on Mars will rely on detection of biomarkers, physical or chemical structures that can be associated with Life. As a possible payload for the ESA ExoMars rover mission planned in 2013 and other future missions a Life Marker Chip instrument is being developed. This instrument uses immuno-assay techniques to detect the relevant biomarkers. This paper describes the typical targets it will search for, its operating principle and the status of development. 63 biomarker targets have been identified and assays have been developed for a limited subset. Assay development includes use of recombinant DNA techniques to generate the molecular receptors (antibodies). This type of instrument has applications in terrestrial research e.g. sub-glacial lakes as well as planetary exploration. Breadboard demonstrators have been built of the assay system and key components of the micro-fluidics. Results from these breadboards will be presented, along with plans for future development.
Reducing myocardial infarct size: challenges and future opportunities
Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J
2016-01-01
Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is ‘myocardial reperfusion injury’, a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies—however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. PMID:26674987
Community challenges in biomedical text mining over 10 years: success, failure and the future
Huang, Chung-Chi
2016-01-01
One effective way to improve the state of the art is through competitions. Following the success of the Critical Assessment of protein Structure Prediction (CASP) in bioinformatics research, a number of challenge evaluations have been organized by the text-mining research community to assess and advance natural language processing (NLP) research for biomedicine. In this article, we review the different community challenge evaluations held from 2002 to 2014 and their respective tasks. Furthermore, we examine these challenge tasks through their targeted problems in NLP research and biomedical applications, respectively. Next, we describe the general workflow of organizing a Biomedical NLP (BioNLP) challenge and involved stakeholders (task organizers, task data producers, task participants and end users). Finally, we summarize the impact and contributions by taking into account different BioNLP challenges as a whole, followed by a discussion of their limitations and difficulties. We conclude with future trends in BioNLP challenge evaluations. PMID:25935162
Recent research on the high-probability instructional sequence: A brief review.
Lipschultz, Joshua; Wilder, David A
2017-04-01
The high-probability (high-p) instructional sequence consists of the delivery of a series of high-probability instructions immediately before delivery of a low-probability or target instruction. It is commonly used to increase compliance in a variety of populations. Recent research has described variations of the high-p instructional sequence and examined the conditions under which the sequence is most effective. This manuscript reviews the most recent research on the sequence and identifies directions for future research. Recommendations for practitioners regarding the use of the high-p instructional sequence are also provided. © 2017 Society for the Experimental Analysis of Behavior.
Insights into Atherosclerosis Using Nanotechnology
Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.
2010-01-01
A developing forefront in vascular disease research is the application of nanotechnology, the engineering of devices at the molecular scale, for diagnostic and therapeutic applications in atherosclerosis. Promising research in this field over the past decade has resulted in the preclinical validation of nanoscale devices that target cellular and molecular components of the atherosclerotic plaque, including one of its prominent cell types, the macrophage. Nanoscale contrast agents targeting constituents of plaque biology have been adapted for application in multiple imaging modalities, leading toward more detailed diagnostic readouts, whereas nanoscale drug delivery devices can be tailored for site-specific therapeutic activity. This review highlights recent progress in utilizing nanotechnology for the clinical management of atherosclerosis, drawing upon recent preclinical studies relevant to diagnosis and treatment of the plaque and promising future applications. PMID:20425261
Chemical Proteomic Approaches Targeting Cancer Stem Cells: A Review of Current Literature.
Jung, Hye Jin
2017-01-01
Cancer stem cells (CSCs) have been proposed as central drivers of tumor initiation, progression, recurrence, and therapeutic resistance. Therefore, identifying stem-like cells within cancers and understanding their properties is crucial for the development of effective anticancer therapies. Recently, chemical proteomics has become a powerful tool to efficiently determine protein networks responsible for CSC pathophysiology and comprehensively elucidate molecular mechanisms of drug action against CSCs. This review provides an overview of major methodologies utilized in chemical proteomic approaches. In addition, recent successful chemical proteomic applications targeting CSCs are highlighted. Future direction of potential CSC research by integrating chemical genomic and proteomic data obtained from a single biological sample of CSCs are also suggested in this review. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Inhibitors of Protein Methyltransferases and Demethylases
2017-01-01
Post-translational modifications of histones by protein methyltransferases (PMTs) and histone demethylases (KDMs) play an important role in the regulation of gene expression and transcription and are implicated in cancer and many other diseases. Many of these enzymes also target various nonhistone proteins impacting numerous crucial biological pathways. Given their key biological functions and implications in human diseases, there has been a growing interest in assessing these enzymes as potential therapeutic targets. Consequently, discovering and developing inhibitors of these enzymes has become a very active and fast-growing research area over the past decade. In this review, we cover the discovery, characterization, and biological application of inhibitors of PMTs and KDMs with emphasis on key advancements in the field. We also discuss challenges, opportunities, and future directions in this emerging, exciting research field. PMID:28338320
Peters, Betts; Bieker, Gregory; Heckman, Susan M; Huggins, Jane E; Wolf, Catherine; Zeitlin, Debra; Fried-Oken, Melanie
2015-03-01
More than 300 researchers gathered at the 2013 International Brain-Computer Interface (BCI) Meeting to discuss current practice and future goals for BCI research and development. The authors organized the Virtual Users' Forum at the meeting to provide the BCI community with feedback from users. We report on the Virtual Users' Forum, including initial results from ongoing research being conducted by 2 BCI groups. Online surveys and in-person interviews were used to solicit feedback from people with disabilities who are expert and novice BCI users. For the Virtual Users' Forum, their responses were organized into 4 major themes: current (non-BCI) communication methods, experiences with BCI research, challenges of current BCIs, and future BCI developments. Two authors with severe disabilities gave presentations during the Virtual Users' Forum, and their comments are integrated with the other results. While participants' hopes for BCIs of the future remain high, their comments about available systems mirror those made by consumers about conventional assistive technology. They reflect concerns about reliability (eg, typing accuracy/speed), utility (eg, applications and the desire for real-time interactions), ease of use (eg, portability and system setup), and support (eg, technical support and caregiver training). People with disabilities, as target users of BCI systems, can provide valuable feedback and input on the development of BCI as an assistive technology. To this end, participatory action research should be considered as a valuable methodology for future BCI research. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.
Manson, Robert H.; Ricketts, Taylor H.; Geissert, Daniel
2018-01-01
Payment for hydrological services (PHS) are popular tools for conserving ecosystems and their water-related services. However, improving the spatial targeting and impacts of PHS, as well as their ability to foster synergies with other ecosystem services (ES), remain challenging. We aimed at using spatial analyses to evaluate the targeting performance of México’s National PHS program in central Veracruz. We quantified the effectiveness of areas targeted for PHS in actually covering areas of high HS provision and social priority during 2003–2013. First, we quantified provisioning and spatial distributions of two target (water yield and soil retention), and one non-target ES (carbon storage) using InVEST. Subsequently, pairwise relationships among ES were quantified by using spatial correlation and overlap analyses. Finally, we evaluated targeting by: (i) prioritizing areas of individual and overlapping ES; (ii) quantifying spatial co-occurrences of these priority areas with those targeted by PHS; (iii) evaluating the extent to which PHS directly contribute to HS delivery; and (iv), testing if PHS targeted areas disproportionately covered areas with high ecological and social priority. We found that modelled priority areas exhibited non-random distributions and distinct spatial patterns. Our results show significant pairwise correlations between all ES suggesting synergistic relationships. However, our analysis showed a significantly lower overlap than expected and thus significant mismatches between PHS targeted areas and all types of priority areas. These findings suggest that the targeting of areas with high HS provisioning and social priority by Mexico’s PHS program could be improved significantly. This study underscores: (1) the importance of using maps of HS provisioning as main targeting criteria in PHS design to channel payments towards areas that require future conservation, and (2) the need for future research that helps balance ecological and socioeconomic targeting criteria. PMID:29462205
Determining research priorities for adolescent and young adult cancer in Australia.
Medlow, S; Patterson, P
2015-07-01
The Australian Youth Cancer Service (YCS) is part of a growing international movement to provide advocacy and better targeted health-care services for adolescents and young adults (AYAs) with cancer. One of the key initiatives of the YCS is to determine and implement priorities within Australian AYA cancer research. The YCS used the value-weighting online survey technique of allocating 100 hypothetical units of funding across pre-determined topics of research in order to determine Australian consumers' and health professionals' AYA cancer research priorities. A total of 101 participants (26 consumers and 75 health professionals) took part in the online survey. Biomedical and Clinical Medicine Research was allocated the greatest proportion of available funding. A number of priority populations were also identified, although these were distributed across pre-treatment and post-treatment stages. The preferences of consumers and health professionals to invest available AYA cancer research funds in Biomedical and Clinical Medicine Research will be an important consideration in guiding the Australian YCS decision-making process in the immediate future. 'Prevention, screening and early detection' was also an important research funding target, along with survivorship populations. © 2015 John Wiley & Sons Ltd.
Future directions of multiple behavior change research.
Geller, Karly; Lippke, Sonia; Nigg, Claudio R
2017-02-01
Non-communicable diseases (i.e., chronic diseases including cardiovascular disease, cancer, chronic respiratory disease, diabetes and obesity) result in 36 million deaths each year. Individuals' habitual participation in a single health-risk behaviors substantially contribute to morbidity and mortality (e.g., tobacco use, daily fast food intake, etc.); however, more concerning is the impact of typically co-occurring or clustering of multiple health-risk behaviors. This burden can be minimized through successful cessation of health-risk behaviors and adoption of healthy behaviors; namely healthy lifestyle adoption or multiple health behavior change (MHBC). MHBC is a developing field and future research recommendations are provided to advance MHBC research. A valid measure of MHBC (i.e., lifestyle) is warranted to provide the needed basis for MHBC investigations and evaluations. MHBC is thought to occur through shared co-variation of underlying motivating mechanisms, but how these relationships influence behavior remains unclear. A better understanding of the relationship between behaviors and the related motivating mechanisms (and potential cross-relationship of influences) is needed. Future research should also aim to improve lifestyles through understanding how to change multiple health behaviors. Finally, MHBC research should target the development of sustainable interventions which result in lasting effects (e.g., capacity, systems, policy and environmental changes), with dissemination considered during development. Focusing MHBC research in these areas will increase our understanding and maximize the impact on the health of populations.
ERIC Educational Resources Information Center
Reid, Ericka L.
2010-01-01
African American women compose a critical proportion of the potential science, technology, engineering, and mathematics (STEM) workforce of the future, yet are disproportionately represented and largely underutilized. While various programs and initiatives have been designed and implemented to target women and underrepresented minorities, the…
ERIC Educational Resources Information Center
Scott, Catherine
2010-01-01
Education as an institution fulfils the key social functions of promulgation of knowledge and the development of future citizens. Rather than these key functions earning it respect, education and its practitioners are the targets of criticism and what Labaree calls "scorn". This article seeks to progress the work done by Labaree on the origins of…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zayas, Jose; Derby, Mike; Ralston, Kiersten
Atmosphere to Electrons (A2e) is a multi-year U.S. Department of Energy (DOE) research initiative targeting significant reductions in the cost of wind energy through an improved understanding of the complex physics governing electricity generation by wind plants. The goal of A2e is to ensure future wind plants are sited, built, and operated in a way that produces the most cost-effective, usable electric power.
Shaping the Future of Nanomedicine: Anisotropy in Polymeric Nanoparticle Design
Meyer, Randall A.; Green, Jordan J.
2015-01-01
Nanofabrication and biomedical applications of polymeric nanoparticles have become important areas of research. Biocompatible polymeric nanoparticles have been investigated for their use as delivery vehicles for therapeutic and diagnostic agents. Although polymeric nanoconstructs have traditionally been fabricated as isotropic spheres, anisotropic, non-spherical nanoparticles have gained interest in the biomaterials community due to their unique interactions with biological systems. Polymeric nanoparticles with different forms of anisotropy have been manufactured utilizing a variety of novel methods in recent years. In addition, they have enhanced physical, chemical, and biological properties compared to spherical nanoparticles, including increased targeting avidity and decreased non-specific in vivo clearance. With these desirable properties, anisotropic nanoparticles have been successfully utilized in many biomedical settings and have performed superiorly to analogous spherical nanoparticles. We summarize the current state-of-the-art fabrication methods for anisotropic polymeric nanoparticles including top-down, bottom-up, and microfluidic design approaches. We also summarize the current and potential future applications of these nanoparticles, including drug delivery, biological targeting, immunoengineering, and tissue engineering. Ongoing research into the properties and utility of anisotropic polymeric nanoparticles will prove critical to realizing their potential in nanomedicine. PMID:25981390
Rare isotope accelerator project in Korea and its application to high energy density sciences
NASA Astrophysics Data System (ADS)
Chung, M.; Chung, Y. S.; Kim, S. K.; Lee, B. J.; Hoffmann, D. H. H.
2014-01-01
As a national science project, the Korean government has recently established the Institute for Basic Science (IBS) with the goal of conducting world-class research in basic sciences. One of the core facilities for the IBS will be the rare isotope accelerator which can produce high-intensity rare isotope beams to investigate the fundamental properties of nature, and also to support a broad research program in material sciences, medical and biosciences, and future nuclear energy technologies. The construction of the accelerator is scheduled to be completed by approximately 2017. The design of the accelerator complex is optimized to deliver high average beam current on targets, and to maximize the production of rare isotope beams through the simultaneous use of Isotope Separation On-Line (ISOL) and In-Flight Fragmentation (IFF) methods. The proposed accelerator is, however, not optimal for high energy density science, which usually requires very high peak currents on the target. In this study, we present possible beam-plasma experiments that can be done within the scope of the current accelerator design, and we also investigate possible future extension paths that may enable high energy density science with intense pulsed heavy ion beams.
Advantages of Structure-Based Drug Design Approaches in Neurological Disorders
Aarthy, Murali; Panwar, Umesh; Selvaraj, Chandrabose; Singh, Sanjeev Kumar
2017-01-01
Objective: The purpose of the review is to portray the theoretical concept on neurological disorders from research data. Background: The freak changes in chemical response of nerve impulse causes neurological disorders. The research evidence of the effort done in the older history suggests that the biological drug targets and their effective feature with responsive drugs could be valuable in promoting the future development of health statistics structure for improved treatment for curing the nervous disorders. Methods: In this review, we summarized the most iterative theoretical concept of structure based drug design approaches in various neurological disorders to unfathomable understanding of reported information for future drug design and development. Results: On the premise of reported information we analyzed the model of theoretical drug designing process for understanding the mechanism and pathology of the neurological diseases which covers the development of potentially effective inhibitors against the biological drug targets. Finally, it also suggests the management and implementation of the current treatment in improving the human health system behaviors. Conclusion: With the survey of reported information we concluded the development strategies of diagnosis and treatment against neurological diseases which leads to supportive progress in the drug discovery. PMID:28042767
[Advances in CRISPR-Cas-mediated genome editing system in plants].
Wang, Chun; Wang, Kejian
2017-10-25
Targeted genome editing technology is an important tool to study the function of genes and to modify organisms at the genetic level. Recently, CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins) system has emerged as an efficient tool for specific genome editing in animals and plants. CRISPR-Cas system uses CRISPR-associated endonuclease and a guide RNA to generate double-strand breaks at the target DNA site, subsequently leading to genetic modifications. CRISPR-Cas system has received widespread attention for manipulating the genomes with simple, easy and high specificity. This review summarizes recent advances of diverse applications of the CRISPR-Cas toolkit in plant research and crop breeding, including expanding the range of genome editing, precise editing of a target base, and efficient DNA-free genome editing technology. This review also discusses the potential challenges and application prospect in the future, and provides a useful reference for researchers who are interested in this field.
2017 Report for New LANL Physical Vapor Deposition Capability
DOE Office of Scientific and Technical Information (OSTI.GOV)
Roman, Audrey Rae; Zhao, Xinxin; Bond, Evelyn M.
There is an urgent need at LANL to achieve uniform, thin film actinide targets that are essential for nuclear physics experiments. The target preparation work is currently performed externally by Professor Walter Loveland at Oregon State University, who has made various evaporated actinide targets such as Th and U for use on several nuclear physics measurements at LANSCE. We are developing a vapor deposition capability, with the goal of evaporating Th and U in the Actinide Research Facility (ARF) at TA-48. In the future we plan to expand this work to evaporating transuranic elements, such as Pu. The ARF ismore » the optimal location for evaporating actinides because this lab is specifically dedicated to actinide research. There are numerous instruments in the ARF that can be used to provide detailed characterization of the evaporated thin films such as: Table top Scanning Electron Microscope, In-situ X-Ray Diffraction, and 3D Raman spectroscopy. These techniques have the ability to determine the uniformity, surface characterization, and composition of the deposits.« less
Developing technology for surgery in the UK: a multidisciplinary meeting of engineers and surgeons.
Taylor, G W
2007-03-01
There is an increasing necessity for surgeons and engineers to work together in order to target future technological developments at clinical need and cost-effectiveness. This is a report of two linked meetings with these objectives, held at the Institute of Mechanical Engineers, London, UK. The two meetings were organized by the same faculty members and held on consecutive days. Delegates included surgeons, academic mechanical engineers, researchers and industrial representatives. The programme was made up of varied presentations by surgeons and engineers as well as open discussion of the topics covered. Delegates were updated on the current state of surgical robotics in the UK in four surgical specialties; urology, neurosurgery, orthopaedics and ENT. This included clinical and experimental evidence, together with discussion of future advances. Minimally invasive surgery, real-time imaging and the development of more compact and cost effective surgical robots were identified as key areas for future research. Copyright 2006 John Wiley & Sons, Ltd.
Interventions to improve immigrant health. A scoping review
Ortiz-Barreda, Gaby; Ben-Shlomo, Yoav; Holdsworth, Michelle; Salami, Bukola; Rammohan, Anu; Chung, Roger Yat-Nork; Padmadas, Sabu S.; Krafft, Thomas
2017-01-01
Abstract Background: Disparities in health between immigrants and their host populations have been described across countries and continents. Hence, interventions for improving health targeting general populations are not necessarily effective for immigrants. Aims: To conduct a systematic search of the literature evaluating health interventions for immigrants; to map the characteristics of identified studies including range of interventions, immigrant populations and their host countries, clinical areas targeted and reported evaluations, challenges and limitations of the interventions identified. Following the results, to develop recommendations for research in the field. Methods: A scoping review approach was chosen to provide an overview of the type, extent and quantity of research available. Studies were included if they empirically evaluated health interventions targeting immigrants and/or their descendants, included a control group, and were published in English (PubMed and Embase from 1990 to 2015). Results: Most of the 83 studies included were conducted in the USA, encompassed few immigrant groups and used a randomized controlled trial (RCT) or cluster RCT design. Most interventions addressed chronic and non-communicable diseases and attendance at cancer screening services, used individual targeted approaches, targeted adult women and recruited participants from health centres. Outcome measures were often subjective, with the exception of interventions for cardiovascular risk and diabetes. Generally, authors claimed that interventions were beneficial, despite a number of reported limitations. Conclusions: Recommendations for enhancing interventions to improve immigrant health are provided to help researchers, funders and health care commissioners when deciding upon the scope, nature and design of future research in this area. PMID:28339883
Progress and Future Directions in Research on the Psychosis Prodrome: A Review for Clinicians
Woodberry, Kristen A; Shapiro, Daniel I; Bryant, Caitlin; Seidman, Larry J.
2016-01-01
The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and testing early intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that better engage youth, their environmental contexts, and neurodevelopmental targets to improve functional outcomes. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it. PMID:26954594
The Theory of Value-Based Payment Incentives and Their Application to Health Care.
Conrad, Douglas A
2015-12-01
To present the implications of agency theory in microeconomics, augmented by behavioral economics, for different methods of value-based payment in health care; and to derive a set of future research questions and policy recommendations based on that conceptual analysis. Original literature of agency theory, and secondarily behavioral economics, combined with applied research and empirical evidence on the application of those principles to value-based payment. Conceptual analysis and targeted review of theoretical research and empirical literature relevant to value-based payment in health care. Agency theory and secondarily behavioral economics have powerful implications for design of value-based payment in health care. To achieve improved value-better patient experience, clinical quality, health outcomes, and lower costs of care-high-powered incentives should directly target improved care processes, enhanced patient experience, and create achievable benchmarks for improved outcomes. Differing forms of value-based payment (e.g., shared savings and risk, reference pricing, capitation, and bundled payment), coupled with adjunct incentives for quality and efficiency, can be tailored to different market conditions and organizational settings. Payment contracts that are "incentive compatible"-which directly encourage better care and reduced cost, mitigate gaming, and selectively induce clinically efficient providers to participate-will focus differentially on evidence-based care processes, will right-size and structure incentives to avoid crowd-out of providers' intrinsic motivation, and will align patient incentives with value. Future research should address the details of putting these and related principles into practice; further, by deploying these insights in payment design, policy makers will improve health care value for patients and purchasers. © Health Research and Educational Trust.
Miller-Kleinhenz, Jasmine M; Bozeman, Erica N; Yang, Lily
2015-01-01
Effective treatment of triple-negative breast cancer (TNBC) with its aggressive tumor biology, highly heterogeneous tumor cells, and poor prognosis requires an integrated therapeutic approach that addresses critical issues in cancer therapy. Multifunctional nanoparticles with the abilities of targeted drug delivery and noninvasive imaging for monitoring drug delivery and responses to therapy, such as theranostic nanoparticles, hold great promise toward the development of novel therapeutic approaches for the treatment of TNBC using a single therapeutic platform. The biological and pathological characteristics of TNBC provide insight into several potential molecular targets for current and future nanoparticle-based therapeutics. Extensive tumor stroma, highly proliferative cells, and a high rate of drug resistance are all barriers that must be appropriately addressed in order for these nanotherapeutic platforms to be effective. Utilization of the enhanced permeability and retention effect coupled with active targeting of cell surface receptors expressed by TNBC cells, and tumor-associated endothelial cells, stromal fibroblasts, and macrophages is likely to overcome such barriers to facilitate more effective drug delivery. An in-depth summary of current studies investigating targeted nanoparticles in preclinical TNBC mouse and human xenograft models is presented. This review aims to outline the current status of nanotherapeutic options for TNBC patients, identification of promising molecular targets, challenges associated with the development of targeted nanotherapeutics, the research done by our group as well as by others, and future perspectives on the nanomedicine field and ways to translate current preclinical studies into the clinic. © 2015 Wiley Periodicals, Inc.
[Pulmonary hypertension: the future has begun].
Olschewski, Horst
2006-04-15
In recent years, pulmonary hypertension got into the focus of research due to the development of efficacious medications and the discovery of important pathologic mechanisms of disease. Currently, prostanoids, endothelin receptor antagonists and phosphodiesterase 5 inhibitors are the most important substance groups used for treatment. Substances that are emerging in tumor therapy (tyrosine kinase inhibitors, epidermal growth factor [EGF] und platelet-derived growth factor [PDGF] receptor blockers), vasoactive intestinal peptide (VIP), rho-kinase inhibitors and targeted drugs for endothelial dysfunction will be evaluated as future drugs for pulmonary hypertension. Improving early diagnosis of pulmonary hypertension will be an important task in the future. Both the development of diagnostic methods with increased sensitivity and specificity and a broad awareness program will be necessary to achieve this goal.
Challenging Futures Studies To Enhance Participatory River Basin Management
NASA Astrophysics Data System (ADS)
van der Helm, R.
Can the field of futures research help advance participatory management of river basins? This question is supposed to be answered by the present study of which this paper will mainly address the theoretical and conceptual point of view. The 2000 EU Framework directive on water emphasises at least two aspects that will mark the future management of river basins: the need for long-term planning, and a demand for participation. Neither the former nor the latter are new concepts as such, but its combination is in some sense revolutionary. Can long-term plans be made (and implemented) in a participative way, what tools could be useful in this respect, and does this lead to a satisfactory situation in terms of both reaching physical targets and enhancing social-institutional manageability? A possibly rich way to enter the discussion is to challenge futures research as a concept and a practice for enabling multiple stakeholders to design appropriate policies. Futures research is the overall field in which several methods and techniques (like scenario analysis) are mobilised to systematically think through and/or design the future. As such they have proven to be rich exercises to trigger ideas, stimulate debate and design desirable futures (and how to get there). More importantly these exercises have the capability to reconstitute actor relations, and by nature go beyond the institutional boundaries. Arguably the relation between futures research and the planning process is rather distant. Understandably commitments on the direct implementation of the results are hardly ever made, but its impact on changes in the capabilities of the network of actors involved may be large. As a hypothesis we consider that the distant link between an image of the future and the implementation in policy creates sufficient distance for actors to participate (in terms of responsibilities, legal constraints, etc.) and generate potentials, and enough degrees of freedom needed for a successful implementation. However, critical conceptual and design requirements have to be met in order to realise futures research potentials. Since the beginning of the 1990s futures studies are becoming (again) more and more widespread in many different domains (technology, education, urban development, agriculture, environment, etc.). Recently, experiences have been launched and are currently being launched in the water sector (of which the World Water Vision is a well -known - but not necessarily the most representative - example). Although futures studies on a river basin level are still scarce, they will offer already sufficient material for empirical analysis. The research, effectuated within a larger framework study on the implications of futures studies for environmental research, offers at this stage initially a conceptual understanding.
Ebneter, Daria S; Latner, Janet D
2013-04-01
The aim of the current article was to compare stigmatizing attitudes toward eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED), with stigma toward another weight-related condition (obesity) and a non-weight-related mental disorder (major depressive disorder [MDD]). Participants (N = 447) read five vignettes describing a woman with AN, BN, BED, obesity, or MDD and responded to questionnaires examining stigmatizing attitudes. The targets with EDs were blamed more for their condition than the targets with MDD, whereas persons with obesity were held more responsible for their condition than any other target. On the other hand, the target with MDD was perceived as more impaired than any other target. Lack of self-discipline was attributed more to the development of BED and obesity than to any other condition. Stigmatizing attitudes vary across mental health disorders, and future research should aim to specifically target stigmatizing beliefs to reduce and prevent discrimination toward mental health disorders and obesity.
Plan demographics, participants' saving behavior, and target-date fund investments.
Park, Youngkyun
2009-05-01
This analysis explores (1) whether plan demographic characteristics would affect individual participant contribution rates and target-date fund investments and (2) equity glide paths for participants in relation to plan demographics by considering target replacement income and its success rate. PLAN DEMOGRAPHIC CHARACTERISTICS IN PARTICIPANT CONTRIBUTION RATES: This study finds empirical evidence that 401(k) plan participants' contribution rates differ by plan demographics based on participants' income and/or tenure. In particular, participants in 401(k) plans dominated by those with low income and short tenure tend to contribute less than those in plans dominated by participants with high income and long tenure. Future research will explore how participant contribution behavior may also be influenced by incentives provided by employers through matching formulae. PLAN DEMOGRAPHIC CHARACTERISTICS IN TARGET-DATE FUND INVESTMENTS: The study also finds empirical evidence that participants' investments in target-date funds with different equity allocations differ by plan demographics based on participants' income and/or tenure. In particular, target-date fund users with 90 percent or more of their account balances in target-date funds who are in 401(k) plans dominated by low-income and short-tenure participants tend to hold target-date funds with lower equity allocations, compared with their counterparts in plans dominated by high-income and long-tenure participants. Future research will focus on the extent to which these characteristics might influence the selection of target-date funds by plan sponsors. EQUITY GLIDE PATHS: Several stylized equity glide paths as well as alternative asset allocations are compared for participants at various starting ages to demonstrate the interaction between plan demographics and equity glide paths/asset allocations in terms of success rates in meeting various replacement income targets. The equity glide path/asset allocation providing the highest success rate at a particular replacement rate target will vary with the assumed starting date of the participant (see Figure 17). Given the highly stylized nature of the simulations in this Issue Brief it is important to note that the results are not intended to provide a single equity glide path solution in relation to plan demographics. Instead, they serve as a framework to be considered when plan sponsors make a selection concerning which target-date funds to include in their plan. IMPORTANCE OF PARTICIPANT CONTRIBUTION RATES: This analysis finds that although target-date funds with different equity glide paths affect the retirement income replacement success rate, participant contribution rates corresponding to different plan demographic characteristics have a stronger impact. AUTO FEATURES OF THE PPA: This Issue Brief provides a stylized study using observed contribution rates as of the 2007 plan year. However, with the passage of the Pension Protection Act of 2006 and its likely impact on plan design in the future (increased utilization of automatic enrollment and automatic contribution escalations), it is likely that contribution rates among the participants may become more homogenous. In such a scenario, it may be more likely that a single equity glide path would meet a wide range of demographic profiles.
Effects of the time dimension and presentation on incidental memory.
Toyota, Hiroshi
2009-08-01
Undergraduates were presented targets on two occasions, and each time they were asked to choose one of two alternatives (past or future) associated with the targets in the orienting task, followed by an unexpected free recall. For the pleasant targets, the spaced presentation led to a better recall than the massed presentation for both past and future time. However, for unpleasant targets, the spacing effect was found in recall of targets associated with the past but the effect was not observed in recall of targets associated with the future. These results were interpreted as indicating that the quantity and the quality of the episodes associated with the targets were processed differently as a function of emotional attribute and time dimension.
NASA Astrophysics Data System (ADS)
Otiougova, Polina; Bergmann, Ryan; Kiselev, Daniela; Talanov, Vadim; Wohlmuther, Michael
2017-09-01
The Paul Scherrer Institute (PSI) is the largest national research center in Switzerland. Its multidisciplinary research is dedicated to a wide ↓eld in natural science and technology as well as particle physics. The High Intensity Proton Accelerator Facility (HIPA) has been in operation at PSI since 1974. It includes an 870 keV Cockroft-Walton pre-accelerator, a 72 MeV injector cyclotron as well as a 590 MeV ring cyclotron. The experimental facilities, the meson production graphite targets, Target E and Target M, and the spallation target stations (SINQ and UCN) are used for material research and particle physics. In order to ful↓ll the request of the regulatory authorities and to be reported to the regulators, the expected radioactive waste and nuclide inventory after an anticipated ↓nal shutdown in the far future has to be estimated. In this contribution, calculations for the 20 m long beamline between Target E and the 590 MeV beam dump of HIPA are presented. The ↓rst step in the calculations was determining spectra and spatial particle distributions around the beamlines using the Monte-Carlo particle transport code MCNPX2.7.0 [1]. To perform the analysis of the MCNPX output and to determine the radionuclide inventory as well as the speci↓c activity of the nuclides, an activation script [2] using the FISPACT10 code with the cross sections from the European Activation File (EAF2010) [3] was applied. The speci↓c activity values were compared to the currently existing Swiss exemption limits (LE) [4] as well as to the Swiss liberation limits (LL) [5], becoming e↑ective in the near future. The obtained results were used to estimate the total volume of the radioactive waste produced at HIPA and have to be reported to the Swiss regulatory authorities. The comparison of the performed calculations to measurements is discussed as well. Note to the reader: the pdf file has been changed on September 22, 2017.
Controllability in Multi-Stage Laser Ion Acceleration
NASA Astrophysics Data System (ADS)
Kawata, S.; Kamiyama, D.; Ohtake, Y.; Barada, D.; Ma, Y. Y.; Kong, Q.; Wang, P. X.; Gu, Y. J.; Li, X. F.; Yu, Q.
2015-11-01
The present paper shows a concept for a future laser ion accelerator, which should have an ion source, ion collimators, ion beam bunchers and ion post acceleration devices. Based on the laser ion accelerator components, the ion particle energy and the ion energy spectrum are controlled, and a future compact laser ion accelerator would be designed for ion cancer therapy or for ion material treatment. In this study each component is designed to control the ion beam quality. The energy efficiency from the laser to ions is improved by using a solid target with a fine sub-wavelength structure or a near-critical density gas plasma. The ion beam collimation is performed by holes behind the solid target or a multi-layered solid target. The control of the ion energy spectrum and the ion particle energy, and the ion beam bunching are successfully realized by a multi-stage laser-target interaction. A combination of each component provides a high controllability of the ion beam quality to meet variable requirements in various purposes in the laser ion accelerator. The work was partly supported by MEXT, JSPS, ASHULA project/ ILE, Osaka University, CORE (Center for Optical Research and Education, Utsunomiya University, Japan), Fudan University and CDI (Creative Dept. for Innovation) in CCRD, Utsunomiya University.
Ecdysone receptor agonism leading to lethal molting ...
Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, several classes of pesticides used in agriculture and aquaculture specifically target key endocrine regulators of the molting process. These chemicals may also pose hazards to non-target species by causing molting defects, thus affecting the health of the ecosystems. The present review summarized the available knowledge on molting-related endocrine regulation and disruption in arthropods (with special focus on insects and crustaceans), in order to identify research gaps and develop a toxicity mechanism-based model for environmental hazard and risk assessment. Based on the review, multiple targets in the molting processes that EDCs can interact with were characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and evaluated for weight of evidence using the Evolved Bradford Hill Criteria. This review proposed the first invertebrate endocrine disruption AOP and may serve as a knowledge foundation for future environmental studies and AOP development. Development of high throughput toxicology (HTT) programs (e.g., ToxCast, Tox21) and potential a
NASA Astrophysics Data System (ADS)
Quirion, Nate
Unmanned Aerial Systems (UASs) today are fulfilling more roles than ever before. There is a general push to have these systems feature more advanced autonomous capabilities in the near future. To achieve autonomous behavior requires some unique approaches to control and decision making. More advanced versions of these approaches are able to adapt their own behavior and examine their past experiences to increase their future mission performance. To achieve adaptive behavior and decision making capabilities this study used Reinforcement Learning algorithms. In this research the effects of sensor performance, as modeled through Signal Detection Theory (SDT), on the ability of RL algorithms to accomplish a target localization task are examined. Three levels of sensor sensitivity are simulated and compared to the results of the same system using a perfect sensor. To accomplish the target localization task, a hierarchical architecture used two distinct agents. A simulated human operator is assumed to be a perfect decision maker, and is used in the system feedback. An evaluation of the system is performed using multiple metrics, including episodic reward curves and the time taken to locate all targets. Statistical analyses are employed to detect significant differences in the comparison of steady-state behavior of different systems.
Proteolytic activity during senescence of plants
NASA Technical Reports Server (NTRS)
Huffaker, R. C.
1990-01-01
Although information has rapidly developed concerning the intracellular localization of plant proteins, relatively few reports concern the intracellular location of endo- and exo-proteolytic activities. Relatively few proteases have been purified, characterized, and associated with a specific cellular location. With the exception of the processing proteases involved in transport of proteins across membranes, little progress has yet been made concerning determination of in vivo products of specific proteases. Information on the turnover of individual proteins and the assessment of rate-limiting steps in pathways as proteins are turned over is steadily appearing. Since chloroplasts are the major site of both protein synthesis and, during senescence, degradation, it was important to show unambiguously that chloroplasts can degrade their own constituents. Another important contribution was to obtain evidence that the chloroplasts contain proteases capable of degrading their constituents. This work has been more tenuous because of the low activities found and the possibility of contamination by vacuolar enzymes during the isolation of organelles. The possible targeting of cytoplasmic proteins for degradation by facilitating their transport into vacuoles is a field which hopefully will develop more rapidly in the future. Information on targeting of proteins for degradation via the ubiquitin (Ub) degradation pathway is developing rapidly. Future research must determine how much unity exists across the different eukaryotic systems. At present, it has important implications for protein turnover in plants, since apparently Ub is involved in the degradation of phytochrome. Little information has been developed regarding what triggers increased proteolysis with the onset of senescence, although it appears to involve protein synthesis. Thus far, the evidence indicates that the complement of proteases prior to senescence is sufficient to carry out the observed protein degradation. This field of study has great practical implications, e.g. maintaining photosynthesis during seed-fill in order to obtain greater crop yields. The current use of stay green' variants in the populations of several crop plants to produce increased yields shows the potential for future development. The near future should see exciting discoveries in these areas of research that will have far reaching effects on the construction of transgenic plants for future research accomplishments and agricultural use.
Knoeferle, Pia; Carminati, Maria Nella; Abashidze, Dato; Essig, Kai
2011-01-01
Eye-tracking findings suggest people prefer to ground their spoken language comprehension by focusing on recently seen events more than anticipating future events: When the verb in NP1-VERB-ADV-NP2 sentences was referentially ambiguous between a recently depicted and an equally plausible future clipart action, listeners fixated the target of the recent action more often at the verb than the object that hadn’t yet been acted upon. We examined whether this inspection preference generalizes to real-world events, and whether it is (vs. isn’t) modulated by how often people see recent and future events acted out. In a first eye-tracking study, the experimenter performed an action (e.g., sugaring pancakes), and then a spoken sentence either referred to that action or to an equally plausible future action (e.g., sugaring strawberries). At the verb, people more often inspected the pancakes (the recent target) than the strawberries (the future target), thus replicating the recent-event preference with these real-world actions. Adverb tense, indicating a future versus past event, had no effect on participants’ visual attention. In a second study we increased the frequency of future actions such that participants saw 50/50 future and recent actions. During the verb people mostly inspected the recent action target, but subsequently they began to rely on tense, and anticipated the future target more often for future than past tense adverbs. A corpus study showed that the verbs and adverbs indicating past versus future actions were equally frequent, suggesting long-term frequency biases did not cause the recent-event preference. Thus, (a) recent real-world actions can rapidly influence comprehension (as indexed by eye gaze to objects), and (b) people prefer to first inspect a recent action target (vs. an object that will soon be acted upon), even when past and future actions occur with equal frequency. A simple frequency-of-experience account cannot accommodate these findings. PMID:22207858
Goswami, Chandan; Islam, Md Shahidul
2010-01-01
More than 150 participants from 25 countries gathered in Stockholm during 25(th) to 27(th) Sept 2009 to attend the meeting "TRP channels: from sensory signaling to human disease" and enjoyed an international, intensive and vibrant meeting. This meeting shed lights on the recent advances made in this field of research in different sectors of biology, and identified directions for future research and the areas where TRP channels could be used as potential targets for prevention and treatment of human diseases. The participants of this meeting shared their recent largely unpublished data, state-of-the-art techniques and their critical views which would push research in this field forward in the new decade. Another major outcome of this meeting was the realization that extensive work remains to be done to develop the necessary tools and enhance the quality of research in this area so that the prevailing controversies can be resolved. In this report we summarize the latest scientific excitements, some critical issues, as well as some future directions for research that were addressed and discussed in this meeting.
Toyota, Hiroshi
2011-02-01
The present study examined the effects of emotion elicited by episodes (past events or expected future events) and the relationship between individual differences in emotional intelligence and memory. Participants' emotional intelligence was assessed on the Japanese version of Emotional Skills and Competence Questionnaire. They rated the pleasantness of episodes they associated with targets, and then performed unexpected free recall tests. When the targets were associated with episodes that were past events, all participants recalled more of the targets associated with pleasant and unpleasant episodes than those associated with neutral episodes. However, when the targets were associated with episodes expected to occur in the future, only participants with higher emotional intelligence scores recalled more of the targets associated with pleasant and unpleasant episodes. The participants with lower emotional intelligence scores recalled the three target types with similar accuracy. These results were interpreted as showing that emotional intelligence is associated with the processing of targets associated with future episodes as retrieval cues.
Smoking Beliefs Among Chinese Secondary School Students: A Theory-Based Qualitative Study.
Zhao, Xiang; White, Katherine M; Young, Ross McD; Obst, Patricia L
2018-02-07
China has the world's greatest number of smokers but theory-based smoking interventions are rare. To develop an effective intervention, understanding the determinants of Chinese adolescent smoking is crucial. The Theory of Planned Behavior (TPB) is empirically supported to predict and assist in informing intervention strategies to change health-related behaviors. Based on the TPB, the elicitation of shared smoking beliefs among adolescents can inform future intervention designs among this at-risk population. We investigated the beliefs from six focus groups (N = 30) of one senior secondary school in Kunming, Yunnan Province, China. We used semi-structured questions based on the TPB framework, including prompts about behavioral (advantages and disadvantages), normative (important referents), and control (barriers and facilitators) beliefs. Following the Consensual Qualitative Research (CQR) methodology, data were discussed until consensus was reached. Auditing was undertaken by an external researcher. Seven domains (advantages, disadvantages, approvers, disapprovers, facilitators, barriers, and smoker images) were examined. Smoking as a gendered behavior, smoking as influenced by cultural and environmental contexts, smoking as a strategy to cope with stress, and awareness of the harm of smoking, are highlighted themes across domains. Data suggested an extended-TPB framework as an appropriate approach to adopt when addressing smoking beliefs among the target population. These beliefs can be utilized to inform future school-based interventions and public health campaigns targeting smoking among Chinese adolescents. A modified TPB approach has potential for future smoking interventions among Chinese adolescents. Beliefs elicited in this study form a strong basis for designing a location- and population-specific antismoking programme. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Ringsberg, K C; Olander, E; Tillgren, P; Thualagant, N; Trollvik, A
2018-02-01
Health literacy is an essential social determinant for promoting and maintaining the health of a population. From a health promotion perspective, explore health literacy issues, concerns and future challenges among Nordic practitioners and researchers. Data were collected in a workshop at the 8 th Nordic Health Promotion Conference, and in a literature review, with articles from five databases. The search included title and abstract with the search terms health literacy* and health literacy as a MeSH term and all the Nordic countries. Qualitative and quantitative analysis were used. Twenty-five persons participated in the workshop. The discussions were summarized in six themes: concept of health literacy in national language; risk of victim blaming; measuring health literacy; content in school curricula on health literacy; new technologies for information and communication; communication and collaboration between different actors in support of health. Forty-three articles on health literacy were identified, mainly conducted within three fields: development, test and adaptation of instruments for measuring health literacy; measurement of health literacy among patients, or other defined target groups and on populations; and developing and evaluating methods/tools for the training of personnel groups or different target groups. There is a need for further studies providing a more in-depth understanding of the health literacy concept, knowledge on how to measure health literacy, ethical aspects, application in intersectoral collaboration as well as the adaptation to new technologies for information and communication in education supporting health literacy. As health literacy is an essential social health determinant, a concern and a future challenge must be, to make the health literacy concept familiar and visible in health promotion policies, research and practice such as health education.
The NASA Materials Science Research Program - It's New Strategic Goals and Plans
NASA Technical Reports Server (NTRS)
Schlagheck, Ronald A.
2003-01-01
In 2001, the NASA created a separate science enterprise, the Office of Biological and Physical Research (OBPR), to perform strategical and fundamental research bringing together physics, chemistry, biology, and engineering to solve problems needed for future agency mission goals. The Materials Science Program is one of basic research disciplines within this new Enterprise's Division of Physical Sciences Research. The Materials Science Program participates to utilize effective use of International Space Station (ISS) experimental facilities, target new scientific and technology questions, and transfer results for Earth benefits. The program has recently pursued new investigative research in areas necessary to expand NASA knowledge base for exploration of the universe, some of which will need access to the microgravity of space. The program has a wide variety of traditional ground and flight based research related types of basic science related to materials crystallization, fundamental processing, and properties characterization in order to obtain basic understanding of various phenomena effects and relationships to the structures, processing, and properties of materials. A summary of the types and sources for this research is presented and those experiments planned for the space. Areas to help expand the science basis for NASA future missions are described. An overview of the program is given including the scope of the current and future NASA Research Announcements with emphasis on new materials science initiatives. A description of the planned flight experiments to be conducted on the International Space Station program along with the planned facility class Materials Science Research Rack (MSRR) and Microgravity Glovebox (MSG) type investigations.
Gunn, Martin L; Marin, Jennifer R; Mills, Angela M; Chong, Suzanne T; Froemming, Adam T; Johnson, Jamlik O; Kumaravel, Manickam; Sodickson, Aaron D
2016-08-01
In May 2015, the Academic Emergency Medicine consensus conference "Diagnostic imaging in the emergency department: a research agenda to optimize utilization" was held. The goal of the conference was to develop a high-priority research agenda regarding emergency diagnostic imaging on which to base future research. In addition to representatives from the Society of Academic Emergency Medicine, the multidisciplinary conference included members of several radiology organizations: American Society for Emergency Radiology, Radiological Society of North America, the American College of Radiology, and the American Association of Physicists in Medicine. The specific aims of the conference were to (1) understand the current state of evidence regarding emergency department (ED) diagnostic imaging utilization and identify key opportunities, limitations, and gaps in knowledge; (2) develop a consensus-driven research agenda emphasizing priorities and opportunities for research in ED diagnostic imaging; and (3) explore specific funding mechanisms available to facilitate research in ED diagnostic imaging. Through a multistep consensus process, participants developed targeted research questions for future research in six content areas within emergency diagnostic imaging: clinical decision rules; use of administrative data; patient-centered outcomes research; training, education, and competency; knowledge translation and barriers to imaging optimization; and comparative effectiveness research in alternatives to traditional computed tomography use.
Improving the Quality of Survivorship for Older Adults with Cancer
Mohile, Supriya G.; Hurria, Arti; Cohen, Harvey J.; Rowland, Julia H.; Leach, Corinne R.; Arora, Neeraj K.; Canin, Beverly; Muss, Hyman; Magnuson, Allison; Flannery, Marie; Lowenstein, Lisa; Allore, Heather; Mustian, Karen; Demark-Wahnefried, Wendy; Extermann, Martine; Ferrell, Betty; Inouye, Sharon; Studenski, Stephanie; Dale, William
2016-01-01
In May 2015, the Cancer and Aging Research Group (CARG), in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent decline or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) utilize standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the prior two U13 meetings, this conference provides the framework for future research to improve the evidence base for the clinical care of older adults with cancer. PMID:27172129
Sirtuins in dermatology: applications for future research and therapeutics.
Serravallo, Melissa; Jagdeo, Jared; Glick, Sharon A; Siegel, Daniel M; Brody, Neil I
2013-05-01
Sirtuins are a family of seven proteins in humans (SIRT1-SIRT7) that are involved in multiple cellular processes relevant to dermatology. The role of sirtuins in other organ systems is established. However, the importance of these proteins in dermatology is less defined. Recently, sirtuins gained international attention because of their role as "longevity proteins" that may extend and enhance human life. Sirtuins function in the cell via histone deacetylase and/or adenosine diphosphate ribosyltransferase enzymatic activity that target histone and non-histone substrates, including transcription regulators, tumor suppressors, structural proteins, DNA repair proteins, cell signaling proteins, transport proteins, and enzymes. Sirtuins are involved in cellular pathways related to skin structure and function, including aging, ultraviolet-induced photoaging, inflammation, epigenetics, cancer, and a variety of cellular functions including cell cycle, DNA repair and proliferation. This review highlights sirtuin-related cellular pathways, therapeutics and pharmacological targets in atopic dermatitis, bullous dermatoses, collagen vascular disorders, psoriasis, systemic lupus erythematosus, hypertrophic and keloid scars, cutaneous infections, and non-melanoma and melanoma skin cancer. Also discussed is the role of sirtuins in the following genodermatoses: ataxia telangiectasia, Cowden's syndrome, dyskeratosis congenita, Rubenstein-Taybi, Werner syndrome, and xeroderma pigmentosum. The pathophysiology of these inherited diseases is not well understood, and sirtuin-related processes represent potential therapeutic targets for diseases lacking suitable alternative treatments. The goal of this review is to bring attention to the dermatology community, physicians, and scientists, the importance of sirtuins in dermatology and provide a foundation and impetus for future discussion, research and pharmacologic discovery.
Nanobody-derived nanobiotechnology tool kits for diverse biomedical and biotechnology applications.
Wang, Yongzhong; Fan, Zhen; Shao, Lei; Kong, Xiaowei; Hou, Xianjuan; Tian, Dongrui; Sun, Ying; Xiao, Yazhong; Yu, Li
2016-01-01
Owing to peculiar properties of nanobody, including nanoscale size, robust structure, stable and soluble behaviors in aqueous solution, reversible refolding, high affinity and specificity for only one cognate target, superior cryptic cleft accessibility, and deep tissue penetration, as well as a sustainable source, it has been an ideal research tool for the development of sophisticated nanobiotechnologies. Currently, the nanobody has been evolved into versatile research and application tool kits for diverse biomedical and biotechnology applications. Various nanobody-derived formats, including the nanobody itself, the radionuclide or fluorescent-labeled nanobodies, nanobody homo- or heteromultimers, nanobody-coated nanoparticles, and nanobody-displayed bacteriophages, have been successfully demonstrated as powerful nanobiotechnological tool kits for basic biomedical research, targeting drug delivery and therapy, disease diagnosis, bioimaging, and agricultural and plant protection. These applications indicate a special advantage of these nanobody-derived technologies, already surpassing the "me-too" products of other equivalent binders, such as the full-length antibodies, single-chain variable fragments, antigen-binding fragments, targeting peptides, and DNA-based aptamers. In this review, we summarize the current state of the art in nanobody research, focusing on the nanobody structural features, nanobody production approach, nanobody-derived nanobiotechnology tool kits, and the potentially diverse applications in biomedicine and biotechnology. The future trends, challenges, and limitations of the nanobody-derived nanobiotechnology tool kits are also discussed.
ALK-targeted therapy for lung cancer: ready for prime time.
Husain, Hatim; Rudin, Charles M
2011-06-01
Lung cancer remains the leading cause of cancer-related death in the United States. Ongoing research into the molecular basis of lung cancer has yielded insight into various critical pathways that are deregulated in lung tumorigenesis, and in particular key driver mutations integral to cancer cell survival and proliferation. One of the most recent examples of this has been definition of translocations and functional dysregulation of the anaplastic lymphoma kinase (ALK) gene in a subset of patients with non-small-cell lung cancer. The pace of research progress in this area has been remarkable: chromosomal rearrangements involving this gene in lung cancer were first reported in 2007 by a team of investigators in Japan. Less than 3 years later, an early-phase clinical trial of a targeted ALK inhibitor has yielded impressive responses in patients with advanced lung cancer containing ALK rearrangements, and mechanisms of acquired resistance to ALK-targeted therapy are being reported. A definitive study randomizing patients with ALK-mutant lung cancer to crizotinib (also known as PF-02341066 or 1066) versus standard therapy has recently completed enrollment.Taken together, these data describe a trajectory of research progress from basic discovery science to real-world implementation that should serve as a model for future integration of preclinical and clinical therapeutic research.
Daniels, Benjamin; Lord, Sarah J; Kiely, Belinda E; Houssami, Nehmat; Haywood, Philip; Lu, Christine Y; Ward, Robyn L; Pearson, Sallie-Anne
2017-01-01
Background The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2-targeted therapies in Australia. Methods/design Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2-targeted therapies to undertake this research. Ethics and dissemination Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments. PMID:28119394
NASA Technical Reports Server (NTRS)
Rhatigan, Jennifer L.; Robinson, Julie A.; Sawin, Charles F.; Ahlf, Peter R.
2005-01-01
In January, 2004, the US President announced a vision for space exploration, and charged NASA with utilizing the International Space Station (ISS) for research and technology targeted at supporting the US space exploration goals. This paper describes: 1) what we have learned from the first four years of research on ISS relative to the exploration mission, 2) the on-going research being conducted in this regard, 3) our current understanding of the major exploration mission risks that the ISS can be used to address, and 4) current progress in realigning NASA s research portfolio for ISS to support exploration missions. Specifically, we discuss the focus of research on solving the perplexing problems of maintaining human health on long-duration missions, and the development of countermeasures to protect humans from the space environment, enabling long duration exploration missions. The interchange between mission design and research needs is dynamic, where design decisions influence the type of research needed, and results of research influence design decisions. The fundamental challenge to science on ISS is completing experiments that answer key questions in time to shape design decisions for future exploration. In this context, exploration-relevant research must do more than be conceptually connected to design decisions-it must become a part of the mission design process.
Clarke, Amanda R.; Goddu, Anna P.; Nocon, Robert S.; Stock, Nicholas W.; Chyr, Linda C.; Akuoko, Jaleesa A.S.; Chin, Marshall H.
2013-01-01
Background A systematic scan of the disparities intervention literature will allow researchers, providers, and policymakers to understand which interventions are being evaluated to improve minority health and which areas require further research. Methods We systematically categorized 391 disparities intervention articles published between 1979 and 2011, covering 11 diseases. We developed a taxonomy of disparities interventions using qualitative theme analysis. We identified the tactic, or what was done to intervene; the strategy, or a group of tactics with common characteristics; and the level, or who was targeted by the effort. Results The taxonomy included 44 tactics, nine strategies, and six levels. Delivering education and training was the most common strategy (37%). Within education and training, the most common tactics were education about disease (14%) and self-management (11%), while communication-skills training (3%) and decision-making aids (1%) were less frequent. The strategy of actively engaging the community through tactics such as community health workers and outreach efforts accounted for 6.5% of tactics. Interventions most commonly targeted patients (50%) and community members who were not established patients of the intervening organization (32%). Interventions targeting providers (7%), the microsystem (immediate care team) (9%), organizations (3%), and policies (0.1%) were less common. Conclusions Disparities researchers have predominantly focused on the patient as the target for change; future research should also investigate how to improve the system that serves minority patients. Areas for further study include interventions that engage the community, educational interventions that address communication barriers, and the impact of policy reform on disparities in care. PMID:24128746
Basics and applications of genome editing technology.
Yamamoto, Takashi; Sakamoto, Naoaki
2016-01-01
Genome editing with programmable site-specific nucleases is an emerging technology that enables the manipulation of targeted genes in many organisms and cell lines. Since the development of the CRISPR-Cas9 system in 2012, genome editing has rapidly become an indispensable technology for all life science researchers, applicable in various fields. In this seminar, we will introduce the basics of genome editing and focus on the recent development of genome editing tools and technologies for the modification of various organisms and discuss future directions of the genome editing research field, from basic to medical applications.
Sager, Monica; Yeat, Nai Chien; Pajaro-Van der Stadt, Stefan; Lin, Charlotte; Ren, Qiuyin; Lin, Jimmy
2015-01-01
Transcriptomic technologies are evolving to diagnose cancer earlier and more accurately to provide greater predictive and prognostic utility to oncologists and patients. Digital techniques such as RNA sequencing are replacing still-imaging techniques to provide more detailed analysis of the transcriptome and aberrant expression that causes oncogenesis, while companion diagnostics are developing to determine the likely effectiveness of targeted treatments. This article examines recent advancements in molecular profiling research and technology as applied to cancer diagnosis, clinical applications and predictions for the future of personalized medicine in oncology.
The application of UAS towards tornado research and forecasting
NASA Astrophysics Data System (ADS)
Houston, A. L.; Argrow, B. M.; Frew, E.; Weiss, C.
2014-12-01
UAS hold significant potential to advance the understanding of tornadoes and improve tornado warning skill. While the current regulatory environment places limits on the application of UAS towards these ends, demonstrated success targeting tornadic and non-tornadic supercells proves the general feasibility of this work. In this presentation we will summarize the successes using UAS to collect data in the vicinity of supercell thunderstorms and discuss ways that these data, along with additional data collected in future field campaigns, can be used answer basic research questions concerning tornado formation and applied research questions concerning the value of UAS in the tornado warning decision process. The associative relationship between the rear-flank downdraft (RFD) and tornadogenesis has long been recognized. Yet, despite decades of research focused on tornadoes, the causal relationship between the RFD and tornadogenesis remains unresolved. In the presentation, we will describe ways that UAS could be used to test hypotheses posed to explain this causal relationship. We will also present a strategy to quantify the impact of UAS on tornado warning skill. Through controlled forecast experiments conducted using data collected through small field campaigns that leverage prior success targeting supercell thunderstorms with UAS, the value of targeted surveillance of potentially tornadic storms using UAS can be assessed. Significant changes to the existing regulatory environment are likely required for UAS, operated in a targeted surveillance mode, to contribute to improving tornado warning skill, but progress can be made today towards quantifying the impact that UAS could make.
EXPOsOMICS: final policy workshop and stakeholder consultation.
Turner, Michelle C; Vineis, Paolo; Seleiro, Eduardo; Dijmarescu, Michaela; Balshaw, David; Bertollini, Roberto; Chadeau-Hyam, Marc; Gant, Timothy; Gulliver, John; Jeong, Ayoung; Kyrtopoulos, Soterios; Martuzzi, Marco; Miller, Gary W; Nawrot, Timothy; Nieuwenhuijsen, Mark; Phillips, David H; Probst-Hensch, Nicole; Samet, Jonathan; Vermeulen, Roel; Vlaanderen, Jelle; Vrijheid, Martine; Wild, Christopher; Kogevinas, Manolis
2018-02-15
The final meeting of the EXPOsOMICS project "Final Policy Workshop and Stakeholder Consultation" took place 28-29 March 2017 to present the main results of the project and discuss their implications both for future research and for regulatory and policy activities. This paper summarizes presentations and discussions at the meeting related with the main results and advances in exposome research achieved through the EXPOsOMICS project; on other parallel research initiatives on the study of the exposome in Europe and in the United States and their complementarity to EXPOsOMICS; lessons learned from these early studies on the exposome and how they may shape the future of research on environmental exposure assessment; and finally the broader implications of exposome research for risk assessment and policy development on environmental exposures. The main results of EXPOsOMICS in relation to studies of the external exposome and internal exposome in relation to both air pollution and water contaminants were presented as well as new technologies for environmental health research (adductomics) and advances in statistical methods. Although exposome research strengthens the scientific basis for policy development, there is a need in terms of showing added value for public health to: improve communication of research results to non-scientific audiences; target research to the broader landscape of societal challenges; and draw applicable conclusions. Priorities for future work include the development and standardization of methodologies and technologies for assessing the external and internal exposome, improved data sharing and integration, and the demonstration of the added value of exposome science over conventional approaches in answering priority policy questions.
The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets.
VanPatten, Sonya; Al-Abed, Yousef
2017-01-01
Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. Over the years, researchers have revealed much about its regulation, properties of its receptors and features of the downstream signaling that influence its terminal effects. The acetylcholine system, traditionally associated with neuromuscular communication, is now known to play a crucial part in modulation of the immune system and other 'rest and digest' effects. Recent research seeks to elucidate the system's role in brain functions including cognition, sleep, arousal, motivation, reward and pain. We highlight clinically approved and experimental drugs that modulate the acetylcholine receptors. The complexities in targeting the acetylcholine receptors are vast and finding future indications for drug development associated with specific acetylcholine receptors remains a challenge. Copyright © 2016 Elsevier Ltd. All rights reserved.
[Social marketing and public policies for health: campaign to promote smoke-free spaces in Mexico].
Villalobos, Víctor; Ramírez, Olivia Ortiz; Thrasher, James F; Santillán, Edna Arillo; Hernández, Rosaura Pérez; Cedillo, Claudia; González, Wendy
2010-01-01
"Porque todos respiramos lo mismo" is a mass media campaign to promote smoke-free places (SFP). The development stages were: strategic planning; formative research; message development; media plan; and impact evaluation. Development involved formation of a coalition of key actors in various sectors. The target population was smokers and nonsmokers, with the aim of changing social norms around SFP. Nonsmokers were targeted because they comprised the majority and were most likely to appreciate the benefits of SFPs. Campaign materials were aired on television, radio, print and on billboards. One key limitation was the lack of evidence for previous campaigns, which increased the importance of formative research and of including a rigorous evaluation for this one. The campaign evaluation indicates a significant impact, which suggests that future campaigns use similar strategies in their development.
Diamond High Assurance Security Program: Trusted Computing Exemplar
2002-09-01
computing component, the Embedded MicroKernel Prototype. A third-party evaluation of the component will be initiated during development (e.g., once...target technologies and larger projects is a topic for future research. Trusted Computing Reference Component – The Embedded MicroKernel Prototype We...Kernel The primary security function of the Embedded MicroKernel will be to enforce process and data-domain separation, while providing primitive
Khochikar, Makarand V
2017-03-01
Renal cell carcinoma accounts for 3% of adult solid malignant tumours. Approximately 25% of the patients present with metastatic disease at presentation. In the era of immunotherapy (interferon alpha-2b and interleukin-2), studies showed significant survival benefit with cytoreductive nephrectomy (CRN) followed by interferon alpha-2b than interferon alpha 2-b alone. Introduction of targeted therapies (vascular endothelial growth factor receptor-tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors) in 2005 generated a great interest in the management of metastatic renal cell carcinoma (mRCC) as these drugs exhibited tumour shrinkage in the primary tumour as well as in the metastatic site/s. Though there is no level 1 evidence, many studies have shown the usefulness of cytoreductive nephrectomy along with targeted therapy as against to targeted therapy alone. This review is aimed at the rationale behind the cytoreductive nephrectomy in mRCC, the current evidence and what is in store for the future. A detailed search on the management of mRCC was carried out on MEDLINE, Embase, CANCERLIT and Cochrane Library databases using the key words "cytoreductive nephrectomy", "immunotherapy" and "targeted therapy" since 1980 till 2015. Original articles, review articles, monograms, book chapters on metastatic renal cancer and textbooks on urologic oncology, oncology and urology were reviewed. Various international guidelines on this issue were also studied. An identical search was performed using the American Society of Clinical Oncology Abstract database. Trials in the progress or recently completed that were relevant to this paper were identified through clinicaltrials.gov. The latest information for new articles ahead of publication was last accessed in November 2015. CRN has remained an integral part to the management of metastatic renal cell carcinoma mainly for the patients with good performance status, life expectancy of more than 12 months and in the absence of adverse prognostic factors. It had shown measurable survival benefit in the era of immunotherapy (CRN + immunotherapy vs. immunotherapy alone). In the era of targeted therapy, many studies have shown significant survival benefit with CRN + targeted therapy. However, there is no clear level 1 evidence to support this. The ongoing trials (CARMENA and European Organisation for Research and Treatment of Cancer SURTIME) would perhaps guide us in the way in which we should manage mRCC disease in the future. Maybe we may find some answers on the issues of the effectiveness of targeted therapy, the timing of CRN and sequencing these treatment arms once the results of these ongoing and future trials are through.
Imbert, Isabelle; Botto, Jean-Marie; Farra, Claude D; Domloge, Nouha
2012-06-01
Telomere shortening is considered as one of the main characteristics of cellular aging by limiting cellular division. Besides the fundamental advances through the discoveries of telomere and telomerase, which were recognized by a Nobel Prize, telomere protection remains an essential area of research. Recently, it was evidenced that studying the cross-talks between the proteins associated with telomere should provide a better understanding of the mechanistic basis for telomere-associated aging phenotypes. In this review, we discuss the current knowledge on telomere shortening, telomerase activity, and the essential role of telomere binding proteins in telomere stabilization and telomere-end protection. This review highlights the capacity of telomere binding proteins to limit cellular senescence and to maintain skin tissue homeostasis, which is of key importance to reduce accelerated tissue aging. Future studies addressing telomere protection and limitation of DNA damage response in human skin should include investigations on telomere binding proteins. As little is known about the expression of telomere binding proteins in human skin and modulation of their expression with aging, it remains an interesting field of skin research and a key area for future skin protection and anti-aging developments. © 2012 Wiley Periodicals, Inc.
Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A; Huang, Yongping; Tan, Anjiang
2017-04-15
We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 ( ie-1 ) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy. IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species. Copyright © 2017 Chen et al.
Not Just Fun and Games: Toy Advertising on Television Targeting Children Promotes Sedentary Play.
Potvin Kent, Monique; Velkers, Clive
2017-10-01
To examine the volume of television toy advertising targeting Canadian children and to determine if it promotes active or sedentary play, targets males or females more frequently, and has changed over time. Data for toy/game advertising from 27 television stations in Toronto for the month of May in 2006 and 2013 were licensed from Neilsen Media Research (Montreal, Quebec, Canada). A content analysis was performed on all ads to determine what age group and gender were targeted and whether physical or sedentary activity was being promoted. Comparisons were made between 2006 and 2013. There were 3.35 toy ads/h/children's specialty station in 2013 (a 15% increase from 2006). About 88% of toy ads promoted sedentary play in 2013, a 27% increase from 2006 levels, while toy ads promoting active play decreased by 33%. In both 2006 and 2013, a greater number of sedentary toy ads targeted males (n = 1519, May 2006; n = 2030, May 2013) compared with females (n = 914, May 2006; n = 1619, May 2013), and between 2006 and 2013, these ads increased significantly for both males and females. Future research should explore whether such advertising influences children's preferences for activities and levels of physical activity.
Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A.
2017-01-01
ABSTRACT We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 (ie-1) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy. IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species. PMID:28122981
Fatty Acid Synthase Activity as a Target for c-Met Driven Prostate Cancer
2013-07-01
to aid future studies. Identification is a highly significant finding with regard to the potential for future therapeutic development targeted at...Met trafficking, stability, and ultimately oncogenic potential . Palmitoylation defective mutants will be used in animal models of c-Met driven tumor...growth (Aim 2). In addition, future work toward identifying the enzyme responsible for palmitoylation of c- Met will provide a new specific target
Past Strategies and Future Directions for Identifying AMP-Activated Protein Kinase (AMPK) Modulators
Sinnett, Sarah E.; Brenman, Jay E.
2014-01-01
AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs. PMID:24583089
The NASA Materials Science Research Program: It's New Strategic Goals and Opportunities
NASA Technical Reports Server (NTRS)
Schlagheck, Ronald A.; Stagg, Elizabeth
2004-01-01
In the past year, the NASA s Office of Biological and Physical Research (OBPR) has formulated a long term plan to perform strategical and fundamental research bringing together physics, chemistry, biology, and engineering to solve problems needed for current and future agency mission goals. Materials Science is one of basic disciplines within the Enterprise s Division of Physical Sciences Research. The Materials Science Program participates to utilize effective use of International Space Station (ISS) and various world class ground laboratory facilities to solve new scientific and technology questions and transfer these results for public and agency benefits. The program has recently targeted new investigative research in strategic areas necessary to expand NASA knowledge base for exploration of the universe and some of these experiments will need access to the microgravity of space. The program is implementing a wide variety of traditional ground and flight based research related types of fundamental science related to materials crystallization, fundamental processing, and properties characterization in order to obtain basic understanding of various phenomena effects and relationships to the structures, processing, and properties of materials. , In addition new initiatives in radiation protection, materials for propulsion and In-space fabrication and repair focus on research helping the agency solve problems needed for future transportation into the solar system. A summary of the types and sources for this research is presented including those experiments planned for a low gravity environment. Areas to help expand the science basis for NASA future missions are described. An overview of the program is given including the scope of the current and future NASA Research Announcements with emphasis on new materials science initiatives. A description of the planned flight experiments to be conducted on the International Space Station program along with the planned facility class Materials Science Research Rack (MSRR) and Microgravity Glovebox (MSG) type investigations. Some initial results from the first three materials experiments are given.
Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry
2014-01-01
We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets' locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research.
Who confronts prejudice?: the role of implicit theories in the motivation to confront prejudice.
Rattan, Aneeta; Dweck, Carol S
2010-07-01
Despite the possible costs, confronting prejudice can have important benefits, ranging from the well-being of the target of prejudice to social change. What, then, motivates targets of prejudice to confront people who express explicit bias? In three studies, we tested the hypothesis that targets who hold an incremental theory of personality (i.e., the belief that people can change) are more likely to confront prejudice than targets who hold an entity theory of personality (i.e., the belief that people have fixed traits). In Study 1, targets' beliefs about the malleability of personality predicted whether they spontaneously confronted an individual who expressed bias. In Study 2, targets who held more of an incremental theory reported that they would be more likely to confront prejudice and less likely to withdraw from future interactions with an individual who expressed prejudice. In Study 3, we manipulated implicit theories and replicated these findings. By highlighting the central role that implicit theories of personality play in targets' motivation to confront prejudice, this research has important implications for intergroup relations and social change.
Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank
2016-07-22
Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets.
Influences on Adoption of Greenhouse Gas Reduction Targets among US States, 1998-2008
Cale, Tabitha M.; Reams, Margaret A.
2016-01-01
While the United States has not established federal regulations for greenhouse gas (GHG) reduction targets, many US states have adopted their own standards and guidelines. In this study we examine state adoption of targets for GHG reductions during the ten-year period of 1998–2008, and identify factors that explain variation in target adoption. Potential influences are drawn from research from the public policy formulation and diffusion literature, and from studies specific to climate policy adoption. Potential influences on GHG reduction efforts among US states include socioeconomic attributes of residents, political and ideological orientations of citizens and state government, interest group activities, environmental pressures, and proximity to other states that have adopted GHG reduction targets. The findings of the multinomial logistic regression analysis indicate that states are more likely to adopt GHG reduction targets if they share a border with another state with a similar climate program and if their citizens are more ideologically liberal. Other factors including socioeconomic resources and interest group activities were not found to be associated with policy adoption. The findings yield insights into the conditions under which states are more likely to take action to reduce GHG’s, and are relevant both to state policy makers and residents with an interest in climate planning, and for researchers attempting to estimate future greenhouse gas reduction scenarios. PMID:27471657
Bar-Zeev, Maya; Livney, Yoav D; Assaraf, Yehuda G
2017-03-01
Intrinsic anticancer drug resistance appearing prior to chemotherapy as well as acquired resistance due to drug treatment, remain the dominant impediments towards curative cancer therapy. Hence, novel targeted strategies to overcome cancer drug resistance constitute a key aim of cancer research. In this respect, targeted nanomedicine offers innovative therapeutic strategies to overcome the various limitations of conventional chemotherapy, enabling enhanced selectivity, early and more precise cancer diagnosis, individualized treatment as well as overcoming of drug resistance, including multidrug resistance (MDR). Delivery systems based on nanoparticles (NPs) include diverse platforms enabling a plethora of rationally designed therapeutic nanomedicines. Here we review NPs designed to enhance antitumor drug uptake and selective intracellular accumulation using strategies including passive and active targeting, stimuli-responsive drug activation or target-activated release, triggered solely in the cancer cell or in specific organelles, cutting edge theranostic multifunctional NPs delivering drug combinations for synergistic therapy, while facilitating diagnostics, and personalization of therapeutic regimens. In the current paper we review the recent findings of the past four years and discuss the advantages and limitations of the various novel NPs-based drug delivery systems. Special emphasis is put on in vivo study-based evidences supporting significant therapeutic impact in chemoresistant cancers. A future perspective is proposed for further research and development of complex targeted, multi-stage responsive nanomedical drug delivery systems for personalized cancer diagnosis and efficacious therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
A Method for Analyzing Commonalities in Clinical Trial Target Populations
He, Zhe; Carini, Simona; Hao, Tianyong; Sim, Ida; Weng, Chunhua
2014-01-01
ClinicalTrials.gov presents great opportunities for analyzing commonalities in clinical trial target populations to facilitate knowledge reuse when designing eligibility criteria of future trials or to reveal potential systematic biases in selecting population subgroups for clinical research. Towards this goal, this paper presents a novel data resource for enabling such analyses. Our method includes two parts: (1) parsing and indexing eligibility criteria text; and (2) mining common eligibility features and attributes of common numeric features (e.g., A1c). We designed and built a database called “Commonalities in Target Populations of Clinical Trials” (COMPACT), which stores structured eligibility criteria and trial metadata in a readily computable format. We illustrate its use in an example analytic module called CONECT using COMPACT as the backend. Type 2 diabetes is used as an example to analyze commonalities in the target populations of 4,493 clinical trials on this disease. PMID:25954450
Recent Advances in Targeted Therapy for Glioma.
Lin, Lin; Cai, Jinquan; Jiang, Chuanlu
2017-01-01
Gliomas are the most common primary malignant brain tumors, which have a universally fatal outcome. Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment. This article reviewed the researches focused on the advanced strategies of various target therapies for improving the glioma treatment efficacy, and discussed the challenges and future directions for glioma therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Ishii, Masaru
2017-07-01
Recent advances in the bioengineering of monoclonal antibodies (mAbs) have revolutionized the treatment of several immunological and rheumatic diseases. mAbs exhibit high specificity and affinity, and are very effective targeting agents, associated with minimal off-target adverse effects. Of several relevant immunological diseases, rheumatoid arthritis was the condition initially treated with mAbs, with great success. Currently, many immunological disorders are targeted and successfully treated using such novel approaches; these include inflammatory bowel diseases, multiple sclerosis, lupus and psoriasis. Today, the efforts of researchers in basic immunology (with a long history) have borne fruit; bioengineered mAbs are employed in clinical practice. In this brief review, I will describe the current and emerging therapeutic mAbs and molecular targeted agents, and discuss the future of the field, especially from the viewpoint of pharmacology. © 2017 The British Pharmacological Society.
Rouillard, Andrew D; Hurle, Mark R; Agarwal, Pankaj
2018-05-01
Target selection is the first and pivotal step in drug discovery. An incorrect choice may not manifest itself for many years after hundreds of millions of research dollars have been spent. We collected a set of 332 targets that succeeded or failed in phase III clinical trials, and explored whether Omic features describing the target genes could predict clinical success. We obtained features from the recently published comprehensive resource: Harmonizome. Nineteen features appeared to be significantly correlated with phase III clinical trial outcomes, but only 4 passed validation schemes that used bootstrapping or modified permutation tests to assess feature robustness and generalizability while accounting for target class selection bias. We also used classifiers to perform multivariate feature selection and found that classifiers with a single feature performed as well in cross-validation as classifiers with more features (AUROC = 0.57 and AUPR = 0.81). The two predominantly selected features were mean mRNA expression across tissues and standard deviation of expression across tissues, where successful targets tended to have lower mean expression and higher expression variance than failed targets. This finding supports the conventional wisdom that it is favorable for a target to be present in the tissue(s) affected by a disease and absent from other tissues. Overall, our results suggest that it is feasible to construct a model integrating interpretable target features to inform target selection. We anticipate deeper insights and better models in the future, as researchers can reuse the data we have provided to improve methods for handling sample biases and learn more informative features. Code, documentation, and data for this study have been deposited on GitHub at https://github.com/arouillard/omic-features-successful-targets.
Heifetz, Alexander; Schertler, Gebhard F X; Seifert, Roland; Tate, Christopher G; Sexton, Patrick M; Gurevich, Vsevolod V; Fourmy, Daniel; Cherezov, Vadim; Marshall, Fiona H; Storer, R Ian; Moraes, Isabel; Tikhonova, Irina G; Tautermann, Christofer S; Hunt, Peter; Ceska, Tom; Hodgson, Simon; Bodkin, Mike J; Singh, Shweta; Law, Richard J; Biggin, Philip C
2015-08-01
G-protein coupled receptors (GPCRs) are the targets of over half of all prescribed drugs today. The UniProt database has records for about 800 proteins classified as GPCRs, but drugs have only been developed against 50 of these. Thus, there is huge potential in terms of the number of targets for new therapies to be designed. Several breakthroughs in GPCRs biased pharmacology, structural biology, modelling and scoring have resulted in a resurgence of interest in GPCRs as drug targets. Therefore, an international conference, sponsored by the Royal Society, with world-renowned researchers from industry and academia was recently held to discuss recent progress and highlight key areas of future research needed to accelerate GPCR drug discovery. Several key points emerged. Firstly, structures for all three major classes of GPCRs have now been solved and there is increasing coverage across the GPCR phylogenetic tree. This is likely to be substantially enhanced with data from x-ray free electron sources as they move beyond proof of concept. Secondly, the concept of biased signalling or functional selectivity is likely to be prevalent in many GPCRs, and this presents exciting new opportunities for selectivity and the control of side effects, especially when combined with increasing data regarding allosteric modulation. Thirdly, there will almost certainly be some GPCRs that will remain difficult targets because they exhibit complex ligand dependencies and have many metastable states rendering them difficult to resolve by crystallographic methods. Subtle effects within the packing of the transmembrane helices are likely to mask and contribute to this aspect, which may play a role in species dependent behaviour. This is particularly important because it has ramifications for how we interpret pre-clinical data. In summary, collaborative efforts between industry and academia have delivered significant progress in terms of structure and understanding of GPCRs and will be essential for resolving problems associated with the more difficult targets in the future.
Strandroth, Johan
2015-03-01
When targeting a society free from serious and fatal road-traffic injuries, it has been a common practice in many countries and organizations to set up time-limited and quantified targets for the reduction of fatalities and injuries. In setting these targets EU and other organizations have recognized the importance to monitor and predict the development toward the target as well as the efficiency of road safety policies and interventions. This study aims to validate a method to forecast future road safety challenges by applying it to the fatal crashes in Sweden in 2000 and using the method to explain the change in fatalities based on the road safety interventions made until 2010. The estimation of the method is then compared to the true outcome in 2010. The aim of this study was to investigate if a residual of crashes produced by a partial analysis could constitute a sufficient base to describe the characteristics of future crashes. show that out of the 332 car occupants killed in 2000, 197 were estimated to constitute the residual in 2010. Consequently, 135 fatalities from 2000 were estimated by the model to be prevented by 2010. That is a predicted reduction of 41% compared to the reduction in the real outcome of 53%, from 332 in 2000 to 156 in 2010. The method was found able to generate a residual of crashes in 2010 from the crashes in 2000 that had a very similar nature, with regards to crash type, as the true outcome of 2010. It was also found suitable to handle double counting and system effects. However, future research is needed in order to investigate how external factors as well as random and systematic variation should be taken into account in a reliable manner. Copyright © 2015 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wallner, Paul E., E-mail: pwallner@theabr.org; Anscher, Mitchell S.; Barker, Christopher A.
In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective ofmore » relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report.« less
Wallner, Paul E; Anscher, Mitchell S; Barker, Christopher A; Bassetti, Michael; Bristow, Robert G; Cha, Yong I; Dicker, Adam P; Formenti, Silvia C; Graves, Edward E; Hahn, Stephen M; Hei, Tom K; Kimmelman, Alec C; Kirsch, David G; Kozak, Kevin R; Lawrence, Theodore S; Marples, Brian; McBride, William H; Mikkelsen, Ross B; Park, Catherine C; Weidhaas, Joanne B; Zietman, Anthony L; Steinberg, Michael
2014-01-01
In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report. Copyright © 2014 Elsevier Inc. All rights reserved.
Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe
2015-11-01
Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.
New advances in targeted gastric cancer treatment
Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian
2016-01-01
Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417
Master plans for pedestrian and bicycle transportation: community characteristics.
Steinman, Lesley; Doescher, Mark; Levinger, David; Perry, Cynthia; Carter, Louise; Eyler, Amy; Aytur, Semra; Cradock, Angie L I; Evenson, Kelly R; Heinrich, Katie; Kerr, Jacqueline; Litt, Jill; Severcan, Yucel; Voorhees, Carolyn
2010-03-01
Recent research demonstrates the importance of targeting the built environment to support individual physical activity, particularly for people experiencing health disparities. Master plans to promote biking and/or pedestrians (BPMPs) are a potential method for environmental change. This descriptive study aims to provide a snapshot of plan attributes and better understand demographic, social and transportation characteristics of communities with BPMPs. We collected a census sample of BPMPs from 4 states. Population and commuting data were obtained from national statistics. 294 master plans were included, with most plans representing municipalities. 62% of plans targeted biking only, one-fifth targeted biking and walking, and 15% targeted walking only. The sampled locations have a similar demographic profile as the overall U.S. for median age and household income, people of color, high school education, and income inequality. The degree of racial diversity of sampled communities is slightly less than the U.S. average and the percentage of people who walk to work were slightly higher. Given that communities with master plans have a similar profile as the overall U.S., BPMPs could feasibly be spread to communities throughout the country. Further research is planned to describe BPMPs in detail toward informing future plan development.
New advances in targeted gastric cancer treatment.
Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian
2016-08-14
Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.
Evidence-Based Reading Instruction for Individuals with Autism Spectrum Disorders
Whalon, Kelly J.; Al Otaiba, Stephanie; Delano, Monica E.
2009-01-01
Legislation mandates that all children, including children with autism spectrum disorders (ASD) be taught to read in ways that are consistent with reading research, and target the five components of evidence-based reading instruction: phonemic awareness, phonics, reading fluency, vocabulary and comprehension strategies. The purpose of this review is to synthesize the literature on reading instruction for children with ASD that encompasses one or more of the five components of reading. The review yielded 11 studies with 61 participants ages 4 to 17. Results indicate that children with ASD can benefit from reading instruction consistent with reading research. Research in this area is still preliminary, and more research is needed to guide practice. Possible directions for future research are provided. PMID:20161582
VALUE: A trans-disciplinary research project - and some challenges in its implementation
NASA Astrophysics Data System (ADS)
Huebener, Heike
2013-04-01
The EU-COST-action VALUE ("Validating and Integrating Downscaling Methods for Climate Change Research") is composed as a trans-disciplinary network activity, meaning that stakeholders and end-users not only from different scientific disciplines (i.e. inter-disciplinary research) but also from outside science are included in the design, planning and progress of the project. This gives the optimal chance to produce really workable project results for the intended end-users. However, some considerable challenges lie this way. These challenges start with identifying and motivating the target-stakeholders, they cover communication in different user-specific languages and reach as far as the question of the freedom of research when under the prompting of politics or economy. We will cover only some of the mentioned challenges; focusing on the identification of the target-stakeholders or end-users, their motivation to participate in the project and on some typical problems arising in this constellation. First experiences from the project will be presented. The aim of the presentation is to instigate discussion on developing workable project structures for trans-disciplinary research, as this will become more and more relevant in future research funding.
Plummer, Sara-Beth; Findley, Patricia A
2012-01-01
While studies suggest that the rate of abuse of women with disabilities is similar or higher compared to the general population, there continues to be a lack of attention to this issue. Women with disabilities are at particularly high risk of abuse, both through typical forms of violence (physical, sexual, and emotional) and those that target one's disability. In an effort to highlight the need for increased attention to this issue, this article reviews the current peer-reviewed research in this field. The authors outline recommendations for future research goals and provide implications for research, practice, and policy.
Breaugh, James A
2013-01-01
The way an organization recruits can influence the type of employees it hires, how they perform, and their retention rate. This article provides a selective review of research that has addressed recruitment targeting, recruitment methods, the recruitment message, recruiters, the organizational site visit, the job offer, and the timing of recruitment actions. These and other topics (e.g., the job applicant's perspective) are discussed in terms of their potential influence on prehire (e.g., the quality of job applicants) and posthire (e.g., new employee retention) recruitment outcomes. In reviewing research, attention is given to the current state of scientific knowledge, limitations of previous research, and important issues meriting future investigation.
NASA Technical Reports Server (NTRS)
Johnson, Walter W.; Liao, Min-Ju; Granada, Stacie
2003-01-01
This study investigated visual search performance for target aircraft symbols on a Cockpit Display of Traffic Information (CDTI). Of primary interest was the influence of target brightness (intensity) and highlighting validity (search directions) on the ability to detect a target aircraft among distractor aircraft. Target aircraft were distinguished by an airspace course that conflicted with Ownship (that is, the participant's aircraft). The display could present all (homogeneous) bright aircraft, all (homogeneous) dim aircraft, or mixed bright and dim aircraft, with the target aircraft being either bright or dim. In the mixed intensity condition, participants may or may not have been instructed whether the target was bright or dim. Results indicated that highlighting validity facilitated better detection times. However, instead of bright targets being detected faster, dim targets were found to be detected more slowly in the mixed intensity display than in the homogeneous display. This relative slowness may be due to a delay in confirming the dim aircraft to be a target when it it was among brighter distractor aircraft. This hypothesis will be tested in future research. Funding for this work was provided by the Advanced Air Transportation Technologies Project of NASA's Airspace Operation Systems Program.
Commissioning a Rotating Target Wheel Assembly for Heavy Element Studies
NASA Astrophysics Data System (ADS)
Fields, L. D.; Bennett, M. E.; Mayorov, D. A.; Folden, C. M.
2013-10-01
The heaviest elements are produced artificially by fusing nuclei of light elements within an accelerator to form heavier nuclei. The most direct method to increase the production rate of nuclei is to increase the beam intensity, necessitating the use of a rotating target to minimize damage to the target by deposited heat. Such a target wheel was constructed for heavy element research at Texas A&M University, Cyclotron Institute, consisting of a wheel with three banana-shaped target cutouts. The target is designed to rotate at 1700 rpm, and a fiber optic cable provides a signal to trigger beam pulsing in order to avoid irradiating the spokes between target segments. Following minor mechanical modifications and construction of a dedicated electrical panel, the rotating target assembly was commissioned for a beam experiment. A 15 MeV/u beam of 20Ne was delivered from the K500 cyclotron and detected by a ruggedized silicon detector. The beam pulsing response time was characterized as a function of the rational frequency of the target wheel. Preliminary analysis suggests that the K500 is capable of pulsing at rates of up to 250 Hz, which is sufficient for planned future experiments. Funded by DOE and NSF-REU Program.
Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease
Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter
2016-01-01
Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799
Antiadhesion agents against Gram-positive pathogens.
Cascioferro, Stella; Cusimano, Maria Grazia; Schillaci, Domenico
2014-01-01
A fundamental step of Gram-positive pathogenesis is the bacterial adhesion to the host tissue involving interaction between bacterial surface molecules and host ligands. This review is focused on antivirulence compounds that target Gram-positive adhesins and on their potential development as therapeutic agents alternative or complementary to conventional antibiotics in the contrast of pathogens. In particular, compounds that target the sortase A, wall theicoic acid inhibitors, carbohydrates able to bind bacterial proteins and proteins capable of influencing the bacterial adhesion, were described. We further discuss the advantages and disadvantages of this strategy in the development of novel antimicrobials and the future perspective of this research field still at its first steps.
Summary of Tactile User Interfaces Techniques and Systems
NASA Technical Reports Server (NTRS)
Spirkovska, Lilly
2005-01-01
Mental workload can be de.ned as the ratio of demand to allocated resources. Multiple-resource theory stresses the importance of distribution of tasks and information across various human sensory channels to reduce mental workload. One sensory channel that has been of interest since the late 1800s is touch. Unlike the more typical displays that target vision or hearing, tactile displays present information to the user s sense of touch. We present a summary of different methods for tactile display, historic and more recent systems that incorporate tactile display for information presentation, advantages and disadvantages of targeting the tactile channel, and future directions in tactile display research.
Summary of Tactile User Interfaces Techniques and Systems
NASA Technical Reports Server (NTRS)
Spirkovska, Lilly
2004-01-01
Mental workload can be defined as the ratio of demand to allocated resources. Multiple- resource theory stresses the importance of distribution of tasks and information across various sensory channels of the human to reduce mental workload. One sensory channel that has been of interest since the late 1800s is touch. Unlike the more typical displays that target vision or hearing, tactile displays present information to the user s sense of touch. We present a summary of different methods for tactile display; historic and more recent systems that incorporate tactile display for information presentation; advantages and disadvantages of targeting the tactile channel; and future directions in tactile display research.
Weiss, Emily; Wilson, Sandra
2003-01-01
A variety of nonhuman animals in zoo and research settings have been the subjects of classical and operant conditioning techniques. Much of the published work has focused on mammals, husbandry training, and veterinary issues. However, several zoos are training reptiles and birds for similar procedures, but there has been little of this work published. Using positive reinforcement techniques enabled the training of 2 male and 2 female Aldabra tortoises (Geochelone gigantea) to approach a target, hold steady on target, and stretch and hold for venipuncture. This article discusses training techniques, venipuncture sight, and future training.
The four hundred years of planetary science since Galileo and Kepler.
Burns, Joseph A
2010-07-29
For 350 years after Galileo's discoveries, ground-based telescopes and theoretical modelling furnished everything we knew about the Sun's planetary retinue. Over the past five decades, however, spacecraft visits to many targets transformed these early notions, revealing the diversity of Solar System bodies and displaying active planetary processes at work. Violent events have punctuated the histories of many planets and satellites, changing them substantially since their birth. Contemporary knowledge has finally allowed testable models of the Solar System's origin to be developed and potential abodes for extraterrestrial life to be explored. Future planetary research should involve focused studies of selected targets, including exoplanets.
Parametric investigations of target normal sheath acceleration experiments
NASA Astrophysics Data System (ADS)
Zani, Alessandro; Sgattoni, Andrea; Passoni, Matteo
2011-10-01
One of the most important challenges related to laser-driven ion acceleration research is to actively control some important ion beam features. This is a peculiar topic in the light of future possible technological applications. In the present work we make use of one theoretical model for target normal sheath acceleration in order to reproduce recent experimental parametric studies about maximum ion energy dependencies on laser parameters. The key role played by pulse energy and intensity is enlightened. Finally the effective dependence of maximum ion energy on intensity is evaluated using a combined theoretical approach, obtained by means of an analytical and a particle-in-cell numerical investigation.
Escalante, Derek A.; Wang, He; Fundakowski, Christopher E.
2016-01-01
ABSTRACT Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms. The discovery and characterization of novel fusion proteins in neoplasms originating from the thyroid, nasopharynx, salivary glands, and midline head and neck structures offer substantial contributions to our understanding of the pathogenesis and biological behavior of these neoplasms, while raising new therapeutic and diagnostic opportunities. Further characterization of these fusion proteins promises to facilitate advances on par with those already achieved with regard to hematologic malignancies in the precise, molecularly guided diagnosis and treatment of head and neck neoplasms. The following is a subsite specific review of the clinical implications of fusion proteins in head and neck neoplasms and the future potential for diagnostic targeting. PMID:27636353
Assessing the Generalizability of Randomized Trial Results to Target Populations
Stuart, Elizabeth A.; Bradshaw, Catherine P.; Leaf, Philip J.
2014-01-01
Recent years have seen increasing interest in and attention to evidence-based practices, where the “evidence” generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as “internal validity”), they do not always yield relevant information about the effects in a particular target population (known as “external validity”). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a pre-specified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of School-wide Positive Behavioral Interventions and Supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population. PMID:25307417
Assessing the generalizability of randomized trial results to target populations.
Stuart, Elizabeth A; Bradshaw, Catherine P; Leaf, Philip J
2015-04-01
Recent years have seen increasing interest in and attention to evidence-based practices, where the "evidence" generally comes from well-conducted randomized trials. However, while those trials yield accurate estimates of the effect of the intervention for the participants in the trial (known as "internal validity"), they do not always yield relevant information about the effects in a particular target population (known as "external validity"). This may be due to a lack of specification of a target population when designing the trial, difficulties recruiting a sample that is representative of a prespecified target population, or to interest in considering a target population somewhat different from the population directly targeted by the trial. This paper first provides an overview of existing design and analysis methods for assessing and enhancing the ability of a randomized trial to estimate treatment effects in a target population. It then provides a case study using one particular method, which weights the subjects in a randomized trial to match the population on a set of observed characteristics. The case study uses data from a randomized trial of school-wide positive behavioral interventions and supports (PBIS); our interest is in generalizing the results to the state of Maryland. In the case of PBIS, after weighting, estimated effects in the target population were similar to those observed in the randomized trial. The paper illustrates that statistical methods can be used to assess and enhance the external validity of randomized trials, making the results more applicable to policy and clinical questions. However, there are also many open research questions; future research should focus on questions of treatment effect heterogeneity and further developing these methods for enhancing external validity. Researchers should think carefully about the external validity of randomized trials and be cautious about extrapolating results to specific populations unless they are confident of the similarity between the trial sample and that target population.
Present Status and Future Prospects of Silicon Thin-Film Solar Cells
NASA Astrophysics Data System (ADS)
Konagai, Makoto
2011-03-01
In this report, an overview of the recent status of photovoltaic (PV) power generation is first presented from the viewpoint of reducing CO2 emission. Next, the Japanese roadmap for the research and development (R&D) of PV power generation and the progress in the development of various solar cells are explained. In addition, the present status and future prospects of amorphous silicon (a-Si) thin-film solar cells, which are expected to enter the stage of full-scale practical application in the near future, are described. For a-Si single-junction solar cells, the conversion efficiency of their large-area modules has now reached 6-8%, and their practical application to megawatt solar systems has started. Meanwhile, the focus of R&D has been shifting to a-Si and microcrystalline silicon (µc-Si) tandem solar cells. Thus far, a-Si/µc-Si tandem solar cell modules with conversion efficiency exceeding 13% have been reported. In addition, triple-junction solar cells, whose target year for practical application is 2025 or later, are introduced, as well as innovative thin-film full-spectrum solar cells, whose target year of realization is 2050.
Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.
Yang, Ye; Zhang, Jianyun; Yao, Yijun
2017-01-01
Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.
A content analysis of Internet resources about the risks of seafood consumption.
Henderson, Heather C; Hong, Jie; Friedman, Daniela B; Porter, Dwayne E; Halfacre, Angela C; Scott, Geoffrey I; Lead, Jamie R
2016-08-01
Seafood consumption is a main source of human exposure to certain environmental contaminants. Therefore, it is valuable to assess the online health risk messages focused on this topic, as people in the US are increasingly accessing the Internet for health-related information. Previous research indicates that online health information tends to be written at a reading level that is more advanced than ability of the general population. The purpose of this research was to examine the content and readability of Internet resources targeted toward consumers in the US regarding the health risks from consumption of contaminated seafood. Sources for analysis were gathered through a targeted search of state and national government websites, as well as through a Google search. The overall mean readability level was Grade 9.21, which is slightly above the average reading level of US adults. Future research should evaluate the accuracy of the health risk messages, as well as consumer perceptions of risk.
Effects of Background Pressure on Relativistic Laser-Plasma Interaction Ion Acceleration
NASA Astrophysics Data System (ADS)
Peterson, Andrew; Orban, C.; Feister, S.; Ngirmang, G.; Smith, J. T.; Klim, A.; Frische, K.; Morrison, J.; Chowdhury, E.; Roquemore, W. M.
2016-10-01
Typically, ultra-intense laser-accelerated ion experiments are carried out under high-vacuum conditions and with a repetition rate up to several shots per day. Looking to the future there is a need to perform these experiments with a much larger repetition rate. A continuously flowing liquid target is more suitable than a solid target for this purpose. However liquids vaporize below their vapor pressure, and the experiment cannot be performed under high-vacuum conditions. The effects of this non-negligible high chamber pressure acceleration of charged particles is not yet well understood. We investigate this phenomena using Particle-in-Cell simulations, exploring the effect of the background pressure on the accelerated ion spectrum. Experiments in this regime are being performed at the Air Force Research Laboratory at Wright-Patterson Air Force Base. This research was sponsored by the Quantum and Non-Equilibrium Processes Division of the Air Force Office of Scientific Research, under the management of Dr. Enrique Parra, Program Manager and significant support from the DOD HPCMP Internship Program.
CRISPR system for genome engineering: the application for autophagy study.
Cui, Jianzhou; Chew, Shirley Jia Li; Shi, Yin; Gong, Zhiyuan; Shen, Han-Ming
2017-05-01
CRISPR/Cas9 is the latest tool introduced in the field of genome engineering and is so far the best genome-editing tool as compared to its precedents such as, meganucleases, zinc finger nucleases (ZFNs) and transcription activator-like effectors (TALENs). The simple design and assembly of the CRISPR/Cas9 system makes genome editing easy to perform as it uses small guide RNAs that correspond to their DNA targets for high efficiency editing. This has helped open the doors for multiplexible genome targeting in many species that were intractable using old genetic perturbation techniques. Currently, The CRISPR system is revolutionizing the way biological researches are conducted and paves a bright future not only in research but also in medicine and biotechnology. In this review, we evaluated the history, types and structure, the mechanism of action of CRISPR/Cas System. In particular, we focused on the application of this powerful tool in autophagy research. [BMB Reports 2017; 50(5): 247-256].
[Therapeutic strategies targeting brain tumor stem cells].
Toda, Masahiro
2009-07-01
Progress in stem cell research reveals cancer stem cells to be present in a variety of malignant tumors. Since they exhibit resistance to anticancer drugs and radiotherapy, analysis of their properties has been rapidly carried forward as an important target for the treatment of intractable malignancies, including brain tumors. In fact, brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods and isolation methods for side population (SP) cells, which have high drug-efflux capacity. Although the analysis of the properties of BCSCs is the most important to developing methods in treating BCSCs, the absence of BCSC purification methods should be remedied by taking it up as an important research task in the immediate future. Thus far, there are no effective treatment methods for BCSCs, and several treatment methods have been proposed based on the cell biology characteristics of BCSCs. In this article, I outline potential treatment methods damaging treatment-resistant BCSCs, including immunotherapy which is currently a topic of our research.
ASHA-Life Intervention Perspectives Voiced by Rural Indian Women Living With AIDS.
Nyamathi, Adeline; Ekstrand, Maria; Srivastava, Neha; Carpenter, Catherine L; Salem, Benissa E; Al-Harrasi, Shawana; Ramakrishnan, Padma; Sinha, Sanjeev
2016-01-01
In this focus group study, we explored the experiences of 16 rural women living with AIDS (WLA) who participated in the Asha-Life (AL) intervention to gain an understanding of the environmental, psychosocial, and cultural impact of the AL on their lives. Four themes emerged among AL participants: (a) the importance of tangible support, (b) need for social support, (c) ongoing challenges to accessing antiretroviral therapy (ART), and (d) perspectives on future programs. Our research findings support the development of future programs targeting mother-child dyads which emphasize nutritional knowledge, while reducing barriers to receiving ART, and physical, emotional, and financial support.
Beyond 2013 - The Future of European Scientific Drilling Research - An introduction.
NASA Astrophysics Data System (ADS)
Camoin, G.; Stein, R.
2009-04-01
The Integrated Ocean Drilling Program (IODP) is funded for the period 2003-2013, and is now starting to plan the future of ocean drilling beyond 2013, including the development of new technologies, new emerging research fields as and the societal relevance of this programme. In this context an interdisciplinary and multinational (USA, Europe, Japan, Asian and Oceanian countries), key conference - INVEST IODP New Ventures in Exploring Scientific Targets - addressing all international IODP partners is therefore planned for September 23rd-25th 2009 in Bremen, Germany (more information at http://www.iodp.org and http://marum.de/iodp-invest.html) to discuss future directions of ocean drilling research and related aspects such as ventures with related programmes or with industry. The first critical step of INVEST is to define the scientific research goals of the second phase of the Integrated Ocean Drilling Program (IODP), which is expected to begin in late 2013. INVEST will be open to all interested scientists and students and will be the principal opportunity for the international science community to help shape the future of scientific ocean drilling. The outcome of the conference will be the base to draft a science plan in 2010 and to define new goals and strategies to effectively meet the challenges of society and future ocean drilling. The current EGU Session and the related two days workshop which will be held at the University of Vienna will specifically address the future of European scientific drilling research. The major objectives of those two events are to sharpen the European interests in the future IODP and to prepare the INVEST Conference and are therefore of prime importance to give weight to the European propositions in the program renewal processes, both on science, technology and management, and to provide the participants with information about the status/process of ongoing discussions and negotiations regarding program structure, and provide them with the expected framework (available drilling platforms and anticipated funding levels). The key items that should be addressed during the EGU Session and the workshop will especially include : (1) The future of ECORD (science, technology, management). (2) New research initiatives and emerging fields in scientific drilling (3) Relationships between IODP and other programs (e.g. ICDP, IMAGES etc). (4) Collaboration between academia and industry. (5) New technologies and the Mission Specific Platform approach.
Jiang, Yu; Simon, Steve; Mayo, Matthew S; Gajewski, Byron J
2015-02-20
Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research. Copyright © 2014 John Wiley & Sons, Ltd.
Increased experience amplifies the activation of task-irrelevant category representations.
Wu, Rachel; Pruitt, Zoe; Zinszer, Benjamin D; Cheung, Olivia S
2017-02-01
Prior research has demonstrated the benefits (i.e., task-relevant attentional selection) and costs (i.e., task-irrelevant attentional capture) of prior knowledge on search for an individual target or multiple targets from a category. This study investigated whether the level of experience with particular categories predicts the degree of task-relevant and task-irrelevant activation of item and category representations. Adults with varying levels of dieting experience (measured via 3 subscales of Disinhibition, Restraint, Hunger; Stunkard & Messick, Journal of Psychosomatic Research, 29(1), 71-83, 1985) searched for targets defined as either a specific food item (e.g., carrots), or a category (i.e., any healthy or unhealthy food item). Apart from the target-present trials, in the target-absent "foil" trials, when searching for a specific item (e.g., carrots), irrelevant items from the target's category (e.g., squash) were presented. The ERP (N2pc) results revealed that the activation of task-relevant representations (measured via Exemplar and Category N2pc amplitudes) did not differ based on the degree of experience. Critically, however, increased dieting experience, as revealed by lower Disinhibition scores, predicted activation of task-irrelevant representations (i.e., attentional capture of foils from the target item category). Our results suggest that increased experience with particular categories encourages the rapid activation of category representations even when category information is task irrelevant, and that the N2pc in foil trials could potentially serve as an indication of experience level in future studies on categorization.
Targeting Hispanic populations: future research and prevention strategies.
Ramirez, A G; McAlister, A; Gallion, K J; Villarreal, R
1995-01-01
Minority populations face a wide variety of economic, institutional, and cultural barriers to health care. These barriers and low levels of education and income pose significant challenges for health professionals in developing cancer research and prevention-control strategies. It is suggested that specific segments of Hispanic populations fit the model of an underdeveloped country in the intermediate stage of epidemiological transition. Since noncommunicable diseases have not yet fully emerged in some of these Hispanic population segments, the opportunity exists to apply primordial prevention strategies. Such campaigns would focus on dissuading members of these populations from adopting negative health behaviors while promoting positive lifestyle choices. Optimal programs would increase cancer screening participation and discourage risk behaviors through community-oriented, population-based interventions. Future directions in prevention and control efforts for minority populations should include expanded health insurance coverage, improved access to health care, greater emphasis on minority recruitment in health care fields, focused epidemiologic and clinical research, and identification and replication of effective components within existing prevention-control programs. PMID:8741800
Towards Pervasive Augmented Reality: Context-Awareness in Augmented Reality.
Grubert, Jens; Langlotz, Tobias; Zollmann, Stefanie; Regenbrecht, Holger
2017-06-01
Augmented Reality is a technique that enables users to interact with their physical environment through the overlay of digital information. While being researched for decades, more recently, Augmented Reality moved out of the research labs and into the field. While most of the applications are used sporadically and for one particular task only, current and future scenarios will provide a continuous and multi-purpose user experience. Therefore, in this paper, we present the concept of Pervasive Augmented Reality, aiming to provide such an experience by sensing the user's current context and adapting the AR system based on the changing requirements and constraints. We present a taxonomy for Pervasive Augmented Reality and context-aware Augmented Reality, which classifies context sources and context targets relevant for implementing such a context-aware, continuous Augmented Reality experience. We further summarize existing approaches that contribute towards Pervasive Augmented Reality. Based our taxonomy and survey, we identify challenges for future research directions in Pervasive Augmented Reality.
Heymsfield, Steven B; Avena, Nicole M; Baier, Leslie; Brantley, Phillip; Bray, George A; Burnett, Lisa C; Butler, Merlin G; Driscoll, Daniel J; Egli, Dieter; Elmquist, Joel; Forster, Janice L; Goldstone, Anthony P; Gourash, Linda M; Greenway, Frank L; Han, Joan C; Kane, James G; Leibel, Rudolph L; Loos, Ruth J F; Scheimann, Ann O; Roth, Christian L; Seeley, Randy J; Sheffield, Val; Tauber, Maïthé; Vaisse, Christian; Wang, Liheng; Waterland, Robert A; Wevrick, Rachel; Yanovski, Jack A; Zinn, Andrew R
2014-02-01
Hyperphagia is a central feature of inherited disorders (e.g., Prader-Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments. International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates. The reviewed collective research and clinical experience provides a critical body of new and novel information on hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified. This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research. Copyright © 2013 The Obesity Society.
Heymsfield, Steven B.; Avena, Nicole M.; Baier, Leslie; Brantley, Phillip; Bray, George A.; Burnett, Lisa C.; Butler, Merlin G.; Driscoll, Daniel J.; Egli, Dieter; Elmquist, Joel; Forster, Janice L.; Goldstone, Anthony P.; Gourash, Linda M.; Greenway, Frank L.; Han, Joan C.; Kane, James G.; Leibel, Rudolph L.; Loos, Ruth J.F.; Scheimann, Ann O.; Roth, Christian L.; Seeley, Randy J.; Sheffield, Val; Tauber, Maïthé; Vaisse, Christian; Wang, Liheng; Waterland, Robert A.; Wevrick, Rachel; Yanovski, Jack A.; Zinn, Andrew R.
2014-01-01
Objective Hyperphagia is a central feature of inherited disorders (e.g., Prader–Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms and treatments. Substantial gaps in understanding the molecular basis of inherited hyperphagia syndromes are present as are a lack of mechanistic of mechanistic targets that can serve as a basis for pharmacologic and behavioral treatments. Design and Methods International conference with 28 experts, including scientists and caregivers, providing presentations, panel discussions, and debates. Results The reviewed collective research and clinical experience provides a critical body of new and novel information on hyperphagia at levels ranging from molecular to population. Gaps in understanding and tools needed for additional research were identified. Conclusions This report documents the full scope of important topics reviewed at a comprehensive international meeting devoted to the topic of hyperphagia and identifies key areas for future funding and research. PMID:24574081
CRISPR/Cas9 for genome editing: progress, implications and challenges.
Zhang, Feng; Wen, Yan; Guo, Xiong
2014-09-15
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) protein 9 system provides a robust and multiplexable genome editing tool, enabling researchers to precisely manipulate specific genomic elements, and facilitating the elucidation of target gene function in biology and diseases. CRISPR/Cas9 comprises of a nonspecific Cas9 nuclease and a set of programmable sequence-specific CRISPR RNA (crRNA), which can guide Cas9 to cleave DNA and generate double-strand breaks at target sites. Subsequent cellular DNA repair process leads to desired insertions, deletions or substitutions at target sites. The specificity of CRISPR/Cas9-mediated DNA cleavage requires target sequences matching crRNA and a protospacer adjacent motif locating at downstream of target sequences. Here, we review the molecular mechanism, applications and challenges of CRISPR/Cas9-mediated genome editing and clinical therapeutic potential of CRISPR/Cas9 in future. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
The 1999 Leonid Multi-Instrument Aircraft Campaign - An Early Review
NASA Astrophysics Data System (ADS)
Jenniskens, Peter; Butow, Steven J.; Fonda, Mark
Two B707-type research aircraft of the 452^nd Flight Test Squadron at Edwards Air Force Base were deployed to study the Leonid meteor storm of 1999 over the Mediterranean Sea on Nov. 18. The mission was sponsored by various science programs of NASA, and offered an international team of 35 researchers observing conditions free of clouds and low altitude extinction at a prime location for viewing the storm. This 1999 Leonid Multi-Instrument Aircraft Campaign followed a similar effort in 1998, improving upon mission strategy and scope. As before, spectroscopic and imaging experiments targeted meteors and persistent trains, but also airglow, aurora, elves and sprites. The research aimed to address outstanding questions in astrobiology, planetary science, astronomy, and upper atmospheric research. In addition, USAF co-sponsored the mission to provide near real-time flux measurements for space weather awareness. First results are presented in these issues of Earth, Moon, and Planets in preparation for future missions that will target the exceptional Leonid returns of 2001 and 2002. An early review of the scientific achievements in the context of campaign objectives is given.
Cunningham, Jennifer; Miller, Stephania T; Joosten, Yvonne; Elzey, Jared D; Israel, Tiffany; King, Christine; Luther, Patrick; Vaughn, Yolanda; Wilkins, Consuelo H
2015-10-01
The study goal is to highlight strategies for promoting relevance of research capacity-building efforts targeting community organizations (CO)s. Two community partners, representing two COs, were invited to participate in CO research development trainings, Community Research Forums (Forum)s. Their contributions were documented via Forum document review. Forum participants, representatives from other COs, completed post-Forum surveys to identify additional training needs and rate Forum impact relative to their training expectations. A content-based analysis and descriptive statistics were used to summarize needs assessment- and impact-related survey responses, respectively. Community partners were involved in eight Forum-related activities including marketing (planning), facilitation (implementation), and manuscript coauthorship (dissemination). Eighty-one individuals, representing 55 COs, attended the Forums. Needs assessment responses revealed a desire for additional assistance with existing Forum topics (e.g., defining research priorities) and a need for new ones (e.g., promoting organizational buy in for research). Ninety-one percent of participants agreed that the Forum demonstrated the value of research to COs and how to create a research agenda. Including community partners in all Forum phases ensured that CO perspectives were integrated throughout. Post-Forum needs and impact assessment results will help in tailoring, where needed, future training topics and strategies, respectively. © 2015 Wiley Periodicals, Inc.
Aging, the Central Nervous System, and Mobility in Older Adults: Interventions
Hausdorff, Jeffrey M.; Studenski, Stephanie A.; Rosano, Caterina; Camicioli, Richard; Alexander, Neil B.; Chen, Wen G.; Lipsitz, Lewis A.; Carlson, Michelle C.
2016-01-01
Background: Research suggests that the central nervous system (CNS) and mobility are closely linked. CNS-mediated mobility impairment may represent a potentially new and prevalent syndrome within the older adult populations. Interventions targeting this group may have the potential to improve mobility and cognition and prevent disability. Methods: In 2012, the Gerontological Society of America (GSA) and the National Institute on Aging (NIA) sponsored a 3-year conference workshop series, “Aging, the CNS, and Mobility.” The goal of this third and final conference was to (i) report on the state of the science of interventions targeting CNS-mediated mobility impairment among community-dwelling older adults and (ii) partnering with the NIA, explore the future of research and intervention design focused on a potentially novel aging syndrome. Results: Evidence was presented in five main intervention areas: (i) pharmacology and diet; (ii) exercise; (iii) electrical stimulation; (iv) sensory stimulation/deprivation; and (v) a combined category of multimodal interventions. Workshop participants identified important gaps in knowledge and key recommendations for future interventions related to recruitment and sample selection, intervention design, and methods to measure effectiveness. Conclusions: In order to develop effective preventive interventions for this prevalent syndrome, multidisciplinary teams are essential particularly because of the complex nature of the syndrome. Additionally, integrating innovative methods into the design of interventions may help researchers better measure complex mechanisms, and finally, the value of understanding the link between the CNS and mobility should be conveyed to researchers across disciplines in order to incorporate cognitive and mobility measurements into study protocols. PMID:27154905
Sohail, Muhammad Farhan; Rehman, Mubashar; Sarwar, Hafiz Shoaib; Naveed, Sara; Salman, Omer; Bukhari, Nadeem Irfan; Hussain, Irshad; Webster, Thomas J; Shahnaz, Gul
2018-01-01
The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research. PMID:29922053
Schaeffer, Nora Cate; Dykema, Jennifer
2011-01-01
We begin with a look back at the field to identify themes of recent research that we expect to continue to occupy researchers in the future. As part of this overview, we characterize the themes and topics examined in research about measurement and survey questions published in Public Opinion Quarterly in the past decade. We then characterize the field more broadly by highlighting topics that we expect to continue or to grow in importance, including the relationship between survey questions and the total survey error perspective, cognitive versus interactional approaches, interviewing practices, mode and technology, visual aspects of question design, and culture. Considering avenues for future research, we advocate for a decision-oriented framework for thinking about survey questions and their characteristics. The approach we propose distinguishes among various aspects of question characteristics, including question topic, question type and response dimension, conceptualization and operationalization of the target object, question structure, question form, response categories, question implementation, and question wording. Thinking about question characteristics more systematically would allow study designs to take into account relationships among these characteristics and identify gaps in current knowledge. PMID:24970951
Community challenges in biomedical text mining over 10 years: success, failure and the future.
Huang, Chung-Chi; Lu, Zhiyong
2016-01-01
One effective way to improve the state of the art is through competitions. Following the success of the Critical Assessment of protein Structure Prediction (CASP) in bioinformatics research, a number of challenge evaluations have been organized by the text-mining research community to assess and advance natural language processing (NLP) research for biomedicine. In this article, we review the different community challenge evaluations held from 2002 to 2014 and their respective tasks. Furthermore, we examine these challenge tasks through their targeted problems in NLP research and biomedical applications, respectively. Next, we describe the general workflow of organizing a Biomedical NLP (BioNLP) challenge and involved stakeholders (task organizers, task data producers, task participants and end users). Finally, we summarize the impact and contributions by taking into account different BioNLP challenges as a whole, followed by a discussion of their limitations and difficulties. We conclude with future trends in BioNLP challenge evaluations. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.
Sohail, Muhammad Farhan; Rehman, Mubashar; Sarwar, Hafiz Shoaib; Naveed, Sara; Salman, Omer; Bukhari, Nadeem Irfan; Hussain, Irshad; Webster, Thomas J; Shahnaz, Gul
2018-01-01
The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.
Kohl, Alain; Pondeville, Emilie; Schnettler, Esther; Crisanti, Andrea; Supparo, Clelia; Christophides, George K.; Kersey, Paul J.; Maslen, Gareth L.; Takken, Willem; Koenraadt, Constantianus J. M.; Oliva, Clelia F.; Busquets, Núria; Abad, F. Xavier; Failloux, Anna-Bella; Levashina, Elena A.; Wilson, Anthony J.; Veronesi, Eva; Pichard, Maëlle; Arnaud Marsh, Sarah; Simard, Frédéric; Vernick, Kenneth D.
2016-01-01
Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector–pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations. PMID:27677378
Zhao, Xiaoquan; Villagran, Melinda M; Kreps, Gary L; McHorney, Colleen
2012-01-01
This study investigated the joint effect of message framing and time perspective in adherence-promoting communication targeting patients with chronic diseases. Based on previous framing and time perspective research, it was hypothesized that the gain frame would show an advantage over the loss frame among future-oriented patients; for present-oriented patients, it was hypothesized that the framing effect would be relatively indistinct. In total, 1,108 currently nonadherent patients with chronic disease participated in an experiment where they were randomly assigned to either gain- or loss-framed messages addressing key beliefs underlying their nonadherence or a no-message control condition. Intention and attitude regarding future adherence as well as message perceptions were measured after message presentation. Results of this study generally supported the hypotheses. Message topics-whether the messages addressed patients' perceived need for medications or concerns about side effects-did not moderate the effect of framing or the interaction between framing and time perspective. Theoretical and practical implications are discussed.
Future therapeutic targets for the treatment and prevention of cholesterol gallstones.
Castro-Torres, Ibrahim Guillermo; de Jesús Cárdenas-Vázquez, René; Velázquez-González, Claudia; Ventura-Martínez, Rosa; De la O-Arciniega, Minarda; Naranjo-Rodríguez, Elia Brosla; Martínez-Vázquez, Mariano
2015-10-15
The formation of cholesterol gallstones involves very complex imbalances, such as alterations in the secretion of biliary lipids (which involves the ABCG5, ABCG8, ABCB4 and ABCB11 transporters), biochemical and immunological reactions in the gallbladder that produce biliary sludge (mucins), physicochemical changes in the structure of cholesterol (crystallization), alterations in gallbladder motility, changes in the intestinal absorption of cholesterol (ABCG5/8 transporters and Niemann-Pick C1L1 protein) and alterations in small intestine motility. Some of these proteins have been studied at the clinical and experimental levels, but more research is required. In this review, we discuss the results of studies on some molecules involved in the pathophysiology of gallstones that may be future therapeutic targets to prevent the development of this disease, and possible sites for treatment based mainly on the absorption of intestinal cholesterol (Niemann-Pick C1L1 and ABCG5/8 proteins). Copyright © 2015. Published by Elsevier B.V.
Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
Liu, Jie; Lee, Wen-hui; Zhang, Yun
2014-01-01
The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research. PMID:25105297
Maity, Amit Ranjan; Stepensky, David
2015-12-30
Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting. Copyright © 2015 Elsevier B.V. All rights reserved.
ERIC Educational Resources Information Center
Troutman, Frank H.; And Others
To assist educators and employers in manpower planning and development, this study attempted to provide a useful and comprehensive picture of the number and kinds of occupational skills needed in Arkansas in the next decade. The study estimated future manpower needs by applying a target year industry-occupational matrix to industry employment…
ERIC Educational Resources Information Center
Lewis, Mary Ellen James
A decade ago, the business community began to pursue tentative, new relationships with schools; the focus was on long-term educational improvement, frequently targeted to core academic subjects. Now partnerships are everywhere, involving thousands of schools and hundreds of thousands of local people. This essay discusses the resources brought to…
ERIC Educational Resources Information Center
Carey, Susan; And Others
Developing a constructivist view of scientific inquiry and knowledge is considered to be important to the training of future scientists, as well as to the understanding of scientific information by all citizens. The research reported targets the junior high school grades. Curricular materials that introduce seventh graders to the constructivist…
The Effect of Branding on the Success or Failure of Nonviolent Mass Movements
2015-06-12
future researchers and practitioners desiring to develop a system for the United States to use nonviolent mass movements to further policy... develop a brand for their organization? How do nonviolent mass movements develop a brand for their message? How do nonviolent mass movements enforce...phase, develop understanding of the issues, involves educating the target audience about the problems that will be addressed by the movement . The
Zhang, Hua; Uselman, Ryan R; Yee, Douglas
2011-05-01
Near-infrared fluorescent (NIRF) imaging is a rapidly growing research field which has the potential to be an important imaging modality in cancer diagnosis. Various exogenous NIR fluorophores have been developed for the technique, including small molecule fluorophores and nanoparticles. NIRF imaging has been used in animal models for the detection of cancer overthe last twenty years and has in recent years been used in human clinical trials. This article describes the types and characteristics of exogenous fluorophores available for in vivo fluorescent cancer imaging. The article also discusses the progression of NIRF cancer imaging over recent years and its future challenges, from both a biological and clinical perspective. in The review also looks at its application for lymph node mapping, tumor targeting and characterization, and tumor margin definition for surgical guidance. NIRF imaging is not in routine clinical cancer practice; yet, the authors predict that techniques using NIR fluorophores for tumor margin definition and lymph node mapping will enter clinical practice in the near future. The authors also anticipate that NIRF imaging research will lead to the development of flurophores with 'high brightness' that will overcome the limited penetration of this modality and be better suited for non invasive tumor targeting.
Johnson, Judith; Hall, Louise H; Berzins, Kathryn; Baker, John; Melling, Kathryn; Thompson, Carl
2018-02-01
Rising levels of burnout and poor well-being in healthcare staff are an international concern for health systems. The need to improve well-being and reduce burnout has long been acknowledged, but few interventions target mental healthcare staff, and minimal improvements have been seen in services. This review aimed to examine the problem of burnout and well-being in mental healthcare staff and to present recommendations for future research and interventions. A discursive review was undertaken examining trends, causes, implications, and interventions in burnout and well-being in healthcare staff working in mental health services. Data were drawn from national surveys, reports, and peer-reviewed journal articles. These show that staff in mental healthcare report poorer well-being than staff in other healthcare sectors. Poorer well-being and higher burnout are associated with poorer quality and safety of patient care, higher absenteeism, and higher turnover rates. Interventions are effective, but effect sizes are small. The review concludes that grounding interventions in the research literature, emphasizing the positive aspects of interventions to staff, building stronger links between healthcare organizations and universities, and designing interventions targeting burnout and improved patient care together may improve the effectiveness and uptake of interventions by staff. © 2017 Australian College of Mental Health Nurses Inc.
Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy.
Nogueira-Librelotto, Daniele R; Codevilla, Cristiane F; Farooqi, Ammad; Rolim, Clarice M B
2017-01-01
A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Their pain, our pleasure: stereotype content and schadenfreude.
Cikara, Mina; Fiske, Susan T
2013-09-01
People often fail to empathize with others, and sometimes even experience schadenfreude-pleasure at others' misfortunes. One potent predictor of schadenfreude is envy, which, according to the stereotype content model, is elicited by high-status, competitive targets. Here we review our recent research program investigating the relationships among stereotypes, envy, schadenfreude, and harm. Experiment 1 demonstrates that stereotypes are sufficient to influence affective responses to targets' misfortunes; participants not only report feeling less negative when misfortunes befall high-status, competitive targets as compared to other targets, they also smile more (assessed with facial EMG). Experiment 2 replicates the self-report findings from Experiment 1 and assesses behavioral tendencies toward envied targets; participants are more willing to endorse harming high-status, competitive targets as compared to other targets. Experiment 3 turns off the schadenfreude response by manipulating status and competition-relevant information regarding envied targets. Finally, Experiment 4 investigates affective and neural markers of intergroup envy and schadenfreude in the context of a long-standing sports rivalry and the extent to which neurophysiological correlates of schadenfreude are related to self-reported likelihood of harming rival team fans. We conclude with implications and future directions. © 2013 New York Academy of Sciences.
Targeting as the basis for pre-test market of lithium-ion battery
NASA Astrophysics Data System (ADS)
Yuniaristanto, Zakaria, R.; Saputri, V. H. L.; Sutopo, W.; Kadir, E. A.
2017-11-01
This article discusses about market segmentation and targeting as a first step in pre-test market of a new technology. The benefits of targeting towards pre-test market are pre-test market can be conducted to focus on selected target markets so there is no bias during the pre-test market. In determining the target market then do some surveys to identify the state of market in the future, so that the marketing process is not misplaced. Lithium ion battery which is commercialized through start-up companies is the case study. This start-up companies must be able to respond the changes and bring in customers as well as maintain them so that companies can survive and evolve to achieve its objectives. The research aims to determine market segments and target market effectively. Marketing strategy (segmentation and targeting) is used to make questionnaire and cluster analysis in data processing. Respondents were selected by purposive sampling and have obtained data as many as 80 samples. As the results study, there are three segments for lithium ion battery with their own distinguished characteristics and there are two segments that can be used as the target market for the company.
Isotope production and target preparation for nuclear astrophysics data
NASA Astrophysics Data System (ADS)
Schumann, Dorothea; Dressler, Rugard; Maugeri, Emilio Andrea; Heinitz, Stephan
2017-09-01
Targets are in many cases an indispensable ingredient for successful experiments aimed to produce nuclear data. With the recently observed shift to study nuclear reactions on radioactive targets, this task can become extremely challenging. Concerted actions of a certain number of laboratories able to produce isotopes and manufacture radioactive targets are urgently needed. We present here some examples of successful isotope and target production at PSI, in particular the production of 60Fe samples used for half-life measurements and neutron capture cross section experiments, the chemical processing and fabrication of lanthanide targets for capture cross section experiments at n_TOF (European Organization for Nuclear Research (CERN), Switzerland) as well as the recently performed manufacturing of highly-radioactive 7Be targets for the measurement of the 7Be(n,α)4He cross section in the energy range of interest for the Big-Bang nucleosynthesis contributing to the solving of the cosmological Li-problem. The two future projects: "Determination of the half-life and experiments on neutron capture cross sections of 53Mn" and "32Si - a new chronometer for nuclear dating" are briefly described. Moreover, we propose to work on the establishment of a dedicated network on isotope and target producing laboratories.
Their pain, our pleasure: stereotype content and schadenfreude
Cikara, Mina; Fiske, Susan T.
2015-01-01
People often fail to empathize with others, and sometimes even experience schadenfreude – pleasure at others' misfortunes. One potent predictor of schadenfreude is envy, which, according to the stereotype content model, is elicited by high-status, competitive targets. Here we review our recent research program investigating the relationships among stereotypes, envy, schadenfreude, and harm. Experiment 1 demonstrates that stereotypes are sufficient to influence affective responses to targets' misfortunes; participants not only report feeling less negative when misfortunes befall high-status, competitive targets as compared to other targets, they also smile more (assessed with facial EMG). Experiment 2 replicates the self-report findings from Experiment 1 and assesses behavioral tendencies toward envied targets; participants are more willing to endorse harming high-status, competitive targets as compared to other targets. Experiment 3 turns off the schadenfreude response by manipulating status and competition-relevant information regarding envied targets. Finally, Experiment 4 investigates affective and neural markers of intergroup envy and schadenfreude in the context of a long-standing sports rivalry and the extent to which neurophysiological correlates of schadenfreude are related to self-reported likelihood of harming rival team fans. We conclude with implications and future directions. PMID:25708079
Emerging pathways and future targets for the molecular therapy of pancreatic cancer.
Vaccaro, Vanja; Melisi, Davide; Bria, Emilio; Cuppone, Federica; Ciuffreda, Ludovica; Pino, Maria Simona; Gelibter, Alain; Tortora, Giampaolo; Cognetti, Francesco; Milella, Michele
2011-10-01
Pancreatic cancer treatment remains a challenge for clinicians and researchers. Despite undisputable advances in the comprehension of the molecular mechanisms underlying cancer development and progression, early disease detection and clinical management of patients has made little, if any, progress in the past 20 years. Clinical development of targeted agents directed against validated pathways, such as the EGF/EGF receptor axis, the mutant KRAS protein, MMPs, and VEGF-mediated angiogenesis, alone or in combination with gemcitabine-based standard chemotherapy, has been disappointing. This review explores the preclinical rationale for clinical approaches aimed at targeting the TGF-β, IGF, Hedgehog, Notch and NF-κB signaling pathways, to develop innovative therapeutic strategies for pancreatic cancer. Although some of the already clinically explored approaches (particularly EGFR and KRAS targeting) deserve further clinical consideration, by employing more innovative and creative clinical trial designs than the gemcitabine-targeted agent paradigm that has thus far invariably failed, the targeting of emerging and relatively unexplored signaling pathways holds great promise to increase our understanding of the complex molecular biology and to advance the clinical management of pancreatic cancer.
Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects.
Jones, Nathaniel G; Catta-Preta, Carolina M C; Lima, Ana Paula C A; Mottram, Jeremy C
2018-04-13
There has been a very limited number of high-throughput screening campaigns carried out with Leishmania drug targets. In part, this is due to the small number of suitable target genes that have been shown by genetic or chemical methods to be essential for the parasite. In this perspective, we discuss the state of genetic target validation in the field of Leishmania research and review the 200 Leishmania genes and 36 Trypanosoma cruzi genes for which gene deletion attempts have been made since the first published case in 1990. We define a quality score for the different genetic deletion techniques that can be used to identify potential drug targets. We also discuss how the advances in genome-scale gene disruption techniques have been used to assist target-based and phenotypic-based drug development in other parasitic protozoa and why Leishmania has lacked a similar approach so far. The prospects for this scale of work are considered in the context of the application of CRISPR/Cas9 gene editing as a useful tool in Leishmania.
2016-01-01
The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy. PMID:25826710
Computational challenges of structure-based approaches applied to HIV.
Forli, Stefano; Olson, Arthur J
2015-01-01
Here, we review some of the opportunities and challenges that we face in computational modeling of HIV therapeutic targets and structural biology, both in terms of methodology development and structure-based drug design (SBDD). Computational methods have provided fundamental support to HIV research since the initial structural studies, helping to unravel details of HIV biology. Computational models have proved to be a powerful tool to analyze and understand the impact of mutations and to overcome their structural and functional influence in drug resistance. With the availability of structural data, in silico experiments have been instrumental in exploiting and improving interactions between drugs and viral targets, such as HIV protease, reverse transcriptase, and integrase. Issues such as viral target dynamics and mutational variability, as well as the role of water and estimates of binding free energy in characterizing ligand interactions, are areas of active computational research. Ever-increasing computational resources and theoretical and algorithmic advances have played a significant role in progress to date, and we envision a continually expanding role for computational methods in our understanding of HIV biology and SBDD in the future.
Targeting G protein coupled receptor-related pathways as emerging molecular therapies
Ghanemi, Abdelaziz
2013-01-01
G protein coupled receptors (GPCRs) represent the most important targets in modern pharmacology because of the different functions they mediate, especially within brain and peripheral nervous system, and also because of their functional and stereochemical properties. In this paper, we illustrate, via a variety of examples, novel advances about the GPCR-related molecules that have been shown to play diverse roles in GPCR pathways and in pathophysiological phenomena. We have exemplified how those GPCRs’ pathways are, or might constitute, potential targets for different drugs either to stimulate, modify, regulate or inhibit the cellular mechanisms that are hypothesized to govern some pathologic, physiologic, biologic and cellular or molecular aspects both in vivo and in vitro. Therefore, influencing such pathways will, undoubtedly, lead to different therapeutical applications based on the related pharmacological implications. Furthermore, such new properties can be applied in different fields. In addition to offering fruitful directions for future researches, we hope the reviewed data, together with the elements found within the cited references, will inspire clinicians and researchers devoted to the studies on GPCR’s properties. PMID:25972730
Future Orientation among Students Exposed to School Bullying and Cyberbullying Victimization
Låftman, Sara B.; Alm, Susanne; Sandahl, Julia; Modin, Bitte
2018-01-01
Future orientation can be defined as an individual’s thoughts, beliefs, plans, and hopes for the future. Earlier research has shown adolescents’ future orientation to predict outcomes later in life, which makes it relevant to analyze differences in future orientation among youth. The aim of the present study was to analyze if bullying victimization was associated with an increased likelihood of reporting a pessimistic future orientation among school youth. To be able to distinguish between victims and bully-victims (i.e., students who are both bullies and victims), we also took perpetration into account. The data were derived from the Stockholm School Survey performed in 2016 among ninth grade students (ages 15–16 years) (n = 5144). Future orientation and involvement in school bullying and in cyberbullying were based on self-reports. The statistical method used was binary logistic regression. The results demonstrated that victims and bully-victims of school bullying and of cyberbullying were more likely to report a pessimistic future orientation compared with students not involved in bullying. These associations were shown also when involvement in school bullying and cyberbullying were mutually adjusted. The findings underline the importance of anti-bullying measures that target both school bullying and cyberbullying. PMID:29584631
Future Orientation among Students Exposed to School Bullying and Cyberbullying Victimization.
Låftman, Sara B; Alm, Susanne; Sandahl, Julia; Modin, Bitte
2018-03-27
Future orientation can be defined as an individual's thoughts, beliefs, plans, and hopes for the future. Earlier research has shown adolescents' future orientation to predict outcomes later in life, which makes it relevant to analyze differences in future orientation among youth. The aim of the present study was to analyze if bullying victimization was associated with an increased likelihood of reporting a pessimistic future orientation among school youth. To be able to distinguish between victims and bully-victims (i.e., students who are both bullies and victims), we also took perpetration into account. The data were derived from the Stockholm School Survey performed in 2016 among ninth grade students (ages 15-16 years) ( n = 5144). Future orientation and involvement in school bullying and in cyberbullying were based on self-reports. The statistical method used was binary logistic regression. The results demonstrated that victims and bully-victims of school bullying and of cyberbullying were more likely to report a pessimistic future orientation compared with students not involved in bullying. These associations were shown also when involvement in school bullying and cyberbullying were mutually adjusted. The findings underline the importance of anti-bullying measures that target both school bullying and cyberbullying.
de Souza, Amancio; Wang, Jin-Zheng; Dehesh, Katayoon
2017-04-28
Interorganellar cooperation maintained via exquisitely controlled retrograde-signaling pathways is an evolutionary necessity for maintenance of cellular homeostasis. This signaling feature has therefore attracted much research attention aimed at improving understanding of the nature of these communication signals, how the signals are sensed, and ultimately the mechanism by which they integrate targeted processes that collectively culminate in organellar cooperativity. The answers to these questions will provide insight into how retrograde-signal-mediated regulatory mechanisms are recruited and which biological processes are targeted, and will advance our understanding of how organisms balance metabolic investments in growth against adaptation to environmental stress. This review summarizes the present understanding of the nature and the functional complexity of retrograde signals as integrators of interorganellar communication and orchestrators of plant development, and offers a perspective on the future of this critical and dynamic area of research.
Seeking new acne treatment from natural products, devices and synthetic drug discovery.
Yang, Ji Hoon; Yoon, Ji Young; Kwon, Hyuck Hoon; Min, Seonguk; Moon, Jungyoon; Suh, Dae Hun
2017-01-01
Despite lots of research on the pathogenesis of acne, the development of new therapeutic agents is still stagnant. Conventional agents which target multiple pathological processes have some serious side effects and this makes seeking new treatment options important for treating acne. As new therapeutic options, researchers are focusing on natural products, synthetic drugs and devices. From natural products, epigallocatechin-3 gallate, lupeol, cannabidiol and Lactobacillus fermented Chamaecyperis obtusa were reported to be possible candidates for novel drugs, targeting multiple pathogenic factors. Synthetic anti- P.acnes agent, nitric oxide nanoparticles and α-mangostin nanoparticles are shown to be effective in acne treatment. Device or procedural methods such as fractional microneedling radiofrequency, cryolysis, photothermolysis and daylight photodynamic therapy have potential as new treatment options for acne. Further large clinical trials comparing these new treatments with existing agents will be necessary in the future.
2017-05-04
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8 + T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?
Acoustic Levitation Containerless Processing
NASA Technical Reports Server (NTRS)
Whymark, R. R.; Rey, C. A.
1985-01-01
This research program consists of the development of acoustic containerless processing systems with applications in the areas of research in material sciences, as well as the production of new materials, solid forms with novel and unusual microstructures, fusion target spheres, and improved optical fibers. Efforts have been focused on the containerless processing at high temperatures for producing new kinds of glasses. Also, some development has occurred in the areas of containerlessly supporting liquids at room temperature, with applications in studies of fluid dynamics, potential undercooling of liquids, etc. The high temperature area holds the greatest promise for producing new kinds of glasses and ceramics, new alloys, and possibly unusual structural shapes, such as very uniform hollow glass shells for fusion target applications. High temperature acoustic levitation required for containerless processing has been demonstrated in low-g environments as well as in ground-based experiments. Future activities include continued development of the signals axis acoustic levitator.
Skylab-4 visual observations project: Geological features of southwestern North America
NASA Technical Reports Server (NTRS)
Silver, L. T.
1975-01-01
Visual observations conducted by Skylab-4 crewmen on seven designated geological target areas and other targets of opportunity in parts of southwestern United States and northwestern Mexico were described. The experiments were designed to learn how effectively geologic features could be observed from orbit and what research information could be obtained from the observations when supported by ground studies. For the limited preparation they received, the crewmen demonstrated exceptional observational ability and produced outstanding photographic studies. They also formulated cogent opinions on how to improve future observational and photo-documentation techniques. From the photographs and other observations, it was possible to obtain significant research contributions to on-going field investigations. These contributions were integrated into other aspects of the ground investigations to the following topics: major faults, regional stratigraphy, occurrence of Precambrian crystalline rocks, mapping of Mesozoic volcanic rocks, regional geology.
Recent progresses in biomedical applications of aptamer-functionalized systems.
Ding, Fei; Gao, Yangguang; He, Xianran
2017-09-15
Aptamers, known as "chemical antibodies" are screened via a combinational technology of systematic evolution of ligands by exponential enrichment (SELEX). Due to their specific targeting ability, high binding affinity, low immunogenicity and easy modification, aptamer-functionalized systems have been extensively applied in various fields and exhibit favorable results. However, there is still a long way for them to be commercialized, and few aptamer-functionalized systems have yet successfully entered clinical and industrial use. Thus, it is necessary to overview the recent research progresses of aptamer-functionalized systems for the researchers to improve or design novel and better aptamer-functionalized systems. In this review, we first introduce the recent progresses of aptamer-functionalized systems' applications in biosensing, targeted drug delivery, gene therapy and cancer cell imaging, followed by a discussion of the challenges faced with extensive applications of aptamer-functionalized systems and speculation of the future prospects of them. Copyright © 2017 Elsevier Ltd. All rights reserved.
Seeking new acne treatment from natural products, devices and synthetic drug discovery
Yoon, Ji Young; Kwon, Hyuck Hoon; Min, Seonguk; Suh, Dae Hun
2017-01-01
ABSTRACT Despite lots of research on the pathogenesis of acne, the development of new therapeutic agents is still stagnant. Conventional agents which target multiple pathological processes have some serious side effects and this makes seeking new treatment options important for treating acne. As new therapeutic options, researchers are focusing on natural products, synthetic drugs and devices. From natural products, epigallocatechin-3 gallate, lupeol, cannabidiol and Lactobacillus fermented Chamaecyperis obtusa were reported to be possible candidates for novel drugs, targeting multiple pathogenic factors. Synthetic anti-P.acnes agent, nitric oxide nanoparticles and α-mangostin nanoparticles are shown to be effective in acne treatment. Device or procedural methods such as fractional microneedling radiofrequency, cryolysis, photothermolysis and daylight photodynamic therapy have potential as new treatment options for acne. Further large clinical trials comparing these new treatments with existing agents will be necessary in the future. PMID:29484092
ALK mutation and inhibition in lung cancer
Le, Tri; Gerber, David E.
2016-01-01
The advent of precision medicine in non-small cell lung cancer has remarkably altered the direction of research and improved clinical outcomes. The identification of molecular subsets with differential response to targeted therapies began with the identification of epidermal growth factor receptor mutated tumors in subsets of non-small cell lung cancer (NSCLC). Emboldened by unprecedented response rates to kinase inhibitors seen in that subset, the oncologic community searched for other molecular subsets featuring oncogene addiction. An early result of this search was the discovery of NSCLC driven by activating rearrangements of the anaplastic lymphoma kinase (ALK) gene. In an astoundingly brief period following the recognition of ALK-positive NSCLC, details of the biology, clinicopathologic features, development of targeted inhibitors, mechanisms of therapeutic resistance, and new generations of treatment were elucidated. This review summarizes the current understanding of the pathologic features, diagnostic approach, treatment options, resistance mechanisms, and future research areas for ALK-positive NSCLC. PMID:27637426
Zloza, Andrew; Karolina Palucka, A; Coussens, Lisa M; Gotwals, Philip J; Headley, Mark B; Jaffee, Elizabeth M; Lund, Amanda W; Sharpe, Arlene H; Sznol, Mario; Wainwright, Derek A; Wong, Kwok-Kin; Bosenberg, Marcus W
2017-09-19
Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future. This full-day program provided an introduction to the most common immunocompetent and humanized models used in cancer immunology and immunotherapy research, and addressed the use of models to evaluate immune-targeting therapies. Here, we summarize the workshop presentations and subsequent panel discussion.
The hydrogen technology assessment, phase 1
NASA Technical Reports Server (NTRS)
Bain, Addison
1991-01-01
The purpose of this phase 1 report is to begin to form the information base of the economics and energy uses of hydrogen-related technologies on which the members of the National Hydrogen Association (NHA) can build a hydrogen vision of the future. The secondary goal of this report is the development of NHA positions on national research, development, and demonstration opportunities. The third goal, with the aid of the established hydrogen vision and NHA positions, is to evaluate ongoing federal research goals and activities. The evaluations will be performed in a manner that compares the costs associated with using systems that achieve those goals against the cost of performing those tasks today with fossil fuels. From this ongoing activity should emerge an NHA information base, one or more hydrogen visions of the future, and cost and performance targets for hydrogen applications to complete in the market place.
Chew, Boon-How; Lee, Ping-Yein; Cheong, Ai-Theng; Ismail, Mastura; Shariff-Ghazali, Sazlina; Goh, Pik-Pin
2016-10-01
A persistent and increasing prevalence of diagnosed and undiagnosed diabetes mellitus has recently been reported in the National Health and Morbidity Survey 2015. This commentary recapitulates the relevant and valuable lessons in the Malaysian national diabetes registries to inform the healthcare stakeholders and policy makers on potential areas of clinical practice improvement and future researches. Under performance of the process measures and sub-optimal control of HbA1c, blood pressure and lipids profile were prevalent (<40% achieved treatment targets). Although these had improved slightly from 2009 to 2012, diabetes co-morbidities (hypertension and dyslipidaemia) and complications had also increased. Prevalence of insulin use had doubled, and lipid lowering agent use had increased about 50% in 2012 compared to 2009. We identified six clinical areas for urgent attention and improvement, and three potential areas for future research. Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
Melatonin and mitochondrial function during ischemia/reperfusion injury.
Ma, Zhiqiang; Xin, Zhenlong; Di, Wencheng; Yan, Xiaolong; Li, Xiaofei; Reiter, Russel J; Yang, Yang
2017-11-01
Ischemia/reperfusion (IR) injury occurs in many organs and tissues, and contributes to morbidity and mortality worldwide. Melatonin, an endogenously produced indolamine, provides a strong defense against IR injury. Mitochondrion, an organelle for ATP production and a decider for cell fate, has been validated to be a crucial target for melatonin to exert its protection against IR injury. In this review, we first clarify the mechanisms underlying mitochondrial dysfunction during IR and melatonin's protection of mitochondria under this condition. Thereafter, special focus is placed on the protective actions of melatonin against IR injury in brain, heart, liver, and others. Finally, we explore several potential future directions of research in this area. Collectively, the information compiled here will serve as a comprehensive reference for the actions of melatonin in IR injury identified to date and will hopefully aid in the design of future research and increase the potential of melatonin as a therapeutic agent.
Üner, Melike; Yener, Gülgün
2007-01-01
Solid lipid nanoparticles (SLN) have been reported to be an alternative system to emulsions, liposomes, microparticles and their polymeric counterparts for various application routes since the early 1990s due to their advantages. Various research groups have also increasingly focused on improving their stability in body fluids after administration by coating of particles with hydrophilic molecules such as poly(ethylene)glycol (PEG) derivatives. Altering surface characteristics by coating SLN with hydrophilic molecules improves plasma stability and biodistribution, and subsequent bioavailability of drugs entrapped. Their storage stability is also increased. This paper basicly reviews types of SLN, principles of drug loading and models of drug incorporation. The influence of PEG coating on particle size and surface characteristics is discussed followed by alteration in pharmacokinetics and bioavailability of drugs in order to target the site of action via SLN. The future direction of research and clinical implications of SLN is also considered. PMID:18019829
Graphical Environment Tools for Application to Gamma-Ray Energy Tracking Arrays
DOE Office of Scientific and Technical Information (OSTI.GOV)
Todd, Richard A.; Radford, David C.
2013-12-30
Highly segmented, position-sensitive germanium detector systems are being developed for nuclear physics research where traditional electronic signal processing with mixed analog and digital function blocks would be enormously complex and costly. Future systems will be constructed using pipelined processing of high-speed digitized signals as is done in the telecommunications industry. Techniques which provide rapid algorithm and system development for future systems are desirable. This project has used digital signal processing concepts and existing graphical system design tools to develop a set of re-usable modular functions and libraries targeted for the nuclear physics community. Researchers working with complex nuclear detector arraysmore » such as the Gamma-Ray Energy Tracking Array (GRETA) have been able to construct advanced data processing algorithms for implementation in field programmable gate arrays (FPGAs) through application of these library functions using intuitive graphical interfaces.« less
Castellini, Claudio; Artemiadis, Panagiotis; Wininger, Michael; Ajoudani, Arash; Alimusaj, Merkur; Bicchi, Antonio; Caputo, Barbara; Craelius, William; Dosen, Strahinja; Englehart, Kevin; Farina, Dario; Gijsberts, Arjan; Godfrey, Sasha B.; Hargrove, Levi; Ison, Mark; Kuiken, Todd; Marković, Marko; Pilarski, Patrick M.; Rupp, Rüdiger; Scheme, Erik
2014-01-01
One of the hottest topics in rehabilitation robotics is that of proper control of prosthetic devices. Despite decades of research, the state of the art is dramatically behind the expectations. To shed light on this issue, in June, 2013 the first international workshop on Present and future of non-invasive peripheral nervous system (PNS)–Machine Interfaces (MI; PMI) was convened, hosted by the International Conference on Rehabilitation Robotics. The keyword PMI has been selected to denote human–machine interfaces targeted at the limb-deficient, mainly upper-limb amputees, dealing with signals gathered from the PNS in a non-invasive way, that is, from the surface of the residuum. The workshop was intended to provide an overview of the state of the art and future perspectives of such interfaces; this paper represents is a collection of opinions expressed by each and every researcher/group involved in it. PMID:25177292
2015 Science Mission Directorate Technology Highlights
NASA Technical Reports Server (NTRS)
Seablom, Michael S.
2016-01-01
The role of the Science Mission Directorate (SMD) is to enable NASA to achieve its science goals in the context of the Nation's science agenda. SMD's strategic decisions regarding future missions and scientific pursuits are guided by Agency goals, input from the science community including the recommendations set forth in the National Research Council (NRC) decadal surveys and a commitment to preserve a balanced program across the major science disciplines. Toward this end, each of the four SMD science divisions -- Heliophysics, Earth Science, Planetary Science, and Astrophysics -- develops fundamental science questions upon which to base future research and mission programs. Often the breakthrough science required to answer these questions requires significant technological innovation, e.g., instruments or platforms with capabilities beyond the current state of the art. SMD's targeted technology investments fill technology gaps, enabling NASA to build the challenging and complex missions that accomplish groundbreaking science.
SMD Technology Development Story for NASA Annual Technology report
NASA Technical Reports Server (NTRS)
Seablom, Michael S.
2017-01-01
The role of the Science Mission Directorate (SMD) is to enable NASA to achieve its science goals in the context of the Nation's science agenda. SMD's strategic decisions regarding future missions and scientific pursuits are guided by Agency goals, input from the science community-including the recommendations set forth in the National Research Council (NRC) decadal surveys-and a commitment to preserve a balanced program across the major science disciplines. Toward this end, each of the four SMD science divisions-Heliophysics, Earth Science, Planetary Science, and Astrophysics-develops fundamental science questions upon which to base future research and mission programs. Often the breakthrough science required to answer these questions requires significant technological innovation-e.g., instruments or platforms with capabilities beyond the current state of the art. SMD's targeted technology investments fill technology gaps, enabling NASA to build the challenging and complex missions that accomplish groundbreaking science.
The Luminosity Measurement for the DZERO Experiment at Fermilab
DOE Office of Scientific and Technical Information (OSTI.GOV)
Snow, Gregory R.
Primary project objective: The addition of University of Nebraska-Lincoln (UNL) human resources supported by this grant helped ensure that Fermilab’s DZERO experiment had a reliable luminosity measurement through the end of Run II data taking and an easily-accessible repository of luminosity information for all collaborators performing physics analyses through the publication of its final physics results. Secondary project objective: The collaboration between the UNL Instrument Shop and Fermilab’s Scintillation Detector Development Center enhanced the University of Nebraska’s future role as a particle detector R&D and production facility for future high energy physics experiments. Overall project objective: This targeted project enhancedmore » the University of Nebraska’s presence in both frontier high energy physics research in DZERO and particle detector development, and it thereby served the goals of the DOE Office of Science and the Experimental Program to Stimulate Competitive Research (EPSCoR) for the state of Nebraska.« less
Cook, Jonathan A; Hislop, Jennifer; Adewuyi, Temitope E; Harrild, Kirsten; Altman, Douglas G; Ramsay, Craig R; Fraser, Cynthia; Buckley, Brian; Fayers, Peter; Harvey, Ian; Briggs, Andrew H; Norrie, John D; Fergusson, Dean; Ford, Ian; Vale, Luke D
2014-05-01
The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to the design and validity of a RCT is a calculation of the number of participants needed (the sample size). The value used to determine the sample size can be considered the 'target difference'. From both a scientific and an ethical standpoint, selecting an appropriate target difference is of crucial importance. Determination of the target difference, as opposed to statistical approaches to calculating the sample size, has been greatly neglected though a variety of approaches have been proposed the current state of the evidence is unclear. The aim was to provide an overview of the current evidence regarding specifying the target difference in a RCT sample size calculation. The specific objectives were to conduct a systematic review of methods for specifying a target difference; to evaluate current practice by surveying triallists; to develop guidance on specifying the target difference in a RCT; and to identify future research needs. The biomedical and social science databases searched were MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, Education Resources Information Center (ERIC) and Scopus for in-press publications. All were searched from 1966 or the earliest date of the database coverage and searches were undertaken between November 2010 and January 2011. There were three interlinked components: (1) systematic review of methods for specifying a target difference for RCTs - a comprehensive search strategy involving an electronic literature search of biomedical and some non-biomedical databases and clinical trials textbooks was carried out; (2) identification of current trial practice using two surveys of triallists - members of the Society for Clinical Trials (SCT) were invited to complete an online survey and respondents were asked about their awareness and use of, and willingness to recommend, methods; one individual per triallist group [UK Clinical Research Collaboration (UKCRC)-registered Clinical Trials Units (CTUs), Medical Research Council (MRC) UK Hubs for Trials Methodology Research and National Institute for Health Research (NIHR) UK Research Design Services (RDS)] was invited to complete a survey; (3) production of a structured guidance document to aid the design of future trials - the draft guidance was developed utilising the results of the systematic review and surveys by the project steering and advisory groups. Methodological review incorporating electronic searches, review of books and guidelines, two surveys of experts (membership of an international society and UK- and Ireland-based triallists) and development of guidance. The two surveys were sent out to membership of the SCT and UK- and Ireland-based triallists. The review focused on methods for specifying the target difference in a RCT. It was not restricted to any type of intervention or condition. Methods for specifying the target difference for a RCT were considered. The search identified 11,485 potentially relevant studies. In total, 1434 were selected for full-text assessment and 777 were included in the review. Seven methods to specify the target difference for a RCT were identified - anchor, distribution, health economic, opinion-seeking, pilot study, review of evidence base (RoEB) and standardised effect size (SES) - each having important variations in implementation. A total of 216 of the included studies used more than one method. A total of 180 (15%) responses to the SCT survey were received, representing 13 countries. Awareness of methods ranged from 38% (n =69) for the health economic method to 90% (n =162) for the pilot study. Of the 61 surveys sent out to UK triallist groups, 34 (56%) responses were received. Awareness ranged from 97% (n =33) for the RoEB and pilot study methods to only 41% (n =14) for the distribution method. Based on the most recent trial, all bar three groups (91%, n =30) used a formal method. Guidance was developed on the use of each method and the reporting of the sample size calculation in a trial protocol and results paper. There is a clear need for greater use of formal methods to determine the target difference and better reporting of its specification. Raising the standard of RCT sample size calculations and the corresponding reporting of them would aid health professionals, patients, researchers and funders in judging the strength of the evidence and ensuring better use of scarce resources. The Medical Research Council UK and the National Institute for Health Research Joint Methodology Research programme.
Improving the quality of survivorship for older adults with cancer.
Mohile, Supriya G; Hurria, Arti; Cohen, Harvey J; Rowland, Julia H; Leach, Corinne R; Arora, Neeraj K; Canin, Beverly; Muss, Hyman B; Magnuson, Allison; Flannery, Marie; Lowenstein, Lisa; Allore, Heather G; Mustian, Karen M; Demark-Wahnefried, Wendy; Extermann, Martine; Ferrell, Betty; Inouye, Sharon K; Studenski, Stephanie A; Dale, William
2016-08-15
In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. Cancer 2016;122:2459-68. © 2016 American Cancer Society. © 2016 American Cancer Society.
Neural Correlates of Antidepressant Treatment Response in Adolescents with Major Depressive Disorder
Klimes-Dougan, Bonnie; Vu, Dung Pham; Westlund Schreiner, Melinda; Mueller, Bryon A.; Eberly, Lynn E.; Camchong, Jazmin; Westervelt, Ana; Lim, Kelvin O.
2016-01-01
Abstract Objective: The neural changes underlying response to antidepressant treatment in adolescents are unknown. Identification of neural change correlates of treatment response could (1) aid in understanding mechanisms of depression and its treatment and (2) serve as target biomarkers for future research. Method: Using functional magnetic resonance imaging, we examined changes in brain activation and functional connectivity in 13 unmedicated adolescents with major depressive disorder (MDD) before and after receiving treatment with a selective serotonin reuptake inhibitor medication for 8 weeks. Specifically, we examined brain activation during a negative emotion task and resting-state functional connectivity (RSFC), focusing on the amygdala to capture networks relevant to negative emotion. We conducted whole-brain analyses to identify how symptom improvement was related to change in brain activation during a negative emotion task or amygdala RSFC. Results: After treatment, clinical improvement was associated with decreased task activation in rostral and subgenual anterior cingulate cortex and increased activation in bilateral insula, bilateral middle frontal cortices, right parahippocampus, and left cerebellum. Analysis of change in amygdala RSFC showed that treatment response was associated with increased amygdala RSFC with right frontal cortex, but decreased amygdala RSFC with right precuneus and right posterior cingulate cortex. Conclusion: The findings represent a foothold for advancing understanding of pathophysiology of MDD in adolescents by revealing the critical neural circuitry changes that underlie a positive response to a standard treatment. Although preliminary, the present study provides a research platform for future work needed to confirm these biomarkers at a larger scale before using them in future target engagement studies of novel treatments. PMID:27159204
Treating juvenile idiopathic arthritis to target: recommendations of an international task force.
Ravelli, Angelo; Consolaro, Alessandro; Horneff, Gerd; Laxer, Ronald M; Lovell, Daniel J; Wulffraat, Nico M; Akikusa, Jonathan D; Al-Mayouf, Sulaiman M; Antón, Jordi; Avcin, Tadej; Berard, Roberta A; Beresford, Michael W; Burgos-Vargas, Ruben; Cimaz, Rolando; De Benedetti, Fabrizio; Demirkaya, Erkan; Foell, Dirk; Itoh, Yasuhiko; Lahdenne, Pekka; Morgan, Esi M; Quartier, Pierre; Ruperto, Nicolino; Russo, Ricardo; Saad-Magalhães, Claudia; Sawhney, Sujata; Scott, Christiaan; Shenoi, Susan; Swart, Joost F; Uziel, Yosef; Vastert, Sebastiaan J; Smolen, Josef S
2018-06-01
Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
NASA Technical Reports Server (NTRS)
Abell, Paul A.
2011-01-01
Human exploration of near-Earth objects (NEOs) beginning circa 2025 - 2030 is one of the stated objectives of U.S. National Space Policy. Piloted missions to these bodies would further development of deep space mission systems and technologies, obtain better understanding of the origin and evolution of our Solar System, and support research for asteroid deflection and hazard mitigation strategies. This presentation will discuss some of the physical characteristics of NEOs and review some of the current plans for NEO research and exploration from both a human and robotic mission perspective.
Lactate biosensors: current status and outlook.
Rassaei, Liza; Olthuis, Wouter; Tsujimura, Seiya; Sudhölter, Ernst J R; van den Berg, Albert
2014-01-01
Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors for direct applications. In this review, we provide an overview of the most immediate and relevant developments toward this end, and we discuss and assess common transduction approaches. Further, we critically describe the pros and cons of current commercial lactate sensors and envision how future sensing design may benefit from emerging new technologies.
Proceedings of the Ocean Energy Information Dissemination Workshop
NASA Astrophysics Data System (ADS)
Petty, D.
1980-04-01
The workshop was held to discuss the status of marketing ocean energy information and to develop an understanding of information needs and how to satisfy them. Presentations were made by the Solar Energy Research Institute (SERI) staff and media consultants about the effective use of audio visual and print products, the mass media, and audience needs. Industry and government representatives reported on current efforts in each of their communication programs and outlined future plans. Four target audiences (DOE contractors, researchers, influencers, and general public) were discussed with respect to developing priorities for projects to enhance the commercialization of ocean energy technology.
Gil-González, D; Ruiz-Cantero, M T; Alvarez-Dardet, C
2009-04-01
The Millennium Development Goals (MDG) progress targets have not been met. Nevertheless, the United Nations (UN) has not yet undertaken in-depth review in order to discover the reasons behind this lack of progress in achieving the MDG. From a political epidemiology perspective, the intention here is to identify the political elements affecting the social factors impeding MDG fulfilment and, at the same time, to suggest future public policies and appropriate proposals that are both more coherent and supported by broader, empirical knowledge of the relevant issues.
Bermudez-Tamayo, Clara; Mukamana, Olive; Carabali, Mabel; Osorio, Lyda; Fournet, Florence; Dabiré, Kounbobr Roch; Turchi Marteli, Celina; Contreras, Adolfo; Ridde, Valéry
2016-12-01
This paper highlights the critical importance of evidence on vector-borne diseases (VBD) prevention and control interventions in urban settings when assessing current and future needs, with a view to setting policy priorities that promote inclusive and equitable urban health services. Research should produce knowledge about policies and interventions that are intended to control and prevent VBDs at the population level and to reduce inequities. Such interventions include policy, program, and resource distribution approaches that address the social determinants of health and exert influence at organizational and system levels.
Progress in understanding the immunopathogenesis of psoriasis
Mak, R.K.H.; Hundhausen, C.; Nestle, F.O.
2010-01-01
This review emphasizes how translation from bench research to clinical knowledge and vice versa has resulted in considerable progress in understanding the immunopathogenesis of psoriasis. First, the journey in understanding the pathogenic mechanisms behind psoriasis is described. The roles of different components of the adaptive and innate immune systems involved in driving the inflammatory response are explained. Discovery of new immune pathways i.e. the IL23/Th17 axis and its subsequent impact on the development of novel biological therapies is highlighted. Identification of potential targets warranting further research for future therapeutic development are also discussed. PMID:20096156
Sarcoma-The standard-bearer in cancer discovery.
Potter, Jared W; Jones, Kevin B; Barrott, Jared J
2018-06-01
Sarcoma is a rare tumor type that occurs most frequently in connective tissue. Despite its uncommon occurrence, sarcoma research has provided the means for groundbreaking research that has advanced our understanding of general cancer mechanisms. It is through sarcoma research that the pioneering efforts of cancer immunotherapy were explored, that we understand the inherent genetic nature of cancer mutations, and that we appreciate the subclassification of general cancer types to make more accurate prognoses. This review explores the brief history of sarcoma research and what sarcomas can still teach us about the future of cancer research, especially in regard to novel immunotherapy targets, the role of epigenetics in disease progression and chemoresistance, and the benefits of more focused clinical trials. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Interpersonal and systemic aspects of emotional abuse at work: the target's perspective.
Keashly, L
2001-06-01
The most frequent form of workplace aggression is not physical, it is emotional and psychological in nature. Known by many names, emotional abuse at work is rapidly becoming recognized as pervasive and costly both in individual and organizational terms. Most of the research to date on emotional abuse at work has utilized survey and other quantitative methodologies in an effort to document the presence, prevalence, and impact of these behaviors. However, these methodologies are based on researchers' definitions and theories of what constitutes emotional abuse rather than on the meaning given to these experiences by the targets of these behaviors. A thorough understanding of this phenomenon requires a scholarly appreciation of the target's experience. Taking "feeling abused" as the criterion variable, this study examined target's experiences based on interviews with people who self-identifed as having experienced difficulties with a boss, coworker, or subordinate. The interpersonal aspects of emotional abuse focused on the nature of behaviors exhibited and the respondents' labeling of their experience. Consistent with elements of researchers' definitions, behaviors were defined as abusive when they were repetitive, resulted in injury or harm to target, and were experienced as a lack of recognition of the individual's integrity. Judgments of violation of standards of conduct and unsolicited nature of the behaviors were also related to respondents' experiences. Relative power differential was also an important element. However, contrary to researchers' definitions, actor intent was not central in defining the experience as abusive. The systemic aspect of emotional abuse was illustrated in the nature of organizational responding to concerns raised by respondents. These responses were of critical importance in respondents' labeling of their experiences as abusive. The focus on the meaning of the behaviors for the respondents provides an enriched picture of key definitional elements. Implications of the findings for future research are discussed.
Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.
2015-07-01
Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less
Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela
2013-12-01
There is an immense interest among the researchers to identify new herbicides which are effective against the herbs without affecting the environment. In this work, photosynthetic pigments are used as the ligands to predict their herbicidal activity. The enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase is a good target for the herbicides. Homology modeling of the target enzyme is done using Modeler 9.11 and the model is validated. Docking studies were performed with AutoDock Vina algorithm to predict the binding of the natural pigments such as β-carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin to the target. β-carotene, phycoerythrin and phycocyanin have higher binding energies indicating the herbicidal activity of the pigments. This work reports a procedure to screen herbicides with computational molecular approach. These pigments will serve as potential bioherbicides in the future.
A novel method to reduce time investment when processing videos from camera trap studies.
Swinnen, Kristijn R R; Reijniers, Jonas; Breno, Matteo; Leirs, Herwig
2014-01-01
Camera traps have proven very useful in ecological, conservation and behavioral research. Camera traps non-invasively record presence and behavior of animals in their natural environment. Since the introduction of digital cameras, large amounts of data can be stored. Unfortunately, processing protocols did not evolve as fast as the technical capabilities of the cameras. We used camera traps to record videos of Eurasian beavers (Castor fiber). However, a large number of recordings did not contain the target species, but instead empty recordings or other species (together non-target recordings), making the removal of these recordings unacceptably time consuming. In this paper we propose a method to partially eliminate non-target recordings without having to watch the recordings, in order to reduce workload. Discrimination between recordings of target species and non-target recordings was based on detecting variation (changes in pixel values from frame to frame) in the recordings. Because of the size of the target species, we supposed that recordings with the target species contain on average much more movements than non-target recordings. Two different filter methods were tested and compared. We show that a partial discrimination can be made between target and non-target recordings based on variation in pixel values and that environmental conditions and filter methods influence the amount of non-target recordings that can be identified and discarded. By allowing a loss of 5% to 20% of recordings containing the target species, in ideal circumstances, 53% to 76% of non-target recordings can be identified and discarded. We conclude that adding an extra processing step in the camera trap protocol can result in large time savings. Since we are convinced that the use of camera traps will become increasingly important in the future, this filter method can benefit many researchers, using it in different contexts across the globe, on both videos and photographs.
Kang, Sonia K; Chasteen, Alison L; Cadieux, Jonathan; Cary, Lindsey A; Syeda, Maisha
2014-09-01
Individuals can be simultaneously categorized into multiple social groups (e.g., racial, gender, age), and stereotypes about one social group may conflict with another. Two such conflicting stereotype sets are those associated with older adults (e.g., frail, kind) and with Black people (e.g., violent, hostile). Recent research shows that young adult perceivers evaluate elderly Black men more positively than young Black men, suggesting that components of the elderly stereotype moderate the influence of conflicting Black stereotypes (Kang & Chasteen, 2009). The current research begins to examine whether this pattern of perceiving multiply-categorizable individuals is maintained among older adults or altered, perhaps due to aging-related cognitive and motivational changes. In three studies using different targets and evaluative tasks, both young and older participants showed evidence of an interplay between Black and elderly stereotypes, such that they perceived elderly Black targets more positively than young Black targets. A similar pattern was observed when assessing emotion change (Study 1), making ratings of warmth and power in the past, present, and future (Study 2), and when directly comparing young and old Black and White targets on traits related to warmth and power (Study 3). The absence of age differences suggests that evaluation of multiply-categorizable targets follows comparable underlying patterns of stereotype activation and inhibition in younger and older adults. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon
2015-07-01
Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Recent patents in the discovery of small molecule inhibitors of JAK3.
Wilson, Lawrence J
2010-05-01
Protein kinase enzymes have become increasingly important as the target of many disease modification drug discovery programs. Disruption of JAK3 function results in quantitative and qualitative deficiencies in both B- and T-cell compartments of the immune system of JAK3 deficient mice and development of severe combined immunodeficiency in humans with the JAK3 genetic aberration. JAK3 plays a specific role in immune function and lymphoid development and it only resides in the hematopoietic system, thus the rationale for selective targeting. Inhibitors of JAK3 have shown utility in many different autoimmune disorders, including allograft rejection during transplantation, acute lymphoblastic leukemia, Type 1 diabetes, rheumatoid arthritis and allergic and asthmatic diseases. These inhibitors are making their way into clinical trials with profound effects, thus, validating the target and strategy. A review that covers around 90 patents and patent applications made in the last 10 years in the area involving JAK3 inhibitors is provided. Specifically, what this content will provide is the genus, highlighted compounds of particular interest, filing organization and some biological measure of these compounds as inhibitors of this protein kinase or none if it is not provided. Some information from original research articles appearing in peer reviewed literature is provided, but this article is not a review of the literature. Furthermore, an overview of the current clinical status and future outcomes of this field is provided as summary. A strong understanding for the current state of the art in patents dealing with inhibitors of JAK3 including genus and species designations, potential commercial interest of this target in the pharmaceutical community, depth of coverage by numbers of examples and selected proof of action against the target. Also, a brief understanding of the biology and pharmacology involved in the processes involving the research, discovery, characterization and clinical status of JAK3 inhibitors. This review is intended for medicinal chemists and patent agents who want to get a quick understanding of the state of the art in the field of JAK3 inhibitors. It further serves as a reference point to go into more depth on any series reported and to be able to evaluate any original research ideas in this area in the future.
Status and future prospects of laser fusion and high power laser applications
NASA Astrophysics Data System (ADS)
Mima, Kunioki
2010-08-01
In Asia, there are many institutes for the R&D of high power laser science and applications. They are 5 major institutes in Japan, 4 major institutes in China, 2 institutes in Korea, and 3 institutes in India. The recent achievements and future prospects of those institutes will be over viewed. In the laser fusion research, the FIREX-I project in Japan has been progressing. The 10kJ short pulse LFEX laser has completed and started the experiments with a single beam. About 1kJ pulse energy will be injected into a cone target. The experimental results of the FIREX experiments will be presented. As the target design for the experiments, a new target, namely, a double cone target was proposed, in which the high energy electrons are well confined and the heating efficiency is significantly improved. Together with the fusion experiments, Osaka University has carried out laboratory astrophysics experiments on photo ionizing plasmas to observe a unique X-ray spectrum from non-LTE plasmas. In 2008, Osaka university has started a new Photon research center in relation with the new program: Consortium for Photon Science and Technology: C-PhoST, in which ultra intense laser plasmas research and related education will be carried out for 10 years. At APRI, JAEA, the fundamental science on the relativistic laser plasmas and the applications of laser particle acceleration has been developed. The application of laser ion acceleration has been investigated on the beam cancer therapy since 2007. In China, The high power glass laser: Shenguan-II and a peta watt beam have been operated to work on radiation hydro dynamics at SIOFM Shanghai. The laser material and optics are developed at SIOFM and LFRC. The IAPCM and the IOP continued the studies on radiation hydrodynamics and on relativistic laser plasmas interactions. At LFRC in China, the construction of Shenguan III glass laser of 200kJ in blue has progressed and will be completed in 2012. Together with the Korean program, I will overview the above Asian programs.
Rivera, Echo A; Kubiak, Sheryl P; Bybee, Deborah
2014-12-01
Research on women's aggression typically focuses on relational aggression. However, the study of violence must include multiple forms of violence such as aggression against partners and non-partner others, while also considering victimization experiences by partners and non-partners. The focus of this study is the multiple experiences of violence (perpetration and victimization) of women who are incarcerated. Incarcerated women are likely to experience higher rates of both than women in community settings, but most will be released in a brief period of time. Using a random sample (N = 580) we conducted cluster analyses to identify five patterns of women's aggression. Clusters varied depending on the target/s of aggression (i.e., partner and/or others), and type of aggression (i.e., physical and/or intimidation). Multinomial logistic regression was performed to determine the relationship between women's membership in a perpetration cluster and their victimization. Victimization history was related to an increased risk of perpetrating aggression, and varied depending on the target and type of aggression. Our findings provide support that research and interventions addressing women's use of aggression must also address their victimization history. Furthermore, results indicate that for some women, aggression towards partners and others is related. Future research should investigate multiple forms of aggression.
Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L
2017-12-01
The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.
Targeting EGFR in lung cancer: Lessons learned and future perspectives
Steuer, Conor E.; Ramalingam, Suresh S.
2016-01-01
The development of individualized therapies has become the focus of current oncology research. Precision medicine has demonstrated great potential for bringing safe and effective drugs to those patients stricken with cancer, and is becoming a reality as more oncogenic drivers of malignancy are discovered. The discovery of Epidermal Growth Factor Receptor (EGFR) mutations as a driving mutation in non-small cell lung cancer (NSCLC) and the subsequent success of the tyrosine kinase inhibitors (TKI) have led the way for NSCLC to be at the forefront of biomarker-based drug development. However, this direction was not always so clear, and this article describes the lessons learned in targeted therapy development from EGFR in NSCLC. PMID:26022942
Overview of research on Bombyx mori microRNA
Wang, Xin; Tang, Shun-ming; Shen, Xing-jia
2014-01-01
Abstract MicroRNAs (miRNAs) constitute some of the most significant regulatory factors involved at the post-transcriptional level after gene expression, contributing to the modulation of a large number of physiological processes such as development, metabolism, and disease occurrence. This review comprehensively and retrospectively explores the literature investigating silkworm, Bombyx mori L. (Lepidoptera: Bombicidae), miRNAs published to date, including discovery, identification, expression profiling analysis, target gene prediction, and the functional analysis of both miRNAs and their targets. It may provide experimental considerations and approaches for future study of miRNAs and benefit elucidation of the mechanisms of miRNAs involved in silkworm developmental processes and intracellular activities of other unknown non-coding RNAs. PMID:25368077
Antiparasitic chemotherapy – from genomes to mechanisms
Horn, David; Duraisingh, Manoj T.
2015-01-01
Due to the absence of antiparistic vaccines, and the constant threat of drug resistance, the development of novel antiparasitic chemotherapies remains of major importance for disease control. A better understanding of drug transport (uptake and efflux), metabolism and the identification of drug targets, as well as potential drug resistance mechanisms would facilitate the development of more effective therapies. Here, we focus on malaria and African tyrpanosaomiasis. We review existing drugs and drug development, emphasizing high-throughput genomic and genetic approaches, which hold great promise for elucidating anti-parasitic mechanisms. We describe the approaches and technologies that have been influential for each parasite and develop some new ideas for future research directions, including strategies for target deconvolution. PMID:24050701
Pallesen, Ståle; Nielsen, Morten B.; Magerøy, Nils; Andreassen, Cecilie S.; Einarsen, Ståle
2017-01-01
Previous studies on the personality of bullies and targets have exclusively been based on self-report. Against this backdrop we conducted a between group experimental vignette study with three conditions, describing a bully, a target and a control, respectively. Students (n = 242) were recruited as participants and rated the target on the observer rating version of the NEO Five Factor Inventory-Revised reflecting the personality dimensions Neuroticism, Extroversion, Openness to experience, Agreeableness and Conscientiousness. A MANOVA showed an overall significant effect of the experimental conditions. On Neuroticism significant differences between all conditions were found with targets rated highest and the control lowest. In terms of Extroversion the target was rated as lower than the control and the bully. No main effect was found for Openness. On Agreeableness the bully was rated as lower than both the target and the control. The bully was rated lower on Conscientiousness than the control. The significant differences reflected medium to large effect sizes. By and large the results are in agreement with comparable self-report data. The results are discussed in terms of practical implications and directions for future research are outlined. PMID:28690574
Pallesen, Ståle; Nielsen, Morten B; Magerøy, Nils; Andreassen, Cecilie S; Einarsen, Ståle
2017-01-01
Previous studies on the personality of bullies and targets have exclusively been based on self-report. Against this backdrop we conducted a between group experimental vignette study with three conditions, describing a bully, a target and a control, respectively. Students ( n = 242) were recruited as participants and rated the target on the observer rating version of the NEO Five Factor Inventory-Revised reflecting the personality dimensions Neuroticism, Extroversion, Openness to experience, Agreeableness and Conscientiousness. A MANOVA showed an overall significant effect of the experimental conditions. On Neuroticism significant differences between all conditions were found with targets rated highest and the control lowest. In terms of Extroversion the target was rated as lower than the control and the bully. No main effect was found for Openness. On Agreeableness the bully was rated as lower than both the target and the control. The bully was rated lower on Conscientiousness than the control. The significant differences reflected medium to large effect sizes. By and large the results are in agreement with comparable self-report data. The results are discussed in terms of practical implications and directions for future research are outlined.
Combined Auditory and Vibrotactile Feedback for Human-Machine-Interface Control.
Thorp, Elias B; Larson, Eric; Stepp, Cara E
2014-01-01
The purpose of this study was to determine the effect of the addition of binary vibrotactile stimulation to continuous auditory feedback (vowel synthesis) for human-machine interface (HMI) control. Sixteen healthy participants controlled facial surface electromyography to achieve 2-D targets (vowels). Eight participants used only real-time auditory feedback to locate targets whereas the other eight participants were additionally alerted to having achieved targets with confirmatory vibrotactile stimulation at the index finger. All participants trained using their assigned feedback modality (auditory alone or combined auditory and vibrotactile) over three sessions on three days and completed a fourth session on the third day using novel targets to assess generalization. Analyses of variance performed on the 1) percentage of targets reached and 2) percentage of trial time at the target revealed a main effect for feedback modality: participants using combined auditory and vibrotactile feedback performed significantly better than those using auditory feedback alone. No effect was found for session or the interaction of feedback modality and session, indicating a successful generalization to novel targets but lack of improvement over training sessions. Future research is necessary to determine the cognitive cost associated with combined auditory and vibrotactile feedback during HMI control.
Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M. Teresa; Buchholz, Frank
2016-01-01
Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945
Forero, Roberto; Nahidi, Shizar; De Costa, Josephine; Mohsin, Mohammed; Fitzgerald, Gerry; Gibson, Nick; McCarthy, Sally; Aboagye-Sarfo, Patrick
2018-02-17
The main objective of this methodological manuscript was to illustrate the role of using qualitative research in emergency settings. We outline rigorous criteria applied to a qualitative study assessing perceptions and experiences of staff working in Australian emergency departments. We used an integrated mixed-methodology framework to identify different perspectives and experiences of emergency department staff during the implementation of a time target government policy. The qualitative study comprised interviews from 119 participants across 16 hospitals. The interviews were conducted in 2015-2016 and the data were managed using NVivo version 11. We conducted the analysis in three stages, namely: conceptual framework, comparison and contrast and hypothesis development. We concluded with the implementation of the four-dimension criteria (credibility, dependability, confirmability and transferability) to assess the robustness of the study, RESULTS: We adapted four-dimension criteria to assess the rigour of a large-scale qualitative research in the emergency department context. The criteria comprised strategies such as building the research team; preparing data collection guidelines; defining and obtaining adequate participation; reaching data saturation and ensuring high levels of consistency and inter-coder agreement. Based on the findings, the proposed framework satisfied the four-dimension criteria and generated potential qualitative research applications to emergency medicine research. We have added a methodological contribution to the ongoing debate about rigour in qualitative research which we hope will guide future studies in this topic in emergency care research. It also provided recommendations for conducting future mixed-methods studies. Future papers on this series will use the results from qualitative data and the empirical findings from longitudinal data linkage to further identify factors associated with ED performance; they will be reported separately.
Mouesca, Juan P
2015-12-01
Child maltreatment is a common and serious problem. It harms children in the short and long term, affecting their future health and their offspring. Primary, secondary, tertiary and quaternary preventing interventions target on child abuse are described. Evidence-based recommendations on child abuse prevention and examples of researches with proven efficacy are detailed. Risk factors, protective factors and triggers of child abuse and their relationships are described.
2012-05-15
Method for Ubiquitous Robots Based on Wireless Sensor Networks , in 1st European Conference on Smart Sensing and Context2006, Springer: Enschede, The...SUBJECT TERMS Directed Energy, Lasers, Networking , Wireless , Threat, Remote, Sensors , Database, Targets, Security, Transmit, Mobile, Unmanned...the researchers explore the potential for a network that could transport any type of sensor data now or in the future. 29 3. Methods , Assumptions
Atmosphere to Electrons (A2e): Enabling the Wind Plant of Tomorrow
Zayas, Jose; Derby, Mike; Ralston, Kiersten; Clark, Charlton; Brake, Dan; Johnson, Nick
2018-01-16
Atmosphere to Electrons (A2e) is a multi-year U.S. Department of Energy (DOE) research initiative targeting significant reductions in the cost of wind energy through an improved understanding of the complex physics governing electricity generation by wind plants. The goal of A2e is to ensure future wind plants are sited, built, and operated in a way that produces the most cost-effective, usable electric power.
van Rijt, Sabine H.; Sadler, Peter J.
2010-01-01
This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry with many new approaches to the design of innovative metal-based anticancer drugs emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action, and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy. PMID:19782150
History, Current Knowledge, and Future Directions on Bacteriocin Research in Lactic Acid Bacteria
NASA Astrophysics Data System (ADS)
Nes, Ingolf F.
All organisms, both eukaryotic organisms and bacteria, are able to produce ribosomally antimicrobial peptides. In bacteria, such compounds are referred to as bacteriocins. The history of bacteriocins goes back to the early 1920s. One has experienced many disappointments in the efforts how to put these compounds into practical use despite being one of the most promising groups of antimicrobial agents to fight bacterial pathogens. However, today, we see new possibilities how to take advantage of such peptides for the benefit of man and animals. Bacteriocin production has become an important property of probiotic bacteria, and targeted use of bacteriocins to fight certain pathogens may have a future.
Potential applications of biosurfactant rhamnolipids in agriculture and biomedicine.
Chen, Jianwei; Wu, Qihao; Hua, Yi; Chen, Jun; Zhang, Huawei; Wang, Hong
2017-12-01
Rhamnolipids have recently emerged as promising bioactive molecules due to their novel structures, diverse and versatile biological functions, lower toxicity, higher biodegradability, as well as production from renewable resources. The advantages of rhamnolipids make them attractive targets for research in a wide variety of applications. Especially rhamnolipids are likely to possess potential applications of the future in areas such as biomedicine, therapeutics, and agriculture. The purpose of this mini review is to provide a comprehensive prospective of biosurfactant rhamnolipids as potential antimicrobials, immune modulators, and virulence factors, and anticancer agents in the field of biomedicine and agriculture that may meet the ever-increasing future pharmacological treatment and food safety needs in human health.
[Advances in genome editing technologies for treating muscular dystrophy.
Makita, Yukimasa; Hozumi, Hiroyuki; Hotta, Akitsu
Recent advances in genome editing technologies have opened the possibility for treating genetic diseases, such as Duchenne muscular dystrophy(DMD), by correcting the causing gene mutations in dystrophin gene. In fact, there are several reports that demonstrated the restoration of the mutated dystrophin gene in DMD patient-derived iPS cell or functional recovery of forelimb grip strength in DMD model mice. For future clinical applications, there are several aspects that need to be taken into consideration:efficient delivery of the genome editing components, risk of off-target mutagenesis and immunogenicity against genome editing enzyme. In this review, we summarize the current status and future prospective of the research in applying genome editing technologies to DMD.
Novel biomarkers for cardiovascular risk assessment: current status and future directions.
MacNamara, James; Eapen, Danny J; Quyyumi, Arshed; Sperling, Laurence
2015-09-01
Cardiovascular disease (CVD) is the leading cause of mortality in the modern world. Traditional risk algorithms may miss up to 20% of CVD events. Therefore, there is a need for new cardiac biomarkers. Many fields of research are dedicated to improving cardiac risk prediction, including genomics, transcriptomics and proteomics. To date, even the most promising biomarkers have only demonstrated modest associations and predictive ability. Few have undergone randomized control trials. A number of biomarkers are targets to new therapies aimed to reduce cardiovascular risk. Currently, some of the most promising risk prediction has been demonstrated with panels of multiple biomarkers. This article reviews the current state and future of proteomic biomarkers and aggregate biomarker panels.
Turning point or tipping point: new FDA draft guidances and the future of DTC advertising.
Pitts, Peter J
2004-01-01
According to Food and Drug Administration (FDA) research, direct-to-consumer (DTC) drug ads are not as empowering as they were even three years ago. How will the FDA's new draft guidances reverse this trend and affect the future of DTC advertising? Will they be a turning point, resulting in pharmaceutical companies' embracing an educational public health imperative, or a tipping point with politicians and the public zeroing in on aggressively targeted DTC ads as the postimportation pharmaceutical bête noire? The FDA believes that its new guidances strengthen the strategic argument that a better-informed consumer lays the groundwork for a better potential customer.
Restoration for the future: endpoints, targets, and indicators of progress and success
Daniel C. Dey; Callie Jo. Schweitzer
2014-01-01
Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly described and quantitative endpoints and intermediary targets are needed to...
Recruitment of multiple stakeholders to health services research: lessons from the front lines.
Kho, Michelle E; Rawski, Ellen; Makarski, Julie; Brouwers, Melissa C
2010-05-13
Self-administered surveys are an essential methodological tool for health services and knowledge translation research, and engaging end-users of the research is critical. However, few documented accounts of the efforts invested in recruitment of multiple different stakeholders to one health services research study exist. Here, we highlight the challenges of recruiting key stakeholders (policy-makers, clinicians, guideline developers) to a Canadian Institutes of Health Research (CIHR) funded health services research (HSR) study aimed to develop an updated and refined version of a guideline appraisal tool, the AGREE. Using evidence-based methods of recruitment, our goal was to recruit 192 individuals: 80 international guideline developers, 80 Canadian clinicians and 32 Canadian policy/decision-makers. We calculated the participation rate and the recruitment efficiency. We mailed 873 invitation letters. Of 838 approached, our participation rate was 29%(240) and recruitment efficiency, 19%(156). One policy-maker manager did not allow policy staff to participate in the study. Based on the results from this study, we suggest that future studies aiming to engage similar stakeholders in HSR over sample by at least 5 times to achieve their target sample size and allow for participant withdrawals. We need continued efforts to communicate the value of research between researchers and end-users of research (policy-makers, clinicians, and other researchers), integration of participatory research strategies, and promotion of the value of end-user involvement in research. Future research to understand methods of improving recruitment efficiency and engaging key stakeholders in HSR is warranted.
Um, JungIn; Lee, Ji-Hyung; Jung, Da-Woon; Williams, Darren R
2018-04-01
Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.
Programmed Cell Death-1/Programmed Death-ligand 1 Pathway: A New Target for Sepsis.
Liu, Qiang; Li, Chun-Sheng
2017-04-20
Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment. Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database. English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated. Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells. The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.
Engineering mesenchymal stem cells for regenerative medicine and drug delivery.
Park, Ji Sun; Suryaprakash, Smruthi; Lao, Yeh-Hsing; Leong, Kam W
2015-08-01
Researchers have applied mesenchymal stem cells (MSC) to a variety of therapeutic scenarios by harnessing their multipotent, regenerative, and immunosuppressive properties with tropisms toward inflamed, hypoxic, and cancerous sites. Although MSC-based therapies have been shown to be safe and effective to a certain degree, the efficacy remains low in most cases when MSC are applied alone. To enhance their therapeutic efficacy, researchers have equipped MSC with targeted delivery functions using genetic engineering, therapeutic agent incorporation, and cell surface modification. MSC can be genetically modified virally or non-virally to overexpress therapeutic proteins that complement their innate properties. MSC can also be primed with non-peptidic drugs or magnetic nanoparticles for enhanced efficacy and externally regulated targeting, respectively. Furthermore, MSC can be functionalized with targeting moieties to augment their homing toward therapeutic sites using enzymatic modification, chemical conjugation, or non-covalent interactions. These engineering techniques are still works in progress, requiring optimization to improve the therapeutic efficacy and targeting effectiveness while minimizing any loss of MSC function. In this review, we will highlight the advanced techniques of engineering MSC, describe their promise and the challenges of translation into clinical settings, and suggest future perspectives on realizing their full potential for MSC-based therapy. Copyright © 2015 Elsevier Inc. All rights reserved.
Poot, Antonius J.; de Waard, Claudia S.; Wind, Annet W.; Caljouw, Monique A. A.; Gussekloo, Jacobijn
2017-01-01
Evaluation of the implementation of integrated care can differ from trial-based research due to complexity. Therefore, we examined whether a theory-based method for process description of implementation can contribute to improvement of evidence-based care. MOVIT, a Dutch project aimed at implementing integrated care for older vulnerable persons in residential care homes, was used as a case study. The project activities were defined according to implementation taxonomy and mapped in a matrix of theoretical levels and domains. Project activities mainly targeted professionals (both individual and group). A few activities targeted the organizational level, whereas none targeted the policy level, or the patient, or the “social, political, and legal” domains. However, the resulting changes in care delivery arrangement had consequences for professionals, patients, organizations, and the social, political, and legal domains. A structured process description of a pragmatic implementation project can help assess the fidelity and quality of the implementation, and identify relevant contextual factors for immediate adaptation and future research. The description showed that, in the MOVIT project, there was a discrepancy between the levels and domains targeted by the implementation activities and those influenced by the resulting changes in delivery arrangement. This could have influenced, in particular, the adoption and sustainability of the project. PMID:29161944
Poot, Antonius J; de Waard, Claudia S; Wind, Annet W; Caljouw, Monique A A; Gussekloo, Jacobijn
2017-01-01
Evaluation of the implementation of integrated care can differ from trial-based research due to complexity. Therefore, we examined whether a theory-based method for process description of implementation can contribute to improvement of evidence-based care. MOVIT, a Dutch project aimed at implementing integrated care for older vulnerable persons in residential care homes, was used as a case study. The project activities were defined according to implementation taxonomy and mapped in a matrix of theoretical levels and domains. Project activities mainly targeted professionals (both individual and group). A few activities targeted the organizational level, whereas none targeted the policy level, or the patient, or the "social, political, and legal" domains. However, the resulting changes in care delivery arrangement had consequences for professionals, patients, organizations, and the social, political, and legal domains. A structured process description of a pragmatic implementation project can help assess the fidelity and quality of the implementation, and identify relevant contextual factors for immediate adaptation and future research. The description showed that, in the MOVIT project, there was a discrepancy between the levels and domains targeted by the implementation activities and those influenced by the resulting changes in delivery arrangement. This could have influenced, in particular, the adoption and sustainability of the project.
DD-ligases as a potential target for antibiotics: past, present and future.
Tytgat, I; Colacino, E; Tulkens, P M; Poupaert, J H; Prévost, M; Van Bambeke, F
2009-01-01
DD-ligases catalyze the synthesis of the D-Ala-D-Ala and D-Ala-D-Ser dipeptides or the D Ala-D-Lac depsipeptide in an early step of peptidoglycan synthesis. Their function is essential for bacterial growth and specific to bacteria, making them attractive targets for the development of novel antibiotics. This review examines the biochemical and structural features of these enzymes and presents the main families of inhibitors described so far. Over the last 20 years, 7 structures of DD-ligases have been solved by X-ray crystallography, giving a detailed view of the general topology of the active site and of the residues in the catalytic pocket that play a central role in substrate recognition. This has paved the way to the rational design of inhibitors, which can be classified as (i) analogues of substrates, (ii) analogues of the product of the reaction, (iii) analogues of the transition state, and (iv) original scaffolds discovered by screening or by rational computer-aided design. The three first strategies have led to molecules that are polar by nature and have therefore poor access to their cytosolic target. The fourth one is potentially most promising as it yields more diverse structures. The most active molecules show affinity constants in the microM range, but microbiological evaluation remains scarce (typical MIC 1-8 mg/L for the tested compounds). These data strongly suggest targeting DD-ligases is a promising approach for discovery of new antibiotics. Future research should, however, aim at finding more potent inhibitors endowed with the appropriate pharmacokinetic properties that ensure access to their intracellular target.
Neuropsychology of Learning Disabilities: The Past and the Future.
Fletcher, Jack M; Grigorenko, Elena L
2017-10-01
Over the past 50 years, research on children and adults with learning disabilities has seen significant advances. Neuropsychological research historically focused on the administration of tests sensitive to brain dysfunction to identify putative neural mechanisms underlying learning disabilities that would serve as the basis for treatment. Led by research on classifying and identifying learning disabilities, four pivotal changes in research paradigms have produced a contemporary scientific, interdisciplinary, and international understanding of these disabilities. These changes are (1) the emergence of cognitive science, (2) the development of quantitative and molecular genetics, (3) the advent of noninvasive structural and functional neuroimaging, and (4) experimental trials of interventions focused on improving academic skills and addressing comorbid conditions. Implications for practice indicate a need to move neuropsychological assessment away from a primary focus on systematic, comprehensive assessment of cognitive skills toward more targeted performance-based assessments of academic achievement, comorbid conditions, and intervention response that lead directly to evidence-based treatment plans. Future research will continue to cross disciplinary boundaries to address questions regarding the interaction of neurobiological and contextual variables, the importance of individual differences in treatment response, and an expanded research base on (a) the most severe cases, (b) older people with LDs, and (c) domains of math problem solving, reading comprehension, and written expression. (JINS, 2017, 23, 930-940).
New FINESSE Faculty Institutes for NASA Earth and Space Science Education
NASA Astrophysics Data System (ADS)
Slater, Timothy F.; Slater, Stephanie; Marshall, Sunette Sophia; Stork, Debra; Pomeroy, J. Richard R
2014-06-01
In a systematic effort to improve the preparation of future science teachers, scholars coordinated by the CAPER Center for Astronomy & Physics Education Research are providing a series of high-quality, 2-day professional development workshops, with year-round follow-up support, for college and university professors who prepare future science teachers to work with highly diverse student populations. These workshops focus on reforming and revitalizing undergraduate science teaching methods courses and Earth and Space science content courses that future teachers most often take to reflect contemporary pedagogies and data-rich problem-based learning approaches steeped in authentic scientific inquiry, which consistently demonstrate effectiveness with diverse students. Participants themselves conduct science data-rich research projects during the institutes using highly regarded approaches to inquiry using proven models. In addition, the Institute allocates significant time to illustrating best practices for working with diverse students. Moreover, participants leave with a well-formulated action plan to reform their courses targeting future teachers to include more data-rich scientific inquiry lessons and to be better focused on improving science education for a wide diversity of students. Through these workshops faculty use a backwards faded scaffolding mechanism for working inquiry into a deeper understanding of science by using existing on-line data to develop and research astronomy, progressing from creating a valid and easily testable question, to simple data analysis, arriving at a conclusion, and finally presenting and supporting that conclusion in the classroom. An updated schedule is available at FINESSEProgram.org
Rosenow, Felix; van Alphen, Natascha; Becker, Albert; Chiocchetti, Andreas; Deichmann, Ralf; Deller, Thomas; Freiman, Thomas; Freitag, Christine M; Gehrig, Johannes; Hermsen, Anke M; Jedlicka, Peter; Kell, Christian; Klein, Karl Martin; Knake, Susanne; Kullmann, Dimitri M; Liebner, Stefan; Norwood, Braxton A; Omigie, Diana; Plate, Karlheinz; Reif, Andreas; Reif, Philipp S; Reiss, Yvonne; Roeper, Jochen; Ronellenfitsch, Michael W; Schorge, Stephanie; Schratt, Gerhard; Schwarzacher, Stephan W; Steinbach, Joachim P; Strzelczyk, Adam; Triesch, Jochen; Wagner, Marlies; Walker, Matthew C; von Wegner, Frederic; Bauer, Sebastian
2017-11-01
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy. In the context of these advances, the First International Symposium on Personalized Translational Epilepsy Research (1st ISymPTER) was held in Frankfurt on September 8, 2016, to discuss novel approaches and future perspectives for personalized translational research. These included new developments and ideas in a range of experimental and clinical areas such as deep phenotyping, quantitative brain imaging, EEG/MEG-based analysis of network dysfunction, tissue-based translational studies, innate immunity mechanisms, microRNA as treatment targets, functional characterization of genetic variants in human cell models and rodent organotypic slice cultures, personalized treatment approaches for monogenic epilepsies, blood-brain barrier dysfunction, therapeutic focal tissue modification, computational modeling for target and biomarker identification, and cost analysis in (monogenic) disease and its treatment. This report on the meeting proceedings is aimed at stimulating much needed investments of time and resources in personalized translational epilepsy research. Part I includes the clinical phenotyping and diagnostic methods, EEG network-analysis, biomarkers, and personalized treatment approaches. In Part II, experimental and translational approaches will be discussed (Bauer et al., 2017) [1]. Copyright © 2017 Elsevier Inc. All rights reserved.
Aging, the Central Nervous System, and Mobility in Older Adults: Interventions.
Varma, Vijay R; Hausdorff, Jeffrey M; Studenski, Stephanie A; Rosano, Caterina; Camicioli, Richard; Alexander, Neil B; Chen, Wen G; Lipsitz, Lewis A; Carlson, Michelle C
2016-11-01
Research suggests that the central nervous system (CNS) and mobility are closely linked. CNS-mediated mobility impairment may represent a potentially new and prevalent syndrome within the older adult populations. Interventions targeting this group may have the potential to improve mobility and cognition and prevent disability. In 2012, the Gerontological Society of America (GSA) and the National Institute on Aging (NIA) sponsored a 3-year conference workshop series, "Aging, the CNS, and Mobility." The goal of this third and final conference was to (i) report on the state of the science of interventions targeting CNS-mediated mobility impairment among community-dwelling older adults and (ii) partnering with the NIA, explore the future of research and intervention design focused on a potentially novel aging syndrome. Evidence was presented in five main intervention areas: (i) pharmacology and diet; (ii) exercise; (iii) electrical stimulation; (iv) sensory stimulation/deprivation; and (v) a combined category of multimodal interventions. Workshop participants identified important gaps in knowledge and key recommendations for future interventions related to recruitment and sample selection, intervention design, and methods to measure effectiveness. In order to develop effective preventive interventions for this prevalent syndrome, multidisciplinary teams are essential particularly because of the complex nature of the syndrome. Additionally, integrating innovative methods into the design of interventions may help researchers better measure complex mechanisms, and finally, the value of understanding the link between the CNS and mobility should be conveyed to researchers across disciplines in order to incorporate cognitive and mobility measurements into study protocols. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Genomes2Drugs: Identifies Target Proteins and Lead Drugs from Proteome Data
Toomey, David; Hoppe, Heinrich C.; Brennan, Marian P.; Nolan, Kevin B.; Chubb, Anthony J.
2009-01-01
Background Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. Methodology/Principal Findings To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. Conclusions/Significance Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under ‘change-of-application’ patents. PMID:19593435
Konstas, Anastasios G P; Holló, Gabor
2016-06-01
Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.
Danhier, F
2016-12-28
Tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents and to provide clinicians the ability to overcome shortcomings of current cancer treatment. The major underlying mechanism of the design of nanomedicines was the Enhanced Permeability and Retention (EPR) effect, considered as the "royal gate" in the drug delivery field. However, after the publication of thousands of research papers, the verdict has been handed down: the EPR effect works in rodents but not in humans! Thus the basic rationale of the design and development of nanomedicines in cancer therapy is failing making it necessary to stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be proved in the clinic. It is probably time to dethrone the EPR effect and to ask the question: what is the future of nanomedicines without the EPR effect? The aim of this review is to provide a general overview on (i) the current state of the EPR effect, (ii) the future of nanomedicine and (iii) the strategies of modulation of the tumor microenvironment to improve the delivery of nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.
Laser diode arrays for naval reconnaissance
NASA Astrophysics Data System (ADS)
Holloway, John H., Jr.; Crosby, Frank J.; Petee, Danny A.; Suiter, Harold R.; Witherspoon, Ned H.
2003-09-01
The Airborne Littoral Reconnaissance Technologies (ALRT) Project has demonstrated a nighttime operational minefield detection capability using commercial off-the-shelf high-power Laser Diode Arrays (LDAs). Historically, optical aerial detection of minefields has primarily been limited to daytime operations but LDAs promise compact and efficient lighting to allow for enhanced reconnaissance operations for future mine detection systems. When combined with high-resolution intensified imaging systems, LDAs can illuminate otherwise unseen areas. Future wavelength options will open the way for active multispectral imaging with LDAs. The Coastal Systems Station working for the Office of Naval Research on the ALRT project has designed, developed, integrated, and tested both prototype and commercial arrays from a Cessna airborne platform. Detailed test results show the ability to detect several targets of interest in a variety of background conditions. Initial testing of the prototype arrays, reported on last year, was completed and further investigations of the commercial versions were performed. Polarization-state detection studies were performed, and advantageous properties of the source-target-sensor geometry noted. Current project plans are to expand the field-of-view coverage for Naval exercises in the summer of 2003. This paper describes the test collection, data library products, array information, on-going test analysis results, and future planned testing of the LDAs.
CRISPR-Cas9 for medical genetic screens: applications and future perspectives.
Xue, Hui-Ying; Ji, Li-Juan; Gao, Ai-Mei; Liu, Ping; He, Jing-Dong; Lu, Xiao-Jie
2016-02-01
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9) systems have emerged as versatile and convenient (epi)genome editing tools and have become an important player in medical genetic research. CRISPR-Cas9 and its variants such as catalytically inactivated Cas9 (dead Cas9, dCas9) and scaffold-incorporating single guide sgRNA (scRNA) have been applied in various genomic screen studies. CRISPR screens enable high-throughput interrogation of gene functions in health and diseases. Compared with conventional RNAi screens, CRISPR screens incur less off-target effects and are more versatile in that they can be used in multiple formats such as knockout, knockdown and activation screens, and can target coding and non-coding regions throughout the genome. This powerful screen platform holds the potential of revolutionising functional genomic studies in the near future. Herein, we introduce the mechanisms of (epi)genome editing mediated by CRISPR-Cas9 and its variants, introduce the procedures and applications of CRISPR screen in functional genomics, compare it with conventional screen tools and at last discuss current challenges and opportunities and propose future directions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Novel targets for HIV therapy.
Greene, Warner C; Debyser, Zeger; Ikeda, Yasuhiro; Freed, Eric O; Stephens, Edward; Yonemoto, Wes; Buckheit, Robert W; Esté, José A; Cihlar, Tomas
2008-12-01
There are currently 25 drugs belonging to 6 different inhibitor classes approved for the treatment of human immunodeficiency virus (HIV) infection. However, new anti-HIV agents are still needed to confront the emergence of drug resistance and various adverse effects associated with long-term use of antiretroviral therapy. The 21st International Conference on Antiviral Research, held in April 2008 in Montreal, Canada, therefore featured a special session focused on novel targets for HIV therapy. The session included presentations by world-renowned experts in HIV virology and covered a diverse array of potential targets for the development of new classes of HIV therapies. This review contains concise summaries of discussed topics that included Vif-APOBEC3G, LEDGF/p75, TRIM 5alpha, virus assembly and maturation, and Vpu. The described viral and host factors represent some of the most noted examples of recent scientific breakthroughs that are opening unexplored avenues to novel anti-HIV target discovery and validation, and should feed the antiretroviral drug development pipeline in the near future.
Cell cycle proteins as promising targets in cancer therapy.
Otto, Tobias; Sicinski, Piotr
2017-01-27
Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.
Meeusen, Cecil; Kern, Anna
2016-01-01
The goal of this paper was to investigate the generalizability of prejudice across contexts by analyzing associations between different types of prejudice in a cross-national perspective and by investigating the relation between country-specific contextual factors and target-specific prejudices. Relying on the European Social Survey (2008), results indicated that prejudices were indeed positively associated, confirming the existence of a generalized prejudice component. Next to substantial cross-national differences in associational strength, also within country variance in target-specific associations was observed. This suggested that the motivations for prejudice largely vary according to the intergroup context. Two aspects of the intergroup context - economic conditions and cultural values - showed to be related to generalized and target-specific components of prejudice. Future research on prejudice and context should take an integrative approach that considers both the idea of generalized and specific prejudice simultaneously. Copyright © 2015 Elsevier Inc. All rights reserved.
Aziz, Noreen M; Grady, Patricia A; Curtis, J Randall
2013-12-01
There has been a dramatic increase in attention to the field of palliative care and end-of-life (PCEOL) research over the past 20 years. This increase is particularly notable in the development of palliative care clinical and educational programs. However, there remain important shortcomings in the evidence base to ensure access to and delivery of effective palliative care for patients with life-limiting illness and their families. Development of this evidence base will require that we train the next generation of researchers to focus on issues in PCEOL. The purpose of this article was to explore the current status of the recruitment, training, and retention of future investigators in PCEOL research in the U.S. and propose recommendations to move us forward. Some key contextual issues for developing and supporting this research workforce are articulated, along with timely and important research areas that will need to be addressed during research training and career development. We provide targeted key recommendations to facilitate the nurturing and support of the future research workforce that is needed to ensure the development and implementation of the science necessary for providing high-quality, evidence-based palliative care to all who need and desire it. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
21st century trucking: A trajectory for ergonomics and road freight.
Bedinger, M; Walker, G H; Piecyk, M; Greening, P
2016-03-01
Over the past decade there has been significant pressure to minimise emissions and safety risks related to commercial driving. This pressure to meet the triple bottom line of cost, environment, and society has often resulted in the rapid application of vehicle technologies designed to mitigate undesired effects. Often the cognitive and behavioural effects of technologies on the commercial driver have not received in-depth analysis to determine comprehensive viability. As such, this paper aims to identify a timescale for implementation for future technologies for UK road freight, and likely associated human factors issues, improving upon the currently employed 'trial-and-error' approach to implementation which may carry high economic, environmental, safety-related risk. Thought experiments are carried out to broadly explore these future systems. Furthermore, this work aims to examine whether technology alone will be enough to meet future CO2 reduction targets, and assess the role of behavioural and systems interventions for future research. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.
Dara, Ajay; Sangamwar, Abhay T.
2014-01-01
Background In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India’s largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. Methodology/Principal Findings The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. Conclusions/Significance The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide. PMID:25083710
Dara, Ajay; Sangamwar, Abhay T
2014-01-01
In a search for an effective anticancer therapy the R&D units from leading universities and institutes reveal numerous technologies in the form of patent documents. The article addressed comparative anticancer patent landscape and technology assessment of Council of Scientific and Industrial Research (CSIR): India's largest R&D organisation with top twenty international public funded universities and institutes from eight different countries. The methodology include quantitative and qualitative assessment based on the bibliometric parameters and manual technology categorisation to understand the changing patent trends and recent novel technologies. The research finding analysed 25,254 patent documents from the year 1993 to 2013 and reported the insights of latest anticancer technologies and targets through categorisation studies at the level of drug discovery, development and treatment & diagnosis. The article has reported the technology correlation matrix of twelve secondary class technologies with 34 tertiary sub-class research area to identify the leading technologies and scope of future research through whitespaces analysis. In addition, the results have also addressed the target analysis, leading inventor, assignee, collaboration network, geographical distribution, patent trend analysis, citation maps and technology assessment with respect to international patent classification systems such as CPC, IPC and CPI codes. The result suggested peptide technology as the dominating research area next to gene therapy, vaccine and medical preparation containing organic compounds. The Indian CSIR has ranked itself at seventh position among the top 20 universities. Globally, the anticancer research was focused in the area of genetics and immunology, whereas Indian CSIR reported more patents related to plant extract and organic preparation. The article provided a glimpse of two decade anticancer scenario with respect to top public funded universities worldwide.
Canine Detection of the Volatilome: A Review of Implications for Pathogen and Disease Detection.
Angle, Craig; Waggoner, Lowell Paul; Ferrando, Arny; Haney, Pamela; Passler, Thomas
2016-01-01
The volatilome is the entire set of volatile organic compounds (VOC) produced by an organism. The accumulation of VOC inside and outside of the body reflects the unique metabolic state of an organism. Scientists are developing technologies to non-invasively detect VOC for the purposes of medical diagnosis, therapeutic monitoring, disease outbreak containment, and disease prevention. Detection dogs are proven to be a valuable real-time mobile detection technology for the detection of VOC related to explosives, narcotics, humans, and many other targets of interests. Little is known about what dogs are detecting when searching for biological targets. It is important to understand where biological VOC originates and how dogs might be able to detect biological targets. This review paper discusses the recent scientific literature involving VOC analysis and postulates potential biological targets for canine detection. Dogs have shown their ability to detect pathogen and disease-specific VOC. Future research will determine if dogs can be employed operationally in hospitals, on borders, in underserved areas, on farms, and in other operational environments to give real-time feedback on the presence of a biological target.
Nguyen, Thi Quynh Ngoc; Lim, Kah Wai; Phan, Anh Tuân
2017-09-20
Small-molecule ligands targeting nucleic acids have been explored as potential therapeutic agents. Duplex groove-binding ligands have been shown to recognize DNA in a sequence-specific manner. On the other hand, quadruplex-binding ligands exhibit high selectivity between quadruplex and duplex, but show limited discrimination between different quadruplex structures. Here we propose a dual-specific approach through the simultaneous application of duplex- and quadruplex-binders. We demonstrated that a quadruplex-specific ligand and a duplex-specific ligand can simultaneously interact at two separate binding sites of a quadruplex-duplex hybrid harbouring both quadruplex and duplex structural elements. Such a dual-specific targeting strategy would combine the sequence specificity of duplex-binders and the strong binding affinity of quadruplex-binders, potentially allowing the specific targeting of unique quadruplex structures. Future research can be directed towards the development of conjugated compounds targeting specific genomic quadruplex-duplex sites, for which the linker would be highly context-dependent in terms of length and flexibility, as well as the attachment points onto both ligands.
Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.
Wu, Tzung-Ju; Wang, Xiaowen; Zhang, Yanjie; Meng, Linghua; Kerrigan, John E; Burley, Stephen K; Zheng, X F Steven
2015-04-21
Protein kinases are therapeutic targets for human cancer. However, "gatekeeper" mutations in tyrosine kinases cause acquired clinical resistance, limiting long-term treatment benefits. mTOR is a key cancer driver and drug target. Numerous small-molecule mTOR kinase inhibitors have been developed, with some already in human clinical trials. Given our clinical experience with targeted therapeutics, acquired drug resistance in mTOR is thought likely, but not yet documented. Herein, we describe identification of a hot spot (L2185) for drug-resistant mutations, which is distinct from the gatekeeper site, and a chemical scaffold refractory to drug-resistant mutations. We also provide new insights into mTOR kinase structure and function. The hot spot mutations are potentially useful as surrogate biomarkers for acquired drug resistance in ongoing clinical trials and future treatments and for the design of the next generation of mTOR-targeted drugs. Our study provides a foundation for further research into mTOR kinase function and targeting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick
2014-01-01
Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...
Karlsen, Micaela C; Lichtenstein, Alice H; Economos, Christina D; Folta, Sara C; Rogers, Gail; Jacques, Paul F; Livingston, Kara A; Rancaño, Katherine M; McKeown, Nicola M
2018-01-01
Abstract Background Although there is interest in popular diets such as vegan and vegetarian, Paleo, and other “whole food” diets, existing cohort studies lack data for these subgroups. The use of electronic data capture and Web-based surveys in nutrition research may be valuable for future studies by allowing targeting of specific dietary subgroups. Objective The aim was to perform a Feasibility Survey (FS) to assess the practicality of Web-based research methods to gather data and to maximize response rates among followers of popular diets. Methods The FS was an open, voluntary, 15-min survey conducted over 8 wk in the summer of 2015. Recruitment targeted self-identified followers of popular diets from a convenience sample, offering no incentives, via social media and e-newsletters shared by recruitment partners. Feasibility was assessed by number of responses, survey completion rate, distribution of diets, geographic location, and willingness to participate in future research. Results A total of 14,003 surveys were initiated; 13,787 individuals consented, and 9726 completed the survey (71% of consented). The numbers of unique visitors to the questionnaire site, view rate, and participation rate were not captured. Among respondents with complete demographic data, 83% were female and 93% were white. Diet designations were collapsed into the following groups: whole-food, plant-based (25%); vegan and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and pescatarian (9%); whole food (8%); Weston A Price (5%); and low-carbohydrate (low-carb) (4%). Forced-response, multiple-choice questions produced the highest response rates (0–2% selected “prefer not to answer”). The percentage who were willing to complete future online questionnaires was 86%, diet recall was 93%, and food diary was 75%; the percentages willing to provide a finger-stick blood sample, venipuncture blood sample, urine sample, and stool sample were 60%, 44%, 58%, and 42%, respectively. Conclusions This survey suggests that recruiting followers of popular diets is feasible with the use of Web-based methods. The unbalanced sample with respect to sex and race/ethnicity could be corrected with specific recruitment strategies using targeted online marketing techniques. PMID:29955724
Robot Tracking of Human Subjects in Field Environments
NASA Technical Reports Server (NTRS)
Graham, Jeffrey; Shillcutt, Kimberly
2003-01-01
Future planetary exploration will involve both humans and robots. Understanding and improving their interaction is a main focus of research in the Intelligent Systems Branch at NASA's Johnson Space Center. By teaming intelligent robots with astronauts on surface extra-vehicular activities (EVAs), safety and productivity can be improved. The EVA Robotic Assistant (ERA) project was established to study the issues of human-robot teams, to develop a testbed robot to assist space-suited humans in exploration tasks, and to experimentally determine the effectiveness of an EVA assistant robot. A companion paper discusses the ERA project in general, its history starting with ASRO (Astronaut-Rover project), and the results of recent field tests in Arizona. This paper focuses on one aspect of the research, robot tracking, in greater detail: the software architecture and algorithms. The ERA robot is capable of moving towards and/or continuously following mobile or stationary targets or sequences of targets. The contributions made by this research include how the low-level pose data is assembled, normalized and communicated, how the tracking algorithm was generalized and implemented, and qualitative performance reports from recent field tests.
NASA Technical Reports Server (NTRS)
Domingue, D. L.; Allain, J.-P.; Banks, M.; Christoffersen, R.; Cintala, M.; Clark, R.; Cloutis, E.; Graps, A.; Hendrix, A. R.; Hsieh, H.;
2018-01-01
The Toolbox for Research and Exploration (TREX) is a NASA SSERVI (Solar System Exploration Research Virtual Institute) node. TREX (trex.psi.edu) aims to decrease risk to future missions, specifically to the Moon, the Martian moons, and near- Earth asteroids, by improving mission success and assuring the safety of astronauts, their instruments, and spacecraft. TREX studies will focus on characteristics of the fine grains that cover the surfaces of these target bodies - their spectral characteristics and the potential resources (such as H2O) they may harbor. TREX studies are organized into four Themes (Laboratory- Studies, Moon-Studies, Small-Bodies Studies, and Field-Work). In this presentation, we focus on the work targeted by the Small-Bodies Theme. The Small-Bodies' Theme delves into several topics, many which overlap or are synergistic with the other TREX Themes. The main topics include photometry, spectral modeling, laboratory simulations of space weathering processes relevant to asteroids, the assembly of an asteroid regolith database, the dichotomy between nuclear and reflectance spectroscopy, and the dynamical evolution of asteroids and the implications for the retention of volatiles.
Anterior eye segment drug delivery systems: current treatments and future challenges.
Molokhia, Sarah A; Thomas, Samuel C; Garff, Kevin J; Mandell, Kenneth J; Wirostko, Barbara M
2013-03-01
New technologies for delivery of drugs, such as small molecules and biologics, are of growing interest among clinical and pharmaceutical researchers for use in treating anterior segment eye disease. The challenge is to deliver effective drugs at therapeutic concentrations to the targeted ocular tissue with minimal side effects. To achieve this, a better understanding of the unmet needs, what is required of the various methods of delivery to achieve successful delivery, and the potential challenges of anterior segment drug delivery is necessary and the primarily aim of this review. This review covers the various physiological and anatomical barriers that exist for effective delivery to the targeted tissue of the eye, the pathological conditions of the anterior segment, and the unmet needs for treatment of these ocular diseases. Second, it reviews the novel delivery technologies that have the potential to maintain and/or improve the drug's therapeutic index and improving both patient adherence for chronic therapy and potential patient outcomes. This review bridges the pharmaceutical and clinical research/challenges and provides a detailed overview of anterior segment drug delivery accomplishments thus far, for researchers and clinicians.
Concentrating solar power (CSP) power cycle improvements through application of advanced materials
NASA Astrophysics Data System (ADS)
Siefert, John A.; Libby, Cara; Shingledecker, John
2016-05-01
Concentrating solar power (CSP) systems with thermal energy storage (TES) capability offer unique advantages to other renewable energy technologies in that solar radiation can be captured and stored for utilization when the sun is not shining. This makes the technology attractive as a dispatchable resource, and as such the Electric Power Research Institute (EPRI) has been engaged in research and development activities to understand and track the technology, identify key technical challenges, and enable improvements to meet future cost and performance targets to enable greater adoption of this carbon-free energy resource. EPRI is also involved with technically leading a consortium of manufacturers, government labs, and research organizations to enable the next generation of fossil fired power plants with advanced ultrasupercritical (A-USC) steam temperatures up to 760°C (1400°F). Materials are a key enabling technology for both of these seemingly opposed systems. This paper discusses how major strides in structural materials for A-USC fossil fired power plants may be translated into improved CSP systems which meet target requirements.
Siegfried, Alexa L; Carbone, Eric G; Meit, Michael B; Kennedy, Mallory J; Yusuf, Hussain; Kahn, Emily B
2017-10-01
This study describes findings from an assessment conducted to identify perceived knowledge gaps, information needs, and research priorities among state, territorial, and local public health preparedness directors and coordinators related to public health emergency preparedness and response (PHPR). The goal of the study was to gather information that would be useful for ensuring that future funding for research and evaluation targets areas most critical for advancing public health practice. We implemented a mixed-methods approach to identify and prioritize PHPR research questions. A web survey was sent to all state, city, and territorial health agencies funded through the Public Health Emergency Preparedness (PHEP) Cooperative Agreement program and a sample of local health departments (LHDs). Three focus groups of state and local practitioners and subject matter experts from the Centers for Disease Control and Prevention (CDC) were subsequently conducted, followed by 3 meetings of an expert panel of PHPR practitioners and CDC experts to prioritize and refine the research questions. We identified a final list of 44 research questions that were deemed by study participants as priority topics where future research can inform PHPR programs and practice. We identified differences in perceived research priorities between PHEP awardees and LHD survey respondents; the number of research questions rated as important was greater among LHDs than among PHEP awardees (75%, n=33, compared to 24%, n=15). The research questions identified provide insight into public health practitioners' perceived knowledge gaps and the types of information that would be most useful for informing and advancing PHPR practice. The study also points to a higher level of information need among LHDs than among PHEP awardees. These findings are important for CDC and the PHPR research community to ensure that future research studies are responsive to practitioners' needs and provide the information required to enhance their capacity to meet the needs of the communities and jurisdictions they serve. (Disaster Med Public Health Preparedness. 2017;11:552-561).
Token Economy: A Systematic Review of Procedural Descriptions.
Ivy, Jonathan W; Meindl, James N; Overley, Eric; Robson, Kristen M
2017-09-01
The token economy is a well-established and widely used behavioral intervention. A token economy is comprised of six procedural components: the target response(s), a token that functions as a conditioned reinforcer, backup reinforcers, and three interconnected schedules of reinforcement. Despite decades of applied research, the extent to which the procedures of a token economy are described in complete and replicable detail has not been evaluated. Given the inherent complexity of a token economy, an analysis of the procedural descriptions may benefit future token economy research and practice. Articles published between 2000 and 2015 that included implementation of a token economy within an applied setting were identified and reviewed with a focus on evaluating the thoroughness of procedural descriptions. The results show that token economy components are regularly omitted or described in vague terms. Of the articles included in this analysis, only 19% (18 of 96 articles reviewed) included replicable and complete descriptions of all primary components. Missing or vague component descriptions could negatively affect future research or applied practice. Recommendations are provided to improve component descriptions.
Nontechnical skill training and the use of scenarios in modern surgical education.
Brunckhorst, Oliver; Khan, Muhammad S; Dasgupta, Prokar; Ahmed, Kamran
2017-07-01
Nontechnical skills are being increasingly recognized as a core reason of surgical errors. Combined with the changing nature of surgical training, there has therefore been an increase in nontechnical skill research in the literature. This review therefore aims to: define nontechnical skillsets, assess current training methods, explore assessment modalities and suggest future research aims. The literature demonstrates an increasing understanding of the components of nontechnical skills within surgery. This has led to a greater availability of validated training methods for its training, including the use of didactic teaching, e-learning and simulation-based scenarios. In addition, there are now various extensively validated assessment tools for nontechnical skills including NOTSS, the Oxford NOTECHS and OTAS. Finally, there is now more focus on the development of tools which target individual nontechnical skill components and an attempt to understand which of these play a greater role in specific procedures such as laparoscopic or robotic surgery. Current evidence demonstrates various training methods and tools for the training of nontechnical skills. Future research is likely to focus increasingly on individual nontechnical skill components and procedure-specific skills.
Rodent models in Down syndrome research: impact and future opportunities
2017-01-01
ABSTRACT Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage-sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets. PMID:28993310
Rodent models in Down syndrome research: impact and future opportunities.
Herault, Yann; Delabar, Jean M; Fisher, Elizabeth M C; Tybulewicz, Victor L J; Yu, Eugene; Brault, Veronique
2017-10-01
Down syndrome is caused by trisomy of chromosome 21. To date, a multiplicity of mouse models with Down-syndrome-related features has been developed to understand this complex human chromosomal disorder. These mouse models have been important for determining genotype-phenotype relationships and identification of dosage-sensitive genes involved in the pathophysiology of the condition, and in exploring the impact of the additional chromosome on the whole genome. Mouse models of Down syndrome have also been used to test therapeutic strategies. Here, we provide an overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome. We also speculate on possible and probable future directions of research in this fast-moving field. As our understanding of the syndrome improves and genome engineering technologies evolve, it is necessary to coordinate efforts to make all Down syndrome models available to the community, to test therapeutics in models that replicate the whole trisomy and design new animal models to promote further discovery of potential therapeutic targets. © 2017. Published by The Company of Biologists Ltd.
Proteases for Processing Proneuropeptides into Peptide Neurotransmitters and Hormones
Hook, Vivian; Funkelstein, Lydiane; Lu, Douglas; Bark, Steven; Wegrzyn, Jill; Hwang, Shin-Rong
2009-01-01
Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell-cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease. PMID:18184105
Emotion regulation and mental health: recent findings, current challenges, and future directions.
Berking, Matthias; Wupperman, Peggilee
2012-03-01
In recent years, deficits in emotion regulation have been studied as a putative maintaining factor and promising treatment target in a broad range of mental disorders. This article aims to provide an integrative review of the latest theoretical and empirical developments in this rapidly growing field of research. Deficits in emotion regulation appear to be relevant to the development, maintenance, and treatment of various forms of psychopathology. Increasing evidence demonstrates that deficits in the ability to adaptively cope with challenging emotions are related to depression, borderline personality disorder, substance-use disorders, eating disorders, somatoform disorders, and a variety of other psychopathological symptoms. Unfortunately, studies differ with regard to the conceptualization and assessment of emotion regulation, thus limiting the ability to compare findings across studies. Future research should systematically work to use comparable methods in order to clarify the following: which individuals have; what kinds of emotion regulation difficulties with; which types of emotions; and what interventions are most effective in alleviating these difficulties. Despite some yet to be resolved challenges, the concept of emotion regulation has a broad and significant heuristic value for research in mental health.
Chen, Kuan-Hua; Wells, Jenna L; Otero, Marcela C; Lwi, Sandy J; Haase, Claudia M; Levenson, Robert W
2017-01-01
Behavioral symptoms in patients with neurodegenerative diseases can be particularly challenging for caregivers. Previously, we reported that patients with frontotemporal dementia (FTD) and Alzheimer's disease (AD) experienced emotions that were atypical or incongruent with a given situation (i.e., non-target emotions). We tested the hypothesis that greater experience of non-target emotions by patients is associated with lower caregiver emotional well-being. 178 patients with FTD, AD, or other neurodegenerative diseases and 35 healthy individuals watched 3 films designed to induce amusement, sadness, and disgust, and then reported their emotions during the films. Caregivers of the patients reported their own emotional well-being on the Medical Outcomes Study 36-item Short-Form Health Survey. In response to the amusement and sadness (but not disgust) films, greater experience of non-target emotions by patients was related to lower caregiver emotional well-being. These effects were specific to patients' experience of negative non-target emotions (i.e., not found for positive non-target emotions or for negative or positive target emotions). The findings reveal a previously unstudied patient behavior that is related to worse caregiver emotional well-being. Future research and clinical assessment may benefit from evaluating non-target emotions in patients. © 2017 S. Karger AG, Basel.
Lai, Byron; Young, Hui-Ju; Bickel, C Scott; Motl, Robert W; Rimmer, James H
2017-10-01
This review synthesized physical activity and exercise intervention literature for the past 10 yrs for people with physical and cognitive disabilities including intervention characteristics, behavior change strategies, and types of technologies used to improve targeted outcomes. Systematic searches yielded 132 eligible studies. The major disability groups were multiple sclerosis (41%), stroke (15%), and spinal cord injury (12%). Research designs primarily involved randomized controlled trials (61%) versus quasi-experimental designs (39%). Approximately 20% of the interventions used some form of the following technology: information and communication technology (48%), interactive technology (37%), or electronic gauges (30%). Eighteen percent of studies used intervention strategies based on behavioral theory, which was typically combined with technology to promote activity and increase adherence in generally larger study samples. The three prevailing theories included social cognitive theory (58%), supportive accountability theory (21%), and transtheoretical model (21%). Upon completing the intervention, studies reported primarily significant outcomes (80%). Exercise research for PWD has grown in both quantity and quality, but several gaps remain. Study findings provide a roadmap for future exercise trials on understudied populations and highlight technology and behavior change theory as drivers of future intervention research.
Considering future pharmacotherapy for PTSD.
Friedman, Matthew J; Bernardy, Nancy C
2017-05-10
Posttraumatic stress disorder (PTSD) is a prevalent, disabling, and often chronic condition that may develop following exposure to a traumatic event. Despite the immense social and economic ramifications of PTSD, there has been relatively little recent development of new pharmacotherapies. The majority of pharmacological randomized clinical trials (RCTs) that has been conducted are now dated. Existing treatments for PTSD primarily have come out of research that tested medications developed for other disorders such as antidepressants, anti-hypertensives, antipsychotics, anticonvulsants, and anxiolytics. With an improved understanding of the complex pathophysiology of PTSD, we consider why it has taken so long to identify important targets to advance the field by addressing the underlying pathophysiology in pharmacological interventions. Exciting developments include research into PTSD-related abnormalities associated with dysregulation of adrenergic, hypothalamic-pituitary-adrenocortical, monoaminergic, peptide, glutamatergic, GABAergic, cannabinoid, opioid, and other neurotransmitter and neuroendocrine systems. Yet, this is a broad list and there are many unanswered questions. Current research on biomarkers associated with different clinical phenotypes of PTSD should lead to novel and more specific pharmacotherapeutic strategies. In this brief review, we consider key questions regarding current knowledge on pharmacological treatments for PTSD and highlight evolving practices in future research. Copyright © 2016. Published by Elsevier B.V.
Greenshell™ Mussels: A Review of Veterinary Trials and Future Research Directions.
Eason, Charles T; Adams, Serean L; Puddick, Jonathan; Romanazzi, Donato; Miller, Matthew R; King, Nick; Johns, Sarah; Forbes-Blom, Elizabeth; Hessian, Paul A; Stamp, Lisa K; Packer, Michael A
2018-03-27
The therapeutic benefits of Greenshell™ mussel (GSM; Perna canaliculus ) preparations have been studied using in vitro test systems, animal models, and human clinical trials focusing mainly on anti-inflammatory and anti-arthritic effects. Activity is thought to be linked to key active ingredients that include omega-3 polyunsaturated fatty acids, a variety of carotenoids and other bioactive compounds. In this paper, we review the studies that have been undertaken in dogs, cats, and horses, and outline new research directions in shellfish breeding and high-value nutrition research programmes targeted at enhancing the efficacy of mussel and algal extracts. The addition of GSM to animal diets has alleviated feline degenerative joint disease and arthritis symptoms, and chronic orthopaedic pain in dogs. In horses, GSM extracts decreased the severity of lameness and joint pain and provided improved joint flexion in limbs with lameness attributed to osteoarthritis. Future research in this area should focus on elucidating the key active ingredients in order to link concentrations of these active ingredients with their pharmacokinetics and therapeutic effects. This would enable consistent and improved efficacy from GSM-based products for the purpose of improved animal health.
Daston, George; Knight, Derek J; Schwarz, Michael; Gocht, Tilman; Thomas, Russell S; Mahony, Catherine; Whelan, Maurice
2015-01-01
The development of non-animal methodology to evaluate the potential for a chemical to cause systemic toxicity is one of the grand challenges of modern science. The European research programme SEURAT is active in this field and will conclude its first phase, SEURAT-1, in December 2015. Drawing on the experience gained in SEURAT-1 and appreciating international advancement in both basic and regulatory science, we reflect here on how SEURAT should evolve and propose that further research and development should be directed along two complementary and interconnecting work streams. The first work stream would focus on developing new 'paradigm' approaches for regulatory science. The goal here is the identification of 'critical biological targets' relevant for toxicity and to test their suitability to be used as anchors for predicting toxicity. The second work stream would focus on integration and application of new approach methods for hazard (and risk) assessment within the current regulatory 'paradigm', aiming for acceptance of animal-free testing strategies by regulatory authorities (i.e. translating scientific achievements into regulation). Components for both work streams are discussed and may provide a structure for a future research programme in the field of predictive toxicology.
Hill, Andrew; Redd, Christopher; Gotham, Dzintars; Erbacher, Isabelle; Meldrum, Jonathan; Harada, Ryo
2017-01-01
Objectives The aim of this study was to estimate lowest possible treatment costs for four novel cancer drugs, hypothesising that generic manufacturing could significantly reduce treatment costs. Setting This research was carried out in a non-clinical research setting using secondary data. Participants There were no human participants in the study. Four drugs were selected for the study: bortezomib, dasatinib, everolimus and gefitinib. These medications were selected according to their clinical importance, novel pharmaceutical actions and the availability of generic price data. Primary and secondary outcome measures Target costs for treatment were to be generated for each indication for each treatment. The primary outcome measure was the target cost according to a production cost calculation algorithm. The secondary outcome measure was the target cost as the lowest available generic price; this was necessary where export data were not available to generate an estimate from our cost calculation algorithm. Other outcomes included patent expiry dates and total eligible treatment populations. Results Target prices were £411 per cycle for bortezomib, £9 per month for dasatinib, £852 per month for everolimus and £10 per month for gefitinib. Compared with current list prices in England, these target prices would represent reductions of 74–99.6%. Patent expiry dates were bortezomib 2014–22, dasatinib 2020–26, everolimus 2019–25 and gefitinib 2017. The total global eligible treatment population in 1 year is 769 736. Conclusions Our findings demonstrate that affordable drug treatment costs are possible for novel cancer drugs, suggesting that new therapeutic options can be made available to patients and doctors worldwide. Assessing treatment cost estimations alongside cost-effectiveness evaluations is an important area of future research. PMID:28110283
2014-01-01
Background Amid continuing social unrest from the Great East Japan Earthquake and subsequent Fukushima nuclear accident of 2011, the Japanese government announced plans for a major biobanking project in the disaster-stricken areas, to be administered by the ‘Tohoku Medical Megabank Organization’ (ToMMo). This project differs from previous biobanking projects in that it 1) was initiated mainly to boost post-disaster recovery and reconstruction; and 2) targets the area’s survivors as its primary subjects. Here, we review the ethics of the ToMMo biobanking project within the wider context of disaster remediation. Discussion Private citizens in the Tohoku region have criticized the project proposal, asking for further review of the ethics of targeting disaster survivors for this study. They claim the project violates the Declaration of Helsinki’s ethical provisions in that (1) government and university researchers initiated it without consulting any Tohoku survivors; (2) survivors already suffering extreme losses may view study involvement as meaningless or even undesirable, yet feel forced to participate in exchange for tenuous promises of future assistance, thus exploiting those most in need. Although the ToMMo has promised certain future social benefits for the target population in exchange for participating in its biobanking research, it is questionable whether such research can address the immediate health needs of the Tohoku disaster survivors in any significant fashion. The ethics of recruiting still-struggling survivors is also questionable. Summary This case analysis demonstrates that conducting a post-disaster biobanking project on survivors poses issues concerning potential exploitation and the just distribution of benefits and burdens. Though the ToMMo emphasizes the project’s importance for individual survivors and regional recovery, it is questionable whether such research can justly respond to the survivors’ immediate health needs and whether truly voluntary participation can be ensured in such a crisis. Our society must enhance this nationwide debate and reexamine our priorities for recovery in the disaster-stricken regions. We should evaluate both whether and how this project can truly contribute to the survivors’ quality of life. PMID:24996254
Matsui, Kenji; Tashiro, Shimon
2014-07-04
Amid continuing social unrest from the Great East Japan Earthquake and subsequent Fukushima nuclear accident of 2011, the Japanese government announced plans for a major biobanking project in the disaster-stricken areas, to be administered by the 'Tohoku Medical Megabank Organization' (ToMMo). This project differs from previous biobanking projects in that it 1) was initiated mainly to boost post-disaster recovery and reconstruction; and 2) targets the area's survivors as its primary subjects. Here, we review the ethics of the ToMMo biobanking project within the wider context of disaster remediation. Private citizens in the Tohoku region have criticized the project proposal, asking for further review of the ethics of targeting disaster survivors for this study. They claim the project violates the Declaration of Helsinki's ethical provisions in that (1) government and university researchers initiated it without consulting any Tohoku survivors; (2) survivors already suffering extreme losses may view study involvement as meaningless or even undesirable, yet feel forced to participate in exchange for tenuous promises of future assistance, thus exploiting those most in need.Although the ToMMo has promised certain future social benefits for the target population in exchange for participating in its biobanking research, it is questionable whether such research can address the immediate health needs of the Tohoku disaster survivors in any significant fashion. The ethics of recruiting still-struggling survivors is also questionable. This case analysis demonstrates that conducting a post-disaster biobanking project on survivors poses issues concerning potential exploitation and the just distribution of benefits and burdens. Though the ToMMo emphasizes the project's importance for individual survivors and regional recovery, it is questionable whether such research can justly respond to the survivors' immediate health needs and whether truly voluntary participation can be ensured in such a crisis. Our society must enhance this nationwide debate and reexamine our priorities for recovery in the disaster-stricken regions. We should evaluate both whether and how this project can truly contribute to the survivors' quality of life.
Coates, Laura C; FitzGerald, Oliver; Merola, Joseph F; Smolen, Josef; van Mens, Leonieke J J; Bertheussen, Heidi; Boehncke, Wolf-Henning; Callis Duffin, Kristina; Campbell, Willemina; de Wit, Maarten; Gladman, Dafna; Gottlieb, Alice; James, Jana; Kavanaugh, Arthur; Kristensen, Lars Erik; Kvien, Tore K; Luger, Thomas; McHugh, Neil; Mease, Philip; Nash, Peter; Ogdie, Alexis; Rosen, Cheryl F; Strand, Vibeke; Tillett, William; Veale, Douglas J; Helliwell, Philip S
2018-03-01
A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA). Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey. Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA. Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies. © 2017, American College of Rheumatology.
Hongvivatana, T
1986-09-01
Human behavior in malaria is often narrowly referred to behavior of the target populations in transmission and control of malaria. In this presentation it was discussed that such view is too narrow. A broader framework incorporating illness behavior and human behavior in malaria control bureaucracies is needed for the success of national malaria control programme. Literature under the three broad categories of human behavior in malaria is reviewed to justify future directions in human behavior research and their significance for successful malaria control.
GPCRs and EGFR - Cross-talk of membrane receptors in cancer.
Köse, Meryem
2017-08-15
G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation. It will give an overview about the current status of the research and future directions, highlight recent trends in the field, and discuss the potential of therapeutic strategies combining GPCR and EGFR targeting on the one hand and specific targeting of the cross-talk on the other hand in cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.
[Targeted drug delivery system: potential application to resveratrol].
Farghali, Hassan; Kameníková, Ludmila
2017-01-01
Drug delivery system (DDS) is intended to increasing effectiveness of drugs through targeted distribution and to reducing of unwanted effects. In this mini-review, the basic principles of nanotechnology that were developed for DDS were reported including sections on the present research in key areas that are important for future investigations. Attention is paid on resveratrol as a model phytochemical with interesting pharmacologic profile which was demonstrated in great numbers of studies and for its wide use as supplemental therapy. Due to complicated pharmacokinetic profile of resveratrol that is characterized by very low bioavailability in spite of high oral absorption, the effects of resveratrol is being studied in new nanotechnology preparations of pharmaceutical formulation. Herein we report on results of present in vitro and in vivo investigations with resveratrol in new types of drug formulations using different nanoparticles as liposomes, solid lipid particles, cyclodextrins and micelles.Key words: targeted drug delivery nanotechnology resveratrol.
Moderating factors of video-modeling with other as model: a meta-analysis of single-case studies.
Mason, Rose A; Ganz, Jennifer B; Parker, Richard I; Burke, Mack D; Camargo, Siglia P
2012-01-01
Video modeling with other as model (VMO) is a more practical method for implementing video-based modeling techniques, such as video self-modeling, which requires significantly more editing. Despite this, identification of contextual factors such as participant characteristics and targeted outcomes that moderate the effectiveness of VMO has not previously been explored. The purpose of this study was to meta-analytically evaluate the evidence base of VMO with individuals with disabilities to determine if participant characteristics and targeted outcomes moderate the effectiveness of the intervention. Findings indicate that VMO is highly effective for participants with autism spectrum disorder (IRD=.83) and moderately effective for participants with developmental disabilities (IRD=.68). However, differential effects are indicated across levels of moderators for diagnoses and targeted outcomes. Implications for practice and future research are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
Androgens and endometrium: New insights and new targets.
Simitsidellis, Ioannis; Saunders, Philippa T K; Gibson, Douglas A
2018-04-15
Androgens are synthesised in both the ovary and adrenals in women and play an important role in the regulation of female fertility, as well as in the aetiology of disorders such as polycystic ovarian syndrome, endometriosis and endometrial cancer. The endometrium is an androgen target tissue and the impact of AR-mediated effects has been studied using human endometrial tissue samples and rodent models. In this review we highlight recent evidence that endometrial androgen biosynthesis and intracrine action is important in preparation of a tissue microenvironment that can support implantation and establishment of pregnancy. The impact of androgens on endometrial cell proliferation, in repair of the endometrial wound at the time of menstruation and in endometrial disorders is discussed. Future directions for research focused on AR function as a therapeutic target are considered. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.
Cole, Suzanne M.; McKenney-Shubert, Shannon J.; Jones, Sonya J.; Peterson, Karen E.
2016-01-01
Objective To explore how a sample of Mexican American mothers with preschool-aged children recruited from a Midwestern WIC clinic obtain information about 4 behaviors associated with childhood obesity risk: eating, physical activity, screen time and sleep. Methods One-on-1, structured interviews, in which participants were asked how they communicated with family, learned to take care of their first infant and obtained information about the 4 targeted behaviors for their preschool-aged child. Setting An urban WIC clinic in the Midwest. Participants Forty Mexican-descent WIC mothers with children ages 3–4. Phenomenon of Interest Exposure to information about the 4 targeted behaviors among Mexican-descent mothers participating in WIC. Analysis Quantitative and qualitative data were used to characterize and compare across participants. Results Participants primarily obtained information from their child’s maternal grandmother during their first child’s infancy and from health professionals for their preschool-aged child. Participants typically obtained information through interpersonal communication, television and magazines. Participants were most interested in healthy eating information and least interested in screen time information. Some participants did not seek information. Conclusions Participants engaged in different patterns of information seeking across their child’s development and the 4 behaviors, suggesting that future research should be behaviorally specific. Findings from this study suggest several hypotheses to test in future research. PMID:27876321
NASA Astrophysics Data System (ADS)
Laursen, Sandra L.; Hassi, Marja-Liisa; Hough, Sarah
2016-02-01
This mixed-methods study describes classroom characteristics and student outcomes from university mathematics courses that are based in mathematics departments, targeted to future pre-tertiary teachers, and taught with inquiry-based learning (IBL) approaches. The study focused on three two-term sequences taught at two research universities, separately targeting elementary and secondary pre-service teachers. Classroom observation established that the courses were taught with student-centred methods that were comparable to those used in IBL courses for students in mathematics-intensive fields at the same institutions. To measure pre-service teachers' gains in mathematical knowledge for teaching, we administered the Learning Mathematics for Teaching (LMT) instrument developed by Hill, Ball and Schilling for in-service teacher professional development. Results from the LMT show that pre-service teachers made significant score gains from beginning to end of their course, while data from interviews and from surveys of learning gains show that pre-service teachers viewed their gains as relevant to their future teaching work. Measured changes on pre-/post-surveys of attitudes and beliefs were generally supportive of learning mathematics but modest in magnitude. The study is distinctive in applying the LMT to document pre-service teachers' growth in mathematical knowledge for teaching. The study also suggests IBL is an approach well suited to mathematics departments seeking to strengthen their pre-service teacher preparation offerings in ways consistent with research-based recommendations.
Bullet Impact Safety Study of PBX-9502
NASA Astrophysics Data System (ADS)
Ferranti, Louis
2013-06-01
A new small arms capability for performing bullet impact testing into energetic materials has recently been activated at Lawrence Livermore National Laboratory located in the High Explosives Applications Facility (HEAF). The initial capability includes 0.223, 0.30, and 0.50 testing calibers with the flexibility to add other barrels in the near future. An initial test series has been performed using the 0.50 caliber barrel shooting bullets into targets using the TATB based explosive PBX-9502 and shows an expected non-violent reaction. Future experiments to evaluate the safety of new explosive formulations to bullet impact are planned. A highlight of the new capability along with discussion of the initial experiments to date will be presented including future areas of research. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.
Michiels, Sarah; De Hertogh, Willem; Truijen, Steven; November, Danny; Wuyts, Floris; Van de Heyning, Paul
2013-05-01
Cervical sensorimotor control (CSMC) becomes increasingly important in the assessment and treatment of patients with neck pain. This review aims to compare commonly used CSMC measuring methods in terms of required tasks, measuring device and clinimetric properties. A systematic review of two databases, followed by methodological quality assessment (CBO guidelines). The methodological quality of 34 included articles was generally good (five to seven out of eight), the inter-rater agreement was excellent (κw=0.966, p<0.01). Following tasks were found: head repositioning accuracy to the neutral head position (HRA-to-NHP) and to a target position (HRA-to-target), a virtual reality test, a continuous linear movement technique (CLMT) and an object following non-linear movement technique (NLMT) (The Fly™). Test-retest reliability was fair to excellent (ICC 0.35-0.87) for the HRA-to-NHP, very bad to excellent (ICC 0.01-0.90) for the HRA-to-target, fair to good (ICC 0.25-0.77) for the virtual reality test and moderate to excellent (ICC: 0.60-0.86) for The Fly™. The reliability of the CLMT was not documented. The HRA-to-NHP, The Fly™ and the CLMT can discriminate between patients with neck complaints and controls (discriminant validity). Currently, only The Fly™ can discriminate between different patient populations (post-traumatic and non-traumatic neck pain). The sensitivity, specificity and responsiveness of the methods have to be assessed in future research. The dynamic method The Fly™ appears to be more reliable than the HRA-to-NHP and is able to discriminate between different patient populations. The diagnostic potential is to be confirmed in future research. Copyright © 2012 Elsevier B.V. All rights reserved.
Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry
2014-01-01
We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets’ locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research. PMID:25339978
Management of recurrent or metastatic thyroid cancer.
Tahara, Makoto
2018-01-01
Recently, vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) have become available for the treatment of recurrent or metastatic thyroid cancer. However, a number of clinical challenges that impact the use of VEGFR-targeted TKI in daily clinical practice have arisen. Toxicity is considerable, to the extent that most physicians hesitate to start VEGFR-targeted TKI and prefer to continue a watch-and-wait approach until the patient's disease markedly worsens. This delayed use of VEGFR-targeted TKI leads to a higher incidence of serious adverse events than was reported in clinical trials. Moreover, the watch-and-wait approach has several demerits, including a worsening of quality of life, worsening of outcomes in patients of older age or with follicular thyroid cancer and increased risk of brain metastasis or bleeding. Thus, optimal timing for the start of VEGFR-targeted TKI requires careful consideration. Moreover, management of VEGFR-targeted TKI toxicities requires appropriate supportive care, well-organised infrastructure in the outpatient clinic and patient education. Future treatment will progress to precision medicine based on molecular testing. Promotion of precision medicine requires the establishment of a system of easy access to molecular testing and the promotion of translational research for the development of new drugs.
Promoting family meals: a review of existing interventions and opportunities for future research
Dwyer, Laura; Oh, April; Patrick, Heather; Hennessy, Erin
2015-01-01
Evidence suggests that regular family meals protect against unhealthy eating and obesity during childhood and adolescence. However, there is limited information on ways to promote family meals as part of health promotion and obesity prevention efforts. The primary aim of this review was to synthesize the literature on strategies to promote family meals among families with school-aged children and adolescents. First, we reviewed interventions that assess family meals as an outcome and summarized strategies that have been used in these interventions. Second, we reviewed correlates and barriers to family meals to identify focal populations and target constructs for consideration in new interventions. During May 26–27, 2014, PubMed and PsycInfo databases were searched to identify literature on family meals published between January 1, 2000 and May 27, 2014. Two reviewers coded 2,115 titles/abstracts, yielding a sample of 139 articles for full-text review. Six interventions and 43 other studies presenting data on correlates of or barriers to family meals were included in the review. Four interventions resulted in greater family meal frequency. Although there were a small number of interventions, intervention settings were diverse and included the home, community, medical settings, the workplace, and the Internet. Common strategies were goal setting and interactive group activities, and intervention targets included cooking and food preparation, cost, shopping, and adolescent influence. Although methodological nuances may contribute to mixed findings, key correlates of family meals were employment, socioeconomic and demographic factors, family structure, and psychosocial constructs. Barriers to consider in future interventions include time and scheduling challenges, cost, and food preferences. Increasing youth involvement in mealtime, tailoring interventions to family characteristics, and providing support for families experiencing time-related barriers are suggested strategies for future research. PMID:26124690
Promoting family meals: a review of existing interventions and opportunities for future research.
Dwyer, Laura; Oh, April; Patrick, Heather; Hennessy, Erin
2015-01-01
Evidence suggests that regular family meals protect against unhealthy eating and obesity during childhood and adolescence. However, there is limited information on ways to promote family meals as part of health promotion and obesity prevention efforts. The primary aim of this review was to synthesize the literature on strategies to promote family meals among families with school-aged children and adolescents. First, we reviewed interventions that assess family meals as an outcome and summarized strategies that have been used in these interventions. Second, we reviewed correlates and barriers to family meals to identify focal populations and target constructs for consideration in new interventions. During May 26-27, 2014, PubMed and PsycInfo databases were searched to identify literature on family meals published between January 1, 2000 and May 27, 2014. Two reviewers coded 2,115 titles/abstracts, yielding a sample of 139 articles for full-text review. Six interventions and 43 other studies presenting data on correlates of or barriers to family meals were included in the review. Four interventions resulted in greater family meal frequency. Although there were a small number of interventions, intervention settings were diverse and included the home, community, medical settings, the workplace, and the Internet. Common strategies were goal setting and interactive group activities, and intervention targets included cooking and food preparation, cost, shopping, and adolescent influence. Although methodological nuances may contribute to mixed findings, key correlates of family meals were employment, socioeconomic and demographic factors, family structure, and psychosocial constructs. Barriers to consider in future interventions include time and scheduling challenges, cost, and food preferences. Increasing youth involvement in mealtime, tailoring interventions to family characteristics, and providing support for families experiencing time-related barriers are suggested strategies for future research.
The Role of Bacillithiol in Gram-Positive Firmicutes
Chandrangsu, Pete; Loi, Vu Van
2018-01-01
Abstract Significance: Since the discovery and structural characterization of bacillithiol (BSH), the biochemical functions of BSH-biosynthesis enzymes (BshA/B/C) and BSH-dependent detoxification enzymes (FosB, Bst, GlxA/B) have been explored in Bacillus and Staphylococcus species. It was shown that BSH plays an important role in detoxification of reactive oxygen and electrophilic species, alkylating agents, toxins, and antibiotics. Recent Advances: More recently, new functions of BSH were discovered in metal homeostasis (Zn buffering, Fe-sulfur cluster, and copper homeostasis) and virulence control in Staphylococcus aureus. Unexpectedly, strains of the S. aureus NCTC8325 lineage were identified as natural BSH-deficient mutants. Modern mass spectrometry-based approaches have revealed the global reach of protein S-bacillithiolation in Firmicutes as an important regulatory redox modification under hypochlorite stress. S-bacillithiolation of OhrR, MetE, and glyceraldehyde-3-phosphate dehydrogenase (Gap) functions, analogous to S-glutathionylation, as both a redox-regulatory device and in thiol protection under oxidative stress. Critical Issues: Although the functions of the bacilliredoxin (Brx) pathways in the reversal of S-bacillithiolations have been recently addressed, significantly more work is needed to establish the complete Brx reduction pathway, including the major enzyme(s), for reduction of oxidized BSH (BSSB) and the targets of Brx action in vivo. Future Directions: Despite the large number of identified S-bacillithiolated proteins, the physiological relevance of this redox modification was shown for only selected targets and should be a subject of future studies. In addition, many more BSH-dependent detoxification enzymes are evident from previous studies, although their roles and biochemical mechanisms require further study. This review of BSH research also pin-points these missing gaps for future research. Antioxid. Redox Signal. 28, 445–462. PMID:28301954
Balasubramanian, M; Brennan, D S; Spencer, A J; Watkins, K; Short, S D
2015-03-01
The international migration of dentists is an issue of pressing significance that poses several complex policy challenges. Policy-making is mainly constrained by the lack of workforce surveillance, research evidence and political advocacy - all three are required to work together, yet with different purposes. We first discuss the inconsistencies in migrant dentist surveillance in major country-level governmental systems (immigration departments, dentist registration authorities and workforce agencies). We argue that the limitations in surveillance collections affect independent research and in turn scholarly contributions to dental workforce policy. Differences in country-level surveillance collections also hinder valid cross-country comparisons on migrant dentist data, impeding global policy efforts. Due to these limitations, advocacy, or the political process to influence health policy, suffers, but is integral to future challenges on dentist migration. Country-level advocacy is best targeted at improving migrant dentist surveillance systems. Research interest can be invigorated through targeted funding allocations for migration research and by improving the availability of dentist surveillance data for research purposes. At the global level, the WHOs global code of practice for international recruitment of health personnel (a crucial advocacy tool) needs to be strengthened. Global organisations such as the FDI World Dental Federation have an important role to play in advocating for improved migrant dentist workforce surveillance and research evidence, especially in low- and middle-income countries.
Youth and digital media: a policy research agenda.
Montgomery, K
2000-08-01
At a time when researchers are still sorting out the complex relationship between adolescents and the mass media, the entire nature of the media system is undergoing dramatic change. The explosive growth of the Internet is ushering in a new digital media culture. Youth are embracing the new technologies much more rapidly than adults. In addition, because of their increased spending power, youth have become a valuable target market for advertisers. These trends have spurred the proliferation of Web sites and other forms of new-media content specifically designed for teens and children. The burgeoning digital marketplace has spawned a new generation of market research companies, and market research on children and youth is outpacing academic research on youth and the newer media. The emergence of this new media culture holds both promise and peril for youth. Whether the positive or negative vision of the digital future prevails will be determined, in large part, by decisions being made now and in the next few years in the halls of government and in corporate boardrooms. Research has contributed to the resolutions of several recent legislative and policy decisions in areas including television violence and the V-chip, children's educational television programming, and privacy and marketing to children on the Web. Future research needs to be designed with the public policy agenda in mind. The academic community has much to contribute to the debates over new developments in the digital age.
Toward a Fast-Response Active Turbine Tip Clearance Control
NASA Technical Reports Server (NTRS)
Melcher, Kevin J.; Kypuros, Javier A.
2003-01-01
This paper describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, technologies developed for clearance control can benefit a broad spectrum of current and future turbomachinery. The first portion of the paper addresses the research from a programmatic viewpoint. Recent studies that provide motivation for the work, identification of key technologies, and NASA's plan for addressing deficiencies in the technologies are discussed. The later portion of the paper drills down into one of the key technologies by presenting equations and results for a preliminary dynamic model of the tip clearance phenomena.
#2) EPA Perspective - Exposure and Effects Prediction and ...
Outline •Biomarkers as a risk assessment tool–exposure assessment & risk characterization•CDC’s NHANES as a source of biomarker data–history, goals & available data•Review of NHANES publications (1999-2013)–chemicals, uses, trends & challenges•NHANES biomarker case study–recommendations for future research The National Exposure Research Laboratory (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA mission to protect human health and the environment. HEASD research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
In the loop: promoter–enhancer interactions and bioinformatics
Mora, Antonio; Sandve, Geir Kjetil; Gabrielsen, Odd Stokke
2016-01-01
Enhancer–promoter regulation is a fundamental mechanism underlying differential transcriptional regulation. Spatial chromatin organization brings remote enhancers in contact with target promoters in cis to regulate gene expression. There is considerable evidence for promoter–enhancer interactions (PEIs). In the recent years, genome-wide analyses have identified signatures and mapped novel enhancers; however, being able to precisely identify their target gene(s) requires massive biological and bioinformatics efforts. In this review, we give a short overview of the chromatin landscape and transcriptional regulation. We discuss some key concepts and problems related to chromatin interaction detection technologies, and emerging knowledge from genome-wide chromatin interaction data sets. Then, we critically review different types of bioinformatics analysis methods and tools related to representation and visualization of PEI data, raw data processing and PEI prediction. Lastly, we provide specific examples of how PEIs have been used to elucidate a functional role of non-coding single-nucleotide polymorphisms. The topic is at the forefront of epigenetic research, and by highlighting some future bioinformatics challenges in the field, this review provides a comprehensive background for future PEI studies. PMID:26586731
Optimal Management of Metastatic Melanoma: Current Strategies and Future Directions
Batus, Marta; Waheed, Salman; Ruby, Carl; Petersen, Lindsay; Bines, Steven D.; Kaufman, Howard L.
2013-01-01
Melanoma is increasing in incidence and remains a major public health threat. Although the disease may be curable when identified early, advanced melanoma is characterized by widespread metastatic disease and a median survival of less than 10 months. In recent years, however, major advances in our understanding of the molecular nature of melanoma and the interaction of melanoma cells with the immune system have resulted in several new therapeutic strategies that are showing significant clinical benefit. Current therapeutic approaches include surgical resection of metastatic disease, chemotherapy, immunotherapy, and targeted therapy. Dacarbazine, interleukin-2, ipilimumab, and vemurafenib are now approved for the treatment of advanced melanoma. In addition, new combination chemotherapy regimens, monoclonal antibodies blocking the programmed death-1 (PD-1)/PD-ligand 1 pathway, and targeted therapy against CKIT, mitogen-activated protein/extracellular signal-regulated kinase (MEK), and other putative signaling pathways in melanoma are beginning to show promise in early-phase clinical trials. Further research on these modalities alone and in combination will likely be the focus of future clinical investigation and may impact the outcomes for patients with advanced melanoma. PMID:23677693
An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders.
Yang, Yang; Jiang, Shuai; Yan, Juanjuan; Li, Yue; Xin, Zhenlong; Lin, Yan; Qu, Yan
2015-02-01
Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chan, Chi Yuet X’avia; Gritsenko, Marina A.; Smith, Richard D.
Protein phosphorylation is a fundamental regulatory mechanism in many cellular processes and aberrant perturbation of phosphorylation has been revealed in various human diseases. Kinases and their cognate inhibitors have been hotspot for drug development. Therefore, the emerging tools, which enable a system-wide quantitative profiling of phosphoproteome, would offer a powerful impetus in unveiling novel signaling pathways, drug targets and/or biomarkers for the disease of interest. In this review, we will highlight recent advances in phosphoproteomics, the current state-of-the-art of the technologies, and the challenges and future perspectives of this research area. Finally, we will underscore some exemplary applications of phosphoproteomicsmore » in diabetes research.« less
Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.
Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D
2015-09-01
For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised. © 2014 EVJ Ltd.
[Research of RAAS: progress and perspective].
Akazawa, Hiroshi; Komuro, Issei
2012-09-01
Pharmacological inhibitions of the renin-angiotensin-aldosterone system (RAAS) are crowned with one of the greatest success in the current field of cardiovascular medicine. In addition to the systemic effects including elevation of blood pressure and retention of sodium and water, sustained and excessive RAAS activation has direct and deleterious effects on a wide variety of tissues. Recent studies have deciphered the regulatory mechanisms underlying tissue RAAS activation at cellular and molecular levels, and suggested pathogenic roles of RAAS activation in hitherto unanticipated disorders such as muscular dystrophy, osteoporosis, cancer, and aging itself. Novel drugs targeting RAAS are under research and development in search for further efficacy, specificity, and even multifunctionality. This review will discuss the current progress and future perspective of RAAS research.
Summary of the 2016 Alcohol and Immunology Research Interest Group (AIRIG) meeting.
Boule, Lisbeth A; Ju, Cynthia; Agudelo, Marisela; Parira, Tiyash; Cannon, Abigail; Davis, Booker; Eby, Jonathan; Cresci, Gail; Samuelson, Derrick R; Shukla, Pradeep; Alrefai, Waddah A; Sureshchandra, Suhas; Pandey, Subhash C; Schnabl, Bernd; Curtis, Brenda J; Wyatt, Todd A; Choudhry, Mashkoor A; Kovacs, Elizabeth J
2018-02-01
On November 18, 2016 the 21st annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the Center for Translational Research and Education at Loyola University Chicago's Health Sciences Campus in Maywood, IL. The 2016 meeting focused broadly on alcohol and inflammation, epigenetics, and the microbiome. The four plenary sessions of the meeting were Alcohol, Inflammation, and Immunity; Alcohol and Epigenetics; Alcohol, Transcriptional Regulation, and Epigenetics; and Alcohol, Intestinal Mucosa, and the Gut Microbiome. Presentations in all sessions of the meeting explored putative underlying causes for chronic diseases and mortality associated with alcohol consumption, shedding light on future work and potential therapeutic targets to alleviate the negative effects of alcohol misuse. Copyright © 2017 Elsevier Inc. All rights reserved.
Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.
Comi, Anne M; Sahin, Mustafa; Hammill, Adrienne; Kaplan, Emma H; Juhász, Csaba; North, Paula; Ball, Karen L; Levin, Alex V; Cohen, Bernard; Morris, Jill; Lo, Warren; Roach, E Steve
2016-05-01
Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS. Copyright © 2016. Published by Elsevier Inc.
NASA Astrophysics Data System (ADS)
Ford, James D.; Pearce, Tristan
2010-01-01
This letter systematically reviews and synthesizes scientific and gray literature publications (n = 420) to identify and characterize the nature of climate change vulnerability in the Inuvialuit Settlement Region of the western Canadian Arctic and identify gaps in understanding. The literature documents widespread evidence of climate change, with implications for human and biophysical systems. Adaptations are being employed to manage changing conditions and are indicative of a high adaptive capacity. However, barriers to adaptation are evident and are expected to constrain adaptive capacity to future climate change. Continued climate change is predicted for the region, with differential exposure sensitivity for communities, groups and sectors: a function of social-economic-biophysical characteristics and projected future climatic conditions. Existing climate risks are expected to increase in magnitude and frequency, although the interaction between projected changes and socio-economic-demographic trends has not been assessed. The capacity for adapting to future climate change has also not been studied. The review identifies the importance of targeted vulnerability research that works closely with community members and other stakeholders to address research needs. Importantly, the fully categorized list of reviewed references accompanying this letter will be a valuable resource for those working or planning to work in the region, capturing climate change research published since 1990. At a broader level, the systematic review methodology offers a promising tool for climate/environmental change studies in general where there is a large and emerging body of research but limited understanding of research gaps and needs.
Using qualitative methods to develop a contextually tailored instrument: Lessons learned.
Lee, Haeok; Kiang, Peter; Kim, Minjin; Semino-Asaro, Semira; Colten, Mary Ellen; Tang, Shirley S; Chea, Phala; Peou, Sonith; Grigg-Saito, Dorcas C
2015-01-01
To develop a population-specific instrument to inform hepatitis B virus (HBV) and human papilloma virus (HPV) prevention education and intervention based on data and evidence obtained from the targeted population of Khmer mothers reflecting their socio-cultural and health behaviors. The principles of community-based participatory research (CBPR) guided the development of a standardized survey interview. Four stages of development and testing of the survey instrument took place in order to inform the quantitative health survey used to collect data in stage five of the project. This article reports only on Stages 1-4. This process created a new quantitative measure of HBV and HPV prevention behavior based on the revised Network Episode Model and informed by the targeted population. The CBPR method facilitated the application and translation of abstract theoretical ideas of HBV and HPV prevention behavior into culturally-relevant words and expressions of Cambodian Americans (CAs). The design of an instrument development process that accounts for distinctive socio-cultural backgrounds of CA refugee/immigrant women provides a model for use in developing future health surveys that are intended to aid minority-serving health care professionals and researchers as well as targeted minority populations.
Immune checkpoint inhibitors in lung cancer: current status and future directions.
Fan, Yun; Mao, Weimin
2017-04-01
Recently, the immune checkpoint inhibitors that target programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) have made a breakthrough in treating advanced non-small cell lung cancer (NSCLC) with the efficacy of approximately 20%; among which, nivolumab has acquired treatment indications in lung squamous cell carcinoma. The inhibitors targeting cytotoxic T lymphocyte associated antigen 4 (CTLA-4) are also undergoing clinical trials. Researches on immune checkpoint inhibitors have been rapidly implemented in a variety of different types of lung cancer, such as small cell lung cancer (SCLC) and locally advanced NSCLC, and these inhibitors began to be applied in combination with some established treatments, including chemotherapy, targeting therapy and radiotherapy. Undoubtedly, the immune checkpoint inhibitors have become a hot spot in the research and treatment of lung cancer. However, many problems wait to be solved, such as searching for ideal biomarkers, constituting the best criteria for curative effect evaluation, exploring different combination treatment models, and clearly understanding the mechanisms of primary or secondary drug resistance. Along with these problems to be successfully solved, the immune checkpoint inhibitors will have more broad applications in lung cancer therapy.
Using qualitative methods to develop a contextually tailored instrument: Lessons learned
Lee, Haeok; Kiang, Peter; Kim, Minjin; Semino-Asaro, Semira; Colten, Mary Ellen; Tang, Shirley S.; Chea, Phala; Peou, Sonith; Grigg-Saito, Dorcas C.
2015-01-01
Objective: To develop a population-specific instrument to inform hepatitis B virus (HBV) and human papilloma virus (HPV) prevention education and intervention based on data and evidence obtained from the targeted population of Khmer mothers reflecting their socio-cultural and health behaviors. Methods: The principles of community-based participatory research (CBPR) guided the development of a standardized survey interview. Four stages of development and testing of the survey instrument took place in order to inform the quantitative health survey used to collect data in stage five of the project. This article reports only on Stages 1-4. Results: This process created a new quantitative measure of HBV and HPV prevention behavior based on the revised Network Episode Model and informed by the targeted population. The CBPR method facilitated the application and translation of abstract theoretical ideas of HBV and HPV prevention behavior into culturally-relevant words and expressions of Cambodian Americans (CAs). Conclusions: The design of an instrument development process that accounts for distinctive socio-cultural backgrounds of CA refugee/immigrant women provides a model for use in developing future health surveys that are intended to aid minority-serving health care professionals and researchers as well as targeted minority populations. PMID:27981114
Next stop for the CRISPR revolution: RNA-guided epigenetic regulators.
Vora, Suhani; Tuttle, Marcelle; Cheng, Jenny; Church, George
2016-09-01
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins offer a breakthrough platform for cheap, programmable, and effective sequence-specific DNA targeting. The CRISPR-Cas system is naturally equipped for targeted DNA cutting through its native nuclease activity. As such, groups researching a broad spectrum of biological organisms have quickly adopted the technology with groundbreaking applications to genomic sequence editing in over 20 different species. However, the biological code of life is not only encoded in genetics but also in epigenetics as well. While genetic sequence editing is a powerful ability, we must also be able to edit and regulate transcriptional and epigenetic code. Taking inspiration from work on earlier sequence-specific targeting technologies such as zinc fingers (ZFs) and transcription activator-like effectors (TALEs), researchers quickly expanded the CRISPR-Cas toolbox to include transcriptional activation, repression, and epigenetic modification. In this review, we highlight advances that extend the CRISPR-Cas toolkit for transcriptional and epigenetic regulation, as well as best practice guidelines for these tools, and a perspective on future applications. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Electromembrane extraction--three-phase electrophoresis for future preparative applications.
Gjelstad, Astrid; Pedersen-Bjergaard, Stig
2014-09-01
The purpose of this article is to discuss the principle and the future potential for electromembrane extraction (EME). EME was presented in 2006 as a totally new sample preparation technique for ionized target analytes, based on electrokinetic migration across a supported liquid membrane under the influence of an external electrical field. The principle of EME is presented, and typical performance data for EME are discussed. Most work with EME up to date has been performed with low-molecular weight pharmaceutical substances as model analytes, but the principles of EME should be developed in other directions in the future to fully explore the potential. Recent research in new directions is critically reviewed, with focus on extraction of different types of chemical and biochemical substances, new separation possibilities, new approaches, and challenges related to mass transfer and background current. The intention of this critical review is to give a flavor of EME and to stimulate into more research in the area of EME. Unlike other review articles, the current one is less comprehensive, but put more emphasis on new directions for EME. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
A new method of small target detection based on neural network
NASA Astrophysics Data System (ADS)
Hu, Jing; Hu, Yongli; Lu, Xinxin
2018-02-01
The detection and tracking of moving dim target in infrared image have been an research hotspot for many years. The target in each frame of images only occupies several pixels without any shape and structure information. Moreover, infrared small target is often submerged in complicated background with low signal-to-clutter ratio, making the detection very difficult. Different backgrounds exhibit different statistical properties, making it becomes extremely complex to detect the target. If the threshold segmentation is not reasonable, there may be more noise points in the final detection, which is unfavorable for the detection of the trajectory of the target. Single-frame target detection may not be able to obtain the desired target and cause high false alarm rate. We believe the combination of suspicious target detection spatially in each frame and temporal association for target tracking will increase reliability of tracking dim target. The detection of dim target is mainly divided into two parts, In the first part, we adopt bilateral filtering method in background suppression, after the threshold segmentation, the suspicious target in each frame are extracted, then we use LSTM(long short term memory) neural network to predict coordinates of target of the next frame. It is a brand-new method base on the movement characteristic of the target in sequence images which could respond to the changes in the relationship between past and future values of the values. Simulation results demonstrate proposed algorithm can effectively predict the trajectory of the moving small target and work efficiently and robustly with low false alarm.
Rapid target foraging with reach or gaze: The hand looks further ahead than the eye
2017-01-01
Real-world tasks typically consist of a series of target-directed actions and often require choices about which targets to act on and in what order. Such choice behavior can be assessed from an optimal foraging perspective whereby target selection is shaped by a balance between rewards and costs. Here we evaluated such decision-making in a rapid movement foraging task. On a given trial, participants were presented with 15 targets of varying size and value and were instructed to harvest as much reward as possible by either moving a handle to the targets (hand task) or by briefly fixating them (eye task). The short trial duration enabled participants to harvest about half the targets, ensuring that total reward was due to choice behavior. We developed a probabilistic model to predict target-by-target harvesting choices that considered the rewards and movement-related costs (i.e., target distance and size) associated with the current target as well as future targets. In the hand task, in comparison to the eye task, target choice was more strongly influenced by movement-related costs and took into account a greater number of future targets, consistent with the greater costs associated with arm movement. In both tasks, participants exhibited near-optimal behaviour and in a constrained version of the hand task in which choices could only be based on target positions, participants consistently chose among the shortest movement paths. Our results demonstrate that people can rapidly and effectively integrate values and movement-related costs associated with current and future targets when sequentially harvesting targets. PMID:28683138
Potential and problems in ultrasound-responsive drug delivery systems
Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping
2013-01-01
Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531
Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam
2018-02-01
Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.
Aldosterone and cardiovascular disease: the heart of the matter
He, B. Julie; Anderson, Mark E.
2012-01-01
Aldosterone contributes to the endocrine basis of heart failure and studies on cardiac aldosterone signaling have reinforced its value as a therapeutic target. Recent focus has shifted to new roles of aldosterone that appear to depend on co-existing pathologic stimuli, cell type, and disease etiology. This review evaluates recent advances in mechanisms underlying aldosterone-induced cardiac disease and highlights the interplay between aldosterone and Ca2+ and calmodulin dependent protein kinase II, whose hyperactivity during heart failure contributes to disease progression. Increasing evidence implicates aldosterone in diastolic dysfunction, and there is need to develop more targeted therapeutics such as aldosterone synthase inhibitors and molecularly specific anti-oxidants. Despite accumulating knowledge, many questions still persist and will likely dictate areas of future research. PMID:23040074
Identification accuracy of children versus adults: a meta-analysis.
Pozzulo, J D; Lindsay, R C
1998-10-01
Identification accuracy of children and adults was examined in a meta-analysis. Preschoolers (M = 4 years) were less likely than adults to make correct identifications. Children over the age of 5 did not differ significantly from adults with regard to correct identification rate. Children of all ages examined were less likely than adults to correctly reject a target-absent lineup. Even adolescents (M = 12-13 years) did not reach an adult rate of correct rejection. Compared to simultaneous lineup presentation, sequential lineups increased the child-adult gap for correct rejections. Providing child witnesses with identification practice or training did not increase their correct rejection rates. Suggestions for children's inability to correctly reject target-absent lineups are discussed. Future directions for identification research are presented.
Cierpicki, Tomasz; Grembecka, Jolanta
2015-01-01
Summary Over the past several years, there has been an increasing research effort focused on inhibition of protein-protein interactions (PPIs) to develop novel therapeutic approaches for cancer, including hematologic malignancies. These efforts have led to development of small molecule inhibitors of PPIs, some of which already advanced to the stage of clinical trials while others are at different stages of pre-clinical optimization, emphasizing PPIs as an emerging and attractive class of drug targets. Here, we review several examples of recently developed inhibitors of protein-protein interactions highly relevant to hematologic cancers. We address the existing skepticism about feasibility of targeting PPIs and emphasize potential therapeutic benefit from blocking PPIs in hematologic malignancies. We then use these examples to discuss the approaches for successful identification of PPI inhibitors and provide analysis of the protein-protein interfaces, with the goal to address ‘druggability’ of new PPIs relevant to hematology. We discuss lessons learned to improve the success of targeting new protein-protein interactions and evaluate prospects and limits of the research in this field. We conclude that not all PPIs are equally tractable for blocking by small molecules, and detailed analysis of PPI interfaces is critical for selection of those with the highest chance of success. Together, our analysis uncovers patterns that should help to advance drug discovery in hematologic malignancies by successful targeting of new protein-protein interactions. PMID:25510283
[Current status and future prospects of research on Fukuyama muscular dystrophy].
Toda, Tatsushi
2015-08-01
Fukuyama congenital muscular dystrophy(FCMD) is a second common childhood muscular dystrophy in Japan. All FCMD patients have ancestral insertion of the SVA retrotransposal element into fukutin. We show that aberrant mRNA splicing induced by SVA exon-trapping caused FCMD. Introduction of 3 cocktailed antisense oligonucleotides(AONs) targeting around these splice sites prevented pathogenic splicing in FCMD patient cells and model mice, and normalized protein production and functions of Fukutin as well as O-glycosylation of α-dystroglycan. We show the promise of splicing modulation therapy as the first radical clinical treatment for FCMD in the near future. We also show that fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression. Recent advances in FCMD are discussed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Steven R. Billingsley
2010-03-18
This report summarizes the activities of the INRA Water Research Consortium (IWRC) for the period beginning September 15, 2005 and ending December 16, 2010. This report compares accomplishments to project objectives, documents the activities associated with this project, and lists products developed during the course of the project. The Water Resources Research Needs Assessment team received funding from the Inland Northwest Research Alliance Water Resources Steering Committee to facilitate a structured needs assessment process that could provide a basis for future targeted research efforts to improve regional water resources management in the Inland Northwest region. The original INRA proposal specificallymore » mentions the need to conduct a detailed assessment of the information and research needs of policy makers and water user groups during a period of increasing competition for scarce water supplies. A particular focus of this assessment would be to understand what types of research might facilitate water resource management during periods of drought. The specific goals of the Needs Assessment project were to: (1) Quickly ascertain the perceptions of diverse stakeholders in this region; (2) Condense this complex information into a format that can be shared with the INRA scientific panel, and (3) Develop of a realistic set of research needs & priorities that can shape future INRA-funded research activities.« less
Analysis of the development of missile-borne IR imaging detecting technologies
NASA Astrophysics Data System (ADS)
Fan, Jinxiang; Wang, Feng
2017-10-01
Today's infrared imaging guiding missiles are facing many challenges. With the development of targets' stealth, new-style IR countermeasures and penetrating technologies as well as the complexity of the operational environments, infrared imaging guiding missiles must meet the higher requirements of efficient target detection, capability of anti-interference and anti-jamming and the operational adaptability in complex, dynamic operating environments. Missileborne infrared imaging detecting systems are constrained by practical considerations like cost, size, weight and power (SWaP), and lifecycle requirements. Future-generation infrared imaging guiding missiles need to be resilient to changing operating environments and capable of doing more with fewer resources. Advanced IR imaging detecting and information exploring technologies are the key technologies that affect the future direction of IR imaging guidance missiles. Infrared imaging detecting and information exploring technologies research will support the development of more robust and efficient missile-borne infrared imaging detecting systems. Novelty IR imaging technologies, such as Infrared adaptive spectral imaging, are the key to effectively detect, recognize and track target under the complicated operating and countermeasures environments. Innovative information exploring techniques for the information of target, background and countermeasures provided by the detection system is the base for missile to recognize target and counter interference, jamming and countermeasure. Modular hardware and software development is the enabler for implementing multi-purpose, multi-function solutions. Uncooled IRFPA detectors and High-operating temperature IRFPA detectors as well as commercial-off-the-shelf (COTS) technology will support the implementing of low-cost infrared imaging guiding missiles. In this paper, the current status and features of missile-borne IR imaging detecting technologies are summarized. The key technologies and its development trends of missiles' IR imaging detecting technologies are analyzed.
Assessment of the Air Quality Improvement Potentials for Seoul Metropolitan Area using GAINS-Korea
NASA Astrophysics Data System (ADS)
Kim, Y.; Woo, J. H.; Ahn, Y. H.; Kim, J.; Bu, C.; Lee, Y.; Choi, K. C.; Amann, M.; Kim, S. K.
2016-12-01
Urban areas are very important places for climate change and air pollution because they have been emitting a significant amount of Green House Gases (GHGs) and air pollutants. Cause they have massive pollutant emissions and high population density with amount of vehicles. Korea's government has set the 2nd phase capital air quality improvement program called Seoul metropolitan area Air Quality Management Plan(SAQMP), targeting the year 2024. The air quality improvement targets are to achieve annual mean PM10 and pm2.5concentration for SMA Area 30 ug/m3 and 20 ug/m3, respectively. To achieve this target, emissions of PM10, PM2.5 are required to be decreased up to 35%, 45%, respectively, from their future baseline level. In this study, we found the emission level of some pollutants for the year 2030 will be decreased compare with the baseline level but the concentration cannot meet their target even with more stringent control measures. The more in-depth analysis of future PM concentration, estimated from Source-Receptor(S-R) relationship, were conducted for more accurate air quality improvement assessment. As the result, we found that secondary and transboundary pollution have been plying significant role in Seoul Metro air quality. Not only direct/in-region measures, therefore, but indirect measures/international cooperation have to be conducted to achieve target air quality. ** This subject is supported by Korea Ministry of Environment as "Climate Change Correspondence Program". This work was supported by a grant from the National Institute of Environment Research (NIER), funded by the Ministry of Environment (MOE) of the Republic of Korea.
Russell, Bayden D.; Harley, Christopher D. G.; Wernberg, Thomas; Mieszkowska, Nova; Widdicombe, Stephen; Hall-Spencer, Jason M.; Connell, Sean D.
2012-01-01
Most studies that forecast the ecological consequences of climate change target a single species and a single life stage. Depending on climatic impacts on other life stages and on interacting species, however, the results from simple experiments may not translate into accurate predictions of future ecological change. Research needs to move beyond simple experimental studies and environmental envelope projections for single species towards identifying where ecosystem change is likely to occur and the drivers for this change. For this to happen, we advocate research directions that (i) identify the critical species within the target ecosystem, and the life stage(s) most susceptible to changing conditions and (ii) the key interactions between these species and components of their broader ecosystem. A combined approach using macroecology, experimentally derived data and modelling that incorporates energy budgets in life cycle models may identify critical abiotic conditions that disproportionately alter important ecological processes under forecasted climates. PMID:21900317