Is Schooling Good for the Development of Society?: The Case of South Africa

ERIC Educational Resources Information Center

Harber, Clive; Mncube, Vusi

2011-01-01

This paper is concerned with three possible theoretical relationships, between education and social, economic and political development, that--(a) education improves society, (b) education reproduces society as it is and (c) education actually makes society worse. The paper then uses South Africa as a case study to critically analyse these…

Creating Sustainable Societies: Developing Emerging Professionals through Transforming Current Mindsets

ERIC Educational Resources Information Center

Griswold, Wendy

2017-01-01

Future professionals will bear the brunt of creating sustainable societies. Equipping them for the task is the challenge of current educators. Educational experiences facilitating the development of sustainable habits of mind are needed. This research reports on the experiences of developing scientists and engineers engaged in a sustainable energy…

The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

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

Ataman, Ozlem U., E-mail: ouataman@hotmail.com; Sambrook, Sally J.; Wilks, Chris

2012-11-15

Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, andmore » PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests

[The development of World Federation of Acupuncture-Moxibustion Societies].

PubMed

Wang, Hong-cai; Deng, Liang-yue; Liu, Bao-yan

2014-10-01

From cooperation between World Federation of Acupuncture-Moxibustion Societies (WFAS) and World Health Organization, works of academics and standardization, acupuncture-moxibustion education, technique service, organization development, etc., the 27-year development of WFAS since 1987 was summarized and reviewed in details. The growth of WFAS witnesses and promotes the development of acupuncture and moxibustion in the world, so by learning the experience and lessons, WFAS could have a wider path, becoming a core organization for communicating and promoting the development of acupuncture, even the traditional medicine in the world.

The 2017 Focused Update of the Guidelines of the Taiwan Society of Cardiology (TSOC) and the Taiwan Hypertension Society (THS) for the Management of Hypertension.

PubMed

Chiang, Chern-En; Wang, Tzung-Dau; Lin, Tsung-Hsien; Yeh, Hung-I; Liu, Ping-Yen; Cheng, Hao-Min; Chao, Ting-Hsing; Chen, Chen-Huan; Shyu, Kou-Gi; Ueng, Kwo-Chang; Chen, Chung-Yin; Chu, Pao-Hsien; Sung, Shih-Hsien; Wang, Kang-Ling; Li, Yi-Heng; Wang, Kuo-Yang; Chiang, Fu-Tien; Lai, Wen-Ter; Chen, Jyh-Hong; Chen, Wen-Jone; Yeh, San-Jou; Chen, Ming-Fong; Lin, Shing-Jong; Lin, Jiunn-Lee

2017-05-01

Hypertension (HT) is the most important risk factor for cardiovascular diseases. Over the past 25 years, the number of individuals with hypertension and the estimated associated deaths has increased substantially. There have been great debates in the past few years on the blood pressure (BP) targets. The 2013 European Society of Hypertension and European Society of Cardiology HT guidelines suggested a unified systolic BP target of 140 mmHg for both high-risk and low-risk patients. The 2014 Joint National Committee report further raised the systolic BP targets to 150 mmHg for those aged ≥ 60 years, including patients with stroke or coronary heart disease, and raised the systolic BP target to 140 mmHg for diabetes. Instead, the 2015 Hypertension Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society suggested more aggressive BP targets of < 130/80 mmHg for patients with diabetes, coronary heart disease, chronic kidney disease with proteinuria, and atrial fibrillation patients on antithrombotic therapy. Based on the main findings from the Systolic Blood Pressure Intervention Trial (SPRINT) and several recent meta-analyses, the HT committee members of the Taiwan Society of Cardiology and the Taiwan Hypertension Society convened and finalized the revised BP targets for management of HT. We suggested a new systolic BP target to < 120 mmHg for patients with coronary heart disease, chronic kidney disease with an eGFR of 20-60 ml/min/1.73 m 2 , and elderly patients aged ≥ 75 years, using unattended automated office BP measurement. When traditional office BP measurement is applied, we suggested BP target of < 140/90 mmHg for elderly patients with an age ≥ 75 years. Other BP targets with traditional office BP measurement remain unchanged. With these more aggressive BP targets, it is foreseeable that the cardiovascular events will decrease substantially in Taiwan.

Current trends of sugar consumption in developing societies.

PubMed

Ismail, A I; Tanzer, J M; Dingle, J L

1997-12-01

This paper reviews recent data on sugar consumption in developing countries that may lead to a potential increase in caries prevalence. A search of the business, dental and nutritional literature was conducted through May 1995. There is evidence that sugar (sucrose) use was increasing in China, India, and Southeast Asia. In South and Central America (except Haiti) sugar use was either equivalent to or higher than that in most developed societies. In the Middle East, average sugar use was higher than that of other developing areas. However, it was either lower than or equivalent to the levels reported by other developed countries. Many central African countries consumed less than 15 kg of sugar/ person/year. Of particular concern is a rise in the consumption of sugar-containing carbonated beverages in a number of developing societies: China, India, Vietnam, Thailand, and other Southeast Asian countries are currently major growth markets for the soft drink industry. Consumption of high-sugar desserts and snacks may also be increasing in urban centers in some developing countries. To counteract the potential increase in the prevalence of dental caries in some developing countries, preventive and oral health promotion programs should be planned and implemented. We contend that taxation of sugar-containing products as well as efforts to reduce the level of sugar consumption to "safe" levels may be impractical, and in most countries, cannot be supported for political, economic, or health reasons. Instead, we recommend that collaboration be established between public health authorities and manufacturers/distributors of soft drinks and sweets in developing countries to establish a dental health fund that could be used to support caries preventive programs. The fund could be supported through donations from manufacturers based on the principle of the "milli-cent" (1 cent for every 1000 cents of sales). This minimal contribution would provide enough financial support for

The state and the development of an information society: Greek policy and experience.

PubMed

Boucas, Dimitris

2017-09-01

The paper looks into the dynamics of information society policy and its implementation in the Greek context. It argues that information society development is a contested process, influenced by pre-existing state, economy and society relations. Based on this, it looks into the different aspects of the idiosyncratic path which the evolution of the Greek information society has followed, particularly after 2000. Using Bob Jessop's strategic-relational approach (SRA) to the state as an analytical framework and drawing on a number of in-depth interviews with relevant political actors, it provides insights into policy implementation by examining: the public management of information technology projects, how such projects were received in bureaucratic structures and practices, as well as the relationship between the state and the information and communication technology (ICT) sector in public procurement processes. The emphasis is on the period 2000-2008, during which a major operational programme on the information society in Greece was put into effect. The paper also touches upon the post-2008 experience, suggesting that information society developments might include dynamics operating independently and even in contradiction to the state agenda. © London School of Economics and Political Science 2017.

Molecular targeting agents in cancer therapy: science and society.

PubMed

Shaikh, Asim Jamal

2012-01-01

The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

Coping in a Developing Society: Academic Librarianship in India.

ERIC Educational Resources Information Center

Rutstein, Joel S.

Based on observations made during a 1979-80 study trip, this paper presents a critical view of academic librarianship and libraries in India, emphasizing issues confronting the library profession and its ability to fulfill library objectives in a developing nation. It is noted that modern India is a society closely tied to tradition while at the…

Hierarchical mechanism of development of wealth and structure for a premodern local society

NASA Astrophysics Data System (ADS)

Matsuo, Miki Y.

2011-06-01

We propose a hierarchical model of social development composed of two associated hierarchies, each of which describes economic and noneconomic activities in society, respectively. The model is designed to explain the development of wealth distribution and social structure over 50 years in a premodern Japanese local society. Data analysis shows that the wealth distribution has a well-known universal power-law tail throughout the observed period, while the Pareto index gradually decreases with time. We further show that the noneconomic social properties, such as the household number, average family size, and number of collaterals in a household, of the local society, also have decreasing or increasing trends throughout the observed period. We show that the hierarchical model consistently demonstrates the correlations of these economic and noneconomic properties.

Targeting bacterial central metabolism for drug development.

PubMed

Murima, Paul; McKinney, John D; Pethe, Kevin

2014-11-20

Current antibiotics, derived mainly from natural sources, inhibit a narrow spectrum of cellular processes, namely DNA replication, protein synthesis, and cell wall biosynthesis. With the worldwide explosion of drug resistance, there is renewed interest in the investigation of alternate essential cellular processes, including bacterial central metabolic pathways, as a drug target space for the next generation of antibiotics. However, the validation of targets in central metabolism is more complex, as essentiality of such targets can be conditional and/or contextual. Bearing in mind our enhanced understanding of prokaryotic central metabolism, a key question arises: can central metabolism be bacteria's Achilles' heel and a therapeutic target for the development of new classes of antibiotics? In this review, we draw lessons from oncology and attempt to address some of the open questions related to feasibility of targeting bacterial central metabolism as a strategy for developing new antibacterial drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

The history and development of the Human Genetics Society of Australasia.

PubMed

Sutherland, Grant R

2008-08-01

The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.

Creating Inquiry Between Technology Developers and Civil Society Actors: Learning from Experiences Around Nanotechnology.

PubMed

Krabbenborg, Lotte

2016-06-01

Engaging civil society actors as knowledgeable dialogue partners in the development and governance of emerging technologies is a new challenge. The starting point of this paper is the observation that the design and orchestration of current organized interaction events shows limitations, particularly in the articulation of issues and in learning how to address the indeterminacies that go with emerging technologies. This paper uses Dewey's notion of 'publics' and 'reflective inquiry' to outline ways of doing better and to develop requirements for a more productive involvement of civil society actors. By studying four novel spaces for interaction in the domain of nanotechnology, this paper examines whether and how elements of Dewey's thought are visible and under what conditions. One of the main findings is that, in our society, special efforts are needed in order for technology developers and civil society actors to engage in a joint inquiry on emerging nanotechnology. Third persons, like social scientists and philosophers, play a role in this respect in addition to external input such as empirically informed scenarios and somewhat protected spaces.

Food Insecurity and Diabetes in Developed Societies.

PubMed

Essien, Utibe R; Shahid, Naysha N; Berkowitz, Seth A

2016-09-01

Food insecurity is an important issue in public health even in developed societies, particularly for vulnerable populations. Food insecurity refers to the uncertain or limited access to adequate and safe foods. Emerging evidence shows an association between food insecurity, type 2 diabetes risk factors, and management of type 1 and type 2 diabetes. A review of the current literature describing the association between food insecurity and diabetes reveals possible mechanisms and pathophysiologic pathways. There is less evidence for effective interventions, and much of the current literature is limited to cross-sectional studies. Future work should evaluate longitudinal associations and ways to help vulnerable patients with diabetes access adequate food for effective diabetes management.

Civil society: the catalyst for ensuring health in the age of sustainable development.

PubMed

Smith, Julia; Buse, Kent; Gordon, Case

2016-07-16

Sustainable Development Goal Three is rightly ambitious, but achieving it will require doing global health differently. Among other things, progressive civil society organisations will need to be recognised and supported as vital partners in achieving the necessary transformations. We argue, using illustrative examples, that a robust civil society can fulfill eight essential global health functions. These include producing compelling moral arguments for action, building coalitions beyond the health sector, introducing novel policy alternatives, enhancing the legitimacy of global health initiatives and institutions, strengthening systems for health, enhancing accountability systems, mitigating the commercial determinants of health and ensuring rights-based approaches. Given that civil society activism has catalyzed tremendous progress in global health, there is a need to invest in and support it as a global public good to ensure that the 2030 Agenda for Sustainable Development can be realised.

Developing an Inclusive System in a Rapidly Changing European Society

ERIC Educational Resources Information Center

Drudy, Sheelagh; Kinsella, William

2009-01-01

This paper uses Ireland--one of Europe's most rapidly changing societies--as a case study and examines progress towards an inclusive education system. It explores policy and progress on developing an inclusive system under a number of key headings: social class, ethnicity, gender and disability. On the basis of analysis of official statistics and…

Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

PubMed

Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

2016-07-15

In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The development of human social learning across seven societies.

PubMed

van Leeuwen, Edwin J C; Cohen, Emma; Collier-Baker, Emma; Rapold, Christian J; Schäfer, Marie; Schütte, Sebastian; Haun, Daniel B M

2018-05-25

Social information use is a pivotal characteristic of the human species. Avoiding the cost of individual exploration, social learning confers substantial fitness benefits under a wide variety of environmental conditions, especially when the process is governed by biases toward relative superiority (e.g., experts, the majority). Here, we examine the development of social information use in children aged 4-14 years (n = 605) across seven societies in a standardised social learning task. We measured two key aspects of social information use: general reliance on social information and majority preference. We show that the extent to which children rely on social information depends on children's cultural background. The extent of children's majority preference also varies cross-culturally, but in contrast to social information use, the ontogeny of majority preference follows a U-shaped trajectory across all societies. Our results demonstrate both cultural continuity and diversity in the realm of human social learning.

Sixty years of the Interamerican Society of Psychology (SIP): origins and development.

PubMed

Gallegos, Miguel

2013-01-01

This paper presents a historical overview of the Interamerican Society of Psychology, which was founded on December 17, 1951, in Mexico City. Firstly, the historical circumstances of the foundation period are presented, as well as the people who made this organization possible, and the state of psychology on the American continent at that time. Secondly, the most important activities that the Interamerican Society of Psychology has developed during its 60 years are mentioned, such as the publication of books and scientific journals, the creation of several task forces and the Interamerican Congresses of Psychology. Basically, the purpose of this paper is to review the history of the Interamerican Society of Psychology through the recovery and use of various documentary sources.

Derivation of Building Energy Use Intensity Targets for ASHRAE Standard 100

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

Sharp, Terry R

2014-06-01

The steps to develop the building energy use intensity targets for American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) Standard 100, Energy Efficiency in Existing Buildings are outlined in this report. The analyses were conducted by Oak Ridge National Laboratory (ORNL) in collaboration with the ASHRAE Standard 100 committee and Dr. Alexander Zhivov, the subcommittee chair responsible for targets development.

Did Educational Expansion Trigger the Development of an Education Society? Chances and Risks of a New Model of Society

ERIC Educational Resources Information Center

Haunberger, Sigrid

2010-01-01

This article focuses on the question of whether educational expansion leads to a new type of society, the education society. Taking into consideration the combined elements of three models of society (the post-industrial society, the knowledge society and the information society)--the chances and risks of an educational society will be elicited…

Role of ?reative Social Practices in the Development of United Activities in Russian Society

ERIC Educational Resources Information Center

Volkov, Yury Grigorievich; Kulikov, Sergey Pavlovich; Krotov, Dmitry Valerievich; Salogub, Anzhela Mikhailovna; Gnatyuk, Maksim Aleksandrovich

2016-01-01

The article reveals the role of creative social practices in the development of united activities in Russian society. Creative social practices in Russian society are implemented by different social groups and strata for the purpose of self-realization, participation in socially important affairs when agreed by state institutions, ensuring safety…

Credentialism, National Targets, and the Learning Society: Perspectives on Educational Attainment in the UK Steel Industry.

ERIC Educational Resources Information Center

Fuller, Alison; Unwin, Lorna

1999-01-01

The UK's National Learning Targets for Education and Training, embracing 11- to 21-year-olds, adults, and employers, promote a credentialist approach to economic and social development. This article shows how the steel industry measures up. Using qualifications-based targets as a proxy for adult workforce capability is misguided. (Contains 40…

NGOs, Civil Society, and Development: Is There a Third Way?

ERIC Educational Resources Information Center

Klees, Steven J.

2008-01-01

For more than a decade, there has been talk by politicians, academics, and others of a "third way," referring to means and principles of social organization other than the State and the market. Most of this discussion about a third way for development focuses on the roles that can be played by NGOs and other elements of civil society. In this…

Visualizing the application of GIS in transformation towards a sustainable development and a low carbon society

NASA Astrophysics Data System (ADS)

Ahmad, M. H.; Ariffin, A.; Malik, T. A.

2014-02-01

A strategy for sustainable development is a significant milestone on the road to a more socially, economically and environmentally responsible society. It creates a framework within which the stakeholders can make a strong contribution to a better future. Because of the merits and growing interest in sustainable development, the race is on for researchers and stakeholders in the construction sector to initiate actions to reduce the negative impacts of development and sharpen their competitive edge. The cities should be created with a vision which supports harmonious communities and living conditions through sustainable urban development. The resources must be used efficiently while reducing the development impact on human health and environment during the buildings' life cycle. Environmental auditing and pressure-state response based models to monitor sustainable development in Malaysia should be developed. A data availability and sharing system should be developed and implemented to facilitate for the use in the establishment of sustainable development and low carbon society. Ideas which affect millions of people and guide the policies of nations must be accessible to all. Only thus can they permeate the institutions from the local to the global level. Creating sustainable development and low carbon societies depends on the knowledge and involvement of all stakeholders in the industry. So what is our level of understanding of GIS and its application? The development of geospatial data in Malaysia is important because the successful implementation of sustainable development and low carbon projects depend largely on the availability of geospatial information. It would facilitate the stakeholders and resolve some of the problems regarding the availability, quality, organisation, accessibility and sharing of spatial information. The introduction of GIS may change the way for better sustainable urban development and low carbon society performance. The use of GIS is to

Development of a systematic feedback isolation approach for targeted strains from mixed culture systems.

PubMed

Poudel, Pramod; Tashiro, Yukihiro; Miyamoto, Hirokuni; Miyamoto, Hisashi; Okugawa, Yuki; Sakai, Kenji

2017-01-01

Elucidation of functions of bacteria in a mixed culture system (MCS) such as composting, activated sludge system is difficult, since the system is complicating with many unisolated bacteria. Here, we developed a systematic feedback isolation strategy for the isolation and rapid screening of multiple targeted strains from MCS. Six major strains (Corynebacterium sphenisci, Bacillus thermocloacae, Bacillus thermoamylovorans, Bacillus smithii, Bacillus humi, and Bacillus coagulans), which are detected by denaturing gradient gel electrophoresis (DGGE) analysis in our previous study on MCS for l-lactic acid production, were targeted for isolation. Based on information of suitable cultivation conditions (e.g., media, pH, temperature) from the literature, feedback isolation was performed to form 136 colonies. The following direct colony matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was optimised as the second screening to narrow down 20 candidate colonies from similar spectra patterns with six closest type strains. This step could distinguish bacteria at the species level with distance similarity scores ≥0.55 corresponding to 16S rRNA gene sequence similarity ≥98.2%, suggesting that this is an effective technique to minimize isolates close to targeted type strains. Analysis of 16S rRNA gene sequences indicated that two targeted strains and one strain related to the target had successfully been isolated, showing high similarities (99.5-100%) with the sequences from the DGGE bands, and that the other candidates were affiliated with three strains that were closely related to the target species. This study proposes a new method for systematic feedback isolation that may be useful for isolating targeted strains from MCS for further investigation. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Avoiding Praetorian Societies: Focusing U.S. Strategy on Political Development

DTIC Science & Technology

2014-03-01

decay results in Praetorian societies—societies without a shared civic culture .12 The second factor is that military approaches over- emphasize the...village communities to impersonal urban ones; and the transition from communal to individualistic social relationships.25 Modernization theory...extended families, tribes, or clans. These social units develop their own culture , norms, and values which inform group members on how to behave, interact

Recent Development of Anticancer Therapeutics Targeting Akt

PubMed Central

Morrow, John K.; Du-Cuny, Lei; Chen, Lu; Meuillet, Emmanuelle J.; Mash, Eugene A.; Powis, Garth; Zhang, Shuxing

2013-01-01

The serine/threonine kinase Akt has proven to be a significant signaling target, involved in various biological functions. Because of its cardinal role in numerous cellular responses, Akt has been implicated in many human diseases, particularly cancer. It has been established that Akt is a viable and feasible target for anticancer therapeutics. Analysis of all Akt kinases reveals conserved homology for an N-terminal regulatory domain, which contains a pleckstrin-homology (PH) domain for cellular translocation, a kinase domain with serine/threonine specificity, and a C-terminal extension domain. These well defined regions have been targeted, and various approaches, including in silico methods, have been implemented to develop Akt inhibitors. In spite of unique techniques and a prolific body of knowledge surrounding Akt, no targeted Akt therapeutics have reached the market yet. Here we will highlight successes and challenges to date on the development of anticancer agents modulating the Akt pathway in recent patents as well as discuss the methods employed for this task. Special attention will be given to patents with focus on those discoveries using computer-aided drug design approaches. PMID:21110830

Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol.

PubMed

Klonoff, David C; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A; Arreaza-Rubin, Guillermo; Burk, Robert D; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W

2016-05-01

Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled "Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program" is attached as supplementary material. This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. © 2015 Diabetes Technology Society.

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology.

PubMed

Sepulveda, Antonia R; Hamilton, Stanley R; Allegra, Carmen J; Grody, Wayne; Cushman-Vokoun, Allison M; Funkhouser, William K; Kopetz, Scott E; Lieu, Christopher; Lindor, Noralane M; Minsky, Bruce D; Monzon, Federico A; Sargent, Daniel J; Singh, Veena M; Willis, Joseph; Clark, Jennifer; Colasacco, Carol; Rumble, R Bryan; Temple-Smolkin, Robyn; Ventura, Christina B; Nowak, Jan A

2017-03-01

To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. Twenty-one guideline statements were established. Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented. Key Words: Molecular diagnostics; Gastrointestinal; Histology; Genetics; Oncology. Copyright © 2017 American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, American Society for Clinical Oncology, and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Promising Targets in Anti-cancer Drug Development: Recent Updates.

PubMed

Kumar, Bhupinder; Singh, Sandeep; Skvortsova, Ira; Kumar, Vinod

2017-01-01

Cancer is a multifactorial disease and its genesis and progression are extremely complex. The biggest problem in the anticancer drug development is acquiring of multidrug resistance and relapse. Classical chemotherapeutics directly target the DNA of the cell, while the contemporary anticancer drugs involve molecular-targeted therapy such as targeting the proteins possessing abnormal expression inside the cancer cells. Conventional strategies for the complete eradication of the cancer cells proved ineffective. Targeted chemotherapy was successful in certain malignancies however, the effectiveness has often been limited by drug resistance and side effects on normal tissues and cells. Since last few years, many promising drug targets have been identified for the effective treatment of cancer. The current review article describes some of these promising anticancer targets that include kinases, tubulin, cancer stem cells, monoclonal antibodies and vascular targeting agents. In addition, promising drug candidates under various phases of clinical trials are also described. Multi-acting drugs that simultaneously target different cancer cell signaling pathways may facilitate the process of effective anti-cancer drug development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sensor development at the semiconductor laboratory of the Max-Planck-Society

NASA Astrophysics Data System (ADS)

Bähr, A.; Lechner, P.; Ninkovic, J.

2017-12-01

For more than twenty years the semiconductor laboratory of the Max-Planck Society (MPG-HLL) is developing high-performing, specialised, scientific silicon sensors including the integration of amplifying electronics on the sensor chip. This paper summarises the actual status of these devices like pnCCDs and DePFET Active Pixel Sensors and their applications.

[The development of novel tumor targeting delivery strategy].

PubMed

Gao, Hui-le; Jiang, Xin-guo

2016-02-01

Tumor is one of the most serious threats for human being. Although many anti-tumor drugs are approved for clinical use, the treatment outcome is still modest because of the poor tumor targeting efficiency and low accumulation in tumor. Therefore, it is important to deliver anti-tumor drug into tumor efficiently, elevate drug concentration in tumor tissues and reduce the drug distribution in normal tissues. And it has been one of the most attractive directions of pharmaceutical academy and industry. Many kinds of strategies, especially various nanoparticulated drug delivery systems, have been developed to address the critical points of complex tumor microenvironment, which are partially or mostly satisfied for tumor treatment. In this paper, we carefully reviewed the novel targeting delivery strategies developed in recent years. The most powerful method is passive targeting delivery based on the enhanced permeability and retention(EPR) effect, and most commercial nanomedicines are based on the EPR effect. However, the high permeability and retention require different particle sizes, thus several kinds of size-changeable nanoparticles are developed, such as size reducible particles and assemble particles, to satisfy the controversial requirement for particle size and enhance both tumor retention and penetration. Surface charge reversible nanoparticles also shows a high efficiency because the anionic charge in blood circulation and normal organs decrease the unintended internalization. The charge can change into positive in tumor microenvironment, facilitating drug uptake by tumor cells. Additionally, tumor microenvironment responsive drug release is important to decrease drug side effect, and many strategies are developed, such as p H sensitive release and enzyme sensitive release. Except the responsive nanoparticles, shaping tumor microenvironment could attenuate the barriers in drug delivery, for example, decreasing tumor collagen intensity and normalizing tumor

American Rocket Society

NASA Technical Reports Server (NTRS)

2004-01-01

In addition to Dr. Robert Goddard's pioneering work, American experimentation in rocketry prior to World War II grew, primarily in technical societies. This is an early rocket motor designed and developed by the American Rocket Society in 1932.

Development of novel entry inhibitors targeting emerging viruses

PubMed Central

Zhou, Yanchen; Simmons, Graham

2013-01-01

Emerging viral diseases pose a unique risk to public health, and thus there is a need to develop therapies. A current focus of funding agencies, and hence research, is the development of broad-spectrum antivirals, and in particular, those targeting common cellular pathways. The scope of this article is to review screening strategies and recent advances in this area, with a particular emphasis on antivirals targeting the step of viral entry for emerging lipid-enveloped viruses such as Ebola virus and SARS-coronavirus. PMID:23199399

Consumption in the Information Society

ERIC Educational Resources Information Center

Zherebin, V. M.; Ermakova, N. A.; Makhrova, O. N.

2010-01-01

The current state of the economy in the developed countries make it possible to characterize them using concepts and terms such as the postindustrial society, the new economy, the service economy, the creative economy, the posteconomic society, the information society, the knowledge society, and the consumer society. Among these terms and…

The development of ecological environment in China based on the system dynamics method from the society, economy and environment perspective.

PubMed

Guang, Yang; Ge, Song; Han, Liu

2016-01-01

The harmonious development in society, economy and environment are crucial to regional sustained boom. However, the society, economy and environment are not respectively independent, but both mutually promotes one which, or restrict mutually complex to have the long-enduring overall process. The present study is an attempt to investigate the relationship and interaction of society, economy and environment in China based on the data from 2004 to 2013. The principal component analysis (PCA) model was employed to identify the main factors effecting the society, economy and environment subsystems, and SD (system dynamics) method used to carry out dynamic assessment for future state of sustainability from society, economy and environment perspective with future indicator values. Sustainable development in China was divided in the study into three phase from 2004 to 2013 based competitive values of these three subsystems. According to the results of PCA model, China is in third phase, and the economy growth is faster than the environment development, while the social development still maintained a steady and rapid growth, implying that the next step for sustainable development in China should focus on society development, especially the environment development.

Human Resource Development for Knowledge-based Society and Challenges of Nagoya University

NASA Astrophysics Data System (ADS)

Miyata, Takashi

Innovation in the previous century resulted in development of useful products ranging from automobiles and aircraft to cellular phones. However, the innovation and development of science and technology have changed the society and brought about negative issues. The issues emerged in the previous century remain in the excessive forms in the 21st century. The 21st century is seeing the rise of knowledge-based society, and paradigm shift is now going on. Human resources of university for creation of innovation are being called on to contribute to solving issues. Young people who pass through a doctor program must play a role as an innovator who can promote the paradigm shift. However, the higher education system of the universities in Japan is now required to be changed to dissolve the mismatch on the doctor program with industries, government and students. The discussion in the Business-University Forum of Japan for innovation of education system and a few challenges of the Nagoya University are introduced in this paper.

Advertising: Art as Society's Mirror.

ERIC Educational Resources Information Center

Coleman, Catherine E. B.

1998-01-01

Provides a historical overview of U.S. print advertising from the 1890s to the 1990s. Demonstrates how advertisers adapt their messages and target audiences to the changes each era brings. Conveys that advertising reflects society by giving an image of an era as it aims to persuade. Offers six teaching activities. (CMK)

Trust and Society: Suggestions for Further Development of Niklas Luhmann's Theory of Trust.

PubMed

Morgner, Christian

2018-05-01

This paper addresses an apparent gap in the work of Niklas Luhmann. While the issue of trust continues to receive widespread attention in the social sciences, Luhmann's interest in this topic declined following the development of his systems theory. It is argued that this decline does not reflect any diminished relevance of trust for systems theory, but rather that the architectural remodeling of theory cannot easily be applied to the issue of trust. Here, the issue of trust is reconceptualized as a connection medium. This entails a reconstruction of Luhmann's early theory of trust, especially with regard to function and social positioning. In this context, trust can in turn be linked to the concept of medium in Luhmann's late work. As a connection medium, trust mediates between the different levels of sociality-interaction, organization, and society. These theoretical considerations are employed to develop a more applied framework for empirical research, with a brief case study from southern Italy. From this perspective, the idea of trust as society's glue is seen to be overly simplistic. The common ethical understanding that more trust leads to a better society is also questioned on the grounds that social cooperation can also lead to social sclerosis. Finally, risk and trust are shown to accommodate the formation of different cultures of trust. The paper shows how Luhmann's updated version of trust can inspire current research and enhance our understanding of how trust operates in contemporary society. © 2018 Canadian Sociological Association/La Société canadienne de sociologie.

Different types of multiethnic societies and different patterns of development and change in the prehistoric Near East.

PubMed

Frangipane, Marcella

2015-07-28

After briefly examining the forms of cultural contact in pre- and protohistoric societies in relation to the problem of the varying perception of territories and their "borders" as well as of "membership" in those societies, and after a brief reconsideration of the concept of culture and ethnicity in such archaic contexts, this paper then examines three examples of multiethnic societies in the Near East, and specifically in Upper Mesopotamia and Southeast Anatolia, in the fifth, fourth, and at the beginning of the third millennia before the common era (BCE), respectively. These examples are dealt with as emblematic cases of different models of society, types of interaction with alien groups, levels of integration, and development dynamics. Each of these cases is examined with respect to its socioeconomic context, the archeological evidence of "multiethnicity," the types of interaction between different components, the degree of cultural integration achieved, and the effects on the dynamics of change and the development of the societies examined. By analyzing and comparing these examples, the paper aims to show how interethnic contact impacted differently on different societies according to their types, the reasons and purposes of the interaction, and the degree of integration achieved.

Trends in Connectivity Technologies and Their Socioeconomic Impacts. Final Report of the Study: Policy Options for the Ubiquitous Internet Society. Technical Report

ERIC Educational Resources Information Center

Cave, Jonathan; van Oranje-Nassau, Constantijn; Schindler, Helen Rebecca; Shehabi, Ala'a; Brutscher, Philipp-Bastian; Robinson, Neil

2009-01-01

This report is intended to inform the European Commission's DG Information Society and Media in developing its policies for the period 2010-2020. It is targeted to policymakers with expert knowledge of the field. The report summarises the work conducted in the study: "Policy Options for the Ubiquitous Internet Society". It builds on…

Multi-target drugs: the trend of drug research and development.

PubMed

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.

Advancing cancer drug discovery towards more agile development of targeted combination therapies.

PubMed

Carragher, Neil O; Unciti-Broceta, Asier; Cameron, David A

2012-01-01

Current drug-discovery strategies are typically 'target-centric' and are based upon high-throughput screening of large chemical libraries against nominated targets and a selection of lead compounds with optimized 'on-target' potency and selectivity profiles. However, high attrition of targeted agents in clinical development suggest that combinations of targeted agents will be most effective in treating solid tumors if the biological networks that permit cancer cells to subvert monotherapies are identified and retargeted. Conventional drug-discovery and development strategies are suboptimal for the rational design and development of novel drug combinations. In this article, we highlight a series of emerging technologies supporting a less reductionist, more agile, drug-discovery and development approach for the rational design, validation, prioritization and clinical development of novel drug combinations.

Taking Steps towards the Knowledge Society: Reflections on the Process of Knowledge Development. CEDEFOP Reference Series.

ERIC Educational Resources Information Center

Nyhan, Barry, Ed.

This 11-chapter book is intended to explore the ways in which professional and vocational education and training (VET) can contribute toward building the emerging "knowledge society," particularly the ways in which the research and development community can take proactive steps to shape the emerging knowledge society. Part 1, on…

Computer Abuse: Vandalizing the Information Society.

ERIC Educational Resources Information Center

Furnell, Steven M.; Warren, Matthew J.

1997-01-01

Computing and telecommunications, key to an information-based society, are increasingly targets for criminals and mischief makers. This article examines the effects of malicious computer abuse: hacking and viruses, highlights the apparent increase in incidents, and examines their effect on public perceptions of technology. Presents broad…

The epididymis as a target for male contraceptive development.

PubMed

Hinton, B T; Cooper, T G

2010-01-01

The epididymis is an excellent target for the development of a male contraceptive. This is because the process of sperm maturation occurs in this organ; spermatozoa become motile and are able to recognise and fertilise an egg once they have traversed the epididymal duct. However, a number of attempts to interfere in sperm maturation and epididymal function or both have not been successful. The use of transgenic animals has proved useful in identifying a few epididymal targets but has yet to open the doors for drug development. Continuous focus on identifying additional epididymal targets and sperm-specific and epididymal-specific drugs is key to bringing a male contraceptive acting on the epididymis to the public.

Applying cognitive training to target executive functions during early development.

PubMed

Wass, Sam V

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development.

Applying cognitive training to target executive functions during early development

PubMed Central

Wass, Sam V.

2015-01-01

Developmental psychopathology is increasingly recognizing the importance of distinguishing causal processes (i.e., the mechanisms that cause a disease) from developmental outcomes (i.e., the symptoms of the disorder as it is eventually diagnosed). Targeting causal processes early in disordered development may be more effective than waiting until outcomes are established and then trying to reverse the pathogenic process. In this review, I evaluate evidence suggesting that neural and behavioral plasticity may be greatest at very early stages of development. I also describe correlational evidence suggesting that, across a number of conditions, early emerging individual differences in attentional control and working memory may play a role in mediating later-developing differences in academic and other forms of learning. I review the currently small number of studies that applied direct and indirect cognitive training targeted at young individuals and discuss methodological challenges associated with targeting this age group. I also discuss a number of ways in which early, targeted cognitive training may be used to help us understand the developmental mechanisms subserving typical and atypical cognitive development. PMID:24511910

The Holistic Targeting (HOT) Methodology as the Means to Improve Information Operations (IO) Target Development and Prioritization

DTIC Science & Technology

2008-09-01

software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi-automated means to...the use of compendium software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi...OBJECTIVES USING COMPENDIUM SOFTWARE .....63 E. HOT TARGET PRIORITIZATION AND DEVELOPMENT USING PALANTIR SOFTWARE .................................69 1

Different types of multiethnic societies and different patterns of development and change in the prehistoric Near East

PubMed Central

Frangipane, Marcella

2015-01-01

After briefly examining the forms of cultural contact in pre- and protohistoric societies in relation to the problem of the varying perception of territories and their “borders” as well as of “membership” in those societies, and after a brief reconsideration of the concept of culture and ethnicity in such archaic contexts, this paper then examines three examples of multiethnic societies in the Near East, and specifically in Upper Mesopotamia and Southeast Anatolia, in the fifth, fourth, and at the beginning of the third millennia before the common era (BCE), respectively. These examples are dealt with as emblematic cases of different models of society, types of interaction with alien groups, levels of integration, and development dynamics. Each of these cases is examined with respect to its socioeconomic context, the archeological evidence of “multiethnicity,” the types of interaction between different components, the degree of cultural integration achieved, and the effects on the dynamics of change and the development of the societies examined. By analyzing and comparing these examples, the paper aims to show how interethnic contact impacted differently on different societies according to their types, the reasons and purposes of the interaction, and the degree of integration achieved. PMID:26015583

The Impact of Tertiary Education on Development of Moderate Society in Pakistan

ERIC Educational Resources Information Center

Atika, Samrana

2010-01-01

The study aimed to find out the impact of tertiary education on development of moderate Islamic society in Pakistan. The population of the study constituted of all the teachers engaged on teaching and all the students studying in the colleges. The study was delimited to the area of public sector college education. Cluster sampling technique was…

Broadening Participation in the Society for Integrative and Comparative Biology.

PubMed

Wilga, Cheryl A D; Nishiguchi, Michele; Tsukimura, Brian

2017-07-01

The goal of the Society for Integrative and Comparative Biology's Broadening Participation Committee (SICB BPC) is to increase the number of underrepresented group (URG) members within the society and to expand their capabilities as future researchers and leaders within SICB. Our short-term 10-year goal was to increase the recruitment and retention of URG members in the society by 10%. Our long-term 25-year goal is to increase the membership of URG in the society through recruitment and retention until the membership demographic mirrors that of the US Census. Our plans to accomplish this included establishment of a formal standing committee, establishment of a moderate budget to support BPC activities, hosting professional development workshops, hosting diversity and mentor socials, and obtaining grant funds to supplement our budget. This paper documents broadening participation activities in the society, discusses the effectiveness of these activities, and evaluates BPC goals after 5 years of targeted funded activities. Over the past 5 years, the number of URG members rose by 5.2% to a total of 16.2%, members who report ethnicity and gender increased by 25.2% and 18%, respectively, and the number of members attending BPC activities has increased to 33% by 2016. SICB has made significant advances in broadening participation, not only through increased expenditures, but also with a commitment by its members and leadership to increase diversity. Most members realize that increasing diversity will both improve the Society's ability to develop different approaches to tackling problems within integrative biology, and help solve larger global issues that are evident throughout science and technology fields. In addition, having URG members as part of the executive committee would provide other URG members role models within the society, as well as have a voice in the leadership that represents diversity and inclusion for all scientists. © The Author 2017. Published by

Extracellular proteases as targets for drug development

PubMed Central

Cudic, Mare

2015-01-01

Proteases constitute one of the primary targets in drug discovery. In the present review, we focus on extracellular proteases (ECPs) because of their differential expression in many pathophysiological processes, including cancer, cardiovascular conditions, and inflammatory, pulmonary, and periodontal diseases. Many new ECP inhibitors are currently under clinical investigation and a significant increase in new therapies based on protease inhibition can be expected in the coming years. In addition to directly blocking the activity of a targeted protease, one can take advantage of differential expression in disease states to selectively deliver therapeutic or imaging agents. Recent studies in targeted drug development for the metalloproteases (matrix metalloproteinases, adamalysins, pappalysins, neprilysin, angiotensin-converting enzyme, metallocarboxypeptidases, and glutamate carboxypeptidase II), serine proteases (elastase, coagulation factors, tissue/urokinase plasminogen activator system, kallikreins, tryptase, dipeptidyl peptidase IV), cysteine proteases (cathepsin B), and renin system are discussed herein. PMID:19689354

Broadening Participation in the Society for Integrative and Comparative Biology

PubMed Central

Wilga, Cheryl A.D.; Nishiguchi, Michele; Tsukimura, Brian

2017-01-01

Synopsis The goal of the Society for Integrative and Comparative Biology’s Broadening Participation Committee (SICB BPC) is to increase the number of underrepresented group (URG) members within the society and to expand their capabilities as future researchers and leaders within SICB. Our short-term 10-year goal was to increase the recruitment and retention of URG members in the society by 10%. Our long-term 25-year goal is to increase the membership of URG in the society through recruitment and retention until the membership demographic mirrors that of the US Census. Our plans to accomplish this included establishment of a formal standing committee, establishment of a moderate budget to support BPC activities, hosting professional development workshops, hosting diversity and mentor socials, and obtaining grant funds to supplement our budget. This paper documents broadening participation activities in the society, discusses the effectiveness of these activities, and evaluates BPC goals after 5 years of targeted funded activities. Over the past 5 years, the number of URG members rose by 5.2% to a total of 16.2%, members who report ethnicity and gender increased by 25.2% and 18%, respectively, and the number of members attending BPC activities has increased to 33% by 2016. SICB has made significant advances in broadening participation, not only through increased expenditures, but also with a commitment by its members and leadership to increase diversity. Most members realize that increasing diversity will both improve the Society’s ability to develop different approaches to tackling problems within integrative biology, and help solve larger global issues that are evident throughout science and technology fields. In addition, having URG members as part of the executive committee would provide other URG members role models within the society, as well as have a voice in the leadership that represents diversity and inclusion for all scientists. PMID:28881934

Role of Mass Media in the Disaster Preparedness and Sustainable Development of Society

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

Seid-Aliyeva, Dinara E.

2006-03-23

Better understanding of the causes and effects of large earthquakes can assists in mitigation of damage and loss of lives as a result of destructive natural events. Well-informed and educated population living in geological hazard-prone regions can reduce catastrophic consequences of natural disasters and guaranty the sustainable development of healthy society. A development of information service for disaster management is of importance in reduction of the disaster's consequences.

Developing plans and priorities for climate science in service to society

NASA Astrophysics Data System (ADS)

Asrar, Ghassem; Busalacchi, Antonio; Hurrell, James

2012-03-01

World Climate Research Programme (WCRP) Open Science Conference; Denver, Colorado, 24-28 October 2011 The WCRP Open Science Conference (OSC), which had the theme "Climate Research in Service to Society," was held to consult with the international community of experts on future plans and priorities for the WCRP. More than 1900 participants, including 541 young scholars from 86 nations and 300 scientists from developing nations, made the conference a success. Several major scientific priorities emerged from OSC.

Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians.

PubMed

Miskowiak, K W; Burdick, K E; Martinez-Aran, A; Bonnin, C M; Bowie, C R; Carvalho, A F; Gallagher, P; Lafer, B; López-Jaramillo, C; Sumiyoshi, T; McIntyre, R S; Schaffer, A; Porter, R J; Purdon, S; Torres, I J; Yatham, L N; Young, A H; Kessing, L V; Vieta, E

2018-05-01

Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeting targeted agents: open issues for clinical trial design.

PubMed

Bria, Emilio; Di Maio, Massimo; Carlini, Paolo; Cuppone, Federica; Giannarelli, Diana; Cognetti, Francesco; Milella, Michele

2009-05-22

Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present). Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

Targeted mutagenesis in sea urchin embryos using TALENs.

PubMed

Hosoi, Sayaka; Sakuma, Tetsushi; Sakamoto, Naoaki; Yamamoto, Takashi

2014-01-01

Genome editing with engineered nucleases such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) has been reported in various animals. We previously described ZFN-mediated targeted mutagenesis and insertion of reporter genes in sea urchin embryos. In this study, we demonstrate that TALENs can induce mutagenesis at specific genomic loci of sea urchin embryos. Injection of TALEN mRNAs targeting the HpEts transcription factor into fertilized eggs resulted in the impairment of skeletogenesis. Sequence analyses of the mutations showed that deletions and/or insertions occurred at the HpEts target site in the TALEN mRNAs-injected embryos. The results suggest that targeted gene disruption using TALENs is feasible in sea urchin embryos. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Strategies that Target Leukocyte Traffic in IBD: Recent Developments

PubMed Central

Rivera-Nieves, Jesús

2015-01-01

Purpose of review We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of IBD. Recent Findings We discuss the most important findings of one published phase II trial that targeted the β7 integrin (Etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1, PF-00547659), a phase II targeting the chemokine IP-10 (CXCL10) in Crohn’s and a phase II trial that targeted the sphingosine-1-phosphate receptor-1 (S1P1): ozanimod in patients with ulcerative colitis (UC). Summary Targeting molecules involved in leukocyte traffic has recently become an effective and safe strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn’s. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin:immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules. PMID:26398681

Drug resistance to targeted therapies: déjà vu all over again.

PubMed

Groenendijk, Floris H; Bernards, René

2014-09-12

A major limitation of targeted anticancer therapies is intrinsic or acquired resistance. This review emphasizes similarities in the mechanisms of resistance to endocrine therapies in breast cancer and those seen with the new generation of targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is frequently the result of reactivation of the signaling pathway, indicating that a major limitation of targeted agents lies in their inability to fully block the cancer-relevant signaling pathway. The development of mechanism-based combinations of targeted therapies together with non-invasive molecular disease monitoring is a logical way forward to delay and ultimately overcome drug resistance development. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology.

PubMed

Sepulveda, Antonia R; Hamilton, Stanley R; Allegra, Carmen J; Grody, Wayne; Cushman-Vokoun, Allison M; Funkhouser, William K; Kopetz, Scott E; Lieu, Christopher; Lindor, Noralane M; Minsky, Bruce D; Monzon, Federico A; Sargent, Daniel J; Singh, Veena M; Willis, Joseph; Clark, Jennifer; Colasacco, Carol; Bryan Rumble, R; Temple-Smolkin, Robyn; B Ventura, Christina; Nowak, Jan A

2017-05-01

- To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. - The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. - Twenty-one guideline statements were established. - Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented.

Teachers' Professional Development. Teachers in Society Series.

ERIC Educational Resources Information Center

Hughes, Phillip, Ed.

This book is the first in a series on teachers and teaching, a result of the Australian Council for Educational Research program of research on teachers. The theme, teachers in society, has been constructed around three broad areas: the context of teaching, teacher education, and teachers' work. The book is divided into 8 chapters as follows: (l)…

Recent developments in emerging therapeutic targets of osteoarthritis.

PubMed

Sun, Margaret Man-Ger; Beier, Frank; Pest, Michael A

2017-01-01

Despite the tremendous individual suffering and socioeconomic burden caused by osteoarthritis, there are currently no effective disease-modifying treatment options. This is in part because of our incomplete understanding of osteoarthritis disease mechanism. This review summarizes recent developments in therapeutic targets identified from surgical animal models of osteoarthritis that provide novel insight into osteoarthritis pathology and possess potential for progression into preclinical studies. Several candidate pathways and processes that have been identified include chondrocyte autophagy, growth factor signaling, inflammation, and nociceptive signaling. Major strategies that possess therapeutic potential at the cellular level include inhibiting autophagy suppression and decreasing reactive oxygen species (ROS) production. Cartilage anabolism and prevention of cartilage degradation has been shown to result from growth factor signaling modulation, such as TGF-β, TGF-α, and FGF; however, the results are context-dependent and require further investigation. Pain assessment studies in rodent surgical models have demonstrated potential in employing anti-NGF strategies for minimizing osteoarthritis-associated pain. Studies of potential therapeutic targets in osteoarthritis using animal surgical models are helping to elucidate osteoarthritis pathology and propel therapeutics development. Further studies should continue to elucidate pathological mechanisms and therapeutic targets in various joint tissues to improve overall joint health.

Development of the Diabetes Technology Society Blood Glucose Monitor System Surveillance Protocol

PubMed Central

Klonoff, David C.; Lias, Courtney; Beck, Stayce; Parkes, Joan Lee; Kovatchev, Boris; Vigersky, Robert A.; Arreaza-Rubin, Guillermo; Burk, Robert D.; Kowalski, Aaron; Little, Randie; Nichols, James; Petersen, Matt; Rawlings, Kelly; Sacks, David B.; Sampson, Eric; Scott, Steve; Seley, Jane Jeffrie; Slingerland, Robbert; Vesper, Hubert W.

2015-01-01

Background: Inaccurate blood glucsoe monitoring systems (BGMSs) can lead to adverse health effects. The Diabetes Technology Society (DTS) Surveillance Program for cleared BGMSs is intended to protect people with diabetes from inaccurate, unreliable BGMS products that are currently on the market in the United States. The Surveillance Program will provide an independent assessment of the analytical performance of cleared BGMSs. Methods: The DTS BGMS Surveillance Program Steering Committee included experts in glucose monitoring, surveillance testing, and regulatory science. Over one year, the committee engaged in meetings and teleconferences aiming to describe how to conduct BGMS surveillance studies in a scientifically sound manner that is in compliance with good clinical practice and all relevant regulations. Results: A clinical surveillance protocol was created that contains performance targets and analytical accuracy-testing studies with marketed BGMS products conducted by qualified clinical and laboratory sites. This protocol entitled “Protocol for the Diabetes Technology Society Blood Glucose Monitor System Surveillance Program” is attached as supplementary material. Conclusion: This program is needed because currently once a BGMS product has been cleared for use by the FDA, no systematic postmarket Surveillance Program exists that can monitor analytical performance and detect potential problems. This protocol will allow identification of inaccurate and unreliable BGMSs currently available on the US market. The DTS Surveillance Program will provide BGMS manufacturers a benchmark to understand the postmarket analytical performance of their products. Furthermore, patients, health care professionals, payers, and regulatory agencies will be able to use the results of the study to make informed decisions to, respectively, select, prescribe, finance, and regulate BGMSs on the market. PMID:26481642

Pittsburgh Science Technology Society Project: Instruction Modules. Interrelationships Science--Technology--Society.

ERIC Educational Resources Information Center

O'Brien, George, Ed.

This collection of instruction modules studies the interactions of science, technology, and society (STS) using five activity sets. The introduction module includes activities which show students the STS relationships in their world, develop good organizational skills, develop an understanding of who and what a scientist is, develop graphing…

Environment, energy, and society

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

Humphrey, C.R.; Buttel, F.R.

1986-01-01

This book delineates the major ways in which human society and the environment affect each other. To study the structure of societies, it employs three conceptual models, or sociological paradigms, conservative, liberal, and radical. The book explains the courses in environmental sociology, international development, natural resources, agriculture, and urban or regional planning.

Role of the International Society for Peritoneal Dialysis (ISPD) in the future of peritoneal dialysis.

PubMed

Lo, Wai Kei

2009-01-01

The International Society for Peritoneal Dialysis (ISPD) was established in 1984. Throughout the years, the ISPD has been playing a pivotal role in the development of peritoneal dialysis (PD) through organizing congresses, publishing the Peritoneal Dialysis International formation of treatment and training guidelines, and supporting international studies. In recent years, it has enhanced its educational programs through organizing PD courses in developing countries, online education videos and a function 'Questions about PD' on its website. Several regional chapters - Asian, North American and Latin American - have been formed to target the special needs of different regions. To move forward, apart from enhancing the current activities, good use of cyber technology for out-reaching and educational purposes, and collaboration with other international or national societies particularly in the area of national policy making are envisaged.

Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis.

PubMed

Tang, An; Hallouch, Oussama; Chernyak, Victoria; Kamaya, Aya; Sirlin, Claude B

2018-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

Developing targets for radiation transport experiments at the Omega laser facility

DOE PAGES

Capelli, Deanna; Charsley-Groffman, C. A.; Randolph, Randall Blaine; ...

2017-07-13

Targets have been developed to measure supersonic radiation transport in aerogel foams using absorption spectroscopy. The target consists of an aerogel foam uniformly doped with either titanium or scandium inserted into an undoped aerogel foam package. This creates a localized doped foam region to provide spatial resolution for the measurement. Development and characterization of the foams is a key challenge in addition to machining and assembling the two foams so they mate without gaps. The foam package is inserted into a beryllium sleeve and mounted on a gold hohlraum. The target is mounted to a holder created using additive manufacturingmore » and mounted on a stalk. As a result, the manufacturing of the components, along with assembly and metrology of the target are described here.« less

Developing targets for radiation transport experiments at the Omega laser facility

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

Capelli, Deanna; Charsley-Groffman, C. A.; Randolph, Randall Blaine

Targets have been developed to measure supersonic radiation transport in aerogel foams using absorption spectroscopy. The target consists of an aerogel foam uniformly doped with either titanium or scandium inserted into an undoped aerogel foam package. This creates a localized doped foam region to provide spatial resolution for the measurement. Development and characterization of the foams is a key challenge in addition to machining and assembling the two foams so they mate without gaps. The foam package is inserted into a beryllium sleeve and mounted on a gold hohlraum. The target is mounted to a holder created using additive manufacturingmore » and mounted on a stalk. As a result, the manufacturing of the components, along with assembly and metrology of the target are described here.« less

Developing Medications Targeting Glutamatergic Dysfunction in Autism: Progress to Date

PubMed Central

Fung, Lawrence K.; Hardan, Antonio Y.

2015-01-01

Pharmacologic treatments targeting specific molecular mechanisms relevant for autism spectrum disorder (ASD) are beginning to emerge in early drug development. This article reviews the evidence for the disruption of glutamatergic neurotransmission in animal models of social deficits and summarizes key pre-clinical and clinical efforts in developing pharmacologic interventions based on modulation of glutamatergic systems in individuals with ASD. Understanding the pathobiology of the glutamatergic system has led to the development of new investigational treatments for individuals with ASD. Specific examples of medications that modulate the glutamatergic system in preclinical and clinical studies are described. Finally, we will discuss the limitations of current strategies and future opportunities in developing medications targeting the glutamatergic system for treating individuals with ASD. PMID:26104862

Lipid Management in a Japanese Community:Attainment Rate of Target Set by the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Nohara, Atsushi; Inazu, Akihiro; Kobayashi, Junji; Yasuda, Kenji; Mabuchi, Hiroshi; Yamagishi, Masakazu; Hayashi, Kenshi

2017-03-01

The Japan Atherosclerosis Society (JAS) guidelines for the prevention of atherosclerotic diseases 2012 (JAS2012) proposed lipid management targets; however, less data is available regarding the attainment rates of each target in community-based settings. Therefore, we assessed the attainment rates of lipid management targets among subjects who underwent Japanese specific health checkups. A total of 85,716 subjects (male=29,282, 34.2%) aged 40-74 years who underwent specific health checkups from 2012 to 2014 in Kanazawa city, Japan, were included in this study. We evaluated the attainment rates of the lipid management targets according to the JAS2012 guideline and investigated the clinical characteristics of the subjects without achieving the targets. The target for LDL cholesterol (LDL-C) was the least attained in all risk categories, 89, 72, 50, and 34% for category I, II, III, and secondary prevention, respectively, in 2014. In addition, these rates inversely correlated with the grade of risk categories (p-value for trends ＜0.001). Attainment rate of the LDL-C target in the suspected chronic kidney disease (CKD) group was significantly lower than in the groups with diabetes, stroke, or absolute risk in category III (49.2, 60.3, 63.5, 54.4%, respectively, p-value ＜0.001 for each). Moreover, the attainment rate of the LDL-C target was significantly lower in subjects that did not receive lipid-lowering therapy than in those who received it in the secondary prevention (27.7 and 40.6%, respectively, p-value ＜0.001). Lipid management is inadequate in community-based settings, particularly, in subjects with CKD and secondary prevention.

Development of a microcapillary column for detecting targeted messenger RNA molecules.

PubMed

Ohnishi, Michihiro

2006-03-24

A capillary column in a rapid-flow system has been developed for detecting targeted messenger RNA (mRNA) molecules. The column has a structure made of two beds-one bed of porous microbeads and one bed of microbeads with a polythymidine base sequence. The targeted eukaryotic mRNA molecules are detected by two-step hybridization (sandwich hybridization) composed of polyadenosine selection of mRNA molecules and formation of a probe-target (targeted mRNA) hybrid. The sandwich hybridization, which is accomplished within 1 h, was tested using synthetic polydeoxynucleotides. Ten picomoles of the targeted polydeoxynucleotide were detected.

Apollo experience report: Development of guidance targeting techniques for the command module and launch vehicle

NASA Technical Reports Server (NTRS)

Yencharis, J. D.; Wiley, R. F.; Davis, R. S.; Holmes, Q. A.; Zeiler, K. T.

1972-01-01

The development of the guidance targeting techniques for the Apollo command module and launch vehicle is discussed for four types of maneuvers: (1) translunar injection, (2) translunar midcourse, (3) lunar orbit insertion, and (4) return to earth. The development of real-time targeting programs for these maneuvers and the targeting procedures represented are discussed. The material is intended to convey historically the development of the targeting techniques required to meet the defined target objectives and to illustrate the solutions to problems encountered during that development.

The druggable genome and support for target identification and validation in drug development.

PubMed

Finan, Chris; Gaulton, Anna; Kruger, Felix A; Lumbers, R Thomas; Shah, Tina; Engmann, Jorgen; Galver, Luana; Kelley, Ryan; Karlsson, Anneli; Santos, Rita; Overington, John P; Hingorani, Aroon D; Casas, Juan P

2017-03-29

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease. Copyright © 2017, American Association for the Advancement of Science.

Economic Development Projects and Jobs: Lessons from the Targeted Jobs Demonstration Program.

ERIC Educational Resources Information Center

Van Horn, Carl; And Others

This guide, based on approaches for targeting jobs and business opportunities that were developed during the Targeted Jobs Demonstration Program (TJDP), contains strategies and techniques for ensuring that some of the benefits of economic development investments are directed to low-income individuals and small and minority businesses. Addressed in…

Does the world need a scientific society for research on how to improve healthcare?

PubMed

Wensing, Michel; Grimshaw, Jeremy M; Eccles, Martin P

2012-02-29

In this editorial, we reflect on the arguments for starting a scientific society focused on research on how to improve healthcare. This society would take an inclusive approach to what constitutes healthcare. For instance, it should include mental health healthcare, treatment for substance abuse, the work of allied health professions, and preventive healthcare. The society would be open to researchers from all traditions. Thus, we take an inclusive approach to what constitutes scientific research, as long as it uses rigorous methods, is focused on improving healthcare, and aims at knowledge that can be transferred across settings. The society would primarily target scientific researchers but would invite others with an interest in this area of research, regardless of their discipline, position, field of application, or group affiliation (e.g., improvement science, behavioral medicine, knowledge translation). A society would need fruitful collaboration with related societies and organizations, which may include having combined meetings. Special links may be developed with one or more journals. A website to provide information on relevant resources, events, and training opportunities is another key activity. It would also provide a voice for the field at funding agencies, political arenas, and similar institutions. An organizational structure and financial resources are required to develop and run these activities. Our aim is to start an international debate, to discover if we can establish a shared vision across academics and stakeholders engaged with creating scientific knowledge on how to improve healthcare. We invite readers to express their views in the online questionnaire accessed by following the URL link provided at the end of the editorial.

HIV-1 Gag as an Antiviral Target: Development of Assembly and Maturation Inhibitors.

PubMed

Spearman, Paul

2016-01-01

HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent the formation and release of infectious particles. Until recently, however, only the catalytic site protease inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors leading the way.

Bacterial Transcription as a Target for Antibacterial Drug Development

PubMed Central

Ma, Cong; Yang, Xiao

2016-01-01

SUMMARY Transcription, the first step of gene expression, is carried out by the enzyme RNA polymerase (RNAP) and is regulated through interaction with a series of protein transcription factors. RNAP and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. Despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. The determination of the three-dimensional structures of RNAP and transcription complexes at high resolution over the last 15 years has led to renewed interest in targeting this essential process for antibiotic development by utilizing rational structure-based approaches. In this review, we describe the inhibition of the bacterial transcription process with respect to structural studies of RNAP, highlight recent progress toward the discovery of novel transcription inhibitors, and suggest additional potential antibacterial targets for rational drug design. PMID:26764017

The beginnings of the Southern Child/Pediatric Neurology Society.

PubMed

Dyken, Paul Richard; Bodensteiner, John B

2015-04-01

The founding and early development of the Southern Pediatric Neurology Society was in many ways parallel to that of the Child Neurology Society. The organization started out as the Southern Child Neurology Society but the name was changed at the time of incorporation so as to avoid confusion of identity and purpose with the larger Child Neurology Society. Although there are archives of early days and the later development of the Southern Pediatric Neurology Society, the details have never been set down in a narrative explaining the events that led to the development of the organization. In this paper, we try to produce a written record of the history of the founding and early development of the Southern Pediatric Neurology Society. © The Author(s) 2014.

Novel and viable acetylcholinesterase target site for developing effective and environmentally safe insecticides.

PubMed

Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-04-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

Indian Vacuum Society: The Indian Vacuum Society

NASA Astrophysics Data System (ADS)

Saha, T. K.

2008-03-01

The Indian Vacuum Society (IVS) was established in 1970. It has over 800 members including many from Industry and R & D Institutions spread throughout India. The society has an active chapter at Kolkata. The society was formed with the main aim to promote, encourage and develop the growth of Vacuum Science, Techniques and Applications in India. In order to achieve this aim it has conducted a number of short term courses at graduate and technician levels on vacuum science and technology on topics ranging from low vacuum to ultrahigh vacuum So far it has conducted 39 such courses at different parts of the country and imparted training to more than 1200 persons in the field. Some of these courses were in-plant training courses conducted on the premises of the establishment and designed to take care of the special needs of the establishment. IVS also regularly conducts national and international seminars and symposia on vacuum science and technology with special emphasis on some theme related to applications of vacuum. A large number of delegates from all over India take part in the deliberations of such seminars and symposia and present their work. IVS also arranges technical visits to different industries and research institutes. The society also helped in the UNESCO sponsored post-graduate level courses in vacuum science, technology and applications conducted by Mumbai University. The society has also designed a certificate and diploma course for graduate level students studying vacuum science and technology and has submitted a syllabus to the academic council of the University of Mumbai for their approval, we hope that some colleges affiliated to the university will start this course from the coming academic year. IVS extended its support in standardizing many of the vacuum instruments and played a vital role in helping to set up a Regional Testing Centre along with BARC. As part of the development of vacuum education, the society arranges the participation of

In honor of the Teratology Society's 50th anniversary: The role of Teratology Society members in the development and evolution of in vivo developmental toxicity test guidelines.

PubMed

Tyl, Rochelle W

2010-06-01

Members of the Teratology Society (established in 1960) were involved in the first governmental developmental and reproductive toxicity testing guidelines (1966) by FDA following the thalidomide epidemic, followed by other national and international governmental testing guidelines. The Segment II (developmental toxicity) study design, described in rodents and rabbits, has evolved with additional enhanced endpoints and better descriptions, mechanistic insights, range-finding studies, and toxico/pharmacokinetic ADME information (especially for pharmaceuticals). Society members were also involved in the development of the current screening assays and tests for endocrine disruptors (beginning in 1996) and are now involved with developing new testing guidelines (e.g., the extended one-generation protocol), and evaluating the current test guidelines and new initiatives under ILSI/HESI sponsorship. New initiatives include ToxCast from the U.S. EPA to screen, prioritize, and predict toxic chemicals by high throughput and high-content in vitro assays, bioinformation, and modeling to reduce (or eliminate) in vivo whole animal studies. Our Society and its journal have played vital roles in the scientific and regulatory accomplishments in birth defects research over the past 50 years and will continue to do so in the future. Happy 50th anniversary! (c) 2010 Wiley-Liss, Inc.

Targeted therapies in development for non-small cell lung cancer

PubMed Central

Reungwetwattana, Thanyanan; Dy, Grace Kho

2013-01-01

The iterative discovery in various malignancies during the past decades that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by “druggable” protein kinases has led to a revolutionary change in drug development. In non-small cell lung cancer (NSCLC), the ErbB family of receptors (e.g., EGFR [epidermal growth factor receptor], HER2 [human epidermal growth factor receptor 2]), RAS (rat sarcoma gene), BRAF (v-raf murine sarcoma viral oncogene homolog B1), MAPK (mitogen-activated protein kinase) c-MET (c-mesenchymal-epithelial transition), FGFR (fibroblast growth factor receptor), DDR2 (discoidin domain receptor 2), PIK3CA (phosphatidylinositol-4,5-bisphosphate3-kinase, catalytic subunit alpha)), PTEN (phosphatase and tensin homolog), AKT (protein kinase B), ALK (anaplastic lym phoma kinase), RET (rearranged during transfection), ROS1 (reactive oxygen species 1) and EPH (erythropoietin-producing hepatoma) are key targets of various agents currently in clinical development. These oncogenic targets exert their selective growth advantage through various intercommunicating pathways, such as through RAS/RAF/MEK, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin and SRC-signal transduction and transcription signaling. The recent clinical studies, EGFR tyrosine kinase inhibitors and crizotinib were considered as strongly effective targeted therapies in metastatic NSCLC. Currently, five molecular targeted agents were approved for treatment of advanced NSCLC: Gefitinib, erlotinib and afatinib for positive EGFR mutation, crizotinib for positive echinoderm microtubule-associated protein-like 4 (EML4)-ALK translocation and bevacizumab. Moreover, oncogenic mutant proteins are subject to regulation by protein trafficking pathways, specifically through the heat shock protein 90 system. Drug combinations affecting various nodes in these signaling and intracellular processes are predicted and demonstrated to be synergistic and

Future Targets for Female Sexual Dysfunction.

PubMed

Farmer, Melissa; Yoon, Hana; Goldstein, Irwin

2016-08-01

Female sexual function reflects a dynamic interplay of central and peripheral nervous, vascular, and endocrine systems. The primary challenge in the development of novel treatments for female sexual dysfunction is the identification and targeted modulation of excitatory sexual circuits using pharmacologic treatments that facilitate the synthesis, release, and/or receptor binding of neurochemicals, peptides, and hormones that promote female sexual function. To develop an evidence-based state-of-the-art consensus report that critically integrates current knowledge of the therapeutic potential for known molecular and cellular targets to facilitate the physiologic processes underlying female sexual function. State-of-the-art review representing the opinions of international experts developed in a consensus process during a 1-year period. Expert opinion was established by grading the evidence-based medical literature, intensive internal committee discussion, public presentation, and debate. Scientific investigation is urgently needed to expand knowledge and foster development of future treatments that maintain genital tissue integrity, enhance genital physiologic responsiveness, and optimize positive subjective appraisal of internal and external sexual cues. This article critically condenses the current knowledge of therapeutic manipulation of molecular and cellular targets within biological systems responsible for female sexual physiologic function. Future treatment targets include pharmacologic modulation of emotional learning circuits, restoration of normal tactile sensation, growth factor therapy, gene therapy, stem cell-based therapies, and regenerative medicine. Concurrent use of centrally and peripherally acting therapies could optimize treatment response. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Quality of care in breast cancer centers: results of benchmarking by the German Cancer Society and German Society for Breast Diseases.

PubMed

Kowalski, Christoph; Ferencz, Julia; Brucker, Sara Y; Kreienberg, Rolf; Wesselmann, Simone

2015-04-01

A total of 218 breast cancer centers, with 274 operating sites, have been certified since 2003 in accordance with the criteria set out by the German Cancer Society (Deutsche Krebsgesellschaft) and the German Society for Breast Diseases (Deutsche Gesellschaft für Senologie). Most of these centers are located in Germany, but centers in Austria, Switzerland, and Italy have also been certified. This paper presents the results for quality indicators (QIs) from 2009 to 2012, based on data from 195,342 primary breast cancer patients, in order to illustrate the development and progress of these centers. Descriptive results on interdisciplinary collaboration (6 QIs), guideline adherence (15 QIs), and specialist expertise (7 QIs) are reported over time. Fulfillment of the certification requirements was high and remained relatively stable over time, with the extent of variation between sites declining. Sites that do not reach the target values are asked to comment on the discrepancies, and their comments, as well as the QI results, are used by centers and auditors during an on-site auditing process and to constantly revise the QIs set out by the guideline and the certification commission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Beyond strong and weak: rethinking postdictatorship civil societies.

PubMed

Riley, Dylan; Fernández, Juan J

2014-09-01

What is the impact of dictatorships on postdictatorial civil societies? Bottom-up theories suggest that totalitarian dictatorships destroy civil society while authoritarian ones allow for its development. Top-down theories of civil society suggest that totalitarianism can create civil societies while authoritarianism is unlikely to. This article argues that both these perspectives suffer from a one-dimensional understanding of civil society that conflates strength and autonomy. Accordingly we distinguish these two dimensions and argue that totalitarian dictatorships tend to create organizationally strong but heteronomous civil societies, while authoritarian ones tend to create relatively autonomous but organizationally weak civil societies. We then test this conceptualization by closely examining the historical connection between dictatorship and civil society development in Italy (a posttotalitarian case) and Spain (a postauthoritarian one). Our article concludes by reflecting on the implications of our argument for democratic theory, civil society theory, and theories of regime variation.

Exploratory of society

NASA Astrophysics Data System (ADS)

Cederman, L.-E.; Conte, R.; Helbing, D.; Nowak, A.; Schweitzer, F.; Vespignani, A.

2012-11-01

A huge flow of quantitative social, demographic and behavioral data is becoming available that traces the activities and interactions of individuals, social patterns, transportation infrastructures and travel fluxes. This has caused, together with innovative computational techniques and methods for modeling social actions in hybrid (natural and artificial) societies, a qualitative change in the ways we model socio-technical systems. For the first time, society can be studied in a comprehensive fashion that addresses social and behavioral complexity. In other words we are in the position to envision the development of large data and computational cyber infrastructure defining an exploratory of society that provides quantitative anticipatory, explanatory and scenario analysis capabilities ranging from emerging infectious disease to conflict and crime surges. The goal of the exploratory of society is to provide the basic infrastructure embedding the framework of tools and knowledge needed for the design of forecast/anticipatory/crisis management approaches to socio technical systems, supporting future decision making procedures by accelerating the scientific cycle that goes from data generation to predictions.

Targeted gene flow for conservation.

PubMed

Kelly, Ella; Phillips, Ben L

2016-04-01

Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

[History in the public communication of specialist scientific societies: history marketing].

PubMed

Moll, F H; Halling, T; Rathert, P; Fangerau, H

2014-10-01

History is nowadays used as an economic factor. The past is therefore specifically targeted and cultivated, which for specialist scientific associations and societies often fullfils totally different functions in comparison to the open market, although the techniques and requirements are similar. Within medical specialties these facts are often still unknown. Museums and archives as well as the historians and curators working in them are very familiar with the special cultures of communication within these scientific communities and they play a major role in the establishment and development of history as a modern part of public relations and public identity.

Testing the Teacher's Report Form Syndromes in 20 Societies

ERIC Educational Resources Information Center

Ivanova, Masha Y.; Achenbach, Thomas M.; Rescorla, Leslie A.; Dumenci, Levent; Almqvist, Fredrik; Bathiche, Marie; Bilenberg, Niels; Bird, Hector; Domuta, Anca; Erol, Nese; Fombonne, Eric; Fonseca, Antonio; Frigerio, Alessandra; Kanbayashi, Yasuko; Lambert, Michael C.; Leung, Patrick; Liu, Xianchen; Minaei, Asghar; Roussos, Alexandra; Simsek, Zeynep; Weintraub, Sheila; Wolanczyk, Tomasz; Zubrick, Stephen; Zukauskiene, Rita; Verhulst, Frank C.

2007-01-01

Standardized assessment instruments developed in one society are often used in other societies. However, it is important to determine empirically how assessment instruments developed in one society function in others. The present study tested the fit of the Teacher's Report Form syndrome structures in 20 diverse societies using data for 30,030 6-…

The contribution of the Estonian Soil Sciences Society to the science, society and education

NASA Astrophysics Data System (ADS)

Rossner, Helis; Reintam, Endla; Astover, Alar; Shanskiy, Merrit

2015-04-01

Predecessor of todays Estonian Soil Science Society was Estonian Branch of All-Union Soil Society of Soil Scientist which acted from 1957 to 1991. In 1957-1964 Estonian Branch was leaded by prof. Osvald Hallik and in 1964-1991 by prof. Loit Reintam. After re-independence of Estonia in 1991 the society acted in informal way and was leaded by prof. L. Reintam. Non-profit organization "Estonian Soil Science Society" was officially (re)established in 10.23.2009. Estonian Soil Science Society (ESSS) is aimed to: • coordinate collaboration between institutions and individuals intrested of soil science, conservation and sustainable use of soils; • promoting soil science education and research, raising awareness of publicity on topics relating to soils in Estonia; • cooperation between local and foreign unions and associations. In recent years the ESSS had managed to reunite the number of soil scientist from different research institutions of Estonia and of related institutions. Also, the ESSS had provided numerous of materials based on later scientific findings. One of most important activity leaded by ESSS is the organizing Soil Day in Estonia with relevant seminar, where the speakers are sharing latest information with target group (researchers, teachers, policy makers, farmers, students etc.). In a frames of Soil Day the Soil of the Year is selected for Estonia. In 2015, the soil of the year is Leptosol. For current, International Year of the Soil ESSS had planned numerous activities to introduce the importance of soils to wider audience. In current presentation we would like to share the soil science researchers experience through- out the decades of soil science research in Estonia, show our latest findings and designed activities for the International Year of SOIL.

Building the Capability of Non-Formal Education Teachers to Develop a Learning Society for Promoting Lifelong Education in Thailand

ERIC Educational Resources Information Center

Sungsri, Sumalee

2018-01-01

This study aims to study Thai non-formal education teachers' perceptions of their opportunities to obtain knowledge about the learning society; identify the knowledge of non-formal education teachers need about the learning society which could be obtained through a distance learning package; and to develop and evaluate distance learning package on…

Novel and Viable Acetylcholinesterase Target Site for Developing Effective and Environmentally Safe Insecticides

PubMed Central

Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-01-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market. PMID:22280344

Monitoring Water Targets in the Post-2015 Development Goals

NASA Astrophysics Data System (ADS)

Lawford, R. G.

2015-12-01

The Water Sustainable Development Goal (SDG) provides a comprehensive approach to developing water services in a way that ensures social equity, health, well-being and sustainability for all. In particular, the water goal includes targets related to sanitation, wastewater, water quality, water efficiency, integrated water management and ecosystems (details to be finalized in September 2015). As part of its implementation, methods to monitor target indicators must be developed. National governments will be responsible for reporting on progress toward these targets using national data sets and possibly information from global data sets that applies to their countries. Oversight of this process through the use of global data sets is desirable for encouraging the use of standardized information for comparison purposes. Disparities in monitoring due to very sparse data networks in some countries can be addressed by using geospatially consistent data products from space-based remote sensing. However, to fully exploit these data, capabilities will be needed to downscale information, to interpolate and assimilate data both in time and space, and to integrate these data with socio-economic data sets, model outputs and survey data in a geographical information system framework. Citizen data and other non-standard data types may also supplement national data systems. A comprehensive and integrated analysis and dissemination system is needed to enable the important contributions that satellites could make to achieving Water SDG targets. This presentation will outline the progress made in assessing the needs for information to track progress on the Water SDG, options for meeting these needs using existing data infrastructure, and pathways for expanding the role of Earth observations in SDG monitoring. It will also discuss the potential roles of Future Earth's Sustainable Water Futures Programme (SWFP) and the Group on Earth Observations (GEO) in coordinating these efforts.

Does the world need a scientific society for research on how to improve healthcare?

PubMed Central

2012-01-01

In this editorial, we reflect on the arguments for starting a scientific society focused on research on how to improve healthcare. This society would take an inclusive approach to what constitutes healthcare. For instance, it should include mental health healthcare, treatment for substance abuse, the work of allied health professions, and preventive healthcare. The society would be open to researchers from all traditions. Thus, we take an inclusive approach to what constitutes scientific research, as long as it uses rigorous methods, is focused on improving healthcare, and aims at knowledge that can be transferred across settings. The society would primarily target scientific researchers but would invite others with an interest in this area of research, regardless of their discipline, position, field of application, or group affiliation (e.g., improvement science, behavioral medicine, knowledge translation). A society would need fruitful collaboration with related societies and organizations, which may include having combined meetings. Special links may be developed with one or more journals. A website to provide information on relevant resources, events, and training opportunities is another key activity. It would also provide a voice for the field at funding agencies, political arenas, and similar institutions. An organizational structure and financial resources are required to develop and run these activities. Our aim is to start an international debate, to discover if we can establish a shared vision across academics and stakeholders engaged with creating scientific knowledge on how to improve healthcare. We invite readers to express their views in the online questionnaire accessed by following the URL link provided at the end of the editorial. PMID:22376988

Development of ion beam sputtering techniques for actinide target preparation

NASA Astrophysics Data System (ADS)

Aaron, W. S.; Zevenbergen, L. A.; Adair, H. L.

1985-06-01

Ion beam sputtering is a routine method for the preparation of thin films used as targets because it allows the use of a minimum quantity of starting material, and losses are much lower than most other vacuum deposition techniques. Work is underway in the Isotope Research Materials Laboratory (IRML) at ORNL to develop the techniques that will make the preparation of actinide targets up to 100 μg/cm 2 by ion beam sputtering a routinely available service from IRML. The preparation of the actinide material in a form suitable for sputtering is a key to this technique, as is designing a sputtering system that allows the flexibility required for custom-ordered target production. At present, development work is being conducted on low-activity actinides in a bench-top system. The system will then be installed in a hood or glove box approved for radioactive materials handling where processing of radium, actinium, and plutonium isotopes among others will be performed.

Development of position measurement unit for flying inertial fusion energy target

NASA Astrophysics Data System (ADS)

Tsuji, R.; Endo, T.; Yoshida, H.; Norimatsu, T.

2016-03-01

We have reported the present status in the development of a position measurement unit (PMU) for a flying inertial fusion energy (IFE) target. The PMU, which uses Arago spot phenomena, is designed to have a measurement accuracy smaller than 1 μm. By employing divergent, pulsed orthogonal laser beam illumination, we can measure the time and the target position at the pulsed illumination. The two-dimensional Arago spot image is compressed into one-dimensional image by a cylindrical lens for real-time processing. The PMU are set along the injection path of the flying target. The local positions of the target in each PMU are transferred to the controller and analysed to calculate the target trajectory. Two methods are presented to calculate the arrival time and the arrival position of the target at the reactor centre.

ALCOHOLIC HEPATITIS: TRANSLATIONAL APPROACHES TO DEVELOP TARGETED THERAPIES

PubMed Central

Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu; Gao, Bin

2016-01-01

Alcoholic liver disease (ALD) is a leading cause of liver related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with ALD. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20–50% at 3 months). Available therapies are not effective in many patients and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. This review article summarizes the unmet needs for translational studies on the pathogenesis of AH, pre-clinical translational tools, and emerging drug targets to benefit the AH patient. PMID:26940353

The development of a multi-target compiler-writing system for flight software development

NASA Technical Reports Server (NTRS)

Feyock, S.; Donegan, M. K.

1977-01-01

A wide variety of systems designed to assist the user in the task of writing compilers has been developed. A survey of these systems reveals that none is entirely appropriate to the purposes of the MUST project, which involves the compilation of one or at most a small set of higher-order languages to a wide variety of target machines offering little or no software support. This requirement dictates that any compiler writing system employed must provide maximal support in the areas of semantics specification and code generation, the areas in which existing compiler writing systems as well as theoretical underpinnings are weakest. This paper describes an ongoing research and development effort to create a compiler writing system which will overcome these difficulties, thus providing a software system which makes possible the fast, trouble-free creation of reliable compilers for a wide variety of target computers.

Education for a Learning Society.

ERIC Educational Resources Information Center

Tempero, Howard E., Ed.

The essays contained in this booklet are 1) "Education for a 'Learning Society': The Challenge" by Ernest Bayles in which he calls for focus on learning to live, developing skills of reflection and judgment applicable to vital issues, and reflective teaching; 2) "Teacher Education in a Learning Society" in which David Turney demands teacher…

School-Based Extracurricular Activities, Personality, Self-Concept, and College Career Development Skills in Chinese Society

ERIC Educational Resources Information Center

Shiah, Yung-Jong; Huang, Ying; Chang, Frances; Chang, Chuan-Feng; Yeh, Lun-Chang

2013-01-01

In the present study, we examined in Chinese society the association of school-based extracurricular activities (SBEAs) in both high school and college with students' career development skills in college, as well as with various personality characteristics and self-concept. Each of 281 college students administered the Lai Personality Inventory,…

Critical questions in development of targeted nanoparticle therapeutics.

PubMed

Korsmeyer, Richard

2016-06-01

One of the fourteen Grand Challenges for Engineering articulated by the US National Academy of Engineering is 'Engineer Better Medicines'. Although there are many ways that better medicines could be engineered, one of the most promising ideas is to improve our ability to deliver the therapeutic molecule more precisely to the desired target. Most conventional drug delivery methods (oral absorption, intravenous infusion etc.) result in systemic exposure to the therapeutic molecule, which places severe constraints on the types of molecules that can be used. A molecule administered by systemic delivery must be effective at low concentrations in the target tissue, yet safe everywhere else in the body. If drug carriers could be developed to deliver therapeutic molecules selectively to the desired target, it should be possible to greatly improve safety and efficacy of therapy. Nanoparticles (and related nanostructures, such as liposomes, nanoemulsions, micelles and dendrimers) are an attractive drug carrier concept because they can be made from a variety of materials engineered to have properties that allow loading and precise delivery of bound therapeutic molecules. The field of targeted nanoparticles has been extraordinarily active in the academic realm, with thousands of articles published over the last few years. Many of these publications seem to demonstrate very promising results in in vitro studies and even in animal models. In addition, a handful of human clinical trials are in progress. Yet, the biopharmaceutical industry has been relatively slow to make major investments in targeted nanoparticle development programs, despite a clear desire to introduce innovative new therapies to the market. What is the reason for such caution? Some degree of caution is no doubt due to the use of novel materials and the unproven nature of targeted nanoparticle technology, but many other unproven technologies have generated intense interest at various times. We believe that the

Emerging molecular therapies targeting myocardial infarction-related arrhythmias.

PubMed

Driessen, Helen E; van Veen, Toon A B; Boink, Gerard J J

2017-04-01

Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate. Devices can terminate rapid rhythms but at best indirectly affect the underlying disease, while ablation, even when appropriately targeted, induces additional tissue damage. In contrast, exploration of gene and cell therapies are expected to provide a targeted, non-destructive, and potentially regenerative approach to ischaemia- and infarction-related arrhythmias. Although these approaches are in the early stages of development, they carry substantial potential to advance arrhythmia prevention and treatment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Molecular targets of alcohol action: translational research for pharmacotherapy development and screening

PubMed Central

Gorini, Giorgio; Bell, Richard L.; Mayfield, R. Dayne

2016-01-01

Summary Alcohol abuse and dependence are multifaceted disorders with neurobiological, psychological, and environmental components. Research on other complex neuropsychiatric diseases suggests that genetically influenced intermediate characteristics affect the risk for heavy alcohol consumption and its consequences. Diverse therapeutic interventions can be developed through identification of reliable biomarkers for this disorder and new pharmacological targets for its treatment. Advances in the fields of genomics and proteomics offer a number of possible targets for the development of new therapeutic approaches. This brain-focused review highlights studies identifying neurobiological systems associated with these targets and possible pharmacotherapies, summarizing evidence from clinically relevant animal and human studies, as well as sketching improvements and challenges facing the fields of proteomics and genomics. Concluding thoughts on using results from these profiling technologies for medication development are also presented. PMID:21199775

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms

PubMed Central

Burd, Christin E.; Gill, Matthew S.; Niedernhofer, Laura J.; Robbins, Paul D.; Austad, Steven N.; Barzilai, Nir

2016-01-01

Through the progress of basic science research, fundamental mechanisms that contribute to age-related decline are being described with increasing depth and detail. Although these efforts have identified new drug targets and compounds that extend life span in model organisms, clinical trials of therapeutics that target aging processes remain scarce. Progress in aging research is hindered by barriers associated with the translation of basic science discoveries into the clinic. This report summarizes discussions held at a 2014 Geroscience Network retreat focused on identifying hurdles that currently impede the preclinical development of drugs targeting fundamental aging processes. From these discussions, it was evident that aging researchers have varied perceptions of the ideal preclinical pipeline. To forge a clear and cohesive path forward, several areas of controversy must first be resolved and new tools developed. Here, we focus on five key issues in preclinical drug development (drug discovery, lead compound development, translational preclinical biomarkers, funding, and integration between researchers and clinicians), expanding upon discussions held at the Geroscience Retreat and suggesting areas for further research. By bringing these findings to the attention of the aging research community, we hope to lay the foundation for a concerted preclinical drug development pipeline. PMID:27535964

Molecular Targets for Antiepileptic Drug Development

PubMed Central

Meldrum, Brian S.; Rogawski, Michael A.

2007-01-01

Summary This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the α subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, α2–δ voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABAA receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABAB and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABAA receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the

HIV-1 Proteins, Tat and gp120, Target the Developing Dopamine System

PubMed Central

Fitting, Sylvia; Booze, Rosemarie M.; Mactutus, Charles F.

2015-01-01

In 2014, 3.2 million children (< 15 years of age) were estimated to be living with HIV and AIDS worldwide, with the 240,000 newly infected children in the past year, i.e., another child infected approximately every two minutes [1]. The primary mode of HIV infection is through mother-to-child transmission (MTCT), occurring either in utero, intrapartum, or during breastfeeding. The effects of HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated, in part, via viral proteins, such as Tat and gp120. The current review focuses on the targets of HIV-1 proteins during the development of the dopamine (DA) system, which appears to be specifically susceptible in HIV-1-infected children. Collectively, the data suggest that the DA system is a clinically relevant target in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS infection, and may be specifically susceptible during development. The present review discusses the development of the DA system, follows the possible targets of the HIV-1 proteins during the development of the DA system, and suggests potential therapeutic approaches. By coupling our growing understanding of the development of the CNS with the pronounced age-related differences in disease progression, new light may be shed on the neurological and neurocognitive deficits that follow HIV-1 infection. PMID:25613135

Beyond cysteine: recent developments in the area of targeted covalent inhibition.

PubMed

Mukherjee, Herschel; Grimster, Neil P

2018-05-29

Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement of a cysteine residue proximal to the small molecule binding site; while this strategy has afforded numerous successes, it necessarily limits the number of proteins that can be targeted by this approach. This drawback has led several research groups to develop novel methodologies that target non-cysteine residues for covalent modification. Herein, we survey the current literature of warheads that covalently modify non-cysteine amino acids in proteins. Copyright © 2018 Elsevier Ltd. All rights reserved.

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation†

PubMed Central

Kamaly, Nazila; Xiao, Zeyu; Valencia, Pedro M.; Radovic-Moreno, Aleksandar F.; Farokhzad, Omid C.

2013-01-01

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development

The role of targeted therapy in the management of patients with AML.

PubMed

Perl, Alexander E

2017-12-08

Drug therapy for acute myeloid leukemia (AML) is finally undergoing major changes in 2017. This is due to the US Food and Drug Administration's approval of several new, targeted agents (midostaurin, enasidenib, and gemtuzumab ozogamicin). Paired with the recent approval of a novel liposomal formulation of daunorubicin/cytarabine (CPX-351/Vyxeos), the standard of care is changing rapidly in AML for subgroups. This review will focus on currently approved agents and promising novel agents in development and will highlight controversial areas in targeted treatment. © 2016 by The American Society of Hematology. All rights reserved.

Advanced information society(2)

NASA Astrophysics Data System (ADS)

Masuyama, Keiichi

Our modern life is full of information and information infiltrates into our daily life. Networking of the telecommunication is extended to society, company, and individual level. Although we have just entered the advanced information society, business world and our daily life have been steadily transformed by the advancement of information network. This advancement of information brings a big influence on economy, and will play they the main role in the expansion of domestic demands. This paper tries to view the image of coming advanced information society, focusing on the transforming businessman's life and the situation of our daily life, which became wealthy by the spread of daily life information and the visual information by satellite system, in the development of the intelligent city.

Higher Education and Civil Society: Compatibility Re-Examined

ERIC Educational Resources Information Center

Khatun, Mahmuda

2012-01-01

Last couple of decades, some developed countries emphasized to develop civil society in developing countries. The main goals were to promote democratic norms and values among citizens who will not be thinking about democratic society otherwise. To establish democratic norms and values, many view that higher education is necessary. The relationship…

Alcoholic hepatitis: Translational approaches to develop targeted therapies.

PubMed

Mandrekar, Pranoti; Bataller, Ramon; Tsukamoto, Hidekazu; Gao, Bin

2016-10-01

Alcoholic liver disease is a leading cause of liver-related mortality worldwide. In contrast to recent advances in therapeutic strategies for patients with viral hepatitis, there is a significant lack of novel therapeutic options for patients with alcoholic liver disease. In particular, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of alcoholic liver disease. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with AH is very high (20%-50% at 3 months). Available therapies are not effective in many patients, and targeted approaches are imminently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce the clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. This review summarizes the unmet needs for translational studies on the pathogenesis of AH, preclinical translational tools, and emerging drug targets to benefit the AH patient. (Hepatology 2016;64:1343-1355). © 2016 by the American Association for the Study of Liver Diseases.

Strategies that target leukocyte traffic in inflammatory bowel diseases: recent developments.

PubMed

Rivera-Nieves, Jesús

2015-11-01

We review the most recent developments regarding the targeting of molecules involved in the traffic of leukocytes for the treatment of inflammatory bowel diseases (IBD). We discuss the most important findings of one published phase II trial that targeted the β7 integrin (etrolizumab), two phase II trials that targeted the α4β7 integrin ligand: mucosal addressin cell adhesion molecule 1 (MAdCAM-1, PF-00547659), a phase II trial targeting the chemokine IP-10 (CXCL10) in Crohn's, and a phase II trial that targeted the sphingosine-1-phosphate receptor-1: ozanimod in patients with ulcerative colitis. Targeting molecules involved in leukocyte traffic has recently become an effective and well tolerated strategy for the treatment of IBD. Novel approaches now not only target the integrins on the lymphocyte surface, but also its endothelial ligand: MAdCAM-1. As with vedolizumab, antibodies against MAdCAM-1 appear most effective in ulcerative colitis rather than in Crohn's. Targeting chemokines or their receptors does not appear to have the same efficacy as those that target the most stable integrin: immunoglobulin superfamily interactions between the lymphocyte and endothelium. Preliminary results also suggest that the sphingosine-1-phosphate pathway might also be targeted therapeutically in IBD, no longer with parenterally administered antibodies but with orally administered small molecules.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

PubMed

Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

2017-03-01

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

PubMed

Fischbach, W; Malfertheiner, P; Hoffmann, J C; Bolten, W; Bornschein, J; Götze, O; Höhne, W; Kist, M; Koletzko, S; Labenz, J; Layer, P; Miehlke, St; Morgner, A; Peitz, U; Preiss, J; Prinz, C; Rosien, U; Schmidt, W; Schwarzer, A; Suerbaum, St; Timmer, A; Treiber, G; Vieth, M

2009-12-01

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

Coevolution of nutrigenomics and society: ethical considerations.

PubMed

Korthals, Michiel

2011-12-01

To optimize the coevolution of nutrigenomics and society (ie, the reciprocal stimulation of both developments), I analyzed chances for a fruitful match between normative concepts and strategies of both developments. Nutrigenomics embodies ≥ 3 normative concepts. First, food is exclusively interpreted in terms of disease prevention. Second, striving for health is interpreted as the quantification of risks and prevention of diseases through positive food-gene interactions. The third normative idea is that disease prevention by the minimization of risks is an individual's task. My thesis was that these concepts of nutrigenomics would not easily match with concepts of food and health of various food styles in Western societies, which, for instance, parents in the case of metabolic programming endorse and with a philosophical view of the relation between food, health, and the meaning of life. Next, I reflected on the nonsynchronized coevolution of nutrigenomics and society because of this mismatch and introduced the concept of the fair representation of food styles in nutrigenomic developments. To synchronize and optimize the coevolution of nutrigenomics and society, I propose that the research policy of nutrigenomics should change to a research partnership with society on the basis of fair representation.

Risk society and the distribution of bads: theorizing class in the risk society.

PubMed

Curran, Dean

2013-03-01

Ulrich Beck states in the Risk Society (1992) that the rise of the social production of risks in the risk society signals that class ceases to be of relevance; instead the hierarchical logic of class will be supplanted by the egalitarian logic of the distribution of risks. Several trenchant critiques of Beck's claim have justified the continued relevance of class to contemporary society. While these accounts have emphasized continuity, they have not attempted to chart, as this paper will, how the growing social production of risk increases the importance of class. This paper argues that it is Beck's undifferentiated, catastrophic account of risk that undergirds his rejection of class, and that by inserting an account of risk involving gradations in both damages and calculability into Beck's framework, his theory of risk society may be used to develop a critical theory of class. Such a theory can be used to reveal how wealth differentials associated with class relations actually increase in importance to individuals' life-chances in the risk society. With the growing production and distribution of bads, class inequalities gain added significance, since it will be relative wealth differentials that both enables the advantaged to minimize their risk exposure and imposes on others the necessity of facing the intensified risks of the risk society. © London School of Economics and Political Science 2013.

Involvement of the European Confederation of the Soil Science Societies in soil protection policy development

NASA Astrophysics Data System (ADS)

Boivin, Pascal

2017-04-01

The European Confederation of the Soil Science Societies (ECSSS) was founded not only to organize the Eurosoil congress, but also to continuously support and promote the soil causes in the European area. A work is in progress to define the best way to achieve this goal, with integrating voices of the European structures and networks, and the national societies. One of the major objectives is to develop a modern approach of soil protection, including leading experimentations shared with all the members, and active lobbying. Such an approach requires the buildup of an efficient interface with policy makers, stake holders, engineering and science, which should be concretized in a new the dimension of the Eurosoil congress. This communication will sketch the on-going work, with reviewing the perspectives, conditions, strengths, questions and difficulties identified.

2015 guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the management of hypertension.

PubMed

Chiang, Chern-En; Wang, Tzung-Dau; Ueng, Kwo-Chang; Lin, Tsung-Hsien; Yeh, Hung-I; Chen, Chung-Yin; Wu, Yih-Jer; Tsai, Wei-Chuan; Chao, Ting-Hsing; Chen, Chen-Huan; Chu, Pao-Hsien; Chao, Chia-Lun; Liu, Ping-Yen; Sung, Shih-Hsien; Cheng, Hao-Min; Wang, Kang-Ling; Li, Yi-Heng; Chiang, Fu-Tien; Chen, Jyh-Hong; Chen, Wen-Jone; Yeh, San-Jou; Lin, Shing-Jong

2015-01-01

It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan. We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to <140/90 mmHg for all patients. We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to <150/90 mmHg for patients between 60-80 years of age. For patients with diabetes, CHD, chronic kidney disease who have proteinuria, and those who are receiving antithrombotic therapy for stroke prevention, we propose BP targets of <130/80 mmHg in our guidelines. BP

[Cerebrospinal fluid diagnostics in Germany since 1950 : Developments in the GDR and FRG in the context of society and science].

PubMed

Reiber, H

2016-12-01

The 40 years of separated development in two countries with extremely different political and social utopias allow consideration of the connection between science and society. The society-dependent development of cerebrospinal fluid (CSF) diagnostics in the German Democratic Republic (GDR) and the Federal Republic of Germany (FRG) is shown in the context of the international scientific development of the post-war era with new paradigms in physics, biology and genetics. As part of this contribution to the philosophy of science the consequences of the complex life science for a new view of disease research are discussed in contrast to the currently dominating, reductionistic medical industrial complex.

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Highly Developed Information-oriented Society and Humanity ; Medical Information Services and Library

NASA Astrophysics Data System (ADS)

Wakimoto, Atsuko

Change in social circumstances caused by arrival of highly developed information-oriented society has altered what information services in medical libraries should be dramatically. Keeping with complication and diversification of needs by users such as medical doctors, researchers, medical technicians and so on medical librarians have been playing important role in the information activities, and are required to master more specialized knowledge. This paper outlines changes in circumstances surrounding medical libraries, discusses role of medical librarians in online information retrieval services, and introduces various curriculum for library education. The author proposes that humanity of librarian him or herself is still a key factor for library services regardless of advancement of computerization.

[Targeted therapies in hepatocellular carcinomas: recent results and future development].

PubMed

Marijon, H; Faivre, S; Raymond, E

2009-05-01

Hepatocellular carcinoma (HCC) is one of the 5th most common cancers around the world with a limited number of systemic therapeutic options. Cytotoxic agents, hormonotherapy and immunotherapy have failed to demonstrate benefit compared to best supportive care in patients with advanced HCC. The recent development of targeted therapies provided hope for the treatment of advanced HCC. We reviewed phases II-III trials presented in 2007 and 2008. Results are promising with a clinical benefit reported with molecular therapies targeting EGF/EGFR and VEGF/VEGFR pathways.

Development of a Plutonium Ceramic Target for the MASHA Separator

NASA Astrophysics Data System (ADS)

Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Lougheed, R. W.; Yeremin, A. V.; Oganessian, Yu. Ts.

2004-04-01

We are participating in the development of the target for the MASHA (Mass Analyzer of Super Heavy Atoms) on-line mass separator in Dubna. Along with recent upgrades of the U400 cyclotron, MASHA will provide for at least a ten-fold increase in the production- and-detection rate for element 114 atoms, and will allow us to measure their atomic masses precisely. The MASHA separator will employ a thick Pu ceramic target capa- ble of tolerating temperatures in the vicinity of 2000 C without vaporizing the actinide compound. Reaction products will diffuse out of the target and will drift to an ECR ion source after which they will be transported through the separator and will impinge on a position-sensitive focal-plane detector array. Furthermore, operation of the MASHA hot target/ion source combination will provide chemical volatility information that will support our assignment of an atomic number of 114 to these nuclei. Taken together, these experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments in which the chemical properties of the heaviest elements are studied.

The Economic and Social Impacts of the Transition from the Industrial Society to a Computer Literate, High Technology, Information Society.

ERIC Educational Resources Information Center

Groff, Warren H.

As our society evolves from an industrial society to a computer literate, high technology, information society, educational planners must reexamine the role of postsecondary education in economic development and in intellectual capital formation. In response to this need, a task force on high technology was established to examine the following…

Development of Targeted, Enzyme-Activated Nano-Conjugates for Hepatic Cancer Therapy

NASA Astrophysics Data System (ADS)

Kuruvilla, Sibu Philip

Hepatocellular carcinoma (HCC) is the 5th most commonly-occurring cancer worldwide and the 2nd highest cause for cancer-related deaths globally. The current treatment strategy is the direct injection of a chemotherapeutic agent (e.g. doxorubicin; DOX) into the hepatic artery, through a process called hepatic arterial infusion (HAI). Unfortunately, HAI is severely hindered by limited therapeutic efficacy against the tumor and high systemic toxicity to surrounding organs (e.g. cardiotoxicity). This thesis focuses on the development of a targeted, nanoparticle-based drug delivery system aimed to improve the clinical treatment of HCC. In particular, we employ generation 5 (G5) poly(amido amine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands attached to the surface through a poly(ethylene glycol) (PEG) brush. DOX is attached to the G5 surface through two different enzyme-sensitive linkages, L3 or L4, to achieve controllable release of the drug inside hepatic cancer cells. The combination of NAcGal-PEG targeting branches with either L3- or L4-DOX linkages led to the development of P1 and P2 particles, respectively. In Part 1, we discuss the development of these particles and measure their ability to target and kill hepatic cancer cells in vitro. In Part 2, we investigate the antitumor activity of P1 and P2 particles in tumor-bearing mice in comparison to the free drug, and we measure the cardiac function of mice undergoing treatment to assess differences in DOX-induced cardiotoxicity. Finally, in Part 3, we explore multi-valent targeting of G5 dendrimers in pursuit of further improving their specificity to hepatic cancer cells. Ultimately, this thesis provides insight into the utility of nanoparticle-based drug delivery systems that can potentially be translated to the clinic to improve cancer therapy.

Therapeutic targets and new directions for antibodies developed for ovarian cancer

PubMed Central

Bax, Heather J.; Josephs, Debra H.; Pellizzari, Giulia; Spicer, James F.; Montes, Ana; Karagiannis, Sophia N.

2016-01-01

ABSTRACT Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets. In turn, potential antibody treatments with various mechanisms of action, including immune activation or toxin-delivery, that are directed at these targets have been developed. Here, we identify established as well as novel targets for antibodies in ovarian cancer, and discuss how they may provide fresh opportunities to identify interventions with enhanced therapeutic potential. PMID:27494775

Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

PubMed

Wilkinson, Trevor C I

2016-06-15

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Accelerating vaccine development and deployment: report of a Royal Society satellite meeting

PubMed Central

Bregu, Migena; Draper, Simon J.; Hill, Adrian V. S.; Greenwood, Brian M.

2011-01-01

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it. PMID:21893549

Mobilising Data in a Knowledge Society

NASA Astrophysics Data System (ADS)

Wessels, Bridgette; Finn, Rachel; Wadhwa, Kush; Bigagli, Lorenzo; Nativi, Stefano; Noorman, Merel

2016-04-01

We address how the open data movement is fostering change in institutions, in data, and in social participation in the mobilisation of knowledge society. The idea of a knowledge society has been raised over the last two decades but the transition to such as society has not been realised. Up to the present time, discussion about a knowledge society have largely focused on a knowledge economy and information society rather than a mobilisation to a knowledge society. These debates have, however, taken place before the rise of open data and big data and the development of an open data movement. We consider the role of the open data movement in fostering transformation to a knowledge society. The characteristics of the open data movement that include the strong conviction of the value of open data for society, the attention to the institutional aspects of making data open in an inclusive way, the practical focus on the technological infrastructure are key in mobilising a knowledge society. At the heart of any mobilisation is an emerging open data ecosystem and new ways of producing and using data - whether 'born digital' data, digitised data or big data - and how that data, when made openly available, can be used in a knowledgeable way by societal actors.

Development and In Vitro Characterization of a Gemcitabine-loaded MUC4-targeted Immunoliposome Against Pancreatic Ductal Adenocarcinoma.

PubMed

Urey, Carlos; Hilmersson, Katarzyma Said; Andersson, Bodil; Ansari, Daniel; Andersson, Roland

2017-11-01

Pancreatic Ductal adeno-carcinoma (PDAC) is a devastating disease. Gemcitabine is the standard chemotherapeutic agent against PDAC but has only limited effectiveness. The aim of the study was to develop and study the targeting affinity and in vitro antiproliferative effect of a MUC4-targeted gemcitabine-loaded immuno-liposome for treatment of PDAC. Gemcitabine-loaded immunoliposomes were developed by grafting anti-MUC4 antibodies to the liposomal surface. Targeting affinity was compared in vitro between immunoliposomes and non-targeted liposomes and anti-proliferative effect was compared in vitro between free drug, non-targeted liposomal gemcitabine and MUC4-targeted immunoliposomal gemcitabine on a MUC4-positive pancreatic cancer cell line, Capan-1. Development of a MUC4-targeted immunoliposome was confirmed and characterized by immunoblots and size characterization. The MUC4-targeted immunoliposome showed a significantly higher targeting affinity compared to the non-targeted liposomes and also showed an improved antiproliferative effect compared to free and non-targeted liposomal drug. Successful development and characterization of a MUC4-targeted immunoliposome shows promising results for a targeted treatment and improved retention of gemcitabine for treatment of PDAC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

The Changing Role of a Professional Society Library.

ERIC Educational Resources Information Center

Lees, Nigel

1997-01-01

Describes developments in the United Kingdom's Royal Society of Chemistry's Library and Information Centre that has changed from a professional and learned society library into a business center. Development of a priced information service, electronic sources of information including online databases and the Internet, and marketing and promotion…

10 × '20 Progress—Development of New Drugs Active Against Gram-Negative Bacilli: An Update From the Infectious Diseases Society of America

PubMed Central

Boucher, Helen W.; Talbot, George H.; Benjamin, Daniel K.; Bradley, John; Guidos, Robert J.; Jones, Ronald N.; Murray, Barbara E.; Bonomo, Robert A.; Gilbert, David

2013-01-01

Infections caused by antibiotic-resistant bacteria, especially the “ESKAPE” pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's “10 × '20 Initiative.” PMID:23599308

10 x '20 Progress--development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America.

PubMed

Boucher, Helen W; Talbot, George H; Benjamin, Daniel K; Bradley, John; Guidos, Robert J; Jones, Ronald N; Murray, Barbara E; Bonomo, Robert A; Gilbert, David

2013-06-01

Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 × '20 Initiative."

The Socio-Politico Development of the Chicano and His Role within Latin American Society. Project Mexico.

ERIC Educational Resources Information Center

Estrada, Lawrence J.

This document is a course outline for a community college Chicano Studies course focusing on the development of the Chicano and his role within Latin American society. The course seeks to examine broad concepts such as colonialism, discrimination, racism, and conflict and cultural pluralism within the Chicano context in the American Southwest and…

Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

PubMed

Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

2017-12-11

Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

Recent advances in developing small molecules targeting RNA.

PubMed

Guan, Lirui; Disney, Matthew D

2012-01-20

RNAs are underexploited targets for small molecule drugs or chemical probes of function. This may be due, in part, to a fundamental lack of understanding of the types of small molecules that bind RNA specifically and the types of RNA motifs that specifically bind small molecules. In this review, we describe recent advances in the development and design of small molecules that bind to RNA and modulate function that aim to fill this void.

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

PubMed Central

Parkkila, Seppo

2017-01-01

The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors. PMID:29181278

Towards a Drug Development Path that Targets Metastatic Progression in Osteosarcoma

PubMed Central

Khanna, Chand; Fan, Timothy M.; Gorlick, Richard; Helman, Lee J; Kleinerman, Eugenie S.; Adamson, Peter C.; Houghton, Peter J.; Tap, William D.; Welch, Danny R.; Steeg, Patricia S.; Merlino, Glenn; Sorensen, Poul HB; Kirsch, David G.; Janeway, Katherine A.; Weigel, Brenda; Randall, R. Lor; Meltzer, Paul; Withrow, Stephen J; Paoloni, Melissa; Kaplan, Rosandra N.; Teicher, Beverly A.; Seibel, Nita L.; Üren, Aykut; Patel, Shreyaskumar R.; Trent, Jeffrey; Savage, Sharon A.; Mirabello, Lisa; Reinke, Denise; Barkauskas, Donald A.; Krailo, Mark; Smith, Malcolm A.; Bernstein, Mark

2014-01-01

Despite successful primary tumor treatment, the development of pulmonary metastasis continues to be the most common cause of mortality in osteosarcoma patients. A conventional drug development path requiring drugs to induce regression of established lesions has not led to improvements for osteosarcoma patients in over 30 years. Based on our growing understanding of metastasis biology, it is now reasonable and essential that we focus on developing therapeutics that target metastatic progression. To advance this agenda a meeting of key opinion leaders and experts in the metastasis and osteosarcoma communities was convened in Bethesda Maryland. The goal of this meeting was to provide a “Perspective” that would establish a preclinical translational path that could support the early evaluation of potential therapeutic agents that uniquely target the metastatic phenotype. Although focused on osteosarcoma the need for this perspective is shared among many cancer types. The consensus achieved from the meeting included the following: That the biology of metastatic progression is associated with metastasis-specific targets/processes that may not influence grossly detectable lesions; targeting of metastasis-specific processes is feasible; rigorous preclinical data is needed to support translation of metastasis-specific agents into human trials where regression of measurable disease is not an expected outcome; preclinical data should include an understanding of mechanism of action, validation of pharmacodynamic markers of effective exposure and response, the use of several murine models of effectiveness, and where feasible the inclusion of the dog with naturally occurring osteosarcoma to define the activity of new drugs in the micro-metastatic disease setting. PMID:24803583

The Oncology Nursing Society Leadership Competency project: developing a road map to professional excellence.

PubMed

Day, Donald D; Hand, Mikel W; Jones, Ann R; Harrington, Nancy Kay; Best, Robyn; LeFebvre, Kristine B

2014-08-01

Combining the recommendations of the Institute of Medicine's report on the future of nursing, an Oncology Nursing Society (ONS) leadership think tank, and current evidence, the ONS Leadership Competencies were developed to provide all nurses with a pathway to advance their leadership skills and abilities. Generated through a systematic approach of literature review, data synthesis, and peer and expert review, the ONS Leadership Competencies are divided into five domains: vision, knowledge, interpersonal effectiveness, systems thinking, and personal mastery. Each of the competencies can be measured at the individual, group, and governance levels. They serve as a means of self-assessment, growth, future planning, and professional development. This article describes the process used to develop the ONS Leadership Competencies and offers examples of how they may be used in practice.

Applying Andragogical Concepts in Creating a Sustainable Lifelong Learning Society

ERIC Educational Resources Information Center

Charungkaittikul, Suwithida; Henschke, John A.

2017-01-01

Today, the world is changing, re-establishing the role of education to have a developed society. This article aims to explore the practical application of Andragogy as a key element for creating a sustainable lifelong learning society, to propose strategies for developing a lifelong learning society using andragogical concepts, to enhance…

Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum.

PubMed

Lubin, Alexandra S; Rueda-Zubiaurre, Ainoa; Matthews, Holly; Baumann, Hella; Fisher, Fabio R; Morales-Sanfrutos, Julia; Hadavizadeh, Kate S; Nardella, Flore; Tate, Edward W; Baum, Jake; Scherf, Artur; Fuchter, Matthew J

2018-04-13

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labeling of Plasmodium lysates and identify similarities between the target profiles of the probe and the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics experiments identified 104 proteins from different classes, many of which are essential, highlighting the suitability of the developed probe as a valuable tool for target identification in Plasmodium falciparum.

Proteomic Identification of Putative MicroRNA394 Target Genes in Arabidopsis thaliana Identifies Major Latex Protein Family Members Critical for Normal Development.

PubMed

Litholdo, Celso G; Parker, Benjamin L; Eamens, Andrew L; Larsen, Martin R; Cordwell, Stuart J; Waterhouse, Peter M

2016-06-01

Expression of the F-Box protein Leaf Curling Responsiveness (LCR) is regulated by microRNA, miR394, and alterations to this interplay in Arabidopsis thaliana produce defects in leaf polarity and shoot apical meristem organization. Although the miR394-LCR node has been documented in Arabidopsis, the identification of proteins targeted by LCR F-box itself has proven problematic. Here, a proteomic analysis of shoot apices from plants with altered LCR levels identified a member of the Latex Protein (MLP) family gene as a potential LCR F-box target. Bioinformatic and molecular analyses also suggested that other MLP family members are likely to be targets for this post-translational regulation. Direct interaction between LCR F-Box and MLP423 was validated. Additional MLP members had reduction in protein accumulation, in varying degrees, mediated by LCR F-Box. Transgenic Arabidopsis lines, in which MLP28 expression was reduced through an artificial miRNA technology, displayed severe developmental defects, including changes in leaf patterning and morphology, shoot apex defects, and eventual premature death. These phenotypic characteristics resemble those of Arabidopsis plants modified to over-express LCR Taken together, the results demonstrate that MLPs are driven to degradation by LCR, and indicate that MLP gene family is target of miR394-LCR regulatory node, representing potential targets for directly post-translational regulation mediated by LCR F-Box. In addition, MLP28 family member is associated with the LCR regulation that is critical for normal Arabidopsis development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Double-stranded RNA targeting calmodulin reveals a potential target for pest management of Nilaparvata lugens.

PubMed

Wang, Weixia; Wan, Pinjun; Lai, Fengxiang; Zhu, Tingheng; Fu, Qiang

2018-07-01

Calmodulin (CaM) is an essential protein in cellular activity and plays important roles in many processes in insect development. RNA interference (RNAi) has been hypothesized to be a promising method for pest control. CaM is a good candidate for RNAi target. However, the sequence and function of CaM in Nilaparvata lugens are unknown. Furthermore, the double-stranded RNA (dsRNA) target to CaM gene in pest control is still unavailable. In the present study, two alternatively spliced variants of CaM transcripts, designated NlCaM1 and NlCaM2, were cloned from N. lugens. The two cDNA sequences exhibited 100% identity to each other in the open reading frame (ORF), and only differed in the 3' untranslated region (UTR). NlCaM including NlCaM1 and NlCaM2 mRNA was detectable in all developmental stages and tissues of N. lugens, with significantly increased expression in the salivary glands. Knockdown of NlCaM expression by RNAi with different dsRNAs led to an inability to molt properly, increased mortality, which ranged from 49.7 to 92.5%, impacted development of the ovaries and led to female infertility. There were no significant reductions in the transcript levels of vitellogenin and its receptor or in the total vitellogenin protein level relative to the control group. However, a significant reduction in vitellogenin protein was detected in ovaries injected with dsNlCaM. In addition, a specific dsRNA of NlCaM for control of N. lugens was designed and tested. NlCaM plays important roles mainly in nymph development and uptake of vitellogenin by ovaries in vitellogenesis in N. lugens. dsRNA derived from the less conserved 3'-UTR of NlCaM shows great potential for RNAi-based N. lugens management. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Development of an algorithm for the management of cervical lymphadenopathy in children: consensus of the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases and the Italian Society of Pediatric Otorhinolaryngology.

PubMed

Chiappini, Elena; Camaioni, Angelo; Benazzo, Marco; Biondi, Andrea; Bottero, Sergio; De Masi, Salvatore; Di Mauro, Giuseppe; Doria, Mattia; Esposito, Susanna; Felisati, Giovanni; Felisati, Dino; Festini, Filippo; Gaini, Renato Maria; Galli, Luisa; Gambini, Claudio; Gianelli, Umberto; Landi, Massimo; Lucioni, Marco; Mansi, Nicola; Mazzantini, Rachele; Marchisio, Paola; Marseglia, Gian Luigi; Miniello, Vito Leonardo; Nicola, Marta; Novelli, Andrea; Paulli, Marco; Picca, Marina; Pillon, Marta; Pisani, Paolo; Pipolo, Carlotta; Principi, Nicola; Sardi, Iacopo; Succo, Giovanni; Tomà, Paolo; Tortoli, Enrico; Tucci, Filippo; Varricchio, Attilio; de Martino, Maurizio; Italian Guideline Panel For Management Of Cervical Lymphadenopathy In Children

2015-01-01

Cervical lymphadenopathy is a common disorder in children due to a wide spectrum of disorders. On the basis of a complete history and physical examination, paediatricians have to select, among the vast majority of children with a benign self-limiting condition, those at risk for other, more complex, diseases requiring laboratory tests, imaging and, finally, tissue sampling. At the same time, they should avoid expensive and invasive examinations when unnecessary. The Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases, the Italian Society of Pediatric Otorhinolaryngology, and other Scientific Societies, issued a National Consensus document, based on the most recent literature findings, including an algorithm for the management of cervical lymphadenopathy in children. The Consensus Conference method was used, following the Italian National Plan Guidelines. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through March 21, 2014. Basing on literature results, an algorithm was developed, including several possible clinical scenarios. Situations requiring a watchful waiting strategy, those requiring an empiric antibiotic therapy, and those necessitating a prompt diagnostic workup, considering the risk for a severe underling disease, have been identified. The present algorithm is a practice tool for the management of pediatric cervical lymphadenopathy in the hospital and the ambulatory settings. A multidisciplinary approach is paramount. Further studies are required for its validation in the clinical field.

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder.

PubMed

de Sousa, Rafael T; Machado-Vieira, Rodrigo; Zarate, Carlos A; Manji, Husseini K

2014-10-01

Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca²⁺) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca²⁺ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents.

Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

PubMed Central

de Sousa, Rafael T; Machado-Vieira, Rodrigo; Zarate, Carlos A

2014-01-01

Introduction Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. Areas covered This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca2+) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca2+ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Expert opinion Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents. PMID:25056514

Society 3.0: How Technology Is Reshaping Education, Work and Society

ERIC Educational Resources Information Center

Wilen-Daugenti, Tracey

2012-01-01

Higher education in the U.S. has traditionally prepared students for work and social success, but with families, work, and society itself undergoing revolutionary change, is this preparation sufficient to develop the 21st-century workforce? This book explores how evolving family structures, new ways of balancing work and personal lives, and rapid…

Landing response of Aedes (Stegomyia) polynesiensis mosquitoes to coloured targets.

PubMed

Chambers, E W; Bossin, H C; Ritchie, S A; Russell, R C; Dobson, S L

2013-09-01

Aedes polynesiensis Marks (Diptera: Culicidae) is the primary vector of lymphatic filariasis (LF) in the island countries and territories of the South Pacific. In the development of a novel control tool, the response of Ae. polynesiensis to six different colours (three solid fabrics, two patterned fabrics and a plastic tarp) was measured using a digital photographic system. Adult mosquitoes were placed into an environmental chamber and allowed to choose between a white target and one of six experimental targets. Mosquito landing frequency and landing duration were calculated. Adult female Ae. polynesiensis preferred all of the experimental targets to the white control target. Mosquito landing frequency was highest for the solid targets (black, navy blue and red) followed in turn by the two colour pattern targets and the polyethylene target. Mosquito landing duration was greater for experimental targets when compared with white control targets. Mosquito landing frequencies did not change over time during the course of the assay. The response of male Ae. polynesiensis was also measured when exposed to a 100% cotton black target. Male mosquitoes preferred the black target to the white control target, although at levels lower than that observed in female mosquitoes. The results suggest that future investigations evaluating the visual responses of Ae. polynesiensis mosquitoes are warranted, with a special emphasis on semi-field and field-based experiments. © 2013 The Royal Entomological Society.

Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

DTIC Science & Technology

2013-08-01

AD_________________ Award Number: W81XWH-12-1-0284 TITLE: Development of Targeted Nanobubbles for...REPORT TYPE Annual 3. DATES COVERED 15 July 2012 - 14 July 2013 4. TITLE AND SUBTITLE Development of Targeted Nanobubbles for Ultrasound...be able to formulate nanodroplets contrast agents with tunable size, PFP content, and shell flexibility to obtain stable and echogenic nanobubbles

The clinical development of histone deacetylase inhibitors as targeted anticancer drugs.

PubMed

Marks, Paul A

2010-09-01

Histone deacetylase (HDAC) inhibitors are being developed as a new, targeted class of anticancer drugs. This review focuses on the mechanisms of action of the HDAC inhibitors, which selectively induce cancer cell death. There are 11 zinc-dependent HDACs in humans and the biological roles of these lysine deacetylases are not completely understood. It is clear that these different HDACs are not redundant in their activity. This review focuses on the mechanisms by which HDAC inhibitors can induce transformed cell growth arrest and cell death, inhibit cell mobility and have antiangiogenesis activity. There are more than a dozen HDAC inhibitors, including hydroxamates, cyclic peptides, benzamides and fatty acids, in various stages of clinical trials and many more compounds in preclinical development. The chemically different HDAC inhibitors may target different HDACs. There are extensive preclinical studies with transformed cells in culture and tumor-bearing animal models, as well as limited clinical studies reported to date, which indicate that HDAC inhibitors will be most useful when used in combination with cytotoxic or other targeted anticancer agents.

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

ERIC Educational Resources Information Center

Shafiq, M. Najeeb

2010-01-01

A targeted educational voucher scheme (TEVS) is often proposed for the poor in developing countries. Essentially, TEVS involves issuing vouchers to poor households, thus enabling them to pay tuition and fees for their children's schooling at participating non-public schools. However, little is known about TEVS' design in developing countries. This…

Customer service: developing a new mindset for today's instant gratification society.

PubMed

Stockburger, W T

1998-01-01

Today's society expects and demands immediate service, results and access to information. Can those of us in leadership positions say that the service we provide is equal to or exceeds what our customers expect? How can we redesign our services so they are better than those we currently provide? Some people look to advances in technology as one means to improve services and access to information, but this should not be the only means. If we are to develop a philosophy of exceptional service, we must develop a vision of those services. We must gain an understanding of our customers, plus a knowledge of products, the availability of resources and any industry constraints. In healthcare, we must look to leadership to achieve our goals. A goal of exceptional customer service must be communicated to all levels of service providers from management. Top-down action by management--leadership by example--is critical. Leadership must gain the trust of both customers and employees by actively listening to both verbal and nonverbal comments at all points of service. Without an understanding of our customers' needs, it won't be possible to deliver services at or above their expectations.

DrugPath: a database for academic investigators to match oncology molecular targets with drugs in development.

PubMed

Shah, Eric D; Fisch, Brandon M A; Arceci, Robert J; Buckley, Jonathan D; Reaman, Gregory H; Sorensen, Poul H; Triche, Timothy J; Reynolds, C Patrick

2014-05-01

Academic laboratories are developing increasingly large amounts of data that describe the genomic landscape and gene expression patterns of various types of cancers. Such data can potentially identify novel oncology molecular targets in cancer types that may not be the primary focus of a drug sponsor's initial research for an investigational new drug. Obtaining preclinical data that point toward the potential for a given molecularly targeted agent, or a novel combination of agents requires knowledge of drugs currently in development in both the academic and commercial sectors. We have developed the DrugPath database ( http://www.drugpath.org ) as a comprehensive, free-of-charge resource for academic investigators to identify agents being developed in academics or industry that may act against molecular targets of interest. DrugPath data on molecular targets overlay the Michigan Molecular Interactions ( http://mimi.ncibi.org ) gene-gene interaction map to facilitate identification of related agents in the same pathway. The database catalogs 2,081 drug development programs representing 751 drug sponsors and 722 molecular and genetic targets. DrugPath should assist investigators in identifying and obtaining drugs acting on specific molecular targets for biological and preclinical therapeutic studies.

Development Module Oriented Science Technology Society Indue Science Literacy Assessment for 7th-Grade Junior High School Students in 2nd -Semester

NASA Astrophysics Data System (ADS)

Arbi, Y. R.; Sumarmin, R.; Putri, D. H.

2018-04-01

The problem in the science learning process is the application of the scientific approach takes a long time in order to provide conceptual understanding to the students, there is no teaching materials that can measure students reasoning and thinking ability, and the assessment has not measured students reasoning and literacy skills.The effort can be done is to develop science technology society module indue science literacy assessment. The purpose of the research was to produce a module oriented society indue science science technology literacy assessment. The research is development research using Plomp model, consist of preliminary, prototyping, and assessment phase. Data collect by questionnare and documantion. The result there is science technology society module indue science literacy assessment is very valid.

Acromegaly: an endocrine society clinical practice guideline.

PubMed

Katznelson, Laurence; Laws, Edward R; Melmed, Shlomo; Molitch, Mark E; Murad, Mohammad Hassan; Utz, Andrea; Wass, John A H

2014-11-01

The aim was to formulate clinical practice guidelines for acromegaly. The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Using an evidence-based approach, this acromegaly guideline addresses important clinical issues regarding the evaluation and management of acromegaly, including the appropriate biochemical assessment, a therapeutic algorithm, including use of medical monotherapy or combination therapy, and management during pregnancy.

Guidelines in the Register of the Association of Scientific Medical Societies in Germany – A Quality Improvement Campaign

PubMed Central

Nothacker, M. J.; Muche-Borowski, C.; Kopp, I. B.

2014-01-01

The Association of Scientific Medical Societies in Germany (AWMF) is the umbrella organization of medical scientific societies in Germany. The development of guidelines goes back to an initiative of the medical scientific societies and is coordinated by the AWMF. Rules for the inclusion of guidelines in the AWMF Guideline Register have been defined including how guidelines are classified. S1 guidelines are based only on recommendations by experts, whereas S2 guidelines require a structured consensus process or a systematic literature review. S3 guidelines include both elements. In addition to compulsory disclosure of any potential conflict of interest, transparent handling of potential conflicts of interest is an important confidence-building measure. For years, the trend has been to develop higher order (S2/S3) guidelines, and the German Society for Gynecology and Obstetrics (DGGG) has been no exception to the trend. In addition to its responsibility for specific S2 and S3 guidelines, the DGGG is also involved in numerous other interdisciplinary guidelines. When developing a guideline, it is essential to define the guidelineʼs scope, identify aspects which require improvement and agree on the goals. Target groups affected by the guidelines should be involved if they are interested. Different formats (long and short versions, practical instructions, conventional or electronic decision aids, patient versions) are useful to disseminate the guideline. The guideline can be adapted to local circumstances to encourage implementation of its recommendations. Implementation can be measured using quality indicators. Feedback from practitioners is important as this highlights areas which require improvement. The medical scientific societies in Germany can look back on almost two decades of work spent on developing guidelines, most of it done by unpaid voluntary contributors, making this a very successful quality initiative. PMID:25061235

Animal Models of Substance Abuse and Addiction: Implications for Science, Animal Welfare, and Society

PubMed Central

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-01-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models. PMID:20579432

Animal models of substance abuse and addiction: implications for science, animal welfare, and society.

PubMed

Lynch, Wendy J; Nicholson, Katherine L; Dance, Mario E; Morgan, Richard W; Foley, Patricia L

2010-06-01

Substance abuse and addiction are well recognized public health concerns, with 2 NIH institutes (the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism) specifically targeting this societal problem. As such, this is an important area of research for which animal experiments play a critical role. This overview presents the importance of substance abuse and addiction in society; reviews the development and refinement of animal models that address crucial areas of biology, pathophysiology, clinical treatments, and drug screening for abuse liability; and discusses some of the unique veterinary, husbandry, and IACUC challenges associated with these models.

Development of a Muon Rotating Target for J-PARC/MUSE

NASA Astrophysics Data System (ADS)

Makimura, Shunsuke; Kobayashi, Yasuo; Miyake, Yasuhiro; Kawamura, Naritoshi; Strasser, Patrick; Koda, Akihiro; Shimomura, Koichiro; Fujimori, Hiroshi; Nishiyama, Kusuo; Kato, Mineo; Kojima, Kenji; Higemoto, Wataru; Ito, Takashi; Shimizu, Ryou; Kadono, Ryosuke

At the J-PARC muon science facility (J-PARC/MUSE), a graphite target with a thickness of 20 mm has been used in vacuum to obtain an intense pulsed muon beam from the RCS 3-GeV proton beam [1], [2]. In the current design, the target frame is constructed using copper with a stainless steel tube embedded for water cooling. The energy deposited by the proton beam at 1 MW is evaluated to be 3.3 kW on the graphite target and 600 W on the copper frame by a Monte-Carlo simulation code, PHITS [3]. Graphite materials are known to lose their crystal structure and can be shrunk under intense proton beam irradiation. Consequently, the lifetime of the muon target is essentially determined by the radiation damage in graphite, and is evaluated to be half a year [4]. Hence, we are planning to distribute the radiation damage by rotating a graphite wheel. Although the lifetime of graphite in this case will be more than 10 years, the design of the bearing must be carefully considered. Because the bearing in JPARC/MUSE is utilized in vacuum, under high radiation, and at high temperature, an inorganic and solid lubricant must be applied to the bearing. Simultaneously, the temperature of the bearing must also be decreased to extend the lifetime. In 2009, a mock-up of the Muon Rotating Target, which could heat up and rotate a graphite wheel, was fabricated. Then several tests were started to select the lubricant and to determine the structure of the Muon Rotating Target, the control system and so on. In this report, the present status of the Muon Rotating Target for J-PARC/MUSE, especially the development of a rotation system in vacuum, is described.

Geosciences: an important tool for the ethical advancement and the economic and cultural development of our society

NASA Astrophysics Data System (ADS)

Vito Graziano, Gian

2013-04-01

The development of a society in economic, cultural and ethical terms is always linked to the growth of the scientific and technical knowledge. It follows that the downsizing of the scientific research brings to a slower growth or even, as it is happening these days in Italy, a real cultural decay. The consequences of the economic crisis are evident to everyone, but it is precisely in times of crisis that the best strategies to restart the economy and give new cultural perspectives to society are studied. The crisis is also contrasted with ideas and ability to put them into practice. This, however, also presupposes a different cultural approach, which has to also include a review of values and beliefs, and a redefinition of the objectives to be pursued. This approach is modeled on the basis of several positive experiences that a country can boast. Among these experiences, there are those arising from the scientific culture: geology, for example, such as chemistry, biology or other sciences, can help to change vision. The research and practice of Earth sciences have important implications on the life and activities of the population and therefore the geoscientists, as active subjects in the society, should question their role and responsibilities. They should be at the service of society, especially in the fields of prevention from natural hazards and valorization of georesources. In this sense they can give important indications for economy and development of their country. The Italian Council of Geologists (Consiglio Nazionale dei Geologi - CNG) acts with the aim of highlighting the social role of geoscientists, hoping for a new cultural Renaissance, which leads to new researches, without obscurantism or prejudices. In an authoritative way, the CNG intends to put this social role before any demand from the professional category. Therefore, it has recently presented its political Manifesto, geared essentially to the good governance of the territory, to all the

Women Empowerment and Participation in Economic Activities: Indispensable Tools for Self-Reliance and Development of Nigerian Society

ERIC Educational Resources Information Center

E. N., Ekesionye; A. N., Okolo

2012-01-01

The objective of the study was to examine women empowerment and participation in economic activities as tools for self-reliance and development of the Nigerian society. Research questions and hypothesis were used to guide the study. Structured questionnaire was used as the major instrument for data collection. Copies of questionnaires were…

Development of Targeted Near-Infrared Imaging Agents for Prostate Cancer

PubMed Central

Wang, Xinning; Huang, Steve S.; Heston, Warren D.W.; Guo, Hong; Wang, Bing-Cheng; Basilion, James P.

2015-01-01

Prostate cancer is the most common noncutaneous malignancy affecting men in North America. Radical prostatectomy remains a definitive treatment for prostate cancer. However, prostate surgeries are still performed “blindly” with the extent of tumor infiltration past the margins of the surgery only being determined postoperatively. An imaging modality that can be used during surgery is needed to help define the tumor margins. With its abundant expression in prostate cancer, prostate-specific membrane antigen (PSMA) is an ideal target for detection of prostate cancer. The purpose of this study was to develop PSMA-targeted near-infrared (NIR) optical imaging probes for intraoperative visualization of prostate cancer. We synthesized a high-affinity PSMA ligand (PSMA-1) with low molecular weight and further labeled it with commercially available NIR dyes IRDy800 and Cy5.5. PSMA-1 and PSMA-1–NIR conjugates had binding affinities better than the parent ligand Cys-CO-Glu. Selective binding was measured for each of the probes in both in vitro and in vivo studies using competitive binding and uptake studies. Interestingly, the results indicated that the pharmacokinetics of the probes was dependent of the fluorophore conjugated to the PSMA-1 ligand and varied widely. These data suggest that PSMA-targeted probes have the potential to be further developed as contrast agents for clinical intraoperative fluorescence-guided surgery. PMID:25239933

Sexual networks in contemporary Western societies

NASA Astrophysics Data System (ADS)

Liljeros, Fredrik

2004-07-01

Sexually transmitted infections continue to be a severe health problem in contemporary Western societies, despite the considerable funds allocated for control programs. In this article, we present and discuss a variety of explanations that have been advanced on why this type of disease is so hard to eradicate, despite the fact that the contact by which it is spread is far less frequent than is the case with most other infectious diseases. We conclude that several processes and mechanisms facilitate the spread of sexually infected diseases, and that both broad and targeted intervention is therefore needed to eradicate such diseases.

Understanding Release from Actinide Targets -- Recent Results from RIB Development

NASA Astrophysics Data System (ADS)

Kronenberg, Andreas; Carter, H. K.; Spejewski, E. H.; Stracener, D. W.

2006-10-01

Development of ion beams of short-lived isotopes is crucial for modern nuclear structure and nuclear astrophysics. The Holifield Radioactive Ion Beam Facility at Oak Ridge National Laboratory uses the ISOL (Isotope Separation Online) technique to provide radioactive ion beams. So far, uranium carbide has been used as a target to produce neutron-rich fission fragments. Thermodynamic calculations indicate the possibility of in-situ chemical side band formations of volatile species of refractory metals, such as V and Re. These elements release out of oxide targets after production in a nuclear reaction, and can occur only through in-situ formation of their volatile oxide. These have been confirmed experimentally. The results from recent, more detailed investigations of ThO2, UB4 and other actinide targets as well as conclusions from systematic studies will be presented. This research was sponsored by the NNSA under Stewardship Science Academic Alliance program through DOE Cooperative Agreement # DE-FC03-3NA00143.

Effects-based strategy development through center of gravity and target system analysis

NASA Astrophysics Data System (ADS)

White, Christopher M.; Prendergast, Michael; Pioch, Nicholas; Jones, Eric K.; Graham, Stephen

2003-09-01

This paper describes an approach to effects-based planning in which a strategic-theater-level mission is refined into operational-level and ultimately tactical-level tasks and desired effects, informed by models of the expected enemy response at each level of abstraction. We describe a strategy development system that implements this approach and supports human-in-the-loop development of an effects-based plan. This system consists of plan authoring tools tightly integrated with a suite of center of gravity (COG) and target system analysis tools. A human planner employs the plan authoring tools to develop a hierarchy of tasks and desired effects. Upon invocation, the target system analysis tools use reduced-order models of enemy centers of gravity to select appropriate target set options for the achievement of desired effects, together with associated indicators for each option. The COG analysis tools also provide explicit models of the causal mechanisms linking tasks and desired effects to one another, and suggest appropriate observable indicators to guide ISR planning, execution monitoring, and campaign assessment. We are currently implementing the system described here as part of the AFRL-sponsored Effects Based Operations program.

Sex Role Socialization Patterns in Selected Societies.

ERIC Educational Resources Information Center

Safilios-Rothschild, Constantina

This document evolved because studies concerning sex role socialization patterns were available from only a limited number of societies. In addition to examining available research findings, the author develops a number of relevant hypotheses with respect to several selected societies--the United States, Russia, Greece, India, and Eastern Europe.…

Developing, implementing, and evaluating a condom promotion program targeting sexually active adolescents.

PubMed

Alstead, M; Campsmith, M; Halley, C S; Hartfield, K; Goldbaum, G; Wood, R W

1999-12-01

This article describes the development, implementation, and evaluation of the Condom Campaign, a 1995 HIV prevention program promoting condom use among sexually active adolescents in three King County, Washington, urban communities. This program employed three main strategies: (a) mobilizing all levels of the target communities to support and guide program development and implementation; (b) creating and implementing a mass media campaign targeting sexually active teenagers that promoted correct condom use and favorable attitudes toward condoms; and (c) recruiting public agencies, community organizations, and businesses to distribute condoms from bins and vending machines. We evaluated the program through a series of cross-sectional interviews conducted in the three communities chosen for their elevated levels of adolescent sexual risk behavior. Overall, 73% of target youth reported exposure to the Condom Campaign; exposure did not differ by age, gender, race, or level of sexual experience. Levels of sexual activity remained stable throughout the media campaign.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease : A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem

2017-12-01

This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities.Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines.A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario.The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will

The society of thoracic surgeons.

PubMed

Alley, R D

1976-11-01

The opportunity to discuss evolving socioeconomic issues affecting the medical profession as a whole was rejected in favor of personalizing The Society of Thoracic Surgeons for a membership that has grown to almost 1,500 persons. Drawing on historical insights gained through participation in the origin, growth, and development of The Society, I take readers behind the scenes and introduce to them the many people and vast resources that serve our membership. Particular attention is focused on the services of The Society's headquarters office, which is housed and managed by Smith, Bucklin and Associates, Inc, of Chicago, a multiple-association management firm that serves 60 national organizations; on our prestigious publisher, Little, Brown and Company of Boston; and on its link with our Editorial Office in Ann Arbor.

The impact of Nordic adult education ideas on the development of a democratic society in Lithuania

NASA Astrophysics Data System (ADS)

Teresevičienė, Margarita; Trepulė, Elena; Trečiokienė, Edita

2017-02-01

This article analyses the role of the cooperation with and the influence of the Nordic countries on the development of a democratic society in Lithuania through adult education since the reinstatement of its independence from Soviet regime in March 1990 to the present. The authors focus on three main areas: (1) the training of Lithuanian adult educators; (2) the establishment and development of NGOs; and (3) the implications for a Lithuanian policy of adult education. Within the framework of Nordic-Baltic cooperation established among five Nordic and three Baltic countries (NB8) in 1992, Lithuanian adult educators seized the opportunity to visit Scandinavian institutions and projects. Experiencing Nordic adult education ideas has resulted in a marked shift in Lithuanian adult educators' values, methodology and careers; and in the establishment of a series of very influential umbrella associations as well as hundreds of NGOs in Lithuania which work with adults and support functioning democratic values in society. This shift is related to the civic responsibility and active participation growing out of the bottom-up approaches of group work, cooperation, discussions and learning circles which are so inherent in the Nordic tradition of adult education. The internalisation of new democratic values was more complicated than expected for many Lithuanian politicians, adult educators and NGO leaders in terms of how political decisions were perceived and implemented. Furthermore, the influence of the Nordic-Baltic cooperation in adult education may also be traced in adult education policy implications in Lithuania. Some changes in the policies of contemporary Lithuania have not been successful and even failed to promote a democratic society.

A history of the Teratology Society.

PubMed

Shepard, T H; Barr, M; Brent, R L; Hendrickx, A; Kochhar, D; Oakley, G; Scott, W J

2000-11-01

The 39-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, along with listings of the Warkany Lectures, the postgraduate courses, and officers of the Society. A year-by-year description of the events, including the scientific and social content of the annual meetings and changes in the business of the Society, is given, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research area of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over four periods. Within the past 10 years, a significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The Society's development is compared with that of a human, and the question is asked: Have we reached the maturational stage of old age or senescence, or is the Society still maturing gracefully? This question needs further discussion by all the members. During the past 40 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as many other prenatal exposures. We must now engage in the political battles to obtain the resources needed to conduct further research and to implement the prevention programs, as well as to provide care and rehabilitation for persons with birth defects. Copyright 2000 Wiley-Liss, Inc.

Can Disaster Risk Education Reduce the Impacts of Recurring Disasters on Developing Societies?

ERIC Educational Resources Information Center

Baytiyeh, Hoda

2018-01-01

The impacts of recurring disasters on vulnerable urban societies have been tragic in terms of destruction and fatalities. However, disaster risk education that promotes risk mitigation and disaster preparedness has been shown to be effective in minimizing the impacts of recurring disasters on urban societies. Although the recent integration of…

The Saudi Thoracic Society guidelines for diagnosis and management of noncystic fibrosis bronchiectasis

PubMed Central

Al-Jahdali, Hamdan; Alshimemeri, Abdullah; Mobeireek, Abdullah; Albanna, Amr S.; Al Shirawi, Nehad N.; Wali, Siraj; Alkattan, Khaled; Alrajhi, Abdulrahman A.; Mobaireek, Khalid; Alorainy, Hassan S.; Al-Hajjaj, Mohamed S.; Chang, Anne B.; Aliberti, Stefano

2017-01-01

This is the first guideline developed by the Saudi Thoracic Society for the diagnosis and management of noncystic fibrosis bronchiectasis. Local experts including pulmonologists, infectious disease specialists, thoracic surgeons, respiratory therapists, and others from adult and pediatric departments provided the best practice evidence recommendations based on the available international and local literature. The main objective of this guideline is to utilize the current published evidence to develop recommendations about management of bronchiectasis suitable to our local health-care system and available resources. We aim to provide clinicians with tools to standardize the diagnosis and management of bronchiectasis. This guideline targets primary care physicians, family medicine practitioners, practicing internists and respiratory physicians, and all other health-care providers involved in the care of the patients with bronchiectasis. PMID:28808486

Rapid detection of proteins in transgenic crops without protein reference standards by targeted proteomic mass spectrometry.

PubMed

Schacherer, Lindsey J; Xie, Weiping; Owens, Michaela A; Alarcon, Clara; Hu, Tiger X

2016-09-01

Liquid chromatography coupled with tandem mass spectrometry is increasingly used for protein detection for transgenic crops research. Currently this is achieved with protein reference standards which may take a significant time or efforts to obtain and there is a need for rapid protein detection without protein reference standards. A sensitive and specific method was developed to detect target proteins in transgenic maize leaf crude extract at concentrations as low as ∼30 ng mg(-1) dry leaf without the need of reference standards or any sample enrichment. A hybrid Q-TRAP mass spectrometer was used to monitor all potential tryptic peptides of the target proteins in both transgenic and non-transgenic samples. The multiple reaction monitoring-initiated detection and sequencing (MIDAS) approach was used for initial peptide/protein identification via Mascot database search. Further confirmation was achieved by direct comparison between transgenic and non-transgenic samples. Definitive confirmation was provided by running the same experiments of synthetic peptides or protein standards, if available. A targeted proteomic mass spectrometry method using MIDAS approach is an ideal methodology for detection of new proteins in early stages of transgenic crop research and development when neither protein reference standards nor antibodies are available. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

DEVELOPMENT OF A METHOD TO DESIGN A LOW-CARBON SOCIETY IN SMALL COMMUNITY AND ITS APPLICATION TO PUTRAJAYA, MALAYSIA

NASA Astrophysics Data System (ADS)

Hayashi, Yuri; Simson, Janice. J.; Gomi, Kei; Matsuoka, Yuzuru

In this study, we developed the method to design Low-carbon society for small communities almost without industry, with regarding of costs for countermeasures. Then we applied it to Putrajaya, Malaysia, and estimate Socio-economic indicators, energy demand, CO2 emission in year 2007 and 2025. For countermeasure case in 2025, we set three cases according to their priority; Transport, Renewable energy, Building, and calculated costs for countermeasures also. As a result, it was shown that it is possible to reduce 45% of CO2 emission by 2025 compared to 2007 level. Renewable energy priority case needs the highest cost, and Building and Transport was estimated to be the second and third highest. C-ExSS will help more realistic discussion on the policy and countermeasures for developing low-carbon society based on their costs.

An Official American Thoracic Society Workshop Report: Chemical Inhalational Disasters. Biology of Lung Injury, Development of Novel Therapeutics, and Medical Preparedness

PubMed Central

Hoyle, Gary W.; Jordt, Sven-Eric; Jugg, Bronwen J.; Martin, James G.; Matalon, Sadis; Patterson, Steven E.; Prezant, David J.; Sciuto, Alfred M.; Svendsen, Erik R.; White, Carl W.; Veress, Livia A.

2017-01-01

This report is based on the proceedings from the Inhalational Lung Injury Workshop jointly sponsored by the American Thoracic Society (ATS) and the National Institutes of Health (NIH) Countermeasures Against Chemical Threats (CounterACT) program on May 21, 2013, in Philadelphia, Pennsylvania. The CounterACT program facilitates research leading to the development of new and improved medical countermeasures for chemical threat agents. The workshop was initiated by the Terrorism and Inhalational Disasters Section of the Environmental, Occupational, and Population Health Assembly of the ATS. Participants included both domestic and international experts in the field, as well as representatives from U.S. governmental funding agencies. The meeting objectives were to (1) provide a forum to review the evidence supporting current standard medical therapies, (2) present updates on our understanding of the epidemiology and underlying pathophysiology of inhalational lung injuries, (3) discuss innovative investigative approaches to further delineating mechanisms of lung injury and identifying new specific therapeutic targets, (4) present promising novel medical countermeasures, (5) facilitate collaborative research efforts, and (6) identify challenges and future directions in the ongoing development, manufacture, and distribution of effective and specific medical countermeasures. Specific inhalational toxins discussed included irritants/pulmonary toxicants (chlorine gas, bromine, and phosgene), vesicants (sulfur mustard), chemical asphyxiants (cyanide), particulates (World Trade Center dust), and respirable nerve agents. PMID:28418689

Development of prostate specific membrane antigen targeted ultrasound microbubbles using bioorthogonal chemistry

PubMed Central

Zlitni, Aimen; Yin, Melissa; Janzen, Nancy; Chatterjee, Samit; Lisok, Ala; Gabrielson, Kathleen L.; Nimmagadda, Sridhar; Pomper, Martin G.; Foster, F. Stuart

2017-01-01

Prostate specific membrane antigen (PSMA) targeted microbubbles (MBs) were developed using bioorthogonal chemistry. Streptavidin-labeled MBs were treated with a biotinylated tetrazine (MBTz) and targeted to PSMA expressing cells using trans-cyclooctene (TCO)-functionalized anti-PSMA antibodies (TCO-anti-PSMA). The extent of MB binding to PSMA positive cells for two different targeting strategies was determined using an in vitro flow chamber. The initial approach involved pretargeting, where TCO-anti-PSMA was first incubated with PSMA expressing cells and followed by MBTz, which subsequently showed a 2.8 fold increase in the number of bound MBs compared to experiments performed in the absence of TCO-anti-PSMA. Using direct targeting, where TCO-anti-PSMA was linked to MBTz prior to initiation of the assay, a 5-fold increase in binding compared to controls was observed. The direct targeting approach was subsequently evaluated in vivo using a human xenograft tumor model and two different PSMA-targeting antibodies. The US signal enhancements observed were 1.6- and 5.9-fold greater than that for non-targeted MBs. The lead construct was also evaluated in a head-to-head study using mice bearing both PSMA positive or negative tumors in separate limbs. The human PSMA expressing tumors exhibited a 2-fold higher US signal compared to those tumors deficient in human PSMA. The results demonstrate both the feasibility of preparing PSMA-targeted MBs and the benefits of using bioorthogonal chemistry to create targeted US probes. PMID:28472168

The use of Space Technology for the Benefit of Society in Context of Planning and Sustainable Development

NASA Astrophysics Data System (ADS)

Kuldeep, Kuldeep; Banu, Vijaya

2016-07-01

The introduction of the novel technology mostly leads to a number of advantages to the society. The space technology has shown such benefits in many fields including the areas of health and education, communication sectors, land and water resources management, weather forecasting and disaster management. It has vast potential for addressing a variety of societal problems of the developing countries especially in India in a effective manner. Large population which is spread over vast and remote areas of the nation, reaching out to them is a difficult task. This manuscript aims to explain the benefits originated from the application of space technology. The satellite imagery and its derived products can better be utilized for local level planning and sustainable development of a region. A case-study using Bhuvan Panchayat Portal developed by National Remote Sensing Centre, ISRO under the project "Space Based Information Support for De-Centralised Planning" towards Digital Empowerment of Society for Panchayat level Planning and Governance has been carried out, which list out the benefits that have accrued from the use of space technology for planning and development at grass root level in India. It covers, in particular, the benefits expected to be derived from the Indian Remote Sensing Satellite (IRS) Images and derived products. Certain conclusions about the benefits from space based inputs have been drawn that may be generally applicable to all developing countries. This paper also investigates the various possibilities and potentials of Remote Sensing technologies for societal applications.

Targeting the androgen receptor in prostate and breast cancer – several new agents in development

PubMed Central

Proverbs-Singh, Tracy; Feldman, Jarett L.; Morris, Michael J.; Autio, Karen A.; Traina, Tiffany A.

2016-01-01

Prostate cancer and breast cancer share similarities as hormone-sensitive cancers with a wide heterogeneity of both phenotype and biology. The androgen receptor (AR) is a hormone receptor involved in both benign and malignant processes. Targeting androgen synthesis and the AR pathway has been and remains central to prostate cancer therapy. Recently, there is increased interest in the role of the AR in breast cancer development and growth, with data suggesting AR co-expression with estrogen, progesterone and human epidermal growth factor receptors, across all intrinsic subtypes of breast cancer. Targeting the AR axis is an evolving field with novel therapies in development which may ultimately be applicable for both tumor types. In this review, we offer an overview of available agents which target the AR axis in both prostate and breast cancer and provide insight into the novel drugs in development for targeting this signaling pathway. PMID:25722318

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management during Cardiopulmonary Bypass.

PubMed

Engelman, Richard; Baker, Robert A; Likosky, Donald S; Grigore, Alina; Dickinson, Timothy A; Shore-Lesserson, Linda; Hammon, John W

2015-09-01

To improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendation.

Orphan Nuclear Receptors as Targets for Drug Development

PubMed Central

Mukherjee, Subhajit

2012-01-01

Orphan nuclear receptors regulate diverse biological processes. These important molecules are ligand-activated transcription factors that act as natural sensors for a wide range of steroid hormones and xenobiotic ligands. Because of their importance in regulating various novel signaling pathways, recent research has focused on identifying xenobiotics targeting these receptors for the treatment of multiple human diseases. In this review, we will highlight these receptors in several physiologic and pathophysiologic actions and demonstrate how their functions can be exploited for the successful development of newer drugs. PMID:20372994

Novelty, Creation, and Society.

ERIC Educational Resources Information Center

Hattiangadi, Jagdish N.

1985-01-01

Individual artistic creativity has no place in the development of art, science, or society. If an intellectual has a thorough understanding of intellectual traditions and appreciation of the situation, s/he needs to be no more than reasonable to produce what have been hitherto considered products of genius. (MT)

[History of the Strasbourg Society of Biology].

PubMed

Antony, Pierre; Romier, Christophe; Mantz, Jean-Marie

2017-01-01

The Society of Biology of Strasbourg (SBS) is a learned society that was created in 1919 based on the model of the Society of Biology of which it is a subsidiary. Like its Parisian colleague, SBS aims at diffusing and promoting scientific knowledge in biology. To achieve this goal, SBS initiated since its creation a dialogue interface between researchers in biology and physicians, and more recently with other scientific disciplines, industry and the civil society. At the dawn of its first century, the Society of Biology of Strasbourg must continue to reinvent itself to pursue its development and to fulfil its mission of sharing scientific knowledge. This work continues in strong collaboration with our partners that share with SBS the willingness to foster excellence in biological research in Strasbourg, its region and beyond. © Société de Biologie, 2017.

The Spanish Society of Soil Science: Main projects and activities developed during the last years

NASA Astrophysics Data System (ADS)

Porta, Jaume; Mataix-Solera, Jorge; Ortiz-Bernad, Irene; Arbelo, Carmen D.; Díaz-Raviña, Montserrat; Badía, David; Alcañiz, Josep M.; Santos, Fernando; Hermosin, M. Carmen; Barral, M. Teresa

2017-04-01

The Spanish Society of Soil Science (in Spanish: Sociedad Española de la Ciencia del Suelo, SECS) was founded in 1947 by the Spanish National Research Council (CSIC) to promote cohesion and collaboration between soil science professionals, and with an innovative spirit and a willingness to serve the society. The objectives are: to promote the study, knowledge, research and protection of the soil; to spread, from a scientific point of view, the role played by the soil in favour of society, through ecosystem services such as the production of food and raw materials; The SECS also focus on the protection of other habitats and the conservation of our archaeological heritage; and to preserve knowledge of the soil, its management and use, both from the production and environmental point of view, leading to the optimization of its capabilities. The activities and services of the SECS are accessible on the web site www.secs.com.es, which is continually updated. In this contribution, we will show some examples of recent projects and activities developed by the SECS such as: the edition of the Spanish Journal of Soil Science (SJSS) since 2011; books like the white book on "Tratamiento del suelo en los libros de texto de ESO y Bachillerato en España" available in http://www.secs.com.es/archivo/libro-suelo.pdf, in which the term "Soil" is analysed in many secondary school books (152) in the Spanish education system; conferences, courses, exhibitions, expositions, calendars, the comic "Vivir en el suelo" in diferent languages, and diverse material to promote and disseminate the importance of the soil to the society; and last but not least, the Multingual Soil Science Dictionary (Spanish, Catalan, Gallician and Potuguese with translations in English and French (in process)) available online: http://cit.iec.cat/GLOSECS/inici.html. The promotion of student teams for soil science contests, the SECS Award to attend the Simposio Latinoamericano de Enseñanza y Educación en Ciencia

Targeted violence against law enforcement officers.

PubMed

Schouten, Ronald; Brennan, Douglas V

2016-09-01

As highly visible representatives and guardians of society, law enforcement officers (LEOs) are very public figures. Injury or death in the line of duty, whether due to accidents or intentional acts of violence, is an occupational hazard for LEOs. Targeted assaults on police officers, referred to as ambushes in previous literature, are a particularly perplexing problem with significant implications for society at large. In the summer of 2016, the latest in a series of high-profile acts of violence aimed at police occurred, leading to increased examination of the acts themselves and their causes. This article examines recent trends in assaults on LEOs, focusing on predatory rather than reactive attacks, and applies a threat assessment model to a case of targeted violence against police. We use State of Washington v. Christopher Monfort (2015), a prosecution for arson, assault with intent to murder, and murder, as a case example, to examine how the threat assessment model, and the concepts of affective versus predatory violence help in understanding targeted violence against LEOs, assessing its risk, and managing it. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

International Youth Justice Systems: Promoting Youth Development and Alternative Approaches: A Position Paper of the Society for Adolescent Health and Medicine.

PubMed

2016-10-01

Youth incarceration is an international public health concern among developed and developing countries. Worldwide, youth are held in incarceration, detention, and other secure settings that are inappropriate for their age and developmental stages, jeopardizing their prosocial development, and reintegration into society. Youth incarceration lacks evidence and cost-effectiveness. The well-being of youth is a key indicator of the welfare of families, communities, and society at large; therefore, the Society for Adolescent Health and Medicine (SAHM) supports a paradigm shift in the role of the justice system as it relates to treatment of youth. SAHM recommends justice systems focus greater attention and resources on identifying and reducing the antecedents of high-risk and criminal behaviors, recognizing the rights and freedom of young persons, and prioritizing the well-being of youth over punitive measures that may harm and disrupt healthy adolescent development. SAHM supports the following positions: (1) incarceration is a last option for selected offenders who have committed the most serious violent crimes and are unable to remain safely in the community; (2) youth justice policies, programs, and practices affecting youth be evidence based and trauma informed; (3) youth justice policies, programs, and practices must incorporate research and ongoing program evaluation; (4) youth justice policies shall protect the privacy and dignity of children younger than 18 years; and (5) health care professionals and media will promote positive portrayals of youth in healthy relationships within their communities and reduce representations and images of youth that are negative, violent, deviant, and threatening. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Update On The Development, Testing, And Manufacture Of High Density LEU-Foil Targets For The Production Of Mo-99

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

Creasy, John T

2015-05-12

This project has the objective to reduce and/or eliminate the use of HEU in commerce. Steps in the process include developing a target testing methodology that is bounding for all Mo-99 target irradiators, establishing a maximum target LEU-foil mass, developing a LEU-foil target qualification document, developing a bounding target failure analysis methodology (failure in reactor containment), optimizing safety vs. economics (goal is to manufacture a safe, but relatively inexpensive target to offset the inherent economic disadvantage of using LEU in place of HEU), and developing target material specifications and manufacturing QC test criteria. The slide presentation is organized under themore » following topics: Objective, Process Overview, Background, Team Structure, Key Achievements, Experiment and Activity Descriptions, and Conclusions. The High Density Target project has demonstrated: approx. 50 targets irradiated through domestic and international partners; proof of concept for two front end processing methods; fabrication of uranium foils for target manufacture; quality control procedures and steps for manufacture; multiple target assembly techniques; multiple target disassembly devices; welding of targets; thermal, hydraulic, and mechanical modeling; robust target assembly parametric studies; and target qualification analysis for insertion into very high flux environment. The High Density Target project has tested and proven several technologies that will benefit current and future Mo-99 producers.« less

Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery Joint Position Statement on Open and Endovascular Surgery for Thoracic Aortic Disease.

PubMed

Appoo, Jehangir J; Bozinovski, John; Chu, Michael W A; El-Hamamsy, Ismail; Forbes, Thomas L; Moon, Michael; Ouzounian, Maral; Peterson, Mark D; Tittley, Jacques; Boodhwani, Munir

2016-06-01

In 2014, the Canadian Cardiovascular Society (CCS) published a position statement on the management of thoracic aortic disease addressing size thresholds for surgery, imaging modalities, medical therapy, and genetics. It did not address issues related to surgical intervention. This joint Position Statement on behalf of the CCS, Canadian Society of Cardiac Surgeons, and the Canadian Society for Vascular Surgery provides recommendations about thoracic aortic disease interventions, including: aortic valve repair, perfusion strategies for arch repair, extended arch hybrid reconstruction for acute type A dissection, endovascular management of arch and descending aortic aneurysms, and type B dissection. The position statement is constructed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and has been approved by the primary panel, an international secondary panel, and the CCS Guidelines Committee. Advent of endovascular technology has improved aortic surgery safety and extended the indications of minimally invasive thoracic aortic surgery. The combination of safer open surgery with endovascular treatment has improved patient outcomes in this rapidly evolving subspecialty field of cardiovascular surgery. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines for Cardiopulmonary Bypass--Temperature Management During Cardiopulmonary Bypass.

PubMed

Engelman, Richard; Baker, Robert A; Likosky, Donald S; Grigore, Alina; Dickinson, Timothy A; Shore-Lesserson, Linda; Hammon, John W

2015-08-01

In order to improve our understanding of the evidence-based literature supporting temperature management during adult cardiopulmonary bypass, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiology and the American Society of ExtraCorporeal Technology tasked the authors to conduct a review of the peer-reviewed literature, including: 1) optimal site for temperature monitoring, 2) avoidance of hyperthermia, 3) peak cooling temperature gradient and cooling rate, and 4) peak warming temperature gradient and rewarming rate. Authors adopted the American College of Cardiology/American Heart Association method for development clinical practice guidelines, and arrived at the following recommendations: No Recommendation No recommendation for a guideline is provided concerning optimal temperature for weaning from CPB due to insufficient published evidence. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Planetary Society

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

Carl Sagan, Bruce Murray and Louis Friedman founded the non-profit Planetary Society in 1979 to advance the exploration of the solar system and to continue the search for extraterrestrial life. The Society has its headquarters in Pasadena, California, but is international in scope, with 100 000 members worldwide, making it the largest space interest group in the world. The Society funds a var...

A target development program for beamhole spallation neutron sources in the megawatt range

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

Bauer, G.S.; Atchison, F.

1995-10-01

Spallation sources as an alternative to fission neutron sources have been operating successfully up to 160 kW of beam power. With the next generation of these facilities aiming at the medium power range between 0.5 and 5 MW, loads on the targets will be high enough to make present experience of little relevance. With the 0.6 MW continuous facility SINQ under construction, and a 5 MW pulsed facility (ESS) under study in Europe, a research and development program is about to be started which aimes at assessing the limits of stationary and moving solid targets and the feasibility and potentialmore » benefits of flowing liquid metal targets. Apart from theoretical work and examination of existing irradiated material, including used targets from ISIS, it is intended to take advantage of the SINQ solid rod target design to improve the relevant data base by building the target in such a way that individual rods can be equipped as irradiation capsules.« less

Society of Forensic Toxicologists, Inc.

Science.gov Websites

you interested in learning more about SOFT? Click here to download and read our brochure. The Society forensic toxicologists and those interested in the discipline for the purpose of promoting and developing

Researching Society and Culture.

ERIC Educational Resources Information Center

Seale, Clive, Ed.

This book provides theoretically informed guidance to practicing the key research methods for investigating society and culture. It is a text in both methods and methodology, in which the importance of understanding the historical, theoretical and institutional context in which particular methods have developed is stressed. The contributors of the…

Expediting SRM assay development for large-scale targeted proteomics experiments

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

Wu, Chaochao; Shi, Tujin; Brown, Joseph N.

2014-08-22

Due to their high sensitivity and specificity, targeted proteomics measurements, e.g. selected reaction monitoring (SRM), are becoming increasingly popular for biological and translational applications. Selection of optimal transitions and optimization of collision energy (CE) are important assay development steps for achieving sensitive detection and accurate quantification; however, these steps can be labor-intensive, especially for large-scale applications. Herein, we explored several options for accelerating SRM assay development evaluated in the context of a relatively large set of 215 synthetic peptide targets. We first showed that HCD fragmentation is very similar to CID in triple quadrupole (QQQ) instrumentation, and by selection ofmore » top six y fragment ions from HCD spectra, >86% of top transitions optimized from direct infusion on QQQ instrument are covered. We also demonstrated that the CE calculated by existing prediction tools was less accurate for +3 precursors, and a significant increase in intensity for transitions could be obtained using a new CE prediction equation constructed from the present experimental data. Overall, our study illustrates the feasibility of expediting the development of larger numbers of high-sensitivity SRM assays through automation of transitions selection and accurate prediction of optimal CE to improve both SRM throughput and measurement quality.« less

Emerging targets for addiction neuropharmacology: From mechanisms to therapeutics.

PubMed

Ubaldi, Massimo; Cannella, Nazzareno; Ciccocioppo, Roberto

2016-01-01

Drug abuse represents a considerable burden of disease and has enormous economic impacts on societies. Over the years, few medications have been developed for clinical use. Their utilization is endowed with several limitations, including partial efficacy or significant side effects. On the other hand, the successful advancement of these compounds provides an important proof of concept for the feasibility of drug development programs in addiction. In recent years, a wealth of information has been generated on the psychological mechanisms, genetic or epigenetic predisposing factors, and neurobiological adaptations induced by drug consumption that interact with each other to contribute to disease progression. It is now clear that addiction develops through phases, from initial recreational use to excessive consumption and compulsive drug seeking, with a shift from positive to negative reinforcement driving motivated behaviors. A greater understanding of these mechanisms has opened new vistas in drug development programs. Researchers' attention has been shifted from investigation of classical targets associated with reward to biological substrates responsible for negative reinforcement, impulse loss of control, and maladaptive mechanisms resulting from protracted drug use. From this research, several new biological targets for the development of innovative therapies have started to emerge. This chapter offers an overview of targets currently under scrutiny for the development of new medications for addiction. This work is not exhaustive but rather it provides a few examples of how this research has advanced in recent years by virtue of studies carried out in our laboratory. © 2016 Elsevier B.V. All rights reserved.

Stabilization of exosome-targeting peptides via engineered glycosylation.

PubMed

Hung, Michelle E; Leonard, Joshua N

2015-03-27

Exosomes are secreted extracellular vesicles that mediate intercellular transfer of cellular contents and are attractive vehicles for therapeutic delivery of bimolecular cargo such as nucleic acids, proteins, and even drugs. Efficient exosome-mediated delivery in vivo requires targeting vesicles for uptake by specific recipient cells. Although exosomes have been successfully targeted to several cellular receptors by displaying peptides on the surface of the exosomes, identifying effective exosome-targeting peptides for other receptors has proven challenging. Furthermore, the biophysical rules governing targeting peptide success remain poorly understood. To evaluate one factor potentially limiting exosome delivery, we investigated whether peptides displayed on the exosome surface are degraded during exosome biogenesis, for example by endosomal proteases. Indeed, peptides fused to the N terminus of exosome-associated transmembrane protein Lamp2b were cleaved in samples derived from both cells and exosomes. To suppress peptide loss, we engineered targeting peptide-Lamp2b fusion proteins to include a glycosylation motif at various positions. Introduction of this glycosylation motif both protected the peptide from degradation and led to an increase in overall Lamp2b fusion protein expression in both cells and exosomes. Moreover, glycosylation-stabilized peptides enhanced targeted delivery of exosomes to neuroblastoma cells, demonstrating that such glycosylation does not ablate peptide-target interactions. Thus, we have identified a strategy for achieving robust display of targeting peptides on the surface of exosomes, which should facilitate the evaluation and development of new exosome-based therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Aging Perceptions in Tsimane' Amazonian Forager-Farmers Compared With Two Industrialized Societies.

PubMed

Sorokowski, Piotr; Sorokowska, Agnieszka; Frackowiak, Tomasz; Löckenhoff, Corinna E

2017-07-01

Cross-cultural studies suggest that aging attitudes show some variation across societies, but this evidence is mostly drawn from industrialized settings. The limited research record on pre-industrial societies is largely qualitative in nature. The present study targeted this gap by adapting an existing multidimensional measure of aging attitudes for use in traditional populations and administering it to samples from one traditional society and two industrialized societies. We administered the adapted multidimensional measure of aging attitudes to samples from one traditional society (Tsimane' Amazonian forager-farmers in Bolivia, n = 90) and two industrialized societies (the United States, n = 91, and Poland, n = 100). Across societies, aging perceptions were more favorable for respect and wisdom than for other domains of functioning, and women were perceived to be aging less favorably. Further, the Tsimane' reported more positive aging perceptions than the U.S. and Polish samples, especially with regard to memory functioning. Within the Tsimane' sample, there was no evidence of an influence of acculturation on aging perceptions. The present study contributed to our understanding of cross-cultural differences in aging attitudes. Theoretical implications and directions for future research are discussed. © The Author 2015. 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.

Development of a Rickettsia bellii-Specific TaqMan Assay Targeting the Citrate Synthase Gene.

PubMed

Hecht, Joy A; Allerdice, Michelle E J; Krawczak, Felipe S; Labruna, Marcelo B; Paddock, Christopher D; Karpathy, Sandor E

2016-11-01

Rickettsia bellii is a rickettsial species of unknown pathogenicity that infects argasid and ixodid ticks throughout the Americas. Many molecular assays used to detect spotted fever group (SFG) Rickettsia species do not detect R. bellii, so that infection with this bacterium may be concealed in tick populations when assays are used that screen specifically for SFG rickettsiae. We describe the development and validation of a R. bellii-specific, quantitative, real-time PCR TaqMan assay that targets a segment of the citrate synthase (gltA) gene. The specificity of this assay was validated against a panel of DNA samples that included 26 species of Rickettsia, Orientia, Ehrlichia, Anaplasma, and Bartonella, five samples of tick and human DNA, and DNA from 20 isolates of R. bellii, including 11 from North America and nine from South America. A R. bellii control plasmid was constructed, and serial dilutions of the plasmid were used to determine the limit of detection of the assay to be one copy per 4 µl of template DNA. This assay can be used to better determine the role of R. bellii in the epidemiology of tick-borne rickettsioses in the Western Hemisphere. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Using a participatory four-step protocol to develop culturally targeted cancer education brochures.

PubMed

Kulukulualani, Manny; Braun, Kathryn L; Tsark, JoAnn U

2008-10-01

Native Hawaiians have a high cancer burden, but few culturally targeted cancer education brochures exist. The authors followed a participatory four-step protocol, involving more than 200 health providers and clients, to develop and test culturally targeted brochures on skin, oral, cervical, prostate, and testicular cancers. The final products featured Hawaiian faces, scenes, words, and activities. They proved more attractive than existing materials, in particular to younger Hawaiians, and posttests suggested good comprehension of intended messages. This protocol may have application in other communities that want to develop brochures that are attractive, acceptable, readable, and useful to minority clients and their providers.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for Multimodality Imaging in Valvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Doherty, John U; Kort, Smadar; Mehran, Roxana; Schoenhagen, Paul; Soman, Prem; Dehmer, Greg J; Doherty, John U; Schoenhagen, Paul; Amin, Zahid; Bashore, Thomas M; Boyle, Andrew; Calnon, Dennis A; Carabello, Blase; Cerqueira, Manuel D; Conte, John; Desai, Milind; Edmundowicz, Daniel; Ferrari, Victor A; Ghoshhajra, Brian; Mehrotra, Praveen; Nazarian, Saman; Reece, T Brett; Tamarappoo, Balaji; Tzou, Wendy S; Wong, John B; Doherty, John U; Dehmer, Gregory J; Bailey, Steven R; Bhave, Nicole M; Brown, Alan S; Daugherty, Stacie L; Dean, Larry S; Desai, Milind Y; Duvernoy, Claire S; Gillam, Linda D; Hendel, Robert C; Kramer, Christopher M; Lindsay, Bruce D; Manning, Warren J; Mehrotra, Praveen; Patel, Manesh R; Sachdeva, Ritu; Wann, L Samuel; Winchester, David E; Wolk, Michael J; Allen, Joseph M

2018-04-01

This document is 1 of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. This document addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas the second, companion document addresses this topic with regard to structural heart disease. Although there is clinical overlap, the documents addressing valvular and structural heart disease are published separately, albeit with a common structure. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of valvular and structural heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association guidelines. A separate, independent rating panel scored the 92 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will

Targeting the Cytochrome bc1 Complex of Leishmania Parasites for Discovery of Novel Drugs.

PubMed

Ortiz, Diana; Forquer, Isaac; Boitz, Jan; Soysa, Radika; Elya, Carolyn; Fulwiler, Audrey; Nilsen, Aaron; Polley, Tamsen; Riscoe, Michael K; Ullman, Buddy; Landfear, Scott M

2016-08-01

Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L. donovani, with 50% inhibitory concentrations (IC50s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome bc1 is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Development of a Ne gas target for {sup 22}Na production by proton irradiation

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

Mandal, Bidhan Ch., E-mail: mechbidhan@gmail.com; Pal, Gautam; Barua, Luna

2016-03-15

The article presents the design and development of a neon gas target for the production of {sup 22}Na using a proton beam from the room temperature cyclotron in Variable Energy Cyclotron Centre, Kolkata. The target design is made to handle a beam power of 85 W (17 MeV, 5 μA). The design is based on simulation using the computer code FLUKA for the beam dump and CFD-CFX for target cooling. The target has been successfully used for the production of {sup 22}Na in a 6 day long 17 MeV, 5 μA proton irradiation run.

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures.

PubMed

Rutter, Matthew D; Senore, Carlo; Bisschops, Raf; Domagk, Dirk; Valori, Roland; Kaminski, Michal F; Spada, Cristiano; Bretthauer, Michael; Bennett, Cathy; Bellisario, Cristina; Minozzi, Silvia; Hassan, Cesare; Rees, Colin; Dinis-Ribeiro, Mário; Hucl, Tomas; Ponchon, Thierry; Aabakken, Lars; Fockens, Paul

2016-02-01

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision. ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients.

Targeted Quantification of Isoforms of a Thylakoid-Bound Protein: MRM Method Development.

PubMed

Bru-Martínez, Roque; Martínez-Márquez, Ascensión; Morante-Carriel, Jaime; Sellés-Marchart, Susana; Martínez-Esteso, María José; Pineda-Lucas, José Luis; Luque, Ignacio

2018-01-01

Targeted mass spectrometric methods such as selected/multiple reaction monitoring (SRM/MRM) have found intense application in protein detection and quantification which competes with classical immunoaffinity techniques. It provides a universal procedure to develop a fast, highly specific, sensitive, accurate, and cheap methodology for targeted detection and quantification of proteins based on the direct analysis of their surrogate peptides typically generated by tryptic digestion. This methodology can be advantageously applied in the field of plant proteomics and particularly for non-model species since immunoreagents are scarcely available. Here, we describe the issues to take into consideration in order to develop a MRM method to detect and quantify isoforms of the thylakoid-bound protein polyphenol oxidase from the non-model and database underrepresented species Eriobotrya japonica Lindl.

Inequality in nature and society

PubMed Central

Scheffer, Marten; van Bavel, Bas; van de Leemput, Ingrid A.; van Nes, Egbert H.

2017-01-01

Most societies are economically dominated by a small elite, and similarly, natural communities are typically dominated by a small fraction of the species. Here we reveal a strong similarity between patterns of inequality in nature and society, hinting at fundamental unifying mechanisms. We show that chance alone will drive 1% or less of the community to dominate 50% of all resources in situations where gains and losses are multiplicative, as in returns on assets or growth rates of populations. Key mechanisms that counteract such hyperdominance include natural enemies in nature and wealth-equalizing institutions in society. However, historical research of European developments over the past millennium suggests that such institutions become ineffective in times of societal upscaling. A corollary is that in a globalizing world, wealth will inevitably be appropriated by a very small fraction of the population unless effective wealth-equalizing institutions emerge at the global level. PMID:29183971

The Pim kinases: new targets for drug development.

PubMed

Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis

2011-12-01

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice Guideline.

PubMed

Gordon, Catherine M; Ackerman, Kathryn E; Berga, Sarah L; Kaplan, Jay R; Mastorakos, George; Misra, Madhusmita; Murad, M Hassan; Santoro, Nanette F; Warren, Michelle P

2017-05-01

The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society. To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA). The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline. FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation. Copyright © 2017 Endocrine Society

An updated history of the Teratology Society.

PubMed

Shepard, Thomas H; Barr, Mason; Brent, Robert L; Hendrickx, Andrew; Kochhar, Devendra; Oakley, Godfrey; Scott, William J; Rogers, John M

2010-05-01

The 49-year history of the Teratology Society is reviewed. An abbreviated history is outlined in table form, with listings of the Warkany Lectures, the Continuing Education Courses, and officers of the society. The original article was updated to include the years 2000 to 2010. A year-by-year description of the events is given, including the scientific and social content of the annual meetings and changes in the business of the society, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research areas of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over successive periods. A significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The society's development is compared to that of a human, and the question was asked by Shephard et al. (2000): Have we reached the maturational stage of old age or senescence, or is the society still maturing gracefully? This question needs further discussion by all the members. By 2010, many positive changes are happening to revitalize the society. During the past 50 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as other prenatal exposures. We are now taking advantage of advances in many fields to begin shaping the Teratology Society of the 21st century. We must now engage in political battles to obtain the resources needed to conduct further research and to implement prevention programs, as well as to provide care and rehabilitation for persons with birth defects. 2010 Wiley-Liss, Inc.

[Cooperation between professional association and scientific society].

PubMed

Schroeder, A; Hakenberg, O W

2013-08-01

Developments in health economics, urological sciences and social as well as demographic conditions pose numerous problems for the field of urology. In order to solve these problems a close cooperation between the professional association and the scientific society are needed which at first sight seem to have very different interests. The increasing complexity and interdependency in all areas of the healthcare system make a simple separation of interests between the scientific society and the professional association impossible. The Professional Association of German Urologists and the German Society of Urology have acknowledged this situation for many years and have intensified their close collaboration.

AAVSO Target Tool: A Web-Based Service for Tracking Variable Star Observations (Abstract)

NASA Astrophysics Data System (ADS)

Burger, D.; Stassun, K. G.; Barnes, C.; Kafka, S.; Beck, S.; Li, K.

2018-06-01

(Abstract only) The AAVSO Target Tool is a web-based interface for bringing stars in need of observation to the attention of AAVSOís network of amateur and professional astronomers. The site currently tracks over 700 targets of interest, collecting data from them on a regular basis from AAVSOís servers and sorting them based on priority. While the target tool does not require a login, users can obtain visibility times for each target by signing up and entering a telescope location. Other key features of the site include filtering by AAVSO observing section, sorting by different variable types, formatting the data for printing, and exporting the data to a CSV file. The AAVSO Target Tool builds upon seven years of experience developing web applications for astronomical data analysis, most notably on Filtergraph (Burger, D., et al. 2013, Astronomical Data Analysis Software and Systems XXII, Astronomical Society of the Pacific, San Francisco, 399), and is built using the web2py web framework based on the python programming language. The target tool is available at http://filtergraph.com/aavso.

Science, Technology, Society: Opportunities.

ERIC Educational Resources Information Center

Lux, Donald G., Ed.

1992-01-01

Recognizing the potential pitfalls resulting from a lack of human foresight lies at the heart of the science-technology-society (STS) movement. This issue of "Theory Into Practice" is the second part of a two-part series that examines the educational opportunities arising as educators attempt to develop student understanding of STS. In the first…

Science, Sex, and Society.

ERIC Educational Resources Information Center

Kammer, Ann E.; And Others

This manual is a compilation of articles about women who pursue careers in science and the multiple sources and forms of discouragement they encounter. It is intended as a guide when developing courses that explore career opportunities and pressures for women in science and a resource in understanding the interaction between science, society, and…

Development of tumor-targeted near infrared probes for fluorescence guided surgery.

PubMed

Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

2013-06-19

Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

Women and the Information Society: Barriers and Participation.

ERIC Educational Resources Information Center

Goulding, Anne; Spacey, Rachel

The development and use of communication and information technologies, notably the Internet, have stimulated huge changes in the organization of work and daily life in Europe, leading to a process of transition from the "Industrial" to the "Information" society. The ultimate aim of the Information Society should be the…

Longevity suppresses conflict in animal societies

PubMed Central

Port, Markus; Cant, Michael A.

2013-01-01

Models of social conflict in animal societies generally assume that within-group conflict reduces the value of a communal resource. For many animals, however, the primary cost of conflict is increased mortality. We develop a simple inclusive fitness model of social conflict that takes this cost into account. We show that longevity substantially reduces the level of within-group conflict, which can lead to the evolution of peaceful animal societies if relatedness among group members is high. By contrast, peaceful outcomes are never possible in models where the primary cost of social conflict is resource depletion. Incorporating mortality costs into models of social conflict can explain why many animal societies are so remarkably peaceful despite great potential for conflict. PMID:24088564

Modeling to Support the Development of Habitat Targets for Piping Plovers on the Missouri River

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

Buenau, Kate E.

2015-05-05

Report on modeling and analyses done in support of developing quantative sandbar habitat targets for piping plovers, including assessment of reference, historical, dams present but not operated, and habitat construction calibrated to meet population viability targets.

Russian Language Teaching and Public Education in Soviet Kirgizia: An Excerpt from "Public Education in Developed Socialist Society."

ERIC Educational Resources Information Center

Karypkulov, A. K.

1985-01-01

The two chapters translated here from the book "Public Education in Developed Socialist Society" discuss (1) the teaching of the Russian language in the republic of Kirgizia (USSR) and (2) the role that education must play in incorporating non-Russian nationalities such as the Kirgiz people into a common, Soviet national culture. (RM)

SWATHtoMRM: Development of High-Coverage Targeted Metabolomics Method Using SWATH Technology for Biomarker Discovery.

PubMed

Zha, Haihong; Cai, Yuping; Yin, Yandong; Wang, Zhuozhong; Li, Kang; Zhu, Zheng-Jiang

2018-03-20

The complexity of metabolome presents a great analytical challenge for quantitative metabolite profiling, and restricts the application of metabolomics in biomarker discovery. Targeted metabolomics using multiple-reaction monitoring (MRM) technique has excellent capability for quantitative analysis, but suffers from the limited metabolite coverage. To address this challenge, we developed a new strategy, namely, SWATHtoMRM, which utilizes the broad coverage of SWATH-MS technology to develop high-coverage targeted metabolomics method. Specifically, SWATH-MS technique was first utilized to untargeted profile one pooled biological sample and to acquire the MS 2 spectra for all metabolites. Then, SWATHtoMRM was used to extract the large-scale MRM transitions for targeted analysis with coverage as high as 1000-2000 metabolites. Then, we demonstrated the advantages of SWATHtoMRM method in quantitative analysis such as coverage, reproducibility, sensitivity, and dynamic range. Finally, we applied our SWATHtoMRM approach to discover potential metabolite biomarkers for colorectal cancer (CRC) diagnosis. A high-coverage targeted metabolomics method with 1303 metabolites in one injection was developed to profile colorectal cancer tissues from CRC patients. A total of 20 potential metabolite biomarkers were discovered and validated for CRC diagnosis. In plasma samples from CRC patients, 17 out of 20 potential biomarkers were further validated to be associated with tumor resection, which may have a great potential in assessing the prognosis of CRC patients after tumor resection. Together, the SWATHtoMRM strategy provides a new way to develop high-coverage targeted metabolomics method, and facilitates the application of targeted metabolomics in disease biomarker discovery. The SWATHtoMRM program is freely available on the Internet ( http://www.zhulab.cn/software.php ).

Target size matters: target errors contribute to the generalization of implicit visuomotor learning.

PubMed

Reichenthal, Maayan; Avraham, Guy; Karniel, Amir; Shmuelof, Lior

2016-08-01

The process of sensorimotor adaptation is considered to be driven by errors. While sensory prediction errors, defined as the difference between the planned and the actual movement of the cursor, drive implicit learning processes, target errors (e.g., the distance of the cursor from the target) are thought to drive explicit learning mechanisms. This distinction was mainly studied in the context of arm reaching tasks where the position and the size of the target were constant. We hypothesize that in a dynamic reaching environment, where subjects have to hit moving targets and the targets' dynamic characteristics affect task success, implicit processes will benefit from target errors as well. We examine the effect of target errors on learning of an unnoticed perturbation during unconstrained reaching movements. Subjects played a Pong game, in which they had to hit a moving ball by moving a paddle controlled by their hand. During the game, the movement of the paddle was gradually rotated with respect to the hand, reaching a final rotation of 25°. Subjects were assigned to one of two groups: The high-target error group played the Pong with a small ball, and the low-target error group played with a big ball. Before and after the Pong game, subjects performed open-loop reaching movements toward static targets with no visual feedback. While both groups adapted to the rotation, the postrotation reaching movements were directionally biased only in the small-ball group. This result provides evidence that implicit adaptation is sensitive to target errors. Copyright © 2016 the American Physiological Society.

African civil society initiatives to drive a biobanking, biosecurity and infrastructure development agenda in the wake of the West African Ebola outbreak

PubMed Central

Abayomi, Akin; Gevao, Sahr; Conton, Brian; Deblasio, Pasquale; Katz, Rebecca

2016-01-01

This paper describes the formation of a civil society consortium, spurred to action by frustration over the Ebola crises, to facilitate the development of infrastructure and frameworks including policy development to support a harmonized, African approach to health crises on the continent. The Global Emerging Pathogens Treatment Consortium, or GET, is an important example of how African academics, scientists, clinicians and civil society have come together to initiate policy research, multilevel advocacy and implementation of initiatives aimed at building African capacity for timely and effective mitigations strategies against emerging infectious and neglected pathogens, with a focus on biobanking and biosecurity. The consortium has been able to establish it self as a leading voice, drawing attention to scientific infrastructure gaps, the importance of cultural sensitivities, and the power of community engagement. The GET consortium demonstrates how civil society can work together, encourage government engagement and strengthen national and regional efforts to build capacity. PMID:28154625

African civil society initiatives to drive a biobanking, biosecurity and infrastructure development agenda in the wake of the West African Ebola outbreak.

PubMed

Abayomi, Akin; Gevao, Sahr; Conton, Brian; Deblasio, Pasquale; Katz, Rebecca

2016-01-01

This paper describes the formation of a civil society consortium, spurred to action by frustration over the Ebola crises, to facilitate the development of infrastructure and frameworks including policy development to support a harmonized, African approach to health crises on the continent. The Global Emerging Pathogens Treatment Consortium, or GET, is an important example of how African academics, scientists, clinicians and civil society have come together to initiate policy research, multilevel advocacy and implementation of initiatives aimed at building African capacity for timely and effective mitigations strategies against emerging infectious and neglected pathogens, with a focus on biobanking and biosecurity. The consortium has been able to establish it self as a leading voice, drawing attention to scientific infrastructure gaps, the importance of cultural sensitivities, and the power of community engagement. The GET consortium demonstrates how civil society can work together, encourage government engagement and strengthen national and regional efforts to build capacity.

New developments in anti-malarial target candidate and product profiles.

PubMed

Burrows, Jeremy N; Duparc, Stephan; Gutteridge, Winston E; Hooft van Huijsduijnen, Rob; Kaszubska, Wiweka; Macintyre, Fiona; Mazzuri, Sébastien; Möhrle, Jörg J; Wells, Timothy N C

2017-01-13

A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

The development of targeted new agents to improve the outcome for children with leukemia.

PubMed

Bautista, Francisco; Van der Lugt, Jasper; Kearns, Pamela R; Mussai, Francis J; Zwaan, C Michel; Moreno, Lucas

2016-11-01

Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias. A comprehensive description of the biological background, adult data and early clinical trials in pediatrics is provided. Expert opinion: Clinical trials are the way to evaluate new agents in pediatric cancer. The development of new drugs in pediatric leukemia must be preceded by a solid biological rationale. Agents in development exploit all possible vulnerabilities of leukemic cells. Drugs targeting cell surface antigens, intracellular signaling pathways and cell cycle inhibitors or epigenetic regulators are most prominent. Major advances have occurred thanks to new developments in engineering leading to optimized molecules such as anti-CD19 bi-specific T-cell engagers (e.g. blinatumomab) and antibody-drug conjugates. The integration of new-targeted therapies in pediatric chemotherapy-based regimens will lead to improved outcomes.

Using a Participatory Four-Step Protocol to Develop Culturally Targeted Cancer Education Brochures

PubMed Central

Kulukulualani, Manny; Braun, Kathryn L.; Tsark, JoAnn U.

2010-01-01

Native Hawaiians have a high cancer burden, but few culturally targeted cancer education brochures exist. The authors followed a participatory four-step protocol, involving more than 200 health providers and clients, to develop and test culturally targeted brochures on skin, oral, cervical, prostate, and testicular cancers. The final products featured Hawaiian faces, scenes, words, and activities. They proved more attractive than existing materials, in particular to younger Hawaiians, and posttests suggested good comprehension of intended messages. This protocol may have application in other communities that want to develop brochures that are attractive, acceptable, readable, and useful to minority clients and their providers. PMID:18353907

Targeting the Hippo signalling pathway for cancer treatment.

PubMed

Nakatani, Keisuke; Maehama, Tomohiko; Nishio, Miki; Goto, Hiroki; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira

2017-03-01

The Hippo signalling pathway monitors cell-cell contact and external factors that shape tissue structure. In mice, tumourigenesis and developmental abnormalities are common consequences of dysregulated Hippo signalling. Expression of Hippo pathway components is also frequently altered in human tumours and correlates with poor prognosis and reduced patient survival. Thus, the Hippo pathway is an attractive anti-cancer target. Here, we provide an overview of the function and regulation of Hippo signalling components and summarize progress to date on the development of agents able to regulate Hippo signalling for cancer therapy. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Inhibition of protein synthesis and malaria parasite development by drug targeting of methionyl-tRNA synthetases.

PubMed

Hussain, Tahir; Yogavel, Manickam; Sharma, Amit

2015-04-01

Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites. Two known bacterial MRS inhibitors, REP3123 and REP8839, hampered Plasmodium growth very effectively in the early and late stages of parasite development. Small-molecule drug-like libraries were screened against modeled PfMRS structures, and several "hit" compounds showed significant effects on parasite growth. We then tested the effects of the hit compounds on protein translation by labeling nascent proteins with (35)S-labeled cysteine and methionine. Three of the tested compounds reduced protein synthesis and also blocked parasite growth progression from the ring stage to the trophozoite stage. Drug docking studies suggested distinct modes of binding for the three compounds, compared with the enzyme product methionyl adenylate. Therefore, this study provides new targets (PfMRSs) and hit compounds that can be explored for development as antimalarial drugs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Towards E-Society Policy Interoperability

NASA Astrophysics Data System (ADS)

Iannella, Renato

The move towards the Policy-Oriented Web is destined to provide support for policy expression and management in the core web layers. One of the most promising areas that can drive this new technology adoption is e-Society communities. With so much user-generated content being shared by these social networks, there is the real danger that the implicit sharing rules that communities have developed over time will be lost in translation in the new digital communities. This will lead to a corresponding loss in confidence in e-Society sites. The Policy-Oriented Web attempts to turn the implicit into the explicit with a common framework for policy language interoperability and awareness. This paper reports on the policy driving factors from the Social Networks experiences using real-world use cases and scenarios. In particular, the key functions of policy-awareness - for privacy, rights, and identity - will be the driving force that enables the e-Society to appreciate new interoperable policy regimes.

An official American thoracic society workshop report: developing performance measures from clinical practice guidelines.

PubMed

Kahn, Jeremy M; Gould, Michael K; Krishnan, Jerry A; Wilson, Kevin C; Au, David H; Cooke, Colin R; Douglas, Ivor S; Feemster, Laura C; Mularski, Richard A; Slatore, Christopher G; Wiener, Renda Soylemez

2014-05-01

Many health care performance measures are either not based on high-quality clinical evidence or not tightly linked to patient-centered outcomes, limiting their usefulness in quality improvement. In this report we summarize the proceedings of an American Thoracic Society workshop convened to address this problem by reviewing current approaches to performance measure development and creating a framework for developing high-quality performance measures by basing them directly on recommendations from well-constructed clinical practice guidelines. Workshop participants concluded that ideally performance measures addressing care processes should be linked to clinical practice guidelines that explicitly rate the quality of evidence and the strength of recommendations, such as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. Under this framework, process-based performance measures would only be developed from strong recommendations based on high- or moderate-quality evidence. This approach would help ensure that clinical processes specified in performance measures are both of clear benefit to patients and supported by strong evidence. Although this approach may result in fewer performance measures, it would substantially increase the likelihood that quality-improvement programs based on these measures actually improve patient care.

Socio-technical Issues for Ubiquitous Information Society in 2010

NASA Astrophysics Data System (ADS)

Funabashi, Motohisa; Homma, Koichi; Sasaki, Toshiro; Sato, Yoshinori; Kido, Kunihiko; Fukumoto, Takashi; Yano, Koujin

Impact of the ubiquitous information technology on our society is so significant that directing technological development and preparing institutional apparatus are quite important and urgent. The present paper elaborates, with the efforts by both humanity and engineering disciplines, to find out the socio-technical issues of ubiquitous information society in 2010 by inspecting social implications of emerging technology as well as social expectations. In order to deliberate the issues, scenarios are developed that describes possible life in ubiquitous information society. The derived issues cover integrating information technology and human body, producing smart sharable environment, protecting individual rights, fostering new service business, and forming community.

Development of a Multi-Target Contingency Management Intervention for HIV Positive Substance Users.

PubMed

Stitzer, Maxine; Calsyn, Donald; Matheson, Timothy; Sorensen, James; Gooden, Lauren; Metsch, Lisa

2017-01-01

Contingency management (CM) interventions generally target a single behavior such as attendance or drug use. However, disease outcomes are mediated by complex chains of both healthy and interfering behaviors enacted over extended periods of time. This paper describes a novel multi-target contingency management (CM) program developed for use with HIV positive substance users enrolled in a CTN multi-site study (0049 Project HOPE). Participants were randomly assigned to usual care (referral to health care and SUD treatment) or 6-months strength-based patient navigation interventions with (PN+CM) or without (PN only) the CM program. Primary outcome of the trial was viral load suppression at 12-months post-randomization. Up to $1160 could be earned over 6 months under escalating schedules of reinforcement. Earnings were divided among eight CM targets; two PN-related (PN visits; paperwork completion; 26% of possible earnings), four health-related (HIV care visits, lab blood draw visits, medication check, viral load suppression; 47% of possible earnings) and two drug-use abatement (treatment entry; submission of drug negative UAs; 27% of earnings). The paper describes rationale for selection of targets, pay amounts and pay schedules. The CM program was compatible with and fully integrated into the PN intervention. The study design will allow comparison of behavioral and health outcomes for participants receiving PN with and without CM; results will inform future multi-target CM development. Copyright © 2016 Elsevier Inc. All rights reserved.

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

ERIC Educational Resources Information Center

Shafiq, M. Najeeb

2009-01-01

Targeted educational voucher schemes [TEVS] are often proposed for poor children in developing countries. This article explores the design of an effective TEVS using three policy instruments: regulation, support services, and finance. The regulation design addresses the rules that must be adhered to by participating households, children, and…

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics.

PubMed

Bertsch, Andreas; Jung, Stephan; Zerck, Alexandra; Pfeifer, Nico; Nahnsen, Sven; Henneges, Carsten; Nordheim, Alfred; Kohlbacher, Oliver

2010-05-07

Targeted proteomic approaches such as multiple reaction monitoring (MRM) overcome problems associated with classical shotgun mass spectrometry experiments. Developing MRM quantitation assays can be time consuming, because relevant peptide representatives of the proteins must be found and their retention time and the product ions must be determined. Given the transitions, hundreds to thousands of them can be scheduled into one experiment run. However, it is difficult to select which of the transitions should be included into a measurement. We present a novel algorithm that allows the construction of MRM assays from the sequence of the targeted proteins alone. This enables the rapid development of targeted MRM experiments without large libraries of transitions or peptide spectra. The approach relies on combinatorial optimization in combination with machine learning techniques to predict proteotypicity, retention time, and fragmentation of peptides. The resulting potential transitions are scheduled optimally by solving an integer linear program. We demonstrate that fully automated construction of MRM experiments from protein sequences alone is possible and over 80% coverage of the targeted proteins can be achieved without further optimization of the assay.

76 FR 6143 - Draft Guidance for Industry on “Target Animal Safety and Effectiveness Protocol Development and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

...] Draft Guidance for Industry on ``Target Animal Safety and Effectiveness Protocol Development and...) entitled ``Target Animal Safety and Effectiveness Protocol Development and Submission.'' The purpose of... Center for Veterinary Medicine (CVM), Office of New Animal Drug Evaluation (ONADE), to reduce the time to...

In Situ Gene Therapy via AAV-CRISPR-Cas9-Mediated Targeted Gene Regulation.

PubMed

Moreno, Ana M; Fu, Xin; Zhu, Jie; Katrekar, Dhruva; Shih, Yu-Ru V; Marlett, John; Cabotaje, Jessica; Tat, Jasmine; Naughton, John; Lisowski, Leszek; Varghese, Shyni; Zhang, Kang; Mali, Prashant

2018-04-25

Development of efficacious in vivo delivery platforms for CRISPR-Cas9-based epigenome engineering will be critical to enable the ability to target human diseases without permanent modification of the genome. Toward this, we utilized split-Cas9 systems to develop a modular adeno-associated viral (AAV) vector platform for CRISPR-Cas9 delivery to enable the full spectrum of targeted in situ gene regulation functionalities, demonstrating robust transcriptional repression (up to 80%) and activation (up to 6-fold) of target genes in cell culture and mice. We also applied our platform for targeted in vivo gene-repression-mediated gene therapy for retinitis pigmentosa. Specifically, we engineered targeted repression of Nrl, a master regulator of rod photoreceptor determination, and demonstrated Nrl knockdown mediates in situ reprogramming of rod cells into cone-like cells that are resistant to retinitis pigmentosa-specific mutations, with concomitant prevention of secondary cone loss. Furthermore, we benchmarked our results from Nrl knockdown with those from in vivo Nrl knockout via gene editing. Taken together, our AAV-CRISPR-Cas9 platform for in vivo epigenome engineering enables a robust approach to target disease in a genomically scarless and potentially reversible manner. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Chemical genetics-based development of small molecules targeting hepatitis C virus.

PubMed

Jin, Guanghai; Lee, Jisu; Lee, Kyeong

2017-09-01

Hepatitis C virus (HCV) infection is a major worldwide problem that has emerged as one of the most significant diseases affecting humans. There are currently no vaccines or efficient therapies without side effects, despite today's advanced medical technology. Currently, the common therapy for most patients (i.e. genotype 1) is combination of HCV-specific direct-acting antivirals (DAAs). Up to 2011, the standard of care (SOC) was a combination of peg-IFNα with ribavirin (RBV). After approval of NS3/4A protease inhibitor, SOC was peg-IFNα and RBV with either the first-generation DAAs boceprevir or telaprevir. In the past several years, various novel small molecules have been discovered and some of them (i.e., HCV polymerase, protease, helicase and entry inhibitors) have undergone clinical trials. Between 2013 and 2016, the second-generation DAA drugs simeprevir, asunaprevir, daclatasvir, dasabuvir, sofosbuvir, and elbasvir were approved, as well as the combinational drugs Harvoni ® , Zepatier ® , Technivie ® , and Epclusa ® . A number of reviews have been recently published describing the structure-activity relationship (SAR) in the development of HCV inhibitors and outlining current therapeutic approaches to hepatitis C infection. Target identification involves studying a drug's mechanism of action (MOA), and a variety of target identification methods have been developed in the past few years. Chemical biology has emerged as a powerful tool for studying biological processes using small molecules. The use of chemical genetic methods is a valuable strategy for studying the molecular mechanisms of the viral lifecycle and screening for anti-viral agents. Two general screening approaches have been employed: forward and reverse chemical genetics. This review reveals information on the small molecules in HCV drug discovery by using chemical genetics for targeting the HCV protein and describes successful examples of targets identified with these methods.

Foundation and progress of Japanese society of toxicologic pathology*.

PubMed

Konishi, Yoichi; Enomoto, Makoto; Hayashi, Yuzo

2011-03-01

The Japanese Society of Toxicologic Pathology (JSTP) has a differing conceptual framework from the Japanese Society of Pathology (JSP) and Japanese Society of Toxicology (JST) and was founded in 1985 by the leadership of late Dr. Yasukazu Nishiyama with the cooperation of several founding members and the support of JSP. The aim of the JSTP is to improve the human and animal health using an interdisciplinary scientific approach based on pathology and toxicology. In its development as a professional society, the JSTP has established society rules and activities. The JSTP has grown in terms of membership and financial aspects and is now recognized not only domestically but also internationally as a well-organized scientific society. To maintain the high professional standard and visibility of JSTP, we here provide the historical background of the society as a basis for current members to contribute to the continued improvement of our scientific organization.

The development of high-performance alkali-hybrid polarized He 3 targets for electron scattering

DOE PAGES

Singh, Jaideep T.; Dolph, Peter A.M.; Tobias, William Al; ...

2015-05-01

We present the development of high-performance polarized ³He targets for use in electron scattering experiments that utilize the technique of alkali-hybrid spin-exchange optical pumping. We include data obtained during the characterization of 24 separate target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. The results presented here document dramatic improvement in the performance of polarized ³He targets, as well as the target properties and operating parameters that made those improvements possible. Included in our measurements were determinations of the so-called X-factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable ³He polarization to well under 100%. The presence of this spin-relaxation mechanism was clearly evident in our data. We also present results from a simulation of the alkali-hydrid spin-exchange optical pumping process that was developed to provide guidance in the design of these targets. Good agreement with actual performance was obtained by including details such as off-resonant optical pumping. Now benchmarked against experimental data, the simulation is useful for the design of future targets. Included in our results is a measurement of the K- ³He spin-exchange rate coefficientmore » $$k^\\mathrm{K}_\\mathrm{se} = \\left ( 7.46 \\pm 0.62 \\right )\\!\\times\\!10^{-20}\\ \\mathrm{cm^3/s}$$ over the temperature range 503 K to 563 K.« less

Developing Culturally Targeted Diabetes Educational Materials for Older Russian-Speaking Immigrants.

PubMed

Van Son, Catherine R

2014-07-01

Older adults who immigrate late in life face many challenges adapting to a new country. Immigrants bring their cultural beliefs and behaviors with them, which can influence their ability to make dietary changes required when they have type 2 diabetes. Culturally targeted patient education materials are needed to improve immigrants' health literacy and abilities to self-manage diabetes. Currently, there is a scarcity of diabetes patient education materials to meet the educational needs of the Russian-speaking immigrant group. The purpose of this article is to describe a project in which culturally targeted diabetes education materials for older Russian-speaking immigrants were designed and developed. Culturally targeted patient education materials are essential if they are to be accepted and used by clients from different ethnic minority populations. The creation of culturally relevant materials requires a team effort and community stakeholder input. The availability of materials on the internet facilitates access and use by health care providers. Culturally targeted education materials are an important component in addressing health literacy in ethnic minority populations. Next steps require that these materials be evaluated to test their impact on diabetes self-management behaviors and clinical outcomes such as adherence, amount of physical activity, and blood glucose levels. © 2014 The Author(s).

The European Society of Gastrointestinal Endoscopy Quality Improvement Initiative: developing performance measures.

PubMed

Rutter, Matthew D; Senore, Carlo; Bisschops, Raf; Domagk, Dirk; Valori, Roland; Kaminski, Michal F; Spada, Cristiano; Bretthauer, Michael; Bennett, Cathy; Bellisario, Cristina; Minozzi, Silvia; Hassan, Cesare; Rees, Colin; Dinis-Ribeiro, Mário; Hucl, Tomas; Ponchon, Thierry; Aabakken, Lars; Fockens, Paul

2016-01-01

The European Society of Gastrointestinal Endoscopy (ESGE) and United European Gastroenterology (UEG) have a vision to create a thriving community of endoscopy services across Europe, collaborating with each other to provide high quality, safe, accurate, patient-centered and accessible endoscopic care. Whilst the boundaries of what can be achieved by advanced endoscopy are continually expanding, we believe that one of the most fundamental steps to achieving our goal is to raise the quality of everyday endoscopy. The development of robust, consensus- and evidence-based key performance measures is the first step in this vision.ESGE and UEG have identified quality of endoscopy as a major priority. This paper explains the rationale behind the ESGE Quality Improvement Initiative and describes the processes that were followed. We recommend that all units develop mechanisms for audit and feedback of endoscopist and service performance using the ESGE performance measures that will be published in future issues of this journal over the next year. We urge all endoscopists and endoscopy services to prioritize quality and to ensure that these performance measures are implemented and monitored at a local level, so that we can provide the highest possible care for our patients. © Georg Thieme Verlag KG Stuttgart · New York.

Development of high-performance alkali-hybrid polarized 3He targets for electron scattering

NASA Astrophysics Data System (ADS)

Singh, Jaideep T.; Dolph, P. A. M.; Tobias, W. A.; Averett, T. D.; Kelleher, A.; Mooney, K. E.; Nelyubin, V. V.; Wang, Yunxiao; Zheng, Yuan; Cates, G. D.

2015-05-01

Background: Polarized 3He targets have been used as effective polarized neutron targets for electron scattering experiments for over twenty years. Over the last ten years, the effective luminosity of polarized 3He targets based on spin-exchange optical pumping has increased by over an order of magnitude. This has come about because of improvements in commercially-available lasers and an improved understanding of the physics behind the polarization process. Purpose: We present the development of high-performance polarized 3He targets for use in electron scattering experiments. Improvements in the performance of polarized 3He targets, target properties, and operating parameters are documented. Methods: We utilize the technique of alkali-hybrid spin-exchange optical pumping to polarize the 3He targets. Spectrally narrowed diode lasers used for the optical pumping greatly improved the performance. A simulation of the alkali-hybrid spin-exchange optical pumping process was developed to provide guidance in the design of the targets. Data was collected during the characterization of 24 separate glass target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. Results: From the data obtained we made determinations of the so-called X -factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable 3He polarization to well under 100%. The presence of the X -factor spin-relaxation mechanism was clearly evident in our data. Good agreement between the simulation and the actual target performance was obtained by including details such as off-resonant optical pumping. Included in our results is a measurement of the K -3He spin-exchange rate coefficient kseK=(7.46 ±0.62 ) ×10-20cm3/s over the temperature range 503 K to 563 K. Conclusions: In order to achieve high performance under the operating conditions described in this paper

Characterization and Targeting of the Aldehyde Dehydrogenase Subpopulation in Ovarian Cancer

DTIC Science & Technology

2012-07-01

Targeting the Hedgehog pathway reverses taxane resistance in ovarian cancer. Proceedings of the 42 nd Annual Society of Gynecologic Oncologists...Meeting, 2011. Steg AD, Ziebarth AA, Katre A, Landen CN Jr. Targeting hedgehog reverses taxane resistance by Gli-dependent and independent mechanisms in...pathways ( Hedgehog , Notch, TGF-b, and Wnt). Select genes of interest were validated as important targets using siRNA-mediated downregulation. Results

A fusion-protein approach enabling mammalian cell production of tumor targeting protein domains for therapeutic development.

PubMed

Hu, Jia; Chen, Xiang; Zhang, Xuhua; Yuan, Xiaopeng; Yang, Mingjuan; Dai, Hui; Yang, Wei; Zhou, Qinghua; Wen, Weihong; Wang, Qirui; Qin, Weijun; Zhao, Aizhi

2018-05-01

A single chain Fv fragment (scFv) is a fusion of the variable regions of heavy (V H ) and light (V L ) chains of immunoglobulins. They are important elements of chimeric antigen receptors for cancer therapy. We sought to produce a panel of 16 extracellular protein domains of tumor markers for use in scFv yeast library screenings. A series of vectors comprising various combinations of expression elements was made, but expression was unpredictable and more than half of the protein domains could not be produced using any of the constructs. Here we describe a novel fusion expression system based on mouse TEM7 (tumor endothelial marker 7), which could facilitate protein expression. With this approach we could produce all but one of the tumor marker domains that could not otherwise be expressed. In addition, we demonstrated that the tumor associated antigen hFZD10 produced as a fusion protein with mTEM7 could be used to enrich scFv antibodies from a yeast display library. Collectively our study demonstrates the potential of specific fusion proteins based on mTEM7 in enabling mammalian cell production of tumor targeting protein domains for therapeutic development. © 2018 The Protein Society.

rno-miR-665 targets BCL2L1 (Bcl-xl) and increases vulnerability to propofol in developing astrocytes.

PubMed

Sun, Wen-Chong; Pei, Ling

2016-07-01

Propofol exerts a cytotoxic influence over immature neurocytes. Our previous study revealed that clinically relevant doses of propofol accelerated apoptosis of primary cultured astrocytes of developing rodent brains via rno-miR-665 regulation. However, the role of rno-miR-665 during the growth spurt of neonatal rodent brains in vivo is still uncertain. Post-natal day 7 (P7) rats received a single injection of propofol 30 mg/kg intraperitoneally (i.p.), and neuroapoptosis of hippocampal astrocytes was analyzed by immunofluorescence and scanning electron microscopy. The differential expression of rno-miR-665, BCL2L1 (Bcl-xl), and cleaved caspase 3 (CC3) was surveyed by qRT-PCR and western blotting. In addition, the utility of A-1155463, a highly potent and BCL2L1-selective antagonist, was aimed to assess the contribution of BCL2L1 for neuroglial survival. Following the intraventricular injection of lentivirus rno-miR-665, neuroprotection was detected by 5-point scale measurement. The single dose of propofol 30 mg/kg triggered dose-dependent apoptosis of developing hippocampal astrocytes. Meanwhile, propofol triggered both rno-miR-665 and CC3, and depressed BCL2L1, which was predicted as one target gene of rno-miR-665. Combination treatment with A-1155463 and propofol induced lower mRNA and protein levels of BCL2L1 and more CC3 activation than propofol treatment alone in vivo. The lentivirus-mediated knockdown of rno-miR-665 elevated BCL2L1 and attenuated CC3 levels, whereas up-regulation of rno-miR-665 suppressed BCL2L1 and induced CC3 expression in vivo. More importantly, rno-miR-665 antagomir infusion improved neurological outcomes of pups receiving propofol during the brain growth spurt. Rno-miR-665, providing a potential target for alternative therapeutics for pediatric anesthesia, is susceptible to propofol by negatively targeting antiapoptotic BCL2L1. Relatively little is known about the association between exposure of astrocytes to brief propofol

Application of liposomes in drug development — focus on gastroenterological targets

PubMed Central

Zhang, Jian-Xin; Wang, Kun; Mao, Zheng-Fa; Fan, Xin; Jiang, De-Li; Chen, Min; Cui, Lei; Sun, Kang; Dang, Sheng-Chun

2013-01-01

Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer. PMID:23630417

Role of Scientific Societies in International Collaboration

NASA Astrophysics Data System (ADS)

Fucugauchi, J. U.

2007-12-01

Geophysical research increasingly requires global multidisciplinary approaches. Understanding how deeply interrelated are Earth components and processes, population growth, increased needs of mineral and energy resources, global impact of human activities, and view of our planet as an interconnected system emphasizes the need of international cooperation. International research collaboration has an immense potential and is needed for further development of Earth science research and education. The Union Session is planned to provide a forum for analysis and discussion of the status of research and education of geosciences in developing countries, international collaboration programs and new initiatives for promoting and strengthening scientific cooperation. A theme of particular relevance in the analyses and discussions is the role of scientific societies in international collaboration. Societies organize meetings, publish journals and books and promote cooperation through academic exchange activities. They may further assist communities in developing countries in providing and facilitating access to scientific literature, attendance to international meetings, short and long-term stays and student and young researcher mobility. What else can be done? This is a complex subject and scientific societies may not be seen independently from the many factors involved in research and education. Developing countries present additional challenges resulting from limited economic resources and social and political problems, while urgently requiring improved educational and research programs. Needed are in-depth analyses of infrastructure and human resources, and identification of major problems and needs. What are the major limitations and needs in research and postgraduate education in developing countries? What and how should international collaboration do? What are the roles of individuals, academic institutions, funding agencies, scientific societies? Here we attempt to

A low carbon economy and society.

PubMed

Urry, John

2013-03-13

This paper examines various aspects of moving from high carbon economies and societies to a cluster of low carbon systems. First, some historical material is considered from the Second World War and the 1970s, periods with some lessons for the contemporary 'powering down' of whole societies. Second, analysis is provided of some green shoots of a powering down of existing systems identifiable in the contemporary developed world. Third, analysis is provided of the array of systems, social practices and innovations that would have to develop in order to effect powering down on a sufficient scale and within an appropriate time period. Most examples are drawn from transport and mobility. Finally, the paper demonstrates just why developing new systems is so hard, especially as this must involve a transformed cluster of systems. The forces that make a new cluster unlikely are exceptionally powerful and make this a very difficult but not impossible outcome.

Life Science Professional Societies Expand Undergraduate Education Efforts

PubMed Central

Matyas, Marsha Lakes; Ruedi, Elizabeth A.; Engen, Katie; Chang, Amy L.

2017-01-01

The Vision and Change in Undergraduate Biology Education reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by societies for undergraduate education and documented changes in support during the Vision and Change era. Society representatives responded to a survey on programs, awards, meetings, membership, teaching resources, publications, staffing, finances, evaluation, and collaborations that address undergraduate faculty and students. A longitudinal comparison group of societies responded to surveys in both 2008 and 2014. Results indicate that life science professional societies are extensively engaged in undergraduate education in their fields, setting standards for their discipline, providing vetted education resources, engaging students in both research and education, and enhancing professional development and recognition/status for educators. Societies are devoting funding and staff to these efforts and engaging volunteer leadership. Longitudinal comparison group responses indicate there have been significant and quantifiable expansions of undergraduate efforts in many areas since 2008. These indicators can serve as a baseline for defining, aligning, and measuring how professional societies can promote sustainable, evidence-based support of undergraduate education initiatives. PMID:28130272

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

PubMed

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, <145-135; 2, <135-125; 3, <125  mmHg); two different LDL-C targets (target A, 2.8-1.8; target B, <1.8  mmol/l). The trial is to be conducted on 7500 patients aged at least 65 years (2500 in Europe, 5000 in China) with hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be

Development of 64Cu-NOTA-Trastuzumab for HER2 targeting: radiopharmaceutical with improved pharmacokinetics for human study.

PubMed

Woo, Sang-Keun; Jang, Su Jin; Seo, Min-Jung; Park, Ju Hui; Kim, Byoung Soo; Kim, Eun Jung; Lee, Yong Jin; Lee, Tae Sup; An, Gwang Il; Song, In Ho; Seo, Youngho; Kim, Kwang Il; Kang, Joo Hyun

2018-05-18

Purpose The purpose of this study was to develop 64 Cu-labeled trastuzumab with improved pharmacokinetics for human epidermal growth factor receptor 2. Methods Trastuzumab was conjugated with SCN-Bn-NOTA and radiolabeled with 64 Cu. Serum stability and immunoreactivity of 64 Cu-NOTA-trastuzumab were tested. Small animal PET imaging and biodistribution study were performed in HER2-positive breast cancer xenograft model (BT-474). Internal dosimetry of experimental animals was performed using the image-based approach with the Monte Carlo N-Particle Code. Results 64 Cu-NOTA-trastuzumab was prepared with high radiolabel yield and radiochemical purity (>98%) and showed high stability in serum and good immunoreactivity. Uptake of 64 Cu-NOTA-trastuzumab was highest at 48 h after injection determined by PET imaging and biodistribution results in BT-474 tumors. The blood radioactivity concentrations of 64 Cu-NOTA-trastuzumab decreased bi-exponentially with time in both mice with and without BT-474 tumor xenografts. The calculated absorbed dose of 64 Cu-NOTA-trastuzumab was 0.048 mGy/MBq for the heart, 0.079 for the liver and 0.047 for the spleen. Conclusion 64 Cu-NOTA-trastuzumab was effectively targeted to the HER2-expressing tumor in vitro and in vivo , and it exhibited relatively low absorbed dose due to short residence time. Therefore, 64 Cu-NOTA-trastuzumab could be applied to select the right patients/right timing for HER2 therapy, to monitor the treatment response after HER2-targeted therapy, and to detect distal or metastatic spread. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Making Sense for Society

NASA Astrophysics Data System (ADS)

van der Heide, J. J.; Grus, M. M.; Nouwens, J. C. A. J.

2017-09-01

The Netherlands is a densely populated country. Cities in the metropolitan area (Randstad) will be growing at a fast pace in the coming decades1. Cities like Amsterdam and Rotterdam are being overrun by tourists. Climate change effects are noticed in cities (heavy rains for instance). Call for circular economy rises. Traffic increases. People are more self-reliant. Public space is shared by many functions. These challenges call for smart answers, more specific and directly than ever before. Sensor data is a cornerstone of these answers. In this paper we'll discuss the approaches of Dutch initiatives using sensor data as the new language to live a happy life in our cities. Those initiatives have been bundled in a knowledge platform called "Making sense for society" 1 target="_blank">https://www.cbs.nl/nl-nl/nieuws/2016/37/pbl-cbs-prognose-groei-steden-zet-door (in dutch)

Effects of seed mixture sowing with resistant and susceptible rice on population dynamics of target planthoppers and non-target stemborers and leaffolders.

PubMed

Li, Zhuo; Wan, Guijun; Wang, Long; Parajulee, Megha N; Zhao, Zihua; Chen, Fajun

2018-07-01

The widespread planting of insect-resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impact on both target and non-target pests worldwide. In this study, we examined the potential effects of six seed mixture ratios of insect-resistance dominance [100% (R100), 95% (S05R95), 90% (S10R90), 80% (S20R80), 60% (S40R60), and 0% (S100)] on target and non-target pests in a 2-year field trial in southern China. The occurrence of the target pests Nilaparvata lugens and Sogatella furcifera decreased with an increase in the ratio of resistant rice, and mixture ratios with ≥90% resistant rice significantly increased the pest suppression efficiency, with the lowest occurrences of the non-target pests Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis for S100 and S10R90 seed mixture ratios. Furthermore, there were no significant differences in the 1000-grain dry weight and grain yield between R100 and other treatments with ≥80% resistant seeds in the mixture (S20R80, S10R90 and S05R95). S10R90 produced a good yield and provided the most effective control of both target and non-target pests, with the potential to significantly reduce the application of chemical pesticides for integrated pest management in paddy fields. It is further presumed that the strategy of seed mixture with resistant and susceptible rice would be advantageous for rice yield stability. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Support Science by Publishing in Scientific Society Journals.

PubMed

Schloss, Patrick D; Johnston, Mark; Casadevall, Arturo

2017-09-26

Scientific societies provide numerous services to the scientific enterprise, including convening meetings, publishing journals, developing scientific programs, advocating for science, promoting education, providing cohesion and direction for the discipline, and more. For most scientific societies, publishing provides revenues that support these important activities. In recent decades, the proportion of papers on microbiology published in scientific society journals has declined. This is largely due to two competing pressures: authors' drive to publish in "glam journals"-those with high journal impact factors-and the availability of "mega journals," which offer speedy publication of articles regardless of their potential impact. The decline in submissions to scientific society journals and the lack of enthusiasm on the part of many scientists to publish in them should be matters of serious concern to all scientists because they impact the service that scientific societies can provide to their members and to science. Copyright © 2017 Schloss et al.

Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

PubMed Central

Pierce, Christopher G.; Lopez-Ribot, Jose L.

2014-01-01

Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

Technology platform development for targeted plasma metabolites in human heart failure.

PubMed

Chan, Cy X'avia; Khan, Anjum A; Choi, Jh Howard; Ng, Cm Dominic; Cadeiras, Martin; Deng, Mario; Ping, Peipei

2013-01-01

Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma:solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic

Development of targeted messages to promote smoking cessation among construction trade workers

PubMed Central

Strickland, J. R.; Smock, N.; Casey, C.; Poor, T.; Kreuter, M. W.; Evanoff, B. A.

2015-01-01

Blue-collar workers, particularly those in the construction trades, are more likely to smoke and have less success in quitting when compared with white-collar workers. Little is known about health communication strategies that might influence this priority population. This article describes our formative work to develop targeted messages to increase participation in an existing smoking cessation program among construction workers. Using an iterative and sequential mixed-methods approach, we explored the culture, health attitudes and smoking behaviors of unionized construction workers. We used focus group and survey data to inform message development, and applied audience segmentation methods to identify potential subgroups. Among 144 current smokers, 65% reported wanting to quit smoking in the next 6 months and only 15% had heard of a union-sponsored smoking cessation program, despite widespread advertising. We tested 12 message concepts and 26 images with the target audience to evaluate perceived relevance and effectiveness. Participants responded most favorably to messages and images that emphasized family and work, although responses varied by audience segments based on age and parental status. This study is an important step towards integrating the culture of a high-risk group into targeted messages to increase participation in smoking cessation activities. PMID:25231165

SuperTarget goes quantitative: update on drug–target interactions

PubMed Central

Hecker, Nikolai; Ahmed, Jessica; von Eichborn, Joachim; Dunkel, Mathias; Macha, Karel; Eckert, Andreas; Gilson, Michael K.; Bourne, Philip E.; Preissner, Robert

2012-01-01

There are at least two good reasons for the on-going interest in drug–target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web-based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330 000 relations to 196 000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget. PMID:22067455

Development of Novel Therapeutics Targeting Isocitrate Dehydrogenase Mutations in Cancer.

PubMed

Sharma, Horrick

2018-05-17

Isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (αKG). IDH 1 and IDH2 regulate several cellular processes, including oxidative respiration, glutamine metabolism, lipogenesis, and cellular defense against oxidative damage. Mutations in IDH1 and IDH2 have recently been observed in multiple tumor types, including gliomas, acute myeloid leukemia, myelodysplastic syndromes, and chondrosarcoma. IDH1 and IDH2 mutations involve a gain in neomorphic activity that catalyze αKG conversion to (R)-2-hydroxyglutarate ((R)-2HG). IDH mutation-mediated accumulation of (R)-2HG result in epigenetic dysregulation, altered gene expression, and a block in cellular differentiation. Targeting mutant IDH by development of small molecule inhibitors is a rapidly emerging therapeutic approach as evidenced by the recent approval of the first selective mutant IDH2 inhibitor AG-221 (Enasidenib) for the treatment of IDH2-mutated AML. This review will focus on mutant isocitrate dehydrogenase as a therapeutic drug target and provides an update on selective and pan-mutant IDH 1/2 inhibitors in clinical trials and other mutant IDH inhibitors that are under development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

The impact of molecular targets in cancer drug development: major hurdles and future strategies.

PubMed

Hebar, Alexandra; Valent, Peter; Selzer, Edgar

2013-01-01

The last decades were characterized by enormous technological advances resulting in a better understanding of disease pathologies and improvement of treatment strategies. The development of targeted drugs, whose beginning can be traced back to Paul Ehrlich's theory of the 'magic bullet' approximately 100 years ago, is today widely appraised as a promising strategy to combat benign, as well as malignant, diseases. Over 40 years after US President Nixon declared the 'war on cancer', treatment outcome, especially of solid tumors in the advanced stages of disease, still lies far behind expectations. In this perspective article, the authors discuss the recent development of targeted cancer drugs and identify major hurdles. The authors further highlight future strategies that might improve and accelerate the drug-development process.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain

PubMed Central

Spiteri, Elizabeth ; Konopka, Genevieve ; Coppola, Giovanni ; Bomar, Jamee ; Oldham, Michael ; Ou, Jing ; Vernes, Sonja C. ; Fisher, Simon E. ; Ren, Bing ; Geschwind, Daniel H. 

2007-01-01

Mutations in FOXP2, a member of the forkhead family of transcription factor genes, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain, therefore, provides a unique tool with which to explore the development of human language and speech. Here, we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) by use of chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; statistically significant overlap of targets in BG and IFC indicates a core set of 34 transcriptional targets of FOXP2. We identified targets specific to IFC or BG that were not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of central nervous system patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study to use human brain tissue, making the FOXP2-target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes. PMID:17999357

Models for discovery of targeted therapy in genetic epileptic encephalopathies.

PubMed

Maljevic, Snezana; Reid, Christopher A; Petrou, Steven

2017-10-01

Epileptic encephalopathies are severe disorders emerging in the first days to years of life that commonly include refractory seizures, various types of movement disorders, and different levels of developmental delay. In recent years, many de novo occurring variants have been identified in individuals with these devastating disorders. To unravel disease mechanisms, the functional impact of detected variants associated with epileptic encephalopathies is investigated in a range of cellular and animal models. This review addresses efforts to advance and use such models to identify specific molecular and cellular targets for the development of novel therapies. We focus on ion channels as the best-studied group of epilepsy genes. Given the clinical and genetic heterogeneity of epileptic encephalopathy disorders, experimental models that can reflect this complexity are critical for the development of disease mechanisms-based targeted therapy. The convergence of technological advances in gene sequencing, stem cell biology, genome editing, and high throughput functional screening together with massive unmet clinical needs provides unprecedented opportunities and imperatives for precision medicine in epileptic encephalopathies. © 2017 International Society for Neurochemistry.

Discrepancy in Vancomycin AUC/MIC Ratio Targeted Attainment Based upon the Susceptibility Testing in Staphylococcus aureus.

PubMed

Eum, Seenae; Bergsbaken, Robert L; Harvey, Craig L; Warren, J Bryan; Rotschafer, John C

2016-09-27

This study demonstrated a statistically significant difference in vancomycin minimum inhibitory concentration (MIC) for Staphylococcus aureus between a common automated system (Vitek 2) and the E-test method in patients with S. aureus bloodstream infections. At an area under the serum concentration time curve (AUC) threshold of 400 mg∙h/L, we would have reached the current Infectious Diseases Society of America (IDSA)/American Society of Health System Pharmacists (ASHP)/Society of Infectious Diseases Pharmacists (SIDP) guideline suggested AUC/MIC target in almost 100% of patients while using the Vitek 2 MIC data; however, we could only generate 40% target attainment while using E-test MIC data ( p < 0.0001). An AUC of 450 mg∙h/L or greater was required to achieve 100% target attainment using either Vitek 2 or E-test MIC results.

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

PubMed Central

Diebold, Becky A.; Smith, Susan M.E.; Li, Yang

2015-01-01

Abstract Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23, 375–405. PMID:24512192

Information exchange of the Atomic Energy Society of Japan with nuclear societies worldwide

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

Hori, Masao; Tomita, Yasushi

2000-07-01

The Atomic Energy Society of Japan (AESJ) exchanges information with nuclear societies worldwide by intersocietal communication through international councils of nuclear societies and through bilateral agreements between foreign societies and by such media as international meetings, publications, and Internet applications.

Development of a software for quantitative evaluation radiotherapy target and organ-at-risk segmentation comparison.

PubMed

Kalpathy-Cramer, Jayashree; Awan, Musaddiq; Bedrick, Steven; Rasch, Coen R N; Rosenthal, David I; Fuller, Clifton D

2014-02-01

Modern radiotherapy requires accurate region of interest (ROI) inputs for plan optimization and delivery. Target delineation, however, remains operator-dependent and potentially serves as a major source of treatment delivery error. In order to optimize this critical, yet observer-driven process, a flexible web-based platform for individual and cooperative target delineation analysis and instruction was developed in order to meet the following unmet needs: (1) an open-source/open-access platform for automated/semiautomated quantitative interobserver and intraobserver ROI analysis and comparison, (2) a real-time interface for radiation oncology trainee online self-education in ROI definition, and (3) a source for pilot data to develop and validate quality metrics for institutional and cooperative group quality assurance efforts. The resultant software, Target Contour Testing/Instructional Computer Software (TaCTICS), developed using Ruby on Rails, has since been implemented and proven flexible, feasible, and useful in several distinct analytical and research applications.

The Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug Targets

PubMed Central

Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

2015-01-01

The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal. PMID:25635061

The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about the development of clinical practice guidelines

PubMed Central

2010-01-01

Flawed clinical practice guidelines may compromise patient care. Commercial conflicts of interest on panels that write treatment guidelines are particularly problematic, because panelists may have conflicting agendas that influence guideline recommendations. Historically, there has been no legal remedy for conflicts of interest on guidelines panels. However, in May 2008, the Attorney General of Connecticut concluded a ground-breaking antitrust investigation into the development of Lyme disease treatment guidelines by one of the largest medical societies in the United States, the Infectious Diseases Society of America (IDSA). Although the investigation found significant flaws in the IDSA guidelines development process, the subsequent review of the guidelines mandated by the settlement was compromised by a lack of impartiality at various stages of the IDSA review process. This article will examine the interplay between the recent calls for guidelines reform, the ethical canons of medicine, and due process considerations under antitrust laws as they apply to the formulation of the IDSA Lyme disease treatment guidelines. The article will also discuss pitfalls in the implementation of the IDSA antitrust settlement that should be avoided in the future. PMID:20529367

EBF factors drive expression of multiple classes of target genes governing neuronal development.

PubMed

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Teaching in the Knowledge Society: Education in the Age of Insecurity.

ERIC Educational Resources Information Center

Hargreaves, Andy

This book discusses challenges facing teachers in the knowledge society today, focusing on the changing world and the changing work of teaching. Seven chapters discuss: (1) "Teaching for the Knowledge Society: Educating for Ingenuity" (e.g., profiting from, developing, and teaching for the knowledge society); (2) "Teaching Beyond…

Web-based educational activities developed by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC): the experience of process, utilization, and expert evaluation.

PubMed

Sharma, Deepak; Bilotta, Federico; Moore, Laurel E; Bebawy, John F; Flexman, Alana M; Rochlen, Lauryn; Gorji, Reza; Avitsian, Rafi

2014-01-01

Web-based delivery of educational material by scientific societies appears to have increased recently. However, the utilization of such efforts by the members of professional societies is unknown. We report the experience with delivery of educational resources on the Web site of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC), and utilization of those resources by members. Three web-based educational initiatives were developed over 1 year to be disseminated through the SNACC Web site (http://www.snacc.org) for society members: (1) The SNACC Bibliography; (2) "Chat with the Author"; and (3) Clinical Case Discussions. Content experts and authors of important new research publications were invited to contribute. Member utilization data were abstracted with the help of the webmaster. For the bibliography, there were 1175 page requests during the 6-month period after its launch by 122/664 (19%) distinct SNACC members. The bibliography was utilized by 107/553 (19%) of the active members and 15/91 (16.5%) of the trainee members. The "Chats with the Authors" were viewed by 56 (9%) members and the Clinical Case Discussions by 51 (8%) members. Educational resources can be developed in a timely manner utilizing member contributions without additional financial implications. However, the member utilization of these resources was lower than expected. These are first estimates of utilization of web-based educational resources by members of a scientific society. Further evaluation of such utilization by members of other societies as well as measures of the effectiveness and impact of such activities is needed.

FOXP2 targets show evidence of positive selection in European populations.

PubMed

Ayub, Qasim; Yngvadottir, Bryndis; Chen, Yuan; Xue, Yali; Hu, Min; Vernes, Sonja C; Fisher, Simon E; Tyler-Smith, Chris

2013-05-02

Forkhead box P2 (FOXP2) is a highly conserved transcription factor that has been implicated in human speech and language disorders and plays important roles in the plasticity of the developing brain. The pattern of nucleotide polymorphisms in FOXP2 in modern populations suggests that it has been the target of positive (Darwinian) selection during recent human evolution. In our study, we searched for evidence of selection that might have followed FOXP2 adaptations in modern humans. We examined whether or not putative FOXP2 targets identified by chromatin-immunoprecipitation genomic screening show evidence of positive selection. We developed an algorithm that, for any given gene list, systematically generates matched lists of control genes from the Ensembl database, collates summary statistics for three frequency-spectrum-based neutrality tests from the low-coverage resequencing data of the 1000 Genomes Project, and determines whether these statistics are significantly different between the given gene targets and the set of controls. Overall, there was strong evidence of selection of FOXP2 targets in Europeans, but not in the Han Chinese, Japanese, or Yoruba populations. Significant outliers included several genes linked to cellular movement, reproduction, development, and immune cell trafficking, and 13 of these constituted a significant network associated with cardiac arteriopathy. Strong signals of selection were observed for CNTNAP2 and RBFOX1, key neurally expressed genes that have been consistently identified as direct FOXP2 targets in multiple studies and that have themselves been associated with neurodevelopmental disorders involving language dysfunction. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The Internet: Friend, Foe or Target?

ERIC Educational Resources Information Center

James, Jonathan D.

2014-01-01

In this chapter, the author provides an overview of how the Internet, a byproduct of our times, is shaping our culture and society in profound ways. He notes some of the major concerns and perils of the Internet age and concludes by pointing out how and why certain countries are targeting the Internet in terms of increased regulation and…

Capture of shrinking targets with realistic shrink patterns.

PubMed

Hoffmann, Errol R; Chan, Alan H S; Dizmen, Coskun

2013-01-01

Previous research [Hoffmann, E. R. 2011. "Capture of Shrinking Targets." Ergonomics 54 (6): 519-530] reported experiments for capture of shrinking targets where the target decreased in size at a uniform rate. This work extended this research for targets having a shrink-size versus time pattern that of an aircraft receding from an observer. In Experiment 1, the time to capture the target in this case was well correlated in terms of Fitts' index of difficulty, measured at the time of capture of the target, a result that is in agreement with the 'balanced' model of Johnson and Hart [Johnson, W. W., and Hart, S. G. 1987. "Step Tracking Shrinking Targets." Proceedings of the human factors society 31st annual meeting, New York City, October 1987, 248-252]. Experiment 2 measured the probability of target capture for varying initial target sizes and target shrink rates constant, defined as the time for the target to shrink to half its initial size. Data of shrink time constant for 50% probability of capture were related to initial target size but did not greatly affect target capture as the rate of target shrinking decreased rapidly with time.

IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA.

PubMed

Klöhn, Peter-Christian; Wuellner, Ulrich; Zizlsperger, Nora; Zhou, Yu; Tavares, Daniel; Berger, Sven; Zettlitz, Kirstin A; Proetzel, Gabriele; Yong, May; Begent, Richard H J; Reichert, Janice M

2013-01-01

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3-6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3-5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4-5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society's special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5-6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy.

Support Science by Publishing in Scientific Society Journals

PubMed Central

Johnston, Mark

2017-01-01

ABSTRACT Scientific societies provide numerous services to the scientific enterprise, including convening meetings, publishing journals, developing scientific programs, advocating for science, promoting education, providing cohesion and direction for the discipline, and more. For most scientific societies, publishing provides revenues that support these important activities. In recent decades, the proportion of papers on microbiology published in scientific society journals has declined. This is largely due to two competing pressures: authors’ drive to publish in “glam journals”—those with high journal impact factors—and the availability of “mega journals,” which offer speedy publication of articles regardless of their potential impact. The decline in submissions to scientific society journals and the lack of enthusiasm on the part of many scientists to publish in them should be matters of serious concern to all scientists because they impact the service that scientific societies can provide to their members and to science. PMID:28951482

Development of HWIL Testing Capabilities for Satellite Target Emulation at AEDC

NASA Astrophysics Data System (ADS)

Lowry, H.; Crider, D.; Burns, J.; Thompson, R.; Goldsmith, G., II; Sholes, W.

Programs involved in Space Situational Awareness (SSA) need the capability to test satellite sensors in a Hardware-in-the-Loop (HWIL) environment. Testing in a ground system avoids the significant cost of on-orbit test targets and the resulting issues such as debris mitigation, and in-space testing implications. The space sensor test facilities at AEDC consist of cryo-vacuum chambers that have been developed to project simulated targets to air-borne, space-borne, and ballistic platforms. The 7V chamber performs calibration and characterization of surveillance and seeker systems, as well as some mission simulation. The 10V chamber is being upgraded to provide real-time target simulation during the detection, acquisition, discrimination, and terminal phases of a seeker mission. The objective of the Satellite Emulation project is to upgrade this existing capability to support the ability to discern and track other satellites and orbital debris in a HWIL capability. It would provide a baseline for realistic testing of satellite surveillance sensors, which would be operated in a controlled environment. Many sensor functions could be tested, including scene recognition and maneuvering control software, using real interceptor hardware and software. Statistically significant and repeatable datasets produced by the satellite emulation system can be acquired during such test and saved for further analysis. In addition, the robustness of the discrimination and tracking algorithms can be investigated by a parametric analysis using slightly different scenarios; this will be used to determine critical points where a sensor system might fail. The radiometric characteristics of satellites are expected to be similar to the targets and decoys that make up a typical interceptor mission scenario, since they are near ambient temperature. Their spectral reflectivity, emissivity, and shape must also be considered, but the projection systems employed in the 7V and 10V chambers should be

The primary care sports medicine fellowship: American Medical Society for Sports Medicine proposed standards of excellence.

PubMed

Asif, Irfan M; Stovak, Mark; Ray, Tracy; Weiss-Kelly, Amanda

2017-09-01

The American Medical Society for Sports Medicine recognises a need to provide direction and continually enhance the quality of sports medicine fellowship training programmes. This document was developed to be an educational resource for sports medicine physicians who teach in a 1-year primary care sports medicine fellowship training programme. It is meant to provide high standards and targets for fellowship training programmes that choose to re-assess their curriculum and seek to make improvements. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Teaching about Crime in Communist Societies.

ERIC Educational Resources Information Center

Reichel, Philip L.

1980-01-01

Provides information on developing a short college level module on crime and societal reaction in communist society. Presented are techniques for gauging student knowledge of crime in communist states, theories by communist criminologists, and comparative criminology suggestions. (Author/DB)

A developmental history of the Society of Pediatric Psychology.

PubMed

White, S

1991-08-01

Presented history of the field of pediatric psychology in general and, more specifically, the development of the Society of Pediatric Psychology. Review began with 1896 concepts of Lightner Witmer and followed with 1960 activities by Logan Wright which led to the formation of the Society. The developmental phases of the Society are described with respect to goals, publications, financial status, training issues, and awards established. Present activities of liaisons with numerous outside organizations and agencies and regional conferences are detailed.

Teaching the Intersection of Climate and Society

NASA Astrophysics Data System (ADS)

Thomson, C.; Ting, M.; Orlove, B. S.

2014-12-01

As the first program of its kind, the M.A. in Climate and Society at Columbia University educates students on how climate affects society and vice versa. The 12-month interdisciplinary Master's program is designed to allow students from a wide variety of backgrounds to gain knowledge in climate science and a deep understanding of social sciences and how they related to climate. There are currently more than 250 alumni applying their skills in fields including energy, economics, disaster mitigation, journalism and climate research in more than a dozen countries worldwide. The presentation will highlight three key components of the program that have contributed to its growth and helped alumni become brokers that can effectively put climate science in the hands of the public and policymakers for the benefit of society. Those components include working with other academic departments at Columbia to successfully integrate social science classes into the curriculum; the development of the course Applications in Climate and Society to help students make an overt link between climate and its impacts on society; and providing students with hands-on activities with practitioners in climate-related fields.

Development, optimization and characterization of glycyrrhetinic acid-chitosan nanoparticles of atorvastatin for liver targeting.

PubMed

Rohilla, Raman; Garg, Tarun; Bariwal, Jitender; Goyal, Amit K; Rath, Goutam

2016-09-01

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.

Current beliefs and practice patterns among urologists regarding prostate magnetic resonance imaging and magnetic resonance-targeted biopsy.

PubMed

Muthigi, Akhil; Sidana, Abhinav; George, Arvin K; Kongnyuy, Michael; Maruf, Mahir; Valayil, Subin; Wood, Bradford J; Pinto, Peter A

2017-01-01

Multiparametric magnetic resonance imaging (MRI) and magnetic resonance (MR) -targeted biopsy have a growing role in the screening and evaluation of prostate cancer. We aim to evaluate the current knowledge, attitude, and practice patterns of urologists regarding this new technique. An anonymous online questionnaire was designed to collect information on urologists' beliefs and use of prostate multiparametric MRI and MR-targeted biopsy. The survey was sent to members of the Society of Urologic Oncology, the Endourological Society, and European Association of Urology. Multivariate logistic regression analysis was performed to determine predictors for use of prostate MRI and MR-targeted biopsy. A total of 302 responses were received (Endourological Society: 175, European Association of Urology: 23, and Society of Urologic Oncology: 104). Most respondents (83.6%) believe MR-targeted biopsy to be moderately to extremely beneficial in the evaluation of prostate cancer. Overall, 85.7% of responders use prostate MRI in their practice, and 63.0% use MR-targeted biopsy. The 2 most common settings for use of MR-targeted biopsy include patients with history of prior negative biopsy result (96.3%) and monitoring patients on active surveillance (72.5%). In those who do not use MR-targeted biopsy, the principal reasons were lack of necessary infrastructure (64.1%) and prohibitive costs (48.1%). On multivariate logistic regression analysis, practice in an academic setting (1.86 [1.02-3.40], P = 0.043) and performing greater than 25 radical prostatectomies per year (2.32 [1.18-4.56], P = 0.015) remained independent predictors for using MR-targeted biopsy. Most respondents of our survey look favorably on use of prostate MRI and MR-targeted biopsy in clinical practice. Over time, reduction in fixed costs and easier access to equipment may lead to further dissemination of this novel and potentially transformative technology. Published by Elsevier Inc.

Development of Small-molecule HIV Entry Inhibitors Specifically Targeting gp120 or gp41

PubMed Central

Lu, Lu; Yu, Fei; Cai, Lifeng; Debnath, Asim K.; Jiang, Shibo

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein surface subunit gp120 and transmembrane subunit gp41 play important roles in HIV-1 entry, thus serving as key targets for the development of HIV-1 entry inhibitors. T20 peptide (enfuvirtide) is the first U.S. FDA-approved HIV entry inhibitor; however, its clinical application is limited by the lack of oral availability. Here, we have described the structure and function of the HIV-1 gp120 and gp41 subunits and reviewed advancements in the development of small-molecule HIV entry inhibitors specifically targeting these two Env glycoproteins. We then compared the advantages and disadvantages of different categories of HIV entry inhibitor candidates and further predicted the future trend of HIV entry inhibitor development. PMID:26324044

MiR-144 regulates hematopoiesis and vascular development by targeting meis1 during zebrafish development.

PubMed

Su, Zhenhong; Si, Wenxia; Li, Lei; Zhou, Bisheng; Li, Xiuchun; Xu, Yan; Xu, Chengqi; Jia, Haibo; Wang, Qing K

2014-04-01

Hematopoiesis is a dynamic process by which peripheral blood lineages are developed. It is a process tightly regulated by many intrinsic and extrinsic factors, including transcriptional factors and signaling molecules. However, the epigenetic regulation of hematopoiesis, for example, regulation via microRNAs (miRNAs), remains incompletely understood. Here we show that miR-144 regulates hematopoiesis and vascular development in zebrafish. Overexpression of miR-144 inhibited primitive hematopoiesis as demonstrated by a reduced number of circulating blood cells, reduced o-dianisidine staining of hemoglobin, and reduced expression of hbαe1, hbβe1, gata1 and pu.1. Overexpression of miR-144 also inhibited definitive hematopoiesis as shown by reduced expression of runx1 and c-myb. Mechanistically, miR-144 regulates hematopoiesis by repressing expression of meis1 involved in hematopoiesis. Both real-time RT-PCR and Western blot analyses showed that overexpression of miR-144 repressed expression of meis1. Bioinformatic analysis predicts a target binding sequence for miR-144 at the 3'-UTR of meis1. Deletion of the miR-144 target sequence eliminated the repression of meis1 expression mediated by miR-144. The miR-144-mediated abnormal phenotypes were partially rescued by co-injection of meis1 mRNA and could be almost completely rescued by injection of both meis1 and gata1 mRNA. Finally, because meis1 is involved in vascular development, we tested the effect of miR-144 on vascular development. Overexpression of miR-144 resulted in abnormal vascular development of intersegmental vessels in transgenic zebrafish with Flk1p-EGFP, and the defect was rescued by co-injection of meis1 mRNA. These findings establish miR-144 as a novel miRNA that regulates hematopoiesis and vascular development by repressing expression of meis1. Copyright © 2014 Elsevier Ltd. All rights reserved.

PCSK9: Regulation and Target for Drug Development for Dyslipidemia.

PubMed

Burke, Amy C; Dron, Jacqueline S; Hegele, Robert A; Huff, Murray W

2017-01-06

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.

In Vitro Evaluation of Molecular Tumor Targets in Nuclear Medicine: Immunohistochemistry Is One Option, but Under Which Conditions?

PubMed

Reubi, Jean Claude

2017-12-01

The identification of new molecular targets for diagnostic and therapeutic applications using in vitro methods is an important challenge in nuclear medicine. One such method is immunohistochemistry, increasingly popular because it is easy to perform. This review presents the case for conducting receptor immunohistochemistry to evaluate potential molecular targets in human tumor tissue sections. The focus is on the immunohistochemistry of G-protein-coupled receptors, one of the largest families of cell surface proteins, representing a major class of drug targets and thus playing an important role in nuclear medicine. This review identifies common pitfalls and challenges and provides guidelines on performing such immunohistochemical studies. An appropriate validation of the target is a prerequisite for developing robust and informative new molecular probes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Cdc7 kinase - a new target for drug development.

PubMed

Swords, Ronan; Mahalingam, Devalingam; O'Dwyer, Michael; Santocanale, Corrado; Kelly, Kevin; Carew, Jennifer; Giles, Francis

2010-01-01

The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.

Development of a macrophage-targeting and phagocytosis-inducing bio-nanocapsule-based nanocarrier for drug delivery.

PubMed

Li, Hao; Tatematsu, Kenji; Somiya, Masaharu; Iijima, Masumi; Kuroda, Shun'ichi

2018-06-01

Macrophage hyperfunction or dysfunction is tightly associated with various diseases, such as osteoporosis, inflammatory disorder, and cancers. However, nearly all conventional drug delivery system (DDS) nanocarriers utilize endocytosis for entering target cells; thus, the development of macrophage-targeting and phagocytosis-inducing DDS nanocarriers for treating these diseases is required. In this study, we developed a hepatitis B virus (HBV) envelope L particle (i.e., bio-nanocapsule (BNC)) outwardly displaying a tandem form of protein G-derived IgG Fc-binding domain and protein L-derived IgG Fab-binding domain (GL-BNC). When conjugated with the macrophage-targeting ligand, mouse IgG2a (mIgG2a), the GL-BNC itself, and the liposome-fused GL-BNC (i.e., GL-virosome) spontaneously initiated aggregation by bridging between the Fc-binding domain and Fab-binding domain with mIgG2a. The aggregates were efficiently taken up by macrophages, whereas this was inhibited by latrunculin B, a phagocytosis-specific inhibitor. The mIgG2a-GL-virosome containing doxorubicin exhibited higher cytotoxicity toward macrophages than conventional liposomes and other BNC-based virosomes. Thus, GL-BNCs and GL-virosomes may constitute promising macrophage-targeting and phagocytosis-inducing DDS nanocarriers. We have developed a novel macrophage-targeting and phagocytosis-inducing bio-nanocapsule (BNC)-based nanocarrier named GL-BNC, which comprises a hepatitis B virus envelope L particle outwardly displaying protein G-derived IgG Fc- and protein L-derived IgG Fab-binding domains in tandem. The GL-BNC alone or liposome-fused form (GL-virosomes) could spontaneously aggregate when conjugated with macrophage-targeting IgGs, inducing phagocytosis by the interaction between IgG Fc of aggregates and FcγR on phagocytes. Thereby these aggregates were efficiently taken up by macrophages. GL-virosomes containing doxorubicin exhibited higher cytotoxicity towards macrophages than ZZ-virosomes and

Identifying vaccine targets for anti-leishmanial vaccine development

PubMed Central

Sundar, Shyam; Singh, Bhawana

2014-01-01

Leishmaniasis is a neglected tropical disease spread by an arthropod vector. It remains a significant health problem with an incidence of 0.2–0.4 million VL and 0.7–1.2 million CL cases each year. There are limitations associated with the current therapeutic regimens for leishmaniasis and the fact that after recovery from infection the host becomes immune to subsequent infection therefore, these factors forces the feasibility of a vaccine for leishmaniasis. Publication of the genome sequence of Leishmania has paved a new way to understand the pathogenesis and host immunological status therefore providing a deep insight in the field of vaccine research. This review is an effort to study the antigenic targets in Leishmania to develop anti-leishmanial vaccine. PMID:24606556

The hERG K+ channel: target and antitarget strategies in drug development.

PubMed

Raschi, Emanuel; Vasina, Valentina; Poluzzi, Elisabetta; De Ponti, Fabrizio

2008-03-01

The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.

Lasting Change: The Children's Aid Society 2010 Annual Report

ERIC Educational Resources Information Center

Children's Aid Society, 2010

2010-01-01

Throughout the first 157 years of The Children's Aid Society, the economy has cycled through highs and lows, some more severe than the recession individuals are still experiencing. And through them all, Children's Aid has remained strong. The society has always developed new and effective strategies to serve New York City's most vulnerable…

The National Cardiac Societies of the European Society of Cardiology.

PubMed

Atar, Dan

2015-06-01

The National Cardiac Societies are one of the Constituent Bodies of the European Society of Cardiology (ESC). They are the backbone of the ESC and together form the "Cardiology of Europe" in 56 European and Mediterranean countries.

Development of targeted messages to promote smoking cessation among construction trade workers.

PubMed

Strickland, J R; Smock, N; Casey, C; Poor, T; Kreuter, M W; Evanoff, B A

2015-02-01

Blue-collar workers, particularly those in the construction trades, are more likely to smoke and have less success in quitting when compared with white-collar workers. Little is known about health communication strategies that might influence this priority population. This article describes our formative work to develop targeted messages to increase participation in an existing smoking cessation program among construction workers. Using an iterative and sequential mixed-methods approach, we explored the culture, health attitudes and smoking behaviors of unionized construction workers. We used focus group and survey data to inform message development, and applied audience segmentation methods to identify potential subgroups. Among 144 current smokers, 65% reported wanting to quit smoking in the next 6 months and only 15% had heard of a union-sponsored smoking cessation program, despite widespread advertising. We tested 12 message concepts and 26 images with the target audience to evaluate perceived relevance and effectiveness. Participants responded most favorably to messages and images that emphasized family and work, although responses varied by audience segments based on age and parental status. This study is an important step towards integrating the culture of a high-risk group into targeted messages to increase participation in smoking cessation activities. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Development of Multifunctional Nanoparticles for Targeted Drug Delivery and Non-invasive Imaging of Therapeutic Effect

PubMed Central

Sajja, Hari Krishna; East, Michael P.; Mao, Hui; Wang, Andrew Y.; Nie, Shuming; Yang, Lily

2011-01-01

Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by non-invasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine. PMID:19275541

Convergence of Molecular Targets for Cancer Prevention and Therapy

Cancer.gov

Waun Ki Hong, MD, American Cancer Society Professor; Samsung Distinguished University Chair in Cancer Medicine at the University of Texas M. D. Anderson Cancer Center, Houston, TX, presented "Convergence of Molecular Targets for Cancer Prevention and Therapy".

Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles.

PubMed

Sugo, Tsukasa; Terada, Michiko; Oikawa, Tatsuo; Miyata, Kenichi; Nishimura, Satoshi; Kenjo, Eriya; Ogasawara-Shimizu, Mari; Makita, Yukimasa; Imaichi, Sachiko; Murata, Shumpei; Otake, Kentaro; Kikuchi, Kuniko; Teratani, Mika; Masuda, Yasushi; Kamei, Takayuki; Takagahara, Shuichi; Ikeda, Shota; Ohtaki, Tetsuya; Matsumoto, Hirokazu

2016-09-10

Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1μg siRNA conjugate showed significant gene-silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Life Science Professional Societies Expand Undergraduate Education Efforts.

PubMed

Matyas, Marsha Lakes; Ruedi, Elizabeth A; Engen, Katie; Chang, Amy L

2017-01-01

The Vision and Change in Undergraduate Biology Education reports cite the critical role of professional societies in undergraduate life science education and, since 2008, have called for the increased involvement of professional societies in support of undergraduate education. Our study explored the level of support being provided by societies for undergraduate education and documented changes in support during the Vision and Change era. Society representatives responded to a survey on programs, awards, meetings, membership, teaching resources, publications, staffing, finances, evaluation, and collaborations that address undergraduate faculty and students. A longitudinal comparison group of societies responded to surveys in both 2008 and 2014. Results indicate that life science professional societies are extensively engaged in undergraduate education in their fields, setting standards for their discipline, providing vetted education resources, engaging students in both research and education, and enhancing professional development and recognition/status for educators. Societies are devoting funding and staff to these efforts and engaging volunteer leadership. Longitudinal comparison group responses indicate there have been significant and quantifiable expansions of undergraduate efforts in many areas since 2008. These indicators can serve as a baseline for defining, aligning, and measuring how professional societies can promote sustainable, evidence-based support of undergraduate education initiatives. © 2017 M. L. Matyas et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Developing a de novo targeted knock-in method based on in utero electroporation into the mammalian brain.

PubMed

Tsunekawa, Yuji; Terhune, Raymond Kunikane; Fujita, Ikumi; Shitamukai, Atsunori; Suetsugu, Taeko; Matsuzaki, Fumio

2016-09-01

Genome-editing technology has revolutionized the field of biology. Here, we report a novel de novo gene-targeting method mediated by in utero electroporation into the developing mammalian brain. Electroporation of donor DNA with the CRISPR/Cas9 system vectors successfully leads to knock-in of the donor sequence, such as EGFP, to the target site via the homology-directed repair mechanism. We developed a targeting vector system optimized to prevent anomalous leaky expression of the donor gene from the plasmid, which otherwise often occurs depending on the donor sequence. The knock-in efficiency of the electroporated progenitors reached up to 40% in the early stage and 20% in the late stage of the developing mouse brain. Furthermore, we inserted different fluorescent markers into the target gene in each homologous chromosome, successfully distinguishing homozygous knock-in cells by color. We also applied this de novo gene targeting to the ferret model for the study of complex mammalian brains. Our results demonstrate that this technique is widely applicable for monitoring gene expression, visualizing protein localization, lineage analysis and gene knockout, all at the single-cell level, in developmental tissues. © 2016. Published by The Company of Biologists Ltd.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

PubMed

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

Development of high resolution target monitor.

DOT National Transportation Integrated Search

2008-01-01

The proposed High-resolution Target Movement Monitor uses triangulation theory but in a unique way. Unlike the commercially available triangulation systems which use sensing diodes to perceive reflected laser signatures and are limited to very short ...

Develop a novel target-basis of anti-virulence strategy for controlling HLB

USDA-ARS?s Scientific Manuscript database

The goal of this CRB-funded research project is to develop target-based anti-virulence therapeutics for Huanglongbing (HLB). Since the first report of citrus HLB in Florida in 2005, the disease is now looming large in Texas and California. In Florida, citrus growers are encountering severe decline o...

Development of target ion source systems for radioactive beams at GANIL

NASA Astrophysics Data System (ADS)

Bajeat, O.; Delahaye, P.; Couratin, C.; Dubois, M.; Franberg-Delahaye, H.; Henares, J. L.; Huguet, Y.; Jardin, P.; Lecesne, N.; Lecomte, P.; Leroy, R.; Maunoury, L.; Osmond, B.; Sjodin, M.

2013-12-01

The GANIL facility (Caen, France) is dedicated to the acceleration of heavy ion beams including radioactive beams produced by the Isotope Separation On-Line (ISOL) method at the SPIRAL1 facility. To extend the range of radioactive ion beams available at GANIL, using the ISOL method two projects are underway: SPIRAL1 upgrade and the construction of SPIRAL2. For SPIRAL1, a new target ion source system (TISS) using the VADIS FEBIAD ion source coupled to the SPIRAL1 carbon target will be tested on-line by the end of 2013 and installed in the cave of SPIRAL1 for operation in 2015. The SPIRAL2 project is under construction and is being design for using different production methods as fission, fusion or spallation reactions to cover a large area of the chart of nuclei. It will produce among others neutron rich beams obtained by the fission of uranium induced by fast neutrons. The production target made from uranium carbide and heated at 2000 °C will be associated with several types of ion sources. Developments currently in progress at GANIL for each of these projects are presented.

Miklós Bodanszky Award Lecture: Advances in the selective targeting of protein phosphatase-1 and phosphatase-2A with peptides.

PubMed

Köhn, Maja

2017-10-01

Protein phosphatase-1 and phosphatase-2A are two ubiquitously expressed enzymes known to catalyze the majority of dephosphorylation reactions on serine and threonine inside cells. They play roles in most cellular processes and are tightly regulated by regulatory subunits in holoenzymes. Their misregulation and malfunction contribute to disease development and progression, such as in cancer, diabetes, viral infections, and neurological as well as heart diseases. Therefore, targeting these phosphatases for therapeutic use would be highly desirable; however, their complex regulation and high conservation of the active site have been major hurdles for selectively targeting them in the past. In the last decade, new approaches have been developed to overcome these hurdles and have strongly revived the field. I will focus here on peptide-based approaches, which contributed to showing that these phosphatases can be targeted selectively and aided in rethinking the design of selective phosphatase modulators. Finally, I will give a perspective on www.depod.org, the human dephosphorylation database, and how it can aid phosphatase modulator design. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd. © 2017 The Authors. Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver stage development

PubMed Central

Lindner, Scott E.; Sartain, Mark J.; Hayes, Kiera; Harupa, Anke; Moritz, Robert L.; Kappe, Stefan H. I.; Vaughan, Ashley M.

2014-01-01

SUMMARY Malaria parasites scavenge nutrients from their host but also harbor enzymatic pathways for de novo macromolecule synthesis. One such pathway is apicoplast-targeted type II fatty acid synthesis, which is essential for late liver stage development in rodent malaria. It is likely that fatty acids synthesized in the apicoplast are ultimately incorporated into membrane phospholipids necessary for exoerythrocytic merozoite formation. We hypothesized that these synthesized fatty acids are being utilized for apicoplast-targeted phosphatidic acid synthesis, the phospholipid precursor. Phosphatidic acid is typically synthesized in a three-step reaction utilizing three enzymes: glycerol 3-phosphate dehydrogenase, glycerol 3-phosphate acyltransferase and lysophosphatidic acid acyltransferase. The Plasmodium genome is predicted to harbor genes for both apicoplast- and cytosol/endoplasmic reticulum-targeted phosphatidic synthesis. Our research shows that apicoplast-targeted P. yoelii glycerol 3-phosphate dehydrogenase and glycerol 3-phosphate acyltransferase are expressed only during liver stage development and deletion of the encoding genes resulted in late liver stage growth arrest and lack of merozoite differentiation. However, the predicted apicoplast-targeted lysophosphatidic acid acyltransferase gene was refractory to deletion and was expressed solely in the endoplasmic reticulum throughout the parasite lifecycle. Our results suggest that P. yoelii has an incomplete apicoplast-targeted phosphatidic acid synthesis pathway that is essential for liver stage maturation. PMID:24330260

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

Climate Literacy and Adaptation Solutions for Society

NASA Astrophysics Data System (ADS)

Sohl, L. E.; Chandler, M. A.

2011-12-01

Many climate literacy programs and resources are targeted specifically at children and young adults, as part of the concerted effort to improve STEM education in the U.S. This work is extremely important in building a future society that is well prepared to adopt policies promoting climate change resilience. What these climate literacy efforts seldom do, however, is reach the older adult population that is making economic decisions right now (or not, as the case may be) on matters that can be impacted by climate change. The result is a lack of appreciation of "climate intelligence" - information that could be incorporated into the decision-making process, to maximize opportunities, minimize risk, and create a climate-resilient economy. A National Climate Service, akin to the National Weather Service, would help provide legitimacy to the need for climate intelligence, and would certainly also be the first stop for both governments and private sector concerns seeking climate information for operational purposes. However, broader collaboration between the scientific and business communities is also needed, so that they become co-creators of knowledge that is beneficial and informative to all. The stakeholder-driven research that is the focus of NOAA's RISA (Regional Integrated Sciences and Assessments) projects is one example of how such collaborations can be developed.

National Cancer Societies and their public statements on alcohol consumption and cancer risk.

PubMed

Amin, Gopal; Siegel, Michael; Naimi, Timothy

2018-04-25

Studies have shown that alcohol consumption is a risk factor for oral, pharyngeal, laryngeal, esophageal, liver, colon, rectal and breast cancer. It would therefore be expected that cancer prevention organizations would incorporate these facts into their public stance on the consumption of alcohol. The aims of this study were to: (1) assess how national cancer societies in developed English-speaking countries [i.e. English-speaking countries belonging to the Organization for Economic Co-operation and Development (OECD)] communicate alcohol-related cancer risk to the public and (2) compare whether these organization's advocacy of increased alcohol taxes is in line with their advocacy of tobacco tax increases to reduce cancer risk. We searched the websites of the following national cancer organizations for all statements related to the relationship between alcohol consumption and cancer risk: Cancer Council Australia, Canadian Cancer Society, Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer Society. A categorical system was developed to code the qualitative data for health statements, alcohol consumption recommendations, and tax policy recommendations. Websites were analyzed in March of 2017. All organizations, with the exception of the American Cancer Society and Canadian Cancer Society, state that alcohol is a group 1 carcinogen and that even low-level alcohol consumption increases risk for some cancers. Additionally, while the American Cancer Society supports increasing tobacco taxes through its cancer action network, it has not advocated for increased alcohol taxes in relation to support for tobacco tax increases. Analysis in 2017 of the websites for national cancer societies in Australia, Canada, Ireland, New Zealand, the United Kingdom and the United States-including Cancer Council Australia, the Canadian Cancer Society, the Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer

Environmental Approach to the Study of the Modern Stage of Information Society Development: Research Prospects

ERIC Educational Resources Information Center

Ivlev, Vitali Yu.; Barkova, Eleonora V.; Ivleva, Marina I.; Buzskaya, Olga M.

2016-01-01

The paper analyses modern information society in terms of an information ecology approach. Its aim is to determine the place of the human being in the human-society-ecosystem relations system and to study the prospects of a humanistic approach to the understanding of the essence of subject-object relationships in the communication space of…

European Society of Gynaecologic Oncology Quality Indicators for Advanced Ovarian Cancer Surgery.

PubMed

Querleu, Denis; Planchamp, François; Chiva, Luis; Fotopoulou, Christina; Barton, Desmond; Cibula, David; Aletti, Giovanni; Carinelli, Silvestro; Creutzberg, Carien; Davidson, Ben; Harter, Philip; Lundvall, Lene; Marth, Christian; Morice, Philippe; Rafii, Arash; Ray-Coquard, Isabelle; Rockall, Andrea; Sessa, Cristiana; van der Zee, Ate; Vergote, Ignace; du Bois, Andreas

2016-09-01

The surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO). Quality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients. Ten structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built. The ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give

IBC’s 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics International Conferences and the 2012 Annual Meeting of The Antibody Society

PubMed Central

Klöhn, Peter-Christian; Wuellner, Ulrich; Zizlsperger, Nora; Zhou, Yu; Tavares, Daniel; Berger, Sven; Zettlitz, Kirstin A.; Proetzel, Gabriele; Yong, May; Begent, Richard H.J.; Reichert, Janice M

2013-01-01

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3–6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3–5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4–5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society’s special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5–6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy. PMID:23575266

Light: A Spectrum of Utility, the 2014-2015 Society of Physics Students Science Outreach Catalyst Kit

NASA Astrophysics Data System (ADS)

Sellers, Mark; Louis-Jean, Kearns; Society of Physics Students Collaboration; National Institute of Standards; Technology Collaboration

2015-03-01

The Science Outreach Catalyst Kit (SOCK) is a set of activities and demonstrations designed to bolster the outreach programs of undergraduate Society of Physics Students (SPS) chapters, creating the framework for a lasting outreach program. Targeted for students ranging from kindergarten to high school, the SOCK allows students to actively engage in hands-on activities that teach them scientific skills and allow them to exercise their natural curiosity. The 2014-2015 SOCK united themes from the 2014 International Year of Crystallography and the 2015 International Year of Light to explore how light is used as a tool every day. This presentation will discuss the contents of the SOCK, which contains a large assortment of materials, such as diffraction glasses, polarizers, ultraviolet flashlights, etc. and describe the research and development of the activities. Each activity explores a different light phenomenon, such as diffraction, polarization, reflection, or fluorescence. These activities will promote critical thinking and analysis of data. This work was supported by the Society of Physics Students summer intern program and by the National Institute of Standards and Technology.

Microfluidics for Drug Discovery and Development: From Target Selection to Product Lifecycle Management

PubMed Central

Kang, Lifeng; Chung, Bong Geun; Langer, Robert; Khademhosseini, Ali

2009-01-01

Microfluidic technologies’ ability to miniaturize assays and increase experimental throughput have generated significant interest in the drug discovery and development domain. These characteristics make microfluidic systems a potentially valuable tool for many drug discovery and development applications. Here, we review the recent advances of microfluidic devices for drug discovery and development and highlight their applications in different stages of the process, including target selection, lead identification, preclinical tests, clinical trials, chemical synthesis, formulations studies, and product management. PMID:18190858

Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides.

PubMed

Dissanayake, Shama; Denny, William A; Gamage, Swarna; Sarojini, Vijayalekshmi

2017-03-28

Efficient intracellular trafficking and targeted delivery to the site of action are essential to overcome the current drawbacks of cancer therapeutics. Cell Penetrating Peptides (CPPs) offer the possibility of efficient intracellular trafficking, and, therefore the development of drug delivery systems using CPPs as cargo carriers is an attractive strategy to address the current drawbacks of cancer therapeutics. Additionally, the possibility of incorporating Tumor Targeting Peptides (TTPs) into the delivery system provides the necessary drug targeting effect. Therefore the conjugation of CPPs and/or TTPs with therapeutics provides a potentially efficient method of improving intracellular drug delivery mechanisms. Peptides used as cargo carriers in DDS have been shown to enhance the cellular uptake of drugs and thereby provide an efficient therapeutic benefit over the drug on its own. After providing a brief overview of various drug targeting approaches, this review focusses on peptides as carriers and targeting moieties in drug-peptide covalent conjugates and summarizes the most recent literature examples where CPPs on their own or CPPs together with TTPs have been conjugated to anticancer drugs such as Doxorubicin, Methotrexate, Paclitaxel, Chlorambucil etc. A short section on CPPs used in multicomponent drug delivery systems is also included. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent Developments in the VISRAD 3-D Target Design and Radiation Simulation Code

NASA Astrophysics Data System (ADS)

Macfarlane, Joseph; Golovkin, Igor; Sebald, James

2017-10-01

The 3-D view factor code VISRAD is widely used in designing HEDP experiments at major laser and pulsed-power facilities, including NIF, OMEGA, OMEGA-EP, ORION, Z, and LMJ. It simulates target designs by generating a 3-D grid of surface elements, utilizing a variety of 3-D primitives and surface removal algorithms, and can be used to compute the radiation flux throughout the surface element grid by computing element-to-element view factors and solving power balance equations. Target set-up and beam pointing are facilitated by allowing users to specify positions and angular orientations using a variety of coordinates systems (e.g., that of any laser beam, target component, or diagnostic port). Analytic modeling for laser beam spatial profiles for OMEGA DPPs and NIF CPPs is used to compute laser intensity profiles throughout the grid of surface elements. VISRAD includes a variety of user-friendly graphics for setting up targets and displaying results, can readily display views from any point in space, and can be used to generate image sequences for animations. We will discuss recent improvements to conveniently assess beam capture on target and beam clearance of diagnostic components, as well as plans for future developments.

ACC/AATS/AHA/ASE/EACTS/HVS/SCA/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for the Treatment of Patients With Severe Aortic Stenosis: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PubMed

Bonow, Robert O; Brown, Alan S; Gillam, Linda D; Kapadia, Samir R; Kavinsky, Clifford J; Lindman, Brian R; Mack, Michael J; Thourani, Vinod H; Dehmer, Gregory J; Bonow, Robert O; Lindman, Brian R; Beaver, Thomas M; Bradley, Steven M; Carabello, Blase A; Desai, Milind Y; George, Isaac; Green, Philip; Holmes, David R; Johnston, Douglas; Leipsic, Jonathon; Mick, Stephanie L; Passeri, Jonathan J; Piana, Robert N; Reichek, Nathaniel; Ruiz, Carlos E; Taub, Cynthia C; Thomas, James D; Turi, Zoltan G; Doherty, John U; Dehmer, Gregory J; Bailey, Steven R; Bhave, Nicole M; Brown, Alan S; Daugherty, Stacie L; Dean, Larry S; Desai, Milind Y; Duvernoy, Claire S; Gillam, Linda D; Hendel, Robert C; Kramer, Christopher M; Lindsay, Bruce D; Manning, Warren J; Mehrotra, Praveen; Patel, Manesh R; Sachdeva, Ritu; Wann, L Samuel; Winchester, David E; Allen, Joseph M

2018-02-01

The American College of Cardiology collaborated with the American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons to develop and evaluate Appropriate Use Criteria (AUC) for the treatment of patients with severe aortic stenosis (AS). This is the first AUC to address the topic of AS and its treatment options, including surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). A number of common patient scenarios experienced in daily practice were developed along with assumptions and definitions for those scenarios, which were all created using guidelines, clinical trial data, and expert opinion in the field of AS. The 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines(1) and its 2017 focused update paper (2) were used as the primary guiding references in developing these indications. The writing group identified 95 clinical scenarios based on patient symptoms and clinical presentation, and up to 6 potential treatment options for those patients. A separate, independent rating panel was asked to score each indication from 1 to 9, with 1-3 categorized as "Rarely Appropriate," 4-6 as "May Be Appropriate," and 7-9 as "Appropriate." After considering factors such as symptom status, left ventricular (LV) function, surgical risk, and the presence of concomitant coronary or other valve disease, the rating panel determined that either SAVR or TAVR is Appropriate in most patients with symptomatic AS at intermediate or high surgical risk; however, situations

Geoethics and the Role of Professional Geoscience Societies

NASA Astrophysics Data System (ADS)

Kieffer, S. W.; Palka, J. M.; Geissman, J. W.; Mogk, D. W.

2014-12-01

Codes of Ethics (Conduct) for geoscientists are formulated primarily by professional societies and the codes must be viewed in the context of the Goals (Missions, Values) of the societies. Our survey of the codes of approximately twenty-five societies reveals that most codes enumerate principles centered on practical issues regarding professional conduct of individuals such as plagiarism, fabrication, and falsification, and the obligation of individuals to the profession and society at large. With the exception of statements regarding the ethics of peer review, there is relatively little regarding the ethical obligations of the societies themselves. In essence, the codes call for traditionally honorable behavior of individual members. It is striking, given that the geosciences are largely relevant to the future of Earth, most current codes of societies fail to address our immediate obligations to the environment and Earth itself. We challenge professional organizations to consider the ethical obligations to Earth in both their statements of goals and in their codes of ethics. Actions by societies could enhance the efforts of individual geoscientists to serve society, especially in matters related to hazards, resources and planetary stewardship. Actions we suggest to be considered include: (1) Issue timely position statements on topics in which there is expertise and consensus (some professional societies such as AGU, GSA, AAAS, and the AMS, do this regularly, yet others not at all.); (2) Build databases of case studies regarding geoethics that can be used in university classes; (3) Hold interdisciplinary panel discussions with ethicists, scientists, and policy makers at annual meetings; (4) Foster publication in society journals of contributions relating to ethical questions; and (5) Aggressively pursue the incorporation of geoethical issues in undergraduate and graduate curricula and in continuing professional development.

Artificial Intelligence and the 'Good Society': the US, EU, and UK approach.

PubMed

Cath, Corinne; Wachter, Sandra; Mittelstadt, Brent; Taddeo, Mariarosaria; Floridi, Luciano

2018-04-01

In October 2016, the White House, the European Parliament, and the UK House of Commons each issued a report outlining their visions on how to prepare society for the widespread use of artificial intelligence (AI). In this article, we provide a comparative assessment of these three reports in order to facilitate the design of policies favourable to the development of a 'good AI society'. To do so, we examine how each report addresses the following three topics: (a) the development of a 'good AI society'; (b) the role and responsibility of the government, the private sector, and the research community (including academia) in pursuing such a development; and (c) where the recommendations to support such a development may be in need of improvement. Our analysis concludes that the reports address adequately various ethical, social, and economic topics, but come short of providing an overarching political vision and long-term strategy for the development of a 'good AI society'. In order to contribute to fill this gap, in the conclusion we suggest a two-pronged approach.

Dual-targeting siRNAs

PubMed Central

Tiemann, Katrin; Höhn, Britta; Ehsani, Ali; Forman, Stephen J.; Rossi, John J.; Sætrom, Pål

2010-01-01

We have developed an algorithm for the prediction of dual-targeting short interfering RNAs (siRNAs) in which both strands are deliberately designed to separately target different mRNA transcripts with complete complementarity. An advantage of this approach versus the use of two separate duplexes is that only two strands, as opposed to four, are competing for entry into the RNA-induced silencing complex. We chose to design our dual-targeting siRNAs as Dicer substrate 25/27mer siRNAs, since design features resembling pre-microRNAs (miRNAs) can be introduced for Dicer processing. Seven different dual-targeting siRNAs targeting genes that are potential targets in cancer therapy have been developed including Bcl2, Stat3, CCND1, BIRC5, and MYC. The dual-targeting siRNAs have been characterized for dual target knockdown in three different cell lines (HEK293, HCT116, and PC3), where they were as effective as their corresponding single-targeting siRNAs in target knockdown. The algorithm developed in this study should prove to be useful for predicting dual-targeting siRNAs in a variety of different targets and is available from http://demo1.interagon.com/DualTargeting/. PMID:20410240

Restoration for the future: endpoints, targets, and indicators of progress and success

Treesearch

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...

Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project.

PubMed

Moreno, Lucas; Caron, Hubert; Geoerger, Birgit; Eggert, Angelika; Schleiermacher, Gudrun; Brock, Penelope; Valteau-Couanet, Dominique; Chesler, Louis; Schulte, Johannes H; De Preter, Katleen; Molenaar, Jan; Schramm, Alexander; Eilers, Martin; Van Maerken, Tom; Johnsen, John Inge; Garrett, Michelle; George, Sally L; Tweddle, Deborah A; Kogner, Per; Berthold, Frank; Koster, Jan; Barone, Giuseppe; Tucker, Elizabeth R; Marshall, Lynley; Herold, Ralf; Sterba, Jaroslav; Norga, Koen; Vassal, Gilles; Pearson, Andrew Dj

2017-08-01

Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term toxicity and to incorporate molecularly targeted therapies into treatment. Many potential drugs are becoming available, but have to be prioritised for clinical trials due to the relatively small numbers of patients. Areas covered: The current drug development model has been slow, associated with significant attrition, and few new drugs have been developed for neuroblastoma. The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs. Drugs showing activity can be rapidly transitioned via parallel randomised trials into front-line studies. Expert opinion: The Neuroblastoma NDDS is based on the premise that optimal drug development is reliant on knowledge of tumour biology and prioritisation. This approach will accelerate neuroblastoma drug development and other poor prognosis childhood malignancies.

Development and evaluation of camptothecin loaded polymer stabilized nanoemulsion: Targeting potential in 4T1-breast tumour xenograft model.

PubMed

Sugumaran, Abimanyu; Ponnusamy, Chandrasekar; Kandasamy, Palanivel; Krishnaswami, Venkateshwaran; Palanichamy, Rajaguru; Kandasamy, Ruckmani; Lakshmanan, Manikandan; Natesan, Subramanian

2018-04-30

Targeted delivery of anticancer agents is poised to improve cancer therapy, for which polymers can serve as targeting ligands or nanocarriers for chemotherapeutic agents. In this study, we have developed and evaluated the efficacy of a camptothecin (CPT)-loaded polymer stabilized nanoemulsion (PSNE) for the passive targeted delivery to breast cancer. Based on the pseudo-ternary phase diagrams, PSNEs were developed using capmul MCM:poloxamer 407 (4:1), solutol HS 15:simulsol P23 (1:2) and water. CPT polymer mixture was developed by solvent evaporation technique. The PSNEs were characterized for droplet size distribution, plasma protein adsorption, drug release, in-vivo targeting potential, hemolytic potential, cytotoxicity, genotoxicity, in-vivo biodistribution and CPT lactone ring stability. The developed PSNEs showed uniform droplet distribution, extended drug release (76.59±6.12% at 24h), acceptable hemolytic potential, significant cytotoxicity (IC 50 =176±4.3ng/mL) and genotoxicity against MCF-7 cancer cells but low DNA damage potential in human peripheral blood lymphocytes. The efficiency of PSNEs for the targeted delivery of CPT into the tumour regions was documented in 4T1-breast tumour xenografted BALB/c mice. In-vivo biodistribution study shows that 7105.84±568.46ng/g of CPT was passively targeted from PSNE to breast cancer tissue. About 80% of the lactone form was stable for 24h. Taken together, our study provides a promising strategy for developing PSNE-targeted drug delivery system for the breast cancer therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development.

PubMed

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie; Barozzi, Iros; Osterwalder, Marco; Akiyama, Jennifer A; Lincoln, Joy; Lopez-Rios, Javier; Visel, Axel; Zuniga, Aimée; Zeller, Rolf

2017-05-23

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost from Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

DOE PAGES

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie; ...

2017-05-23

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost frommore » Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.« less

HAND2 Target Gene Regulatory Networks Control Atrioventricular Canal and Cardiac Valve Development

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

Laurent, Frédéric; Girdziusaite, Ausra; Gamart, Julie

The HAND2 transcriptional regulator controls cardiac development, and we uncover additional essential functions in the endothelial to mesenchymal transition (EMT) underlying cardiac cushion development in the atrioventricular canal (AVC). In Hand2-deficient mouse embryos, the EMT underlying AVC cardiac cushion formation is disrupted, and we combined ChIP-seq of embryonic hearts with transcriptome analysis of wild-type and mutants AVCs to identify the functionally relevant HAND2 target genes. The HAND2 target gene regulatory network (GRN) includes most genes with known functions in EMT processes and AVC cardiac cushion formation. One of these is Snai1, an EMT master regulator whose expression is lost frommore » Hand2-deficient AVCs. Re-expression of Snai1 in mutant AVC explants partially restores this EMT and mesenchymal cell migration. Furthermore, the HAND2-interacting enhancers in the Snai1 genomic landscape are active in embryonic hearts and other Snai1-expressing tissues. These results show that HAND2 directly regulates the molecular cascades initiating AVC cardiac valve development.« less

Targetting Teenagers.

ERIC Educational Resources Information Center

Bernard van Leer Foundation Newsletter, 1995

1995-01-01

This theme issue of the Bernard van Leer Foundation newsletter focuses on the problem of teenage pregnancy and teenage parenthood in developing and developed nations, and examines the problems that teenage mothers face in different societies. It explores societal norms and values related to teenage parenting; the effects of teenage parents on…

Artificial Exo-Society Modeling: a New Tool for SETI Research

NASA Astrophysics Data System (ADS)

Gardner, James N.

2002-01-01

One of the newest fields of complexity research is artificial society modeling. Methodologically related to artificial life research, artificial society modeling utilizes agent-based computer simulation tools like SWARM and SUGARSCAPE developed by the Santa Fe Institute, Los Alamos National Laboratory and the Bookings Institution in an effort to introduce an unprecedented degree of rigor and quantitative sophistication into social science research. The broad aim of artificial society modeling is to begin the development of a more unified social science that embeds cultural evolutionary processes in a computational environment that simulates demographics, the transmission of culture, conflict, economics, disease, the emergence of groups and coadaptation with an environment in a bottom-up fashion. When an artificial society computer model is run, artificial societal patterns emerge from the interaction of autonomous software agents (the "inhabitants" of the artificial society). Artificial society modeling invites the interpretation of society as a distributed computational system and the interpretation of social dynamics as a specialized category of computation. Artificial society modeling techniques offer the potential of computational simulation of hypothetical alien societies in much the same way that artificial life modeling techniques offer the potential to model hypothetical exobiological phenomena. NASA recently announced its intention to begin exploring the possibility of including artificial life research within the broad portfolio of scientific fields comprised by the interdisciplinary astrobiology research endeavor. It may be appropriate for SETI researchers to likewise commence an exploration of the possible inclusion of artificial exo-society modeling within the SETI research endeavor. Artificial exo-society modeling might be particularly useful in a post-detection environment by (1) coherently organizing the set of data points derived from a detected

Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver-stage development.

PubMed

Lindner, Scott E; Sartain, Mark J; Hayes, Kiera; Harupa, Anke; Moritz, Robert L; Kappe, Stefan H I; Vaughan, Ashley M

2014-02-01

Malaria parasites scavenge nutrients from their host but also harbour enzymatic pathways for de novo macromolecule synthesis. One such pathway is apicoplast-targeted type II fatty acid synthesis, which is essential for late liver-stage development in rodent malaria. It is likely that fatty acids synthesized in the apicoplast are ultimately incorporated into membrane phospholipids necessary for exoerythrocytic merozoite formation. We hypothesized that these synthesized fatty acids are being utilized for apicoplast-targeted phosphatidic acid synthesis, the phospholipid precursor. Phosphatidic acid is typically synthesized in a three-step reaction utilizing three enzymes: glycerol 3-phosphate dehydrogenase, glycerol 3-phosphate acyltransferase and lysophosphatidic acid acyltransferase. The Plasmodium genome is predicted to harbour genes for both apicoplast- and cytosol/endoplasmic reticulum-targeted phosphatidic acid synthesis. Our research shows that apicoplast-targeted Plasmodium yoelii glycerol 3-phosphate dehydrogenase and glycerol 3-phosphate acyltransferase are expressed only during liver-stage development and deletion of the encoding genes resulted in late liver-stage growth arrest and lack of merozoite differentiation. However, the predicted apicoplast-targeted lysophosphatidic acid acyltransferase gene was refractory to deletion and was expressed solely in the endoplasmic reticulum throughout the parasite life cycle. Our results suggest that P. yoelii has an incomplete apicoplast-targeted phosphatidic acid synthesis pathway that is essential for liver-stage maturation. © 2013 John Wiley & Sons Ltd.

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

PubMed Central

Mruk, Dolores D.; Silvestrini, Bruno; Cheng, C. Yan

2010-01-01

In multicellular organisms, cell-cell interactions are mediated in part by cell junctions, which underlie tissue architecture. Throughout spermatogenesis, for instance, preleptotene leptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must traverse the blood-testis barrier to enter the adluminal compartment for continued development. At the same time, germ cells must also remain attached to Sertoli cells, and numerous studies have reported extensive restructuring at the Sertoli-Sertoli and Sertoli-germ cell interface during germ cell movement across the seminiferous epithelium. Furthermore, the proteins and signaling cascades that regulate adhesion between testicular cells have been largely delineated. These findings have unveiled a number of potential “druggable” targets that can be used to induce premature release of germ cells from the seminiferous epithelium, resulting in transient infertility. Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis. PMID:18483144

Research and development on materials for the SPES target

NASA Astrophysics Data System (ADS)

Corradetti, Stefano; Andrighetto, Alberto; Manzolaro, Mattia; Scarpa, Daniele; Vasquez, Jesus; Rossignoli, Massimo; Monetti, Alberto; Calderolla, Michele; Prete, Gianfranco

2014-03-01

The SPES project at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro) is focused on the production of radioactive ion beams. The core of the SPES facility is constituted by the target, which will be irradiated with a 40 MeV, 200 µA proton beam in order to produce radioactive species. In order to efficiently produce and release isotopes, the material constituting the target should be able to work under extreme conditions (high vacuum and temperatures up to 2000 °C). Both neutron-rich and proton-rich isotopes will be produced; in the first case, carbon dispersed uranium carbide (UCx) will be used as a target, whereas to produce p-rich isotopes, several types of targets will have to be irradiated. The synthesis and characterization of different types of material will be reported. Moreover, the results of irradiation and isotopes release tests on different uranium carbide target prototypes will be discussed.

A Learned Society's Perspective on Publishing.

PubMed

Suzuki, Kunihiko; Edelson, Alan; Iversen, Leslie L; Hausmann, Laura; Schulz, Jörg B; Turner, Anthony J

2016-10-01

Scientific journals that are owned by a learned society, like the Journal of Neurochemistry (JNC), which is owned by the International Society for Neurochemistry (ISN), benefit the scientific community in that a large proportion of the income is returned to support the scientific mission of the Society. The income generated by the JNC enables the ISN to organize conferences as a platform for members and non-members alike to share their research, supporting researchers particularly in developing countries by travel grants and other funds, and promoting education in student schools. These direct benefits and initiatives for ISN members and non-members distinguish a society journal from pure commerce. However, the world of scholarly publishing is changing rapidly. Open access models have challenged the business model of traditional journal subscription and hence provided free access to publicly funded scientific research. In these models, the manuscript authors pay a publication cost after peer review and acceptance of the manuscript. Over the last decade, numerous new open access journals have been launched and traditional subscription journals have started to offer open access (hybrid journals). However, open access journals follow the general scheme that, of all participating parties, the publisher receives the highest financial benefit. The income is generated by researchers whose positions and research are mostly financed by taxpayers' or funders' money, and by reviewers and editors, who frequently are not reimbursed. Last but not least, the authors pay for the publication of their work after a rigorous and sometimes painful review process. JNC itself has an open access option, at a significantly reduced cost for Society members as an additional benefit. This article provides first-hand insights from two former Editors-in-Chief, Kunihiko Suzuki and Leslie Iversen, about the history of JNC's ownership and about the difficulties and battles fought along the way to

Towards integrative risk management and more resilient societies

NASA Astrophysics Data System (ADS)

Al-Khudhairy, D.; Axhausen, K.; Bishop, S.; Herrmann, H.; Hu, B.; Kröger, W.; Lewis, T.; MacIntosh, J.; Nowak, A.; Pickl, S.; Stauffacher, D.; Tan, E.

2012-11-01

Society depends decisively on the availability of infrastructure systems such as energy, telecommunication, transportation, banking and finance, health care and governmental and public administration. Even selective damages of one of these infrastructures may result in disruptions of governmental, industrial or public functions. Vulnerability of infrastructures therefore provides spectacular leverage for natural disasters as well as criminal and terrorist actions. Threats and risks are part of the technological, economical, and societal development. This article focuses on the development and characterization of an integrative risk-management which, from the perspective of "resilient systems", can be seen as an innovative and pro-active crisis management approach dealing with the increasing amount of complexity in societies in a comprehensive, agile and adaptive way.

Trypanothione Reductase: A Target for the Development of Anti- Trypanosoma cruzi Drugs.

PubMed

Vázquez, Karina; Paulino, Margot; Salas, Cristian O; Zarate-Ramos, Juan J; Vera, Brenda; Rivera, Gildardo

2017-01-01

Chagas disease or American trypanosomiasis is a major parasitic disease in Latin America with restricted available treatment: nifurtimox and benznidazole. These two drugs are ineffective in the chronic phase of the disease; therefore, there is a need for the development of new, efficient and safe drugs for the treatment of this pathology. With this goal, one of the promising targets is trypanothione reductase (TR), a key enzyme in the metabolism of Trypanosoma cruzi. In this review, we analyse the importance of TR as a drug target, as well as the well-known and new inhibitors reported in the last decade as potential therapeutic agents for Chagas disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ceramic Plutonium Target Development for the MASHA Separator for the Synthesis of Element 114

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

Shaughnessy, D A; Wilk, P A; Moody, K J

2005-06-29

We are currently developing a Pu ceramic target for the MASHA mass separator. MASHA will use a Pu ceramic target capable of tolerating temperatures up to 2000 C. Reaction products will diffuse out of the target into an ion source, and transported through the separator to a position-sensitive focal-plane detector array for mass identification. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide data for future experiments on chemical properties of the heaviest elements. In this study (Sm,Zr)O{sub 2-x} ceramics are produced and evaluated for studies on the production ofmore » Pb (homolog of element 114) by the reaction of Ca on Sm. This work will provide an initial analysis on the feasibility of using a ZrO{sub 2}-PuO{sub 2} as a target for the production of element 114.« less

FRAX(®) Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

PubMed

Lewiecki, E Michael; Compston, Juliet E; Miller, Paul D; Adachi, Jonathan D; Adams, Judith E; Leslie, William D; Kanis, John A

2011-01-01

FRAX(®) is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX(®) is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX(®) into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX(®) in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX(®) input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX(®) Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX(®)-related issues. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Molecular basis of Williams-Beuren syndrome: TFII-I regulated targets involved in craniofacial development.

PubMed

Makeyev, Aleksandr V; Bayarsaihan, Dashzeveg

2011-01-01

The aim of this study is to identify gene targets of TFII-I transcription factors involved in craniofacial development. Recent findings in individuals with Williams-Beuren syndrome who show facial dysmorphism and cognitive defects have pointed to TFII-I genes (GTF2I and GTF2IRD1) as the prime candidates responsible for these clinical features. However, TFII-I proteins are multifunctional transcriptional factors regulating a number of genes during development, and how their haploinsufficiency leads to the Williams-Beuren syndrome phenotype is currently unknown. Here we report the identification of three genes with a well-established relevance to craniofacial development as direct TFII-I targets. These genes, craniofacial development protein 1 (Cfdp1), Sec23 homolog A (Sec23a), and nuclear receptor binding SET domain protein 1 (Nsd1), contain consensus TFII-I binding sites in their proximal promoters; the chromatin immunoprecipitation analysis showed that TFII-I transcription factors are recruited to these sites in vivo. The results suggest that transcriptional regulation of these genes by TFII-I proteins could provide a possible genotype-phenotype link in Williams-Beuren syndrome.

Neuroendocrine tumors: insights into innovative therapeutic options and rational development of targeted therapies.

PubMed

Barbieri, Federica; Albertelli, Manuela; Grillo, Federica; Mohamed, Amira; Saveanu, Alexandru; Barlier, Anne; Ferone, Diego; Florio, Tullio

2014-04-01

Neuroendocrine tumors (NETs) are heterogeneous neoplasms with respect to molecular characteristics and clinical outcome. Although slow-growing, NETs are often late diagnosed, already showing invasion of adjacent tissues and metastases. Precise knowledge of NET biological and molecular features has opened the door to the identification of novel pharmacological targets. Therapeutic options include somatostatin analogs, alone or in combination with interferon-α, multi-targeted tyrosine kinase inhibitors (e.g. sunitinib) or mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus). Antiangiogenic approaches and anti insulin-like growth factor receptor (IGFR) compounds have been also proposed as combination therapies with the aforementioned compounds. This review will focus on recent studies that have improved therapeutic strategies in NETs, discussing management challenges such as drug resistance development as well as focusing on the need for predictive biomarkers to design distinct drug combinations and optimize pharmacological control. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Heuristic Model of Consciousness with Applications to the Development of Science and Society

NASA Technical Reports Server (NTRS)

Curreri, Peter A.

2010-01-01

A working model of consciousness is fundamental to understanding of the interactions of the observer in science. This paper examines contemporary understanding of consciousness. A heuristic model of consciousness is suggested that is consistent with psycophysics measurements of bandwidth of consciousness relative to unconscious perception. While the self reference nature of consciousness confers a survival benefit by assuring the all points of view regarding a problem are experienced in sufficiently large population, conscious bandwidth is constrained by design to avoid chaotic behavior. The multiple hypotheses provided by conscious reflection enable the rapid progression of science and technology. The questions of free will and the problem of attention are discussed in relation to the model. Finally the combination of rapid technology growth with the assurance of many unpredictable points of view is considered in respect to contemporary constraints to the development of society.

Development of Peritoneal Tumor-Targeting Vector by In Vivo Screening with a Random Peptide-Displaying Adenovirus Library

PubMed Central

Yoshida, Kimiko; Goto, Naoko; Ohnami, Shumpei; Aoki, Kazunori

2012-01-01

The targeting of gene transfer at the cell-entry level is one of the most attractive challenges in vector development. However, attempts to redirect adenovirus vectors to alternative receptors by engineering the capsid-coding region have shown limited success, because the proper targeting ligands on the cells of interest are generally unknown. To overcome this limitation, we have constructed a random peptide library displayed on the adenoviral fiber knob, and have successfully selected targeted vectors by screening the library on cancer cell lines in vitro. The infection of targeted vectors was considered to be mediated by specific receptors on target cells. However, the expression levels and kinds of cell surface receptors may be substantially different between in vitro culture and in vivo tumor tissue. Here, we screened the peptide display-adenovirus library in the peritoneal dissemination model of AsPC-1 pancreatic cancer cells. The vector displaying a selected peptide (PFWSGAV) showed higher infectivity in the AsPC-1 peritoneal tumors but not in organs and other peritoneal tumors as compared with a non-targeted vector. Furthermore, the infectivity of the PFWSGAV-displaying vector for AsPC-1 peritoneal tumors was significantly higher than that of a vector displaying a peptide selected by in vitro screening, indicating the usefulness of in vivo screening in exploring the targeting vectors. This vector-screening system can facilitate the development of targeted adenovirus vectors for a variety of applications in medicine. PMID:23029088

An efficient case finding strategy to diagnose osteoporosis in a developing society with low treatment frequency.

PubMed

Sørensen, Vibeke Neergaard; Wojtek, Piotr; Pedersen, Dorthe S; Andersen, Stig

2015-08-01

Osteoporosis is a debilitating condition with rising frequency of fragility fractures with advancing age. Life expectancy increases in developing societies with the emergence of osteoporosis. There is a need for a simple protocol to diagnose fractures that merit treatment for osteoporosis. Evaluation of all consecutive lateral chest radiographs performed at the National Hospital in the capital city in Greenland over a 3-month period for vertebral body heights at the anterior, middle and posterior regions. Use of anti-osteoporotic drug was evaluated from records of dispensed drugs from Greenland National Pharmacy. 1869 vertebrae were evaluated on radiographs from 203 subjects. On average 9.2 vertebrae (range 5-13) qualified for evaluation in each individual. Median (range) age was 55 (30-82) years. Any vertebral deformity above 25 (20) % was seen in 28.6 (50.2) %. More than one fracture was seen in 10.3 (27.1) %. Fractures occurred in 18.5 (36.9) % of patients from the General Medicine Clinic and in 33.3 (56.5) % of inpatients (p = 0.029). The occurrence of vertebral fractures increased with age (p < 0.001) and hosting more than one vertebral fracture was markedly more frequent after the age of 60 years [OR, 95 % CI 9.6, 3.1-30 (5.7, 2.9-11); p < 0.001] after correction for gender in logistic regressions. The National Pharmacy handed out anti-osteoporotic drugs equal to the treatment of 36 individuals. Vertebral fractures that merit treatment can be readily diagnosed from lateral chest radiographs taken in routine clinical work-up. They are common in Greenland as demonstrated by this simple protocol to improve diagnosis and treatment of osteoporosis in a developing society.

Social penalty promotes cooperation in a cooperative society.

PubMed

Ito, Hiromu; Yoshimura, Jin

2015-08-04

Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner's dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation.

Social penalty promotes cooperation in a cooperative society

PubMed Central

Ito, Hiromu; Yoshimura, Jin

2015-01-01

Why cooperation is well developed in human society is an unsolved question in biological and human sciences. Vast studies in game theory have revealed that in non-cooperative games selfish behavior generally dominates over cooperation and cooperation can be evolved only under very limited conditions. These studies ask the origin of cooperation; whether cooperation can evolve in a group of selfish individuals. In this paper, instead of asking the origin of cooperation, we consider the enhancement of cooperation in a small already cooperative society. We ask whether cooperative behavior is further promoted in a small cooperative society in which social penalty is devised. We analyze hawk-dove game and prisoner’s dilemma introducing social penalty. We then expand it for non-cooperative games in general. The results indicate that cooperation is universally favored if penalty is further imposed. We discuss the current result in terms of the moral, laws, rules and regulations in a society, e.g., criminology and traffic violation. PMID:26238521

Targeting carbon for crop yield and drought resilience.

PubMed

Griffiths, Cara A; Paul, Matthew J

2017-11-01

Current methods of crop improvement are not keeping pace with projected increases in population growth. Breeding, focused around key traits of stem height and disease resistance, delivered the step-change yield improvements of the green revolution of the 1960s. However, subsequently, yield increases through conventional breeding have been below the projected requirement of 2.4% per year required by 2050. Genetic modification (GM) mainly for herbicide tolerance and insect resistance has been transformational, akin to a second green revolution, although GM has yet to make major inroads into intrinsic yield processes themselves. Drought imposes the major restriction on crop yields globally but, as yet, has not benefited substantially from genetic improvement and still presents a major challenge to agriculture. Much still has to be learnt about the complex process of how drought limits yield and what should be targeted. Mechanisms of drought adaptation from the natural environment cannot be taken into crops without significant modification for the agricultural environment because mechanisms of drought tolerance are often in contrast with mechanisms of high productivity required in agriculture. However, through convergence of fundamental and translational science, it would appear that a mechanism of sucrose allocation in crops can be modified for both productivity and resilience to drought and other stresses. Recent publications show how this mechanism can be targeted by GM, natural variation and a new chemical approach. Here, with an emphasis on drought, we highlight how understanding fundamental science about how crops grow, develop and what limits their growth and yield can be combined with targeted genetic selection and pioneering chemical intervention technology for transformational yield improvements. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors

Incorporating multiple secondary targets into learning trials for individuals with autism spectrum disorder.

PubMed

Nottingham, Casey L; Vladescu, Jason C; Kodak, Tiffany; Kisamore, April N

2017-07-01

The current study examined the outcome of presenting multiple secondary targets in learning trials for individuals with autism spectrum disorder. We compared conditions in which (a) a secondary target was presented in the antecedent and consequence of trials, (b) two secondary targets were presented in the consequence of trials, (c) one secondary target was presented in the consequence of each trial, and (d) no additional targets were presented trials. The participants acquired the majority of secondary targets. Presenting one or multiple secondary targets per trial, regardless of the location of these secondary targets, increased the efficiency of instruction in comparison to a condition with no secondary target. © 2017 Society for the Experimental Analysis of Behavior.

Advanced information society(5)

NASA Astrophysics Data System (ADS)

Tanizawa, Ippei

Based on the advancement of information network technology information communication forms informationalized society giving significant impact on business activities and life style in it. The information network has been backed up technologically by development of computer technology and has got great contribution by enhanced computer technology and communication equipments. Information is transferred by digital and analog methods. Technical development which has brought out multifunctioned modems of communication equipments in analog mode, and construction of advanced information communication network which has come out by joint work of computer and communication under digital technique, are described. The trend in institutional matter and standardization of electrical communication is also described showing some examples of value-added network (VAN).

Curriculum and Civil Society in Afghanistan

ERIC Educational Resources Information Center

Jones, Adele

2009-01-01

Although research has traditionally discussed the ways in which societies in conflict develop educational practices, only recently have scholars begun to examine the role of education in creating or sustaining conflict. In Afghanistan, changing regimes have had an impact on state-sanctioned curricula over the past fifty years, drastically altering…

A Systems Definition of Educational Technology in Society

ERIC Educational Resources Information Center

Luppicini, Rocci

2005-01-01

Conceptual development in the field of Educational Technology provides crucial theoretical grounding for ongoing research and practice. This essay draws from theoretical developments both within and external to the field of Educational Technology to articulate a systems definition of Educational Technology in Society. A systems definition of…

Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

PubMed

Mohammadipanah, Fatemeh; Salimi, Fatemeh

2018-02-01

Sturge-Weber Syndrome (SWS) is a neurocutaneous disease with clinical manifestations including ocular (glaucoma), cutaneous (port-wine birthmark), neurologic (seizures), and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against its progression. Development of such platforms of bioassay can bring along the implementation of high-throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of molecular targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholinesterase, alkaline phosphatase, GABAergic receptors, Hypoxia-Inducible Factor (HIF)-1α and 2α are suggested. © 2017 John Wiley & Sons A/S.

The ontogeny of fairness in seven societies.

PubMed

Blake, P R; McAuliffe, K; Corbit, J; Callaghan, T C; Barry, O; Bowie, A; Kleutsch, L; Kramer, K L; Ross, E; Vongsachang, H; Wrangham, R; Warneken, F

2015-12-10

A sense of fairness plays a critical role in supporting human cooperation. Adult norms of fair resource sharing vary widely across societies, suggesting that culture shapes the acquisition of fairness behaviour during childhood. Here we examine how fairness behaviour develops in children from seven diverse societies, testing children from 4 to 15 years of age (n = 866 pairs) in a standardized resource decision task. We measured two key aspects of fairness decisions: disadvantageous inequity aversion (peer receives more than self) and advantageous inequity aversion (self receives more than a peer). We show that disadvantageous inequity aversion emerged across all populations by middle childhood. By contrast, advantageous inequity aversion was more variable, emerging in three populations and only later in development. We discuss these findings in relation to questions about the universality and cultural specificity of human fairness.

Finding the sweet spots of inhibition: understanding the targets of a functional antibody against Plasmodium vivax Duffy binding protein.

PubMed

Ntumngia, Francis B; King, Christopher L; Adams, John H

2012-11-01

Plasmodium vivax Duffy binding protein region II (DBPII) is an essential ligand for reticulocyte invasion, thereby making this molecule an attractive vaccine candidate against asexual blood-stage P. vivax. Similar to other Plasmodium blood-stage vaccine candidates, strain-specific immunity due to DBPII allelic variation may complicate vaccine efficacy. Targeting immune responses to more conserved epitopes that are potential targets of strain-transcending neutralising immunity is necessary to avoid induction of strain-specific responses to dominant variant epitopes. In this article, we focus on different approaches to optimise the design of DBP immunogenicity to target conserved epitopes, which is important for developing a broadly effective vaccine against P. vivax. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

PubMed

Agrawal, Anurag; Mabalirajan, Ulaganathan

2016-01-15

Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases. Copyright © 2016 the American Physiological Society.

Locating the fourth helix: Rethinking the role of civil society in developing smart learning cities

NASA Astrophysics Data System (ADS)

Borkowska, Katarzyna; Osborne, Michael

2018-06-01

In the Global North and increasingly in the Global South, smart city technologies are enthusiastically seen as a solution to urban problems and as an alternative to austerity. However, to move beyond a narrow technological focus, it is necessary to explore the degree to which smart initiatives are committed to building socially inclusive innovation with learning at its core. Using the particular case of the Future City Demonstrator Initiative in Glasgow, United Kingdom, the most high-profile initiative of its kind funded by government, the authors of this article assess the extent to which this smart city adopts such an inclusive approach. They use the quadruple helix model (government - academia - industry - civil society) as a starting point and develop an analytic framework composed of four strands: (1) supporting participation of citizens in decision-making; (2) implementing technological innovation which positions citizens as active users; (3) implementing technological innovation to benefit the community; and (4) evaluating technological innovation in the light of the experiences and needs of citizens. Unlike most analyses, the principal focus of this article is on the fourth element of the helix, civil society. The authors argue that Glasgow's rhetoric of smart urbanism, while aspiring to problem-solving, devalues certain principles of human agency. They emphasise that urban change, including the city's desire to become technologically innovative, would more fully facilitate active citizenship, social inclusion and learning opportunities for all if it were underpinned by the broader conceptions and frameworks of learning cities.

Society of Pediatric Psychology Workforce Survey: Development of Survey Methods, Sample Characteristics, and Lessons Learned

PubMed Central

Wysocki, Tim; Brosig, Cheryl L.; Hilliard, Marisa E.

2016-01-01

There are few detailed workforce studies of specialty fields within professional psychology, and none have been reported for pediatric psychology since 2006. Availability of such data could facilitate more-informed decision making by students and trainees, psychologists pursuing employment opportunities, and psychologists involved in employment or compensation negotiations. This article describes the work of a task force of the American Psychological Association (APA) Division 54 (Society of Pediatric Psychology) in the design, construction, pretesting, distribution, and data management for the Society of Pediatric Psychology (SPP) Workforce Survey. The 18-member task force was established to design and implement a workforce survey that balanced needs for breadth, clarity, brevity, and protection of confidentiality. The survey solicits information about demographic characteristics; training, licensure and certifications; employment settings, responsibilities, and productivity metrics; compensation; and employment satisfaction. A survey link was distributed via e-mail to full members of the SPP in June 2015. A total of 404 members (32.3% return rate) completed the survey. This article focuses on the development, methodology, and respondent characteristics for this 1st administration of the workforce survey. Separate articles will report detailed analyses of the survey results such as compensation and work satisfaction. Future distributions of the survey will enable compilation of a longitudinal database to track changes in the profession. SPP members and others may propose additional analyses of these data. This work may provide guidance to other groups of specialized psychologists who may wish to implement similar initiatives. PMID:28066693

Scaling up model of social capital: Developing a model of empowerment for poor society in rural areas

NASA Astrophysics Data System (ADS)

Chawa, A. F.; Kusumastuti, A.; Harjo, I. W. W.

2017-06-01

Indonesian government has delivered various community development programs to alleviate poverty problems of rural communities. This is despite the fact that the numbers of people who live in poverty in this area is going to increase. This has given rise to a crucial question in how development programs should be distributed to rural community members. This article present empirical findings of research depicts a model or mechanism by which rural community members who have been involved in Posdaya (Pos Pemberdayaan Keluarga/ Family Empowerment Post) program success in achieving economic empowerment objective by employing their social capital. This study employs qualitative method with an approach of case study and multiple case design. It conducts the logic of ‘replica’, meaning that it would lead the analysed case to be used either for making predictions of similar results (literal logic) or for achieving different results (theoretical replica). The fundamental assumption of the study refers to the lack involvement or participation of the empowered community or social groups. The domination of top-down approach has allowed people to rely on external party. On the other hand, bottom-up approach has not been fully implemented due to the absence of strong social capital in the empowered society. As a consequence, there have been only parts of people controlling and enjoying the presented empowerment program. Social capital is not an existing or a given capital in society. Rather, social capital is a mere potential, and in order to shape and develop it some strategies or endeavours are required. Thus, the study attempts to find out a suitable model to arrange and progress the social capital in the implementation of social empowerment program. Additionally, the study will advance the scaling up model into a wider space with an expectation to create a powerful community.

Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology.

PubMed

Jackson, Neville; Atar, Dan; Borentain, Maria; Breithardt, Günter; van Eickels, Martin; Endres, Matthias; Fraass, Uwe; Friede, Tim; Hannachi, Hakima; Janmohamed, Salim; Kreuzer, Jörg; Landray, Martin; Lautsch, Dominik; Le Floch, Chantal; Mol, Peter; Naci, Huseyin; Samani, Nilesh J; Svensson, Anders; Thorstensen, Cathrine; Tijssen, Jan; Vandzhura, Victoria; Zalewski, Andrew; Kirchhof, Paulus

2016-03-01

Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines. The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development. A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier

Reflective Education as a Means of Changing Teacher Trainers' Attitudes towards Universal Values in the Education System of the Developing Society

ERIC Educational Resources Information Center

Essawi, Mohammad; Abu-Hussain, Jamal; Fadila, Dalia

2014-01-01

The proposed intervention program's aim was to change teacher trainers' attitudes towards universal values. The program takes into account the unique cultural context of the developing society. The goal of the program was to reduce the gap between declared teacher trainers' attitudes and their actual attitudes towards universal values in the…

North American Fuzzy Logic Processing Society (NAFIPS 1992), volume 1

NASA Technical Reports Server (NTRS)

Villarreal, James A. (Compiler)

1992-01-01

This document contains papers presented at the NAFIPS '92 North American Fuzzy Information Processing Society Conference. More than 75 papers were presented at this Conference, which was sponsored by NAFIPS in cooperation with NASA, the Instituto Tecnologico de Morelia, the Indian Society for Fuzzy Mathematics and Information Processing (ISFUMIP), the Instituto Tecnologico de Estudios Superiores de Monterrey (ITESM), the International Fuzzy Systems Association (IFSA), the Japan Society for Fuzzy Theory and Systems, and the Microelectronics and Computer Technology Corporation (MCC). The fuzzy set theory has led to a large number of diverse applications. Recently, interesting applications have been developed which involve the integration of fuzzy systems with adaptive processes such as neural networks and genetic algorithms. NAFIPS '92 was directed toward the advancement, commercialization, and engineering development of these technologies.

North American Fuzzy Logic Processing Society (NAFIPS 1992), volume 2

NASA Technical Reports Server (NTRS)

Villarreal, James A. (Compiler)

1992-01-01

This document contains papers presented at the NAFIPS '92 North American Fuzzy Information Processing Society Conference. More than 75 papers were presented at this Conference, which was sponsored by NAFIPS in cooperation with NASA, the Instituto Tecnologico de Morelia, the Indian Society for Fuzzy Mathematics and Information Processing (ISFUMIP), the Instituto Tecnologico de Estudios Superiores de Monterrey (ITESM), the International Fuzzy Systems Association (IFSA), the Japan Society for Fuzzy Theory and Systems, and the Microelectronics and Computer Technology Corporation (MCC). The fuzzy set theory has led to a large number of diverse applications. Recently, interesting applications have been developed which involve the integration of fuzzy systems with adaptive processes such a neural networks and genetic algorithms. NAFIPS '92 was directed toward the advancement, commercialization, and engineering development of these technologies.

Development of a vision-targeted health-related quality of life item measure

PubMed Central

Slotkin, Jerry; McKean-Cowdin, Roberta; Lee, Paul; Owsley, Cynthia; Vitale, Susan; Varma, Rohit; Gershon, Richard; Hays, Ron D.

2013-01-01

Purpose To develop a vision-targeted health-related quality of life (HRQOL) measure for the NIH Toolbox for the Assessment of Neurological and Behavioral Function. Methods We conducted a review of existing vision-targeted HRQOL surveys and identified color vision, low luminance vision, distance vision, general vision, near vision, ocular symptoms, psychosocial well-being, and role performance domains. Items in existing survey instruments were sorted into these domains. We selected non-redundant items and revised them to improve clarity and to limit the number of different response options. We conducted 10 cognitive interviews to evaluate the items. Finally, we revised the items and administered them to 819 individuals to calibrate the items and estimate the measure’s reliability and validity. Results The field test provided support for the 53-item vision-targeted HRQOL measure encompassing 6 domains: color vision, distance vision, near vision, ocular symptoms, psychosocial well-being, and role performance. The domain scores had high levels of reliability (coefficient alphas ranged from 0.848 to 0.940). Validity was supported by high correlations between National Eye Institute Visual Function Questionnaire scales and the new-vision-targeted scales (highest values were 0.771 between psychosocial well-being and mental health, and 0.729 between role performance and role difficulties), and by lower mean scores in those groups self-reporting eye disease (F statistic with p < 0.01 for all comparisons except cataract with ocular symptoms, psychosocial well-being, and role performance scales). Conclusions This vision-targeted HRQOL measure provides a basis for comprehensive assessment of the impact of eye diseases and treatments on daily functioning and well-being in adults. PMID:23475688

Multisociety consensus quality improvement guidelines for intraarterial catheter-directed treatment of acute ischemic stroke, from the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology.

PubMed

Sacks, David; Black, Carl M; Cognard, Christophe; Connors, John J; Frei, Donald; Gupta, Rishi; Jovin, Tudor G; Kluck, Bryan; Meyers, Philip M; Murphy, Kieran J; Ramee, Stephen; Rüfenacht, Daniel A; Bernadette Stallmeyer, M J; Vorwerk, Dierk

2013-02-01

In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. It is intended that these benchmarks be used in a quality assurance program to assess and improve processes and outcomes in acute stroke revascularization. Members of the writing group were appointed by the American Society of Neuroradiology, Canadian Interventional Radiology Association, Cardiovascular and Interventional Radiological Society of Europe, Society of Cardiac Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, European Society of Minimally Invasive Neurological Therapy, and Society of Vascular and Interventional Neurology. The writing group reviewed the relevant literature from 1986 through February 2012 to create an evidence table summarizing processes and outcomes of care. Performance metrics and thresholds were then created by consensus. The guideline was approved by the sponsoring societies. It is intended that this guideline be fully updated in 3 years. In this international multispecialty document, quality benchmarks for processes of care and clinical outcomes are defined. These include process measures of time to imaging, arterial puncture, and revascularization and measures of clinical outcome up to 90 days. Quality improvement guidelines are provided for endovascular acute ischemic stroke revascularization procedures. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

Participation of women in neurochemistry societies.

PubMed

Lees, Marjorie B

2002-11-01

Women have made important scientific contributions to the field of neurochemistry, and they have also been leaders in neurochemical societies throughout the world. Here I discuss women's involvement and leadership in six neurochemistry societies: American Society for Neurochemistry, Argentine Society for Neurochemistry, International Society for Neurochemistry, European Society for Neurochemistry, Japanese Society for Neurochemistry, and Asian-Pacific Society for Neurochemistry. The number of women who have been active in these societies and the level of their activity vary considerably. Neurochemical societies in the Western hemisphere, i.e., the American and the Argentine Society for Neurochemistry, have much greater numbers of women who have held office, been on council, or engaged in other leadership activities than in the rest of the world. The limited participation of women in the Japanese Neurochemistry Society relates to Japanese cultural views and was not unexpected. However, the relatively few women leaders in the International Society for Neurochemistry was a surprise. The European Society had a somewhat better record of female participation than did the International Society. The reasons for these differences are partly cultural, but factors related to when each society was formed, how it is organized, and how elections are structured undoubtedly play a role. Further analysis of these observations would be of interest from a sociological and a women's studies point of view.

Strategic Protein Target Analysis for Developing Drugs to Stop Dental Caries

PubMed Central

Horst, J.A.; Pieper, U.; Sali, A.; Zhan, L.; Chopra, G.; Samudrala, R.; Featherstone, J.D.B.

2012-01-01

Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries. PMID:22899687

An official American Thoracic Society/European Respiratory Society policy statement: disparities in respiratory health.

PubMed

Schraufnagel, Dean E; Blasi, Francesco; Kraft, Monica; Gaga, Mina; Finn, Patricia W; Rabe, Klaus F

2013-10-01

Health disparities, defined as a significant difference in health between populations, are more common for diseases of the respiratory system than for those of other organ systems, because of the environmental influence on breathing and the variation of the environment among different segments of the population. The lowest social groups are up to 14 times more likely to have respiratory diseases than are the highest. Tobacco smoke, air pollution, environmental exposures, and occupational hazards affect the lungs more than other organs, and occur disproportionately in ethnic minorities and those with lower socioeconomic status. Lack of access to quality health care contributes to disparities. The executive committees of the American Thoracic Society (ATS) and European Respiratory Society (ERS) established a writing committee to develop a policy on health disparities. The document was reviewed, edited, and approved by the full executive committees and boards of directors of the societies. This document expresses a policy to address health disparities by promoting scientific inquiry and training, disseminating medical information and best practices, and monitoring and advocating for public respiratory health. ERS and ATS have strong international commitments, and work with leaders from governments, academia, and organizations to address and reduce avoidable health inequalities. Their training initiatives improve the function of health care systems and health equality. Both the ATS and ERS support all aspects of this document, confer regularly, and act together when possible, but the activities to bring about change may vary because of the differences in the continents where the two organizations carry out most of their activities. The ATS and ERS pledge to frame their actions to reduce respiratory health disparities. The vision of the ATS and ERS is that all persons attain better and sustained respiratory health. They call on all their members and other societies to

Therapeutics targeting Bcl-2 in hematological malignancies.

PubMed

Ruefli-Brasse, Astrid; Reed, John C

2017-10-23

Members of the B-cell lymphoma 2 ( BCL-2 ) gene family are attractive targets for cancer therapy as they play a key role in promoting cell survival, a long-since established hallmark of cancer. Clinical utility for selective inhibition of specific anti-apoptotic Bcl-2 family proteins has recently been realized with the Food and Drug Administration (FDA) approval of venetoclax (formerly ABT-199/GDC-0199) in relapsed chronic lymphocytic leukemia (CLL) with 17p deletion. Despite the impressive monotherapy activity in CLL, such responses have rarely been observed in other B-cell malignancies, and preclinical data suggest that combination therapies will be needed in other indications. Additional selective antagonists of Bcl-2 family members, including Bcl-X L and Mcl-1, are in various stages of preclinical and clinical development and hold the promise of extending clinical utility beyond CLL and overcoming resistance to venetoclax. In addition to direct targeting of Bcl-2 family proteins with BH3 mimetics, combination therapies that aim at down-regulating expression of anti-apoptotic BCL-2 family members or restoring expression of pro-apoptotic BH3 family proteins may provide a means to deepen responses to venetoclax and extend the utility to additional indications. Here, we review recent progress in direct and selective targeting of Bcl-2 family proteins for cancer therapy and the search for rationale combinations. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

State of Early Child Development Research, Practice, and Policy for Most Vulnerable Children: A Global Perspective

ERIC Educational Resources Information Center

Young, Mary Eming

2017-01-01

Interventions to enhance development of children ages 0-6 have profound benefits for children, families, and societies. The benefits are well documented, recognized internationally, and supportive of policies and programs targeting early child development (ECD). Intervening in the early years is a critical first step toward alleviating poverty,…

European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism

PubMed Central

Léger, Juliane; Olivieri, Antonella; Donaldson, Malcolm; Torresani, Toni; Krude, Heiko; van Vliet, Guy; Polak, Michel

2014-01-01

Objective: The aim was to formulate practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). Evidence: A systematic literature search was conducted to identify key articles relating to the screening, diagnosis, and management of CH. The evidence-based guidelines were developed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. Consensus Process: Thirty-two participants drawn from the European Society for Paediatric Endocrinology and five other major scientific societies in the field of pediatric endocrinology were allocated to working groups with assigned topics and specific questions. Each group searched the literature, evaluated the evidence, and developed a draft document. These papers were debated and finalized by each group before presentation to the full assembly for further discussion and agreement. Recommendations: The recommendations include: worldwide neonatal screening, approaches to assess the cause (including genotyping) and the severity of the disorder, the immediate initiation of appropriate L-T4 supplementation and frequent monitoring to ensure dose adjustments to keep thyroid hormone levels in the target ranges, a trial of treatment in patients suspected of transient CH, regular assessments of developmental and neurosensory functions, consulting health professionals as appropriate, and education about CH. The harmonization of diagnosis, management, and routine health surveillance would not only optimize patient outcomes, but should also facilitate epidemiological studies of the disorder. Individuals with CH require monitoring throughout their lives, particularly during early childhood and pregnancy. PMID:24446653

Monoacylglycerol lipase – a target for drug development?

PubMed Central

Fowler, CJ

2012-01-01

The endocannabinoid (eCB) system is involved in processes as diverse as control of appetite, perception of pain and the limitation of cancer cell growth and invasion. The enzymes responsible for eCB breakdown are attractive pharmacological targets, and fatty acid amide hydrolase inhibitors, which potentiate the levels of the eCB anandamide, are now undergoing pharmaceutical development. ‘Drugable’ selective inhibitors of monoacylglycerol lipase, a key enzyme regulating the levels of the other main eCB, 2-arachidonoylglycerol, were however not identified until very recently. Their availability has resulted in a large expansion of our knowledge concerning the pharmacological consequences of monoacylglycerol lipase inhibition and hence the role(s) played by the enzyme in the body. In this review, the pharmacology of monoacylglycerol lipase will be discussed, together with an analysis of the therapeutic potential of monoacylglycerol lipase inhibitors as analgesics and anticancer agents. PMID:22428756

Reflections on civil society and gender.

PubMed

Thacker, P

1997-07-01

This article discusses ways to empower women in rural Nepal. Nepal needs to plan for the expected doubling of its population in the next 28 years. It is important that priorities be established in national development strategies. Nongovernmental organizations (NGOs) and the private sector will also play a role in development. Nepal is a multiethnic society with about 42% of its population living in poverty. About 42% are aged under 15 years. A major task of development is to engender a sense of hopefulness for young people, despite a deteriorating social situation. The government, the private sector, and NGOs must all act in a socially responsible manner by creating job opportunities and building infrastructure. Development should not concentrate on projects alone and should contribute to an equitable and just society, distributive justice, and sustainability. Economic growth is a lesser concern. Activism and intuition are necessary subjective approaches outside the realm of objective academic research. It is important to retain women's knowledge base of indigenous ways of doing things. Women are participating in NGOs in a variety of capacities. Although women's NGO participation may build important bridges of cooperation, their work remains invisible. NGOs are key players in exposing poor people's agenda in international forums. NGOs work with different ideologies and without political bases, which must be surmounted in building cooperation with the private sector. Elites must act responsibly to expose patriarchy and gender insubordination. Development interventions must be based on gender, economic, and social class relations.

Young People in the Information Society

ERIC Educational Resources Information Center

Lebedeva, E. V.

2011-01-01

In the summer of 2007, the Laboratory for the Social Problems of the Development of the Information Society, Institute for Socioeconomic Studies of the Population, Russian Academy of Sciences, in collaboration with the Modern Academy of the Humanities, carried out a survey of the level of use of information and communication technologies (ICT) by…

Liposomes and nanotechnology in drug development: focus on ocular targets

PubMed Central

Honda, Miki; Asai, Tomohiro; Oku, Naoto; Araki, Yoshihiko; Tanaka, Minoru; Ebihara, Nobuyuki

2013-01-01

Poor drug delivery to lesions in patients’ eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases. PMID:23439842

SRNL Development of Recovery Processes for Mark-18A Heavy Actinide Targets

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

Allender, Jeffrey S.; Bridges, Nicholas J.; Loftin, Bradley M.

2015-07-14

Savannah River National Laboratory (SRNL) and Oak Ridge National Laboratory (ORNL) are developing plans for the recovery of rare and unique isotopes contained within heavy-actinide target assemblies, specifically the Mark-18A. Mark-18A assemblies were irradiated in Savannah River Site (SRS) reactors in the 1970s under extremely high neutron-flux conditions and produced, virtually, the world's supply of plutonium-244, an isotope of key importance to high-precision actinide measurement and other scientific and nonproliferation uses; and curium highly enriched in heavy isotopes (e.g., curium-246 and curium-248). In 2015 and 2016, SRNL is pursuing tasks that would reduce program risk and budget requirements, including furthermore » characterization of unprocessed targets; engineering studies for the use of the SRNL Shielded Cells Facility (SCF) for recovery; and development of onsite and offsite shipping methods including a replacement for the heavy (70 ton) cask previously used for onsite transfer of irradiated items at SRS. A status update is provided for the characterization, including modeling using the Monte Carlo N-Particle Transport Code (MCNP); direct non-destructive assay measurements; and cask design.« less

Genomic Target Database (GTD): A database of potential targets in human pathogenic bacteria

PubMed Central

Barh, Debmalya; Kumar, Anil; Misra, Amarendra Narayana

2009-01-01

A Genomic Target Database (GTD) has been developed having putative genomic drug targets for human bacterial pathogens. The selected pathogens are either drug resistant or vaccines are yet to be developed against them. The drug targets have been identified using subtractive genomics approaches and these are subsequently classified into Drug targets in pathogen specific unique metabolic pathways,Drug targets in host-pathogen common metabolic pathways, andMembrane localized drug targets. HTML code is used to link each target to its various properties and other available public resources. Essential resources and tools for subtractive genomic analysis, sub-cellular localization, vaccine and drug designing are also mentioned. To the best of authors knowledge, no such database (DB) is presently available that has listed metabolic pathways and membrane specific genomic drug targets based on subtractive genomics. Listed targets in GTD are readily available resource in developing drug and vaccine against the respective pathogen, its subtypes, and other family members. Currently GTD contains 58 drug targets for four pathogens. Shortly, drug targets for six more pathogens will be listed. Availability GTD is available at IIOAB website http://www.iioab.webs.com/GTD.htm. It can also be accessed at http://www.iioabdgd.webs.com.GTD is free for academic research and non-commercial use only. Commercial use is strictly prohibited without prior permission from IIOAB. PMID:20011153

Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase-a comprehensive drug target database for Lymphatic filariasis

NASA Astrophysics Data System (ADS)

Sharma, Om Prakash; Kumar, Muthuvel Suresh

2016-01-01

Lymphatic filariasis (Lf) is one of the oldest and most debilitating tropical diseases. Millions of people are suffering from this prevalent disease. It is estimated to infect over 120 million people in at least 80 nations of the world through the tropical and subtropical regions. More than one billion people are in danger of getting affected with this life-threatening disease. Several studies were suggested its emerging limitations and resistance towards the available drugs and therapeutic targets for Lf. Therefore, better medicine and drug targets are in demand. We took an initiative to identify the essential proteins of Wolbachia endosymbiont of Brugia malayi, which are indispensable for their survival and non-homologous to human host proteins. In this current study, we have used proteome subtractive approach to screen the possible therapeutic targets for wBm. In addition, numerous literatures were mined in the hunt for potential drug targets, drugs, epitopes, crystal structures, and expressed sequence tag (EST) sequences for filarial causing nematodes. Data obtained from our study were presented in a user friendly database named FiloBase. We hope that information stored in this database may be used for further research and drug development process against filariasis. URL: http://filobase.bicpu.edu.in.

Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures.

PubMed

Doria, Filippo; Nadai, Matteo; Folini, Marco; Di Antonio, Marco; Germani, Luca; Percivalle, Claudia; Sissi, Claudia; Zaffaroni, Nadia; Alcaro, Stefano; Artese, Anna; Richter, Sara N; Freccero, Mauro

2012-04-14

The synthesis, physico-chemical properties and biological effects of a new class of naphthalene diimides (NDIs) capable of reversibly binding telomeric DNA and alkylate it through an electrophilic quinone methide moiety (QM), are reported. FRET and circular dichroism assays showed a marked stabilization and selectivity towards telomeric G4 DNA folded in a hybrid topology. NDI-QMs' alkylating properties revealed a good reactivity on single nucleosides and selectivity towards telomeric G4. A selected NDI was able to significantly impair the growth of melanoma cells by causing telomere dysfunction and down-regulation of telomerase expression. These findings points to our hybrid ligand-alkylating NDIs as possible tools for the development of novel targeted anticancer therapies. This journal is © The Royal Society of Chemistry 2012

Open Targets: a platform for therapeutic target identification and validation

PubMed Central

Koscielny, Gautier; An, Peter; Carvalho-Silva, Denise; Cham, Jennifer A.; Fumis, Luca; Gasparyan, Rippa; Hasan, Samiul; Karamanis, Nikiforos; Maguire, Michael; Papa, Eliseo; Pierleoni, Andrea; Pignatelli, Miguel; Platt, Theo; Rowland, Francis; Wankar, Priyanka; Bento, A. Patrícia; Burdett, Tony; Fabregat, Antonio; Forbes, Simon; Gaulton, Anna; Gonzalez, Cristina Yenyxe; Hermjakob, Henning; Hersey, Anne; Jupe, Steven; Kafkas, Şenay; Keays, Maria; Leroy, Catherine; Lopez, Francisco-Javier; Magarinos, Maria Paula; Malone, James; McEntyre, Johanna; Munoz-Pomer Fuentes, Alfonso; O'Donovan, Claire; Papatheodorou, Irene; Parkinson, Helen; Palka, Barbara; Paschall, Justin; Petryszak, Robert; Pratanwanich, Naruemon; Sarntivijal, Sirarat; Saunders, Gary; Sidiropoulos, Konstantinos; Smith, Thomas; Sondka, Zbyslaw; Stegle, Oliver; Tang, Y. Amy; Turner, Edward; Vaughan, Brendan; Vrousgou, Olga; Watkins, Xavier; Martin, Maria-Jesus; Sanseau, Philippe; Vamathevan, Jessica; Birney, Ewan; Barrett, Jeffrey; Dunham, Ian

2017-01-01

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org. PMID:27899665

Receptor-binding domain as a target for developing SARS vaccines.

PubMed

Zhu, Xiaojie; Liu, Qi; Du, Lanying; Lu, Lu; Jiang, Shibo

2013-08-01

A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.

Developing a novel therapeutic strategy targeting Kallikrein-4 to inhibit prostate cancer growth and metastasis

DTIC Science & Technology

Kallikrein-related peptidase 4 (KLK4) is a rational therapeutic target for prostate cancer (PCa) as it is up-regulated in both localised and bone ...in PCa homing to bone . We therefore hypothesize that blockade of KLK4 activity will inhibit PCa growth and prevent metastasis to secondary sites like... bone . This project aims to develop a novel therapeutic strategy targeting KLK4 specifically in PCa. KLK4 siRNA is incorporated into a novel polymeric

Developing Targeted Hybrid Imaging Probes by Chelator Scaffolding

PubMed Central

2017-01-01

Positron emission tomography (PET) as well as optical imaging (OI) with peptide receptor targeting probes have proven their value for oncological applications but also show restrictions depending on the clinical field of interest. Therefore, the combination of both methods, particularly in a single molecule, could improve versatility in clinical routine. This proof of principle study aims to show that a chelator, Fusarinine C (FSC), can be utilized as scaffold for novel dimeric dual-modality imaging agents. Two targeting vectors (a minigastrin analogue (MG11) targeting cholecystokinin-2 receptor overexpression (CCK2R) or integrin αVβ3 targeting cyclic pentapeptides (RGD)) and a near-infrared fluorophore (Sulfo-Cyanine7) were conjugated to FSC. The probes were efficiently labeled with gallium-68 and in vitro experiments including determination of logD, stability, protein binding, cell binding, internalization, and biodistribution studies as well as in vivo micro-PET/CT and optical imaging in U-87MG αVβ3- and A431-CCK2R expressing tumor xenografted mice were carried out. Novel bioconjugates showed high receptor affinity and highly specific targeting properties at both receptors. Ex vivo biodistribution and micro-PET/CT imaging studies revealed specific tumor uptake accompanied by slow blood clearance and retention in nontargeted tissues (spleen, liver, and kidneys) leading to visualization of tumors at early (30 to 120 min p.i.). Excellent contrast in corresponding optical imaging studies was achieved especially at delayed time points (24 to 72 h p.i.). Our findings show the proof of principle of chelator scaffolding for hybrid imaging agents and demonstrate FSC being a suitable bifunctional chelator for this approach. Improvements to fine-tune pharmacokinetics are needed to translate this into a clinical setting. PMID:28462989

Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

PubMed

Mohammadipanah, Fatemeh; Salimi, Fatemeh

2017-04-29

Sturge-Weber Syndrome (SWS) is among the neurocutaneous diseases, which has several clinical manifestations of ocular (glaucoma), cutaneous (port-wine stain), neurological (seizures) and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for the SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against this syndrome. Development of such platforms of bioassay can bring along the implementation of high throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of biological targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholine esterase, alkaline phosphatase, gamma-aminobutyricacidergic, Hypoxia-Inducible Factor (HIF) -1α and 2α are suggested. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Polyvalent Vaccines Targeting Oncogenic Driver Pathways

Cancer.gov

Mary L. (Nora) Disis, MD, is the Athena Distinguished Professor of Breast Cancer Research and Associate Dean for Translational Health Sciences in the University of Washington (UW) School of Medicine. She is a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics and Gynecology at UW, and a Member of the Fred Hutchinson Cancer Research Center (FHCRC). She is also an American Cancer Society Clinical Professor and a Komen Scholar. In addition to directing work in the Tumor Vaccine Group, Dr. Disis is the Director of the Institute of Translational Health Sciences and the Director for the Center for Translational Medicine in Women’s Health at the UW. Dr. Disis is an expert in breast and ovarian cancer immunology and translational research. She is one of the pioneering investigators who discovered that HER-2/neu is a tumor antigen. Her work has led to several clinical trials which evaluate boosting immunity to HER-2/neu with cancer vaccines. Her research interest is in the discovery of new molecular immunologic targets in solid tumors for the development of vaccine and cellular therapy for the treatment and prevention of common malignancies. Dr. Disis is a member of Alpha Omega Alpha and the American Society of Clinical Investigation. She is also the Editor-in-Chief for JAMA Oncology, and is a member of several committees and task forces for both the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Dr. Disis received her MD from the University of Nebraska Medical School and completed a residency and chief residency in Internal Medicine at the University of Illinois in Chicago and her fellowship in oncology at UW/FHCRC.

Studies in Multifunctional Drug Development: Preparation and Evaluation of 11beta-Substituted Estradiol-Drug Conjugates, Cell Membrane Targeting Imaging Agents, and Target Multifunctional Nanoparticles

NASA Astrophysics Data System (ADS)

Dao, KinhLuan Lenny D.

Cancer is the second leading cause of death after cardiovascular disease in the United State. Despite extensive research in development of antitumor drugs, most of these therapeutic entities often possess nonspecific toxicity, thus they can only be used to treat tumors in higher doses or more frequently. Because of the cytotoxicity and severe side effects, the drug therapeutic window normally is limited. Beside the toxicity issue, antitumor drug are also not selectively taken up by tumor cells, thus the necessitating concentrations that would eradicate the tumor can often not be used. In addition, tumor cells tend to develop resistance against the anticancer drugs after prolonged treatment. Therefore, alleviating the systemic cytotoxicity and side effects, improving in tumor selectivity, high potency, and therapeutic efficacy are still major obstacles in the area of anticancer drug development. A more promising approach for developing a selective agent for cancer is to conjugate a potent therapeutic drug, or an imaging agent with a targeting group, such as antibody or a high binding-specificity small molecule, that selectively recognize the overexpressed antigens or proteins on tumor cells. My research combines several approaches to describe this strategy via using different targeting molecules to different diseases, as well as different potent cytotoxic drugs for different therapies. Three studies related to the preparation and biological evaluation of new therapeutic agents, such as estradiol-drug hybrids, cell membrane targeted molecular imaging agents, and multifunctional NPs will be discussed. The preliminary results of these studies indicated that our new reagents achieved their initial objectives and can be further improved for optimized synthesis and in vivo experiments. The first study describes the method in which we employed a modular assembly approach to synthesize a novel 11beta-substituted steroidal anti-estrogen. The key intermediate was synthesized

Cell signaling molecules as drug targets in lung cancer: an overview.

PubMed

Mukherjee, Tapan K; Paul, Karan; Mukhopadhyay, Srirupa

2011-07-01

Lung being one of the vital and essential organs in the body, lung cancer is a major cause of mortality in the modern human society. Lung cancer can be broadly subdivided into nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Although NSCLC is sometimes treated with surgery, the advanced and metastatic NSCLC and SCLC usually respond better to chemotherapy and radiation. The most important targets of these chemotherapeutic agents are various intracellular signaling molecules. The primary focus of this review article is to summarize the description of various cell signaling molecules involved in lung cancer development and their regulation by chemotherapeutic agents. Extensive research work in recent years has identified several cellular signaling molecules that may be intricately involved in the complexity of lung cancer. Some of these cell signaling molecules are epidermal growth factor receptors, vascular endothelial growth factor receptors, mammalian target of rapamycin, mitogen-activated protein kinase phosphatase-1, peroxisome proliferator-activated receptor-gamma, matrix metalloproteinases and receptor for advanced glycation end-products. The present review will strengthen our current knowledge regarding the efficacy of the above-mentioned cell signaling molecules as potential beneficial drug targets against lung cancer.

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Fleseriu, Maria; Hashim, Ibrahim A; Karavitaki, Niki; Melmed, Shlomo; Murad, M Hassan; Salvatori, Roberto; Samuels, Mary H

2016-11-01

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

A Brief History of the Emergy Society and its Mission in the ...

EPA Pesticide Factsheets

In 2002, H.T. Odum authorized the formation of a society dedicated to research, communication, and education focused on the new ideas of emergy and transformity and their basis in Energy Systems Theory. From this initial concept and after a 5 period of incubation, the International Society for the Advancement of Emergy Research (ISAER), a.k.a., the Emergy Society, was incorporated as a nonprofit corporation in the United States on July 28, 2007. In this talk, the history of the Emergy Society from its origin to the present time will be presented. The key ideas of emergy and transformity and their derivation and importance will be discussed. The structure of the Emergy Society and how it has carried out its mission over its history will be examined, including the formation of the China Chapter of ISAER. In many ways the history of ISAER is a story about its Presidents and the Executive Council members, who worked hard to promote the growth of the Emergy Society and to expand its services to its membership and the world. The development of the Emergy Society website as the major interface to communicate with its members and the general public will be recounted along with the story of the development of the Emergy Society logo and its esoteric meaning. Finally, the accomplishments of ISAER in the United States, China, Brazil and Europe to date will be considered and the future of the Emergy Society explored. This talk was delivered as a plenary address to the asse

Global Fund-supported programmes contribution to international targets and the Millennium Development Goals: an initial analysis.

PubMed

Komatsu, Ryuichi; Low-Beer, Daniel; Schwartländer, Bernhard

2007-10-01

The Global Fund to Fight AIDS, Tuberculosis and Malaria is one of the largest funders to fight these diseases. This paper discusses the programmatic contribution of Global Fund-supported programmes towards achieving international targets and Millennium Development Goals, using data from Global Fund grants. Results until June 2006 of 333 grants supported by the Global Fund in 127 countries were aggregated and compared against international targets for HIV/AIDS, tuberculosis and malaria. Progress reports to the Global Fund secretariat were used as a basis to calculate results. Service delivery indicators for antiretrovirals (ARV) for HIV/AIDS, case detection under the DOTS strategy for tuberculosis (DOTS) and insecticide-treated nets (ITNs) for malaria prevention were selected to estimate programmatic contributions to international targets for the three diseases. Targets of Global Fund-supported programmes were projected based on proposals for Rounds 1 to 4 and compared to international targets for 2009. Results for Global Fund-supported programmes total 544,000 people on ARV, 1.4 million on DOTS and 11.3 million for ITNs by June 2006. Global Fund-supported programmes contributed 18% of international ARV targets, 29% of DOTS targets and 9% of ITNs in sub-Saharan Africa by mid-2006. Existing Global Fund-supported programmes have agreed targets that are projected to account for 19% of the international target for ARV delivery expected for 2009, 28% of the international target for DOTS and 84% of ITN targets in sub-Saharan Africa. Global Fund-supported programmes have already contributed substantially to international targets by mid-2006, but there is a still significant gap. Considerably greater financial support is needed, particularly for HIV, in order to achieve international targets for 2009.

Development of a liquid tin microjet target for an efficient laser-produced plasma extreme ultraviolet source.

PubMed

Higashiguchi, Takeshi; Hamada, Masaya; Kubodera, Shoichi

2007-03-01

A regenerative tin liquid microjet target was developed for a high average power extreme ultraviolet (EUV) source. The diameter of the target was smaller than 160 microm and good vacuum lower than 0.5 Pa was maintained during the operation. A maximum EUV conversion efficiency of 1.8% at the Nd:yttrium-aluminum-garnet laser intensity of around 2 x 10(11) Wcm(2) with a spot diameter of 175 microm (full width at half maximum) was observed. The angular distribution of the EUV emission remained almost isotropic, whereas suprathermal ions mainly emerged toward the target normal.

Development of a liquid tin microjet target for an efficient laser-produced plasma extreme ultraviolet source

NASA Astrophysics Data System (ADS)

Higashiguchi, Takeshi; Hamada, Masaya; Kubodera, Shoichi

2007-03-01

A regenerative tin liquid microjet target was developed for a high average power extreme ultraviolet (EUV) source. The diameter of the target was smaller than 160 μm and good vacuum lower than 0.5 Pa was maintained during the operation. A maximum EUV conversion efficiency of 1.8% at the Nd:yttrium-aluminum-garnet laser intensity of around 2×1011 W/cm2 with a spot diameter of 175 μm (full width at half maximum) was observed. The angular distribution of the EUV emission remained almost isotropic, whereas suprathermal ions mainly emerged toward the target normal.

The creation of a global telemedical information society.

PubMed

Marsh, A

1998-01-01

Healthcare is a major candidate for improvement in any vision of the kinds of "information highways" and "information societies" that are now being visualized. The medical information management market is one of the largest and fastest growing segments of the healthcare device industry. The expected revenue by the year 2000 is US$21 billion. Telemedicine currently accounts for only a small segment but is expanding rapidly. In the United States more than 60% of federal telemedicine projects were initiated in the last two years. The concept of telemedicine captures much of what is developing in terms of technology implementations, especially if it is combined with the growth of the Internet and World Wide Web (WWW). It is foreseen that the World Wide Web (WWW) will become the most important communication medium of any future information society. If the development of such a society is to be on a global scale it should not be allowed to develop in an ad hoc manner. The Euromed Project has identified 20 building blocks resulting in 39 steps requiring multi-disciplinary collaborations. Since, the organization of information is therefore critical especially when concerning healthcare the Euromed Project has also introduced a new (global) standard called "Virtual Medical Worlds" which provides the potential to organize existing medical information and provide the foundations for its integration into future forms of medical information systems. Virtual Medical Worlds, based on 3D reconstructed medical models, utilizes the WWW as a navigational medium to remotely access multimedia medical information systems. The visualisation and manipulation of hyper-graphical 3D "body/organ" templates and patient-specific 3D/4D/and VR models is an attempt to define an information infrastructure in an emerging WWW-based telemedical information society.

The Creation of a global telemedical information society.

PubMed

Marsh, A

1998-04-01

Healthcare is a major candidate for improvement in any vision of the kinds of 'information highways' and 'information societies' that are now being visualized. The medical information management market is one of the largest and fastest growing segments of the healthcare device industry. The expected revenue by the year 2000 is US$21 billion. Telemedicine currently accounts for only a small segment but is expanding rapidly. In the USA more than 60% of federal telemedicine projects were initiated in the last 2 years. The concept of telemedicine captures much of what is developing in terms of technology implementations, especially if it is combined with the growth of the Internet and World Wide Web (WWW). It is foreseen that the World Wide Web (WWW) will become the most important communication medium of any future information society. If the development of such a society is to be on a global scale it should not be allowed to develop in an ad hoc manner. For this reason, the Euromed Project has identified 20 building blocks resulting in 39 steps requiring multi-disciplinary collaborations. Since, the organization of information is therefore critical especially when concerning healthcare the Euromed Project has also introduced a new (global) standard called 'Virtual Medical Worlds' which provides the potential to organize existing medical information and provide the foundations for its integration into future forms of medical information systems. Virtual Medical Worlds, based on 3D reconstructed medical models, utilizes the WWW as a navigational medium to remotely access multi-media medical information systems. The visualization and manipulation of hyper-graphical 3D 'body/organ' templates and patient-specific 3D/4D/and VR models is an attempt to define an information infrastructure in an emerging WWW-based telemedical information society.

Teaching in the Knowledge Society: New Skills and Instruments for Teachers

ERIC Educational Resources Information Center

Cartelli, Antonio, Ed.

2006-01-01

"Teaching in the Knowledge Society: New Skills and Instruments for Teachers" covers a pedagogical survey of the changes induced by information and communication technology (ICT) in today's society and education. It critically analyzes facts, instruments, solutions, and strategies while suggesting interpretations and hypotheses to develop a new way…

New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness.

PubMed

Ritzefeld, Markus; Wright, Megan H; Tate, Edward W

2018-02-01

Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.

Genome-Wide Identification of CBX2 Targets: Insights in the Human Sex Development Network

PubMed Central

Eid, Wassim; Opitz, Lennart

2015-01-01

Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD. PMID:25569159

Frustration in a Chauvinist Society: Japanese Women Today.

ERIC Educational Resources Information Center

Metraux, Daniel A.

1987-01-01

Discusses the status of women in contemporary Japan. Describes their role as mothers and homemakers, the obstacles they face in maintaining developing careers, and the discrimination they face in a patriarchal society. (Author/ABB)

Birth of the Angle Society of Europe.

PubMed

Jacquin, Michel

2006-01-01

The history of the Angle Society of Europe began in 1971 with the meeting of two men: Juan Canut from Spain and Ernst Hösl from Germany. They decided to launch the idea of an association to get ready for the emergence of a new wave of Orthodontics in Europe. The first step was the creation of a Society with small groups of fourteen Orthodontists. The very first principle to be followed was "the plaster on the table" demonstration together with presentations on clinical or general interest subjects. The First Official Meeting took place in Zurich. 32 initial members were in attendance trying to set up the requirements for the development of a high quality Society. The second meeting focused on a scientific program centered on Treatment Timing Topic and the emergence of a new set of Bylaws. The third meeting was devoted to the display of 215 treated cases presented by temporary members to be evaluated by a Scientific Committee under the presidency of Dr. Alton Moore as official representative of the USA Edward H. Angle Society of Orthodontists. The following meetings demonstrated a constant and well monitored increase of new candidates and active members motivated to reach the required excellence level.

Setting scientific standards: publishing in medical societies in nineteenth-century Belgium.

PubMed

Vandendriessche, Joris

2014-01-01

This article examines the publishing procedures of nineteenth-century medical societies, using the Medical Society of Ghent (Belgium) as a case study. It argues, more precisely, that the introduction of formalized review procedures in medical societies can be considered part of the emergence of a professional scientific culture in the first half of the nineteenth century. First, by participating in these procedures physicians took on different stylized roles, for example of the contributing author, the righteous judge, or the punctual secretary, and articulated new professional values such as contributing to science. Second, the publishing procedures of medical societies also provide insight into the mechanisms of reaching consensus in nineteenth-century medicine. By developing new scientific genres, such as the published meeting report, medical societies aimed to extend the community of peers beyond the group of society members and establish trust and agreement throughout the medical community.

Apollo Docking with the LEM Target

NASA Image and Video Library

2012-09-07

Originally the Rendezvous was used by the astronauts preparing for Gemini missions. The Rendezvous Docking Simulator was then modified and used to develop docking techniques for the Apollo program. This picture shows a later configuration of the Apollo docking with the LEM target. A.W. Vogeley described the simulator as follows: The Rendezvous Docking Simulator and also the Lunar Landing Research Facility are both rather large moving-base simulators. It should be noted, however, that neither was built primarily because of its motion characteristics. The main reason they were built was to provide a realistic visual scene. A secondary reason was that they would provide correct angular motion cues (important in control of vehicle short-period motions) even though the linear acceleration cues would be incorrect. -- Published in A.W. Vogeley, Piloted Space-Flight Simulation at Langley Research Center, Paper presented at the American Society of Mechanical Engineers, 1966 Winter Meeting, New York, NY, November 27 - December 1, 1966.

Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

PubMed Central

Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

2008-01-01

Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

Brazilian guidelines on prevention of cardiovascular disease in patients with diabetes: a position statement from the Brazilian Diabetes Society (SBD), the Brazilian Cardiology Society (SBC) and the Brazilian Endocrinology and Metabolism Society (SBEM).

PubMed

Bertoluci, Marcello Casaccia; Moreira, Rodrigo Oliveira; Faludi, André; Izar, Maria Cristina; Schaan, Beatriz D; Valerio, Cynthia Melissa; Bertolami, Marcelo Chiara; Chacra, Ana Paula; Malachias, Marcus Vinicius Bolivar; Vencio, Sérgio; Saraiva, José Francisco Kerr; Betti, Roberto; Turatti, Luiz; Fonseca, Francisco Antonio Helfenstein; Bianco, Henrique Tria; Sulzbach, Marta; Bertolami, Adriana; Salles, João Eduardo Nunes; Hohl, Alexandre; Trujilho, Fábio; Lima, Eduardo Gomes; Miname, Marcio Hiroshi; Zanella, Maria Teresa; Lamounier, Rodrigo; Sá, João Roberto; Amodeo, Celso; Pires, Antonio Carlos; Santos, Raul D

2017-01-01

Since the first position statement on diabetes and cardiovascular prevention published in 2014 by the Brazilian Diabetes Society, the current view on primary and secondary prevention in diabetes has evolved as a result of new approaches on cardiovascular risk stratification, new cholesterol lowering drugs, and new anti-hyperglycemic drugs. Importantly, a pattern of risk heterogeneity has emerged, showing that not all diabetic patients are at high or very high risk. In fact, most younger patients who have no overt cardiovascular risk factors may be more adequately classified as being at intermediate or even low cardiovascular risk. Thus, there is a need for cardiovascular risk stratification in patients with diabetes. The present panel reviews the best current evidence and proposes a practical risk-based approach on treatment for patients with diabetes. The Brazilian Diabetes Society, the Brazilian Society of Cardiology, and the Brazilian Endocrinology and Metabolism Society gathered to form an expert panel including 28 cardiologists and endocrinologists to review the best available evidence and to draft up-to-date an evidence-based guideline with practical recommendations for risk stratification and prevention of cardiovascular disease in diabetes. The guideline includes 59 recommendations covering: (1) the impact of new anti-hyperglycemic drugs and new lipid lowering drugs on cardiovascular risk; (2) a guide to statin use, including new definitions of LDL-cholesterol and in non-HDL-cholesterol targets; (3) evaluation of silent myocardial ischemia and subclinical atherosclerosis in patients with diabetes; (4) hypertension treatment; and (5) the use of antiplatelet therapy. Diabetes is a heterogeneous disease. Although cardiovascular risk is increased in most patients, those without risk factors or evidence of sub-clinical atherosclerosis are at a lower risk. Optimal management must rely on an approach that will cover both cardiovascular disease prevention in

Simulating Society Transitions: Standstill, Collapse and Growth in an Evolving Network Model

PubMed Central

Xu, Guanghua; Yang, Junjie; Li, Guoqing

2013-01-01

We developed a model society composed of various occupations that interact with each other and the environment, with the capability of simulating three widely recognized societal transition patterns: standstill, collapse and growth, which are important compositions of society evolving dynamics. Each occupation is equipped with a number of inhabitants that may randomly flow to other occupations, during which process new occupations may be created and then interact with existing ones. Total population of society is associated with productivity, which is determined by the structure and volume of the society. We ran the model under scenarios such as parasitism, environment fluctuation and invasion, which correspond to different driving forces of societal transition, and obtained reasonable simulation results. This work adds to our understanding of societal evolving dynamics as well as provides theoretical clues to sustainable development. PMID:24086530

Convergent pathogenic pathways in Alzheimer’s and Huntington disease: Shared targets for drug development

PubMed Central

Ehrnhoefer, Dagmar E.; Wong, Bibiana K.Y.; Hayden, Michael R.

2011-01-01

Neurodegenerative diseases exemplified by Alzheimer’s and Huntington disease are characterized by the progressive neuropsychiatric dysfunction and loss of specific neuronal subtypes. Even though there are differences in the exact sites of pathology and clinical profiles only partially overlap, considerable similarities in disease mechanisms and pathogenic pathways can be observed. These shared mechanisms raise the possibility of common therapeutic targets for drug development. Huntington disease with a monogenic cause and the possibility to accurately identify pre-manifest mutation carriers could be exploited as a ‘model’ for Alzheimer’s disease to test the efficacy of therapeutic interventions targeting shared pathogenic pathways. PMID:22015920

An official American Thoracic Society/International Society for Heart and Lung Transplantation/Society of Critical Care Medicine/Association of Organ and Procurement Organizations/United Network of Organ Sharing Statement: ethical and policy considerations in organ donation after circulatory determination of death.

PubMed

Gries, Cynthia J; White, Douglas B; Truog, Robert D; Dubois, James; Cosio, Carmen C; Dhanani, Sonny; Chan, Kevin M; Corris, Paul; Dark, John; Fulda, Gerald; Glazier, Alexandra K; Higgins, Robert; Love, Robert; Mason, David P; Nakagawa, Thomas A; Shapiro, Ron; Shemie, Sam; Tracy, Mary Fran; Travaline, John M; Valapour, Maryam; West, Lori; Zaas, David; Halpern, Scott D

2013-07-01

Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues. To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders. A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders. A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD. The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.