WorldWideScience

Sample records for potentially paradigm-shifting molecular

  1. Laparoscopic paediatric surgery: A potential for paradigm shift in developing countries

    Directory of Open Access Journals (Sweden)

    M A Misauno

    2012-01-01

    Full Text Available Background: Until recently, surgical conditions in children requiring operation were managed by the traditional open method. The introduction of the laparoscopic surgical technique seems to be reversing this trend in many centres. We are pioneering some laparoscopic surgery procedures in our environment and the aim of this study was to document our experience with laparoscopic paediatric surgical procedures in a developing country. Materials and Methods: This was a prospective analysis of all consecutive children that had laparoscopic surgery at 5 hospitals in Northern Nigeria from June 2008 to February 2011. Results: Twenty-one patients had laparoscopic surgeries during the study period with a mean age of 12.5 ± 2.6 years and age range of 10-16 years. There were 14 females and 7 males with a M:F ratio of 1:2. Seven patients (33.3% had cholecystectomies and 13 (61.9% had appendicectomies and the remaining one patient (4.8% had adhesiolysis for partial adhesive intestinal obstruction following previous open appendicectomy. The mean operating time was 89 min with a range of 45-110 min for appendicectomies, 55-150 min for cholecystectomies and the adhesiolysis took 50 min. The mean hospital stay was 2 days except for the conversions that stayed up to 7 days. There were 2 (9.5% conversions with no mortality. Conclusion: We solicit a paradigm shift in our approach to surgical management and implore other centres to embrace laparoscopic surgery in the management of surgical conditions in children since it confers obvious advantages over open surgery.

  2. Paradigm Shifts in Ophthalmic Diagnostics.

    Science.gov (United States)

    Sebag, J; Sadun, Alfredo A; Pierce, Eric A

    2016-08-01

    Future advances in ophthalmology will see a paradigm shift in diagnostics from a focus on dysfunction and disease to better measures of psychophysical function and health. Practical methods to define genotypes will be increasingly important and non-invasive nanotechnologies are needed to detect molecular changes that predate histopathology. This is not a review nor meant to be comprehensive. Specific topics have been selected to illustrate the principles of important paradigm shifts that will influence the future of ophthalmic diagnostics. It is our impression that future evaluation of vision will go beyond visual acuity to assess ocular health in terms of psychophysical function. The definition of disease will incorporate genotype into what has historically been a phenotype-centric discipline. Non-invasive nanotechnologies will enable a paradigm shift from disease detection on a cellular level to a sub-cellular molecular level. Vision can be evaluated beyond visual acuity by measuring contrast sensitivity, color vision, and macular function, as these provide better insights into the impact of aging and disease. Distortions can be quantified and the psychophysical basis of vision can be better evaluated than in the past by designing tests that assess particular macular cell function(s). Advances in our understanding of the genetic basis of eye diseases will enable better characterization of ocular health and disease. Non-invasive nanotechnologies can assess molecular changes in the lens, vitreous, and macula that predate visible pathology. Oxygen metabolism and circulatory physiology are measurable indices of ocular health that can detect variations of physiology and early disease. This overview of paradigm shifts in ophthalmology suggests that the future will see significant improvements in ophthalmic diagnostics. The selected topics illustrate the principles of these paradigm shifts and should serve as a guide to further research and development. Indeed

  3. From molecular imaging to systems diagnostics: Time for another paradigm shift?

    International Nuclear Information System (INIS)

    Li, King C.P.

    2009-01-01

    The term 'Molecular Imaging' has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term 'Systems Diagnostics' and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.

  4. From molecular imaging to systems diagnostics: Time for another paradigm shift?

    Energy Technology Data Exchange (ETDEWEB)

    Li, King C.P. [Department of Radiology, Methodist Hospital, Weill Cornell Medical College, 6565 Fannin Street, D280 Houston, TX 77030 (United States)], E-mail: kli@tmhs.org

    2009-05-15

    The term 'Molecular Imaging' has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term 'Systems Diagnostics' and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.

  5. Gas transmission : a paradigm shift

    International Nuclear Information System (INIS)

    Cornelson, D.W.

    1997-01-01

    The evolution of energy markets in North America was discussed. The investment opportunities that are possible in a deregulated energy market, be it in production or in the generation of energy commodities, in the development of midstream infrastructure, or in the provision of energy services, were outlined. Deregulation of crude oil, natural gas and electricity has resulted in significant changes in the structure of energy markets and the way in which customers are served. One of the advantages of competition regarding power generation is that it has turned energy into a commodity which has resulted in greater customer choice and efficiency. As one example of midstream infrastructure development, the Alliance Pipeline project was described. This project was conceived as a means to enhance the value of western Canadian natural gas. The 1,900 mile pipeline will run from British Columbia, through Alberta into Chicago where it will interconnect with the North American gas transmission grid. The pipeline is an efficient means of transporting energy from Western Canada to North American markets, and Alliance, as a lowest cost transporter, will continue to put pressure on the traditional infrastructure to become even more competitive at the margin. As such, Alliance represents a paradigm shift in energy transportation, and serves as an excellent example of the type of investment opportunity that a deregulated market can provide. It was suggested that innovation and competition in a deregulated North American energy market will continue to increase. As electricity is deregulated, the energy market will respond more quickly to changes in supply and demand than it did in the past, in an effort to satisfy the needs of investors and customers. This will provide increased opportunities for restructuring and further competition

  6. The Prerequisites for a Degrowth Paradigm Shift

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2018-01-01

    What would it take for a degrowth paradigm shift to take place? Drawing on contemporary critical political economy scholarship, this article identifies four prerequisites for socio-economic paradigm shifts: deep crisis, an alternative political project, a comprehensive coalition of social forces...... currently facing humanity. On the other hand, the prospects for a degrowth paradigm shift remain bleak: unlike political projects that became hegemonic in the past, degrowth has neither support from a comprehensive coalition of social forces nor any consent to its agenda among the broader population....

  7. Paradigm shift in psychiatry: what may it involve?

    Science.gov (United States)

    Valent, Paul

    2018-02-01

    This study aims to examine the potential nature of an ongoing paradigm shift in psychiatry that has been suggested to be occurring. New findings in traumatology and neuroscience do form a potential platform for a paradigm shift. Prior conflicting paradigms are suggested to be due to biases arising from mental structures themselves. A new wholist perspective is proposed, which makes sense of and incorporates previous paradigms, and coheres recent understanding of right- and left-brain functioning and biopsychosocial traumatic processes and their ramifications. The perspective makes sense of the great variety of post-traumatic manifestations ranging from somatic to meaning-making dysfunctions. The wholist perspective may well be an important step in solidifying a fresh paradigmatic perspective in psychiatry.

  8. Will Mobile Learning Bring a Paradigm Shift in Higher Education?

    OpenAIRE

    Rajasingham, Lalita

    2011-01-01

    In the light of technology-driven social change that creates new challenges for universities, this paper considers the potential of mobile learning as a subset of e-learning to effect a paradigm shift in higher education. Universities face exponential growth in demand for higher education, significant decreases in government funding for education, a changing in understanding of the nature of knowledge, changing student demographics and expectations, and global competition. At the same time un...

  9. The Underlying Social Dynamics of Paradigm Shifts.

    Science.gov (United States)

    Rodriguez-Sickert, Carlos; Cosmelli, Diego; Claro, Francisco; Fuentes, Miguel Angel

    2015-01-01

    We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  10. The Underlying Social Dynamics of Paradigm Shifts.

    Directory of Open Access Journals (Sweden)

    Carlos Rodriguez-Sickert

    Full Text Available We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm; and ii radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.

  11. From Reified Abstractions to Situated Contexts: Feminist Jurisprudence, Paradigm Shift and Legal Change

    OpenAIRE

    Petoussi, Vassiliki Jr.

    1998-01-01

    This study addresses the extent to which feminist jurisprudence literature has developed the potential to initiate a legal paradigm shift leading to legal and consequent social change that would alleviate gender inequality. Drawing upon Kuhn's (1970) and Stacey and Thorne's (1985) arguments, I theorized that for a paradigm shift centered upon women and women's experiences to occur, feminist jurisprudence, particularly second- and third-phase feminist jurisprudence, needs to be incorporated i...

  12. Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

    Science.gov (United States)

    Fujiwara, Keiichi; McAlpine, Jessica N; Lheureux, Stephanie; Matsumura, Noriomi; Oza, Amit M

    2016-01-01

    The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

  13. Researching Style: Epistemology, Paradigm Shifts and Research Interest Groups

    Science.gov (United States)

    Rayner, Stephen

    2011-01-01

    This paper identifies the need for a deliberate approach to theory building in the context of researching cognitive and learning style differences in human performance. A case for paradigm shift and a focus upon research epistemology is presented, building upon a recent critique of style research. A proposal for creating paradigm shift is made,…

  14. [Essentials of pharmacophylogeny: knowledge pedigree, epistemology and paradigm shift].

    Science.gov (United States)

    Hao, Da-cheng; Xiao, Pei-gen; Liu, Li-wei; Peng, Yong; He, Chun-nian

    2015-09-01

    Chinese materia medica resource (CMM resource) is the foundation of the development of traditional Chinese medicine. In the study of sustainable utilization of CMM resource, adopting innovative theory and method to find new CMM resource is one of hotspots and always highlighted. Pharmacophylogeny interrogates the phylogenetic relationship of medicinal organisms (especially medicinal plants), as well as the intrinsic correlation of morphological taxonomy, molecular phylogeny, chemical constituents, and therapeutic efficacy (ethnopharmacology and pharmacological activity). This new discipline may have the power to change the way we utilize medicinal plant resources and develop plant-based drugs. Phylogenomics is the crossing of evolutionary biology and genomics, in which genome data are utilized for evolutionary reconstructions. Phylogenomics can be integrated into the flow chart of drug discovery and development, and extends the field of pharmacophylogeny at the omic level, thus the concept of pharmacophylogenomics could be redefined in the context of plant pharmaceutical resources. This contribution gives a brief discourse of knowledge pedigree of pharmacophylogeny, epistemology and paradigm shift, highlighting the theoretical and practical values of pharmacophylogenomics. Many medicinally important tribes and genera, such as Clematis, Pulsatilla, Anemone, Cimicifugeae, Nigella, Delphinieae, Adonideae, Aquilegia, Thalictrum, and Coptis, belong to Ranunculaceae family. Compared to other plant families, Ranunculaceae has the most species that are recorded in China Pharmacopoeia (CP) 2010. However, many Ranunculaceae species, e. g., those that are closely related to CP species, as well as those endemic to China, have not been investigated in depth, and their phylogenetic relationship and potential in medicinal use remain elusive. As such, it is proposed to select Ranunculaceae to exemplify the utility of pharmacophylogenomics and to elaborate the new concept

  15. Indian Science Culture Needs a Paradigm Shift.

    Science.gov (United States)

    Sharma, Om P

    2017-06-01

    am sure such a cultural change and paradigm shift from the status quo does not need extra funds and can be surely ushered in without money.

  16. Paradigm Shift in Language Teaching and Language Teacher Education

    Directory of Open Access Journals (Sweden)

    Elaine Ferreira do Vale Borges

    2014-11-01

    Full Text Available In this article, I intend to conduct a short literature review and discussion about paradigm shift in language teaching and language teacher education from Cartesian to the complexity paradigm. For that, I use the Kuhnian notion of scientific revolution to present a short compilation of works related to paradigm shift in different sciences, including psychology, linguistics and, more emphatically, applied linguistics. The main proposal is to show the evolutions of paradigm shift in language and social sciences and its impact on the emergence of the complexity paradigm in language teaching and language teacher education fields.

  17. TIPS (trigger an IIF paradigm shift)

    Energy Technology Data Exchange (ETDEWEB)

    Kilcup, P.E. Glen [Intel Corporation, MS: F9-016, 4100 Sara Road, Rio Rancho, NM 87124 (United States)]. E-mail: glen.w.kilcup@intel.com; Hickox, Dick [Intel Corporation, MS: F9-016, 4100 Sara Road, Rio Rancho, NM 87124 (United States); Reynaga, Adolfo [Intel Corporation, MS: F9-016, 4100 Sara Road, Rio Rancho, NM 87124 (United States)

    2007-04-11

    Challenge: New Mexico Corporate Services (NMCS) recordable injuries have been averaging 2-4 per year for the last 5 years with no statistical improvement. However, we believe all NM employees must go home incident and injury free every day and just as healthy as they came to work. In addition, we have received feedback from several sources, that indicates some employees are reluctant to report injuries. These indicators showed us that continuing our current strategies, making incremental improvement and changes, would not give us the improvement desired. We needed a paradigm shift to get everyone completely engaged in the IIF (Incident and Injury Free) culture, in order to achieve true IIF results. Methods/Strategies: We formed a small (3-person) taskforce consisting of safety representatives from EHS, Site Services and CS Operations. We reviewed 5 years worth of data to determine what was injuring our people. We also decided to review all injuries, not simply those classified as recordable by OSHA standards. First we identified the types of injury information needed to get a true picture of our safety issues. We analyzed IRB (Incident Review Board) data showing us the following factors and whether any of them contributed to the injury: - Date - Incident Description - Severity - Root Cause - Type of Injury - Season - Work Group/Shift - Area - Improper evaluation of hazard - Inadequate work procedures - Incorrect Mental Model - Inadequate PPE Requirement - Failure to Follow or Unaware of PPE Requirement - Shortcut or Schedule Pressure - Last or First Day of Shift or Adjacent to Holiday - OT - Aggravate Existing Condition - Inadequate Training or Passdown - Experience in Task - Corrective Action Taken - Overall Quality of Response. Once this information was collected for all injuries in an Excel file, we graphed it several ways to help reveal trends: - Shift 7 had double the injuries of shift 5 - Night shift injuries were relatively high but lower than Shift 7 -Shift

  18. TIPS (trigger an IIF paradigm shift)

    International Nuclear Information System (INIS)

    Kilcup, P.E. Glen; Hickox, Dick; Reynaga, Adolfo

    2007-01-01

    Challenge: New Mexico Corporate Services (NMCS) recordable injuries have been averaging 2-4 per year for the last 5 years with no statistical improvement. However, we believe all NM employees must go home incident and injury free every day and just as healthy as they came to work. In addition, we have received feedback from several sources, that indicates some employees are reluctant to report injuries. These indicators showed us that continuing our current strategies, making incremental improvement and changes, would not give us the improvement desired. We needed a paradigm shift to get everyone completely engaged in the IIF (Incident and Injury Free) culture, in order to achieve true IIF results. Methods/Strategies: We formed a small (3-person) taskforce consisting of safety representatives from EHS, Site Services and CS Operations. We reviewed 5 years worth of data to determine what was injuring our people. We also decided to review all injuries, not simply those classified as recordable by OSHA standards. First we identified the types of injury information needed to get a true picture of our safety issues. We analyzed IRB (Incident Review Board) data showing us the following factors and whether any of them contributed to the injury: - Date - Incident Description - Severity - Root Cause - Type of Injury - Season - Work Group/Shift - Area - Improper evaluation of hazard - Inadequate work procedures - Incorrect Mental Model - Inadequate PPE Requirement - Failure to Follow or Unaware of PPE Requirement - Shortcut or Schedule Pressure - Last or First Day of Shift or Adjacent to Holiday - OT - Aggravate Existing Condition - Inadequate Training or Passdown - Experience in Task - Corrective Action Taken - Overall Quality of Response. Once this information was collected for all injuries in an Excel file, we graphed it several ways to help reveal trends: - Shift 7 had double the injuries of shift 5 - Night shift injuries were relatively high but lower than Shift 7 -Shift

  19. TIPS (trigger an IIF paradigm shift).

    Science.gov (United States)

    Kilcup P E, Glen; Hickox, Dick; Reynaga, Adolfo

    2007-04-11

    New Mexico Corporate Services (NMCS) recordable injuries have been averaging 2-4 per year for the last 5 years with no statistical improvement. However, we believe all NM employees must go home incident and injury free every day and just as healthy as they came to work. In addition, we have received feedback from several sources, that indicates some employees are reluctant to report injuries. These indicators showed us that continuing our current strategies, making incremental improvement and changes, would not give us the improvement desired. We needed a paradigm shift to get everyone completely engaged in the IIF (Incident & Injury Free) culture, in order to achieve true IIF results. We formed a small (3-person) taskforce consisting of safety representatives from EHS, Site Services and CS Operations. We reviewed 5 years worth of data to determine what was injuring our people. We also decided to review all injuries, not simply those classified as recordable by OSHA standards. First we identified the types of injury information needed to get a true picture of our safety issues. We analyzed IRB (Incident Review Board) data showing us the following factors and whether any of them contributed to the injury: - Date - Incident Description - Severity - Root Cause - Type of Injury - Season - Work Group/Shift - Area - Improper evaluation of hazard - Inadequate work procedures - Incorrect Mental Model - Inadequate PPE Requirement - Failure to Follow or Unaware of PPE Requirement - Shortcut or Schedule Pressure - Last or First Day of Shift or Adjacent to Holiday - OT - Aggravate Existing Condition - Inadequate Training or Passdown - Experience in Task - Corrective Action Taken - Overall Quality of Response. Once this information was collected for all injuries in an Excel file, we graphed it several ways to help reveal trends: Shift 7 had double the injuries of shift 5. Night shift injuries were relatively high but lower than Shift 7. Shift 5 had no severe (recordable

  20. Dynamic Docking: A Paradigm Shift in Computational Drug Discovery

    Directory of Open Access Journals (Sweden)

    Dario Gioia

    2017-11-01

    Full Text Available Molecular docking is the methodology of choice for studying in silico protein-ligand binding and for prioritizing compounds to discover new lead candidates. Traditional docking simulations suffer from major limitations, mostly related to the static or semi-flexible treatment of ligands and targets. They also neglect solvation and entropic effects, which strongly limits their predictive power. During the last decade, methods based on full atomistic molecular dynamics (MD have emerged as a valid alternative for simulating macromolecular complexes. In principle, compared to traditional docking, MD allows the full exploration of drug-target recognition and binding from both the mechanistic and energetic points of view (dynamic docking. Binding and unbinding kinetic constants can also be determined. While dynamic docking is still too computationally expensive to be routinely used in fast-paced drug discovery programs, the advent of faster computing architectures and advanced simulation methodologies are changing this scenario. It is feasible that dynamic docking will replace static docking approaches in the near future, leading to a major paradigm shift in in silico drug discovery. Against this background, we review the key achievements that have paved the way for this progress.

  1. Will Mobile Learning Bring a Paradigm Shift in Higher Education?

    Directory of Open Access Journals (Sweden)

    Lalita Rajasingham

    2011-01-01

    Full Text Available In the light of technology-driven social change that creates new challenges for universities, this paper considers the potential of mobile learning as a subset of e-learning to effect a paradigm shift in higher education. Universities face exponential growth in demand for higher education, significant decreases in government funding for education, a changing in understanding of the nature of knowledge, changing student demographics and expectations, and global competition. At the same time untethered mobile telephony is connecting large numbers of potential learners to communications networks. A review of some empirical literature on the current status of mobile learning that explores alternatives to help universities fulfil core functions of storage, processing, and disseminating knowledge that can be applied to real life problems, is followed by an examination of the strengths and weaknesses of increased connectivity to mobile communications networks to support constructivist, self-directed quality interactive learning for increasingly mobile learners. This paper also examines whether mobile learning can align the developing technology with changing student expectations and the implications of such an alignment for teaching and institutional strategies. Technologies considered include mobile computing and technology, wireless laptop, hand-held PDAs, and mobile telephony.

  2. Paradigm shift from cartography to geo-communication

    DEFF Research Database (Denmark)

    Brodersen, Lars

    2007-01-01

    This paper argues that the domain of GIS, cartography, geo-information etc. is facing a paradigm shift. The implication of a paradigm shift is a complete and necessary re-definition of e.g. the philosophical foundation of the system, as well as with a major upgrade and readjustment of procedures......-information is actually not possible at all without having a usage (a project identity and a purpose) in mind. Objective and neutral geo-information does not exist. Therefore the overall philosophy of the geo-domain will be that it is a communication discipline....

  3. Port Harcourt Medical Journal, a paradigm shift | Eke | Port Harcourt ...

    African Journals Online (AJOL)

    Port Harcourt Medical Journal, a paradigm shift. N Eke. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4103/0795-3038.179439 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  4. Paradigm shifts in orthodontic treatment with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Johnny Joung-Lin Liaw

    2015-01-01

    Full Text Available After the applications of mini-implant anchorage, the envelope of orthodontic treatment was expanded and some treatment modes were changed because of more predictable tooth movement with empowered anchorage. The author tried to share his experience of TADs applications for clarifying the paradigm shifts of orthodontic treatment assisted with the mini-implant anchorage.

  5. What Philanthropy's Paradigm Shift Means for Higher Ed Fundraising

    Science.gov (United States)

    McCully, George

    2015-01-01

    This is an unprecedented era of human history, in which simultaneous transformations of every technically advanced field are being driven by the powerful technological revolution in information and communications. Technically, these transformative changes are "paradigm shifts"--a distinct kind of historical change in which the governing…

  6. A Paradigm Shift for Educational Administrators: The Total Quality Movement.

    Science.gov (United States)

    Hough, M. J.

    This paper reviews the major ideas of the seminal total quality management theorists, such as Deming, Crosby, Juran, Ishikawa, and Imai, to illustrate how total quality management is applicable to education. It is argued that there is a need for a paradigm shift in educational administration. The first part reviews current Australian societal…

  7. Paradigm Shift in Distance Education in the 21st Century

    Directory of Open Access Journals (Sweden)

    Mehmet FIRAT

    2016-10-01

    Full Text Available Information and communication technologies have been one of a driving force which enables higher education expansion and gives a dynamic structure to the science in the twenty-first century. One of the most effective users of this driving force in higher education is distance education. Previously, distance education was considered to be as a method to ensure equality of opportunity in education, and partly to meet the educational needs of citizens in limited circumstances; today it has undergone an incontrovertible paradigm shift by transforming into an interdisciplinary science field with its functional flexibility, strong technology infrastructure, diversity of programs, innovative teaching approaches and rapidly increasing student numbers. In this study, it is aimed to reveal this paradigm shift with a historical point of view, and the information technology supported rise and paradigm shift of distance education is evaluated by a holistic perspective from different point of views of different perspectives from the studies in literature to the current research topics.

  8. Cryptic species as a window into the paradigm shift of the species concept.

    Science.gov (United States)

    Fišer, Cene; Robinson, Christopher T; Malard, Florian

    2018-02-01

    The species concept is the cornerstone of biodiversity science, and any paradigm shift in the delimitation of species affects many research fields. Many biologists now are embracing a new "species" paradigm as separately evolving populations using different delimitation criteria. Individual criteria can emerge during different periods of speciation; some may never evolve. As such, a paradigm shift in the species concept relates to this inherent heterogeneity in the speciation process and species category-which is fundamentally overlooked in biodiversity research. Cryptic species fall within this paradigm shift: they are continuously being reported from diverse animal phyla but are poorly considered in current tests of ecological and evolutionary theory. The aim of this review is to integrate cryptic species in biodiversity science. In the first section, we address that the absence of morphological diversification is an evolutionary phenomenon, a "process" counterpart to the long-studied mechanisms of morphological diversification. In the next section regarding taxonomy, we show that molecular delimitation of cryptic species is heavily biased towards distance-based methods. We also stress the importance of formally naming of cryptic species for better integration into research fields that use species as units of analysis. Finally, we show that incorporating cryptic species leads to novel insights regarding biodiversity patterns and processes, including large-scale biodiversity assessments, geographic variation in species distribution and species coexistence. It is time for incorporating multicriteria species approaches aiming to understand speciation across space and taxa, thus allowing integration into biodiversity conservation while accommodating for species uncertainty. © 2018 John Wiley & Sons Ltd.

  9. SCIENTIFIC PARADIGM SHIFT AS THE BACKGROUND OF LANGUAGE EDUCATION

    Directory of Open Access Journals (Sweden)

    V. D. Tabanakova

    2017-01-01

    Full Text Available Introduction. Recently, there has been a cardinal restructuring of university preparation. Linguistic education takes up nearly the last position in the new model of the higher school dictated by economic interests. Investments in linguistic projects are considered as unprofitable today. The linguistic component in educational programs of a bachelor degree is reduced to a minimum, and focused on language knowledge promoting as communication technologies.The aim of the work purposes to trace how the scientific and the linguistic paradigm shift have an impact on the domestic linguistic education system, and to show the unrealized potential capacity of linguistic knowledge.Methodology and research methods. The methodology of the offered research is based, on the one hand, upon the domestic periodical press review on the linguistic education problems for the last 15 years, on the other – on the philosophical analysis of science historical forms which change has caused the past, the present and the future of linguistics and linguistic education. The inductive methods to integrate different approaches are also used.Theoretical significance. The author emphasizes the need to consider the problems of higher education in philosophical aspect, through the interaction of a scientific and educational paradigm.Results and scientific novelty. At a time of global changes in domestic higher education the linguistic education is considered to be a display of the convergence process of natural sciences, technology and humanities. The philosophical study of the scientific paradigms – classical, non-classical and post-non-classical has revealed the regularities of the linguistic scientific paradigms – structural, communicative and cognitive. Each of the paradigms was traced in the frame of linguistic education functions alternation and constantly changing academic programs.A new take on the U-turn of a centrifugal vector in science has obviously demonstrated

  10. Intelligent e-Learning Systems: An Educational Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Suman Bhattacharya

    2016-12-01

    Full Text Available Learning is the long process of transforming information as well as experience into knowledge, skills, attitude and behaviors. To make up the wide gap between the demand of increasing higher education and comparatively limited resources, more and more educational institutes are looking into instructional technology. Use of online resources not only reduces the cost of education but also meet the needs of society. Intelligent e-learning has become one of the important channels to reach out to students exceeding geographic boundaries. Besides this, the characteristics of e-learning have complicated the process of education, and have brought challenges to both instructors and students. This paper will focus on the discussion of different discipline of intelligent e-learning like scaffolding based e-learning, personalized e-learning, confidence based e-learning, intelligent tutoring system, etc. to illuminate the educational paradigm shift in intelligent e-learning system.

  11. Urban Stormwater Governance: The Need for a Paradigm Shift.

    Science.gov (United States)

    Dhakal, Krishna P; Chevalier, Lizette R

    2016-05-01

    Traditional urban stormwater management involves rapid removal of stormwater through centralized conveyance systems of curb-gutter-pipe networks. This results in many adverse impacts on the environment including hydrological disruption, groundwater depletion, downstream flooding, receiving water quality degradation, channel erosion, and stream ecosystem damage. In order to mitigate these adverse impacts, urban stormwater managers are increasingly using green infrastructure that promote on-site infiltration, restore hydrological functions of the landscape, and reduce surface runoff. Existing stormwater governance, however, is centralized and structured to support the conventional systems. This governance approach is not suited to the emerging distributed management approach, which involves multiple stakeholders including parcel owners, government agencies, and non-governmental organizations. This incongruence between technology and governance calls for a paradigm shift in the governance from centralized and technocratic to distributed and participatory governance. This paper evaluates how five US cities have been adjusting their governance to address the discord. Finally, the paper proposes an alternative governance model, which provides a mechanism to involve stakeholders and implement distributed green infrastructure under an integrative framework.

  12. The PRISM (Pliocene Palaeoclimate) reconstruction: Time for a paradigm shift

    Science.gov (United States)

    Dowsett, Harry J.; Robinson, Marci M.; Stoll, Danielle K.; Foley, Kevin M.; Johnson, Andrew L. A.; Williams, Mark; Riesselman, Christina

    2013-01-01

    Global palaeoclimate reconstructions have been invaluable to our understanding of the causes and effects of climate change, but single-temperature representations of the oceanic mixed layer for data–model comparisons are outdated, and the time for a paradigm shift in marine palaeoclimate reconstruction is overdue. The new paradigm in marine palaeoclimate reconstruction stems the loss of valuable climate information and instead presents a holistic and nuanced interpretation of multi-dimensional oceanographic processes and responses. A wealth of environmental information is hidden within the US Geological Survey's Pliocene Research,Interpretation and Synoptic Mapping (PRISM) marine palaeoclimate reconstruction, and we introduce here a plan to incorporate all valuable climate data into the next generation of PRISM products. Beyond the global approach and focus, we plan to incorporate regional climate dynamics with emphasis on processes, integrating multiple environmental proxies wherever available in order to better characterize the mixed layer, and developing a finer time slice within the Mid-Piacenzian Age of the Pliocene, complemented by underused proxies that offer snapshots into environmental conditions. The result will be a proxy-rich, temporally nested, process-oriented approach in a digital format - a relational database with geographic information system capabilities comprising a three-dimensional grid representing the surface layer, with a plethora of data in each cell.

  13. Enhanced Recovery After Surgery: The Plastic Surgery Paradigm Shift.

    Science.gov (United States)

    Bartlett, Erica L; Zavlin, Dmitry; Friedman, Jeffrey D; Abdollahi, Aariane; Rappaport, Norman H

    2017-12-14

    With a focus on providing high quality care and reducing facility based expenses there has been an evolution in perioperative care by way of enhanced recovery after surgery (ERAS). ERAS allows for a multidisciplinary and multimodal approach to perioperative care which not only expedites recovery but maximizes patient outcomes. This paradigm shift has been generally accepted by most surgical specialties, including plastic surgery. The goal of this study was to evaluate the impact of ERAS on outcomes in cosmetic plastic surgery. A prospective study consisting of phone call questionnaires was designed where patients from two senior plastic surgeons (N.H.R. and J.D.F.) were followed. The treatment group (n = 10) followed an ERAS protocol while the control group (n = 12) followed the traditional recovery after surgery which included narcotic usage. Patients were contacted on postoperative days (POD) 0 through 7+ and surveyed about a number of outcomes measures. The ERAS group demonstrated a significant reduction in postoperative pain on POD 0, 1, 2, and 3 (all P plastic surgery. The utility lies in the ability to expedite patient's recovery while still providing quality care. This study showed a reduction in postoperative complaints by avoiding narcotics without an increase in complications. Our findings signify the importance of ERAS protocols within cosmetic plastic surgery. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  14. From Product to Service Design: A Thinking Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Liliana Rodriguez

    2014-12-01

    Full Text Available Society, industry and the economy are all experiencing changes caused by a shift from products to services. While a “problem-solving” approach is commonly used for the development of products, new design approaches are needed as the primary unit of exchange moves from goods to services.  This research argues that a fundamental transformation in the design world is taking place, manifested in a thinking paradigm shift from problem solving (designing products towards systems thinking (designing services. This paper draws on design literature to identify concepts of systems thinking and problem solving to help understand core elements in the shift from product to service design. It also reports on a series of semi-structured interviews with designers working in five design consultancies that have moved from product design to services design. The results show a change in the way designers think and approach projects when facing the challenges of designing services, confirming a movement from problem solving to systems thinking. However, systems thinking is not replacing problem solving but complementing it. The results also indicate that the growing complexity of the issues designers deal with influences the adoption of systems thinking in responding to service design challenges, as well as current changes in people’s ideas about sustainability and  society.

  15. Paradigm shift in transport legislation or rather at the 'bottleneck'

    International Nuclear Information System (INIS)

    Naeser, Hanns

    2015-01-01

    In the year just started significant decisions with considerable consequences by the Federal Constitutional Court and the Federal Administrative Court in the field of nuclear law are expected. Especially the decision with regards to 'nuclear phase-out' within the 13th amendment of the Atomic Energy Act is being eagerly expected, as with its far-reaching consequences also fundamental constitutional questions need to be answered. The Federal Administrative Court will need to decide on the question, whether she admits the appeal against the Brunsbuettel decision by the Higher Administrative Court Schleswig-Holstein (HAC), which from the view of claimant shifted the fundamental basis of demarcation of responsibilities between the executive and judiciary power. In comparison to these fundamental decisions the awaited decision by the HAC on nuclear transport legislation seems of subordinate importance, although she will proceed with a paradigm shift in the legal area. The decision deals with the question as to whether and when a right of action from a third party within the nuclear transport legislation can be accepted or more precisely under which preconditions a third party has clear standing against a nuclear transport authorisation. As the site selection law (issued on 23 July 2013 BGBI I p. 2552) excludes the recirculation of vitrified waste block canisters from reprocessing spent fuel elements to the transport cask storage facility Gorleben, the decision by the HAC Lueneburg for this site will only be relevant for present unpredictable transportations from the transport cask storage facility Gorleben to a final repository. If necessary interest to seek a declaratory judgment for declaratory action, in concreto danger of recurrence will be approved, is another matter.

  16. Guidelines, editors, pharma and the biological paradigm shift.

    Science.gov (United States)

    Singh, Ajai R; Singh, Shakuntala A

    2007-01-01

    independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a 'gold standard' or which that player thinks has still some 'juice' left.Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady

  17. When Medicine Meets Engineering—Paradigm Shifts in Diagnostics and Therapeutics

    Directory of Open Access Journals (Sweden)

    Aleidy Silva

    2013-02-01

    Full Text Available During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio-medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics.

  18. Remote monitoring of cardiovascular implanted electronic devices: a paradigm shift for the 21st century.

    Science.gov (United States)

    Cronin, Edmond M; Varma, Niraj

    2012-07-01

    Traditional follow-up of cardiac implantable electronic devices involves the intermittent download of largely nonactionable data. Remote monitoring represents a paradigm shift from episodic office-based follow-up to continuous monitoring of device performance and patient and disease state. This lessens device clinical burden and may also lead to cost savings, although data on economic impact are only beginning to emerge. Remote monitoring technology has the potential to improve the outcomes through earlier detection of arrhythmias and compromised device integrity, and possibly predict heart failure hospitalizations through integration of heart failure diagnostics and hemodynamic monitors. Remote monitoring platforms are also huge databases of patients and devices, offering unprecedented opportunities to investigate real-world outcomes. Here, the current status of the field is described and future directions are predicted.

  19. Radical Innovation, Paradigm Shift and Incumbent’s Dilemma The Case of the Auto Industry

    Directory of Open Access Journals (Sweden)

    Eden Yin

    2017-04-01

    & Rothaermel, 2003. These innovations may have the potential to shrink the incumbents’ marketspace, e.g., Gemesis’ synthetic diamonds challenging the natural diamonds (McAdams and Reavis, 2008, EasyJet challenging mainstream airlines such as BA, Netflix challenging the traditional movie rental business (Leonhartdt, 2006, or displace the incumbent market leader, e.g., IBM PC and its clones destroyed minicomputer makers such as DEC, Wang, Apollo and so on. Yet, they do not often disrupt the entire industry. But in recent years, more industry-wide disruptions have occurs due to emerge of not a single radical innovation but an array of them simultaneously from within or outside of a particular industry. In this process, it is not just the incumbent market leader or a few incumbent firms but the entire value chain, ecosystem or industry get displaced, the so-called paradigm shift, e.g., GPS device by software companies such as Google and Waze, desktop computing by mobile devices, and the traditional auto industry centered around the internal combustion engine by peer-to-peer service provider (e.g., Uber, consumer electronics (e.g., Apple, battery-driven vehicle (e.g., Tesla, and software companies (e.g., Google, Amazon. When this happens, incumbents are not fighting against a particular firm or a few firms that have introduced radical innovations based on similar technologies, but an army of very diverse entrants that are disrupting the entire industries from various directions, some of which are from remote industries with vastly different organizational capabilities, mindset and business model. How incumbents of the existing ecosystem should best cope with the massive and dramatic industry-level disruption induced by multiple radical innovations along a number of fronts or paradigm shift has largely remained unexamined. In the face of paradigm shift, can the above mentioned strategies or tactics for incumbents to combat single radical innovation or firm be adequate to deal

  20. Cancer research in need of a scientific revolution: Using 'paradigm shift' as a method of investigation.

    Science.gov (United States)

    Wion, Didier; Appaix, Florence; Burruss, Meriwether; Berger, Francois; van der Sanden, Boudewijn

    2015-09-01

    Despite important human and financial resources and considerable accumulation of scientific publications, patents, and clinical trials, cancer research has been slow in achieving a therapeutic revolution similar to the one that occurred in the last century for infectious diseases. It has been proposed that science proceeds not only by accumulating data but also through paradigm shifts. Here, we propose to use the concept of 'paradigm shift' as a method of investigation when dominant paradigms fail to achieve their promises. The first step in using the 'paradigm shift' method in cancer research requires identifying its founding paradigms. In this review, two of these founding paradigms will be discussed: (i) the reification of cancer as a tumour mass and (ii) the translation of the concepts issued from infectious disease in cancer research. We show how these founding paradigms can generate biases that lead to over-diagnosis and over-treatment and also hamper the development of curative cancer therapies. We apply the 'paradigm shift' method to produce perspective reversals consistent with current experimental evidence. The 'paradigm shift' method enlightens the existence of a tumour physiologic-prophylactic-pathologic continuum. It integrates the target/antitarget concept and that cancer is also an extracellular disease. The 'paradigm shift' method has immediate implications for cancer prevention and therapy. It could be a general method of investigation for other diseases awaiting therapy.

  1. The coming paradigm shift: A transition from manual to automated microscopy.

    Science.gov (United States)

    Farahani, Navid; Monteith, Corey E

    2016-01-01

    The field of pathology has used light microscopy (LM) extensively since the mid-19(th) century for examination of histological tissue preparations. This technology has remained the foremost tool in use by pathologists even as other fields have undergone a great change in recent years through new technologies. However, as new microscopy techniques are perfected and made available, this reliance on the standard LM will likely begin to change. Advanced imaging involving both diffraction-limited and subdiffraction techniques are bringing nondestructive, high-resolution, molecular-level imaging to pathology. Some of these technologies can produce three-dimensional (3D) datasets from sampled tissues. In addition, block-face/tissue-sectioning techniques are already providing automated, large-scale 3D datasets of whole specimens. These datasets allow pathologists to see an entire sample with all of its spatial information intact, and furthermore allow image analysis such as detection, segmentation, and classification, which are impossible in standard LM. It is likely that these technologies herald a major paradigm shift in the field of pathology.

  2. The coming paradigm shift: A transition from manual to automated microscopy

    Directory of Open Access Journals (Sweden)

    Navid Farahani

    2016-01-01

    Full Text Available The field of pathology has used light microscopy (LM extensively since the mid-19 th century for examination of histological tissue preparations. This technology has remained the foremost tool in use by pathologists even as other fields have undergone a great change in recent years through new technologies. However, as new microscopy techniques are perfected and made available, this reliance on the standard LM will likely begin to change. Advanced imaging involving both diffraction-limited and subdiffraction techniques are bringing nondestructive, high-resolution, molecular-level imaging to pathology. Some of these technologies can produce three-dimensional (3D datasets from sampled tissues. In addition, block-face/tissue-sectioning techniques are already providing automated, large-scale 3D datasets of whole specimens. These datasets allow pathologists to see an entire sample with all of its spatial information intact, and furthermore allow image analysis such as detection, segmentation, and classification, which are impossible in standard LM. It is likely that these technologies herald a major paradigm shift in the field of pathology.

  3. The public perception of climate change in Taiwan and its paradigm shift

    International Nuclear Information System (INIS)

    Chou, Kuei Tien

    2013-01-01

    This study attempts to explore the risk perceptions of climate change in Taiwan. It probes into the public's views toward governments' risk communication regarding climate change, citizens' participation in decision-making, and their trust in the capacity of governments toward risk governance, as well as their attitude towards corporate social responsibility. For analysis, we developed ten types of perceptions under three dimensions: namely the severity of climate change (Type 1), the development of sustainable society (Types 2, 3, 4 and 5), and the risk governance and communication (Types 6, 7, 8, 9 and 10) to discuss whether the Taiwanese public's perception of climate change was prepared for a socially reflective paradigm shift. Regarding the three dimensions in the questionnaire design, although this study individually measured the public's risk perception, there was a high correlation between the variance analysis results among the three dimensions. This could systematically explain the potential change of the governance paradigm in Taiwanese society concerning structural transformation. - Highlights: • The public had critical view on the policy decision-making of climate change. • There is low public trust in the government's capacity to resist climate change. • The public requested more risk communication, transparency and participation. • The pursuit of an alternative sustainable economic society is highly expected. • People supported renewable energy by higher prices for carbon reduction

  4. Challenges of Transit Oriented Development (TOD in Iran. The Need for a Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Mahta Mirmoghtadaee

    2016-10-01

    The major contention of this paper is to discuss the general concept of TOD, its benefits and challenges in Iranian urban context. It is discussed here that TOD has several positive outcomes considering the existing urbanization trends in Iran. It may be used as a practical instrument to deal with rapidly urbanizing country in which motorization rate is increasing and air pollution is the serious cause of life loss. However there are several challenges which should be faced. The need for an Iranian version of TOD, which re-narrated the theory according to local situation, is the first challenge. A paradigm shift in the government, shifting the priority from housing schemes to mass transit systems is the second challenge needed to be taken into consideration. The third challenge is the overlapping and parallel institutions dealing with mass transit systems in urban and regional transportation planning and insufficient planning instruments. The integrated transportation and urban planning system is necessary here, and there is an urgent need to develop a national TOD guideline with the potential to develop local versions for each city.

  5. The need for a paradigm shift in toxicology xx.

    Science.gov (United States)

    This manuscript briefly reviews the impact of the NAS report “Toxicity Testing in the 21st Century: A Vision and A Strategy” and it’s potential impact on the field of toxicology. ). This report provides a strategic and tactical framework for attaining the goals of deter...

  6. Paradox of schizophrenia genetics: is a paradigm shift occurring?

    Directory of Open Access Journals (Sweden)

    Doi Nagafumi

    2012-05-01

    Full Text Available Abstract Background Genetic research of schizophrenia (SCZ based on the nuclear genome model (NGM has been one of the most active areas in psychiatry for the past two decades. Although this effort is ongoing, the current situation of the molecular genetics of SCZ seems disappointing or rather perplexing. Furthermore, a prominent discrepancy between persistence of the disease at a relatively high prevalence and a low reproductive fitness of patients creates a paradox. Heterozygote advantage works to sustain the frequency of a putative susceptibility gene in the mitochondrial genome model (MGM but not in the NGM. Methods We deduced a criterion that every nuclear susceptibility gene for SCZ should fulfill for the persistence of the disease under general assumptions of the multifactorial threshold model. SCZ-associated variants listed in the top 45 in the SZGene Database (the version of the 23rd December, 2011 were selected, and the distribution of the genes that could meet or do not meet the criterion was surveyed. Results 19 SCZ-associated variants that do not meet the criterion are located outside the regions where the SCZ-associated variants that could meet the criterion are located. Since a SCZ-associated variant that does not meet the criterion cannot be a susceptibility gene, but instead must be a protective gene, it should be linked to a susceptibility gene in the NGM, which is contrary to these results. On the other hand, every protective gene on any chromosome can be associated with SCZ in the MGM. Based on the MGM we propose a new hypothesis that assumes brain-specific antioxidant defenses in which trans-synaptic activations of dopamine- and N-methyl-d-aspartate-receptors are involved. Most of the ten predictions of this hypothesis seem to accord with the major epidemiological facts and the results of association studies to date. Conclusion The central paradox of SCZ genetics and the results of association studies to date argue against

  7. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

  8. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria.

    Science.gov (United States)

    Nicolle, Lindsay E

    2016-04-19

    Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

  9. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

    Directory of Open Access Journals (Sweden)

    Lindsay E. Nicolle

    2016-04-01

    Full Text Available Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

  10. Lab-oriented radical innovations as drivers of paradigm shifts in science

    NARCIS (Netherlands)

    Coccia, M.

    2014-01-01

    An interesting problem in the economics of innovation and strategic management of labs is to explain the drivers of breakthroughs and paradigm shifts in science. This study confronts the issue by analysing a main case study: the technological determinant of the discovery of quasi-periodic materials

  11. The Paradigm Shift: Leadership Challenges in the Public Sector Schools in Pakistan

    Science.gov (United States)

    Mansoor, Zahida

    2015-01-01

    Previous research has established that school heads as leaders are vital to the successful implementation of educational reforms (Derek, 2009; Robinson, Lloyd, & Rowe, 2008). Education system in Pakistan is going through a paradigm shift from teacher centered to learner centered classrooms using English as the instructional language. The…

  12. Human security from paradigm shift to operationalisation: job description for a human security worker

    NARCIS (Netherlands)

    Glasius, M.

    2008-01-01

    This article shows how human security has functioned as both a paradigm-shifting and a bridging concept, with its most significant implications being, first, the shift from a focus on state security to one on human rights, and, second, the indivisibility of physical and material security. The

  13. paradigm shift

    Indian Academy of Sciences (India)

    2015-07-17

    Jul 17, 2015 ... Cancer research in need of a scientific revolution: .... 'scientific revolution' is not exclusive. For example, ..... Stroma in breast development and disease. Semin. ..... Welch HG and Passow HJ 2014 Quantifying the benefits and.

  14. Evolution of Management Theory within 20 Century: A Systemic Overview of Paradigm Shifts in Management

    OpenAIRE

    Khorasani, Sasan Torabzadeh; Almasifard, Maryam

    2017-01-01

    Significant progress in civilization of human being has been made over 20century. Advance technology; globalization and revolution of communication are the main outcomes of this development. However, it is obvious that these achievements have been significantly influenced by evolution of management theories. The paradigm shift from classical management to modern management can be clustered into several phases. This paper presents an overview of evolution of management theory within 20 century...

  15. Probabilities, beliefs, and dual processing: The paradigm shift in the psychology of reasoning

    OpenAIRE

    Elqayam, Shira; Over, D. E

    2012-01-01

    In recent years, the psychology of reasoning has been undergoing a paradigm shift, with general Bayesian, probabilistic approaches replacing the older, much more restricted binary logic paradigm. At the same time, dual processing theories have been gaining influence. We argue that these developments should be integrated and moreover that such integration is already underway. The new reasoning paradigm should be grounded in dual processing for its algorithmic level of analysis just as it uses ...

  16. Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine paradigm shift in oncological surgery?

    Science.gov (United States)

    Harris, A T; Tanyi, A; Hart, R D; Trites, J; Rigby, M H; Lancaster, J; Nicolaides, A; Taylor, S M

    2018-01-01

    Transoral laser microsurgery applies to the piecemeal removal of malignant tumours of the upper aerodigestive tract using the CO 2 laser under the operating microscope. This method of surgery is being increasingly popularised as a single modality treatment of choice in early laryngeal cancers (T1 and T2) and occasionally in the more advanced forms of the disease (T3 and T4), predominantly within the supraglottis. Thomas Kuhn, the American physicist turned philosopher and historian of science, coined the phrase 'paradigm shift' in his groundbreaking book The Structure of Scientific Revolutions. He argued that the arrival of the new and often incompatible idea forms the core of a new paradigm, the birth of an entirely new way of thinking. This article discusses whether Steiner and colleagues truly brought about a paradigm shift in oncological surgery. By rejecting the principle of en block resection and by replacing it with the belief that not only is it oncologically safe to cut through the substance of the tumour but in doing so one can actually achieve better results, Steiner was able to truly revolutionise the management of laryngeal cancer. Even though within this article the repercussions of his insight are limited to the upper aerodigestive tract oncological surgery, his willingness to question other peoples' dogma makes his contribution truly a genuine paradigm shift.

  17. Paradigm shifts in critical care medicine: the progress we have made.

    Science.gov (United States)

    Vincent, Jean-Louis; Creteur, Jacques

    2015-01-01

    There have really been no single, major, advances in critical care medicine since the specialty came into existence. There has, however, been a gradual, continuous improvement in the process of care over the years, which has resulted in improved patient outcomes. Here, we will highlight just a few of the paradigm shifts we have seen in processes of critical care, including the move from small, closed units to larger, more open ICUs; from a paternal "dictatorship" to more "democratic" team-work; from intermittent to continuous, invasive to less-invasive monitoring; from "more" interventions to "less" thus reducing iatrogenicity; from consideration of critical illness as a single event to realization that it is just one part of a trajectory; and from "four walls" to "no walls" as we take intensive care outside the physical ICU. These and other paradigm shifts have resulted in improvements in the whole approach to patient management, leading to more holistic, humane care for patients and their families. As critical care medicine continues to develop, further paradigm shifts in processes of care are inevitable and must be embraced if we are to continue to provide the best possible care for all critically ill patients.

  18. Paradigm shifts in critical care medicine: the progress we have made

    Science.gov (United States)

    2015-01-01

    There have really been no single, major, advances in critical care medicine since the specialty came into existence. There has, however, been a gradual, continuous improvement in the process of care over the years, which has resulted in improved patient outcomes. Here, we will highlight just a few of the paradigm shifts we have seen in processes of critical care, including the move from small, closed units to larger, more open ICUs; from a paternal "dictatorship" to more "democratic" team-work; from intermittent to continuous, invasive to less-invasive monitoring; from "more" interventions to "less" thus reducing iatrogenicity; from consideration of critical illness as a single event to realization that it is just one part of a trajectory; and from "four walls" to "no walls" as we take intensive care outside the physical ICU. These and other paradigm shifts have resulted in improvements in the whole approach to patient management, leading to more holistic, humane care for patients and their families. As critical care medicine continues to develop, further paradigm shifts in processes of care are inevitable and must be embraced if we are to continue to provide the best possible care for all critically ill patients. PMID:26728199

  19. The effectiveness of the Millennium Development Goals (MDG as global paradigm shift for poverty eradication in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Herman van der Elst

    2012-07-01

    Full Text Available Despite isolated progress there seems to be no clear-cut guideline or solution to the collective eradication of extreme poverty in sub-Saharan Africa. In an attempt to overcome the above reality, the objective of the Millennium Development Goals (MDGs is short term poverty relief to the poorest of the poor by 2015. This is to be achieved through the realisation of eight pro-poor objectives. Since 2000 there has been notable progress. Developmental organisations such as the World Bank, the International Monetary Fund (IMF and the Freedom House Index project that global poverty will have been reduced to below fifteen per cent by 2015. The MDGs can, however, currently only be perceived as partially effective because poverty relief remains restricted to mainly Latin America and South and South East Asia. This partial success is substantiated by the reality that the majority of states in sub-Saharan Africa remains subjected to a cycle of extreme poverty, which seems impossible to overcome. There is consensus amongst many researchers that none of the MDGs will be achieved in this region by 2015. This article aims to critically analyse the nature, objectives and progress of the MDGs as a global developmental paradigm shift. In order to explore future trends and identify potential solutions, an emphasis is, however, placed on the possible reasons for the slow progress of the MDGs, specifically in sub-Saharan Africa. Keywords: Global paradigm shift, new conditionality, extreme poverty, poverty eradication, sub-Saharan Africa, foreign aid, deprivation hypothesis, weak governance, free-market approach and the poverty trap Disciplines: International relations, law, political economy, politics, environmental studies, water studies, communication studies, public management and governance, education, sociology, anthropology and history.

  20. The paradigm shift to an “open” model in drug development

    Directory of Open Access Journals (Sweden)

    Regina Au

    2014-12-01

    Full Text Available The rising cost of healthcare, the rising cost for drug development, the patent cliff for Big pharma, shorter patent protection, decrease reimbursement, and the recession have made it more difficult for the pharmaceutical and biotechnology industry to develop drugs. Due to the unsustainable amount of time and money in developing a drug that will have a significant return on investment (ROI it has become hard to sustain a robust pipeline. The industry is transforming its business model to meet these challenges. In essence a paradigm shift is occurring; the old “closed” model is giving way to a new “open” business model.

  1. India's NCD strategy in the SDG era: are there early signs of a paradigm shift?

    Science.gov (United States)

    Mondal, Shinjini; Van Belle, Sara

    2018-04-25

    The Sustainable Development Goals (SDGs) are seen in most corners as the embodiment of a more inclusive and holistic development approach, key to addressing the numerous and urgent challenges the world faces. In the health realm, a true SDG approach will require a five-fold paradigm shift according to Buse and Hawkes. This article explores whether early traces of this paradigm shift can already be witnessed in the Indian context, focusing on Non-Communicable Diseases (NCDs) more in particular. By now, NCDs make up a large health burden in India, both individually and on the health system. Inspired by an SDG vision, tackling NCDs will require a comprehensive approach rooted in preventive, curative and rehabilitative services. In India, some early momentum in this respect can already be witnessed, certainly in addressing the first two challenges identified by Buse and Hawkes, leadership and intersectoral coherence, and a shift from treatment to prevention. A central plan addressing health through an inter-sectoral approach has shaped the trajectory so far, moving away from silos to engagement with sectors beyond health. New guidelines addressing comprehensive primary healthcare propose a community outreach and preventive approach for NCDs. At a broader level, NCD prevention is also closely linked to tackling the so called "commercial determinants of health" and will require among others strong (central and state level) regulation, teaming up with global advocacy networks and capitalizing on global frameworks, where they exist. Strong political leadership will be indispensable for this, and is according to Buse and Hawkes closely linked to seeing health as a right and the government as accountable when it comes to providing for the right to health through its policies and actions. National stewardship will thus be key, via a more adaptive network governance structure with the central level coordinating with the state level to ensure implementation, while also engaging

  2. Ready for a paradigm shift? Part 1: introducing the philosophy of qualitative research.

    Science.gov (United States)

    Petty, Nicola J; Thomson, Oliver P; Stew, Graham

    2012-08-01

    The manual therapy professions have almost exclusively focused on the use of quantitative research to help inform their practices. This paper argues that a greater use of qualitative research will help develop a more robust and comprehensive knowledge base in manual therapy. The types of knowledge used in practice and generated from the two research paradigms are explored. It is hoped that an understanding of the philosophical and theoretical underpinnings of qualitative research may encourage more manual therapists to value and use this approach to help further inform their practice; for some, this may involve a paradigm shift in thinking. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Will the Meikirch Model, a New Framework for Health, Induce a Paradigm Shift in Healthcare?

    Science.gov (United States)

    Bircher, Johannes; Hahn, Eckhart G

    2017-03-06

    healthcare interact based on the model, mutual understanding of and adherence to treatments and preventive measures will improve. In healthcare, the Meikirch model also makes it plain that neither pay-for-performance nor value-based payment is an adequate response to improve person-centered healthcare. The Meikirch model is not only a unifying theoretical framework for health and disease but also a scaffold for the practice of medicine and public health. It is fully in line with the theory and practice of evidence-based medicine, person-centered healthcare, and integrative medicine. The model offers opportunities to self-motivate people to improve their health-supporting behavior, thereby making preventive approaches and overall healthcare more effective. We believe that the Meikirch model could induce a paradigm shift in healthcare. The healthcare community is hereby invited to acquaint themselves with this model and to consider its potential ramifications.

  4. Paradigm shift, metamorphosis of medical ethics, and the rise of bioethics

    Directory of Open Access Journals (Sweden)

    José Luiz Telles de Almeida

    Full Text Available Both the increasing incorporation of medical technology and new social demands (including those for health care beginning in the 1960s have brought about significant changes in medical practice. This situation has in turn sparked a growth in the philosophical debate over problems pertaining to ethical practice. These issues no longer find answers in the Hippocratic ethical model. The authors believe that the crisis in Hippocratic ethics could be described as a period of paradigm shift in which a new set of values appears to be emerging. Beginning with the bioethics movement, the authors expound on the different ethical theories applied to medical practice and conclude that principlism is the most appropriate approach for solving the new moral dilemma imposed on clinical practice.

  5. Flexible Believers in the Netherlands: A Paradigm Shift toward Transreligious Multiplicity

    Directory of Open Access Journals (Sweden)

    Kalsky Manuela

    2017-01-01

    Full Text Available The Netherlands has undergone a radical religious transformation through secularization, individualization and migration. Expressions of Christian belief are no longer strictly defined by the Church and hybrid forms of religiosity incorporating other religions have emerged. After a brief sketch of Dutch religious plurality, the author focuses on interviews with ‘flexible believers’, people who combine elements from different religious traditions and worldviews. Through interviews, she discovers a number of characteristics of these multiple religious believers (MRB - interviewees - such as ritual praxis, identity-making processes and belonging - and reflects on their impact for the wider picture of religiosity in today‘s post-Christian Dutch network society. She concludes that hybrid forms of lived religion like mrb, present a challenge to traditional concepts of religious identity and belonging. They require a paradigm shift from an ‘either/or’ to a relational ‘as well as’ approach within a rhizomatic network of meaning.

  6. Paradigm Shift: Report on the New Role of Design in Business and Society

    Directory of Open Access Journals (Sweden)

    Gjoko Muratovski

    Full Text Available Corporate cultures' prevailing attitudes towards design have begun to shift. Financial companies and management consultancies now have design teams, and include “design” in their service portfolios. Large corporations are bolstering their in-house design capabilities, and appointing designers to executive roles. Venture capitalist firms and startups increasingly recognize the value of including designers in the early stages of business development. Even global organizations and international foundations now list design on their agendas. A paradigm shift is taking place in the field of design. This study examines some of the latest corporate investments in design, and reflects on what this phenomenon means for the wider field of design. The focus of this study is on the key trend indicators that are defining the current landscape of design, and its changing role in business and society.

  7. Use of dextran nanoparticle: A paradigm shift in bacterial exopolysaccharide based biomedical applications.

    Science.gov (United States)

    Banerjee, Aparna; Bandopadhyay, Rajib

    2016-06-01

    This review is a concise compilation of all the major researches on dextran nanoparticle based biomedical applications. Dextran is a highly biocompatible and biodegradable neutral bacterial exopolysaccharide with simple repeating glucose subunits. It's simple yet unique biopolymeric nature made it highly suitable as nanomedicine, nanodrug carrier, and cell imaging system or nanobiosensor. Most importantly, it is extremely water soluble and shows no post drug delivery cellular toxicity. Complete metabolism of dextran is possible inside body thus possibility of renal failure is minimum. Dextran based nanoparticles have superior aqueous solubility, high cargo capacity and intrinsic viscosity, and short storage period. The main focus area of this review is- past and present of major biomedical applications of dextran based nanomaterials thus showing a paradigm shift in bacterial exopolysaccharide based nanobiotechnology. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Does prospect theory warrant a paradigm shift in the economics of risk?

    Directory of Open Access Journals (Sweden)

    PL Mohapi

    2014-07-01

    Full Text Available This paper assesses whether a paradigm shift should be made from expected utility framework to prospect theory framework – in the economics of choice under risk. A brief overview of the subject is outlined, starting with expected utility theory and noting its descriptive limitations. Proposed theories to make up for these limitations is also provided. Prospect theory emerged as the most serious challenger to expected utility theory. A review of some descriptive predictions of prospect theory, suggests that there is no scientific reason why expected utility should not be ousted from dominance by prospect theory. The shift to prospect theory however is not without costs. Conceptual complexities and non-universality of application associated with prospect theory should be embraced with the shift while not entirely abandoning expected utility theory.

  9. Effects of holistic nursing course: a paradigm shift for holistic health practices.

    Science.gov (United States)

    Downey, Marty

    2007-06-01

    A study of an undergraduate course in holistic nursing was conducted to determine its impact on personal and professional health care practices. A mixed method design was used to examine responses on a sample of 200 participants. Results indicated a positive personal impact with continued application of concepts into professional health practices. Personal and professional nursing practices were influenced from 1 to 7 years after completing the holistic nursing course. After introduction of the concepts of self-care and holistic approaches to health, students and graduates experienced a shift in values and beliefs related to their own health practices. Continued exposure to holistic practices creates a pattern of awareness toward health that affects future personal and professional nursing practice, creating a paradigm shift for emerging nursing students and graduates from the course. This affects the manner in which nurses meet the needs of their clients in a variety of settings.

  10. From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm Shift in Microbiology.

    Science.gov (United States)

    Nai, Corrado; Meyer, Vera

    2018-06-01

    Since the onset of microbiology in the late 19th century, scientists have been growing microorganisms almost exclusively as pure cultures, resulting in a limited and biased view of the microbial world. Only a paradigm shift in cultivation techniques - from axenic to mixed cultures - can allow a full comprehension of the (chemical) communication of microorganisms, with profound consequences for natural product discovery, microbial ecology, symbiosis, and pathogenesis, to name a few areas. Three main technical advances during the last decade are fueling the realization of this revolution in microbiology: microfluidics, next-generation 3D-bioprinting, and single-cell metabolomics. These technological advances can be implemented for large-scale, systematic cocultivation studies involving three or more microorganisms. In this review, we present recent trends in microbiology tools and discuss how these can be employed to decode the chemical language that microorganisms use to communicate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. E-health beyond technology: analyzing the paradigm shift that lies beneath.

    Science.gov (United States)

    Moerenhout, Tania; Devisch, Ignaas; Cornelis, Gustaaf C

    2018-03-01

    Information and computer technology has come to play an increasingly important role in medicine, to the extent that e-health has been described as a disruptive innovation or revolution in healthcare. The attention is very much focused on the technology itself, and advances that have been made in genetics and biology. This leads to the question: What is changing in medicine today concerning e-health? To what degree could these changes be characterized as a 'revolution'? We will apply the work of Thomas Kuhn, Larry Laudan, Michel Foucault and other philosophers-which offers an alternative understanding of progress and revolution in medicine to the classic discovery-oriented approach-to our analysis. Nowadays, the long-standing curative or reactive paradigm in medicine is facing a crisis due to an aging population, a significant increase in chronic diseases and the development of more expensive diagnostic tools and therapies. This promotes the evolution towards a new paradigm with an emphasis on preventive medicine. E-health constitutes an essential part of this new paradigm that seeks to solve the challenges presented by an aging population, skyrocketing costs and so forth. Our approach changes the focus from the technology itself toward the underlying paradigm shift in medicine. We will discuss the relevance of this approach by applying it to the surge in digital self-tracking through health apps and wearables: the recognition of the underlying paradigm shift leads to a more comprehensive understanding of self-tracking than a solely discovery-oriented or technology-focused view can provide.

  12. Revisiting the 'paradigm shift' in opioid use: Developments and implications 10 years later.

    Science.gov (United States)

    Fischer, Benedikt; Rehm, Jürgen

    2017-03-23

    A decade ago, we queried the unfolding of a 'paradigm shift' in illicit opioid use in North America, specifically involving a shift away from heroin to prescription opioid (PO) use. Today, this situation is more acute than ever, with prescription opioid misuse, morbidity and mortality amounting to one of the most severe substance use-related public health crises ever, now even impacting life expectancy in key population segments. Despite medical system-based PO dispensing and practices being recognised as core drivers of the PO crisis, effective policy measures have been long absent or limited-including those to reduce medical PO use to levels supported by best evidence for pain care. At the same time, heroin use has been increasing again, now commonly tied into interdependent opioid use trajectories, initiated with POs yet shifting to heroin as influenced by economic or availability factors. For policy, there are now two major and urgent-yet partly conflicting-tasks: one is to reduce the determinants of PO misuse and harms by reducing medical prescribing to levels supported by good evidence, while the other is to effectively protect those many active problematic PO users from acute harms (including overdose mortality) by providing effective treatment and survival aids (e.g. naloxone). Surprisingly, it appears that a major 'homemade' and medical system-induced drug crisis has been at least as challenging for North American policy systems to address as other, more conventional illicit drug problems. Lessons for policy hence need to be urgently identified and applied for the future. [Fischer B, Rehm J. Revisiting the 'paradigm shift' in opioid use: Developments and implications 10 years later. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

  13. Paradigm shifts about dust on the Moon: From Apollo 11 to Chang'e-4

    Science.gov (United States)

    O'Brien, Brian J.

    2018-07-01

    Strategic purposes of this DAP-2017 report are to update our DAP-2010 report on movements of inescapable fine lunar dust, to summarise key new measurements and to assist rigorous focus. Lunar dust is defined here in two sciences, Apollo dust and Ejecta dust, to end several confusions. The Kuhn Cycle is introduced to stimulate progression of a science about movements of Apollo dust which lacks an agreed paradigm to supply puzzles for scientists to solve and tools for their solution. We populate the cycle with two paradigm shifts. The first was serendipitous invention in 1966 of the Apollo Dust Detector Experiment (DDE), 3 orthogonal solar cells each with a thermometer, which on Apollo 12 measured cause and effect, collective movements of billions to trillions of low-energy Apollo dust particles and changes in temperature they cause. In contrast, Apollo 17 LEAM and LADEE LDEX experiments follow traditions to measure impacts of high-velocity Ejecta dust particles, one by one. In 2015, Apollo 12 DDE discoveries of sunrise-driven storms of Apollo dust stimulated a measurement-based 5-step model of dust transport at astronaut waist height. The discoveries solve (i) 50-year-old mysteries of Horizon Glow, (ii) 30-year-old uncertainties about levitated dust, (iii) processes leading to lunar surfaces being smooth and (iv) immobilisation of the Chang'e-3 lunar rover Yutu in 2014 after its first sunrise. The IAC-2017 Website Abstract of a withdrawn Chang'e-3 presentation may support our views that sunrise-mobilised dust caused immobilisation of Yutu. A precursor to a second paradigm shift was May 2016 announced revision of Chang'e-4 scientific priorities. Using Kuhn terminology of scientific progress, a second shift would follow our "revolution" in 2015 that sunrise-driven dust storms caused the 2014 ″crisis" of immobilisation of Chang'e-3 lunar rover Yutu. No such sequence occurred previously with lunar dust. Measurement-based evidence from Apollo 11 to Chang'e-3 confirms

  14. How To Be Better Prepared For A Paradigm Shift In Economic Theory, And Write Better Articles In The Meantime

    NARCIS (Netherlands)

    P. Welch; W.A. Dolfsma (Wilfred)

    2004-01-01

    textabstractThe development of economic thought is not unlike the development of technological knowledge: paradigms can be discerned over time and across the field. Indeed, in its history economics has experienced paradigm shifts. There is no reason why it will not do so again in the future. In

  15. Misrepresenting Religious Education's Past and Present in Looking Forward: Gearon Using Kuhn's Concepts of Paradigm, Paradigm Shift and Incommensurability

    Science.gov (United States)

    Jackson, Robert

    2015-01-01

    In looking to the future, some writers on religious education (RE) have attempted to evaluate current approaches to the subject. Some have characterised any significant change in approach as a "paradigm shift", a term derived from Thomas Kuhn's work in the philosophy of science. This article examines the uses of the terms…

  16. The New Rule Paradigm Shift: Transforming At-Risk Programs by Matching Business Archetypes Strategies in the Global Market

    Science.gov (United States)

    Stark, Paul S.

    2007-01-01

    The challenge was given to transform aviation-related programs to keep them from being eliminated. These programs were to be discontinued due to enrollment declines, costs, legislative mandates, lack of administrative support, and drastic state budget reductions. The New Rule was a paradigm shift of focus to the global market for program…

  17. Baxter v. Montana, libertarianism, and end-of-life: the ripe time for a paradigm shift.

    Science.gov (United States)

    Ruble, James H

    2010-09-01

    Baxter v. Montana (2009 WL 5155363 [Mont. 2009]) is a recent decision from the Montana Supreme Court that provides new legal insight into the societal issue of aid in dying. This case involves interests of persons with terminal illness, medical practitioners, law enforcement, legislative and judicial bodies, as well as the citizens of Montana. A summary judgment ruling at the Montana district court level was based almost entirely on a constitutional fundamental rights analysis. In contrast, the Montana Supreme Court affirming decision was based almost entirely on a statutory rights analysis. Both rulings from the Montana courts support the position that licensed prescribers in Montana who provide aid in dying assistance to terminally ill patients have some immunity from criminal prosecution. Each side in the case argued what they believed to be the intents and purposes of the people of Montana. Baxter v. Montana illustrates different methods to determine the will of the people concerning aid in dying and public policy. This case very subtly suggests a paradigm shift may be occurring in aid in dying policy.

  18. Non-IID Recommender Systems: A Review and Framework of Recommendation Paradigm Shifting

    Directory of Open Access Journals (Sweden)

    Longbing Cao

    2016-06-01

    Full Text Available While recommendation plays an increasingly critical role in our living, study, work, and entertainment, the recommendations we receive are often for irrelevant, duplicate, or uninteresting products and services. A critical reason for such bad recommendations lies in the intrinsic assumption that recommended users and items are independent and identically distributed (IID in existing theories and systems. Another phenomenon is that, while tremendous efforts have been made to model specific aspects of users or items, the overall user and item characteristics and their non-IIDness have been overlooked. In this paper, the non-IID nature and characteristics of recommendation are discussed, followed by the non-IID theoretical framework in order to build a deep and comprehensive understanding of the intrinsic nature of recommendation problems, from the perspective of both couplings and heterogeneity. This non-IID recommendation research triggers the paradigm shift from IID to non-IID recommendation research and can hopefully deliver informed, relevant, personalized, and actionable recommendations. It creates exciting new directions and fundamental solutions to address various complexities including cold-start, sparse data-based, cross-domain, group-based, and shilling attack-related issues.

  19. Paradigm shifts and the interplay between state, business and civil sectors

    Science.gov (United States)

    Encarnação, Sara; Santos, Fernando P.; Santos, Francisco C.; Blass, Vered; Pacheco, Jorge M.; Portugali, Juval

    2016-12-01

    The recent rise of the civil sector as a main player of socio-political actions, next to public and private sectors, has largely increased the complexity underlying the interplay between different sectors of our society. From urban planning to global governance, analysis of these complex interactions requires new mathematical and computational approaches. Here, we develop a novel framework, grounded on evolutionary game theory, to envisage situations in which each of these sectors is confronted with the dilemma of deciding between maintaining a status quo scenario or shifting towards a new paradigm. We consider multisector conflicts regarding environmentally friendly policies as an example of application, but the framework developed here has a considerably broader scope. We show that the public sector is crucial in initiating the shift, and determine explicitly under which conditions the civil sector-reflecting the emergent reality of civil society organizations playing an active role in modern societies-may influence the decision-making processes accruing to other sectors, while fostering new routes towards a paradigm shift of the society as a whole. Our results are shown to be robust to a wide variety of assumptions and model parametrizations.

  20. The transformation from custodial to recovery-oriented care: a paradigm shift that needed to happen.

    Science.gov (United States)

    McKenna, Brian; Furness, Trentham; Dhital, Deepa; Park, Malcolm; Connally, Fiona

    2014-01-01

    As custodial mental health services are beginning to adopt a recovery-oriented model of care, it is imperative that successes in the transformation to recovery are captured. The aim of this illustrative case study was to describe the organizational procedure that enabled the systematic transformation of a custodial mental health service to a service with a self-professed recovery orientation as its model of service delivery. One-to-one interviews with key stakeholders and a document analysis were completed to thoroughly describe the transformation of the service. Four major themes arose from the data: (a) "We had this whole paradigm shift that needed to happen;" (b) "Think recovery," the development of a manualized guide; (c) "Stepping out my recovery;" adaptation of the service guide to the secure care context; and (d) developing the culture. The "developing the culture" major theme was subcategorized to consist of (a) the right people, (b) education, (c) reflective learning, and (d) leadership. The themes provided insights to assist mental health nurses to understand the processes involved in systems transformation. However, the major successes of the service, although only recently evaluated, commenced over a decade ago and yet continue to evolve.

  1. Regenerative endodontics: a true paradigm shift or a bandwagon about to be derailed?

    Science.gov (United States)

    Nazzal, H; Duggal, M S

    2017-02-01

    Regenerative endodontic techniques (RETs) have been hailed as a paradigm shift for the management of traumatised non-vital immature permanent anterior teeth. In this article the aim was to critically appraise the literature with regards to the outcome of regenerative endodontics on root development. Critical review of the literature where regenerative endodontic techniques have been used in the management of immature non-vital teeth with continuation of root development as the main outcome reported. Most studies published were in the form of case reports and series with very few randomised controlled trials with a high risk of bias. Continuation of root development following the use of RET has been shown to be unpredictable at best with lower success in those teeth losing vitality as a result of dental trauma. Despite the high success of regenerative endodontics in terms of periodontal healing including resolution of clinical and radiographic signs and symptoms of infection, continuation of root development remains an unpredictable outcome. The use of a blood clot as a scaffold in regenerative endodontics should be reviewed carefully as that might offer an environment for repair rather than regeneration. In addition, preservation of structures, such as Hertwig's epithelial root sheath, may have an important bearing on the success of this approach and should be further investigated.

  2. Paradigm shift regarding the transversalis fascia, preperitoneal space, and Retzius' space.

    Science.gov (United States)

    Asakage, N

    2018-06-01

    There has been confusion in the anatomical recognition when performing inguinal hernia operations in Japan. From now on, a paradigm shift from the concept of two-dimensional layer structure to the three-dimensional space recognition is necessary to promote an understanding of anatomy. Along with the formation of the abdominal wall, the extraperitoneal space is formed by the transversalis fascia and preperitoneal space. The transversalis fascia is a somatic vascular fascia originating from an arteriovenous fascia. It is a dense areolar tissue layer at the outermost of the extraperitoneal space that runs under the diaphragm and widely lines the body wall muscle. The umbilical funiculus is taken into the abdominal wall and transformed into the preperitoneal space that is a local three-dimensional cavity enveloping preperitoneal fasciae composed of the renal fascia, vesicohypogastric fascia, and testiculoeferential fascia. The Retzius' space is an artificial cavity formed at the boundary between the transversalis fascia and preperitoneal space. In the underlay mesh repair, the mesh expands in the range spanning across the Retzius' space and preperitoneal space.

  3. Physical Training and Activity in People With Diabetic Peripheral Neuropathy: Paradigm Shift.

    Science.gov (United States)

    Kluding, Patricia M; Bareiss, Sonja K; Hastings, Mary; Marcus, Robin L; Sinacore, David R; Mueller, Michael J

    2017-01-01

    Diabetic peripheral neuropathy (DPN) occurs in more than 50% of people with diabetes and is an important risk factor for skin breakdown, amputation, and reduced physical mobility (ie, walking and stair climbing). Although many beneficial effects of exercise for people with diabetes have been well established, few studies have examined whether exercise provides comparable benefits to people with DPN. Until recently, DPN was considered to be a contraindication for walking or any weight-bearing exercise because of concerns about injuring a person's insensitive feet. These guidelines were recently adjusted, however, after research demonstrated that weight-bearing activities do not increase the risk of foot ulcers in people who have DPN but do not have severe foot deformity. Emerging research has revealed positive adaptations in response to overload stress in these people, including evidence for peripheral neuroplasticity in animal models and early clinical trials. This perspective article reviews the evidence for peripheral neuroplasticity in animal models and early clinical trials, as well as adaptations of the integumentary system and the musculoskeletal system in response to overload stress. These positive adaptations are proposed to promote improved function in people with DPN and to foster the paradigm shift to including weight-bearing exercise for people with DPN. This perspective article also provides specific assessment and treatment recommendations for this important, high-risk group. © 2017 American Physical Therapy Association.

  4. Self-management in chronic obstructive pulmonary disease. Time for a paradigm shift?

    Science.gov (United States)

    Nici, Linda; Bontly, Thomas D; Zuwallack, Richard; Gross, Nicholas

    2014-01-01

    Self-management in chronic obstructive pulmonary disease, centering on an action plan for the exacerbation and enhanced communication between the patient and health care providers, makes good clinical sense. However, five relatively large trials of self-management in chronic obstructive pulmonary disease have had inconsistent results: only two demonstrated reductions in health care utilization and one had to be discontinued prematurely because of increased mortality. Do these discordant findings require a paradigm shift in our concept of self-management? Probably not-but an analysis of the negative studies can give us valuable insights. There are data to support the idea that patients in the trial that showed increased mortality did not self-manage appropriately. Only 4.5% of these patients called in before starting treatment for their exacerbation, the time to initiation of antibiotics or steroids was unsatisfactorily long, and the intervention arm used minimally more prednisone and antibiotics than the control arm. The reasons for a higher mortality will likely never be known, but it is possible that these high-risk patients may have needed earlier assessment by a trained professional, or that self-management led to overconfidence and treatment delays. We clearly need more effective ways to implement self-management and better define which groups of patients stand to benefit (or be harmed) by this intervention. This will require an investment in well-thought-out clinical trials.

  5. Italy’s contribution to global health: the need for a paradigm shift

    Science.gov (United States)

    2014-01-01

    This paper reviews Italian Development Assistance for Health and overall contribution to Global Health from 2001 to 2012. It analyses strategies and roles of central and decentralized authorities as well as those of private non-profit and corporate actors. The research illustrates a very low and unstable official contribution that lags far behind internationally agreed upon objectives, a highly fragmented institutional scenario, and controversial political choices favouring “vertical” global initiatives undermining national health systems, and in contrast with Italian deep-rooted principles, traditional approaches and official guidelines. Italy’s contribution to global health goes beyond official development aid, however. The raising movement toward Universal Health Coverage may offer an extraordinary opportunity for a leading role to a country whose National Health System is founded on the principles of universal and equitable access to care. At the same time, the distinctive experience of Italian decentralized cooperation, with the involvement of a multiplicity actors in a coordinated effort for cooperation in health with homologous partners in developing countries, may offer – if adequately harnessed - new opportunities for an Italian “system” of development cooperation. Nevertheless, the indispensable prerequisite of a substantial increase in public funding is challenged by the current economic crisis and domestic political situation. For a renewed Italian role in development and global health, a paradigm shift is needed, requiring both conceptual revision and deep institutional and managerial reforms to ensure an appropriate strategic direction and an efficient and effective use of resources. PMID:24708890

  6. Maximizing the Impact of e-Therapy and Serious Gaming: Time for a Paradigm Shift.

    Science.gov (United States)

    Fleming, Theresa M; de Beurs, Derek; Khazaal, Yasser; Gaggioli, Andrea; Riva, Giuseppe; Botella, Cristina; Baños, Rosa M; Aschieri, Filippo; Bavin, Lynda M; Kleiboer, Annet; Merry, Sally; Lau, Ho Ming; Riper, Heleen

    2016-01-01

    Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives' paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.

  7. Maximizing the impact of e-therapy and serious gaming: Time for a paradigm shift

    Directory of Open Access Journals (Sweden)

    Theresa M Fleming

    2016-04-01

    Full Text Available Internet interventions for mental health, including serious games, online programs and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS was formed. In this perspectives paper, we call for a paradigm shift to increase the impact of internet interventions towards the ultimate goal of improved population mental health. We propose four pillars for change: 1. Increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modulariziation. 2. Increased emphasis on engagement; utilizing processes such as gaming, gamification, telepresence, and persuasive technology. 3. Increased collaboration in program development, testing and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach. 4. Rapid testing and implementation, including the measurement of reach, engagement and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.

  8. A Paradigm Shift: How Macrobioethics Can Assist in the Transition from Anthropocentrism to Ecocentrism

    Directory of Open Access Journals (Sweden)

    Daniel Borges Moura

    2015-12-01

    Full Text Available Environmental preservation is not made in order to protect the environment, but to the man's own protection. Although there are political and legal instruments to deal with the claim "environmental protection," what we see, in fact, it is the manipulation of nature for the benefit of humanity. The objective of this study is to demonstrate, succinctly, as was the historical evolution to the anthropocentric paradigm, and its consequences on international policies relating to the environment. We Will provide an analysis of the major international treaties involving the environment to demonstrate that, although there is an anthropocentric logic, there are signs, albeit modest, that we are coming to a point of change. With the emergence of "new issues" of international law, as the topics covered in the post- Second World War were called, played down the almost exclusive that security and the economy had in international forums to be an increase in the discussions on, for example, environmental issues. This change of political nature, associated with the emergence of new philosophies, is creating a favorable environment to occur, probably even in the current century, a paradigm shift that transforms the theoretical basis of anthropocentrism to ecocentrism, modifying the way the man It relates to the environment in which it is inserted.

  9. Paradigm shift in urban energy systems through distributed generation: Methods and models

    International Nuclear Information System (INIS)

    Manfren, Massimiliano; Caputo, Paola; Costa, Gaia

    2011-01-01

    The path towards energy sustainability is commonly referred to the incremental adoption of available technologies, practices and policies that may help to decrease the environmental impact of energy sector, while providing an adequate standard of energy services. The evaluation of trade-offs among technologies, practices and policies for the mitigation of environmental problems related to energy resources depletion requires a deep knowledge of the local and global effects of the proposed solutions. While attempting to calculate such effects for a large complex system like a city, an advanced multidisciplinary approach is needed to overcome difficulties in modeling correctly real phenomena while maintaining computational transparency, reliability, interoperability and efficiency across different levels of analysis. Further, a methodology that rationally integrates different computational models and techniques is necessary to enable collaborative research in the field of optimization of energy efficiency strategies and integration of renewable energy systems in urban areas. For these reasons, a selection of currently available models for distributed generation planning and design is presented and analyzed in the perspective of gathering their capabilities in an optimization framework to support a paradigm shift in urban energy systems. This framework embodies the main concepts of a local energy management system and adopts a multicriteria perspective to determine optimal solutions for providing energy services through distributed generation.

  10. Creating a new generation of pediatric dentists: a paradigm shift in training.

    Science.gov (United States)

    Ramos-Gomez, Francisco J; Silva, Daniela Rodrigues P; Law, Clarice S; Pizzitola, Rebecca L; John, Brendan; Crall, James J

    2014-12-01

    The University of California, Los Angeles (UCLA) School of Dentistry has implemented a Health Resources and Services Administration-funded program to prepare dentists for the complex and comprehensive needs of pediatric patients within rapidly changing demographics and a paradigm shift in dentistry. Traditional dental education has focused on how to respond to oral disease, whereas UCLA's program shifts the paradigm to emphasize early assessment, risk-based prevention, and disease management. A holistic approach to dental care that considers social and environmental determinants is used with minimally invasive techniques for restorative care. To support this change, pediatric dental residents receive traditional training combined with new didactics, advocacy opportunities, and applied learning experiences at community-based organizations. These new elements teach residents to recognize the causal factors of disease and to identify interventions that promote oral health at the individual, family, community, and policy level. Consequently, they are better prepared to treat a diverse group of patients who historically have faced the greatest burden of disease as well as an increased number of barriers to accessing oral health care; these consist of low-income, minority, and/or pediatric populations including children with special health needs. The program's ultimate goal is for residents to deploy these skills in treating vulnerable populations and to demonstrate greater interest in collaborating with non-dental health providers and community organizations to increase access to dental services in private or public health practice settings.

  11. Education of tobacco use prevention and cessation for dental professionals--a paradigm shift.

    Science.gov (United States)

    Davis, Joan M; Ramseier, Christoph A; Mattheos, Nikos; Schoonheim-Klein, Meta; Compton, Sharon; Al-Hazmi, Nadia; Polychronopoulou, Argy; Suvan, Jean; Antohé, Magda E; Forna, Doriana; Radley, Nicki

    2010-02-01

    The use of tobacco continues to be a substantial risk factor in the development and progression of oral cancer, periodontitis, implant failure and poor wound healing. Dental and dental hygiene education providers have made great advances towards the incorporation of tobacco education into their curricula in recent years. Unfortunately, however, both medical and dental education research has consistently reported schools providing only basic knowledge-based curricula that rarely incorporate more effective, behaviourally-based components affecting long-term change. The limited training of oral healthcare students, at least in part, is reflected in practising dental professionals continuing to report offering incomplete tobacco interventions. In order to prepare the next generation of oral healthcare providers, this paper proposes a paradigm shift in how tobacco use prevention and cessation (TUPAC) may be incorporated into existing curricula. It is suggested that schools should carefully consider: to what level of competency should TUPAC be trained in dental and dental hygiene schools; the importance of establishing rapport through good communication skills; the core knowledge level for TUPAC; suggested instructional and assessment strategies; the importance of continuing professional education for the enhancement of TUPAC.

  12. Paradigm shifts and the development of the diagnostic and statistical manual of mental disorders: past experiences and future aspirations.

    Science.gov (United States)

    First, Michael B

    2010-11-01

    Work is currently under way on the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, due to be published by the American Psychiatric Association in 2013. Dissatisfaction with the current categorical descriptive approach has led to aspirations for a paradigm shift for DSM-5. A historical review of past revisions of the DSM was performed. Efforts undertaken before the start of the DSM-5 development process to conduct a state-of-the science review and set a research agenda were examined to determine if results supported a paradigm shift for DSM-5. Proposals to supplement DSM-5 categorical diagnosis with dimensional assessments are reviewed and critiqued. DSM revisions have alternated between paradigm shifts (the first edition of the DSM in 1952 and DSM-III in 1980) and incremental improvements (DSM-II in 1968, DSM-III-R in 1987, and DSM-IV in 1994). The results of the review of the DSM-5 research planning initiatives suggest that despite the scientific advances that have occurred since the descriptive approach was first introduced in 1980, the field lacks a sufficiently deep understanding of mental disorders to justify abandoning the descriptive approach in favour of a more etiologically based alternative. Proposals to add severity and cross-cutting dimensions throughout DSM-5 are neither paradigm shifting, given that simpler versions of such dimensions are already a component of DSM-IV, nor likely to be used by busy clinicians without evidence that they improve clinical outcomes. Despite initial aspirations that DSM would undergo a paradigm shift with this revision, DSM-5 will continue to adopt a descriptive categorical approach, albeit with a greatly expanded dimensional component.

  13. A paradigm shift toward a consistent modeling framework to assess climate impacts

    Science.gov (United States)

    Monier, E.; Paltsev, S.; Sokolov, A. P.; Fant, C.; Chen, H.; Gao, X.; Schlosser, C. A.; Scott, J. R.; Dutkiewicz, S.; Ejaz, Q.; Couzo, E. A.; Prinn, R. G.; Haigh, M.

    2017-12-01

    Estimates of physical and economic impacts of future climate change are subject to substantial challenges. To enrich the currently popular approaches of assessing climate impacts by evaluating a damage function or by multi-model comparisons based on the Representative Concentration Pathways (RCPs), we focus here on integrating impacts into a self-consistent coupled human and Earth system modeling framework that includes modules that represent multiple physical impacts. In a sample application we show that this framework is capable of investigating the physical impacts of climate change and socio-economic stressors. The projected climate impacts vary dramatically across the globe in a set of scenarios with global mean warming ranging between 2.4°C and 3.6°C above pre-industrial by 2100. Unabated emissions lead to substantial sea level rise, acidification that impacts the base of the oceanic food chain, air pollution that exceeds health standards by tenfold, water stress that impacts an additional 1 to 2 billion people globally and agricultural productivity that decreases substantially in many parts of the world. We compare the outcomes from these forward-looking scenarios against the common goal described by the target-driven scenario of 2°C, which results in much smaller impacts. It is challenging for large internationally coordinated exercises to respond quickly to new policy targets. We propose that a paradigm shift toward a self-consistent modeling framework to assess climate impacts is needed to produce information relevant to evolving global climate policy and mitigation strategies in a timely way.

  14. Molecular potentials and relaxation dynamics

    International Nuclear Information System (INIS)

    Karo, A.M.

    1981-01-01

    The use of empirical pseudopotentials, in evaluating interatomic potentials, provides an inexpensive and convenient method for obtaining highly accurate potential curves and permits the modeling of core-valence correlation, and the inclusion of relativistic effects when these are significant. Recent calculations of the X 1 Σ + and a 3 Σ + states of LiH, NaH, KH, RbH, and CsH and the X 2 Σ + states of their anions are discussed. Pseudopotentials, including core polarization terms, have been used to replace the core electrons, and this has been coupled with the development of compact, higly-optimized basis sets for the corresponding one- and two-electron atoms. Comparisons of the neutral potential curves with experiment and other ab initio calculations show good agreement (within 1000 cm -1 over most of the potential curves) with the difference curves being considerably more accurate. In the method of computer molecular dynamics, the force acting on each particle is the resultant of all interactions with other atoms in the neighborhood and is obtained as the derivative of an effective many-body potential. Exploiting the pseudopotential approach, in obtaining the appropriate potentials may be very fruitful in the future. In the molecular dynamics example considered here, the conventional sum-of-pairwise-interatomic-potentials (SPP) approximation is used with the potentials derived either from experimental spectroscopic data or from Hartree-Fock calculations. The problem is the collisional de-excitation of vibrationally excited molecular hydrogen at an Fe surface. The calculations have been carried out for an initial vibrotational state v = 8, J = 1 and a translational temperature corresponding to a gas temperature of 500 0 K. Different angles of approach and different initial random impact points on the surface have been selected. For any given collision with the wall, the molecule may pick up or lose vibrotatonal and translational energy

  15. Excavations at Schöningen and paradigm shifts in human evolution.

    Science.gov (United States)

    Conard, Nicholas J; Serangeli, Jordi; Böhner, Utz; Starkovich, Britt M; Miller, Christopher E; Urban, Brigitte; Van Kolfschoten, Thijs

    2015-12-01

    The exceptional preservation at Schöningen together with a mixture of perseverance, hard work, and sheer luck led to the recovery of unique finds in an exceptional context. The 1995 discovery of numerous wooden artifacts, most notably at least 10 carefully made spears together with the skeletons of at least 20 to 25 butchered horses, brought the debate about hunting versus scavenging among late archaic hominins and analogous arguments about the purportedly primitive behavior of Homo heidelbergensis and Neanderthals to an end. Work under H. Thieme's lead from 1992 to 2008 and results from the current team since 2008 demonstrate that late H. heidelbergensis or early Neanderthals used sophisticated artifacts made from floral and faunal materials, in addition to lithic artifacts more typically recovered at Lower Paleolithic sites. The finds from the famous Horse Butchery Site and two dozen other archaeological horizons from the edges of the open-cast mine at Schöningen provide many new insights into the technology and behavioral patterns of hominins about 300 ka BP during MIS 9 on the Northern European Plain. An analysis of the finds from Schöningen and their contexts shows that the inhabitants of the site were skilled hunters at the top of the food chain and exhibited a high level of planning depth. These hominins had command of effective means of communication about the here and now, and the past and the future, that allowed them to repeatedly execute well-coordinated and successful group activities that likely culminated in a division of labor and social and economic patterns radically different from those of all non-human primates. The unique preservation and high quality excavations have led to a major paradigm shift or "Schöningen Effect" that changed our views of human evolution during the late Lower Paleolithic. In this respect, we can view the behaviors documented at Schöningen as a plausible baseline for the behavioral sophistication of archaic hominins

  16. A paradigm shift needed for nuclear reactors. From economies of unit scale to economies of production scale

    International Nuclear Information System (INIS)

    Li, Ning

    2009-01-01

    The success and sustainability of the nascent 'Nuclear Renaissance' will depend heavily on the timely development and deployment SMRs (small and modular reactors) as a new paradigm to increase economic competitiveness and broaden markets and applications for nuclear energy. A critical assessment of the historical and current reactor construction cost data reveals a troubling trend of rapid escalation in practically all countries, while showing little or negative economies of (unit) scale. The escalation cannot be fully accounted for by cost inflation in materials and labors, or by ratcheting regulations and other external factors. Rather, it appears that the intrinsic complexity and the associated risks and costs of extremely large systems have offset all returns of (unit) scale in power engineering and learning effects in practice. The construction heavy nature of the nuclear power plants exacerbates the cost problem as compared to that of the manufactured goods. The power markets have evolved away from the very large monolithic generation units toward modular units more amenable for manufacturing and transportation. This is clearly illustrated through the increasingly bi-modal distribution of generation units around a few MWe (wind, micro-turbines etc) and 100-200 MWe (gas turbine and combined cycle). The rapid market adoption and penetration of these units dwarf the addition rates of the very large units. This is not merely an outcome based on economic and financial risk reduction (important in their own right) or better match of applications - the technological and operational performances are equal or even superior in these smaller modular units. This presentation will use the industry, market and application data analyses, and successful examples from other sectors and industries with different organizing principles to demonstrate the benefits and potentials of SMRs. The resultant paradigm shift, from the singular pursuit of economies of unit scale to

  17. A Paradigm shift to an Old Scheme for Outgoing Longwave Radiation

    Science.gov (United States)

    McDonald, Alastair B.

    2016-04-01

    There are many cases where the climate models do not agree with the empirical data. For instance, the data from radiosondes (and MSUs) do not show the amount of warming in the upper troposphere that is predicted by the models (Thorne et al. 2011). The current scheme for outgoing longwave radiation can be traced back to the great 19th Century French mathematician J-B Joseph Fourier. His anachronistic idea was that the radiation balance at the top of the atmosphere (TOA) is maintained by the conduction of heat from the surface (Fourier 1824). It was based on comparing the atmosphere to the 18th Century Swiss scientist H-B de Saussure's hotbox which he had invented to show that solar radiation is only slightly absorbed by the atmosphere. Saussure also showed that thermal radiation existed and argued that the warmth of the air near the surface of the Earth is due to absorption of that infra red radiation (Saussure 1786). Hence a paradigm shift to Saussure's scheme, where the thermal radiation is absorbed at the base of the atmosphere, rather than throughout the atmosphere as in Fourier's scheme, may solve many climate models problems. In this new paradigm the boundary layer continually exchanges radiation with the surface. Thus only at two instants during the day is there no net gain or loss of heat by the boundary layer from the surface, and so that layer is not in LTE. Moreover, since the absorption of outgoing longwave radiation is saturated within the boundary layer, it has little influence on the TOA balance. That balance is mostly maintained by changes in albedo, e.g. clouds and ice sheets. Use of this paradigm can explain why the excess warming in south western Europe was caused by water vapour close to the surface (Philipona et al. 2005), and may also explain why there are difficulties in closing the surface radiation balance (Wild et al. 2013) and in modelling abrupt climate change (White et al. 2013). References: Fourier, Joseph. 1824. 'Remarques G

  18. Can genotype determine the sports phenotype? A paradigm shift in sports medicine.

    Science.gov (United States)

    Ghosh, Amit; Mahajan, Preetam B

    2016-06-01

    In last two decades, there has been an evolution in sports medicine. Several researchers have worked on different domains of sports medicine, like strength, endurance, sports injury, and psychology. Besides this, several groups have explored the changes at cellular and molecular levels during exercise, which has led to the development of the new domain in sports science known as genetic medicine. Genetic medicine deals with the genotypic basis of sports phenotype. In this article, we try to provide an up-to-date review on genetic determinants of sports performance, which will be like a journey from the nostalgic past towards the traditional present and the romantic future of sports medicine. Endurance and power performance are two important domains of athletes. They vary in individuals, even among trained athletes. Researches indicate that the genetic makeup of sportsmen play a vital role in their performance. Several genetic factors are reported to be responsible for endurance, power, susceptibility to injury, and even psychology of the individual. Besides this, proper training, nutrition, and environment are also important in shaping their potential. The aim of this discussion is to understand the influence of the environment and the genetic makeup on the performance of the athletes. There is sufficient evidence to suggest that genotype determines the sports phenotype in an athlete. Choosing the right sports activity based on genetic endowment is the key for achieving excellence in sports.

  19. A paradigm shift: The mitoproteomes of procyclic and bloodstream Trypanosoma brucei are comparably complex

    Czech Academy of Sciences Publication Activity Database

    Zíková, Alena; Verner, Zdeněk; Nenarokova, Anna; Michele, P. A. M.; Lukeš, Julius

    2017-01-01

    Roč. 13, č. 12 (2017), č. článku e1006679. ISSN 1553-7366 R&D Projects: GA MŠk LL1205; GA MŠk LL1601; GA ČR GA17-22248S; GA ČR GA15-21974S; GA MŠk(CZ) LQ1604 Institutional support: RVO:60077344 Keywords : life-cycle stages * african trypanosomes * adp/atp carrier * krebs cycle * forms * mitochondrion * reveals * protein * metabolism * glucose Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.608, year: 2016

  20. Paradigm shift in consciousness research: the child's self-awareness and abnormalities in autism, ADHD and schizophrenia.

    Science.gov (United States)

    Lou, Hans C

    2012-02-01

    Self-awareness is a pivotal component of any conscious experience and conscious self-regulation of behaviour. A paralimbic network is active, specific and causal in self-awareness. Its regions interact by gamma synchrony. Gamma synchrony develops throughout infancy, childhood and adolescence into adulthood and is regulated by dopamine and other neurotransmitters via GABA interneurons. Major derailments of this network and self-awareness occur in developmental disorders of conscious self-regulation like autism, attention deficit hyperactivity disorder (ADHD) and schizophrenia. Recent research on conscious experience is no longer limited to the study of neural 'correlations' but is increasingly lending itself to the study of causality. This paradigm shift opens new perspectives for understanding the neural mechanisms of the developing self and the causal effects of their disturbance in developmental disorders. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  1. The interface between forensic science and technology: how technology could cause a paradigm shift in the role of forensic institutes in the criminal justice system.

    Science.gov (United States)

    Kloosterman, Ate; Mapes, Anna; Geradts, Zeno; van Eijk, Erwin; Koper, Carola; van den Berg, Jorrit; Verheij, Saskia; van der Steen, Marcel; van Asten, Arian

    2015-08-05

    In this paper, the importance of modern technology in forensic investigations is discussed. Recent technological developments are creating new possibilities to perform robust scientific measurements and studies outside the controlled laboratory environment. The benefits of real-time, on-site forensic investigations are manifold and such technology has the potential to strongly increase the speed and efficacy of the criminal justice system. However, such benefits are only realized when quality can be guaranteed at all times and findings can be used as forensic evidence in court. At the Netherlands Forensic Institute, innovation efforts are currently undertaken to develop integrated forensic platform solutions that allow for the forensic investigation of human biological traces, the chemical identification of illicit drugs and the study of large amounts of digital evidence. These platforms enable field investigations, yield robust and validated evidence and allow for forensic intelligence and targeted use of expert capacity at the forensic institutes. This technological revolution in forensic science could ultimately lead to a paradigm shift in which a new role of the forensic expert emerges as developer and custodian of integrated forensic platforms. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. The interface between forensic science and technology: how technology could cause a paradigm shift in the role of forensic institutes in the criminal justice system

    Science.gov (United States)

    Kloosterman, Ate; Mapes, Anna; Geradts, Zeno; van Eijk, Erwin; Koper, Carola; van den Berg, Jorrit; Verheij, Saskia; van der Steen, Marcel; van Asten, Arian

    2015-01-01

    In this paper, the importance of modern technology in forensic investigations is discussed. Recent technological developments are creating new possibilities to perform robust scientific measurements and studies outside the controlled laboratory environment. The benefits of real-time, on-site forensic investigations are manifold and such technology has the potential to strongly increase the speed and efficacy of the criminal justice system. However, such benefits are only realized when quality can be guaranteed at all times and findings can be used as forensic evidence in court. At the Netherlands Forensic Institute, innovation efforts are currently undertaken to develop integrated forensic platform solutions that allow for the forensic investigation of human biological traces, the chemical identification of illicit drugs and the study of large amounts of digital evidence. These platforms enable field investigations, yield robust and validated evidence and allow for forensic intelligence and targeted use of expert capacity at the forensic institutes. This technological revolution in forensic science could ultimately lead to a paradigm shift in which a new role of the forensic expert emerges as developer and custodian of integrated forensic platforms. PMID:26101289

  3. [Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

    Science.gov (United States)

    Konturek, Peter C; Zopf, Yurdagül

    2016-05-25

    The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

  4. Deep integration: a paradigm shift in the synthesis of active antenna systems

    NARCIS (Netherlands)

    Maaskant, R.

    2017-01-01

    Deep integration is the visionary future trend of merging conducting, semi-conducting and insulating materials into a single heterogeneous structure that is capable of offering multi-functional RF features. This paper introduces the deep integration concept, describes its potential advantages, lists

  5. Identifying future competitive business strategies for the U.S. furniture industry: Benchmarking and paradigm shifts

    Science.gov (United States)

    Albert Schuler; Urs Buehlmann

    2003-01-01

    This paper describes benchmarking activities undertaken to provide a basis for comparing the U.S. wood furniture industry with other nations that have a globally competitive furniture manufacturing industry. The second part of this paper outlines and discusses strategies that have the potential to help the U.S. furniture industry survive and thrive in a global business...

  6. Counseling and Psychotherapy as Moral and Spiritual Practice: Facing a Major Paradigm Shift.

    Science.gov (United States)

    Ivey, Allen E.; Rigazio-DiGilio, Sandra A.

    1992-01-01

    Comments on article by Blakeney and Blakeney in which they offer metatheoretical perspective for counseling and therapy that gives primacy to developmental issues and to understanding worldview of client. Goes on to further demonstrate holistic and integrative nature and potential of Blakeney framework, using Developmental Counseling and Therapy…

  7. Aphasia Centers and the Life Participation Approach to Aphasia: A Paradigm Shift

    Science.gov (United States)

    Elman, Roberta J.

    2016-01-01

    The Aphasia Center is a service delivery model that provides an interactive community for persons with aphasia. This model has been increasing in popularity over the last 20 years. Aphasia Centers are consistent with a social model of health care and disability. They offer the potential for linguistic, communicative, and psychosocial benefits. The…

  8. A paradigm shift for bone quality in dentistry: A literature review.

    Science.gov (United States)

    Kuroshima, Shinichiro; Kaku, Masaru; Ishimoto, Takuya; Sasaki, Muneteru; Nakano, Takayoshi; Sawase, Takashi

    2017-10-01

    The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteoblasts and osteocytes. In dentistry, the term "bone quality" has long been considered to be synonymous with bone mineral density (BMD) based on radiographic and sensible evaluations. In 2000, the NIH proposed the concept of bone quality as "the sum of all characteristics of bone that influence the bone's resistance to fracture," which is completely independent of BMD. The NIH defines bone quality as comprising bone architecture, bone turnover, bone mineralization, and micro-damage accumulation. Moreover, our investigations have demonstrated that BAp, collagen, and bone cells such as osteoblasts and osteocytes play essential roles in controlling the current concept of bone quality in bone around hip and dental implants. The current concept of bone quality is crucial for understanding bone mechanical functions. BAp, collagen and osteocytes are the main factors affecting bone quality. Moreover, mechanical loading dynamically adapts bone quality. Understanding the current concept of bone quality is required in dentistry. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  9. Vanguards of paradigm shift in radiation biology. Radiation-induced adaptive and bystander responses

    International Nuclear Information System (INIS)

    Matsumoto, Hideki; Hamada, Nobuyuki; Kobayashi, Yasuhiko; Takahashi, Akihisa; Ohnishi, Takeo

    2007-01-01

    The risks of exposure to low dose ionizing radiation (below 100 mSv) are estimated by extrapolating from data obtained after exposure to high dose radiation, using a linear no-threshold model (LNT model). However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose/low dose-rate radiation than they do to high dose/high dose-rate radiation. In other words, there are accumulated findings which cannot be explained by the classical ''target theory'' of radiation biology. The radioadaptive response, radiation-induced bystander effects, low-dose radio-hypersensitivity, and genomic instability are specifically observed in response to low dose/low dose-rate radiation, and the mechanisms underlying these responses often involve biochemical/molecular signals that respond to targeted and non-targeted events. Recently, correlations between the radioadaptive and bystander responses have been increasingly reported. The present review focuses on the latter two phenomena by summarizing observations supporting their existence, and discussing the linkage between them from the aspect of production of reactive oxygen and nitrogen species. (author)

  10. Paradigm Shift toward Reducing Overtreatment of Ductal Carcinoma In Situ of Breast

    Directory of Open Access Journals (Sweden)

    Yasuaki Sagara

    2017-08-01

    Full Text Available The prevalence of ductal carcinoma in situ (DCIS of the breast has increased substantially after the introduction of breast cancer screening programs, although the clinical effects of early DCIS detection and treatment remain unclear. The standard treatment for DCIS has involved local breast-conserving surgery (BCS followed by radiotherapy (RT or total mastectomy with/without endocrine therapy, and the choice of local treatment is not usually based on clinicopathologic or biological factors. However, we have investigated the effectiveness of local treatment using breast surgery and RT using Surveillance, Epidemiology, and End Results data, and found that the effectiveness of breast surgery was modified by the nuclear grade. Furthermore, breast cancer-specific survival was identical between patients with low-grade DCIS who did and did not undergo surgery. Moreover, we found that RT after BCS for DCIS was only associated with a survival benefit among patients with risk factors for local recurrence, such as nuclear grade, age, and tumor size. Ongoing clinical trials and translational research have attempted to develop a treatment strategy that prevents the overdiagnosis and overtreatment of low-risk DCIS, as well as a biology-based treatment strategy for using targeted therapy. Therefore, to develop a tailored treatment strategy for DCIS, we need to identify molecular and biological classifications based on the results from translational research, national databases, and clinical trials.

  11. Molecular potentials and relaxation dynamics

    International Nuclear Information System (INIS)

    Karo, A.M.

    1981-01-01

    The use of empirical pseudopotentials, in evaluating interatomic potentials, provides an inexpensive and convenient method for obtaining highly accurate potential curves and permits the modeling of core-valence correlation, and the inclusion of relativistic effects when these are significant. As an example, recent calculations of the chi 1 Σ + and a 3 Σ + states of LiH, NaH, KH, RbH, and CsH and the chi 2 Σ + states of their anions are discussed. Pseudopotentials, including core polarization terms, have been used to replace the core electrons, and this has been coupled with the development of compact, highly-optimized basis sets for the corresponding one- and two-electron atoms. Comparisons of the neutral potential curves with experiment and other ab initio calculations show good agreement (within 1000 cm -1 over most of the potential curves) with the difference curves being considerably more accurate

  12. Evolution of microbes and viruses: A paradigm shift in evolutionary biology?

    Directory of Open Access Journals (Sweden)

    Eugene V. Koonin

    2012-09-01

    Full Text Available When Charles Darwin formulated the central principles of evolutionary biology in the Origin of Species in 1859 and the architects of the Modern Synthesis integrated these principles with population genetics almost a century later, the principal if not the sole objects of evolutionary biology were multicellular eukaryotes, primarily animals and plants. Before the advent of efficient gene sequencing, all attempts to extend evolutionary studies to bacteria have been futile. Sequencing of the rRNA genes in thousands of microbes allowed the construction of the three- domain ‘ribosomal Tree of Life’ that was widely thought to have resolved the evolutionary relationships between the cellular life forms. However, subsequent massive sequencing of numerous, complete microbial genomes revealed novel evolutionary phenomena, the most fundamental of these being: i pervasive horizontal gene transfer (HGT, in large part mediated by viruses and plasmids, that shapes the genomes of archaea and bacteria and call for a radical revision (if not abandonment of the Tree of Life concept, ii Lamarckian-type inheritance that appears to be critical for antivirus defense and other forms of adaptation in prokaryotes, and iii evolution of evolvability, i.e. dedicated mechanisms for evolution such as vehicles for HGT and stress-induced mutagenesis systems. In the non-cellular part of the microbial world, phylogenomics and metagenomics of viruses and related selfish genetic elements revealed enormous genetic and molecular diversity and extremely high abundance of viruses that come across as the dominant biological entities on earth. Furthermore, the perennial arms race between viruses and their hosts is one of the defining factors of evolution. Thus, microbial phylogenomics adds new dimensions to the fundamental picture of evolution even as the principle of descent with modification discovered by Darwin and the laws of population genetics remain at the core of evolutionary

  13. Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.

    Science.gov (United States)

    Pérot, Stéphanie; Sperandio, Olivier; Miteva, Maria A; Camproux, Anne-Claude; Villoutreix, Bruno O

    2010-08-01

    Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.

  14. Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

    Science.gov (United States)

    Yeo, Chien Ing; Ooi, Kah Kooi; Tiekink, Edward R T

    2018-06-11

    A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

  15. A Paradigm Shift in Substellar Classification: Understanding the Apparent Diversity of Substellar Atmospheres through Viewing Geometry

    Science.gov (United States)

    Metchev, Stanimir; Apai, Daniel; Radigan, Jacqueline; Heinze, Aren; Marley, Mark; Artigau, Etienne; Plavchan, Peter; Burgasser, Adam

    2014-12-01

    Results from our Cycle 8 Spitzer Exploration Science program Weather on Other Worlds (WOW) have suggested a potential transformative result for understanding the atmospheric and evolutionary properties of substellar objects. We have found tentative evidence for a correlation between atmospheric appearance and viewing geometry - much as in the now established AGN unification models. In particular, we have found that among L6-T8 dwarfs only those with J-K colors redder than the median are variable. Since apparent variability is enhanced for equator-on viewing geometries, we interpret this as a latitudinal dependence in appearance: redder L6-T8 dwarfs are seen closer to equator-on, and bluer ones are closer to pole-on. This result has the potential to solve the long-standing problem of cloud dissipation in L and T dwarfs: by explaining the broad range in spectroscopic appearance and near-infrared colors of L and T dwarfs as a geometric effect, rather than related to atmospheric dynamics. The implications are substantially broader, and touch on a range of issues in substellar astrophysics, such as the calibration of substellar effective temperatures and bolometric luminosities, and the modeling of ultracool atmospheres and substellar evolution - both of which will require at least a 2-D treatment. We propose an Exploration Science program to map the correspondence between spin-axis orientation, substellar colors, and spectral type. All of the L and T dwarfs in our proposed sample will have measured projected (vsini) rotational velocities within a year. By obtaining photometric periods through sensitive staring observations with Spitzer, and by using the fact that the radii of >1 Gyr-old brown dwarfs are approximately age-independent, we will be able to solve for the spin axis orientations. We will correlate these with variability amplitude, near-infrared colors, and spectral types, to solve for the meridional dependence in the spectroscopic appearance of L and T dwarfs.

  16. Wide and ultra-wide bandgap oxides: where paradigm-shift photovoltaics meets transparent power electronics

    Science.gov (United States)

    Pérez-Tomás, Amador; Chikoidze, Ekaterine; Jennings, Michael R.; Russell, Stephen A. O.; Teherani, Ferechteh H.; Bove, Philippe; Sandana, Eric V.; Rogers, David J.

    2018-03-01

    Oxides represent the largest family of wide bandgap (WBG) semiconductors and also offer a huge potential range of complementary magnetic and electronic properties, such as ferromagnetism, ferroelectricity, antiferroelectricity and high-temperature superconductivity. Here, we review our integration of WBG and ultra WBG semiconductor oxides into different solar cells architectures where they have the role of transparent conductive electrodes and/or barriers bringing unique functionalities into the structure such above bandgap voltages or switchable interfaces. We also give an overview of the state-of-the-art and perspectives for the emerging semiconductor β- Ga2O3, which is widely forecast to herald the next generation of power electronic converters because of the combination of an UWBG with the capacity to conduct electricity. This opens unprecedented possibilities for the monolithic integration in solar cells of both self-powered logic and power electronics functionalities. Therefore, WBG and UWBG oxides have enormous promise to become key enabling technologies for the zero emissions smart integration of the internet of things.

  17. Solar technology and building implementation in Malaysia: A national paradigm shift

    Directory of Open Access Journals (Sweden)

    Syahrul Nizam Kamaruzzaman

    2012-05-01

    Full Text Available Solar technology is becoming increasingly popular. For example, the production of solarcells quadrupled in the 1999-2004 period, with a capacity of four gigawatts worldwide. Renewableenergy including solar power produces few or no harmful emissions and it is becoming increasinglyimportant to exploit it in the future. This paper presents a literature review of the application ofnumerous types of solar technology in buildings in Malaysia and identifies the challenges faced.Although several newly constructed green buildings use solar technology, Malaysia has yet to acceptit wholesale. If solar technology is to be adopted widely, then both public and private sectors mustcooperate to provide large-scale financial incentives and produce specialists in solar technology. Asthe first step, the government has established the Low Energy Office and the Green Energy Office,which use passive solar design and photovoltaic systems in their own buildings. However, the privatesector has yet to follow suit. It is anticipated that the application of solar technology in buildings willencourage sustainable development when all non-renewable energy sources decrease significantly. Ifpeople do not recognise the potential of such technology in daily life, it will soon be too late.

  18. Preventive Biomechanics: A Paradigm Shift With a Translational Approach to Injury Prevention.

    Science.gov (United States)

    Hewett, Timothy E; Bates, Nathaniel A

    2017-09-01

    Preventive medicine techniques have alleviated billions of dollars' worth of the economic burden in the medical care system through the implementation of vaccinations and screenings before the onset of disease symptoms. Knowledge of biomechanical tendencies has progressed rapidly over the past 20 years such that clinicians can identify, in healthy athletes, the underlying mechanisms that lead to catastrophic injuries such as anterior cruciate ligament (ACL) ruptures. As such, preventive medicine concepts can be applied to noncontact musculoskeletal injuries to reduce the economic burden of sports medicine treatments and enhance the long-term health of athletes. To illustrate the practical medical benefits that could be gained from preventive biomechanics applied to the ACL as well as the need and feasibility for the broad implementation of these principles. Literature review. The recent literature pertinent to the screening and prevention of musculoskeletal injuries was reviewed and compiled into a clinical commentary on the current state and applicability of preventive biomechanics. Investigators have identified neuromuscular training protocols that screen for and correct the underlying biomechanical deficits that lead to ACL injuries. The literature shows that when athletes comply with these prescribed training protocols, the incidence of injuries is significantly reduced within that population. Such preventive biomechanics practices employ basic training methods that would be familiar to athletic coaches and have the potential to save billions of dollars in cost in sports medicine. The widespread implementation of preventive biomechanics concepts could profoundly affect the field of sports medicine with a minimum of initial investment.

  19. Cloud-Based Automated Design and Additive Manufacturing: A Usage Data-Enabled Paradigm Shift.

    Science.gov (United States)

    Lehmhus, Dirk; Wuest, Thorsten; Wellsandt, Stefan; Bosse, Stefan; Kaihara, Toshiya; Thoben, Klaus-Dieter; Busse, Matthias

    2015-12-19

    Integration of sensors into various kinds of products and machines provides access to in-depth usage information as basis for product optimization. Presently, this large potential for more user-friendly and efficient products is not being realized because (a) sensor integration and thus usage information is not available on a large scale and (b) product optimization requires considerable efforts in terms of manpower and adaptation of production equipment. However, with the advent of cloud-based services and highly flexible additive manufacturing techniques, these obstacles are currently crumbling away at rapid pace. The present study explores the state of the art in gathering and evaluating product usage and life cycle data, additive manufacturing and sensor integration, automated design and cloud-based services in manufacturing. By joining and extrapolating development trends in these areas, it delimits the foundations of a manufacturing concept that will allow continuous and economically viable product optimization on a general, user group or individual user level. This projection is checked against three different application scenarios, each of which stresses different aspects of the underlying holistic concept. The following discussion identifies critical issues and research needs by adopting the relevant stakeholder perspectives.

  20. Cloud-Based Automated Design and Additive Manufacturing: A Usage Data-Enabled Paradigm Shift

    Science.gov (United States)

    Lehmhus, Dirk; Wuest, Thorsten; Wellsandt, Stefan; Bosse, Stefan; Kaihara, Toshiya; Thoben, Klaus-Dieter; Busse, Matthias

    2015-01-01

    Integration of sensors into various kinds of products and machines provides access to in-depth usage information as basis for product optimization. Presently, this large potential for more user-friendly and efficient products is not being realized because (a) sensor integration and thus usage information is not available on a large scale and (b) product optimization requires considerable efforts in terms of manpower and adaptation of production equipment. However, with the advent of cloud-based services and highly flexible additive manufacturing techniques, these obstacles are currently crumbling away at rapid pace. The present study explores the state of the art in gathering and evaluating product usage and life cycle data, additive manufacturing and sensor integration, automated design and cloud-based services in manufacturing. By joining and extrapolating development trends in these areas, it delimits the foundations of a manufacturing concept that will allow continuous and economically viable product optimization on a general, user group or individual user level. This projection is checked against three different application scenarios, each of which stresses different aspects of the underlying holistic concept. The following discussion identifies critical issues and research needs by adopting the relevant stakeholder perspectives. PMID:26703606

  1. A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI)

    Science.gov (United States)

    Subbarao, G. V.; Sahrawat, K. L.; Nakahara, K.; Rao, I. M.; Ishitani, M.; Hash, C. T.; Kishii, M.; Bonnett, D. G.; Berry, W. L.; Lata, J. C.

    2013-01-01

    environmental perspective, the BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop–livestock systems. PMID:23118123

  2. A paradigm shift towards low-nitrifying production systems: the role of biological nitrification inhibition (BNI).

    Science.gov (United States)

    Subbarao, G V; Sahrawat, K L; Nakahara, K; Rao, I M; Ishitani, M; Hash, C T; Kishii, M; Bonnett, D G; Berry, W L; Lata, J C

    2013-07-01

    BNI function in plants could potentially have a large influence on biogeochemical cycling and closure of the N loop in crop-livestock systems.

  3. The Dynamics of Pheromone Gland Synthesis and Release: a Paradigm Shift for Understanding Sex Pheromone Quantity in Female Moths.

    Science.gov (United States)

    Foster, Stephen P; Anderson, Karin G; Casas, Jérôme

    2018-05-10

    Moths are exemplars of chemical communication, especially with regard to specificity and the minute amounts they use. Yet, little is known about how females manage synthesis and storage of pheromone to maintain release rates attractive to conspecific males and why such small amounts are used. We developed, for the first time, a quantitative model, based on an extensive empirical data set, describing the dynamical relationship among synthesis, storage (titer) and release of pheromone over time in a moth (Heliothis virescens). The model is compartmental, with one major state variable (titer), one time-varying (synthesis), and two constant (catabolism and release) rates. The model was a good fit, suggesting it accounted for the major processes. Overall, we found the relatively small amounts of pheromone stored and released were largely a function of high catabolism rather than a low rate of synthesis. A paradigm shift may be necessary to understand the low amounts released by female moths, away from the small quantities synthesized to the (relatively) large amounts catabolized. Future research on pheromone quantity should focus on structural and physicochemical processes that limit storage and release rate quantities. To our knowledge, this is the first time that pheromone gland function has been modeled for any animal.

  4. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

    Directory of Open Access Journals (Sweden)

    Abdellah Tebani

    2016-09-01

    Full Text Available The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.

  5. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations.

    Science.gov (United States)

    Tebani, Abdellah; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

    2016-09-14

    The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM) are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.

  6. Advances in visual representation of molecular potentials.

    Science.gov (United States)

    Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

    2010-06-01

    The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

  7. Responsibility for the future of the world-paradigm shift in the theory and practice of marketing

    Directory of Open Access Journals (Sweden)

    Gábor Rekettye

    2010-12-01

    Full Text Available En las últimas cuatro décadas muchos estudios científicos fueron publicados sobre los impactos medioambientales que amenazan el futuro de nuestro planeta. Estas manifestaciones apenas han afectado el área de marketing, no ha habido ningún cambio paradigmático. La primera parte del artículo trata de los procesos climáticos que amenazan el medio ambiente y la vida cotidiana de la población, y que pueden ser importantes para la formación del futuro del marketing. Hay una relación estrecha entre el cambio climático y el consumismo que estimula la investigación sobre la responsabilidad y la sostenibilidad del consumo. La segunda parte del artículo trata de esbozar las nuevas tendencias posibles en la teoría y en la práctica del marketing que son necesarias para enfrentar las cambiantes necesidades medioambientales.In the last four decades quite a lot of scientific studies have been published about those dangerous signs which threaten the future of our world. These manifests have only slightly affected the field of marketing; no paradigm shift has taken place. The first part of the paper deals with climate processes threatening the environment and the everyday life of the population, and which may be important in shaping the future of marketing. There is a strong relation between climate change and consumerism enforcing the research about the responsibility and sustainability of consumption. The second part of the study tries to outline those possible new trends in the theory and practice of marketing which are necessary to meet the changing environmental needs.

  8. The Center for Alternatives to Animal Testing - Europe (CAAT-EU): a transatlantic bridge for the paradigm shift in toxicology.

    Science.gov (United States)

    Daneshian, Mardas; Leist, Marcel; Hartung, Thomas

    2010-01-01

    The Center for Alternatives to Animal Testing - Europe (CAAT-EU) was founded based collaboration between the Johns Hopkins Bloomberg School of Public Health and the University of Konstanz. CAAT-EU, housed at the University of Konstanz, will coordinate transatlantic activities to promote humane science in research and education, and participate, as partner or coordinator, in publicly and privately funded European projects. Thomas Hartung will serve as program liaison representing Johns Hopkins University and Marcel Leist as the University of Konstanz liaison. CAAT-EU aims to: 1) Set up transatlantic consortia for international research projects on alternative methods. 2) Establish a CAAT Europe faculty and advisory board composed of sponsor representatives and prominent academics from Europe . 3) Participate in the Transatlantic Think Tank for Toxicology (t4) devoted to conceptual work for the paradigm shift in toxicology. 4) Coordinate a series of information days in Europe on relevant developments in the US, similar to the 2009 series CAAT held in the US on EU issues (one on the 7th Amendment to the EU Cosmetics Directive and one on EU and US chemical regulation). 5) Support ALTEX as the official journal of CAAT and CAAT-EU. 6) Develop strategic projects with sponsors to promote humane science and new toxicology, especially with CAAT faculty members. 7) Develop a joint education program between Johns Hopkins and the University of Konstanz, such as e-courses and the existing Humane Science Certificate program developed by CAAT, a student exchange program, and collaboration with the International Graduate School "Cell-based Characterization of De- and Regeneration" in Konstanz.

  9. Composite paradigms in medicine: analysing Gillies' claim of reclassification of disease without paradigm shift in the case of Helicobacter pylori.

    Science.gov (United States)

    Hutton, Joseph

    2012-09-01

    Since the publication of Kuhn's The Structure of Scientific Revolutions in 1962, the notion of paradigms has shaped the way that philosophy views scientific discovery and how changes in what is regarded as empirical fact occur. This drew heavily on examples from the history of the natural sciences to support Kuhn's hypothesis. However, some argue that medicine is different from the natural sciences. Gillies has proposed another theory of how paradigms apply to medicine; that of composite paradigms. In doing so, Gillies uses the example of Helicobacter pylori and the shift from the excess-acid theory to the current bacterial-infection theory of gastric ulcers to illustrate these fundamental differences between medicine and the natural sciences. Upon analysis of Gillies' claim, it is evident that traditional Kuhnian paradigms are also composite and that the manner in which Gillies proposes disease is classified is insufficient in describing medicine. Furthermore, new local paradigms are demonstrably introduced and the change was accompanied by many of the markers of paradigmatic change including changes in worldview, resistance, incommensurability and the introduction of new questions that could not have existed under the previous paradigm. Whilst this change may not be on the scale of the Chemical revolution, it can still be considered paradigm shift. Thagard also proposes an alternate view of discovery using the case of H. pylori. This has much in common with Kuhnian paradigms but Thagard's theory offers further elucidation and refinement. This allows it to better characterise all of the associated features of discovery relevant in the case of H. pylori, thus provides a preferable tool for examination of this important recent discovery. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Olle Höök Lectureship 2015: The World Health Organization's paradigm shift and implementation of the International Classification of Functioning, Disability and Health in rehabilitation.

    Science.gov (United States)

    Stucki, Gerold

    2016-06-13

    The World Health Organization's (WHO) paradigm shift, implied by the launch of the International Classification of Functioning, Disability and Health (ICF), is inextricably entwined with the emergence of rehabilitation as a key health strategy of the 21st century. To enable health systems to scale up rehabilitation we must spearhead the implementation of the ICF in rehabilitation towards its system-wide implementation in the healthcare system at large. In this essay, based on the Olle Höök lecture 20151, it is argued that the launch of the ICF in 2001 represents a paradigm shift, as it has enabled the WHO to more comprehensively act on its mandate and has guided WHO policies to shape the health system in response to population functioning needs. It is shown that this paradigm shift has important implications for rehabilitation, including its conceptualization and scientific methods. A prerequisite for the system-wide implementation of the ICF in clinical practice, policy, and research, is the availability of practical tools that allow for the universal and standardized description of functioning. Finally, some reflections are presented on how we may foster the system-wide implementation of the ICF by applying approaches from the implementation sciences.

  11. Moving Towards the Age-friendly Hospital: A Paradigm Shift for the Hospital-based Care of the Elderly.

    Science.gov (United States)

    Huang, Allen R; Larente, Nadine; Morais, Jose A

    2011-12-01

    Care of the older adult in the acute care hospital is becoming more challenging. Patients 65 years and older account for 35% of hospital discharges and 45% of hospital days. Up to one-third of the hospitalized frail elderly loses independent functioning in one or more activities of daily living as a result of the 'hostile environment' that is present in the acute hospitals. A critical deficit of health care workers with expertise and experience in the care of the elderly also jeopardizes successful care delivery in the acute hospital setting. We propose a paradigm shift in the culture and practice of event-driven acute hospital-based care of the elderly which we call the Age-friendly Hospital concept. Guiding principles include: a favourable physical environment; zero tolerance for ageism throughout the organization; an integrated process to develop comprehensive services using the geriatric approach; assistance with appropriateness decision-making and fostering links between the hospital and the community. Our current proposed strategy is to focus on delirium management as a hospital-wide condition that both requires and highlights the Geriatric Medicine specialist as an expert of content, for program development and of evaluation. The Age-friendly Hospital concept we propose may lead the way to enable hospitals in the fast-moving health care system to deliver high-quality care without jeopardizing risk-benefit, function, and quality of life balances for the frail elderly. Recruitment and retention of skilled health care professionals would benefit from this positive 'branding' of an institution. Convincing hospital management and managing change are significant challenges, especially with competing priorities in a fiscal environment with limited funding. The implementation of a hospital-wide delirium management program is an example of an intervention that embodies many of the principles in the Age-friendly Hospital concept. It is important to change the way

  12. Paradigm Shift in Transboundary Water Management Policy: Linking Water Environment Energy and Food (weef) to Catchment Hydropolitics - Needs, Scope and Benefits

    Science.gov (United States)

    RAI, S.; Wolf, A.; Sharma, N.; Tiwari, H.

    2015-12-01

    The incessant use of water due to rapid growth of population, enhanced agricultural and industrial activities, degraded environment and ecology will in the coming decades constrain the socioeconomic development of humans. To add on to the precarious situation, political boundaries rarely embrace hydrological boundaries of lakes, rivers, aquifers etc. Hydropolitics relate to the ability of geopolitical institutions to manage shared water resources in a politically sustainable manner, i.e., without tensions or conflict between political entities. Riparian hydropolitics caters to differing objectives, needs and requirements of states making it difficult to administer the catchment. The diverse riparian objectives can be merged to form a holistic catchment objective of sustainable water resources development and management. It can be proposed to make a paradigm shift in the present-day transboundary water policy from riparian hydropolitics (in which the focal point of water resources use is hinged on state's need) to catchment hydropolitics (in which the interest of the basin inhabitants are accorded primacy holistically over state interests) and specifically wherein the water, environment, energy and food (WEEF) demands of the catchment are a priority and not of the states in particular. The demands of the basin pertaining to water, food and energy have to be fulfilled, keeping the environment and ecology healthy in a cooperative political framework; the need for which is overwhelming. In the present scenario, the policy for water resources development of a basin is segmented into independent uncoordinated parts controlled by various riparians; whereas in catchment hydropolitics the whole basin should be considered as a unit. The riparians should compromise a part of national interest and work in collaboration on a joint objective which works on the principle of the whole as against the part. Catchment hydropolitics may find greater interest in the more than 250

  13. Policy Making While Paradigms Shift: Understanding the Development of Policy Drought in the U.S. Congress 1981-2013

    Science.gov (United States)

    McCurdy, K. M.

    2013-12-01

    adversaries. The junior members of Congress embracing 'Movement Republican goals' to reduce the size of government by any means, are impatient with their senior colleagues who held pragmatic views for achieving limited government. Tensions arise in the conference from this lack of goal alignment, and increasingly become public. The give and take between the parties that was normal in the New Deal and Great Society eras has been replaced by intense partisanship in the 21st century, as the number of members who came to government embracing Reagan's maxim that government was the problem gradually increased in magnitude and seniority. It is important to recognize that there is a paradigm shift underway in Congress, related to the demographic changes in Congress as the new Republicans implement their policy goal of reducing the size of government, and that the structure of the institution produces a lag effect for that shift, and that the binary party labels may further mask the shift.

  14. Re-envisioning global agricultural trade: time for a paradigm shift to ensure food security and population health in low-income countries.

    Science.gov (United States)

    Pirkle, Catherine M; Poliquin, Hélène; Sia, Drissa; Kouakou, Kouassi Joseph; Sagna, Tani

    2015-03-01

    In this commentary, we use examples from West Africa to highlight how the liberalization of global agricultural trade exacerbates population health inequalities by threatening the livelihoods and food security of communities in low-income settings. We highlight the exploitative nature of trade agreements with West African countries demonstrating how these agreements disincentivize local agricultural investment and take jobs away from small-scale farmers. Further, we link agricultural trade liberalization to increased food insecurity, malnutrition, and exposure to environmental contaminants. Finally, we propose a paradigm shift that advocates for food sovereignty and the right to food. © The Author(s) 2014.

  15. [The end of discrimination in social security for the elderly? Some remarks on the consequences of the paradigm shift in a life course perspective on gender].

    Science.gov (United States)

    Fachinger, Uwe

    2008-10-01

    Trying to analyse the effects of the paradigm shift in the old age social security system in Germany (GRV) from a life cycle gender perspective yields light and shade - it is a conglomeration of individual- and family-specific transfers, financed by a mix of contributions and taxes, and with measures of explicit and implicit, intended and not intended ex-post and ex-ante redistribution and discrimination.The paradigm shift has increased the complexity of the system and created additional elements of gender specific discrimination as well as reduced established elements of the so called "social compensation". Furthermore, the relevance of complementary private and occupational pensions will increase absolute and relative due to the reduction of the pension level. This will raise the importance of earnings in old age especially those that are without any elements of social security compensation or without elements of recognition of activities beside employment. Overall the paradigm shift has intensified the discrimination of women in two ways and the pension privatisation has caused redistribution from the bottom to the top. In other words, there is an increase in inter- and intra-gender discrimination. Due to the changes and the emphasis of aspects of an independent old age security savings for women the norm of the "male breadwinner model" has increased. The importance of "providing one's own pension" additionally creates distribution conflicts within a partnership. Because of the necessity of constant payments over time within a private insurance and the changes of an individual income and gender-specific life cycle, conflicts may occur time and again. The dependence of life-long partnerships on each other is not reduced or abolished with the strengthening of the individualistic model of protection, but is qualitatively and quantitatively improved. Against this background, the measures of the statutory pension system which are aimed towards the situation of a

  16. Probing molecular potentials with an optical centrifuge

    Science.gov (United States)

    Milner, A. A.; Korobenko, A.; Hepburn, J. W.; Milner, V.

    2017-09-01

    We use an optical centrifuge to excite coherent rotational wave packets in N2O, OCS, and CS2 molecules with rotational quantum numbers reaching up to J ≈465 , 690, and 1186, respectively. Time-resolved rotational spectroscopy at such ultra-high levels of rotational excitation can be used as a sensitive tool to probe the molecular potential energy surface at internuclear distances far from their equilibrium values. Significant bond stretching in the centrifuged molecules results in the growing period of the rotational revivals, which are experimentally detected using coherent Raman scattering. We measure the revival period as a function of the centrifuge-induced rotational frequency and compare it with the numerical calculations based on the known Morse-cosine potentials.

  17. Correlation energy generating potentials for molecular hydrogen

    International Nuclear Information System (INIS)

    Sharma, B.S.; Thakkar, A.J.

    1985-01-01

    A variety of local correlation energy functionals are currently in use. All of them depend, to some extent, on modeling the correlation energy of a homogeneous electron fluid. Since atomic and molecular charge densities are neither uniform nor slowly varying, it is important to attempt to use known high accuracy wave functions to learn about correlation energy functionals appropriate to such systems. We have extended the definition of the correlation energy generating potentials V/sub c/ introduced by Ros. A charge density response to correlation has been allowed for by inclusion of an electron--nuclear component V/sup e/n/sub c/ in addition to the electron--electron component V/sup e/e/sub c/. Two different definitions of V/sup e/n/sub c/ are given. We present the first calculations of V/sub c/ for a molecular system: H 2 . The results show that V/sup e/n/sub c/, in either definition, is by no means negligible. Moreover, V/sup e/e/sub c/ and both forms of V/sup e/n/sub c/ show significant nonlocal dependence on the charge density. Calculations with ten different model correlation energy functionals show that none of them is particularly sensitive to the charge density. However, they are quite sensitive to the parametrization of the electron fluid correlation energy. The schemes which include self-interaction corrections (SIC) are found to be superior to those of Kohn--Sham type. The correlation energy generating potentials implied by the SIC type and empirical correlation energy functionals are found to correspond roughly to averages of one of the accurate potentials

  18. Molecular digital pathology: progress and potential of exchanging molecular data.

    Science.gov (United States)

    Roy, Somak; Pfeifer, John D; LaFramboise, William A; Pantanowitz, Liron

    2016-09-01

    Many of the demands to perform next generation sequencing (NGS) in the clinical laboratory can be resolved using the principles of telepathology. Molecular telepathology can allow facilities to outsource all or a portion of their NGS operation such as cloud computing, bioinformatics pipelines, variant data management, and knowledge curation. Clinical pathology laboratories can electronically share diverse types of molecular data with reference laboratories, technology service providers, and/or regulatory agencies. Exchange of electronic molecular data allows laboratories to perform validation of rare diseases using foreign data, check the accuracy of their test results against benchmarks, and leverage in silico proficiency testing. This review covers the emerging subject of molecular telepathology, describes clinical use cases for the appropriate exchange of molecular data, and highlights key issues such as data integrity, interoperable formats for massive genomic datasets, security, malpractice and emerging regulations involved with this novel practice.

  19. Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation

    Directory of Open Access Journals (Sweden)

    Jed Lipes

    2012-01-01

    Full Text Available Protective ventilation with low tidal volume has been shown to reduce morbidity and mortality in patients suffering from acute lung injury (ALI and acute respiratory distress syndrome (ARDS. Low tidal volume ventilation is associated with particular clinical challenges and is therefore often underutilized as a therapeutic option in clinical practice. Despite some potential difficulties, data have been published examining the application of protective ventilation in patients without lung injury. We will briefly review the physiologic rationale for low tidal volume ventilation and explore the current evidence for protective ventilation in patients without lung injury. In addition, we will explore some of the potential reasons for its underuse and provide strategies to overcome some of the associated clinical challenges.

  20. Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation

    Science.gov (United States)

    Lipes, Jed; Bojmehrani, Azadeh; Lellouche, Francois

    2012-01-01

    Protective ventilation with low tidal volume has been shown to reduce morbidity and mortality in patients suffering from acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Low tidal volume ventilation is associated with particular clinical challenges and is therefore often underutilized as a therapeutic option in clinical practice. Despite some potential difficulties, data have been published examining the application of protective ventilation in patients without lung injury. We will briefly review the physiologic rationale for low tidal volume ventilation and explore the current evidence for protective ventilation in patients without lung injury. In addition, we will explore some of the potential reasons for its underuse and provide strategies to overcome some of the associated clinical challenges. PMID:22536499

  1. Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation

    OpenAIRE

    Lipes, Jed; Bojmehrani, Azadeh; Lellouche, Francois

    2012-01-01

    Protective ventilation with low tidal volume has been shown to reduce morbidity and mortality in patients suffering from acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Low tidal volume ventilation is associated with particular clinical challenges and is therefore often underutilized as a therapeutic option in clinical practice. Despite some potential difficulties, data have been published examining the application of protective ventilation in patients without lung inj...

  2. Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research.

    Science.gov (United States)

    Mochel, Jonathan P; Jergens, Albert E; Kingsbury, Dawn; Kim, Hyun Jung; Martín, Martín G; Allenspach, Karin

    2017-12-12

    Recent advances in our understanding of the intestinal stem cell niche and the role of key signaling pathways on cell growth and maintenance have allowed the development of fully differentiated epithelial cells in 3D organoids. Stem cell-derived organoids carry significant levels of proteins that are natively expressed in the gut and have important roles in drug transport and metabolism. They are, therefore, particularly relevant to study the gastrointestinal (GI) absorption of oral medications. In addition, organoids have the potential to serve as a robust preclinical model for demonstrating the effectiveness of new drugs more rapidly, with more certainty, and at lower costs compared with live animal studies. Importantly, because they are derived from individuals with different genotypes, environmental risk factors and drug sensitivity profiles, organoids are a highly relevant screening system for personalized therapy in both human and veterinary medicine. Lastly, and in the context of patient-specific congenital diseases, orthotopic transplantation of engineered organoids could repair and/or replace damaged epithelial tissues reported in various GI diseases, such as inflammatory bowel disease, cystic fibrosis, and tuft enteropathy. Ongoing translational research on organoids derived from dogs with naturally occurring digestive disorders has the potential to improve the predictability of preclinical models used for optimizing the therapeutic management of severe chronic enteropathies in human patients.

  3. Molecular vibration-rotation spectra starting from the Fues potential

    International Nuclear Information System (INIS)

    Ley Koo, E.

    1976-01-01

    The solution of Schroedinger's equation for the Fues potential is analyzed and compared with the corresponding problems for the Coulomb, harmonic oscillator and molecular potentials. These comparisons allow us to emphasize certain pedagogical, conceptual and computational advantages of the Fues potential which make it a favorable alternative as the starting point in the analysis of molecular vibration-rotation and in the determination of potential energy curves. (author)

  4. Systems thinking perspectives applied to healthcare transition for youth with disabilities: a paradigm shift for practice, policy and research.

    Science.gov (United States)

    Hamdani, Y; Jetha, A; Norman, C

    2011-11-01

    Healthcare transition (HCT) for youth with disabilities is a complex phenomenon influenced by multiple interacting factors, including health, personal and environmental factors. Current research on the transition to adulthood for disabled youth has primarily focused on identifying these multilevel factors to guide the development of interventions to improve the HCT process. However, little is known about how this complex array of factors interacts and contributes to successful HCT. Systems thinking provides a theoretically informed perspective that accounts for complexity and can contribute to enhanced understanding of the interactions among HCT factors. The objective of this paper is to introduce general concepts of systems thinking as applied to HCT practice and research. Several systems thinking concepts and principles are introduced and a discussion of HCT as a complex system is provided. Systems dynamics methodology is described as one systems method for conceptualizing HCT. A preliminary systems dynamics model is presented to facilitate discourse on the application of systems thinking principles to HCT practice, policy and research. An understanding of the complex interactions and patterns of relationships in HCT can assist health policy makers and practitioners in determining key areas of intervention, the impact of these interventions on the system and the potential intended and unintended consequences of change. This paper provides initial examination of applying systems thinking to inform future research and practice on HCT. © 2011 Blackwell Publishing Ltd.

  5. Switching from static to adaptable and dynamic building envelopes: A paradigm shift for the energy efficiency in buildings

    Directory of Open Access Journals (Sweden)

    Marco Perino

    2015-11-01

    Full Text Available The key role of the building envelope in attaining building energy efficiency and satisfactory indoor comfort has long been established. Nevertheless, until recent times, all efforts and attention have mainly been focused on increasing and optimizing the thermal insulation of the envelope components. This strategy was a winning approach for a long time, but its limitations became obvious when users and designers started to consider the overall energy demand of a building and started to aim for Zero Energy Building (ZEB or nearly ZEB goals. New and more revolutionary concepts and technologies needed to be developed to satisfy such challenging requirements. The potential benefits of this technological development are relevant since the building envelope plays a key role in controlling the energy and mass flows from outdoors to indoors (and vice versa and, moreover, the facades offer a significant opportunity for solar energy exploitation. Several researches have demonstrated that the limitation of the existing facades could be overcome only by switching from ‘static’ to ‘responsive’ and ‘dynamic’ systems, such as Multifunctional Facade Modules (MFMs and Responsive Building Elements (RBE. These components are able to continuously and pro-actively react to outdoor and indoor environment conditions and facilitate and enhance the exploitation of renewable and low exergy sources. In order to reduce the energy demand, to maximize the indoor comfort conditions and to produce energy at the site, these almost ‘self-sufficient’, or even ‘positive energy’ building skins frequently incorporate different technologies and are functionally connected to other building services and installations. An overview of the technological evolution of the building envelope that has taken place, ranging from traditional components to the innovative skins, will be given in this paper, while focusing on the different approaches that have characterized this

  6. The needs of having a paradigm shift from public sector to private sector on funding digitizing management work of historical buildings in Malaysia

    Science.gov (United States)

    Kamarudin, M. K.; Yahya, Z.; Harun, R.; Jaapar, A.

    2014-02-01

    In Malaysia, the government agencies that handle the management of historical buildings are finding themselves facing a shortage of funds to provide the necessary work on digitalising management works. Due to the rising cost of management, which also covers maintenance and infrastructure works, there is a need for a paradigm shift from public sector to private sector provision on infrastructure and management works. Therefore the government agencies need to find the suitable mechanism to encourage private sector especially the private property and developers to take part in it. This scenario has encouraged the authorities to look new ways of entering into partnership and collaboration with the private sector to secure the continuity of provision and funding. The paper first reviews the different approach to facilitate off-site local management system of historical buildings and then examines options for both private and public funding in digitalising the historical buildings management works by interviewing government officer, conservator and member of nongovernment agencies. It then explores how the current system of management may adopt the shift to avoid any vulnerability and threat to the existing historical buildings. This paper concludes with a short summary of key issues in management works of historical buildings and recommendations.

  7. The needs of having a paradigm shift from public sector to private sector on funding digitizing management work of historical buildings in Malaysia

    International Nuclear Information System (INIS)

    Kamarudin, M K; Yahya, Z; Jaapar, A; Harun, R

    2014-01-01

    In Malaysia, the government agencies that handle the management of historical buildings are finding themselves facing a shortage of funds to provide the necessary work on digitalising management works. Due to the rising cost of management, which also covers maintenance and infrastructure works, there is a need for a paradigm shift from public sector to private sector provision on infrastructure and management works. Therefore the government agencies need to find the suitable mechanism to encourage private sector especially the private property and developers to take part in it. This scenario has encouraged the authorities to look new ways of entering into partnership and collaboration with the private sector to secure the continuity of provision and funding. The paper first reviews the different approach to facilitate off-site local management system of historical buildings and then examines options for both private and public funding in digitalising the historical buildings management works by interviewing government officer, conservator and member of nongovernment agencies. It then explores how the current system of management may adopt the shift to avoid any vulnerability and threat to the existing historical buildings. This paper concludes with a short summary of key issues in management works of historical buildings and recommendations

  8. Planning and Policy Implications for Renewal and Paradigm Shift in the Curriculum Contents of Vocational and Technology Education Programmes in Nigeria

    Directory of Open Access Journals (Sweden)

    T.L. Adepoju

    2017-06-01

    Full Text Available Vocational and technology education (VTE is widely recognized as agent of technological development, industrial revolution, economic growth and voca-tional independence all over the world. In Nigeria, attempts have been made by various governments to restructure the system so as to keep pace with what operates in developed countries and to meet global competitions and best prac-tices. However, in this paper, the need for the renewal and paradigm shift in the curriculum contents of vocational and technological education is empha-sized. The paper e-rays the historical development of vocational and technolo-gy education in Nigeria from the colonial era. The paper further examines is-sues associated with implementation of a reviewed curriculum and the partici-pation of VTE in industrial revolution and vocational independence. A curvi-linear model and two equations are developed in the paper to explain the as-sumed linear correlation between curriculum renewal and technological break-through (technological development, industrial revolution, economic growth and vocational independence. The challenges facing VTE in Nigeria and the implications of the proposed curriculum renewal for stakeholders are highlight-ed in the paper.

  9. Military Culture. A Paradigm Shift?

    National Research Council Canada - National Science Library

    Dunivin, Karen

    1997-01-01

    In this study, Lt Col Karen O. Dunivin, USAF, examines social change in American military culture and explores the current struggle between the military's traditional and exclusionary combat, masculine-warrior (CMW...

  10. Explaining (Missing) Regulator Paradigm Shifts

    DEFF Research Database (Denmark)

    Wigger, Angela; Buch-Hansen, Hubert

    2014-01-01

    The global financial and economic crisis has prompted some scholars to suggest that a fundamental regulatory shift away from neoliberalism will take place – both in general and in the field of EU competition regulation. This paper shows that so far no radical break with the neoliberal type...... regulation after the crisis in the 1970s, the paper argues that the preconditions for a fundamental shift in this issue area are not present this time around. Several reasons account for this: the current crisis has been construed by economic and political elites as a crisis within and not of neoliberal...

  11. Genetics of preeclampsia: paradigm shifts

    NARCIS (Netherlands)

    Oudejans, Cees B. M.; van Dijk, Marie; Oosterkamp, Marjet; Lachmeijer, Augusta; Blankenstein, Marinus A.

    2007-01-01

    Segregation of preeclampsia into early-onset, placental and late-onset, maternal subtypes along with the acknowledgement of the contribution of epigenetics in placentally expressed genes proved to be a key first step in the identification of essential gene variants associated with preeclampsia.

  12. Crystal structure and pair potentials: A molecular-dynamics study

    Energy Technology Data Exchange (ETDEWEB)

    Parrinello, M.; Rahman, A.

    1980-10-06

    With use of a Lagrangian which allows for the variation of the shape and size of the periodically repeating molecular-dynamics cell, it is shown that different pair potentials lead to different crystal structures.

  13. MOLECULAR ANALYSIS OF HUMAN SPERMATOZOA: POTENTIAL FOR INFERTILITY RESEARCH

    Science.gov (United States)

    Gordon Research Conference: Mammalian Gametogenesis and Embryogenesis New London, CT, July 1-6, 2000Molecular Analysis of Human Spermatozoa: Potential for Infertility ResearchDavid Miller 1, David Dix2, Robert Reid 3, Stephen A Krawetz 3 1Reproductive ...

  14. Paradigm shift in transport legislation or rather at the 'bottleneck'; Paradigmenwechsel im Befoerderungsrecht oder am 'Flaschenhals'

    Energy Technology Data Exchange (ETDEWEB)

    Naeser, Hanns [GNS Gesellschaft fuer Nuklear-Service mbH, Essen (Germany)

    2015-01-15

    In the year just started significant decisions with considerable consequences by the Federal Constitutional Court and the Federal Administrative Court in the field of nuclear law are expected. Especially the decision with regards to 'nuclear phase-out' within the 13th amendment of the Atomic Energy Act is being eagerly expected, as with its far-reaching consequences also fundamental constitutional questions need to be answered. The Federal Administrative Court will need to decide on the question, whether she admits the appeal against the Brunsbuettel decision by the Higher Administrative Court Schleswig-Holstein (HAC), which from the view of claimant shifted the fundamental basis of demarcation of responsibilities between the executive and judiciary power. In comparison to these fundamental decisions the awaited decision by the HAC on nuclear transport legislation seems of subordinate importance, although she will proceed with a paradigm shift in the legal area. The decision deals with the question as to whether and when a right of action from a third party within the nuclear transport legislation can be accepted or more precisely under which preconditions a third party has clear standing against a nuclear transport authorisation. As the site selection law (issued on 23 July 2013 BGBI I p. 2552) excludes the recirculation of vitrified waste block canisters from reprocessing spent fuel elements to the transport cask storage facility Gorleben, the decision by the HAC Lueneburg for this site will only be relevant for present unpredictable transportations from the transport cask storage facility Gorleben to a final repository. If necessary interest to seek a declaratory judgment for declaratory action, in concreto danger of recurrence will be approved, is another matter.

  15. Analysis of the normal optical, Michel and molecular potentials on ...

    Indian Academy of Sciences (India)

    6. — journal of. June 2016 physics pp. 1275–1286. Analysis of the normal ... the levels are obtained for the three optical potentials to estimate the quality ... The experimental angular distribution data for the 40Ca(6Li, d)44Ti reaction .... analysed using the normal optical, Michel and molecular potentials within the framework.

  16. Chronic SSRI stimulation of astrocytic 5-HT2B receptors change multiple gene expressions/editings and metabolism of glutamate, glucose and glycogen: a potential paradigm shift

    Directory of Open Access Journals (Sweden)

    Leif eHertz

    2015-02-01

    Full Text Available It is firmly believed that the mechanism of action of SSRIs in major depression is to inhibit the serotonin transporter, SERT, and increase extracellular concentration of serotonin. However, this undisputed observation does not prove that SERT inhibition is the mechanism, let alone the only mechanism, by which SSRI’s exert their therapeutic effects. It has recently been demonstrated that 5-HT2B receptor stimulation is needed for the antidepressant effect of fluoxetine in vivo. The ability of all 5 currently used SSRIs to stimulate the 5-HT2B receptor equipotentially incultured astrocyteshas been known for several years,and increasing evidence has shown the importance of astrocytes and astrocyte-neuronal interactions for neuroplasticity and complex brain activity. This paper reviews acute and chronic effects of 5-HT2B receptor stimulation in cultured astrocytes and in astrocytes freshly isolated from brains of mice treated with fluoxetine for 14 daystogether with effects ofanti-depressant therapy on turnover of glutamate and GABA and metabolism of glucose and glycogen. It is suggested that these events are causally related to the mechanism of action of SSRIs and of interest for development of newer antidepressant drugs.

  17. Developing a molecular platform for potential carbon dioxide fixing

    DEFF Research Database (Denmark)

    Mikkelsen, Mette; Jørgensen, Mikkel; Krebs, Frederik C

    2010-01-01

    This paper presents an attempt to develop a new system for fixing carbon dioxide from the atmosphere. The proposed molecular system has been designed to have the capacity to spontaneously bind CO2 from the atmosphere with high affinity. The molecular system is furthermore designed to have...... the ability to liberate CO2 at a later stage in the process, i.e., in a separate compartment. The liberated CO2 presents a carbon neutral way of obtaining pure CO2. The proposed molecular system is based on a small stable organic molecule that potentially have two forms: one without bound CO2 and one...

  18. The New world of ';Big Data' Analytics and High Performance Data: A Paradigm shift in the way we interact with very large Earth Observation datasets (Invited)

    Science.gov (United States)

    Purss, M. B.; Lewis, A.; Ip, A.; Evans, B.

    2013-12-01

    The next decade promises an exponential increase in volumes of open data from Earth observing satellites. The ESA Sentinels, the Japan Meteorological Agency's Himawari 8/9 geostationary satellites, various NASA missions, and of course the many EO satellites planned from China, will produce petabyte scale datasets of national and global significance. It is vital that we develop new ways of managing, accessing and using this ';big-data' from satellites, to produce value added information within realistic timeframes. A paradigm shift is required away from traditional ';scene based' (and labour intensive) approaches with data storage and delivery for processing at local sites, to emerging High Performance Data (HPD) models where the data are organised and co-located with High Performance Computational (HPC) infrastructures in a way that enables users to bring themselves, their algorithms and the HPC processing power to the data. Automated workflows, that allow the entire archive of data to be rapidly reprocessed from raw data to fully calibrated products, are a crucial requirement for the effective stewardship of these datasets. New concepts such as arranging and viewing data as ';data objects' which underpin the delivery of ';information as a service' are also integral to realising the transition into HPD analytics. As Australia's national remote sensing and geoscience agency, Geoscience Australia faces a pressing need to solve the problems of ';big-data', in particular around the 25-year archive of calibrated Landsat data. The challenge is to ensure standardised information can be extracted from the entire archive and applied to nationally significant problems in hazards, water management, land management, resource development and the environment. Ultimately, these uses justify government investment in these unique systems. A key challenge was how best to organise the archive of calibrated Landsat data (estimated to grow to almost 1 PB by the end of 2014) in a way

  19. Trying to Learn Lessons for Response to Extreme Events: Paradigm Shifts Affecting Civil Defense in the Trinational Region of Southwestern Amazonia

    Science.gov (United States)

    Santos, G. L. P.

    2015-12-01

    The last ten years have seen several extreme climate events in southwestern Amazonia with historic impacts. The City of Rio Branco, Capital of Acre, Brazil´s westernmost State, suffered its seventh consecutive annual flooding and its worst in March 2015. The city of Tarauacá, also in Acre, registered 12 flooding events between November 2014 and April 2015. The most recent flood of the trinational Acre River in 2015 set historic records for flood stage and number of displaced persons in Cobija, the Capital of Pando, Bolivia. From February to April 2014, floods of the Madeira River disrupted the one highway between Acre and southern Brazil. Puerto Maldonado, the capital in Madre de Dios Region of Peru had its worst flood in 50 years during 2014. In 2005 and 2010, prolonged droughts combined with ignition sources resulted in tens to hundreds of thousands of hectares of fire-damaged rainforests in the Madre de Dios, Acre and Pando (MAP) Region. The Civil Defenses in these three contiguous political units faced several abrupt paradigm shifts that affected their responses: 1) The drought of 2005 showed dramatically that regional rainforests do burn; 2) The recent flooding history, particularly in 2012 and 2015, demolished the cultural icon of a nine-year recurrence interval; 3) What happens outside your territory can be devastating. The Madeira River flood impeded an estimated 200 million dollars from circulating in Acre; 4) The past can be a terrible guide. For Cobija and Rio Branco, the 2015 flood was on the order of a meter higher than any other. Many home dwellers did not evacuate in time because they used past floods as a guide; 5) A collapse in communication - cell phones, land lines, and Internet - can get worse. In 2012, such a collapse occurred in two border towns for 5 days, yet in 2015 it lasted more than 11 days. Research is needed to address how institutions linked to Civil Defense can shift paradigms in time to be more effective.

  20. Photon Upconversion and Molecular Solar Energy Storage by Maximizing the Potential of Molecular Self-Assembly.

    Science.gov (United States)

    Kimizuka, Nobuo; Yanai, Nobuhiro; Morikawa, Masa-Aki

    2016-11-29

    The self-assembly of functional molecules into ordered molecular assemblies and the fulfillment of potentials unique to their nanotomesoscopic structures have been one of the central challenges in chemistry. This Feature Article provides an overview of recent progress in the field of molecular self-assembly with the focus on the triplet-triplet annihilation-based photon upconversion (TTA-UC) and supramolecular storage of photon energy. On the basis of the integration of molecular self-assembly and photon energy harvesting, triplet energy migration-based TTA-UC has been achieved in varied molecular systems. Interestingly, some molecular self-assemblies dispersed in solution or organogels revealed oxygen barrier properties, which allowed TTA-UC even under aerated conditions. The elements of molecular self-assembly were also introduced to the field of molecular solar thermal fuel, where reversible photoliquefaction of ionic crystals to ionic liquids was found to double the molecular storage capacity with the simultaneous pursuit of switching ionic conductivity. A future prospect in terms of innovating molecular self-assembly toward molecular systems chemistry is also discussed.

  1. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    Science.gov (United States)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  2. Paradigm Shift in Radiation Biology/Radiation Oncology-Exploitation of the "H₂O₂ Effect" for Radiotherapy Using Low-LET (Linear Energy Transfer) Radiation such as X-rays and High-Energy Electrons.

    Science.gov (United States)

    Ogawa, Yasuhiro

    2016-02-25

    review, this potential paradigm shift in modern radiation biology/radiation oncology is discussed in detail in terms of overcoming drug/radiation resistance in radiation therapy and/or anti-cancer chemotherapy.

  3. Paradigm Shift in Radiation Biology/Radiation Oncology—Exploitation of the “H2O2 Effect” for Radiotherapy Using Low-LET (Linear Energy Transfer Radiation such as X-rays and High-Energy Electrons

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ogawa

    2016-02-01

    review, this potential paradigm shift in modern radiation biology/radiation oncology is discussed in detail in terms of overcoming drug/radiation resistance in radiation therapy and/or anti-cancer chemotherapy.

  4. Empirical potential for molecular simulation of graphene nanoplatelets

    Science.gov (United States)

    Bourque, Alexander J.; Rutledge, Gregory C.

    2018-04-01

    A new empirical potential for layered graphitic materials is reported. Interatomic interactions within a single graphene sheet are modeled using a Stillinger-Weber potential. Interatomic interactions between atoms in different sheets of graphene in the nanoplatelet are modeled using a Lennard-Jones interaction potential. The potential is validated by comparing molecular dynamics simulations of tensile deformation with the reported elastic constants for graphite. The graphite is found to fracture into graphene nanoplatelets when subjected to ˜15% tensile strain normal to the basal surface of the graphene stack, with an ultimate stress of 2.0 GPa and toughness of 0.33 GPa. This force field is useful to model molecular interactions in an important class of composite systems comprising 2D materials like graphene and multi-layer graphene nanoplatelets.

  5. Strong eld ionization of naphthalene: angular shifts and molecular potential

    DEFF Research Database (Denmark)

    Dimitrovski, Darko; Maurer, Jochen; Christensen, Lauge

    We analyze the photoelectron momentum distributions from strong eld ionization of xed-in-space naphthalene molecules by circularly polarized laser pulses. By direct comparison between experiment and theory, we show that the angular shifts in the photoelectron momentum distributions are very...... sensitive to the exact form of the molecular potential....

  6. Quantum-Accurate Molecular Dynamics Potential for Tungsten

    Energy Technology Data Exchange (ETDEWEB)

    Wood, Mitchell; Thompson, Aidan P.

    2017-03-01

    The purpose of this short contribution is to report on the development of a Spectral Neighbor Analysis Potential (SNAP) for tungsten. We have focused on the characterization of elastic and defect properties of the pure material in order to support molecular dynamics simulations of plasma-facing materials in fusion reactors. A parallel genetic algorithm approach was used to efficiently search for fitting parameters optimized against a large number of objective functions. In addition, we have shown that this many-body tungsten potential can be used in conjunction with a simple helium pair potential1 to produce accurate defect formation energies for the W-He binary system.

  7. Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics.

    Science.gov (United States)

    M'Koma, Amosy E

    2014-11-27

    Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

  8. Molecular polarization potential maps of the nucleic acid bases

    International Nuclear Information System (INIS)

    Alkorta, I.; Perez, J.J.

    1996-01-01

    Ab initio calculations at the SCF level were carried out to compute the polarization potential map NM of the nucleic acid bases: cytosine, thymine, uracil, adedine, and guanine. For this purpose, the Dunning's 9s5p basis set contracted to a split-valence, was selected to perform the calculations. The molecular polarization potential (MPP) at each point was evaluated by the difference between the interaction energy of the molecule with a unit point charge and the molecular electrostatic potential (MEP) at that point. MEPS and MPPS for the different molecules were computed with a density of 5 points/Angstrom 2 on the van der Waals surface of each molecule, defined using the van der Waals radii. Due to the symmetry of the molecules, only half the points were computed. The total number of points calculated was 558 for cytosine, 621 for thymine, 526 for uracil, 666 for adenine, and 699 for guanine. The results of these calculations are analyzed in terms of their implications on the molecular interactions between pairs of nucleic acid bases. 23 refs., 5 figs., 1 tab

  9. Construction of molecular potential energy curves by an optimization method

    Science.gov (United States)

    Wang, J.; Blake, A. J.; McCoy, D. G.; Torop, L.

    1991-01-01

    A technique for determining the potential energy curves for diatomic molecules from measurements of diffused or continuum spectra is presented. It is based on a numerical procedure which minimizes the difference between the calculated spectra and the experimental measurements and can be used in cases where other techniques, such as the conventional RKR method, are not applicable. With the aid of suitable spectral data, the associated dipole electronic transition moments can be simultaneously obtained. The method is illustrated by modeling the "longest band" of molecular oxygen to extract the E 3Σ u- and B 3Σ u- potential curves in analytical form.

  10. Molecular dynamics simulations of solutions at constant chemical potential

    Science.gov (United States)

    Perego, C.; Salvalaglio, M.; Parrinello, M.

    2015-04-01

    Molecular dynamics studies of chemical processes in solution are of great value in a wide spectrum of applications, which range from nano-technology to pharmaceutical chemistry. However, these calculations are affected by severe finite-size effects, such as the solution being depleted as the chemical process proceeds, which influence the outcome of the simulations. To overcome these limitations, one must allow the system to exchange molecules with a macroscopic reservoir, thus sampling a grand-canonical ensemble. Despite the fact that different remedies have been proposed, this still represents a key challenge in molecular simulations. In the present work, we propose the Constant Chemical Potential Molecular Dynamics (CμMD) method, which introduces an external force that controls the environment of the chemical process of interest. This external force, drawing molecules from a finite reservoir, maintains the chemical potential constant in the region where the process takes place. We have applied the CμMD method to the paradigmatic case of urea crystallization in aqueous solution. As a result, we have been able to study crystal growth dynamics under constant supersaturation conditions and to extract growth rates and free-energy barriers.

  11. Forces on nuclei moving on autoionizing molecular potential energy surfaces.

    Science.gov (United States)

    Moiseyev, Nimrod

    2017-01-14

    Autoionization of molecular systems occurs in diatomic molecules and in small biochemical systems. Quantum chemistry packages enable calculation of complex potential energy surfaces (CPESs). The imaginary part of the CPES is associated with the autoionization decay rate, which is a function of the molecular structure. Molecular dynamics simulations, within the framework of the Born-Oppenheimer approximation, require the definition of a force field. The ability to calculate the forces on the nuclei in bio-systems when autoionization takes place seems to rely on an understanding of radiative damages in RNA and DNA arising from the release of slow moving electrons which have long de Broglie wavelengths. This work addresses calculation of the real forces on the nuclei moving on the CPES. By using the transformation of the time-dependent Schrödinger equation, previously used by Madelung, we proved that the classical forces on nuclei moving on the CPES correlated with the gradient of the real part of the CPES. It was proved that the force on the nuclei of the metastable molecules is time independent although the probability to detect metastable molecules exponentially decays. The classical force is obtained from the transformed Schrödinger equation when ℏ=0 and the Schrödinger equation is reduced to the classical (Newtonian) equations of motion. The forces on the nuclei regardless on what potential energy surface they move (parent CPES or product real PESs) vary in time due to the autoionization process.

  12. Comparison of biomolecules on the basis of Molecular Interaction Potentials

    Directory of Open Access Journals (Sweden)

    Rodrigo Jordi

    2002-01-01

    Full Text Available Molecular Interaction Potentials (MIP are frequently used for the comparison of series of compounds displaying related biological behaviors. These potentials are interaction energies between the considered compounds and relevant probes. The interaction energies are computed in the nodes of grids defined around the compounds. There is a need of detailed and objective comparative analyses of MIP distributions in the framework of structure-activity studies. On the other hand, MIP-based studies do not have to be restricted to series of small ligands, since such studies present also interesting possibilities for the analysis and comparison of biological macromolecules. Such analyses can benefit from the application of new methods and computational approaches. The new software MIPSim (Molecular Interaction Potentials Similarity analysis has recently been introduced with the purpose of analyzing and comparing MIP distributions of series of biomolecules. This program is transparently integrated with other programs, like GAMESS or GRID, which can be used for the computation of the potentials to be analyzed or compared. MIPSim incorporates several definitions of similarity coefficients, and is capable of combining several similarity measures into a single one. On the other hand, MIPSim can perform automatic explorations of the maximum similarity alignments between pairs of molecules.

  13. Molecularly imprinted polymers--potential and challenges in analytical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Mahony, J.O. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Nolan, K. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Smyth, M.R. [Dublin City University, School of Chemical Sciences, Glasnevin, Dublin 9 (Ireland); Mizaikoff, B. [Georgia Institute of Technology, School of Chemistry and Biochemistry, 770 State Street, Boggs Building, Atlanta, GA 30332-0400 (United States)]. E-mail: boris.mizaikoff@chemistry.gatech.edu

    2005-04-04

    Among the variety of biomimetic recognition schemes utilizing supramolecular approaches molecularly imprinted polymers (MIPs) have proven their potential as synthetic receptors in numerous applications ranging from liquid chromatography to assays and sensor technology. Their inherent advantages compared to biochemical/biological recognition systems include robustness, storage endurance and lower costs. However, until recently only few contributions throughout the relevant literature describe quantitative analytical applications of MIPs for practically relevant analyte molecules and real-world samples. Increased motivation to thoroughly evaluate the true potential of MIP technology is clearly attributed to the demands of modern analytical chemistry, which include enhanced sensitivity, selectivity and applicability of molecular recognition building blocks at decreasing costs. In particular, the areas of environmental monitoring, food and beverage analysis and industrial process surveillance require analytical tools capable of discriminating chemicals with high molecular specificity considering increasing numbers of complex environmental contaminants, pollution of raw products and rigorous quality control requested by legislation and consumer protection. Furthermore, efficient product improvement and development of new products requires precise qualitative and quantitative analytical methods. Finally, environmental, food and process safety control issues favor the application of on-line in situ analytical methods with high molecular selectivity. While biorecognition schemes frequently suffer from degrading bioactivity and long-term stability when applied in real-world sample environments, MIPs serving as synthetic antibodies have successfully been applied as stationary phase separation matrix (e.g. HPLC and SPE), recognition component in bioassays (e.g. ELISA) or biomimetic recognition layer in chemical sensor systems. Examples such as MIP-based selective analysis of

  14. Molecularly imprinted polymers--potential and challenges in analytical chemistry

    International Nuclear Information System (INIS)

    Mahony, J.O.; Nolan, K.; Smyth, M.R.; Mizaikoff, B.

    2005-01-01

    Among the variety of biomimetic recognition schemes utilizing supramolecular approaches molecularly imprinted polymers (MIPs) have proven their potential as synthetic receptors in numerous applications ranging from liquid chromatography to assays and sensor technology. Their inherent advantages compared to biochemical/biological recognition systems include robustness, storage endurance and lower costs. However, until recently only few contributions throughout the relevant literature describe quantitative analytical applications of MIPs for practically relevant analyte molecules and real-world samples. Increased motivation to thoroughly evaluate the true potential of MIP technology is clearly attributed to the demands of modern analytical chemistry, which include enhanced sensitivity, selectivity and applicability of molecular recognition building blocks at decreasing costs. In particular, the areas of environmental monitoring, food and beverage analysis and industrial process surveillance require analytical tools capable of discriminating chemicals with high molecular specificity considering increasing numbers of complex environmental contaminants, pollution of raw products and rigorous quality control requested by legislation and consumer protection. Furthermore, efficient product improvement and development of new products requires precise qualitative and quantitative analytical methods. Finally, environmental, food and process safety control issues favor the application of on-line in situ analytical methods with high molecular selectivity. While biorecognition schemes frequently suffer from degrading bioactivity and long-term stability when applied in real-world sample environments, MIPs serving as synthetic antibodies have successfully been applied as stationary phase separation matrix (e.g. HPLC and SPE), recognition component in bioassays (e.g. ELISA) or biomimetic recognition layer in chemical sensor systems. Examples such as MIP-based selective analysis of

  15. Calculation of molecular free energies in classical potentials

    International Nuclear Information System (INIS)

    Farhi, Asaf; Singh, Bipin

    2016-01-01

    Free energies of molecules can be calculated by quantum chemistry computations or by normal mode classical calculations. However, the first can be computationally impractical for large molecules and the second is based on the assumption of harmonic dynamics. We present a novel, accurate and complete calculation of molecular free energies in standard classical potentials. In this method we transform the molecule by relaxing potential terms which depend on the coordinates of a group of atoms in that molecule and calculate the free energy difference associated with the transformation. Then, since the transformed molecule can be treated as non-interacting systems, the free energy associated with these atoms is analytically or numerically calculated. This two-step calculation can be applied to calculate free energies of molecules or free energy difference between (possibly large) molecules in a general environment. We demonstrate the method in free energy calculations for methanethiol and butane molecules in vacuum and solvent. We suggest the potential application of free energy calculation of chemical reactions in classical molecular simulations. (paper)

  16. The arbitrary l continuum states of the hyperbolic molecular potential

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Gao-Feng, E-mail: fgwei_2000@163.com [School of Physics and Mechatronics Engineering, Xi' an University of Arts and Science, Xi' an 710065 (China); Chen, Wen-Li, E-mail: physwlchen@163.com [Department of Basic Science, Xi' an Peihua University, Xi' an 710065 (China); Dong, Shi-Hai, E-mail: dongsh2@yahoo.com [Escuela Superior de Física y Matemáticas, Instituto Politécnico Nacional, Edificio 9, Unidad Profesional Adolfo López Mateos, Mexico D.F. 07738 (Mexico); Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803-4001 (United States)

    2014-06-27

    Within the framework of partial-wave method, we study in this Letter the arbitrary l continuum states of the Schrödinger equation with the hyperbolic molecular potential in terms of an improved approximation to the centrifugal term. We present the normalized radial wave functions and obtain analytical formula of phase shifts. In addition, the corresponding bound states are also discussed by studying the analytical properties of the scattering amplitude. We calculate the energy spectra and scattering phase shifts by the improved, previous approximations and the accurate methods, respectively and find that the improved approximation is better than the previous one since the present results are in better agreement with the accurate ones. - Highlights: • The hyperbolic potential with arbitrary l state is solved. • Improved approximation to centrifugal term is used. • Phase shift formula is derived analytically. • Accurate results are compared with the present results.

  17. Nanoparticles and potential neurotoxicity: focus on molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Davide Lovisolo

    2018-01-01

    Full Text Available The last decades have seen an explosive increase in the development of nanoparticles and in their use in consumer, industrial and medical applications. Their fast diffusion has also raised widespread concern about the potential toxic effects on living organisms, including humans: at the nanoscale, they can interact with subcellular components such as membranes, proteins, lipids, nucleic acids, thus inducing unpredicted functional perturbations in cells and tissues. The nervous tissue is a particular sensitive target, because its cellular components (mainly neurons and glial cells are tightly regulated and metabolically exigent biological entities. While the literature on the potential toxicity of nanoparticles has grown in parallel with their utilization, the available data on neurotoxicity are less abundant. In particular, information on the neuronal molecular targets of nanoparticles is still largely incomplete. A better understanding of this issue is highly relevant for the rational and controlled design of nanoparticles, both for their general utilization and more specifically for their use in the promising field of nanoneuromedicine. In this review, we will discuss the available information on the mechanisms involved in the interaction between nanoobjects and cells of the nervous system, focusing on the known molecular actors, both at the plasma membrane and in intracellular compartments.

  18. Dynamic parameterization and ladder operators for the Kratzer molecular potential

    International Nuclear Information System (INIS)

    Devi, O Babynanda; Singh, C Amuba

    2014-01-01

    Introducing independent parameters k and δ to represent the strength of the attractive and repulsive components, respectively, we write the Kratzer molecular potential as V(k,δ)=(ℏ 2 /2 m)(−k/r+δ(δ−1)/r 2 ). This parameterisation is not only natural, but also convenient for the construction of ladder operators for the system. Adopting the straightforward method of deriving recurrence relations among confluent hypergeometric functions, we construct seven pairs of ladder operators for the Kratzer potential system. Detailed analysis of the laddering actions of these operators is given to show that they connect eigenstates of equal energy but belong to a hierarchy of Kratzer potential systems corresponding to different values of the parameters k and δ. Significantly, it is pointed out that it may not be possible to construct, in the position representation, a ladder operator which would connect different eigenstates belonging to the same potential V(k,δ). Transition to the hydrogen atom case is discussed. A number (14 altogether) of functional relations among the confluent hypergeometric functions have been derived and reported separately in an appendix. (paper)

  19. Issues in contemporary and potential future molecular diagnostics for dengue.

    Science.gov (United States)

    Sekaran, Shamala Devi; Soe, Hui Jen

    2017-03-01

    Dengue has been the most common arbovirus infection worldwide with 2.5 billion people living in over 100 endemic tropical and subtropical regions. Due to the high number of asymptomatic cases and the signs and symptoms being rather unspecific, dengue cases are often under-reported and might influence dengue surveillance programs. Therefore, a rapid, easy to use, inexpensive, and highly sensitive and specific diagnostic tool is essential for early and accurate diagnosis to ease the clinical management of patients as well as for the development of new interventions. Areas covered: This report discusses the contemporary dengue diagnostic tool, mainly from the aspect of molecular diagnosis where an overview of several nuclei acid amplification tests has been included. Potential molecular diagnostic tools such as biosensor and microarray are also discussed in this report. Expert commentary: Rapidness and accuracy in terms of sensitivity and specificity is imperative in dengue diagnosis for both clinical management and surveillance of dengue to ensure early treatment and corrective control measures can be carried out. In the next five years it is expected that there will be newer tests developed using not only the lateral flow techniques but more specifically biosensors and nanotechnology. These new technologies will have to be validated with the appropriate number and category of samples and to address the issue of cross-reactivity.

  20. Fluorescence Molecular Tomography: Principles and Potential for Pharmaceutical Research

    Directory of Open Access Journals (Sweden)

    Florian Stuker

    2011-04-01

    Full Text Available Fluorescence microscopic imaging is widely used in biomedical research to study molecular and cellular processes in cell culture or tissue samples. This is motivated by the high inherent sensitivity of fluorescence techniques, the spatial resolution that compares favorably with cellular dimensions, the stability of the fluorescent labels used and the sophisticated labeling strategies that have been developed for selectively labeling target molecules. More recently, two and three-dimensional optical imaging methods have also been applied to monitor biological processes in intact biological organisms such as animals or even humans. These whole body optical imaging approaches have to cope with the fact that biological tissue is a highly scattering and absorbing medium. As a consequence, light propagation in tissue is well described by a diffusion approximation and accurate reconstruction of spatial information is demanding. While in vivo optical imaging is a highly sensitive method, the signal is strongly surface weighted, i.e., the signal detected from the same light source will become weaker the deeper it is embedded in tissue, and strongly depends on the optical properties of the surrounding tissue. Derivation of quantitative information, therefore, requires tomographic techniques such as fluorescence molecular tomography (FMT, which maps the three-dimensional distribution of a fluorescent probe or protein concentration. The combination of FMT with a structural imaging method such as X-ray computed tomography (CT or Magnetic Resonance Imaging (MRI will allow mapping molecular information on a high definition anatomical reference and enable the use of prior information on tissue’s optical properties to enhance both resolution and sensitivity. Today many of the fluorescent assays originally developed for studies in cellular systems have been successfully translated for experimental studies in animals. The opportunity of monitoring molecular

  1. Molecular prognostic markers in ovarian cancer : toward patient-tailored therapy

    NARCIS (Netherlands)

    Crijns, APG; Duiker, EW; de Jong, S; Willemse, PHB; van der Zee, AGJ; de Vries, EGE

    2006-01-01

    In ovarian cancer the ceiling seems to be reached with chemotherapeutic drugs. Therefore a paradigm shift is needed. Instead of treating all patients according to standard guidelines, individualized molecular targeted treatment should be aimed for. This means that molecular profiles of the distinct

  2. Survivin-T34A: molecular mechanism and therapeutic potential

    Directory of Open Access Journals (Sweden)

    Jonathan R Aspe

    2010-12-01

    Full Text Available Jonathan R Aspe, Nathan R WallCenter for Health Disparities Research and Molecular Medicine, Division of Biochemistry and Microbiology, Department of Basic Sciences, Loma Linda University, Loma Linda, CA, USAAbstract: The inhibitor of apoptosis protein survivin's threonine 34 to alanine (T34A mutation abolishes a phosphorylation site for p34(cdc2–cyclin B1, resulting in initiation of the mitochondrial apoptotic pathway in cancer cells; however, it has little known direct effects on normal cells. The possibility that targeting survivin in this way may provide a novel approach for selective cancer gene therapy has yet to be fully evaluated. Although a flurry of work was undertaken in the late 1990s and early 2000s, only minor advances on this mutant have recently taken place. We recently described that cells generated to express a stable form of the mutant protein released this survivin-T34A to the conditioned medium. When this conditioned medium was collected and deposited on naive tumor cells, conditioned medium T34A was as effective as some chemotherapeutics in the induction of tumor cell apoptosis, and when combined with other forms of genotoxic stressors potentiated their killing effects. We hope with this review to revitalize the T34A field, as there is still much that needs to be investigated. In addition to determining the therapeutic dose and the duration of drug therapy required at the disease site, a better understanding of other key factors is also important. These include knowledge of target cell populations, cell-surface receptors, changes that occur in the target tissue at the molecular and cellular level with progression of the disease, and the mechanism and site of therapeutic action.Keywords: survivin, T34A, apoptosis, proliferation, therapy

  3. Development of molecular dynamics potential for uranium silicide fuels

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jianguo; Zhang, Yongfeng; Hales, Jason D.

    2016-09-01

    Use of uranium–silicide (U-Si) in place of uranium dioxide (UO2) is one of the promising concepts being proposed to increase the accident tolerance of nuclear fuels. This is due to a higher thermal conductivity than UO2 that results in lower centerline temperatures. U-Si also has a higher fissile density, which may enable some new cladding concepts that would otherwise require increased enrichment limits to compensate for their neutronic penalty. However, many critical material properties for U-Si have not been determined experimentally. For example, silicide compounds (U3Si2 and U3Si) are known to become amorphous under irradiation. There was clear independent experimental evidence to support a crystalline to amorphous transformation in those compounds. However, it is still not well understood how the amorphous transformation will affect on fuel behavior. It is anticipated that modeling and simulation may deliver guidance on the importance of various properties and help prioritize experimental work. In order to develop knowledge-based models for use at the engineering scale with a minimum of empirical parameters and increase the predictive capabilities of the developed model, inputs from atomistic simulations are essential. First-principles based density functional theory (DFT) calculations will provide the most reliable information. However, it is probably not possible to obtain kinetic information such as amorphization under irradiation directly from DFT simulations due to size and time limitations. Thus, a more feasible way may be to employ molecular dynamics (MD) simulation. Unfortunately, so far no MD potential is available for U-Si to discover the underlying mechanisms. Here, we will present our recent progress in developing a U-Si potential from ab initio data. This work is supported by the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program funded by the U.S. Department of Energy, Office of Nuclear Energy.

  4. Molecular Spectrum Capture by Tuning the Chemical Potential of Graphene

    Directory of Open Access Journals (Sweden)

    Yue Cheng

    2016-05-01

    Full Text Available Due to its adjustable electronic properties and effective excitation of surface plasmons in the infrared and terahertz frequency range, research on graphene has attracted a great deal of attention. Here, we demonstrate that plasmon modes in graphene-coated dielectric nanowire (GNW waveguides can be excited by a monolayer graphene ribbon. What is more the transverse resonant frequency spectrum of the GNW can be flexibly tuned by adjusting the chemical potential of graphene, and amplitude of the resonance peak varies linearly with the imaginary part of the analyte permittivity. As a consequence, the GNW works as a probe for capturing the molecular spectrum. Broadband sensing of toluene, ethanol and sulfurous anhydride thin layers is demonstrated by calculating the changes in spectral intensity of the propagating mode and the results show that the intensity spectra correspond exactly to the infrared spectra of these molecules. This may open an effective avenue to design sensors for detecting nanometric-size molecules in the terahertz and infrared regimes.

  5. Legal Responses to the Commodification of Personal Data in the Era of Big Data: The Paradigm Shift from Data Protection towards Data Ownership

    OpenAIRE

    Douilhet, E.; Karanasiou, Argyro

    2016-01-01

    Big Data is a relatively recent phenomenon, but has already shown its potential to drastically alter the relationships between businesses, individuals, and governments. The issues surrounding privacy of the online users (Mayer-Shoenberger, Cukier 2013) and the overall ethical challenges involved (Schroeder, 2014) make big data a topical issue, especially in the aftermath of the Snowden revelations. Many organisations now control vast amounts of raw data, and those industry players with the re...

  6. Molecular markers: a potential resource for ginger genetic diversity studies.

    Science.gov (United States)

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  7. Ab initio effective core potentials for molecular calculations. Potentials for main group elements Na to Bi

    International Nuclear Information System (INIS)

    Wadt, W.R.; Hay, P.J.

    1985-01-01

    A consistent set of ab initio effective core potentials (ECP) has been generated for the main group elements from Na to Bi using the procedure originally developed by Kahn. The ECP's are derived from all-electron numerical Hartree--Fock atomic wave functions and fit to analytical representations for use in molecular calculations. For Rb to Bi the ECP's are generated from the relativistic Hartree--Fock atomic wave functions of Cowan which incorporate the Darwin and mass--velocity terms. Energy-optimized valence basis sets of (3s3p) primitive Gaussians are presented for use with the ECP's. Comparisons between all-electron and valence-electron ECP calculations are presented for NaF, NaCl, Cl 2 , Cl 2 - , Br 2 , Br 2 - , and Xe 2 + . The results show that the average errors introduced by the ECP's are generally only a few percent

  8. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

  9. Current state of molecular imaging research

    International Nuclear Information System (INIS)

    Grimm, J.; Wunder, A.

    2005-01-01

    The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments. (orig.)

  10. Molecular and chemical engineering of bacteriophages for potential medical applications.

    Science.gov (United States)

    Hodyra, Katarzyna; Dąbrowska, Krystyna

    2015-04-01

    Recent progress in molecular engineering has contributed to the great progress of medicine. However, there are still difficult problems constituting a challenge for molecular biology and biotechnology, e.g. new generation of anticancer agents, alternative biosensors or vaccines. As a biotechnological tool, bacteriophages (phages) offer a promising alternative to traditional approaches. They can be applied as anticancer agents, novel platforms in vaccine design, or as target carriers in drug discovery. Phages also offer solutions for modern cell imaging, biosensor construction or food pathogen detection. Here we present a review of bacteriophage research as a dynamically developing field with promising prospects for further development of medicine and biotechnology.

  11. Paradigm shift in MRI for sciatica

    NARCIS (Netherlands)

    Barzouhi, Abdelilah el

    2013-01-01

    In contrast with the intuitive feeling of physicians many worrisome MRI findings do not correlate with patient outcome in patients with sciatica. Physicians should for example not automatically ascribe persistent or recurrent symptoms of sciatica to the presence of abnormalities visible on MRI. This

  12. Environment and Architecture - a Paradigm Shift

    Science.gov (United States)

    di Battista, Valerio

    The interaction of human cultures and the built environment allows a wide range of interpretations and has been studied inside the domain of many disciplines. This paper discusses three interpretations descending from a systemic approach to the question: - architecture as an "emergence" of the settlement system; - place (and space) as an "accumulator" of time and a "flux" of systems; - landscape as one representation/description of the human settlement. Architecture emerges as a new physical conformation or layout, or as a change in a specific site, arising from actions and representations of political, religious, economical or social powers, being shaped at all times by the material culture belonging to a specific time and place in the course of human evolution. Any inhabited space becomes over time a place as well as a landscape, i.e. a representation of the settlement and a relationship between setting and people. Therefore, any place owns a landscape which, in turn, is a system of physical systems; it could be defined as a system of sites that builds up its own structure stemming from the orographical features and the geometry of land surfaces that set out the basic characters of its space.

  13. School on Cloud: Towards a Paradigm Shift

    Science.gov (United States)

    Koutsopoulos, Kostis C.; Kotsanis, Yannis C.

    2014-01-01

    This paper presents the basic concept of the EU Network School on Cloud: Namely, that present conditions require a new teaching and learning paradigm based on the integrated dimension of education, when considering the use of cloud computing. In other words, it is suggested that there is a need for an integrated approach which is simultaneously…

  14. Soft durum wheat - a paradigm shift

    Science.gov (United States)

    Two traits define most aspects of wheat quality and utilization: kernel texture (hardness) and gluten. The former is far simpler genetically and is controlled by two genes, Puroindoline a and Puroindoline b. Durum wheat lacks puroindolines and has very hard kernels. As such, durum wheat when milled ...

  15. Paradigm shift in plant growth control.

    Science.gov (United States)

    Körner, Christian

    2015-06-01

    For plants to grow they need resources and appropriate conditions that these resources are converted into biomass. While acknowledging the importance of co-drivers, the classical view is still that carbon, that is, photosynthetic CO2 uptake, ranks above any other drivers of plant growth. Hence, theory and modelling of growth traditionally is carbon centric. Here, I suggest that this view is not reflecting reality, but emerged from the availability of methods and process understanding at leaf level. In most cases, poorly understood processes of tissue formation and cell growth are governing carbon demand, and thus, CO2 uptake. Carbon can only be converted into biomass to the extent chemical elements other than carbon, temperature or cell turgor permit. Copyright © 2015. Published by Elsevier Ltd.

  16. Critical Review--Outsourcing: A Paradigm Shift.

    Science.gov (United States)

    Kakabadse, Nada; Kakabadse, Andrew

    2000-01-01

    Discusses trends in outsourcing, provision of goods and services to an organization that were previously delivered in house. Addresses outsourcing in the public sector, advantages and disadvantages, implications for human resource development, and the shift to the new "psychological contract" between employers and employees. (Contains…

  17. Is This the Paradigm Shift We Need?

    Science.gov (United States)

    Mirvis, Jonathan

    2012-01-01

    Dr. Woocher's essay, states Mirvis, is seminal in the field of Jewish education. It proposes a new paradigm for Jewish education in North America. This proposed paradigm is supported by a comprehensive multi-disciplinary research drawing on literature from education, philosophy, history, sociology, psychology, and economics. The essay reflects a…

  18. Cooperate! A paradigm shift for health equity.

    Science.gov (United States)

    Chang, Wei-Ching; Fraser, Joy H

    2017-02-21

    The role of competition and cooperation in relation to the goal of health equity is examined in this paper. The authors explain why the win-lose mentality associated with avoidable competition is ethically questionable and less effective than cooperation in achieving positive outcomes, particularly as it relates to health and health equity. Competition, which differentiates winners from losers, often with the winner-takes-all reward system, inevitably leads to a few winners and many losers, resulting in social inequality, which, in turn, engenders and perpetuates health inequity.Competitive market-driven approaches to healthcare-brought about by capitalism, neo-liberalization, and globalization, based primarily on a competitive framework-are shown to have contributed to growing inequities with respect to the social determinants of health, and have undermined equal opportunity to access health care and achieve health equity. It is possible to redistribute income and wealth to reduce social inequality, but globalization poses increasing challenges to policy makers. John Stuart Mill provided a passionate, philosophical defense of cooperatives, followed by Karl Polanyi who offered an insightful critique of both state socialism and especially the self-regulating market, thereby opening up the cooperative way of shaping the future. We cite Hannah Arendt's "the banality of evil" to characterize the tragic concept of "ethical fading" witnessed in business and everyday life all over the world, often committed (without thinking and reflecting) by ordinary people under competitive pressures.To promote equity in health for all, we recommend the adoption of a radically new cooperation paradigm, applied whenever possible, to everything in our daily lives.

  19. Cervical Cancer: Reality and Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Alfredo Quiñones Ceballos

    2014-09-01

    Full Text Available Invasive cervical carcinoma usually reaches its highest frequency between 35-50 years of age. The Cuban prevention program screens the female population aged 25 to 60 years using the Pap smear and reexamines them every three years. Despite this effort, advanced cancer is diagnosed in young women as well as in those 40 to 60 years of age.

  20. A Paradigm Shift in Nuclear Spectrum Analysis

    Science.gov (United States)

    Westmeier, Wolfram; Siemon, Klaus

    2012-08-01

    An overview of the latest developments in quantitative spectrometry software is presented. New strategies and algorithms introduced are characterized by buzzwords “Physics, no numerology”, “Fuzzy logic” and “Repeated analyses”. With the implementation of these new ideas one arrives at software capabilities that were unreachable before and which are now realized in the GAMMA-W, SODIGAM and ALPS packages.

  1. Alliance - a paradigm shift in energy transportation

    International Nuclear Information System (INIS)

    Cornelson, D.W.

    1997-01-01

    Key components of the Alliance Pipeline Project were outlined. This joint Canada - U.S. venture consists of a $Can 3.7 billion, producer-driven, high-pressure, rich-gas pipeline from producing fields in western Canada to an interconnection with the North American pipeline grid near Chicago. The initial volume for the system is 1.3 Bcfd, with provision for expansion to 2 Bcfd at minimal cost. The project also includes a $Can 200 million, non-regulated, natural gas liquids extraction plant and delivery system originating near Chicago. Alberta ethane supply and demand for 1995 and supply projections for 2010, (for delivery through the Alliance pipeline?), were also highlighted. 11 figs

  2. Research by Design: A paradigm shift?

    DEFF Research Database (Denmark)

    Verbeke, Johan

    2016-01-01

    In this paper we will argue that architectural research is becoming more and more important, not only in academia but also in architectural practice. Moreover, a shift is taking place from using and absorbing research methods from other disciplines towards building on the own specific strength...... of the discipline of architecture, i.e. using design and creative practice as a method to generate knowledge and disclose unknown aspects of reality. In doing so, this paper tries to place the Delft ARENA meeting Architectural Research Network Meeting (November 2013) in perspective....

  3. From sustainability to resilience: a paradigm shift

    CSIR Research Space (South Africa)

    Van Wyk, Llewellyn V

    2015-08-01

    Full Text Available ,000/annum, making it the largest species loss since that of the dinosaurs 65 million years ago at almost 1,000 times the background rate of extinction (Quammen 1998). Again, as Gunderson et al. note, ecological resilience is different from engineering...

  4. Molecular Dynamics and Docking of Biphenyl: A Potential ...

    African Journals Online (AJOL)

    Results: Molecular docking by FireDock web server showed that biPhe-43 and Trp-43-mutated CD4 inhibited the binding of ... In a 5ns MD simulation, biPhe-43 and Trp-43 mutated CD4 .... 'unbound' MD on UMHPC Linux Cluster SGIAltix.

  5. Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

    Science.gov (United States)

    Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

    2018-05-01

    Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

  6. Paradigm shift, metamorphosis of medical ethics, and the rise of bioethics Transição paradigmática, metamorfose da ética médica e emergência da bioética

    Directory of Open Access Journals (Sweden)

    José Luiz Telles de Almeida

    1999-01-01

    Full Text Available Both the increasing incorporation of medical technology and new social demands (including those for health care beginning in the 1960s have brought about significant changes in medical practice. This situation has in turn sparked a growth in the philosophical debate over problems pertaining to ethical practice. These issues no longer find answers in the Hippocratic ethical model. The authors believe that the crisis in Hippocratic ethics could be described as a period of paradigm shift in which a new set of values appears to be emerging. Beginning with the bioethics movement, the authors expound on the different ethical theories applied to medical practice and conclude that principlism is the most appropriate approach for solving the new moral dilemma imposed on clinical practice.A crescente incorporação de tecnologia médica e as novas demandas sociais, inclusive de saúde, que tiveram início nos anos 60, impuseram importantes transformações na prática médica. Tal situação tem estimulado crescente debate filosófico em torno de problemas de ética prática que não mais encontram respostas no âmbito do modelo ético hipocrático. Para os autores, a crise da ética hipocrática poderia ser caracterizada como um período de transição paradigmática em que se estaria formando um novo conjunto de valores. A partir do movimento da bioética, os autores apresentam as diferentes teorias éticas aplicadas à prática médica, concluindo que a abordagem principialista seria mais adequada à resolução dos novos dilemas morais postos à prática clínica.

  7. Nutraceuticals: potential for chondroprotection and molecular targeting of osteoarthritis.

    Science.gov (United States)

    Leong, Daniel J; Choudhury, Marwa; Hirsh, David M; Hardin, John A; Cobelli, Neil J; Sun, Hui B

    2013-11-21

    Osteoarthritis (OA) is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals-food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease-offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.

  8. Nutraceuticals: Potential for Chondroprotection and Molecular Targeting of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Daniel J. Leong

    2013-11-01

    Full Text Available Osteoarthritis (OA is a degenerative joint disease and a leading cause of adult disability. There is no cure for OA, and no effective treatments which arrest or slow its progression. Current pharmacologic treatments such as analgesics may improve pain relief but do not alter OA disease progression. Prolonged consumption of these drugs can result in severe adverse effects. Given the nature of OA, life-long treatment will likely be required to arrest or slow its progression. Consequently, there is an urgent need for OA disease-modifying therapies which also improve symptoms and are safe for clinical use over long periods of time. Nutraceuticals—food or food products that provide medical or health benefits, including the prevention and/or treatment of a disease—offer not only favorable safety profiles, but may exert disease- and symptom-modification effects in OA. Forty-seven percent of OA patients use alternative medications, including nutraceuticals. This review will overview the efficacy and mechanism of action of commonly used nutraceuticals, discuss recent experimental and clinical data on the effects of select nutraceuticals, such as phytoflavonoids, polyphenols, and bioflavonoids on OA, and highlight their known molecular actions and limitations of their current use. We will conclude with a proposed novel nutraceutical-based molecular targeting strategy for chondroprotection and OA treatment.

  9. Molecular mechanism and potential targets for bone metastasis

    International Nuclear Information System (INIS)

    Iguchi, Haruo

    2007-01-01

    The incidence of bone metastasis has been increasing in all cancers in recent years. Bone metastasis is associated with substantial morbidity, including bone pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the management of bone metastasis in patients is a clinically significant issue. In the process of bone metastasis, the primary mechanism responsible for bone destruction is cancer cell-mediated stimulation of osteoclastic bone resorption, which results in osteolysis and release of various growth factors from the bone matrix. These growth factors are prerequisites for successful colonization and subsequent invasive growth of cancer cells in bone, which is called a 'vicious cycle.' Thus, it is important to elucidate what molecules are involved in this step of bone destruction, and the understanding of these molecular mechanisms could lead to develop molecular-target therapies for bone metastasis. Bisphosphonates introduced in the treatment for bone metastasis have been shown to reduce skeletal morbidity. In Japan, the most potent bisphosphonate, zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical trial of humanized anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Denosumab) against bone metastasis is under way as a global study. These new agents, which are targeted to osteoclasts, are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and/or hormone therapy. (author)

  10. An adaptive interpolation scheme for molecular potential energy surfaces

    Science.gov (United States)

    Kowalewski, Markus; Larsson, Elisabeth; Heryudono, Alfa

    2016-08-01

    The calculation of potential energy surfaces for quantum dynamics can be a time consuming task—especially when a high level of theory for the electronic structure calculation is required. We propose an adaptive interpolation algorithm based on polyharmonic splines combined with a partition of unity approach. The adaptive node refinement allows to greatly reduce the number of sample points by employing a local error estimate. The algorithm and its scaling behavior are evaluated for a model function in 2, 3, and 4 dimensions. The developed algorithm allows for a more rapid and reliable interpolation of a potential energy surface within a given accuracy compared to the non-adaptive version.

  11. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

  12. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    Directory of Open Access Journals (Sweden)

    Preeyaporn Koedrith

    2011-12-01

    Full Text Available Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.

  13. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly & Cushing Disease Paradigms

    Directory of Open Access Journals (Sweden)

    Michael Anthony Mooney

    2016-07-01

    Full Text Available The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  14. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    Science.gov (United States)

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.

  15. Electronic structure, molecular bonding and potential energy surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ruedenberg, K. [Ames Laboratory, IA (United States)

    1993-12-01

    By virtue of the universal validity of the generalized Born-Oppenheimer separation, potential energy surfaces (PES`) represent the central conceptual as well as quantitative entities of chemical physics and provide the basis for the understanding of most physicochemical phenomena in many diverse fields. The research in this group deals with the elucidation of general properties of PES` as well as with the quantitative determination of PES` for concrete systems, in particular pertaining to reactions involving carbon, oxygen, nitrogen and hydrogen molecules.

  16. Molecular ordering at electrified interfaces: Template and potential effects

    Directory of Open Access Journals (Sweden)

    Thanh Hai Phan

    2014-09-01

    Full Text Available A combination of cyclic voltammetry and in situ scanning tunneling microscopy was employed to examine the adsorption and phase transition of 1,1’-dibenzyl-4,4’-bipyridinium molecules (abbreviated as DBV2+ on a chloride-modified Cu(111 electrode surface. The cyclic voltammogram (CV of the Cu(111 electrode exposed to a mixture of 10 mM HCl and 0.1 mM DBVCl2 shows three distinguishable pairs of current waves P1/P’1, P2/P’2, and P3/P’3 which are assigned to two reversible electron transfer steps, representing the reduction of the dicationic DBV2+ to the corresponding radical monocationic DBV+• (P1/P’1 and then to the uncharged DBV0 (P3/P’3 species, respectively, as well as the chloride desorption/readsorption processes (P2/P’2. At positive potentials (i.e., above P1 the DBV2+ molecules spontaneously adsorb and form a highly ordered phase on the c(p × √3-precovered Cl/Cu(111 electrode surface. A key element of this DBV2+ adlayer is an assembly of two individual DBV2+ species which, lined up, forms a so-called “herring-bone” structure. Upon lowering the electrode potential the first electron transfer step (at P1 causes a phase transition from the DBV2+-related herring-bone phase to the so-called "alternating stripe" pattern built up by the DBV+• species following a nucleation and growth mechanism. Comparison of both observed structures with those found earlier at different electrode potentials on a c(2 × 2Cl-precovered Cu(100 electrode surface enables a clear assessment of the relative importance of adsorbate–substrate and adsorbate–adsorbate interactions, i.e., template vs self-assembly effects, in the structure formation process of DBV cations on these modified Cu electrode surfaces.

  17. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  18. Brownian diode: Molecular motor based on a semi-permeable Brownian particle with internal potential drop

    International Nuclear Information System (INIS)

    Plyukhin, A.V.

    2013-01-01

    A model of an autonomous isothermal Brownian motor with an internal propulsion mechanism is considered. The motor is a Brownian particle which is semi-transparent for molecules of surrounding ideal gas. Molecular passage through the particle is controlled by a potential similar to that in the transition rate theory, i.e. characterized by two stationary states with a finite energy difference separated by a potential barrier. The internal potential drop maintains the diode-like asymmetry of molecular fluxes through the particle, which results in the particle's stationary drift.

  19. Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Chandrabhan Seniya

    2014-01-01

    Full Text Available Cholinesterase inhibitors (ChE-Is are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA. Additionally, acetylcholinesterase (AChE is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6 to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

  20. A new approach to the method of source-sink potentials for molecular conduction

    Energy Technology Data Exchange (ETDEWEB)

    Pickup, Barry T., E-mail: B.T.Pickup@sheffield.ac.uk, E-mail: P.W.Fowler@sheffield.ac.uk; Fowler, Patrick W., E-mail: B.T.Pickup@sheffield.ac.uk, E-mail: P.W.Fowler@sheffield.ac.uk; Borg, Martha [Department of Chemistry, University of Sheffield, Sheffield S3 7HF (United Kingdom); Sciriha, Irene [Department of Mathematics, University of Malta, Msida (Malta)

    2015-11-21

    We re-derive the tight-binding source-sink potential (SSP) equations for ballistic conduction through conjugated molecular structures in a form that avoids singularities. This enables derivation of new results for families of molecular devices in terms of eigenvectors and eigenvalues of the adjacency matrix of the molecular graph. In particular, we define the transmission of electrons through individual molecular orbitals (MO) and through MO shells. We make explicit the behaviour of the total current and individual MO and shell currents at molecular eigenvalues. A rich variety of behaviour is found. A SSP device has specific insulation or conduction at an eigenvalue of the molecular graph (a root of the characteristic polynomial) according to the multiplicities of that value in the spectra of four defined device polynomials. Conduction near eigenvalues is dominated by the transmission curves of nearby shells. A shell may be inert or active. An inert shell does not conduct at any energy, not even at its own eigenvalue. Conduction may occur at the eigenvalue of an inert shell, but is then carried entirely by other shells. If a shell is active, it carries all conduction at its own eigenvalue. For bipartite molecular graphs (alternant molecules), orbital conduction properties are governed by a pairing theorem. Inertness of shells for families such as chains and rings is predicted by selection rules based on node counting and degeneracy.

  1. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  2. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

  3. Calculation of the electrostatic potential of lipid bilayers from molecular dynamics simulations: methodological issues

    DEFF Research Database (Denmark)

    Gurtovenko, Andrey A; Vattulainen, Ilpo

    2009-01-01

    of the electrostatic potential from atomic-scale molecular dynamics simulations of lipid bilayers. We discuss two slightly different forms of Poisson equation that are normally used to calculate the membrane potential: (i) a classical form when the potential and the electric field are chosen to be zero on one...... systems). For symmetric bilayers we demonstrate that both approaches give essentially the same potential profiles, provided that simulations are long enough (a production run of at least 100 ns is required) and that fluctuations of the center of mass of a bilayer are properly accounted for. In contrast...

  4. Combining a reactive potential with a harmonic approximation for molecular dynamics simulation of failure: construction of a reduced potential

    Science.gov (United States)

    Tejada, I. G.; Brochard, L.; Stoltz, G.; Legoll, F.; Lelièvre, T.; Cancès, E.

    2015-01-01

    Molecular dynamics is a simulation technique that can be used to study failure in solids, provided the inter-atomic potential energy is able to account for the complex mechanisms at failure. Reactive potentials fitted on ab initio results or on experimental values have the ability to adapt to any complex atomic arrangement and, therefore, are suited to simulate failure. But the complexity of these potentials, together with the size of the systems considered, make simulations computationally expensive. In order to improve the efficiency of numerical simulations, simpler harmonic potentials can be used instead of complex reactive potentials in the regions where the system is close to its ground state and a harmonic approximation reasonably fits the actual reactive potential. However the validity and precision of such an approach has not been investigated in detail yet. We present here a methodology for constructing a reduced potential and combining it with the reactive one. We also report some important features of crack propagation that may be affected by the coupling of reactive and reduced potentials. As an illustrative case, we model a crystalline two-dimensional material (graphene) with a reactive empirical bond-order potential (REBO) or with harmonic potentials made of bond and angle springs that are designed to reproduce the second order approximation of REBO in the ground state. We analyze the consistency of this approximation by comparing the mechanical behavior and the phonon spectra of systems modeled with these potentials. These tests reveal when the anharmonicity effects appear. As anharmonic effects originate from strain, stress or temperature, the latter quantities are the basis for establishing coupling criteria for on the fly substitution in large simulations.

  5. Data-mining of potential antitubercular activities from molecular ingredients of traditional Chinese medicines.

    Science.gov (United States)

    Jamal, Salma; Scaria, Vinod

    2014-01-01

    Background. Traditional Chinese medicine encompasses a well established alternate system of medicine based on a broad range of herbal formulations and is practiced extensively in the region for the treatment of a wide variety of diseases. In recent years, several reports describe in depth studies of the molecular ingredients of traditional Chinese medicines on the biological activities including anti-bacterial activities. The availability of a well-curated dataset of molecular ingredients of traditional Chinese medicines and accurate in-silico cheminformatics models for data mining for antitubercular agents and computational filters to prioritize molecules has prompted us to search for potential hits from these datasets. Results. We used a consensus approach to predict molecules with potential antitubercular activities from a large dataset of molecular ingredients of traditional Chinese medicines available in the public domain. We further prioritized 160 molecules based on five computational filters (SMARTSfilter) so as to avoid potentially undesirable molecules. We further examined the molecules for permeability across Mycobacterial cell wall and for potential activities against non-replicating and drug tolerant Mycobacteria. Additional in-depth literature surveys for the reported antitubercular activities of the molecular ingredients and their sources were considered for drawing support to prioritization. Conclusions. Our analysis suggests that datasets of molecular ingredients of traditional Chinese medicines offer a new opportunity to mine for potential biological activities. In this report, we suggest a proof-of-concept methodology to prioritize molecules for further experimental assays using a variety of computational tools. We also additionally suggest that a subset of prioritized molecules could be used for evaluation for tuberculosis due to their additional effect against non-replicating tuberculosis as well as the additional hepato-protection offered by

  6. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  7. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    Science.gov (United States)

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  8. The effect of interatomic potential in molecular dynamics simulation of low energy ion implantation

    International Nuclear Information System (INIS)

    Chan, H.Y.; Nordlund, K.; Peltola, J.; Gossmann, H.-J.L.; Ma, N.L.; Srinivasan, M.P.; Benistant, F.; Chan, Lap

    2005-01-01

    Being able to accurately predict dopant profiles at sub-keV implant energies is critical for the microelectronic industry. Molecular Dynamics (MD), with its capability to account for multiple interactions as energy lowers, is an increasingly popular simulation method. We report our work on sub-keV implantation using MD and investigate the effect of different interatomic potentials on the range profiles. As an approximation, only pair potentials are considered in this work. Density Functional Theory (DFT) is used to calculate the pair potentials for a wide range of dopants (B, C, N, F, Si, P, Ga, Ge, As, In and Sb) in single crystalline silicon. A commonly used repulsive potential is also included in the study. Importance of the repulsive and attractive regions of the potential has been investigated with different elements and we show that a potential depicting the right attractive forces is especially important for heavy elements at low energies

  9. Stable Flocking of Multiple Agents Based on Molecular Potential Field and Distributed Receding Horizon Control

    International Nuclear Information System (INIS)

    Zhang Yun-Peng; Duan Hai-Bin; Zhang Xiang-Yin

    2011-01-01

    A novel distributed control scheme to generate stable flocking motion for a group of agents is proposed. In this control scheme, a molecular potential field model is applied as the potential field function because of its smoothness and unique shape. The approach of distributed receding horizon control is adopted to drive each agent to find its optimal control input to lower its potential at every step. Experimental results show that this proposed control scheme can ensure that all agents eventually converge to a stable flocking formation with a common velocity and the collisions can also be avoided at the same time. (general)

  10. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    International Nuclear Information System (INIS)

    Mahajan, A.; Goh, V.; Basu, S.; Vaish, R.; Weeks, A.J.; Thakur, M.H.; Cook, G.J.

    2015-01-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [ 18 F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

  11. Potentials and limits of modern tomographic methods (CT, MR, PET) in molecular imaging

    International Nuclear Information System (INIS)

    Hentschel, M.; Paul, D.; Moser, E.; Brink, I.

    2007-01-01

    The present survey gives an introduction into the basics of computed tomography, magnetic resonance tomography and positron emission tomography. The current potentials of these methods in relation to their temporal, spatial and contrast resolutions as well as their sensitivities within clinical routine and experimental studies (in vitro, ex vivo) will be presented. Computed tomography constitutes the anatomical reference method with well defined contrast, high spatial resolution but low sensitivity (10 -2 mol/l) for functional and molecular imaging. Magnetic resonance tomography represents the anatomical method for research with variable tissue contrast, physiological image information, highest spatial resolution but moderate sensitivity (10 -3 -10 -5 mol/l) for functional and molecular imaging. Positron emission tomography offers good suitability for molecular imaging due to highest sensitivity (10 -11 -10 -12 mol/l). However, the spatial resolution of positron emission tomography is low. (orig.)

  12. Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

    Science.gov (United States)

    Simal-Gándara, J; Sarria-Vidal, M; Rijk, R

    2000-09-01

    Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

  13. Ozonation of humic substances: Effects on molecular weight distributions of organic carbon and trihalomethane formation potential

    International Nuclear Information System (INIS)

    Amy, G.L.; Kuo, C.J.; Sierka, R.A.

    1988-01-01

    Four different sources of humic substances were studied to determine the effects of ozonation on molecular weight distributions, based on dissolved organic carbon (DOC) and trihalomethane formation potential (THMFP). Solutions of two soil-derived fulvic acids and a one soil-derived humic acid, as well as dissolved organic matter (DOM) associated with a natural water source were studied. Both gel permeation chromatography (GPC) and ultrafiltration (UF) were employed to define apparent molecular weight (AMW). Applied ozone doses ranged from 2.0 to 2.5 mg O 3 /mg DOC. Overall samples of untreated and ozonated waters, as well as individual molecular weight fractions, were characterized according to DOC, uv absorbance, and THMFP. Ozonation resulted in a significant disappearance of higher AMW material with a corresponding increase in lower AMW material. Although little overall reduction in DOC concentration was observed, significant overall reductions in UV absorbance and THMFP levels were observed

  14. Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

    Science.gov (United States)

    Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

    2014-12-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Efficient molecular dynamics simulations with many-body potentials on graphics processing units

    Science.gov (United States)

    Fan, Zheyong; Chen, Wei; Vierimaa, Ville; Harju, Ari

    2017-09-01

    Graphics processing units have been extensively used to accelerate classical molecular dynamics simulations. However, there is much less progress on the acceleration of force evaluations for many-body potentials compared to pairwise ones. In the conventional force evaluation algorithm for many-body potentials, the force, virial stress, and heat current for a given atom are accumulated within different loops, which could result in write conflict between different threads in a CUDA kernel. In this work, we provide a new force evaluation algorithm, which is based on an explicit pairwise force expression for many-body potentials derived recently (Fan et al., 2015). In our algorithm, the force, virial stress, and heat current for a given atom can be accumulated within a single thread and is free of write conflicts. We discuss the formulations and algorithms and evaluate their performance. A new open-source code, GPUMD, is developed based on the proposed formulations. For the Tersoff many-body potential, the double precision performance of GPUMD using a Tesla K40 card is equivalent to that of the LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator) molecular dynamics code running with about 100 CPU cores (Intel Xeon CPU X5670 @ 2.93 GHz).

  16. Influence of the interatomic potentials on molecular dynamics simulations of displacement cascades

    CERN Document Server

    Becquart, C S; Legris, A; Van Duysen, J C

    2000-01-01

    Molecular dynamics (MD) is a powerful tool to study the displacement cascades initiated by the neutrons when they interact with matter. Key components of this technique are the interatomic potentials which model the binding of the different constitutive atoms. There exist many interatomic potentials dedicated to alpha-Fe and we have tested three of them for the study of radiation damage. We have found that the primary damage is potential sensitive. From our study, it appears that some characteristics of the potentials, not always considered, can be correlated to the type of damage produced by displacement cascades. The repulsive part of the potential has a strong influence on the cascade morphology. Moreover, equilibrium properties such as the atoms mean square displacements, the vacancy migration and vacancy-vacancy binding energies also appear to have some influence and should be investigated carefully when simulating radiation damage. It is therefore very important to use extreme care when trying to obtain...

  17. An interatomic potential model for molecular dynamics simulation of silicon etching by Br+-containing plasmas

    International Nuclear Information System (INIS)

    Ohta, H.; Iwakawa, A.; Eriguchi, K.; Ono, K.

    2008-01-01

    An interatomic potential model for Si-Br systems has been developed for performing classical molecular dynamics (MD) simulations. This model enables us to simulate atomic-scale reaction dynamics during Si etching processes by Br + -containing plasmas such as HBr and Br 2 plasmas, which are frequently utilized in state-of-the-art techniques for the fabrication of semiconductor devices. Our potential form is based on the well-known Stillinger-Weber potential function, and the model parameters were systematically determined from a database of potential energies obtained from ab initio quantum-chemical calculations using GAUSSIAN03. For parameter fitting, we propose an improved linear scheme that does not require any complicated nonlinear fitting as that in previous studies [H. Ohta and S. Hamaguchi, J. Chem. Phys. 115, 6679 (2001)]. In this paper, we present the potential derivation and simulation results of bombardment of a Si(100) surface using a monoenergetic Br + beam

  18. Deep Potential Molecular Dynamics: A Scalable Model with the Accuracy of Quantum Mechanics

    Science.gov (United States)

    Zhang, Linfeng; Han, Jiequn; Wang, Han; Car, Roberto; E, Weinan

    2018-04-01

    We introduce a scheme for molecular simulations, the deep potential molecular dynamics (DPMD) method, based on a many-body potential and interatomic forces generated by a carefully crafted deep neural network trained with ab initio data. The neural network model preserves all the natural symmetries in the problem. It is first-principles based in the sense that there are no ad hoc components aside from the network model. We show that the proposed scheme provides an efficient and accurate protocol in a variety of systems, including bulk materials and molecules. In all these cases, DPMD gives results that are essentially indistinguishable from the original data, at a cost that scales linearly with system size.

  19. Molecular profiling techniques as tools to detect potential unintended effects in genetically engineered maize

    CSIR Research Space (South Africa)

    Barros, E

    2010-05-01

    Full Text Available Molecular Profiling Techniques as Tools to Detect Potential Unintended Effects in Genetically Engineered Maize Eugenia Barros Introduction In the early stages of production and commercialization of foods derived from genetically engineered (GE) plants... systems. In a recent paper published in Plant Biotechnology Journal,4 we compared two transgenic white maize lines with the non-transgenic counterpart to investigate two possible sources of variation: genetic engineering and environmental variation...

  20. Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Jinfan Tian

    2017-01-01

    Full Text Available An increasing number of patients diagnosed with diabetes mellitus eventually develop severe coronary atherosclerosis disease. Both type 1 and type 2 diabetes mellitus increase the risk of cardiovascular disease associated with atherosclerosis. The cellular and molecular mechanisms affecting the incidence of diabetic atherosclerosis are still unclear, as are appropriate strategies for the prevention and treatment of diabetic atherosclerosis. In this review, we discuss progress in the study of herbs as potential therapeutic agents for diabetic atherosclerosis.

  1. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

    Science.gov (United States)

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

    2016-01-01

    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

    DEFF Research Database (Denmark)

    Plougmann, Julie Isabelle; Klausen, Pia; Karstensen, John Gásdal

    2017-01-01

    of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During...... the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients...

  3. Characterization of the glass transition of water predicted by molecular dynamics simulations using nonpolarizable intermolecular potentials.

    Science.gov (United States)

    Kreck, Cara A; Mancera, Ricardo L

    2014-02-20

    Molecular dynamics simulations allow detailed study of the experimentally inaccessible liquid state of supercooled water below its homogeneous nucleation temperature and the characterization of the glass transition. Simple, nonpolarizable intermolecular potentials are commonly used in classical molecular dynamics simulations of water and aqueous systems due to their lower computational cost and their ability to reproduce a wide range of properties. Because the quality of these predictions varies between the potentials, the predicted glass transition of water is likely to be influenced by the choice of potential. We have thus conducted an extensive comparative investigation of various three-, four-, five-, and six-point water potentials in both the NPT and NVT ensembles. The T(g) predicted from NPT simulations is strongly correlated with the temperature of minimum density, whereas the maximum in the heat capacity plot corresponds to the minimum in the thermal expansion coefficient. In the NVT ensemble, these points are instead related to the maximum in the internal pressure and the minimum of its derivative, respectively. A detailed analysis of the hydrogen-bonding properties at the glass transition reveals that the extent of hydrogen-bonds lost upon the melting of the glassy state is related to the height of the heat capacity peak and varies between water potentials.

  4. Detailed balance method for chemical potential determination in Monte Carlo and molecular dynamics simulations

    International Nuclear Information System (INIS)

    Fay, P.J.; Ray, J.R.; Wolf, R.J.

    1994-01-01

    We present a new, nondestructive, method for determining chemical potentials in Monte Carlo and molecular dynamics simulations. The method estimates a value for the chemical potential such that one has a balance between fictitious successful creation and destruction trials in which the Monte Carlo method is used to determine success or failure of the creation/destruction attempts; we thus call the method a detailed balance method. The method allows one to obtain estimates of the chemical potential for a given species in any closed ensemble simulation; the closed ensemble is paired with a ''natural'' open ensemble for the purpose of obtaining creation and destruction probabilities. We present results for the Lennard-Jones system and also for an embedded atom model of liquid palladium, and compare to previous results in the literature for these two systems. We are able to obtain an accurate estimate of the chemical potential for the Lennard-Jones system at higher densities than reported in the literature

  5. Calculation of surface potentials at the silica–water interface using molecular dynamics: Challenges and opportunities

    Science.gov (United States)

    Lowe, Benjamin M.; Skylaris, Chris-Kriton; Green, Nicolas G.; Shibuta, Yasushi; Sakata, Toshiya

    2018-04-01

    Continuum-based methods are important in calculating electrostatic properties of interfacial systems such as the electric field and surface potential but are incapable of providing sufficient insight into a range of fundamentally and technologically important phenomena which occur at atomistic length-scales. In this work a molecular dynamics methodology is presented for interfacial electric field and potential calculations. The silica–water interface was chosen as an example system, which is highly relevant for understanding the response of field-effect transistors sensors (FET sensors). Detailed validation work is presented, followed by the simulated surface charge/surface potential relationship. This showed good agreement with experiment at low surface charge density but at high surface charge density the results highlighted challenges presented by an atomistic definition of the surface potential. This methodology will be used to investigate the effect of surface morphology and biomolecule addition; both factors which are challenging using conventional continuum models.

  6. Ab initio effective core potentials for molecular calculations. Potentials for K to Au including the outermost core orbitals

    International Nuclear Information System (INIS)

    Hay, P.J.; Wadt, W.R.

    1985-01-01

    Ab initio effective core potentials (ECP's) have been generated to replace the innermost core electron for third-row (K--Au), fourth-row (Rb--Ag), and fifth-row (Cs--Au) atoms. The outermost core orbitals: corresponding to the ns 2 np 6 configuration for the three rows here: are not replaced by the ECP but are treated on an equal footing with the nd, (n+1)s and (n+1)p valence orbitals. These ECP's have been derived for use in molecular calculations where these outer core orbitals need to be treated explicitly rather than to be replaced by an ECP. The ECP's for the forth and fifth rows also incorporate the mass--velocity and Darwin relativistic effects into the potentials. Analytic fits to the potentials are presented for use in multicenter integral evaluation. Gaussian orbital valence basis sets are developed for the (3s, 3p, 3d, 4s, 4p), (4s, 4p, 4d, 5s, 5p), and (5s, 5p, 5d, 6s, 6p) ortibals of the three respective rows

  7. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. The Influence of Single Nucleotide Polymorphism Microarray-Based Molecular Karyotype on Preimplantation Embryonic Development Potential.

    Directory of Open Access Journals (Sweden)

    Gang Li

    Full Text Available In order to investigate the influence of the molecular karyotype based on single nucleotide polymorphism (SNP microarray on embryonic development potential in preimplantation genetic diagnosis (PGD, we retrospectively analyzed the clinical data generated by PGD using embryos retrieved from parents with chromosome rearrangements in our center. In total, 929 embryos from 119 couples had exact diagnosis and development status. The blastocyst formation rate of balanced molecular karyotype embryos was 56.6% (276/488, which was significantly higher than that of genetic imbalanced embryos 24.5% (108/441 (P35 respectively. Blastocyst formation rates of male and female embryos were 44.5% (183/411 and 38.8% (201/518 respectively, with no significant difference between them (P>0.05. The rates of balanced molecular karyotype embryos vary from groups of embryos with different cell numbers at 68 hours after insemination. The blastocyst formation rate of embryos with 6-8 cells (48.1% was significantly higher than that of embryos with 8 cells (42.9% (P8 cells, embryos with 6-8 blastomeres have higher rate of balanced molecular karyotype and blastocyst formation.

  9. Molecular Insights into the Potential Toxicological Interaction of 2-Mercaptothiazoline with the Antioxidant Enzyme—Catalase

    Science.gov (United States)

    Huang, Zhenxing; Huang, Ming; Mi, Chenyu; Wang, Tao; Chen, Dong; Teng, Yue

    2016-01-01

    2-mercaptothiazoline (2-MT) is widely used in many industrial fields, but its residue is potentially harmful to the environment. In this study, to evaluate the biological toxicity of 2-MT at protein level, the interaction between 2-MT and the pivotal antioxidant enzyme—catalase (CAT) was investigated using multiple spectroscopic techniques and molecular modeling. The results indicated that the CAT fluorescence quenching caused by 2-MT should be dominated by a static quenching mechanism through formation of a 2-MT/CAT complex. Furthermore, the identifications of the binding constant, binding forces, and the number of binding sites demonstrated that 2-MT could spontaneously interact with CAT at one binding site mainly via Van der Waals’ forces and hydrogen bonding. Based on the molecular docking simulation and conformation dynamic characterization, it was found that 2-MT could bind into the junctional region of CAT subdomains and that the binding site was close to enzyme active sites, which induced secondary structural and micro-environmental changes in CAT. The experiments on 2-MT toxicity verified that 2-MT significantly inhibited CAT activity via its molecular interaction, where 2-MT concentration and exposure time both affected the inhibitory action. Therefore, the present investigation provides useful information for understanding the toxicological mechanism of 2-MT at the molecular level. PMID:27537873

  10. Marine Diterpenes: Molecular Modeling of Thrombin Inhibitors with Potential Biotechnological Application as an Antithrombotic

    Directory of Open Access Journals (Sweden)

    Rebeca Cristina Costa Pereira

    2017-03-01

    Full Text Available Thrombosis related diseases are among the main causes of death and incapacity in the world. Despite the existence of antithrombotic agents available for therapy, they still present adverse effects like hemorrhagic risks which justify the search for new options. Recently, pachydictyol A, isopachydictyol A, and dichotomanol, three diterpenes isolated from Brazilian marine brown alga Dictyota menstrualis were identified as potent antithrombotic molecules through inhibition of thrombin, a key enzyme of coagulation cascade and a platelet agonist. Due to the biotechnological potential of these marine metabolites, in this work we evaluated their binding mode to thrombin in silico and identified structural features related to the activity in order to characterize their molecular mechanism. According to our theoretical studies including structure-activity relationship and molecular docking analysis, the highest dipole moment, polar surface area, and lowest electronic density of dichotomanol are probably involved in its higher inhibition percentage towards thrombin catalytic activity compared to pachydictyol A and isopachydictyol A. Interestingly, the molecular docking studies also revealed a good shape complementarity of pachydictyol A and isopachydictyol A and interactions with important residues and regions (e.g., H57, S195, W215, G216, and loop-60, which probably justify their thrombin inhibitor effects demonstrated in vitro. Finally, this study explored the structural features and binding mode of these three diterpenes in thrombin which reinforced their potential to be further explored and may help in the design of new antithrombotic agents.

  11. The effect of empirical potential functions on modeling of amorphous carbon using molecular dynamics method

    International Nuclear Information System (INIS)

    Li, Longqiu; Xu, Ming; Song, Wenping; Ovcharenko, Andrey; Zhang, Guangyu; Jia, Ding

    2013-01-01

    Empirical potentials have a strong effect on the hybridization and structure of amorphous carbon and are of great importance in molecular dynamics (MD) simulations. In this work, amorphous carbon at densities ranging from 2.0 to 3.2 g/cm 3 was modeled by a liquid quenching method using Tersoff, 2nd REBO, and ReaxFF empirical potentials. The hybridization, structure and radial distribution function G(r) of carbon atoms were analyzed as a function of the three potentials mentioned above. The ReaxFF potential is capable to model the change of the structure of amorphous carbon and MD results are in a good agreement with experimental results and density function theory (DFT) at low density of 2.6 g/cm 3 and below. The 2nd REBO potential can be used when amorphous carbon has a very low density of 2.4 g/cm 3 and below. Considering the computational efficiency, the Tersoff potential is recommended to model amorphous carbon at a high density of 2.6 g/cm 3 and above. In addition, the influence of the quenching time on the hybridization content obtained with the three potentials is discussed.

  12. Water models based on a single potential energy surface and different molecular degrees of freedom

    Science.gov (United States)

    Saint-Martin, Humberto; Hernández-Cobos, Jorge; Ortega-Blake, Iván

    2005-06-01

    Up to now it has not been possible to neatly assess whether a deficient performance of a model is due to poor parametrization of the force field or the lack of inclusion of enough molecular properties. This work compares several molecular models in the framework of the same force field, which was designed to include many-body nonadditive effects: (a) a polarizable and flexible molecule with constraints that account for the quantal nature of the vibration [B. Hess, H. Saint-Martin, and H. J. C. Berendsen, J. Chem. Phys. 116, 9602 (2002), H. Saint-Martin, B. Hess, and H. J. C. Berendsen, J. Chem. Phys. 120, 11133 (2004)], (b) a polarizable and classically flexible molecule [H. Saint-Martin, J. Hernández-Cobos, M. I. Bernal-Uruchurtu, I. Ortega-Blake, and H. J. C. Berendsen, J. Chem. Phys. 113, 10899 (2000)], (c) a polarizable and rigid molecule, and finally (d) a nonpolarizable and rigid molecule. The goal is to determine how significant the different molecular properties are. The results indicate that all factors—nonadditivity, polarizability, and intramolecular flexibility—are important. Still, approximations can be made in order to diminish the computational cost of the simulations with a small decrease in the accuracy of the predictions, provided that those approximations are counterbalanced by the proper inclusion of an effective molecular property, that is, an average molecular geometry or an average dipole. Hence instead of building an effective force field by parametrizing it in order to reproduce the properties of a specific phase, a building approach is proposed that is based on adequately restricting the molecular flexibility and/or polarizability of a model potential fitted to unimolecular properties, pair interactions, and many-body nonadditive contributions. In this manner, the same parental model can be used to simulate the same substance under a wide range of thermodynamic conditions. An additional advantage of this approach is that, as the force

  13. Design of potentially active ligands for SH2 domains by molecular modeling methods

    Directory of Open Access Journals (Sweden)

    Hurmach V. V.

    2014-07-01

    Full Text Available Search for new chemical structures possessing specific biological activity is a complex problem that needs the use of the latest achievements of molecular modeling technologies. It is well known that SH2 domains play a major role in ontogenesis as intermediaries of specific protein-protein interactions. Aim. Developing an algorithm to investigate the properties of SH2 domain binding, search for new potential active compounds for the whole SH2 domains class. Methods. In this paper, we utilize a complex of computer modeling methods to create a generic set of potentially active compounds targeting universally at the whole class of SH2 domains. A cluster analysis of all available three-dimensional structures of SH2 domains was performed and general pharmacophore models were formulated. The models were used for virtual screening of collection of drug-like compounds provided by Enamine Ltd. Results. The design technique for library of potentially active compounds for SH2 domains class was proposed. Conclusions. The original algorithm of SH2 domains research with molecular docking method was developed. Using our algorithm, the active compounds for SH2 domains were found.

  14. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    Science.gov (United States)

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Electric potential calculation in molecular simulation of electric double layer capacitors

    International Nuclear Information System (INIS)

    Wang, Zhenxing; Laird, Brian B; Olmsted, David L; Asta, Mark

    2016-01-01

    For the molecular simulation of electric double layer capacitors (EDLCs), a number of methods have been proposed and implemented to determine the one-dimensional electric potential profile between the two electrodes at a fixed potential difference. In this work, we compare several of these methods for a model LiClO 4 -acetonitrile/graphite EDLC simulated using both the traditional fixed-charged method (FCM), in which a fixed charge is assigned a priori to the electrode atoms, or the recently developed constant potential method (CPM) (2007 J. Chem. Phys . 126 084704), where the electrode charges are allowed to fluctuate to keep the potential fixed. Based on an analysis of the full three-dimensional electric potential field, we suggest a method for determining the averaged one-dimensional electric potential profile that can be applied to both the FCM and CPM simulations. Compared to traditional methods based on numerically solving the one-dimensional Poisson’s equation, this method yields better accuracy and no supplemental assumptions. (paper)

  16. Isolation, enumeration, molecular identification and probiotic potential evaluation of lactic acid bacteria isolated from sheep milk

    OpenAIRE

    Acurcio, L.B.; Souza, M.R.; Nunes, A.C.; Oliveira, D.L.S.; Sandes, S.H.C.; Alvim, L.B.

    2014-01-01

    Lactic acid bacteria species were molecularly identified in milk from Lacaune, Santa Inês and crossbred sheep breeds and their in vitro probiotic potential was evaluated. The species identified were Enterococcus faecium (56.25%), E. durans (31.25%) and E. casseliflavus (12.5%). No other lactic acid bacteria species, such as lactobacilli, was identified. Most of the isolated enterococci were resistant to gastric pH (2.0) and to 0.3% oxgall. All tested enterococci were resistant to ceftazidime,...

  17. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

    Science.gov (United States)

    Ocak, S; Sos, M L; Thomas, R K; Massion, P P

    2009-08-01

    During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

  18. Primary intraosseous smooth muscle tumor of uncertain malignant potential: original report and molecular characterization

    Directory of Open Access Journals (Sweden)

    Lauren Kropp

    2016-11-01

    Full Text Available We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive followup is warranted for this potentially life-threatening neoplasm.

  19. Primary Intraosseous Smooth Muscle Tumor of Uncertain Malignant Potential: Original Report and Molecular Characterization.

    Science.gov (United States)

    Kropp, Lauren; Siegal, Gene P; Frampton, Garrett M; Rodriguez, Michael G; McKee, Svetlana; Conry, Robert M

    2016-11-17

    We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP) which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive follow-up is warranted for this potentially life-threatening neoplasm.

  20. Bisindolylmethane thiosemicarbazides as potential inhibitors of urease: Synthesis and molecular modeling studies.

    Science.gov (United States)

    Taha, Muhammad; Ullah, Hayat; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Muhammad Naseem; Rahim, Fazal; Ahmat, Norizan; Javid, Muhammad Tariq; Ali, Muhammad; Khan, Khalid Mohammed

    2018-01-01

    Bisindolylmethane thiosemicarbazides 1-18 were synthesized, characterized by 1 H NMR and ESI MS and evaluated for urease inhibitory potential. All analogs showed outstanding urease inhibitory potentials with IC 50 values ranging between 0.14 ± 0.01 to 18.50 ± 0.90 μM when compared with the standard inhibitor thiourea having IC 50 value 21.25 ± 0.90 μM. Among the series, analog 9 (0.14 ± 0.01 μM) with di-chloro substitution on phenyl ring was identified as the most potent inhibitor of urease. The structure activity relationship has been also established on the basis of binding interactions of the active analogs. These binding interactions were identified by molecular docking studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Atomistic simulations of TeO₂-based glasses: interatomic potentials and molecular dynamics.

    Science.gov (United States)

    Gulenko, Anastasia; Masson, Olivier; Berghout, Abid; Hamani, David; Thomas, Philippe

    2014-07-21

    In this work we present for the first time empirical interatomic potentials that are able to reproduce TeO2-based systems. Using these potentials in classical molecular dynamics simulations, we obtained first results for the pure TeO2 glass structure model. The calculated pair distribution function is in good agreement with the experimental one, which indicates a realistic glass structure model. We investigated the short- and medium-range TeO2 glass structures. The local environment of the Te atom strongly varies, so that the glass structure model has a broad Q polyhedral distribution. The glass network is described as weakly connected with a large number of terminal oxygen atoms.

  2. How to combine binary collision approximation and multi-body potential for molecular dynamics

    International Nuclear Information System (INIS)

    Saito, Seiki; Nakamura, Hiroaki; Takayama, Arimichi; Ito, Atsushi M.; Kenmotsu, Takahiro

    2010-01-01

    Our group has been developing a hybrid simulation of the molecular dynamics (MD) and the binary collision approximation (BCA) simulation. One of the main problems of this hybridization model is that the multi-body potential suddenly appears at the moment when the simulation method switches from the BCA to the MD. This instantaneously emerged multi-body potential causes the acceleration or deceleration of atoms of the system. To solve this problem, the kinetic energy of atoms should be corrected to conserve the total energy in the system. This paper gives the solution. The hybrid simulation for hydrogen atom injection into a graphite material is executed in order to demonstrate the solution. (author)

  3. Explicit polarization (X-Pol) potential using ab initio molecular orbital theory and density functional theory.

    Science.gov (United States)

    Song, Lingchun; Han, Jaebeom; Lin, Yen-lin; Xie, Wangshen; Gao, Jiali

    2009-10-29

    The explicit polarization (X-Pol) method has been examined using ab initio molecular orbital theory and density functional theory. The X-Pol potential was designed to provide a novel theoretical framework for developing next-generation force fields for biomolecular simulations. Importantly, the X-Pol potential is a general method, which can be employed with any level of electronic structure theory. The present study illustrates the implementation of the X-Pol method using ab initio Hartree-Fock theory and hybrid density functional theory. The computational results are illustrated by considering a set of bimolecular complexes of small organic molecules and ions with water. The computed interaction energies and hydrogen bond geometries are in good accord with CCSD(T) calculations and B3LYP/aug-cc-pVDZ optimizations.

  4. Molecular imaging by cardiovascular MR.

    Science.gov (United States)

    Cyrus, Tillmann; Lanza, Gregory M; Wickline, Samuel A

    2007-01-01

    Do molecularly-targeted contrast agents have what it takes to usher in a paradigm shift as to how we will image cardiovascular disease in the near future? Moreover, are non-invasive vulnerable plaque detection and preemptive treatments with these novel nanoparticulate agents within reach for clinical applications? In this article, we attempt to make a compelling case for how the advent of molecularly-targeted nanoparticle technology may change the way we detect atherosclerotic lesions, determine their clinical significance and even provide non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview of the latest developments in this rapidly evolving field of so-called "intelligent" contrast agents that are able to interrogate the vascular wall and various complementary advanced imaging technologies are presented.

  5. Potential curves and spectroscopic study of the electronic states of the molecular ion LiCs+

    International Nuclear Information System (INIS)

    Moughrabi, A.; Korek, M.; Allouche, A.R.

    2004-01-01

    Full text.Due to a very accurate high-resolution techniques and to the spectacular developments in ultracold alkali atom trapping developments which are at the root of photo association spectroscopy there has been a renewed interest on the spectroscopic study of alkali dimers. The existence of new experimental data on these species has stimulated theoretical approaches, necessary to provide predictions accurate enough to be useful for interpretation and evenly for guidance of experiments. With the aim of improving the accuracy of predictions we will perform a theoretical study of the electronic structure of the molecular ion LiCs + , using a method mainly in the way by which core-valence effects are taken into account. To investigate the electronic structure of LiCs + we will use the package CIPSI (Configuration Interaction by Perturbation of a multiconfiguration wave function Selected Interactively) of the Laboratoire de Physique Quantique (Toulouse, France). The atoms Li and Cs will be treated through non-empirical effective one electron core potentials of Durand and Barthelat type. Molecular orbitals for LiCs + will be derived from Self Consistent Field Calculations (SCF) and full valence Configuration Interaction (IC) calculations. A core-core interaction more elaborated than the usual approximation 1/R will be taken into account as the sum of an exponential repulsive term plus a long range dispersion term approximated by the well known London formula. Potential energy calculations will be performed for different molecular states, for numerous values of the inter-nuclear distance R in a wide range. Spectroscopic constants have been derived for the bound states with a regular shape A ro vibrational study have been performed for the ground states with a calculation of the rotational and centrifugal distortion constants. A calculation for the transition dipole moment and matrix elements have been done for the bound states

  6. Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kandel, Saugat; Salomon-Ferrer, Romelia; Larsen, Adrien B.; Vaidehi, Nagarajan, E-mail: nvaidehi@coh.org [Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010 (United States); Jain, Abhinandan, E-mail: Abhi.Jain@jpl.nasa.gov [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, California 91109 (United States)

    2016-01-28

    The Internal Coordinate Molecular Dynamics (ICMD) method is an attractive molecular dynamics (MD) method for studying the dynamics of bonded systems such as proteins and polymers. It offers a simple venue for coarsening the dynamics model of a system at multiple hierarchical levels. For example, large scale protein dynamics can be studied using torsional dynamics, where large domains or helical structures can be treated as rigid bodies and the loops connecting them as flexible torsions. ICMD with such a dynamic model of the protein, combined with enhanced conformational sampling method such as temperature replica exchange, allows the sampling of large scale domain motion involving high energy barrier transitions. Once these large scale conformational transitions are sampled, all-torsion, or even all-atom, MD simulations can be carried out for the low energy conformations sampled via coarse grained ICMD to calculate the energetics of distinct conformations. Such hierarchical MD simulations can be carried out with standard all-atom forcefields without the need for compromising on the accuracy of the forces. Using constraints to treat bond lengths and bond angles as rigid can, however, distort the potential energy landscape of the system and reduce the number of dihedral transitions as well as conformational sampling. We present here a two-part solution to overcome such distortions of the potential energy landscape with ICMD models. To alleviate the intrinsic distortion that stems from the reduced phase space in torsional MD, we use the Fixman compensating potential. To additionally alleviate the extrinsic distortion that arises from the coupling between the dihedral angles and bond angles within a force field, we propose a hybrid ICMD method that allows the selective relaxing of bond angles. This hybrid ICMD method bridges the gap between all-atom MD and torsional MD. We demonstrate with examples that these methods together offer a solution to eliminate the potential

  7. Black Carbon (Biochar) In Water/Soil Environments: Molecular Structure, Sorption, Stability, and Potential Risk.

    Science.gov (United States)

    Lian, Fei; Xing, Baoshan

    2017-12-05

    Black carbon (BC) is ubiquitous in the environments and participates in various biogeochemical processes. Both positive and negative effects of BC (especially biochar) on the ecosystem have been identified, which are mainly derived from its diverse physicochemical properties. Nevertheless, few studies systematically examined the linkage between the evolution of BC molecular structure with the resulted BC properties, environmental functions as well as potential risk, which is critical for understanding the BC environmental behavior and utilization as a multifunctional product. Thus, this review highlights the molecular structure evolution of BC during pyrolysis and the impact of BC physicochemical properties on its sorption behavior, stability, and potential risk in terrestrial and aqueous ecosystems. Given the wide application of BC and its important role in biogeochemical processes, future research should focus on the following: (1) establishing methodology to more precisely predict and design BC properties on the basis of pyrolysis and phase transformation of biomass; (2) developing an assessment system to evaluate the long-term effect of BC on stabilization and bioavailability of contaminants, agrochemicals, and nutrient elements in soils; and (3) elucidating the interaction mechanisms of BC with plant roots, microorganisms, and soil components.

  8. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  9. Molecular identification of Lutzomyia migonei (Diptera: Psychodidae) as a potential vector for Leishmania infantum (Kinetoplastida: Trypanosomatidae).

    Science.gov (United States)

    Rodrigues, Ana Caroline Moura; Melo, Luciana Magalhães; Magalhães, Rafaela Damasceno; de Moraes, Nélio Batista; de Souza Júnior, Antônio Domingos; Bevilaqua, Claudia Maria Leal

    2016-04-15

    Visceral leishmaniasis (VL) in Brazil is caused by the protozoan Leishmania infantum. This parasite is transmitted by the bite of a female sand fly. The most important sand fly species in VL transmission is Lutzomyia longipalpis. In Fortaleza, the capital of Ceará State, Brazil, the simultaneous occurrence of Lutzomyia migonei and L. longipalpis was detected in localities where VL transmission is observed. The purpose of this study was to determine conclusively if L. migonei can be found naturally infected with L. infantum in key focus in Fortaleza. Using a CDC traps we performed phlebotomine capture during one year. External morphological features and qPCR targeting species-specific gene sequences of Lutzomyia species were used to identify the female phlebotomine sand flies. The molecular identification of the Leishmania species was performed using qPCR targeting species-specific gene sequences of L. infantum and Leishmania braziliensis. The males L. migonei abundance was higher in the rainy season. Humidity and rainfall positively correlated with males L. migonei abundance, while temperature showed a negative correlation. The correlation between the density of L. migonei female with rainfall, relative air humidity, and temperature were not statistically significant. According to the molecular data produced by qPCR amplifications, three positive sand flies were identified as L. longipalpis, and one was identified as L. migonei. The infection rate was 0.35% and 0.18%, respectively. The parasite load was 32,492±2572 L. infantum in L. migonei while the L. longipalpis had parasite loads between 2,444,964.6±116,000 and 6,287,130±124,277. Our findings confirm L. migonei as a potential vector of VL in Fortaleza at a molecular level. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Integrated network analysis reveals potentially novel molecular mechanisms and therapeutic targets of refractory epilepsies.

    Directory of Open Access Journals (Sweden)

    Hongwei Chu

    Full Text Available Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE. Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor". Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1 located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

  11. Functional and molecular imaging with MRI: potential applications in paediatric radiology

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Gallagher, Ferdia A.

    2011-01-01

    MRI is a very versatile tool for noninvasive imaging and it is particularly attractive as an imaging technique in paediatric patients given the absence of ionizing radiation. Recent advances in the field of MRI have enabled tissue function to be probed noninvasively, and increasingly MRI is being used to assess cellular and molecular processes. For example, dynamic contrast-enhanced MRI has been used to assess tissue vascularity, diffusion-weighted imaging can quantify molecular movements of water in tissue compartments and MR spectroscopy provides a quantitative assessment of metabolite levels. A number of targeted contrast agents have been developed that bind specifically to receptors on the vascular endothelium or cell surface and there are several MR methods for labelling cells and tracking cellular movements. Hyperpolarization techniques have the capability of massively increasing the sensitivity of MRI and these have been used to image tissue pH, successful response to drug treatment as well as imaging the microstructure of the lungs. Although there are many challenges to be overcome before these techniques can be translated into routine paediatric imaging, they could potentially be used to aid diagnosis, predict disease outcome, target biopsies and determine treatment response noninvasively. (orig.)

  12. An overview of potential molecular mechanisms involved in VSMC phenotypic modulation.

    Science.gov (United States)

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Yan-Qin; Wang, Xu; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-02-01

    The fully differentiated medial vascular smooth muscle cells (VSMCs) of mature vessels keep quiescent and contractile. However, VSMC can exhibit the plasticity in phenotype switching from a differentiated and contractile phenotype to a dedifferentiated state in response to alterations in local environmental cues, which is called phenotypic modulation or switching. Distinguishing from its differentiated state expressing more smooth muscle (SM)-specific/selective proteins, the phenotypic modulation in VSMC is characterized by an increased rate of proliferation, migration, synthesis of extracellular matrix proteins and decreased expression of SM contractile proteins. Although it has been well demonstrated that phenotypic modulation of VSMC contributes to the occurrence and progression of many proliferative vascular diseases, little is known about the details of the molecular mechanisms of VSMC phenotypic modulation. Growing evidence suggests that variety of molecules including microRNAs, cytokines and biochemical factors, membrane receptors, ion channels, cytoskeleton and extracellular matrix play important roles in controlling VSMC phenotype. The focus of the present review is to provide an overview of potential molecular mechanisms involved in VSMC phenotypic modulation in recent years. To clarify VSMC differentiation and phenotypic modulation mechanisms will contribute to producing cell-based therapeutic interventions for aberrant VSMC differentiation-related diseases.

  13. Estimation of Nanodiamond Surface Charge Density from Zeta Potential and Molecular Dynamics Simulations.

    Science.gov (United States)

    Ge, Zhenpeng; Wang, Yi

    2017-04-20

    Molecular dynamics simulations of nanoparticles (NPs) are increasingly used to study their interactions with various biological macromolecules. Such simulations generally require detailed knowledge of the surface composition of the NP under investigation. Even for some well-characterized nanoparticles, however, this knowledge is not always available. An example is nanodiamond, a nanoscale diamond particle with surface dominated by oxygen-containing functional groups. In this work, we explore using the harmonic restraint method developed by Venable et al., to estimate the surface charge density (σ) of nanodiamonds. Based on the Gouy-Chapman theory, we convert the experimentally determined zeta potential of a nanodiamond to an effective charge density (σ eff ), and then use the latter to estimate σ via molecular dynamics simulations. Through scanning a series of nanodiamond models, we show that the above method provides a straightforward protocol to determine the surface charge density of relatively large (> ∼100 nm) NPs. Overall, our results suggest that despite certain limitation, the above protocol can be readily employed to guide the model construction for MD simulations, which is particularly useful when only limited experimental information on the NP surface composition is available to a modeler.

  14. Molecular characterization of Giardia intestinalis haplotypes in marine animals: variation and zoonotic potential.

    Science.gov (United States)

    Lasek-Nesselquist, Erica; Bogomolni, Andrea L; Gast, Rebecca J; Welch, David Mark; Ellis, Julie C; Sogin, Mitchell L; Moore, Michael J

    2008-08-19

    Giardia intestinalis is a microbial eukaryotic parasite that causes diarrheal disease in humans and other vertebrates worldwide. The negative effect on quality of life and economics caused by G. intestinalis may be increased by its potential status as a zoonosis, or a disease that can be transmitted from animals to humans. The zoonotic potential of G. intestinalis has been implied for over 2 decades, with human-infecting genotypes (belonging to the 2 major subgroups, Assemblages A and B) occurring in wildlife and domesticated animals. There are recent reports of G. intestinalis in shellfish, seals, sea lions and whales, suggesting that marine animals are also potential reservoirs of human disease. However, the prevalence, genetic diversity and effect of G. intestinalis in marine environments and the role that marine animals play in transmission of this parasite to humans are relatively unexplored. Here, we provide the first thorough molecular characterization of G. intestinalis in marine vertebrates. Using a multi-locus sequencing approach, we identify human-infecting G. intestinalis haplotypes of both Assemblages A and B in the fecal material of dolphins, porpoises, seals, herring gulls Larus argentatus, common eiders Somateria mollissima and a thresher shark Alopias vulpinus. Our results indicate that G. intestinalis is prevalent in marine ecosystems, and a wide range of marine hosts capable of harboring zoonotic forms of this parasite exist. The presence of G. intestinalis in marine ecosystems raises concerns about how this disease might be transmitted among different host species.

  15. Tests of potential functional barriers for laminated multilayer food packages. Part I: Low molecular weight permeants.

    Science.gov (United States)

    Simal-Gándara, J; Sarria-Vidal, M; Koorevaar, A; Rijk, R

    2000-08-01

    The advent of the functional barrier concept in food packaging has brought with it a requirement for fast tests of permeation through potential barrier materials. In such tests it would be convenient for both foodstuffs and materials below the functional barrier (sub-barrier materials) to be represented by standard simulants. By means of inverse gas chromatography, liquid paraffin spiked with appropriate permeants was considered as a potential simulant of sub-barrier materials based on polypropylene (PP) or similar polyolefins. Experiments were performed to characterize the kinetics of the permeation of low molecular weight model permeants (octene, toluene and isopropanol) from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick oriented PP) into the food stimulants olive oil and 3% (w/v) acetic acid. These permeation results were interpreted in terms of three permeation kinetic models regarding the solubility of a particular model permeant in the post-barrier medium (i.e. the food simulant). The results obtained justify the development and evaluation of liquid sub-barrier simulants that would allow flexible yet rigorous testing of new laminated multilayer packaging materials.

  16. Potential of plant alkaloids as dengue ns3 protease inhibitors: Molecular docking and simulation approach

    Directory of Open Access Journals (Sweden)

    Muhammad Tahir ul Qamar

    2014-08-01

    Full Text Available Dengue infection has become a worldwide health problem and infection rate is increasing each year. Alkaloids are important phytochemicals of medicinal plant and can be used as vaccine candidates for viruses. Therefore, present study was designed to find potential alkaloids inhibitors against the Dengue virus NS2B/NS3 protease which can inhibit the viral replication inside the host cell. Through molecular docking it was investigated that most of the alkaloids bound deeply in the binding pocket of Dengue virus NS2B/NS3 protease and had potential interactions with catalytic triad. Five alkaloids (6’-desmethylthalifaboramin; 3,5-dihydroxythalifaboramine; Betanin; Reserpic acid and Tubulosine successfully blocked the catalytic triad of NS2B/NS3 protease and these alkaloids can serve as a potential drug candidate to stop viral replication. It can be concluded from this study that these alkaloids could serve as important inhibitors to inhibit the replication of DENV and need further in-vitro investigations to confirm their efficacy and drug ability.

  17. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

    Directory of Open Access Journals (Sweden)

    Dorothy Moseti

    2016-01-01

    Full Text Available Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ, and the CCAAT/enhancer binding proteins (C/EBPs such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4, adiponectin, and fatty acid synthase (FAS are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.

  18. Bacterial CRISPR Regions: General Features and their Potential for Epidemiological Molecular Typing Studies.

    Science.gov (United States)

    Karimi, Zahra; Ahmadi, Ali; Najafi, Ali; Ranjbar, Reza

    2018-01-01

    CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci as novel and applicable regions in prokaryotic genomes have gained great attraction in the post genomics era. These unique regions are diverse in number and sequence composition in different pathogenic bacteria and thereby can be a suitable candidate for molecular epidemiology and genotyping studies. Results:Furthermore, the arrayed structure of CRISPR loci (several unique repeats spaced with the variable sequence) and associated cas genes act as an active prokaryotic immune system against viral replication and conjugative elements. This property can be used as a tool for RNA editing in bioengineering studies. The aim of this review was to survey some details about the history, nature, and potential applications of CRISPR arrays in both genetic engineering and bacterial genotyping studies.

  19. Molecular Dynamics simulations of Inhibitor of Apoptosis Proteins and identification of potential small molecule inhibitors.

    Science.gov (United States)

    Jayakumar, Jayanthi; Anishetty, Sharmila

    2014-05-01

    Chemotherapeutic resistance due to over expression of Inhibitor of Apoptosis Proteins (IAPs) XIAP, survivin and livin has been observed in various cancers. In the current study, Molecular Dynamics (MD) simulations were carried out for all three IAPs and a common ligand binding scaffold was identified. Further, a novel sequence based motif specific to these IAPs was designed. SMAC is an endogenous inhibitor of IAPs. Screening of ChemBank for compounds similar to lead SMAC-non-peptidomimetics yielded a cemadotin related compound NCIMech_000654. Cemadotin is a derivative of natural anti-tumor peptide dolastatin-15; hence these compounds were docked against all three IAPs. Based on our analysis, we propose that NCIMech_000654/dolastatin-15/cemadotin derivatives may be investigated for their potential in inhibiting XIAP, survivin and livin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Ion-induced molecular emission of polymers: analytical potentialities of FTIR and mass spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Picq, V.; Balanzat, E. E-mail: balanzat@ganil.fr

    1999-05-02

    The release of small gaseous molecules is a general phenomenon of irradiated polymers. Polyethylene (PE), polypropylene (PP) and polybutene (PB) were irradiated with ions of different electronic stopping power. We show that the gas emission can provide important information on the damage process if a reliable chemical identification of the molecules released and accurate yield values are obtained. The outgassing products were analysed by two techniques: (1) by a novel set-up using a Fourier Transform Infrared (FTIR) analysis of the gas mixture released from the polymer film and (2) by residual gas analysis (RGA) with a quadrupole mass spectrometer. Comparing the analytical potentialities of both methods we come to the conclusion that the FTIR method gives a more straightforward and accurate determination of the chemical nature and of the yield of most of the released molecules. However, RGA provides complementary information on the gas release kinetics and also on the release of heavy hydrocarbon molecules and symmetric molecules like molecular hydrogen.

  1. Recent Progress Toward Hydrogen Medicine: Potential of Molecular Hydrogen for Preventive and Therapeutic Applications

    Science.gov (United States)

    Ohta, Shigeo

    2011-01-01

    Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H2) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. There are several methods to ingest or consume H2, including inhaling hydrogen gas, drinking H2-dissolved water (hydrogen water), taking a hydrogen bath, injecting H2-dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H2 by bacteria. Since the publication of the first H2 paper in Nature Medicine in 2007, the biological effects of H2 have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H2 remain elusive. PMID:21736547

  2. Status of potential PfATP6 molecular markers for artemisinin resistance in Suriname

    Directory of Open Access Journals (Sweden)

    Adhin Malti R

    2012-09-01

    Full Text Available Abstract Background Polymorphisms within the PfATP6 gene have been indicated as potential molecular markers for artemisinin efficacy. Since 2004, the use of artemisinin combination therapy (ACT was introduced as first-line treatment of the uncomplicated malaria cases in Suriname. The aim of this research was to determine changes in Suriname in the status of the polymorphic markers in the PfATP6 gene before and after the adoption of the ACT-regimen, particularly of the S769N mutation, which was reported to be associated with in vitro Artemether resistance in the neighboring country French Guiana. Methods The PfATP6 gene from Plasmodium falciparum parasites in Suriname was investigated in 28 samples using PCR amplification and restriction enzyme analysis, to assess and determine the prevalence of potentially interesting single nucleotide polymorphisms. The polymorphisms [L263E; A623E; S769N], which may be associated with the artemisinin resistant phenotype were characterized in parasites from three endemic regions before and after the adoption of the ACT-regimen. In addition, the status of these molecular markers was compared in paired P. falciparum isolates from patients with recurring malaria after controlled ACT. Results All the investigated samples exhibit the wild-type genotype at all three positions; L263, A623, S769. Conclusion All investigated isolates before and after the adoption of the ACT-regimen and independent of endemic region harbored the wild-type genotype for the three investigated polymorphisms. The study revealed that decreased artemisinin susceptibility could occur independent from PfATP6 mutations, challenging the assumption that artemisinin resistance is associated with these mutations in the PfATP6 gene.

  3. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    Science.gov (United States)

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  4. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments.

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-06-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration.

  5. Isolation, enumeration, molecular identification and probiotic potential evaluation of lactic acid bacteria isolated from sheep milk

    Directory of Open Access Journals (Sweden)

    L.B. Acurcio

    2014-06-01

    Full Text Available Lactic acid bacteria species were molecularly identified in milk from Lacaune, Santa Inês and crossbred sheep breeds and their in vitro probiotic potential was evaluated. The species identified were Enterococcus faecium (56.25%, E. durans (31.25% and E. casseliflavus (12.5%. No other lactic acid bacteria species, such as lactobacilli, was identified. Most of the isolated enterococci were resistant to gastric pH (2.0 and to 0.3% oxgall. All tested enterococci were resistant to ceftazidime, oxacillin and streptomycin and sensible to clindamycin, erythromycin and penicillin. The resistance to ciprofloxacin, gentamicin, tetracycline and vancomycin varied among tested species. All tested enterococci strongly inhibited (P<0.05 Escherichia coli and Listeria monocytogenes, moderately inhibited E. faecalis and Staphylococcus aureus and did not inhibit Pseudomonas aeruginosa, Salmonella enterica var. Typhimurium and also one E. durans sample isolated from sheep milk. Four samples of E. faecium, one of E. durans and one of E. casseliflavus presented the best probiotic potential.

  6. Molecular breeding to create optimized crops: from genetic manipulation to potential applications in plant factories

    Directory of Open Access Journals (Sweden)

    Kyoko eHiwasa-Tanase

    2016-04-01

    Full Text Available Crop cultivation in controlled environment plant factories offers great potential to stabilize the yield and quality of agricultural products. However, many crops are currently unsuited to these environments, particularly closed cultivation systems, due to space limitations, low light intensity, high implementation costs, and high energy requirements. A major barrier to closed system cultivation is the high running cost, which necessitates the use of high-margin crops for economic viability. High-value crops include those with enhanced nutritional value or containing additional functional components for pharmaceutical production or with the aim of providing health benefits. In addition, it is important to develop cultivars equipped with growth parameters that are suitable for closed cultivation. Small plant size is of particular importance due to the limited cultivation space. Other advantageous traits are short production cycle, the ability to grow under low light, and high nutriculture availability. Cost-effectiveness is improved from the use of cultivars that are specifically optimized for closed system cultivation. This review describes the features of closed cultivation systems and the potential application of molecular breeding to create crops that are optimized for cost-effectiveness and productivity in closed cultivation systems.

  7. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-01-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration. PMID:28587319

  8. Molecular Characterization of Brevibacillus laterosporus and Its Potential Use in Biological Control

    Science.gov (United States)

    de Oliveira, Edmar Justo; Rabinovitch, Leon; Monnerat, Rose Gomes; Passos, Liana Konovaloff Jannotti; Zahner, Viviane

    2004-01-01

    Thirty-three strains of Brevibacillus laterosporus, including three novel strains isolated from Brazilian soil samples, were examined for genetic variability by the use of different PCR-based methods. Molecular markers that could characterize bacterial strains with regards to their pathogenic potential were investigated. In addition, toxicity was assessed by the use of insects belonging to the orders Lepidoptera and Coleoptera and the mollusk Biomphalaria glabrata. Among the targets tested, Biomphalaria glabrata demonstrated the highest degree of sensitivity to B. laterosporus, with some strains inducing 90 to 100% mortality in snails aged 3 and 12 days posteclosion. Larvae of the coleopteron Anthonomus grandis were also susceptible, presenting mortality levels of between 33 and 63%. Toxicity was also noted towards the lepidopteron Anticarsia gemmatalis. In contrast, no mortality was recorded among test populations of Tenebrio molitor or Spodoptera frugiperda. The application of intergenic transcribed spacer PCR and BOX-PCR generated 15 and 17 different genotypes, respectively. None of the molecular techniques allowed the identification of a convenient marker that was associated with any entomopathogenic phenotype. However, a 1,078-bp amplicon was detected for all strains of B. laterosporus when a primer for amplification of the BOXA1R region was used. Similarly, a 900-bp amplicon was generated from all isolates by use of the primer OPA-11 for randomly amplified polymorphic DNA analysis. These amplicons were not detected for other phenotypically related Brevibacillus species, indicating that they represent markers that are specific for B. laterosporus, which may prove useful for the isolation and identification of new strains of this species. PMID:15528531

  9. Molecular characterization, transcriptional profiling, and antibacterial potential of G-type lysozyme from seahorse (Hippocampus abdominalis).

    Science.gov (United States)

    Ko, Jiyeon; Wan, Qiang; Bathige, S D N K; Lee, Jehee

    2016-11-01

    Lysozymes are a family of enzymes that catalyze the hydrolysis of bacterial cell wall, acting as antimicrobial effectors of the innate immune system. In the present study, an ortholog of goose-type lysozyme (ShLysG) from the big-belly seahorse (Hippocampus abdominalis) was identified and characterized structurally and functionally. The full-length cDNA sequence (1213 bp) of ShLysG is comprised of an open reading frame made up of 552 bp, encoding a polypeptide of 184 amino acid (aa) with a predicted molecular mass of 20 kDa. In silico analysis of ShLysG revealed the absence of signal peptide and the presence of a characteristic bacterial soluble lytic transglycosylase (SLT) domain bearing three catalytic residues (Glu 71 , Asp 84 , and Asp 95 ) and seven N-acetyl-d-glucosamine binding sites (Glu 71 , Asp 95 , Tyr 98 , His 99 , Ile 117 , Tyr 145 , and Asn 146 ). Homology analysis demonstrated that the aa sequence of ShLysG shared 60.7-67.4% identity and 72.6-79.3% similarity with the orthologs of other teleosts. Phylogenetic analysis of ShLysG indicated a closest relationship with the ortholog from Gadus morhua. In healthy seahorse, ShLysG mRNA showed a constitutive expression in all the tissues examined, with the highest expression in kidney and the least expression in liver. The ShLysG mRNA levels were also shown significant elevation upon the bacterial and pathogen-associated molecular pattern (PAMPs) challenges. Furthermore, lytic activities of ShLysG recombinant protein were detected against several Gram-negative and Gram-positive bacterial species. Taken together, these results suggest that ShLysG might possess a potential immune defensive role against invading microbial pathogens in seahorse. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Mapping the Diffusion Potential of a Reconstructed Au(111) Surface at Nanometer Scale with 2D Molecular Gas

    International Nuclear Information System (INIS)

    Yan Shi-Chao; Xie Nan; Gong Hui-Qi; Guo Yang; Shan Xin-Yan; Lu Xing-Hua; Sun Qian

    2012-01-01

    The adsorption and diffusion behaviors of benzene molecules on an Au(111) surface are investigated by low-temperature scanning tunneling microscopy. A herringbone surface reconstruction of the Au(111) surface is imaged with atomic resolution, and significantly different behaviors are observed for benzene molecules adsorbed on step edges and terraces. The electric field induced modification in the molecular diffusion potential is revealed with a 2D molecular gas model, and a new method is developed to map the diffusion potential over the reconstructed Au(111) surface at the nanometer scale. (condensed matter: structure, mechanical and thermal properties)

  11. Enzymatic depolymerization of gum tragacanth: bifidogenic potential of low molecular weight oligosaccharides.

    Science.gov (United States)

    Gavlighi, Hassan Ahmadi; Michalak, Malwina; Meyer, Anne S; Mikkelsen, J Dalgaard

    2013-02-13

    Gum tragacanth derived from the plant "goat's horn" (Astragalus sp.) has a long history of use as a stabilizing, viscosity-enhancing agent in food emulsions. The gum contains pectinaceous arabinogalactans and fucose-substituted xylogalacturonans. In this work, gum tragacanth from Astragalus gossypinus was enzymatically depolymerized using Aspergillus niger pectinases (Pectinex BE Color). The enzymatically degraded products were divided into three molecular weight fractions via membrane separation: HAG1 10 kDa. Compositional and linkage analyses showed that these three fractions also varied with respect to composition and structural elements: HAG1 and HAG2 were enriched in arabinose, galactose, and galacturonic acid, but low in fucose and xylose, whereas HAG3 was high in (terminal) xylose, fucose, and 1,4-bonded galacturonic acid, but low in arabinose and galactose content. The growth-stimulating potential of the three enzymatically produced gum tragacanth fractions was evaluated via growth assessment on seven different probiotic strains in single-culture fermentations on Bifidobacterium longum subsp. longum (two strains), B. longum subsp. infantis (three strains), Lactobacillus acidophilus , B. lactis, and on one pathogenic strain of Clostridium perfringens . The fractions HAG1 and HAG2 consistently promoted higher growth of the probiotic strains than HAG3, especially of the three B. longum subsp. infantis strains, and the growth promotion on HAG1 and HAG2 was better than that on galactan (control). HAG3 completely inhibited the growth of the C. perfringens strain. Tragacanth gum is thus a potential source of prebiotic carbohydrates that exert no viscosity effects and which may find use as natural functional food ingredients.

  12. First principles molecular dynamics of metal/water interfaces under bias potential

    Science.gov (United States)

    Pedroza, Luana; Brandimarte, Pedro; Rocha, Alexandre; Fernandez-Serra, Marivi

    2014-03-01

    Understanding the interaction of the water-metal system at an atomic level is extremely important in electrocatalysts for fuel cells, photocatalysis among other systems. The question of the interface energetics involves a detailed study of the nature of the interactions between water-water and water-substrate. A first principles description of all components of the system is the most appropriate methodology in order to advance understanding of electrochemically processes. In this work we describe, using first principles molecular dynamics simulations, the dynamics of a combined surface(Au and Pd)/water system both in the presence and absence of an external bias potential applied to the electrodes, as one would come across in electrochemistry. This is accomplished using a combination of density functional theory (DFT) and non-equilibrium Green's functions methods (NEGF), thus accounting for the fact that one is dealing with an out-of-equilibrium open system, with and without van der Waals interactions. DOE Early Career Award No. DE-SC0003871.

  13. Molecular dynamics simulation of nano-indentation of (111) cubic boron nitride with optimized Tersoff potential

    International Nuclear Information System (INIS)

    Zhao, Yinbo; Peng, Xianghe; Fu, Tao; Huang, Cheng; Feng, Chao; Yin, Deqiang; Wang, Zhongchang

    2016-01-01

    Highlights: • We optimize Tersoff potential to simulate the cBN better under nanoidentation. • Dislocations slip more easily along and directions on the {111} plane. • Shuffle-set dislocation slip along direction on {111} plane first. • A tetrahedron structure is found in the initial stage of the indentation. - Abstract: We conduct molecular dynamics simulation of nanoindentation on (111) surface of cubic boron nitride and find that shuffle-set dislocations slip along direction on {111} plane at the initial stage of the indentation. The shuffle-set dislocations are then found to meet together, forming surfaces of a tetrahedron. We also find that the surfaces are stacking-fault zones, which intersect with each other, forming edges of stair-rod dislocations along direction. Moreover, we also calculate the generalized stacking fault (GSF) energies along various gliding directions on several planes and find that the GSF energies of the {111} and {111} systems are relatively smaller, indicating that dislocations slip more easily along and directions on the {111} plane.

  14. Molecular dynamics simulation of nano-indentation of (111) cubic boron nitride with optimized Tersoff potential

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yinbo [College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Peng, Xianghe, E-mail: xhpeng@cqu.edu.cn [College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044 (China); Fu, Tao; Huang, Cheng; Feng, Chao [College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Yin, Deqiang [School of Manufacturing Science and Engineering, Sichuan University, Chengdu 610065 (China); Wang, Zhongchang, E-mail: zcwang@wpi-aimr.tohoku.ac.jp [College of Aerospace Engineering, Chongqing University, Chongqing 400044 (China); Advanced Institute for Materials Research, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan)

    2016-09-30

    Highlights: • We optimize Tersoff potential to simulate the cBN better under nanoidentation. • Dislocations slip more easily along <110> and <112> directions on the {111} plane. • Shuffle-set dislocation slip along <112> direction on {111} plane first. • A tetrahedron structure is found in the initial stage of the indentation. - Abstract: We conduct molecular dynamics simulation of nanoindentation on (111) surface of cubic boron nitride and find that shuffle-set dislocations slip along <112> direction on {111} plane at the initial stage of the indentation. The shuffle-set dislocations are then found to meet together, forming surfaces of a tetrahedron. We also find that the surfaces are stacking-fault zones, which intersect with each other, forming edges of stair-rod dislocations along <110> direction. Moreover, we also calculate the generalized stacking fault (GSF) energies along various gliding directions on several planes and find that the GSF energies of the <112>{111} and <110>{111} systems are relatively smaller, indicating that dislocations slip more easily along <110> and <112> directions on the {111} plane.

  15. Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents

    Directory of Open Access Journals (Sweden)

    Mukesh C. Sharma

    2014-01-01

    Full Text Available A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r2=0.8499, q2=0.8267, and pred_r2=0.7729 with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN method for molecular field analysis (MFA have cross-validated coefficient q2 value of 0.7663 and predicted r2 value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity.

  16. Potential applications of luminescent molecular rotors in food science and engineering.

    Science.gov (United States)

    Alhassawi, Fatemah M; Corradini, Maria G; Rogers, Michael A; Ludescher, Richard D

    2017-06-29

    Fluorescent molecular rotors (MRs) are compounds whose emission is modulated by segmental mobility; photoexcitation generates a locally excited (LE), planar state that can relax either by radiative decay (emission of a photon) or by formation of a twisted intramolecular charge transfer (TICT) state that can relax nonradiatively due to internal rotation. If the local environment around the probe allows for rapid internal rotation in the excited state, fast non-radiative decay can either effectively quench the fluorescence or generate a second, red-shifted emission band. Conversely, any environmental restriction to twisting in the excited state due to free volume, crowding or viscosity, slows rotational relaxation and promotes fluorescence emission from the LE state. The environmental sensitivity of MRs has been exploited extensively in biological applications to sense microviscosity in biofluids, the stability and physical state of biomembranes, and conformational changes in macromolecules. The application of MRs in food research, however, has been only marginally explored. In this review, we summarize the main characteristics of fluorescent MRs, their current applications in biological research and their current and potential applications as sensors of physical properties in food science and engineering.

  17. Sequence-Related Amplified Polymorphism (SRAP Markers: A Potential Resource for Studies in Plant Molecular Biology

    Directory of Open Access Journals (Sweden)

    Daniel W. H. Robarts

    2014-07-01

    Full Text Available In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR, random-amplified polymorphic DNA (RAPD, and amplified fragment length polymorphism (AFLP to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use. highly variable marker with inherent biological significance.

  18. Molecular heterogeneity in major urinary proteins of Mus musculus subspecies: potential candidates involved in speciation

    Science.gov (United States)

    Hurst, Jane L.; Beynon, Robert J.; Armstrong, Stuart D.; Davidson, Amanda J.; Roberts, Sarah A.; Gómez-Baena, Guadalupe; Smadja, Carole M.; Ganem, Guila

    2017-01-01

    When hybridisation carries a cost, natural selection is predicted to favour evolution of traits that allow assortative mating (reinforcement). Incipient speciation between the two European house mouse subspecies, Mus musculus domesticus and M.m.musculus, sharing a hybrid zone, provides an opportunity to understand evolution of assortative mating at a molecular level. Mouse urine odours allow subspecific mate discrimination, with assortative preferences evident in the hybrid zone but not in allopatry. Here we assess the potential of MUPs (major urinary proteins) as candidates for signal divergence by comparing MUP expression in urine samples from the Danish hybrid zone border (contact) and from allopatric populations. Mass spectrometric characterisation identified novel MUPs in both subspecies involving mostly new combinations of amino acid changes previously observed in M.m.domesticus. The subspecies expressed distinct MUP signatures, with most MUPs expressed by only one subspecies. Expression of at least eight MUPs showed significant subspecies divergence both in allopatry and contact zone. Another seven MUPs showed divergence in expression between the subspecies only in the contact zone, consistent with divergence by reinforcement. These proteins are candidates for the semiochemical barrier to hybridisation, providing an opportunity to characterise the nature and evolution of a putative species recognition signal. PMID:28337988

  19. Molecular diagnostics on the toxigenic potential of Fusarium spp. plant pathogens.

    Science.gov (United States)

    Dawidziuk, A; Koczyk, G; Popiel, D; Kaczmarek, J; Buśko, M

    2014-06-01

    We propose and test an efficient and rapid protocol for the detection of toxigenic Fusarium isolates producing three main types of Fusarium-associated mycotoxins (fumonisins, trichothecenes and zearelanone). The novel approach utilizes partially multiplexed markers based on genes essential for mycotoxin biosynthesis (fumonisin--fum6, fum8; trichothecenes--tri5, tri6; zearalenone, zea2) in Fusarium spp. The protocol has been verified by screening a collection of 96 isolates representing diverse species of filamentous fungi. Each Fusarium isolate was taxonomically identified through both molecular and morphological techniques. The results demonstrate a reliable detection of toxigenic potential for trichothecenes (sensitivity 100%, specificity 95%), zearalenone (sensitivity 100%, specificity 100%) and fumonisins (sensitivity 94%, specificity 88%). Both presence and identity of toxin biosynthetic genes were further confirmed by direct sequencing of amplification products. The cross-species-specific PCR markers for key biosynthetic genes provide a sensitive detection of toxigenic fungal isolates, contaminating biological material derived from agricultural fields. The conducted study shows that a PCR-based assay of biosynthetic genes is a reliable, cost-effective, early warning system against Fusarium contamination. Its future use as a high-throughput detection strategy complementing chemical assays enables effective targeted application of crop protection products. © 2014 The Authors. published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.

  20. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    Directory of Open Access Journals (Sweden)

    Hua Wan

    2016-01-01

    Full Text Available TAL effectors (TALEs contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE.

  1. Kohn-Sham orbitals and potentials from quantum Monte Carlo molecular densities

    International Nuclear Information System (INIS)

    Varsano, Daniele; Barborini, Matteo; Guidoni, Leonardo

    2014-01-01

    In this work we show the possibility to extract Kohn-Sham orbitals, orbital energies, and exchange correlation potentials from accurate Quantum Monte Carlo (QMC) densities for atoms (He, Be, Ne) and molecules (H 2 , Be 2 , H 2 O, and C 2 H 4 ). The Variational Monte Carlo (VMC) densities based on accurate Jastrow Antisymmetrised Geminal Power wave functions are calculated through different estimators. Using these reference densities, we extract the Kohn-Sham quantities with the method developed by Zhao, Morrison, and Parr (ZMP) [Phys. Rev. A 50, 2138 (1994)]. We compare these extracted quantities with those obtained form CISD densities and with other data reported in the literature, finding a good agreement between VMC and other high-level quantum chemistry methods. Our results demonstrate the applicability of the ZMP procedure to QMC molecular densities, that can be used for the testing and development of improved functionals and for the implementation of embedding schemes based on QMC and Density Functional Theory

  2. Transforming education in South Africa: paradigm shift or change ...

    African Journals Online (AJOL)

    The transformation of the content of the educational curriculum in South Africa is an imperative of historical justice. Though the final constitution of South Africa represents a substantive improvement on the rights condition of many South Africans, it is at the same time an impediment to transformation. This is because it is not ...

  3. [The need for a paradigm shift in radiotherapy].

    Science.gov (United States)

    Mayer, Árpád; Katona, Csilla; Farkas, Róbert; Póti, Zsuzsa

    2015-11-01

    The status and indications of radiotherapy have significantly changed in the past decade because novel techniques, radiobiological research and major advances in informatics have made better local control possible. Using supplemented marking of the target volume with computer tomography based other image-making methods adapted made it possible to define the tumor and intact surrounding tissues more precisely. With novel radiotherapy techniques the dosage of the homogenity and the covering in the target volume can be raised optimally, especially with intensity modulated arc radiotherapy (volumetric modulated arc therapy) without causing radiation injury or damage to intact surrounding tissues. Furthermore, with novel techniques and target volume marking, new indications have appeared in clinical practice and besides stereotactic radiotherapy for intracranial metastases, the extracranial so-called oligometastic conditions can be maintained close to a curative state (or in remission) for many years. Among these, perhaps the most striking is the stereotactic radiotherapy treatment of liver, lung and spinal cord metastases in one or more fractions, for which the indispensable condition is the image or respiratory guided technique.

  4. Palliative care and neurology: time for a paradigm shift.

    Science.gov (United States)

    Boersma, Isabel; Miyasaki, Janis; Kutner, Jean; Kluger, Benzi

    2014-08-05

    Palliative care is an approach to the care of patients and families facing progressive and chronic illnesses that focuses on the relief of suffering due to physical symptoms, psychosocial issues, and spiritual distress. As neurologists care for patients with chronic, progressive, life-limiting, and disabling conditions, it is important that they understand and learn to apply the principles of palliative medicine. In this article, we aim to provide a practical starting point in palliative medicine for neurologists by answering the following questions: (1) What is palliative care and what is hospice care? (2) What are the palliative care needs of neurology patients? (3) Do neurology patients have unique palliative care needs? and (4) How can palliative care be integrated into neurology practice? We cover several fundamental palliative care skills relevant to neurologists, including communication of bad news, symptom assessment and management, advance care planning, caregiver assessment, and appropriate referral to hospice and other palliative care services. We conclude by suggesting areas for future educational efforts and research. © 2014 American Academy of Neurology.

  5. Intellectual Innovation: A Paradigm Shift in Workforce Development

    Science.gov (United States)

    2016-08-01

    training courses or objectives, organizations should develop a tailored plan that focuses on what each employee needs to learn . Time and effort are...the organizations’ missions or operational requirements. Here lies the challenge. How can organizations find, develop and keep employees in this...supervisors trying to develop their respective employees so they can meet their unique workforce requirements. But employing existing technology or

  6. Ibrutinib: a paradigm shift in management of CLL.

    Science.gov (United States)

    Badar, Talha; Burger, Jan A; Wierda, William G; O'Brien, Susan

    2014-12-01

    B-cell receptor (BCR) signaling plays a vital role in B-cell malignancies; Bruton tyrosine kinase is a critical mediator of this signaling. BCR signaling, either constitutively or following antigen binding, leads to activation of several downstream pathways involved in cell survival, proliferation and migration. The efficacy observed in studies of the Bruton tyrosine kinase inhibitor, ibrutinib, confirms that BCR signaling is critical for the growth of B-cell malignancies. Ibrutinib characteristically induces redistribution of malignant B cells from tissues into the peripheral blood and rapid resolution of adenopathy. Furthermore, ibrutinib therapy results in normalization of lymphocyte counts and improvement in cytopenias. Ibrutinib has been shown to have an excellent safety profile and does not cause myelosuppression. Early data from combination studies of ibrutinib with anti-CD20 monoclonal antibodies have shown more rapid responses compared to those seen with ibrutinib monotherapy. Current data strongly support continued clinical evaluation of ibrutinib in B-cell malignancies.

  7. Turkey and the European Union: Will the Paradigm Shift?

    National Research Council Canada - National Science Library

    Henderson, Alonzo

    1996-01-01

    .... Most significant among these are increased exposure to Greek-Turkish issues, Turkish economic strength in areas of little interest to Europe, and an exploding population which is expected to surpass Germany's by 2010...

  8. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria

    OpenAIRE

    Nicolle, Lindsay E.

    2016-01-01

    Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequenc...

  9. Addressing shipboard cultural diversity: A paradigm shift required to ...

    African Journals Online (AJOL)

    The past few decades have witnessed a tremendous technological and social transformation on board ships and with it some very significant operational challenges. Much of the social challenges have been the result of a new maritime workforce that has now become largely much more culturally diverse than ever.

  10. Higher Education Transformation: A Paradigm Shift in South Africa ...

    African Journals Online (AJOL)

    South Africa\\'s higher education system is struggling to become a socially relevant ivory tower: that is, a university system that pays close attention to its calling of research while staying linked to the existential and political struggles of the people, the primary stakeholders in the system. Africa Insight Vol.34(2/3) 2004: 65-72 ...

  11. Paradigm Shift in HIV Testing; Getting Along or Getting Behind ...

    African Journals Online (AJOL)

    In the last twenty five years, the Human Immunodeficiency Virus (HIV), the causative organism of the Acquired Immune Deficiency Syndrome (AIDS) has assumed a frontline position worldwide in health discourse. In the early days of the characterization of the clinical spectrum caused by infection with this virus, screening ...

  12. Paradigm shifts in medical education: implications for medical/health ...

    African Journals Online (AJOL)

    Contemporary health and medical education in the present information dispensation must actively engage healthcare providers in opportunities for knowledge seeking, learning to learn, and motivation to continue learning. The favored pedagogical design to achieve this is Problem-Based Learning (PBL) enhanced with the ...

  13. Diagnosis, staging and control of hypertension – the paradigm shift ...

    African Journals Online (AJOL)

    Hypertension is an important medical and public health issue affecting one billion people worldwide and accounting for approximately 7.1 million deaths per year. The relative importance of systolic blood pressure (SBP) and diastolic blood pressure (DBP) has been a subject of much debate since the introduction of ...

  14. Engineering Biomaterials to Integrate and Heal: The Biocompatibility Paradigm Shifts

    Science.gov (United States)

    Bryers, James D.; Giachelli, Cecilia M.; Ratner, Buddy D.

    2012-01-01

    This article focuses on one of the major failure routes of implanted medical devices, the foreign body reaction (FBR)—that is, the phagocytic attack and encapsulation by the body of the so-called “biocompatible” biomaterials comprising the devices. We then review strategies currently under development that might lead to biomaterial constructs that will harmoniously heal and integrate into the body. We discuss in detail emerging strategies to inhibit the FBR by engineering biomaterials that elicit more biologically pertinent responses. PMID:22592568

  15. Paradigm shift: efficient and cost effective real-time nutritional ...

    African Journals Online (AJOL)

    African Journal of Food, Agriculture, Nutrition and Development ... the assessment of nutritional status and growth monitoring for individuals and at population level. ... water, sanitation, maternal and child health data in the smartphone platform.

  16. Educational Paradigm Shift: Are We Ready to Adopt MOOC?

    OpenAIRE

    Jayakumar Sadhasivam

    2014-01-01

    This paper summarizes the findings from an empirical study carry out the online learning. The impact of information technology in our day-to-day life has been profound. Among many cross disciplines that have been enriched (or benefited) by information technology, educational media is not an exception. MOOC (Massive Open Online Courses brings learning, teaching and assessment. MOOC is a Web-based distance-learning program that is designed for the participation of large numbers of geographicall...

  17. Educational Paradigm Shift: Are We Ready to Adopt MOOC?

    Directory of Open Access Journals (Sweden)

    Jayakumar Sadhasivam

    2014-06-01

    Full Text Available This paper summarizes the findings from an empirical study carry out the online learning. The impact of information technology in our day-to-day life has been profound. Among many cross disciplines that have been enriched (or benefited by information technology, educational media is not an exception. MOOC (Massive Open Online Courses brings learning, teaching and assessment. MOOC is a Web-based distance-learning program that is designed for the participation of large numbers of geographically dispersed students. In addition, Google and other companies are involving to design and fund to low-cost eLearning. Niche market provides nine certification courses via MOOC, to satisfy the employees specific needs. However, in the present day context the opinion on embracing MOOC by an University has been quite debatable. Addressing this debate on both sides, this papers presents the opinion expressed by the stakeholders in education towards embracing MOOC. Based on the findings from the study, the paper will discuss the challenge and broad concerns applicable to eLearning. The survey is focused on providing a consolidated fact that based on penetration of eLearning. This paper is aimed at providing a solid analysis of eLearning with the help of IT infrastructure in India. The survey contains demographic distribution of faculties; student and system administrator ratio is 39.6. Among a total of 792 of 2000 participants. It is focused that eLearning strategy in India.

  18. Developmental psychopathology: a paradigm shift or just a relabeling?

    Science.gov (United States)

    Rutter, Michael

    2013-11-01

    Developmental psychopathology is described as a conceptual approach that involves a set of research methods that capitalize on developmental and psychopathological variations to ask questions about mechanisms and processes. Achievements are described in relation to attachment and attachment disorders, autism, schizophrenia, childhood antecedents of adult psychopathology, testing for environmental mediation of risk effects, gene-environment interplay, intellectual and language functioning, effects of mentally ill parents on the children, stress and vulnerability to depression, ethnicity and schizophrenia, and drug response. Continuities and discontinuities over the course of development are discussed in relation to attention-deficit/hyperactivity disorder, antisocial behavior, eating disorders, substance abuse and dependency, pharmacological and behavioral addictions, and a range of other disorders. Research challenges are considered in relation to spectrum concepts, the adolescent development of a female preponderance for depression, the mechanisms involved in age differences in response to drugs and to lateralized brain injury, the processing of experiences, the biological embedding of experiences, individual differences in response to environmental hazards, nature-nurture integration, and brain plasticity.

  19. Building blocks toward contemporary trauma theory: Ferenczi 's paradigm shift.

    Science.gov (United States)

    Mészáros, Judit

    2010-12-01

    In laying down the building blocks of contemporary trauma theory, Ferenczi asserted that trauma is founded on real events and that it occurs in the interpersonal and intersubjective dynamics of object relations. He stressed the significance of the presence or lack of a trusted person in the post-traumatic situation. After the trauma, the loneliness and later the isolation of the victim represent a serious pathogenic source. In the traumatic situation, the victim and the persecutor/aggressor operate differing ego defense mechanisms. Ferenczi was the first to describe the ego defense mechanism of identification with the aggressor. Ferenczi pointed out the characteristic features of the role of analyst/therapist with which (s)he may assist the patient in working through the trauma, among them being the development of a therapeutic atmosphere based on trust, so that the traumatic experiences can be relived, without which effective therapeutic change cannot be achieved. For the analyst, countertransference, as part of authentic communication, is incorporated into the therapeutic process. These are the key building blocks that are laid down by Ferenczi in his writings and appear in later works on trauma theory.

  20. Paradigm Shift Additive Manufacturing and the New Way of War

    Science.gov (United States)

    2016-12-01

    the DoD must actively pivot away from the acquisition, logis- tics, sustainment and contracting practices developed from more than 100 years of...replenished during the duration of the operation, and returned to the warehouse at the end of operation. Pivoting to AM’s New Paradigm Contrast conventional...program managers and even operators. No amount of computer based training, PowerPoint presentations, and white papers will convey the digital

  1. Weight Science: Evaluating the Evidence for a Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Aphramor Lucy

    2011-01-01

    Full Text Available Abstract Current guidelines recommend that "overweight" and "obese" individuals lose weight through engaging in lifestyle modification involving diet, exercise and other behavior change. This approach reliably induces short term weight loss, but the majority of individuals are unable to maintain weight loss over the long term and do not achieve the putative benefits of improved morbidity and mortality. Concern has arisen that this weight focus is not only ineffective at producing thinner, healthier bodies, but may also have unintended consequences, contributing to food and body preoccupation, repeated cycles of weight loss and regain, distraction from other personal health goals and wider health determinants, reduced self-esteem, eating disorders, other health decrement, and weight stigmatization and discrimination. This concern has drawn increased attention to the ethical implications of recommending treatment that may be ineffective or damaging. A growing trans-disciplinary movement called Health at Every Size (HAES challenges the value of promoting weight loss and dieting behavior and argues for a shift in focus to weight-neutral outcomes. Randomized controlled clinical trials indicate that a HAES approach is associated with statistically and clinically relevant improvements in physiological measures (e.g., blood pressure, blood lipids, health behaviors (e.g., eating and activity habits, dietary quality, and psychosocial outcomes (such as self-esteem and body image, and that HAES achieves these health outcomes more successfully than weight loss treatment and without the contraindications associated with a weight focus. This paper evaluates the evidence and rationale that justifies shifting the health care paradigm from a conventional weight focus to HAES.

  2. Paradigm Shift in the Management of the Atrophic Posterior Maxilla

    Directory of Open Access Journals (Sweden)

    Rabah Nedir

    2014-01-01

    Full Text Available When the posterior maxilla is atrophic, the reference standard of care would be to perform sinus augmentation with an autologous bone graft through the lateral approach and delayed implant placement. However, placement of short implants with the osteotome sinus floor elevation technique and without graft can be proposed for an efficient treatment of clinical cases with a maxillary residual bone height of 4 to 8 mm. The use of grafting material is recommended only when the residual bone height is ≤4 mm. Indications of the lateral sinus floor elevation are limited to cases with a residual bone height ≤ 2 mm and fused corticals, uncompleted healing of the edentulous site, and absence of flat cortical bone crest or when the patient wishes to wear a removable prosthesis during the healing period. The presented case report illustrates osteotome sinus floor elevation with and without grafting and simultaneous implant placement in extreme conditions: atrophic maxilla, short implant placement, reduced healing time, and single crown rehabilitation. After 6 years, all placed implants were functional with an endosinus bone gain.

  3. Health Paradigm Shifts in the 20th Century

    Directory of Open Access Journals (Sweden)

    Jose Miguel DeAngulo

    2015-01-01

    Full Text Available The application of systems theory and the study of complexity to medicine and human health allows for a more comprehensive understanding and a more holistic view of what it means to be human. Such application overcomes the limitations of the traditional, fragmented understanding of phenomena and problems based on the mechanistic or Newtonian worldview. It recognizes that phenomena are interrelated, and that individual parts cannot be understood by only focusing on the analysis of their individual qualities. Rather, the individual parts can only be understood in relation to the whole and by being analyzed in the context of their interaction with the whole. The door is opened to previously unimagined models of thinking.In the 20th Century there have been shifts in the paradigms that have governed medicine and human health in the modern western world. There has been a shift from the focus on specific biological analysis and pathological diagnostics to complex human interactions with the environment and with sociopolitical and economic processes. There are complex models of systems in immunology, in neuroscience, and in genetics, as well as complex ways of understanding interactions as in epidemic modeling, in social media technologies, socioeconomic factors, and artificial intelligence.In this paper we describe three paradigms of the health-disease process that in some degree correspond to the historical development of modern medicine and healthcare over the previous century. The oldest paradigm focused on specific disease mechanisms and treatment. This gave way to paradigms that historically were broader and more inclusive, such as “international health”. The international health paradigm focused primarily on the control of epidemics across national borders and considered government as the only health actor. However, this perspective has come to be seen as excessively reductionist and excluded many critical components essential to a robust understanding. The old “international health” has in turn been replaced by the paradigm of “global health” that exercises more comprehensive claims, and paved the way for emerging paradigms of complexity in the 21st Century.

  4. A radical paradigm shift for a new definition of architecture

    Directory of Open Access Journals (Sweden)

    Alessio Erioli

    2015-11-01

    Full Text Available Architecture is facing a period of great challenges and possibilities, typical of all crises. In such periods, the paradigms we have taken for granted so far are the same ones that generated the crisis, therefore they should undergo a critical revision and new modes of thought and operation (driven by computation can be actively explored and pursued. Instead of retreating to intellectual “safe houses”, architecture should open itself up to and be restructured by the accelerated pace of change imposed by reality, renouncing obsolete methods of anticipating and exerting control and welcoming a more proactive behaviour. It is therefore of primary importance to promote the exercise of projective imagination.

  5. Research Methodologies Explored for a Paradigm Shift in University Teaching.

    Science.gov (United States)

    Venter, I. M.; Blignaut, R. J.; Stoltz, D.

    2001-01-01

    Innovative teaching methods such as collaborative learning, teamwork, and mind maps were introduced to teach computer science and statistics courses at a South African university. Soft systems methodology was adapted and used to manage the research process of evaluating the effectiveness of the teaching methods. This research method provided proof…

  6. A paradigm shift in organisational safety culture evaluation and training

    OpenAIRE

    Cram, Robert; Sime, Julie-Ann

    2015-01-01

    The focus of this research is to explore the issues surrounding traditional approaches towards understanding the safety culture of an organisation operating in a high risk environment and to identify an effective technique to educate corporate management in how to measure and evaluate the underlying safety culture of their own organisations. The results of the first part of the research highlight the concerns being expressed by both academic and industrial communities that current safety cult...

  7. Paradigm shift: contribution of field epidemiology training in ...

    African Journals Online (AJOL)

    The occurrence of major zoonotic disease outbreaks in Sub-Saharan Africa has had a significant impact on the already constrained public health systems. This has, as a result, justified the need to identify creative strategies to address threats from emerging and re-emerging infectious diseases at the ...

  8. BBB disruption with unfocused ultrasound alone-A paradigm shift

    Science.gov (United States)

    Kyle, Al

    2012-10-01

    One paradigm for ultrasound-enabled blood brain barrier disruption uses image guided focused ultrasound and preformed microbubble agents to enable drug delivery to the brain. We propose an alternative approach: unguided, unfocused ultrasound with no adjunctive agent. Compared with the focused approach, the proposed method affects a larger region of the brain, and is aimed at treatment of regional neurological disease including glioblastoma multiforme (GBM). Avoidance of image guidance and focusing reduces cost for equipment and staff training. Avoidance of adjunctive agents also lowers cost and is enabled by a longer exposure time. Since 2004, our group has worked with two animal models, three investigators in four laboratories to safely deliver five compounds, increasing the concentration of large molecule markers in brain tissue two fold or more. Safety and effectiveness data for four studies have been presented at the Ultrasound Industry Association meetings in 2007 and 2010. This paper describes new safety and effectiveness results for a fifth study. We present evidence of delivery of large molecules - including Avastin-to the brains of a large animal model correlated with acoustic pressure, and summarize the advantages and disadvantages of this novel approach.

  9. Tissue engineering skin: a paradigm shift in wound care.

    Science.gov (United States)

    Mason, C

    2005-12-01

    Tissue-engineered skin for the treatment of burns and ulcers is a clinical success, but making it commercially viable is more problematic. This article examines the industry, its techniques and suggests the way forward.

  10. The design & delivery of quality services: A paradigm shift

    Directory of Open Access Journals (Sweden)

    D. B.H. Smith

    2002-12-01

    Full Text Available As result of the increasingly important role information technology (IT is playing in service provision, less person-to-person contact will in future be made during service provision. Highly skilled specialists will make the remaining contact. Emphasis will shift to speed of delivery, with logistics playing an important role. The designers of services must take these factors into account if they wish to design quality services.

  11. Leadership Style Paradigm Shift and Organisational Performance: A ...

    African Journals Online (AJOL)

    Mrs Afam

    which leadership approach suits best their organization. Given this ... leadership styles in business organisations ((Boehunke, Bontis, Distefano and. Distefano ..... adjust their leadership styles to the situational circumstances as well as the people .... leadership style on organisational performance: A survey of selected small.

  12. Work-Engaged Learning: Towards a Paradigm Shift in Assessment

    Science.gov (United States)

    Yorke, Mantz

    2011-01-01

    Student engagement with the world of work or voluntary service has become increasingly prominent in higher education curricula as nations and states seek competitive advantage for their economies. Developments in assessment have lagged behind developments in curricula. It is argued that the incorporation of work-engaged learning into curricula…

  13. A Paradigm shift in the concept for making dental impressions

    OpenAIRE

    Nayar, Sanjna; Mahadevan, R.

    2015-01-01

    Digital dental impression is a revolutionary technological advancement that so surpasses the accuracy and efficiency of former techniques for obtaining replicas of prepared teeth for the purpose of fabricating restorations that its adoption by dentists is rapidly eclipsing the use of elastomeric impression materials. The ultimate goals of dentists dedicated to quality restorative dentistry are to make their treatment of patients as accurate, stressless, and efficient as possible. By eliminati...

  14. A Paradigm shift in the concept for making dental impressions.

    Science.gov (United States)

    Nayar, Sanjna; Mahadevan, R

    2015-04-01

    Digital dental impression is a revolutionary technological advancement that so surpasses the accuracy and efficiency of former techniques for obtaining replicas of prepared teeth for the purpose of fabricating restorations that its adoption by dentists is rapidly eclipsing the use of elastomeric impression materials. The ultimate goals of dentists dedicated to quality restorative dentistry are to make their treatment of patients as accurate, stressless, and efficient as possible. By elimination of the everyday problems described above, there is no question that the significant advantages of digital impressions will make intraoral digital scanning standard procedure in most dental offices within the next several years. Furthermore, digital impressions have proven to reduce remakes and returns, as well as increase overall efficiency. The patient also benefits by being provided a far more positive experience. Finally, through the use of digital impression making, it has been determined that laboratory products become more consistent and require less chair time at insertion.

  15. A Paradigm shift in the concept for making dental impressions

    Directory of Open Access Journals (Sweden)

    Sanjna Nayar

    2015-01-01

    Full Text Available Digital dental impression is a revolutionary technological advancement that so surpasses the accuracy and efficiency of former techniques for obtaining replicas of prepared teeth for the purpose of fabricating restorations that its adoption by dentists is rapidly eclipsing the use of elastomeric impression materials. The ultimate goals of dentists dedicated to quality restorative dentistry are to make their treatment of patients as accurate, stressless, and efficient as possible. By elimination of the everyday problems described above, there is no question that the significant advantages of digital impressions will make intraoral digital scanning standard procedure in most dental offices within the next several years. Furthermore, digital impressions have proven to reduce remakes and returns, as well as increase overall efficiency. The patient also benefits by being provided a far more positive experience. Finally, through the use of digital impression making, it has been determined that laboratory products become more consistent and require less chair time at insertion.

  16. Municipal resilience: A paradigm shift in emergency and continuity management.

    Science.gov (United States)

    Solecki, Greg; Luchia, Mike

    More than a decade of emergency and continuity management vision was instrumental in providing the unprecedented level of response and recovery from the great flood of 2013. Earlier assessments, planning and validation promulgated development of corporate continuity, emergency and contingency plans along with tactical, strategic and recovery operations centres that all led to a reliable emergency management model that will continue to provide the backbone for municipal resilience.

  17. Towards a Paradigm Shift in Educational Research: A Case of ...

    African Journals Online (AJOL)

    The postcolonial theory paradigm guided the study. The article reviews literature on the postcolonial theory with the objective of illustrating how this research paradigm may be employed in the field of education in a postcolonial context. The origin, purpose and relevance of the postcolonial theory are brought to the fore as ...

  18. e-Teaching in pediatric cardiology: A paradigm shift.

    Science.gov (United States)

    Maheshwari, Sunita; Zheleva, Bistra; Rajasekhar, Veeralakshmi; Batra, Bipin

    2015-01-01

    Training of postgraduate students has traditionally been done in person in a hospital setting with hands-on training with each faculty member imparting knowledge to 2 to 4 students per year. Supplementing their practical education with online instruction could make a significant difference in standardizing pediatric cardiology education in India. To present the rationale, methods and survey results of a live e-Teaching methodology implemented for Pediatric cardiology trainees in association with the National Board of Examinations, India. Between March 2010 and March 2014, 310 e-classes were conducted in the Pediatric cardiac sciences by 24 e-teachers. Content of the e-Learning program was based on a 2-year pediatric cardiology curriculum and included twice-weekly live online video training sessions, a library of recorded sessions and online test quizzes for the students. A total of 231 students accessed the program at various times over the 4-year period. In our study, requests for access to the e-lectures increased from 10/year the first year to 100/year by the fourth year with feedback surveys conveying a high satisfaction level from the students and a high need for this knowledge. The advantages of virtual live e-Learning included the fact that one teacher can teach multiple students in multiple geographic locations at the same time, obviating the issue of quality teacher shortage and the same content can be disseminated to all students undergoing specialist training so there is a national consensus on diagnostic and management approach among all trainees. Additionally, the e-classes can be recorded and replayed so they can be viewed repeatedly by the same group or new trainees. This is the first sustained use of e-Teaching in a medical super-specialty in India. We believe that e-Teaching is an innovative solution that can be applied, not just to Pediatric Cardiology as we have done, but to all branches of specialist and super-specialist medical training in India and globally.

  19. Career Management Paradigm Shift: Prosperity for Citizens, Windfalls for Governments.

    Science.gov (United States)

    Jarvis, Philip S.

    The knowledge economy is changing the way people work. New labor market entrants can expect to experience a succession of jobs in a number of industry sectors during their working lives. They may have concurrent part-time jobs at one time, and no paid work at other times. Work periods will be interspersed with periods of learning, either full- or…

  20. The 'Turn to Parenting': Paradigm shift or work in progress?

    NARCIS (Netherlands)

    Hopman, M.; Knijn, G.C.M.

    In the field of child and youth support, preventive and parent-oriented support programs are currently emphasized. This is understood as a new paradigm of parenting support, which is sometimes referred to as “the turn to parenting.” Using Campbell’s (Annual Review of Sociology, 28:21–38, 2002),

  1. From Power to Empowerment: A Paradigm Shift in Leadership

    Science.gov (United States)

    Dambe, M.; Moorad, F.

    2008-01-01

    This article argues that there has been a clear shift in leadership approaches from those where the leader is in control and commanding i.e., power-based leadership to one where there is empowerment. Here the power comes from the followers and is shared. Burns concepts of transactional and transformational leadership are used interchangeably with…

  2. [On the influence of local molecular environment on the redox potential of electron transfer cofactors in bacterial photosynthetic reaction centers].

    Science.gov (United States)

    Krasil'nikov, P M; Noks, P P; Rubin, A B

    2011-01-01

    The addition of cryosolvents (glycerol, dimethylsulfoxide) to a water solution containing bacterial photosynthetic reaction centers changes the redox potential of the bacteriochlorophyll dimer, but does not affect the redox potential of the quinone primary acceptor. It has been shown that the change in redox potential can be produced by changes of the electrostatic interactions between cofactors and the local molecular environment modified by additives entered into the solution. The degree of influence of a solvent on the redox potential of various cofactors is determined by degree of availability of these cofactors for molecules of solvent, which depends on the arrangement of cofactors in the structure of reaction centers.

  3. Osmotic Pressure of Aqueous Electrolyte Solutions via Molecular Simulations of Chemical Potentials: Application to NaCl.

    Czech Academy of Sciences Publication Activity Database

    Smith, W.R.; Moučka, F.; Nezbeda, Ivo

    2016-01-01

    Roč. 407, Sl (2016), s. 76-83 ISSN 0378-3812 Grant - others:NSERC(CA) OGP1041 Institutional support: RVO:67985858 Keywords : osmotic pressure * chemical potential * molecular simulation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.473, year: 2016

  4. NGX6 gene mediated by promoter methylation as a potential molecular marker in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Shen Shourong

    2010-04-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma associated gene 6 (NGX6 is down-regulated in most colon cancer cell lines and tumor tissues when compared with their normal tissue samples. As a novel suppress tumor gene, it could inhibit colon cancer cell growth and cell cycle progression. However, little is known about the transcriptional mechanisms controlling NGX6 gene expression. Recent findings suggest that epigenetic inactivation of multiple tumor suppressor genes plays an important role in the tumorigenesis of colorectal carcinoma (CRC. In this study, we explored the role of DNA methylation in regulation of NGX6 transcription. Methods In the present study, we cloned the NGX6 promoter with characteristics of a CpG island by luciferase reporter assay. Then, the CpG methylation status around the NGX6 promoter region in colon cancer cell lines and colorectal tumor tissues was examined by methylation-specific PCR and bisulfite DNA sequencing. Finally, 5-Aza-2'-deoxycytidine (5-Aza-dC treatment was used to confirm the correlation between NGX6 promoter methylation and its gene inactivation. Results The sequence spanning positions -157 to +276 was identified as the NGX6 promoter, in which no canonical TATA boxes were found, while two CAAT boxes and GC boxes were discovered. Methylation status was observed more frequently in 40 colorectal cancer samples than in 40 adjacent normal mucosa samples (18/40 versus 7/40; P Conclusions Down-regulation of NGX6 gene is related to the promoter methylation. DNA methylation of NGX6 promoter might be a potential molecular marker for diagnosis or prognosis, or serve as a therapeutic target.

  5. Molecular characteristics and virulence potential of Listeria monocytogenes isolates from Chinese food systems.

    Science.gov (United States)

    Chen, Jianshun; Luo, Xiaokai; Jiang, Lingli; Jin, Peijie; Wei, Wei; Liu, Dongyou; Fang, Weihuan

    2009-02-01

    In this study, we examined Listeria monocytogenes isolates from Chinese food sources in an attempt to gain further insights on the molecular characteristics and virulence potential of this important foodborne pathogen. Of the 88 L. monocytogenes food isolates recovered, 42 (47.7%) were of serovars 1/2a or 3a; 23 (26.1%) of serovars 1/2b or 3b; 15 (17.0%) of 1/2c or 3c; 6 (6.8%) of serovars 4b, 4d or 4e; and 2 (2.2%) of serovars 4a or 4c. In contrast to inlAB locus conserved in all serovars, internalin cluster between ascB and dapE varies with different serovars, with inlC2DE, inlGC2DE and inlGHE predominantly in serovars 1/2b or 4b, serovar 1/2a and serovar 1/2c. While inlF existed in all the inlGHE- and inlGC2DE-containing isolates but 17.4% of those having inlC2DE, lmo2026 existed in all the inlGHE-containing isolates but 20.0% of those bearing inlGC2DE, suggesting that inlF might have co-evolved with inlGC2DE and inlGHE while lmo2026 with inlGHE only. With the exception of serovar 4a isolate, most serovar isolates demonstrated remarkable ability to form plaques on L929 cells and produced significant mouse mortality irrespective of the internalin gene organization and whether an intact actA gene is present or not. These results indicate that majority of these food isolates may have the potential to cause human diseases if ingested via contaminated foods. Given that serovar 4b accounts for nearly half of human clinical listeriosis cases documented, the relative low proportion of serovar 4b food isolates suggests that this serovar is probably more tolerant of the adverse conditions in the host's stomach and/or more efficient in entering host cells than serovars 1/2a, 1/2b and 1/2c.

  6. Using Molecular Docking Analysis to Discovery Dregea sinensis Hemsl. Potential Mechanism of Anticancer, Antidepression, and Immunoregulation.

    Science.gov (United States)

    Liu, Xiujie; Shi, Yu; Deng, Yulin; Dai, Rongji

    2017-01-01

    Dregea sinensis Hemsl. plant of the genus Dregea volubilis (Asclepiadaceae), plays a vital role in anticancer, antidepression, and immunoregulation. Steroidal glycosides are the main constituents of this herb, which were significant biological active ingredients. The objective of this study is to recognize the mechanism of anticancer, antidepression, and immunoregulation of D. sinensis Hemsl. Seventy-two steroidal glycosides of D. sinensis Hemsl. were evaluated on the docking behavior of tumor-associated proteins (PI3K, Akt, mTOR), depression-related proteins (MAO-A, MAO-B) and immune-related proteins (tumor necrosis factor-α [TNF-α], tumor necrosis factor receptor 2 [TNFR2], interleukin-2Rα [IL-2Rα]) using Discovery Studio version 3.1 (Accelrys, San Diego, USA). The molecular docking analysis revealed that mostly steroidal glycosides of D. sinensis Hemsl. exhibited powerful interaction with the depression-related protein (MAO-A) and the immune-related proteins (TNFR2, IL-2Rα). Some ligands exhibited high binding energy for the tumor-associated proteins (PI3K, Akt, mTOR) and the immune-related protein (TNF-α), but MAO-B showed none interaction with the ligands. This study has paved better understanding of steroidal glycosides from D. sinensis Hemsl. as potential constituents to the prevention of associated cancer, depression and disorders of immunoregulation. The ligand database was consist of 72 steroidal glycosides from Dregea sinensis HemslSteroidal glycosides had the potential to dock with the tumor-associated proteins (PI3K, Akt, mTOR)Steroidal glycosides were bounded with MAO-A rather than MAO-B, accorded with the inhibitor selectivity of MAOs, can be considered as potent candidate inhibitors of MAO-A72 ligands got high interaction with TNFR2 and IL-2Rα, regard the steroidal glycoside as powerful candidate inhibitors of TNFR2 and IL-2Rα. Abbreviations used: PI3K: Phosphatidyl inositol 3-kinase; Akt: Protein kinase B; mTOR: Mammalian target of

  7. The role of binary and many-centre molecular interactions in spin crossover in the solid state. Part II. Non-ideality parameters defined via binary molecular potentials

    International Nuclear Information System (INIS)

    Koudriavtsev, A.B.; Linert, W.

    2005-01-01

    Parameters of the formalism [1-6] describing spin crossover in the solid state have been defined via molecular potentials in model systems of neutral and ionic complexes. In the first instance Lennard-Jones and electric dipole-dipole potentials have been used whereas in ionic systems Lennard-Jones and electric point-charge potentials have been used. Electric dipole-dipole interaction of neutral complexes brings about a positive excess energy controlled by the difference of electric dipole moments of HS and LS molecules. Differences of the order of Δμ = 1-2D cause an abrupt spin crossover in systems with T 1/2 = 100-150K. Magnetic coupling contributes both to the excess energy and excess entropy, however the overall effect is equivalent to a modest positive excess energy. Ionic systems in the absence of specific interactions are characterized by very small excess energies corresponding to practically linear van't Hoff plots. Detectable positive and negative excess energies in these systems may arise from interactions of ligands belonging to neighbouring complexes. The HOMO-LUMO overlap in HS-LS pairs can bring about a nontrivial variation of the shape of transition curves. Examples of regression analysis of experimental transition curves in terms of molecular potentials are given. (author)

  8. Molecular View of Cholesterol Flip-Flop and Chemical Potential in Different Membrane Environments

    NARCIS (Netherlands)

    Bennett, W. F. Drew; MacCallum, Justin L.; Hinner, Marlon J.; Marrink, Siewert J.; Tieleman, D. Peter

    2009-01-01

    The relative stability of cholesterol in cellular membranes and the thermodynamics of fluctuations from equilibrium have important consequences for sterol trafficking and lateral domain formation. We used molecular dynamics computer simulations to investigate the partitioning of cholesterol in a

  9. Nuclear Magnetic Shielding Constants from Quantum Mechanical/Molecular Mechanical Calculations Using Polarizable Embedding: Role of the Embedding Potential

    DEFF Research Database (Denmark)

    Steinmann, Casper; Olsen, Jógvan Magnus Haugaard; Kongsted, Jacob

    2014-01-01

    We present NMR shielding constants obtained through quantum mechanical/molecular mechanical (QM/MM) embedding calculations. Contrary to previous reports, we show that a relatively small QM region is sufficient, provided that a high-quality embedding potential is used. The calculated averaged NMR...... shielding constants of both acrolein and acetone solvated in water are based on a number of snapshots extracted from classical molecular dynamics simulations. We focus on the carbonyl chromophore in both molecules, which shows large solvation effects, and we study the convergence of shielding constants...

  10. A new hydrocarbon empirical potential in angle bending calculation for the molecular dynamics simulation

    Energy Technology Data Exchange (ETDEWEB)

    Ping, Tan Ai; Hoe, Yeak Su [Department of Mathematical Sciences, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor Bahru, Johor Darul Takzim (Malaysia)

    2014-07-10

    Typically, short range potential only depends on neighbouring atoms and its parameters function can be categorized into bond stretching, angle bending and bond rotation potential. In this paper, we present our work called Angle Bending (AB) potential, whereas AB potential is the extension of our previous work namely Bond Stretching (BS) potential. Basically, potential will tend to zero after truncated region, potential in specific region can be represented by different piecewise polynomial. We proposed the AB piecewise potential which is possible to solve a system involving three atoms. AB potential able to handle the potential of covalent bonds for three atoms as well as two atoms cases due to its degeneracy properties. Continuity for the piecewise polynomial has been enforced by coupling with penalty methods. There are still plenty of improvement spaces for this AB potential. The improvement for three atoms AB potential will be studied and further modified into torsional potential which are the ongoing current research.

  11. Scientific evidence contradicts findings and assumptions of Canadian Safety Panel 6: microwaves act through voltage-gated calcium channel activation to induce biological impacts at non-thermal levels, supporting a paradigm shift for microwave/lower frequency electromagnetic field action.

    Science.gov (United States)

    Pall, Martin L

    2015-01-01

    This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of action was further supported by hundreds of studies showing microwave changes in calcium fluxes and intracellular calcium [Ca2+]i signaling. The biophysical properties of VGCCs/similar channels make them particularly sensitive to low intensity, non-thermal EMF exposures. Non-thermal studies have shown that in most cases pulsed fields are more active than are non-pulsed fields and that exposures within certain intensity windows have much large biological effects than do either lower or higher intensity exposures; these are both consistent with a VGCC role but inconsistent with only a heating/thermal role. Downstream effects of VGCC activation include calcium signaling, elevated nitric oxide (NO), NO signaling, peroxynitrite, free radical formation, and oxidative stress. Downstream effects explain repeatedly reported biological responses to non-thermal exposures: oxidative stress; single and double strand breaks in cellular DNA; cancer; male and female infertility; lowered melatonin/sleep disruption; cardiac changes including tachycardia, arrhythmia, and sudden cardiac death; diverse neuropsychiatric effects including depression; and therapeutic effects. Non-VGCC non-thermal mechanisms may occur, but none have been shown to have effects in mammals. Biologically relevant safety standards can be developed through studies of cell lines/cell cultures with high levels of different VGCCs, measuring their responses to different EMF exposures. The 2014 Canadian Report by a panel of experts only recognizes thermal effects regarding safety standards for non-ionizing radiation exposures. Its position is therefore contradicted by each

  12. Molecular methods for pathogen and microbial community detection and characterization: current and potential application in diagnostic microbiology.

    Science.gov (United States)

    Sibley, Christopher D; Peirano, Gisele; Church, Deirdre L

    2012-04-01

    Clinical microbiology laboratories worldwide have historically relied on phenotypic methods (i.e., culture and biochemical tests) for detection, identification and characterization of virulence traits (e.g., antibiotic resistance genes, toxins) of human pathogens. However, limitations to implementation of molecular methods for human infectious diseases testing are being rapidly overcome allowing for the clinical evaluation and implementation of diverse technologies with expanding diagnostic capabilities. The advantages and limitation of molecular techniques including real-time polymerase chain reaction, partial or whole genome sequencing, molecular typing, microarrays, broad-range PCR and multiplexing will be discussed. Finally, terminal restriction fragment length polymorphism (T-RFLP) and deep sequencing are introduced as technologies at the clinical interface with the potential to dramatically enhance our ability to diagnose infectious diseases and better define the epidemiology and microbial ecology of a wide range of complex infections. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to Hg

    International Nuclear Information System (INIS)

    Hay, P.J.; Wadt, W.R.

    1985-01-01

    Ab initio effective core potentials (ECP's) have been generated to replace the Coulomb, exchange, and core-orthogonality effects of the chemically inert core electron in the transition metal atoms Sc to Hg. For the second and third transition series relative ECP's have been generated which also incorporate the mass--velocity and Darwin relativistic effects into the potential. The ab initio ECP's should facilitate valence electron calculations on molecules containing transition-metal atoms with accuracies approaching all-electron calculations at a fraction of the computational cost. Analytic fits to the potentials are presented for use in multicenter integral evaluation. Gaussian orbital valence basis sets are developed for the (3d,4s,4p), (4d,5s,5p), and (5d,6s,6p) orbitals of the first, second, and third transition series atoms, respectively. All-electron and valence-electron atomic excitation energies are also compared for the low-lying states of Sc--Hg, and the valence-electron calculations are found to reproduce the all-electron excitation energies (typically within a few tenths of an eV)

  14. Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications.

    Science.gov (United States)

    Reid, Michelle D; Saka, Burcu; Balci, Serdar; Goldblum, Andrew S; Adsay, N Volkan

    2014-02-01

    To summarize the most clinically and biologically relevant advances in molecular/genetic characteristics of various pancreatic neoplasms, with morphologic correlation. Whole-exome sequencing of numerous benign and malignant pancreatic tumors, along with the plethora of highly sensitive molecular studies now available for analyzing these tumors, provide mounting evidence to support the long-held belief that cancer is essentially a genetic disease. These genetic discoveries have not only helped to confirm the age-old, morphology-based classifications of pancreatic neoplasia but have shed new light on their mechanisms. Many of these molecular discoveries are currently being used in preoperative diagnosis. Mutations in KRAS, P16/CDKN2A, TP53, and SMAD4/DPC4 are commonly seen in ductal neoplasia but not in nonductal tumors; ductal adenocarcinomas with SMAD4/DPC4 loss are associated with widespread metastasis and poor prognosis. GNAS and RNF43 mutations have been discovered in most intraductal pancreatic mucinous neoplasms, providing critical molecular fingerprints for their diagnosis. Mutation in DAXX/ATRX is only seen in pancreatic neuroendocrine tumors, making it a useful potential marker in distinguishing these tumors from mimics. When combined with morphologic observations, molecular studies will increase our understanding of the pathogenesis and morphomolecular signatures associated with specific neoplasms and provide new horizons for precision medicine and targeted therapies.

  15. Molecular simulation of fluids with non-identical intermolecular potentials: Thermodynamic properties of 10-5 + 12-6 Mie potential binary mixtures

    International Nuclear Information System (INIS)

    Stiegler, Thomas; Sadus, Richard J.

    2015-01-01

    General methods for combining interactions between particles characterised by non-identical intermolecular potentials are investigated. The combination methods are tested by performing molecular dynamics simulations to determine the pressure, energy, isochoric and isobaric heat capacities, thermal expansion coefficient, isothermal compressibility, Joule-Thomson coefficient, and speed of sound of 10-5 + 12-6 Mie potential binary mixtures. In addition to the two non-identical Mie potentials, mixtures are also studied with non-identical intermolecular parameters. The combination methods are compared with results obtained by simply averaging the Mie exponents. When either the energy or size parameters are non-identical, very significant differences emerge in the thermodynamic properties predicted by the alternative combination methods. The isobaric heat capacity is the thermodynamic property that is most affected by the relative magnitude of the intermolecular potential parameters and the method for combining non-identical potentials. Either the arithmetic or geometric combination of potentials provides a simple and effective way of performing simulations involving mixtures of components characterised by non-identical intermolecular potentials, which is independent of their functional form

  16. Virtual screening for potential inhibitors of Mcl-1 conformations sampled by normal modes, molecular dynamics, and nuclear magnetic resonance

    Directory of Open Access Journals (Sweden)

    Glantz-Gashai Y

    2017-06-01

    Full Text Available Yitav Glantz-Gashai,* Tomer Meirson,* Eli Reuveni, Abraham O Samson Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel *These authors contributed equally to this work Abstract: Myeloid cell leukemia-1 (Mcl-1 is often overexpressed in human cancer and is an important target for developing antineoplastic drugs. In this study, a data set containing 2.3 million lead-like molecules and a data set of all the US Food and Drug Administration (FDA-approved drugs are virtually screened for potential Mcl-1 ligands using Protein Data Bank (PDB ID 2MHS. The potential Mcl-1 ligands are evaluated and computationally docked on to three conformation ensembles generated by normal mode analysis (NMA, molecular dynamics (MD, and nuclear magnetic resonance (NMR, respectively. The evaluated potential Mcl-1 ligands are then compared with their clinical use. Remarkably, half of the top 30 potential drugs are used clinically to treat cancer, thus partially validating our virtual screen. The partial validation also favors the idea that the other half of the top 30 potential drugs could be used in the treatment of cancer. The normal mode-, MD-, and NMR-based conformation greatly expand the conformational sampling used herein for in silico identification of potential Mcl-1 inhibitors. Keywords: virtual screening, Mcl-1, molecular dynamics, NMR, normal modes

  17. Controlling the transmission line shape of molecular t-stubs and potential thermoelectric applications

    DEFF Research Database (Denmark)

    Stadler, Robert; Markussen, Troels

    2011-01-01

    Asymmetric line shapes can occur in the transmission function describing electron transport in the vicinity of a minimum caused by quantum interference effects. Such asymmetry can be used to increase the thermoelectric efficiency of molecular junctions. So far, however, asymmetric line shapes hav...... calculations for a variety of t-stub molecules and also address their suitability for thermoelectric applications....

  18. Computational study of molecular electrostatic potential, docking and dynamics simulations of gallic acid derivatives as ABL inhibitors.

    Science.gov (United States)

    Raghi, K R; Sherin, D R; Saumya, M J; Arun, P S; Sobha, V N; Manojkumar, T K

    2018-04-05

    Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP). To investigate the inhibitory activity of Gallic acid derivatives towards the ABL receptor, we have applied molecular docking and molecular dynamics (MD) simulation approaches. A comparative study was performed using Bosutinib as the standard which is an approved CML drug acting on the same receptor. Furthermore, the novel compounds designed and reported here in were evaluated for ADME properties and the results indicate that they show acceptable pharmacokinetic properties. Accordingly these compounds are predicted to be drug like with low toxicity potential. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. The inherent dynamics of a molecular liquid: Geodesic pathways through the potential energy landscape of a liquid of linear molecules

    Science.gov (United States)

    Jacobson, Daniel; Stratt, Richard M.

    2014-05-01

    Because the geodesic pathways that a liquid follows through its potential energy landscape govern its slow, diffusive motion, we suggest that these pathways are logical candidates for the title of a liquid's "inherent dynamics." Like their namesake "inherent structures," these objects are simply features of the system's potential energy surface and thus provide views of the system's structural evolution unobstructed by thermal kinetic energy. This paper shows how these geodesic pathways can be computed for a liquid of linear molecules, allowing us to see precisely how such molecular liquids mix rotational and translational degrees of freedom into their dynamics. The ratio of translational to rotational components of the geodesic path lengths, for example, is significantly larger than would be expected on equipartition grounds, with a value that scales with the molecular aspect ratio. These and other features of the geodesics are consistent with a picture in which molecular reorientation adiabatically follows translation—molecules largely thread their way through narrow channels available in the potential energy landscape.

  20. Effect of temperature dependence of the Langmuir constant molecular pair potentials on gas hydrates formation mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Mokhtari, B.; Enayati, M. [Iranian Offshore Oil Co., Tehran (Iran, Islamic Republic of); Heidaryan, E. [Islamic Azad Univ., Tehran (Iran, Islamic Republic of). Masjidosolayman Branch

    2008-07-01

    Theoretical methods show that crystalline hydrates can form from single-phase systems consisting of both vapor water with gaseous hydrate former and liquid water with dissolved hydrate former. Two phase systems consist of both liquid water with gaseous hydrate former and with liquid hydrate former on the surface. This paper presented a Langmuir constant related model for the prediction of equilibrium pressures and cage occupancies of pure component hydrates. Intermolecular potentials were fit to quantum mechanical energies to obtain the Langmuir constants, which differed from the procedure utilized with the vdWP model. The paper described the experimental method and model calculations. This included the Fugacity model and Van der Waals and Platteeuw model. The paper also discussed pair potential of non-spherical molecules, including the multicentre (site-site) potential; Gaussian overlap potential; Lennard-Jones potential; and Kihara generalized pair potential. It was concluded that fraction of occupied cavities is a function of pair potentials between hard core and empty hydrate lattice. These pair potentials could be calculated from some model as Kihara cell potential, Gaussian potential, Lennard-Jones potential and multicentre pair potential. 49 refs., 3 figs.

  1. Development of EEM based silicon–water and silica–water wall potentials for non-reactive molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Junghan; Iype, Eldhose; Frijns, Arjan J.H.; Nedea, Silvia V.; Steenhoven, Anton A. van

    2014-07-01

    Molecular dynamics simulations of heat transfer in gases are computationally expensive when the wall molecules are explicitly modeled. To save computational time, an implicit boundary function is often used. Steele's potential has been used in studies of fluid–solid interface for a long time. In this work, the conceptual idea of Steele's potential was extended in order to simulate water–silicon and water–silica interfaces. A new wall potential model is developed by using the electronegativity-equalization method (EEM), a ReaxFF empirical force field and a non-reactive molecular dynamics package PumMa. Contact angle simulations were performed in order to validate the wall potential model. Contact angle simulations with the resulting tabulated wall potentials gave a silicon–water contact angle of 129°, a quartz–water contact angle of 0°, and a cristobalite–water contact angle of 40°, which are in reasonable agreement with experimental values.

  2. Molecular versus squared Woods-Saxon α-nucleus potentials in the 27Al(α, t)28Si reaction

    International Nuclear Information System (INIS)

    Abdullah, M N A; Das, S K; Tariq, A S B; Mahbub, M S; Mondal, A S; Uddin, M A; Basak, A K; Gupta, H M Sen; Malik, F B

    2003-01-01

    The differential cross-section of the 27 Al(α, t) 28 Si reaction for 64.5 MeV incident energy has been reanalysed in DWBA with full finite range using a squared Woods-Saxon (Michel) α-nucleus potential with the modified value of the depth parameter α = 2.0 as reported in a comment article by Michel and Reidemeister. This new value produces significant improvement in fitting the data of the reaction with its overall performance, in some cases, close to that previously observed for the molecular potential. Although the non-monotonic shallow molecular potential with a soft repulsive core and the Michel potentials produce the same quality fits to the elastic scattering and non-elastic processes, they are not phase equivalent. The two types of potential produce altogether different cross-sections, particularly at large reaction angles. The importance of the experimental cross-sections at large angles for both elastic scattering and non-elastic processes is elucidated

  3. Optical-based molecular imaging: contrast agents and potential medical applications

    International Nuclear Information System (INIS)

    Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

    2003-01-01

    Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

  4. Potential origin and formation for molecular components of humic acids in soils

    Science.gov (United States)

    Hatcher, Patrick; DiDonato, Nicole; Waggoner, Derek

    2016-04-01

    Humification is defined as the process by which plant and microbial debris are transformed in to humic substances. Proposed pathways for the formation of humic substances, include the lignin and lignin decomposition theories, the lignin-polyphenol theory as well as the melanoidin pathway. It is generally accepted that a combination of several of these pathways with some modifications may be responsible for producing humic substances. The current study examines humic acids from numerous soil samples to demonstrate their molecular composition. In addition we provide an explanation for the formation of these molecules that introduces a new perspective of the humification process. Our work utilizes advanced analytical techniques such as ESI-FTICR-MS and solid state NMR to more completely characterize humic acids at the molecular level. Methods Humic acids were extracted from soils using 0.5 M NaOH followed by treatment with a Dowex™ ion-exchange resin to remove sodium ions. Solid State 13C NMR spectra were obtained on a Bruker 400 MHz Avance II spectrometer equipped with a 4 mm solid state MAS probe. ESI-FTICR-MS analysis was conducted in the negative ion mode on a Bruker Daltonics 12 Tesla Apex Qe FTICR-MS instrument equipped with an Apollo II ESI source. Results: Soil humic acids from numerous soils were investigated in this study. The molecular formulas calculated from ultrahigh resolution mass spectra of well humified soils fall clearly into two predominant regions consisting of condensed aromatic molecules as well as high H/C, low O/C carboxyl-containing aliphatic molecules (CCAM). In contrast, the spectral data for humic acids from a poorly humified spodosol soil show a less dramatic separation of these regions, with relatively more molecular formula plotting in the lignin-like region and relatively fewer condensed aromatic molecules. From the mass spectral observations made for the humic acids, we can readily discern a relationship based on degree of

  5. Potential of luminescence based molecular animal imaging in research areas pertaining to cancer biology and therapy

    International Nuclear Information System (INIS)

    Yadav, Hansa D.; Shetake, Neena G.; Balla Murali, M.S.; Kumar, Amit; Pandey, B.N.

    2017-01-01

    Animal imaging is getting tremendous importance in biomedical research areas including drug delivery, radiobiology and cancer research. Even though, imaging techniques like CT, PET, SPECT, MRI are available for experimental animals, luminescence-based molecular imaging is still considered as crucial and common tool for biomedical laboratories due to easy handling/maintenance, cost effectiveness and various strategies available to manipulate the molecules/cells employed for imaging purposes. The Molecular Animal Imaging System available in our laboratory is being utilized for various cancer research activities including measurement of tumor growth kinetics, angiogenesis, therapeutic efficacy evaluation and metastasis studies. Moreover, the imaging system is also been used for radio-luminescence imaging based on Cherenkov radiation of radio-pharmaceuticals. (author)

  6. Efficient Exploration of Reactive Potential Energy Surfaces Using Car-Parrinello Molecular Dynamics

    OpenAIRE

    Iannuzzi, Marcella; Laio, Alessandro; Parrinello, Michele

    2003-01-01

    The possibility of observing chemical reactions in ab initio molecular dynamics runs is severely hindered by the short simulation time accessible. We propose a new method for accelerating the reaction process, based on the ideas of the extended Lagrangian and coarse-grained non-Markovian metady- namics. We demonstrate that by this method it is possible to simulate reactions involving complex atomic rearrangements and very large energy barriers in runs of a few picoseconds.

  7. Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction

    OpenAIRE

    Morino, Katsutaro; Petersen, Kitt Falk; Shulman, Gerald I.

    2006-01-01

    Recent studies using magnetic resonance spectroscopy have shown that decreased insulin-stimulated muscle glycogen synthesis due to a defect in insulin-stimulated glucose transport activity is a major factor in the pathogenesis of type 2 diabetes. The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to increases in intramyocellular lipid metabolites such as fatty acyl CoAs and diacylglycerol, which in turn activate a serine/threonine kina...

  8. Machine learning predictions of molecular properties: Accurate many-body potentials and nonlocality in chemical space

    International Nuclear Information System (INIS)

    Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; Lilienfeld, O. Anatole von; Müller, Klaus-Robert; Tkatchenko, Alexandre

    2015-01-01

    Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the 'holy grail' of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies

  9. On computing stress in polymer systems involving multi-body potentials from molecular dynamics simulation

    Science.gov (United States)

    Fu, Yao; Song, Jeong-Hoon

    2014-08-01

    Hardy stress definition has been restricted to pair potentials and embedded-atom method potentials due to the basic assumptions in the derivation of a symmetric microscopic stress tensor. Force decomposition required in the Hardy stress expression becomes obscure for multi-body potentials. In this work, we demonstrate the invariance of the Hardy stress expression for a polymer system modeled with multi-body interatomic potentials including up to four atoms interaction, by applying central force decomposition of the atomic force. The balance of momentum has been demonstrated to be valid theoretically and tested under various numerical simulation conditions. The validity of momentum conservation justifies the extension of Hardy stress expression to multi-body potential systems. Computed Hardy stress has been observed to converge to the virial stress of the system with increasing spatial averaging volume. This work provides a feasible and reliable linkage between the atomistic and continuum scales for multi-body potential systems.

  10. [Molecular-Genetic Diagnosis and Molecular-Targeted Therapy in Cancer: Challenges in the Era of Precision Medicine].

    Science.gov (United States)

    Miyachi, Hayato

    2015-10-01

    Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis.

  11. Molecular, biochemical, and morphometric characterization of Fasciola species potentially causing zoonotic disease in Egypt.

    Science.gov (United States)

    El-Rahimy, Hoda H; Mahgoub, Abeer M A; El-Gebaly, Naglaa Saad M; Mousa, Wahid M A; Antably, Abeer S A E

    2012-09-01

    Fascioliasis is an important disease caused by Fasciola hepatica and Fasciola gigantica. The distributions of both species overlap in many areas of Asia and Africa including Egypt. Fifty adult Fasciola worms were collected from livers of cattle and sheep slaughtered in abattoirs, Cairo, Egypt. They were subjected to morphological and metric assessment of external features of fresh adults, morphological and metric assessment of internal anatomy of stained mounted worms, determination of electrophorezed bands of crude adult homogenates using SDS-PAGE, and molecular characterization of species-specific DNA segments using RFLP-PCR. It was found that the correlation between conventional morphology and its morphotype was statistically significant (P value = 0.00). Using SDS-PAGE, 13 bands were detected among both genotypes of Fasciola (35.7, 33.6, 32.4, 29.3, 27.5, 26, 24.4, 23, 21.45, 19, 16.75, 12.5, and 9.1 kDa).The most prevalent bands were that with a molecular weight of 29.3, 26, and 19 kDa. Bands detected were common for both species, but protein bands could not distinguish between F. hepatica and F. gigantica. The result of PCR for the amplification of the selected 28S rDNA fragment with the designed primer set yielded 618 bp long PCR products for F. hepatica and F. gigantica. Different band patterns generated after digestion of the 618 bp segment by the enzyme AvaII obtained with F. hepatica showed segments of the length 529, 62, 27 bp, while with F. gigantica 322, 269, 27 bp bands were obtained. Genotyping revealed no equivocal results. The conventional morphological parameters for species determination of Fasciola spp. endemic in Egypt were evaluated versus protein bands characterization and genotyping. It was concluded that conventional morphological and metric assessments were not useful for differentiation between F. gigantica and F. hepatica due to extensive overlap in the relative ranges. Similar conclusion was reached concerning protein band

  12. Equilibrium Molecular Dynamics (MD Simulation Study of Thermal Conductivity of Graphene Nanoribbon: A Comparative Study on MD Potentials

    Directory of Open Access Journals (Sweden)

    Asir Intisar Khan

    2015-12-01

    Full Text Available The thermal conductivity of graphene nanoribbons (GNRs has been investigated using equilibrium molecular dynamics (EMD simulation based on Green-Kubo (GK method to compare two interatomic potentials namely optimized Tersoff and 2nd generation Reactive Empirical Bond Order (REBO. Our comparative study includes the estimation of thermal conductivity as a function of temperature, length and width of GNR for both the potentials. The thermal conductivity of graphene nanoribbon decreases with the increase of temperature. Quantum correction has been introduced for thermal conductivity as a function of temperature to include quantum effect below Debye temperature. Our results show that for temperatures up to Debye temperature, thermal conductivity increases, attains its peak and then falls off monotonically. Thermal conductivity is found to decrease with the increasing length for optimized Tersoff potential. However, thermal conductivity has been reported to increase with length using 2nd generation REBO potential for the GNRs of same size. Thermal conductivity, for the specified range of width, demonstrates an increasing trend with the increase of width for both the concerned potentials. In comparison with 2nd generation REBO potential, optimized Tersoff potential demonstrates a better modeling of thermal conductivity as well as provides a more appropriate description of phonon thermal transport in graphene nanoribbon. Such comparative study would provide a good insight for the optimization of the thermal conductivity of graphene nanoribbons under diverse conditions.

  13. Molecular Characterization and Antioxidant Potential of Three Wild Culinary-Medicinal Mushrooms from Tripura, Northeast India.

    Science.gov (United States)

    Das, Aparajita Roy; Borthakur, Madhusmita; Saha, Ajay Krishna; Joshi, Santa Ram; Das, Panna

    2017-01-01

    The aim of this study was to characterize 3 wild culinary-medicinal mushrooms using molecular tools and to analyze their antioxidant activity. Antioxidant properties were studied by evaluating free radical scavenging, reducing power, and chelating effect. The mushrooms were identified as Lentinus squarrosulus, L. tuber-regium, and Macrocybe gigantean by amplifying internal transcribed spacer regions of ribosomal DNA. The results demonstrated that the methanolic extract of M. gigantean has the highest free radical scavenging effect and chelating effect, whereas the methanolic extract of L. squarrosulus has the highest reducing power. The highest total phenol content and the most ascorbic acid were found in the M. gigantean extracts. Among the 3 mushroom extracts, M. gigantean displayed the most potent antioxidant activity. Molecular characterization using the nuclear ribosomal internal transcribed spacer region as a universal DNA marker was an effective tool in the identification and phylogenetic analysis of the studied mushrooms. The study also indicated that these wild macrofungi are rich sources of natural antioxidants.

  14. Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

    Science.gov (United States)

    Ahmed, Hanaa H; Shousha, Wafaa Gh; El-Mezayen, Hatem A; El-Toumy, Sayed A; Sayed, Alaa H; Ramadan, Aesha R

    2017-01-01

    Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (Panaplasia. Interestingly, treatment with Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.

  15. Potential toxicity of sarafloxacin to catalase: Spectroscopic, ITC and molecular docking descriptions

    Science.gov (United States)

    Cao, Zhaozhen; Liu, Rutao; Yang, Bingjun

    2013-11-01

    The interaction between sarafloxacin and catalase (CAT) was studied by fluorescence spectroscopy, UV-visible absorption spectroscopy, circular dichroism (CD) spectroscopy, isothermal titration microcalorimetry (ITC) and molecular docking method. After deducting the inner filter effect, the fluorescence of CAT was quenched regularly by different concentrations of sarafloxacin. The quenching mechanism was studied by lifetime measurement, and it was proved to be mostly due to static quenching. The formation of sarafloxacin-CAT complex alters the micro-environment of amide moieties and tryptophan (Trp) residues, reduces the α-helix content of the enzyme, changes the peripheral substituents on the porphyrin ring of heme and leads to the inhibition of the enzyme activity. Molecular docking study reveals that sarafloxacin is located between two α-helix of CAT near to Trp 182 and Trp 185 residues, which supports the experimental results and helps to have a more clear understanding about the interaction mechanism. The change in the relative position of His 74 to heme induced by the variation of secondary structure is considered to be the major reason for the reduction of CAT activity. Moreover, sarafloxacin binds into a hydrophobic area of CAT mainly through hydrophobic interactions, which is consistent with the ITC analysis.

  16. Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential.

    Science.gov (United States)

    Soeiro, Vinicius C; Melo, Karoline R T; Alves, Monique G C F; Medeiros, Mayara J C; Grilo, Maria L P M; Almeida-Lima, Jailma; Pontes, Daniel L; Costa, Leandro S; Rocha, Hugo A O

    2016-08-19

    Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis.

  17. Polyacetylenes and Cumulenes, Potential Elements for Molecular Machines and Precursors of Carbon Clusters: A Theoretical Study

    Czech Academy of Sciences Publication Activity Database

    Zahradník, Rudolf; Šroubková, Libuše

    2003-01-01

    Roč. 86, - (2003), s. 979- 1000 ISSN 0018-019X Institutional research plan: CEZ:AV0Z4040901 Keywords : polyacetylenes * cummulenes * potential elemens Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.861, year: 2003

  18. Exponential-Six Potential Scaling for the Calculation of Tree Energies in Molecular Simulations

    Czech Academy of Sciences Publication Activity Database

    Sellers, M.S.; Lísal, Martin; Brennan, J.K.

    2015-01-01

    Roč. 113, č. 1 (2015), s. 45-54 ISSN 0026-8976 R&D Projects: GA MŠk LH12020 Grant - others:US ARL(US) W911NF-10-2-0039 Institutional support: RVO:67985858 Keywords : exponential-six potential * free energy * potential scaling Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.837, year: 2015

  19. Effect of an improved molecular potential on strong-field tunneling ionization of molecules

    International Nuclear Information System (INIS)

    Zhao Songfeng; Jin Cheng; Le, Anh-Thu; Lin, C. D.

    2010-01-01

    We study the effect of one-electron model potentials on the tunneling ionization rates of molecules in strong fields. By including electron correlation using the modified Leeuwen-Baerends (LB α) model, the binding energies of outer shells of molecules are significantly improved. However, we show that the tunneling ionization rates from the LB α do not differ much from the earlier calculations [Phys. Rev. A 81, 033423 (2010)], in which the local correlation potential was neglected.

  20. Microgravity research in plant biological systems: Realizing the potential of molecular biology

    Science.gov (United States)

    Lewis, Norman G.; Ryan, Clarence A.

    1993-01-01

    The sole all-pervasive feature of the environment that has helped shape, through evolution, all life on Earth is gravity. The near weightlessness of the Space Station Freedom space environment allows gravitational effects to be essentially uncoupled, thus providing an unprecedented opportunity to manipulate, systematically dissect, study, and exploit the role of gravity in the growth and development of all life forms. New and exciting opportunities are now available to utilize molecular biological and biochemical approaches to study the effects of microgravity on living organisms. By careful experimentation, we can determine how gravity perception occurs, how the resulting signals are produced and transduced, and how or if tissue-specific differences in gene expression occur. Microgravity research can provide unique new approaches to further our basic understanding of development and metabolic processes of cells and organisms, and to further the application of this new knowledge for the betterment of humankind.

  1. Pseudo hard-sphere potential for use in continuous molecular-dynamics simulation of spherical and chain molecules.

    Science.gov (United States)

    Jover, J; Haslam, A J; Galindo, A; Jackson, G; Müller, E A

    2012-10-14

    We present a continuous pseudo-hard-sphere potential based on a cut-and-shifted Mie (generalized Lennard-Jones) potential with exponents (50, 49). Using this potential one can mimic the volumetric, structural, and dynamic properties of the discontinuous hard-sphere potential over the whole fluid range. The continuous pseudo potential has the advantage that it may be incorporated directly into off-the-shelf molecular-dynamics code, allowing the user to capitalise on existing hardware and software advances. Simulation results for the compressibility factor of the fluid and solid phases of our pseudo hard spheres are presented and compared both to the Carnahan-Starling equation of state of the fluid and published data, the differences being indistinguishable within simulation uncertainty. The specific form of the potential is employed to simulate flexible chains formed from these pseudo hard spheres at contact (pearl-necklace model) for m(c) = 4, 5, 7, 8, 16, 20, 100, 201, and 500 monomer segments. The compressibility factor of the chains per unit of monomer, m(c), approaches a limiting value at reasonably small values, m(c) theory. Simulation results are also presented for highly asymmetric mixtures of pseudo hard spheres, with diameter ratios of 3:1, 5:1, 20:1 over the whole composition range.

  2. Potentialities and limits of QSPR and molecular modeling in the design of the extraction solvents used in hydrometallurgy

    International Nuclear Information System (INIS)

    Cote, G.; Chagnes, A.

    2010-01-01

    Due to new challenges, new extraction solvents based on innovative extractants are needed in hydrometallurgy for specific tasks. Thus, the aim of the present paper is to discuss the potentialities and limits of QSPR and molecular modeling for identifying new extractants. QSPR methods may have useful applications in such a complex problem as the design of ligands for metal separation. Nevertheless, the degree of reliability of the predictions is still limited and, in the present state of the art, these techniques are likely more useful for optimization within a given family of extractants than to build in silico new reagents. The molecular modeling techniques provide binding energies between target metals and given ligands, as well as optimized chemical structures of the formed complexes. Thus, in principle, the information which can be deduced from the molecular modeling computations is richer than that provided by QSPR methods. Nevertheless, an effort should be made to establish more tangible links between the calculated binding energies and the physical parameters used by the hydrometallurgists, such as the complexation constants in aqueous phase (β MAn ) or better the extraction constants (K ex ). (author)

  3. Recent Progress in Molecular Simulation of Aqueous Electrolytes: Force Fields, Chemical Potentials and Solubility.

    Czech Academy of Sciences Publication Activity Database

    Nezbeda, Ivo; Moučka, F.; Smith, W.R.

    2016-01-01

    Roč. 114, č. 11 (2016), s. 1665-1690 ISSN 0026-8976 R&D Projects: GA ČR GA15-19542S Grant - others:NSERC(CA) OGP1041 Institutional support: RVO:67985858 Keywords : force fields * chemical potentials * aqueous electrolytes Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.870, year: 2016

  4. Molecular dynamics simulation study of the influence of the lattice atom potential function upon atom ejection processes

    International Nuclear Information System (INIS)

    Harrison, D.E. Jr.; Webb, R.P.

    1982-01-01

    A molecular dynamics simulation has been used to investigate the sensitivity of atom ejection processes from a single-crystal target to changes in the atom-atom potential function. Four functions, three constructed from the Gibson potentials with Anderman's attractive well, and a fouth specifically developed for this investigation, were investigated in the Cu/Ar/sup +/ system over a range of ion energies from 1.0 to 10.0 kev with the KSE-B ion-atom potential. Well depths and widths also were varied. The calculations were done at normal incidence on the fcc (111) crystal orientation. Computed values were compared with experimental data where they exist. Sputtering yields, multimer yield ratios, layer yield ratios, and the ejected atom energy distribution vary systematically with the parameters of the atom-atom potential function. Calculations also were done with the modified Moliere function. Yields and other properties fall exactly into the positions predicted from the Born-Mayer function analysis. Simultaneous analysis of the ejected atom energy distribution and the ion energy dependence of the sputtering yield curve provides information about the parameters of both the wall and well portions of the atom-atom potential function

  5. Optimised cut-off function for Tersoff-like potentials for a BN nanosheet: a molecular dynamics study

    International Nuclear Information System (INIS)

    Kumar, Rajesh; Rajasekaran, G; Parashar, Avinash

    2016-01-01

    In this article, molecular dynamics based simulations were carried out to study the tensile behaviour of boron nitride nanosheets (BNNSs). Four different sets of Tersoff potential parameters were used in the simulations for estimating the interatomic interactions between boron and nitrogen atoms. Modifications were incorporated in the Tersoff cut-off function to improve the accuracy of results with respect to fracture stress, fracture strain and Young’s modulus. In this study, the original cut-off function was optimised in such a way that small and large cut-off distances were made equal, and hence a single cut-off distance was used with all sets of Tersoff potential parameters. The single value of cut-off distance for the Tersoff potential was chosen after analysing the potential energy and bond forces experienced by boron and nitrogen atoms subjected to bond stretching. The simulations performed with the optimised cut-off function help in identifying the Tersoff potential parameters that reproduce the experimentally evaluated mechanical behaviour of BNNSs. (paper)

  6. Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

    Science.gov (United States)

    Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

    2015-10-01

    The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

  7. Nephrogenic Diabetes Insipidus: Essential Insights into the Molecular Background and Potential Therapies for Treatment

    Science.gov (United States)

    Rittig, Søren

    2013-01-01

    The water channel aquaporin-2 (AQP2), expressed in the kidney collecting ducts, plays a pivotal role in maintaining body water balance. The channel is regulated by the peptide hormone arginine vasopressin (AVP), which exerts its effects through the type 2 vasopressin receptor (AVPR2). Disrupted function or regulation of AQP2 or the AVPR2 results in nephrogenic diabetes insipidus (NDI), a common clinical condition of renal origin characterized by polydipsia and polyuria. Over several years, major research efforts have advanced our understanding of NDI at the genetic, cellular, molecular, and biological levels. NDI is commonly characterized as hereditary (congenital) NDI, arising from genetic mutations in the AVPR2 or AQP2; or acquired NDI, due to for exmple medical treatment or electrolyte disturbances. In this article, we provide a comprehensive overview of the genetic, cell biological, and pathophysiological causes of NDI, with emphasis on the congenital forms and the acquired forms arising from lithium and other drug therapies, acute and chronic renal failure, and disturbed levels of calcium and potassium. Additionally, we provide an overview of the exciting new treatment strategies that have been recently proposed for alleviating the symptoms of some forms of the disease and for bypassing G protein-coupled receptor signaling. PMID:23360744

  8. Molecular Targets of Nutraceuticals Derived from Dietary Spices: Potential Role in Suppression of Inflammation and Tumorigenesis

    Science.gov (United States)

    Aggarwal, Bharat B.; Van Kuiken, Michelle E.; Iyer, Laxmi H.; Harikumar, Kuzhuvelil B.; Sung, Bokyung

    2011-01-01

    Despite the fact cancer is primarily a preventable disease, recent statistics indicate cancer will become the number one killer worldwide in 2010. Since certain cancers are more prevalent in the people of some countries than others, suggests the role of lifestyle. For instance cancer incidence among people from the Indian subcontinent, where most spices are consumed, is much lower than that in the Western World. Spices have been consumed for centuries for a variety of purposes—as flavoring agents, colorants, and preservatives. However, there is increasing evidence for the importance of plant-based foods in regular diet to lowering the risk of most chronic diseases, so spices are now emerging as more than just flavor aids, but as agents that can not only prevent but may even treat disease. In this article, we discuss the role of 41 common dietary spices with over 182 spice-derived nutraceuticals for their effects against different stages of tumorigenesis. Besides suppressing inflammatory pathways, spice-derived nutraceuticals can suppress survival, proliferation, invasion, and angiogenesis of tumor cells. We discuss how spice-derived nutraceuticals mediate such diverse effects and what their molecular targets are. Overall our review suggests “adding spice to your life” may serve as a healthy and delicious way to ward off cancer and other chronic diseases. PMID:19491364

  9. Molecular effects of resistance elicitors from biological origin and their potential for crop protection

    Directory of Open Access Journals (Sweden)

    Lea eWiesel

    2014-11-01

    Full Text Available Plants contain a sophisticated innate immune network to prevent pathogenic microbes from gaining access to nutrients and from colonising internal structures. The first layer of inducible response is governed by the plant following the perception of microbe- or modified plant-derived molecules. As the perception of these molecules results in a plant response that can provide efficient resistance towards non-adapted pathogens they can also be described as ‘defence elicitors’. In compatible plant/microbe interactions, adapted microorganisms have means to avoid or disable this resistance response and promote virulence. However, this requires a detailed spatial and temporal response from the invading pathogens. In agricultural practice, treating plants with isolated defence elicitors in the absence of pathogens can promote plant resistance by uncoupling defence activation from the effects of pathogen virulence determinants. The plant responses to plant, bacterial, oomycete or fungal-derived elicitors are not, in all cases, universal and need elucidating prior to the application in agriculture. This review provides an overview of currently known elicitors of biological rather than synthetic origin and places their activity into a molecular context.

  10. Exploration of the speleotherapeutic potential through the cellular and molecular biology techniques

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-02-01

    Full Text Available Objective: Exploring the speleotherapy effects on morphology and physiology of dermal and pulmonary fibroblast obtained from Wistar rats tissue in normal conditions and after induction of experimental “astma” awareness with ovalbumin. Materials and methods: Before initiation of dermal and pulmonary fibroblast cultures, 60 of Wistar rats 75-100 g were divided into two groups: control and sensitized with ovalalbumin. 10 animals of each group were sent to Cacica and Dej salt mines and maintained in a speleotherapy regime. Another 10 animals in each group were monitored separately in INRMFB Biobase . Dermal and pulmonary fibroblast cultures were initiated by enzymatic techniques from appropriate tissue taken of each group Wistar rats. Morphological monitoring was done by phase contast microscopy; biochemical and molecular changes of cultures obtained from animals treated speleothropic compared to control, was experimental establised by electrophoresis and Western Blotting techniques.Results: Experimental data revealed the expression of several proteins after the speleotherapeutic treatment. These data were analysed compared with control, using a specific software.Conclusions: Speleotherapeutic treatment of Wistar rats caused significant differences in morphology and protein expression of dermal and pulmonary fibroblatst grown in the laboratory. These differences support the protective effects of speleotherapy compared with data obtained from animals untreated and sensitized with ovalbumin, having induced experimental asthma status.

  11. [Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

    Science.gov (United States)

    Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

    2014-01-01

    Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

  12. Glass Formation of n-Butanol: Coarse-grained Molecular Dynamics Simulations Using Gay-Berne Potential Model

    Science.gov (United States)

    Xie, Gui-long; Zhang, Yong-hong; Huang, Shi-ping

    2012-04-01

    Using coarse-grained molecular dynamics simulations based on Gay-Berne potential model, we have simulated the cooling process of liquid n-butanol. A new set of GB parameters are obtained by fitting the results of density functional theory calculations. The simulations are carried out in the range of 290-50 K with temperature decrements of 10 K. The cooling characteristics are determined on the basis of the variations of the density, the potential energy and orientational order parameter with temperature, whose slopes all show discontinuity. Both the radial distribution function curves and the second-rank orientational correlation function curves exhibit splitting in the second peak. Using the discontinuous change of these thermodynamic and structure properties, we obtain the glass transition at an estimate of temperature Tg=120±10 K, which is in good agreement with experimental results 110±1 K.

  13. Water extraction of coals - potential for estimating low molecular weight organic acids as carbon feedstock for the deep terrestrial biosphere

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, A.; Mangelsdorf, K.; Sykes, R.; Horsfield, B. [Geoforschungszentrum Potsdam, Potsdam (Germany)

    2008-08-15

    With the recent increasing interest in the deep biosphere, the question arises as to where the carbon sources that support deep microbial communities are derived from. Our research was focussed on the water-soluble, low molecular weight (LMW) organic acids that are potentially available from different sedimentary lithologies to serve as a carbon source to feed the deep biosphere. A series of Eocene-Pleistocene coals, mudstones and sandstones of varying rank (maturity) and total organic carbon (TOC) content from the Waikato Basin, New Zealand, has been Soxhlet-extracted using water. The combined concentration of recovered formate, acetate and oxalate range from 366 to 2499 {mu} g/g sediment and appear to be dependent on rank, organofacies and TOC. The yields indicate the potential of carbonaceous sediments to feed the local deep terrestrial biosphere over geological periods of time. The existence of living microbial organisms in the mudstones and sandstones was proved by the identification of intact phospholipids (PLs).

  14. Amorphization induced by chemical disorder in crystalline NiZr2: A molecular-dynamics study based on an n-body potential

    International Nuclear Information System (INIS)

    Massobrio, C.; Pontikis, V.; Martin, G.

    1989-01-01

    We present the first molecular-dynamics study of the amorphization of a crystalline alloy (NiZr 2 ) induced by chemical disorder. We used a n-body potential in conjunction with isobaric-isothermal molecular dynamics. The behavior of the pair distribution function suggests that the instability leading to the amorphous state is a first-order phase transformation

  15. Enzymatic depolymerization of gum Tragacanth: Bifidogenic potential of low molecular weight oligosaccharides

    DEFF Research Database (Denmark)

    Ahmadi Gavlighi, Hassan; Michalak, Malwina; Meyer, Anne S.

    2013-01-01

    Gum tragacanth derived from the plant “goat’s horn” (Astragalus sp.) has a long history of use as a stabilizing, viscosity-enhancing agent in food emulsions. The gum contains pectinaceous arabinogalactans and fucose-substituted xylogalacturonans. In this work, gum tragacanth from Astragalus...... and galactose content. The growth-stimulating potential of the three enzymatically produced gum tragacanth fractions was evaluated via growth assessment on seven different probiotic strains in single culture fermentations on: Bifidobacterium longum subsp. longum (2 strains), B. longum subsp. infantis (3 strains...... that on galactan (control). HAG3 completely inhibited the growth of the Cl. perfringens strain. Tragacanth gum is thus a potential source of prebiotic carbohydrates that exert no viscosity effects and which may find use as natural functional food ingredients....

  16. Molecular Methods Used for the Identification of Potentially Probiotic Lactobacillus reuteri Strains

    OpenAIRE

    Weiss, Agnes; Lettner, Hans Peter; Kramer, Walter; Mayer, Helmut Karl; Kneifel, Wolfgang

    2005-01-01

    Forty potentially probiotic Lactobacillus strains as well as reference strains of different genera were grown under standardised conditions. Cell masses were harvested and DNA was isolated. For identification, all strains were subjected to genus-specific polymerase chain reaction (PCR), and the affiliation with the genus Lactobacillus was confirmed for all isolates. Using two species-specific primer-pairs for Lactobacillus reuteri, specific amplicons were observed for eight of the forty inves...

  17. Molecular genetic improvements of cyanobacteria to enhance the industrial potential of the microbe: A review.

    Science.gov (United States)

    Johnson, Tylor J; Gibbons, Jaimie L; Gu, Liping; Zhou, Ruanbao; Gibbons, William R

    2016-11-01

    The rapid increase in worldwide population coupled with the increasing demand for fossil fuels has led to an increased urgency to develop sustainable sources of energy and chemicals from renewable resources. Using microorganisms to produce high-value chemicals and next-generation biofuels is one sustainable option and is the focus of much current research. Cyanobacteria are ideal platform organisms for chemical and biofuel production because they can be genetically engineered to produce a broad range of products directly from CO 2 , H 2 O, and sunlight, and require minimal nutrient inputs. The purpose of this review is to provide an overview on advances that have been or could be made to improve strains of cyanobacteria for industrial purposes. First, the benefits of using cyanobacteria as a platform for chemical and biofuel production are discussed. Next, an overview of cyanobacterial strain improvements by genetic engineering is provided. Finally, mutagenesis techniques to improve the industrial potential of cyanobacteria are described. Along with providing an overview on various areas of research that are currently being investigated to improve the industrial potential of cyanobacteria, this review aims to elucidate potential targets for future research involving cyanobacteria as an industrial microorganism. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1357-1371, 2016. © 2016 American Institute of Chemical Engineers.

  18. Emblica officinalis (Amla): A review for its phytochemistry, ethnomedicinal uses and medicinal potentials with respect to molecular mechanisms.

    Science.gov (United States)

    Variya, Bhavesh C; Bakrania, Anita K; Patel, Snehal S

    2016-09-01

    Medicinal plants, having great elementary and therapeutic importance, are the gift to mankind to acquire healthy lifestyle. Emblica officinalis Gaertn. or Phyllanthus emblica Linn. (Euphorbeaceae), commonly known as Indian gooseberry or Amla, has superior value in entirely indigenous traditional system of medicine, including folklore Ayurveda, for medicinal and nutritional purposes to build up lost vitality and vigor. In this article, numerous phytochemicals isolated from E. officinalis and its ethnomedical and pharmacological potentials with molecular mechanisms are briefly deliberated and recapitulated. The information documented in the present review was collected from more than 270 articles, published or accepted in the last five to six decades, and more than 20 e-books using various online database. Additional information was obtained from various botanical books and dissertations. The extracts from various parts of E. officinalis, especially fruit, contain numerous phytoconstituents viz. higher amount of polyphenols like gallic acid, ellagic acid, different tannins, minerals, vitamins, amino acids, fixed oils, and flavonoids like rutin and quercetin. The extract or plant is identified to be efficacious against diversified ailments like inflammation, cancer, osteoporosis, neurological disorders, hypertension together with lifestyle diseases, parasitic and other infectious disorders. These actions are attributed to either regulation of various molecular pathway involved in several pathophysiologies or antioxidant property which prevents the damage of cellular compartments from oxidative stress. However, serious efforts are required in systemic research to identify, isolate and evaluate the chemical constituents for nutritional and therapeutic potentials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. In vitro fermentation and prebiotic potential of novel low molecular weight polysaccharides derived from agar and alginate seaweeds.

    Science.gov (United States)

    Ramnani, Priya; Chitarrari, Roberto; Tuohy, Kieran; Grant, John; Hotchkiss, Sarah; Philp, Kevin; Campbell, Ross; Gill, Chris; Rowland, Ian

    2012-02-01

    Fermentation properties and prebiotic potential of novel low molecular weight polysaccharides (LMWPs) derived from agar and alginate bearing seaweeds was investigated. Ten LMWPs were supplemented to pH, temperature controlled anaerobic batch cultures inoculated with human feces from three donors, in triplicate. Microbiota changes were monitored using Fluorescent in-situ hybridization and short chain fatty acids, the fermentation end products were analysed using gas chromatography. Of the ten LMWPs tested, Gelidium seaweed CC2253 of molecular weight 64.64 KDa showed a significant increase in bifidobacterial populations from log(10) 8.06 at 0 h to log(10) 8.55 at 24 h (p = 0.018). For total bacterial populations, alginate powder CC2238 produced a significant increase from log(10) 9.01 at 0 h to log(10) 9.58 at 24 h (p = 0.032). No changes were observed in the other bacterial groups tested viz. Bacteroides, Lactobacilli/Enterococci, Eubacterium rectale/Clostridium coccoides and Clostridium histolyticum. The polysaccharides also showed significant increases in total SCFA production, particularly acetic and propionic acids, indicating that they were readily fermented. In conclusion, some LMWPs derived from agar and alginate bearing seaweeds were fermented by gut bacteria and exhibited potential to be used a novel source of prebiotics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures

    Science.gov (United States)

    Dugbartey, George J.; Peppone, Luke J.; de Graaf, Inge A.M.

    2017-01-01

    Cisplatin is currently one of the most widely-used chemotherapeutic agents against various malignancies. Its clinical application is limited, however, by inherent renal and cardiac toxicities and other side effects, of which the underlying mechanisms are only partly understood. Experimental studies show cisplatin generates reactive oxygen species, which impair the cell’s antioxidant defense system, causing oxidative stress and potentiating injury, thereby culminating in kidney and heart failure. Understanding the molecular mechanisms of cisplatin-induced renal and cardiac toxicities may allow clinicians to prevent or treat this problem better and may also provide a model for investigating drug-induced organ toxicity in general. This review discusses some of the major molecular mechanisms of cisplatin-induced renal and cardiac toxicities including disruption of ionic homeostasis and energy status of the cell leading to cell injury and cell death. We highlight clinical manifestations of both toxicities as well as (novel)biomarkers such as kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We also present some current treatment challenges and propose potential protective strategies with novel pharmacological compounds that might mitigate or prevent these toxicities, which include the use of hydrogen sulfide. PMID:27717837

  1. Towards a molecular basis of oligometastatic disease: potential role of micro-RNAs.

    Science.gov (United States)

    Uppal, Abhineet; Ferguson, Mark K; Posner, Mitchell C; Hellman, Samuel; Khodarev, Nikolai N; Weichselbaum, Ralph R

    2014-08-01

    Oligometastasis is a cancer disease state characterized by a limited number of metastatic tumors involving single or few organs and with biological properties that make them potentially amenable to locoregional antitumor therapy. Current clinical data show that they are potentially curable with surgical resection or/and radiotherapy. Yet, mechanisms of progression from primary tumor to oligometastasis, rather than to polymetastases, is lacking in detail. In the current review we focus on the role of micro-RNAs in the regulation of metastases development and the role they may play in the differentiation of oligometastatic from polymetastatic progression. We also discuss the analyses of metastatic samples from oligo-and polymetastatic patients, which suggest that oligometastasis is a distinct biologic entity regulated in part by micro-RNAs. In addition, a review of the known functions of oligometastatic-specific micro-RNAs suggest that they regulate multiple steps in the metastatic cascade, including epithelial-mesenchymal transition, tumor invasion, intravasation, distant vascular extravasation and proliferation in a distant organ. Understanding the role of micro-RNAs and their target genes in oligometastatic disease may allow for the development of targeted therapies to effectively conrol the spread of metastases.

  2. Preparing isolated vibrational wave packets with light-induced molecular potentials by chirped laser pulses

    Science.gov (United States)

    Vatasescu, Mihaela

    2012-05-01

    We consider a specific wave packet preparation arising from the control of tunneling in the 0g-(6s,6p3/2) double well potential of a Cs2 cold molecule with chirped laser pulses. Such a possibility to manipulate the population dynamics in the 0g-(6s,6p3/2) potential appears in a pump-dump scheme designed to form cold molecules by photoassociation of two cold cesium atoms. The initial population in the 0g-(6s,6p3/2) double well is a wave packet prepared in the outer well at large interatomic distances (94 a0) by a photoassociation step with a first chirped pulse, being a superposition of several vibrational states whose energies surround the energy of a tunneling resonance. Our present work is focused on a second delayed chirped pulse, coupling the 0g-(6s,6p3/2) surface with the a3Σu+(6s,6s) one in the zone of the double well barrier (15 a0) and creating deeply bound cold molecules in the a3Σu+(6s,6s) state. We explore the parameters choice (intensity, duration, chirp rate and sign) for this second pulse, showing that picoseconds pulses with a negative chirp can lead to trapping of population in the inner well in strongly bound vibrational states, out of the resonant tunneling able to transfer it back to the outer well.

  3. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Directory of Open Access Journals (Sweden)

    Paul Smolen

    Full Text Available Protein synthesis-dependent, late long-term potentiation (LTP and depression (LTD at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  4. Molecular constraints on synaptic tagging and maintenance of long-term potentiation: a predictive model.

    Science.gov (United States)

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

    2012-01-01

    Protein synthesis-dependent, late long-term potentiation (LTP) and depression (LTD) at glutamatergic hippocampal synapses are well characterized examples of long-term synaptic plasticity. Persistent increased activity of protein kinase M ζ (PKMζ) is thought essential for maintaining LTP. Additional spatial and temporal features that govern LTP and LTD induction are embodied in the synaptic tagging and capture (STC) and cross capture hypotheses. Only synapses that have been "tagged" by a stimulus sufficient for LTP and learning can "capture" PKMζ. A model was developed to simulate the dynamics of key molecules required for LTP and LTD. The model concisely represents relationships between tagging, capture, LTD, and LTP maintenance. The model successfully simulated LTP maintained by persistent synaptic PKMζ, STC, LTD, and cross capture, and makes testable predictions concerning the dynamics of PKMζ. The maintenance of LTP, and consequently of at least some forms of long-term memory, is predicted to require continual positive feedback in which PKMζ enhances its own synthesis only at potentiated synapses. This feedback underlies bistability in the activity of PKMζ. Second, cross capture requires the induction of LTD to induce dendritic PKMζ synthesis, although this may require tagging of a nearby synapse for LTP. The model also simulates the effects of PKMζ inhibition, and makes additional predictions for the dynamics of CaM kinases. Experiments testing the above predictions would significantly advance the understanding of memory maintenance.

  5. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Directory of Open Access Journals (Sweden)

    Monica Marzagalli

    2016-10-01

    Full Text Available Cutaneous melanoma is an aggressive tumor with its incidence increasing faster than any other cancer in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies.Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ER and ERβ that exert opposite effects on cancer growth: ER is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant estrogen receptor in melanoma and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation. However, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention

  6. Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

    Science.gov (United States)

    Marzagalli, Monica; Montagnani Marelli, Marina; Casati, Lavinia; Fontana, Fabrizio; Moretti, Roberta Manuela; Limonta, Patrizia

    2016-01-01

    Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to

  7. Analytic ab initio-based molecular interaction potential for the BrO⋅H{sub 2}O complex

    Energy Technology Data Exchange (ETDEWEB)

    Hoehn, Ross D.; Kais, Sabre [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Qatar Environment and Energy Research Institute, HBKU, Doha (Qatar); Yeole, Sachin D. [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Francisco, Joseph S., E-mail: jfrancisco3@unl.edu [Department of Chemistry, Purdue University, West Lafayette, Indiana 47907 (United States); Departments of Chemistry, University of Nebraska, Lincoln, Nebraska 68588 (United States)

    2016-05-28

    Radical halogen oxide species play important roles within atmospheric processes, specifically those responsible for the removal of O{sub 3}. To facilitate future investigations on this family of compounds, RCCSD(T)/aug-cc-pVQZ-level electronic structure calculations were employed to generate individual-molecule optimized geometries, as well as to determine the global minimum energy structure for the BrO⋅H{sub 2}O complex. This information facilitated the generation of several one-dimensional potential energy surface (PES) scans for the BrO⋅H{sub 2}O complex. Scans were performed for both the ground state and the first excited state; this inclusion is due to a low-lying first electronic excited-state energy. These rigid-geometry PES scans were used both to generate a novel analytic interaction potential by modifying the existing Thole-type model used for water and to the fitted potential function. This interaction potential features anisotropic atomic polarizabilities facilitating appropriate modeling of the physics regarding the unpaired electron residing within the p-orbitals of the oxygen atom of the bromine oxide radical. The intention of this work is to facilitate future molecular dynamics simulations involving the interaction between the BrO radical and water clusters as a first step in devising possible novel chemistries taking place at the water interface of clouds within the atmosphere.

  8. Molecular wave function and effective adiabatic potentials calculated by extended multi-configuration time-dependent Hartree-Fock method

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Tsuyoshi; Ide, Yoshihiro; Yamanouchi, Kaoru [Department of Chemistry, School of Science, The University of Tokyo, 7-3-1, Hongo Bunkyo-ku, Tokyo, 113-0033 (Japan)

    2015-12-31

    We first calculate the ground-state molecular wave function of 1D model H{sub 2} molecule by solving the coupled equations of motion formulated in the extended multi-configuration time-dependent Hartree-Fock (MCTDHF) method by the imaginary time propagation. From the comparisons with the results obtained by the Born-Huang (BH) expansion method as well as with the exact wave function, we observe that the memory size required in the extended MCTDHF method is about two orders of magnitude smaller than in the BH expansion method to achieve the same accuracy for the total energy. Second, in order to provide a theoretical means to understand dynamical behavior of the wave function, we propose to define effective adiabatic potential functions and compare them with the conventional adiabatic electronic potentials, although the notion of the adiabatic potentials is not used in the extended MCTDHF approach. From the comparison, we conclude that by calculating the effective potentials we may be able to predict the energy differences among electronic states even for a time-dependent system, e.g., time-dependent excitation energies, which would be difficult to be estimated within the BH expansion approach.

  9. Screening of Potential Lead Molecule as Novel MurE Inhibitor: Virtual Screening, Molecular Dynamics and In Vitro Studies.

    Science.gov (United States)

    Zaveri, Kunal; Kiranmayi, Patnala

    2017-01-01

    The prevalence of multi-drug resistance S. aureus is one of the most challenging tasks for the treatment of nosocomial infections. Proteins and enzymes of peptidoglycan biosynthesis pathway are one among the well-studied targets, but many of the enzymes are unexplored as targets. MurE is one such enzyme featured to be a promising target. As MurE plays an important role in ligating the L-lys to stem peptide at third position that is crucial for peptidoglycan synthesis. To screen the potential MurE inhibitor by in silico approach and evaluate the best potential lead molecule by in vitro methods. In the current study, we have employed structure based virtual screening targeting the active site of MurE, followed by Molecular dynamics and in vitro studies. Virtual screening resulted in successful screening of potential lead molecule ((2R)-2-[[1-[(2R)- 2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan). The molecular dynamics of the MurE and Lead molecule complex emphasizes that lead molecule has shown stable interactions with active site residues Asp 406 and with Glu 460. In vitro studies demonstrate that the lead molecule shows antibacterial activity close to standard antibiotic Vancomycin and higher than that of Ampicillin, Streptomycin and Rifampicin. The MIC of lead molecule at 50μg/mL was observed to be 3.75 μg/mL, MBC being bactericidal with value of 6.25 μg/mL, cytotoxicity showing 34.44% and IC50 of 40.06μg/mL. These results suggest ((2R)-2-[[1-[(2R)-2-(benzyloxycarbonylamino) propanoyl] piperidine-4-carbonyl]amino]-5-guanidino-pentan) as a promising lead molecule for developing a MurE inhibitor against treatment of S. aureus infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Born-Oppenheimer potential energy for interaction of antihydrogen with molecular hydrogen

    International Nuclear Information System (INIS)

    Strasburger, Krzysztof

    2005-01-01

    Inelastic collisions with hydrogen molecules are claimed to be an important channel of antihydrogen Hbar losses (Armour and Zeman 1999 Int. J. Quantum Chem. 74 645). In the present work, interaction energies for the H 2 -Hbar system in the ground state have been calculated within the Born-Oppenheimer approximation. The leptonic problem was solved variationally with the basis of explicitly correlated Gaussian functions. The geometry of H 2 was fixed at equilibrium geometry and the Hbar atom approached the molecule from two directions-along or perpendicularly to the bond axis. Purely attractive potential energy curve has been obtained for the first nuclear configuration, while a local maximum (lower than the energy at infinite separation) has been found for the second one

  11. Born Oppenheimer potential energy for interaction of antihydrogen with molecular hydrogen

    Science.gov (United States)

    Strasburger, Krzysztof

    2005-09-01

    Inelastic collisions with hydrogen molecules are claimed to be an important channel of antihydrogen (\\overlineH) losses (Armour and Zeman 1999 Int. J. Quantum Chem. 74 645). In the present work, interaction energies for the H_{2}\\--\\overlineH system in the ground state have been calculated within the Born-Oppenheimer approximation. The leptonic problem was solved variationally with the basis of explicitly correlated Gaussian functions. The geometry of H2 was fixed at equilibrium geometry and the \\overlineH atom approached the molecule from two directions—along or perpendicularly to the bond axis. Purely attractive potential energy curve has been obtained for the first nuclear configuration, while a local maximum (lower than the energy at infinite separation) has been found for the second one.

  12. Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological Evolution of Pregnancy

    Directory of Open Access Journals (Sweden)

    Dragos Cretoiu

    2016-01-01

    Full Text Available MicroRNAs represent nonprotein coding small RNA molecules that are very stable to degradation and responsible for gene silencing in most eukaryotic cells. Increased evidence has been accumulating over the years about their potential value as biomarkers for several diseases. MicroRNAs were predicted to be involved in nearly all biological processes from development to oncogenesis. In this review, we address the importance of circulating microRNAs in different conditions associated with pregnancy starting with the implantation period to preeclampsia and we shortly describe the correlation between placental circulating miRNAs and pregnancy status. We also discuss the importance of microRNAs in recurrent abortion and ectopic pregnancy.

  13. Molecular Methods Used for the Identification of Potentially Probiotic Lactobacillus reuteri Strains

    Directory of Open Access Journals (Sweden)

    Agnes Weiss

    2005-01-01

    Full Text Available Forty potentially probiotic Lactobacillus strains as well as reference strains of different genera were grown under standardised conditions. Cell masses were harvested and DNA was isolated. For identification, all strains were subjected to genus-specific polymerase chain reaction (PCR, and the affiliation with the genus Lactobacillus was confirmed for all isolates. Using two species-specific primer-pairs for Lactobacillus reuteri, specific amplicons were observed for eight of the forty investigated strains. For differentiation, these eight strains as well as the reference strains of the species L. reuteri and closely related species were subjected to randomly amplified polymorphic DNA (RAPD-PCR using fourteen arbitrary primers. Two selected strains as well as probiotic and common reference strains were further investigated applying pulsed field gel electrophoresis (PFGE. With the latter two methods, individual profiles were found for most strains, but no difference between probiotic and common strains could be made out.

  14. Anticancer potential of phytochemicals against breast cancer: Molecular docking and simulation approach

    Directory of Open Access Journals (Sweden)

    Bilal Ahmed

    2014-12-01

    Full Text Available Breast cancer malignancy is prevailing among the women not only from the developing countries but also from the developed one at the rate of 18% of total population worldwide. One of the main causes of breast cancer is estrogen receptor alpha. Overexpression of estrogen receptor is seen in number of cases of breast cancer. Tamoxifen was used as a reference drug in present study. Almost 80,000 species of plants are used as a source of medicines. Current study was totally based on the screening of phytochemicals to find out the biomolecules having strong bonding actions as compared to tamoxifen. Present study exhibited that 10 molecules (kushenol K, silybin, taxifolin 3-O-acetate, rosemarinic acid, secundifloran, kushenol N, kurarinol, podophyllotoxone, AC1LCW2L, leachianone G have successful and potential binding with the target molecule as compared to tamoxifen. These molecules can be used for the treatment of breast cancer and birth control.

  15. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers.

    Science.gov (United States)

    Skotland, Tore; Ekroos, Kim; Kauhanen, Dimple; Simolin, Helena; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2017-01-01

    Exosomes have recently appeared as a novel source of noninvasive cancer biomarkers, since these nanovesicles contain molecules from cancer cells and can be detected in biofluids. We have here investigated the potential use of lipids in urinary exosomes as prostate cancer biomarkers. A high-throughput mass spectrometry quantitative lipidomic analysis was performed to reveal the lipid composition of urinary exosomes in prostate cancer patients and healthy controls. Control samples were first analysed to characterise the lipidome of urinary exosomes and test the reproducibility of the method. In total, 107 lipid species were quantified in urinary exosomes. Several differences, for example, in cholesterol and phosphatidylcholine, were found between urinary exosomes and exosomes derived from cell lines, thus showing the importance of in vivo studies for biomarker analysis. The 36 most abundant lipid species in urinary exosomes were then quantified in 15 prostate cancer patients and 13 healthy controls. Interestingly, the levels of nine lipids species were found to be significantly different when the two groups were compared. The highest significance was shown for phosphatidylserine (PS) 18:1/18:1 and lactosylceramide (d18:1/16:0), the latter also showed the highest patient-to-control ratio. Furthermore, combinations of these lipid species and PS 18:0-18:2 distinguished the two groups with 93% sensitivity and 100% specificity. Finally, in agreement with the reported dysregulation of sphingolipid metabolism in cancer cells, alteration in specific sphingolipid lipid classes were observed. This study shows for the first time the potential use of exosomal lipid species in urine as prostate cancer biomarkers. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Phylogenetic Molecular Species Delimitations Unravel Potential New Species in the Pest Genus Spodoptera Guenée, 1852 (Lepidoptera, Noctuidae)

    Science.gov (United States)

    Dumas, Pascaline; Barbut, Jérôme; Le Ru, Bruno; Silvain, Jean-François; Clamens, Anne-Laure; d’Alençon, Emmanuelle; Kergoat, Gael J.

    2015-01-01

    Nowadays molecular species delimitation methods promote the identification of species boundaries within complex taxonomic groups by adopting innovative species concepts and theories (e.g. branching patterns, coalescence). As some of them can efficiently deal with large single-locus datasets, they could speed up the process of species discovery compared to more time consuming molecular methods, and benefit from the existence of large public datasets; these methods can also particularly favour scientific research and actions dealing with threatened or economically important taxa. In this study we aim to investigate and clarify the status of economically important moths species belonging to the genus Spodoptera (Lepidoptera, Noctuidae), a complex group in which previous phylogenetic analyses and integrative approaches already suggested the possible occurrence of cryptic species and taxonomic ambiguities. In this work, the effectiveness of innovative (and faster) species delimitation approaches to infer putative species boundaries has been successfully tested in Spodoptera, by processing the most comprehensive dataset (in terms of number of species and specimens) ever achieved; results are congruent and reliable, irrespective of the set of parameters and phylogenetic models applied. Our analyses confirm the existence of three potential new species clusters (for S. exigua (Hübner, 1808), S. frugiperda (J.E. Smith, 1797) and S. mauritia (Boisduval, 1833)) and support the synonymy of S. marima (Schaus, 1904) with S. ornithogalli (Guenée, 1852). They also highlight the ambiguity of the status of S. cosmiodes (Walker, 1858) and S. descoinsi Lalanne-Cassou & Silvain, 1994. This case study highlights the interest of molecular species delimitation methods as valuable tools for species discovery and to emphasize taxonomic ambiguities. PMID:25853412

  17. Phylogenetic molecular species delimitations unravel potential new species in the pest genus Spodoptera Guenée, 1852 (Lepidoptera, Noctuidae.

    Directory of Open Access Journals (Sweden)

    Pascaline Dumas

    Full Text Available Nowadays molecular species delimitation methods promote the identification of species boundaries within complex taxonomic groups by adopting innovative species concepts and theories (e.g. branching patterns, coalescence. As some of them can efficiently deal with large single-locus datasets, they could speed up the process of species discovery compared to more time consuming molecular methods, and benefit from the existence of large public datasets; these methods can also particularly favour scientific research and actions dealing with threatened or economically important taxa. In this study we aim to investigate and clarify the status of economically important moths species belonging to the genus Spodoptera (Lepidoptera, Noctuidae, a complex group in which previous phylogenetic analyses and integrative approaches already suggested the possible occurrence of cryptic species and taxonomic ambiguities. In this work, the effectiveness of innovative (and faster species delimitation approaches to infer putative species boundaries has been successfully tested in Spodoptera, by processing the most comprehensive dataset (in terms of number of species and specimens ever achieved; results are congruent and reliable, irrespective of the set of parameters and phylogenetic models applied. Our analyses confirm the existence of three potential new species clusters (for S. exigua (Hübner, 1808, S. frugiperda (J.E. Smith, 1797 and S. mauritia (Boisduval, 1833 and support the synonymy of S. marima (Schaus, 1904 with S. ornithogalli (Guenée, 1852. They also highlight the ambiguity of the status of S. cosmiodes (Walker, 1858 and S. descoinsi Lalanne-Cassou & Silvain, 1994. This case study highlights the interest of molecular species delimitation methods as valuable tools for species discovery and to emphasize taxonomic ambiguities.

  18. Molecular basis of albinism in India: evaluation of seven potential candidate genes and some new findings.

    Science.gov (United States)

    Mondal, M; Sengupta, M; Samanta, S; Sil, A; Ray, K

    2012-12-15

    Albinism represents a group of genetic disorders with a broad spectrum of hypopigmentary phenotypes dependent on the genetic background of the patients. Oculocutaneous albinism (OCA) patients have little or no pigment in their eyes, skin and hair, whereas ocular albinism (OA) primarily presents the ocular symptoms, and the skin and hair color may vary from near normal to very fair. Mutations in genes directly or indirectly regulating melanin production are responsible for different forms of albinism with overlapping clinical features. In this study, 27 albinistic individuals from 24 families were screened for causal variants by a PCR-sequencing based approach. TYR, OCA2, TYRP1, SLC45A2, SLC24A5, TYRP2 and SILV were selected as candidate genes. We identified 5 TYR and 3 OCA2 mutations, majority in homozygous state, in 8 unrelated patients including a case of autosomal recessive ocular albinism (AROA). A homozygous 4-nucleotide novel insertion in SLC24A5 was detected in a person showing with extreme cutaneous hypopigmentation. A potential causal variant was identified in the TYRP2 gene in a single patient. Haplotype analyses in the patients carrying homozygous mutations in the classical OCA genes suggested founder effect. This is the first report of an Indian AROA patient harboring a mutation in OCA2. Our results also reveal for the first time that mutations in SLC24A5 could contribute to extreme hypopigmentation in humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Molecular characterization and serodiagnostic potential of a novel dithiol glutaredoxin 1 from Echinococcus granulosus.

    Science.gov (United States)

    Song, Xingju; Yan, Min; Hu, Dandan; Wang, Yu; Wang, Ning; Gu, Xiaobin; Peng, Xuerong; Yang, Guangyou

    2016-08-17

    The larval stage of Echinococcus granulosus is the etiological agent of cystic echinococcosis (CE), which causes serious morbidity and mortality in many areas. There is no reliable method to monitor sheep CE. Here, we characterize E. granulosus glutaredoxin 1 (Eg-Grx1) and report an improved immunodiagnostic method for CE. We cloned and expressed recombinant Eg-Grx1 and generated antibodies. We analyzed the location of the protein in different parasite stages by fluorescence immunohistochemistry, detected the immunogenicity of recombinant Eg-Grx1, and developed an indirect ELISA (iELISA) for CE serodiagnosis. Eg-Grx1 is a classic dithiol Grx with several GSH-binding motifs. Native Eg-Grx1 protein was distributed in the tegument of protoscoleces, the whole germinal layer, and the parenchymatous tissue of adult worms. Recombinant Eg-Grx1 exhibited good immunoreactivity to CE-infected sheep serum. An iELISA using this antigen showed specificity of 64.3 % (9/14) and sensitivity of 1:3200, and the diagnostic accordance rate was 97.9 % (47/48) compared with the results of necropsy. We characterized a novel Grx (Eg-Grx1) from a parasitic helminth and present a comprehensive analysis of the sequence and structure of this protein. The recombinant Eg-Grx1 protein showed good potential serodiagnostic performance, and we established an iELISA method, which may contribute to the surveillance of sheep CE in epidemic areas.

  20. Pair Potential That Reproduces the Shape of Isochrones in Molecular Liquids

    DEFF Research Database (Denmark)

    Veldhorst, Arno; Schrøder, Thomas; Dyre, Jeppe C.

    2016-01-01

    -dependent function of density, h(ρ), which for real liquids is well approximated by a power law, ργ. However, in simulations, a power law is not adequate when density changes are large; typical models, such as Lennard-Jones liquids, show that γ(ρ) ≡ d ln h(ρ)/d ln ρ is a decreasing function of density. This article...... presents results from computer simulations using a new pair potential that diverges at a nonzero distance and can be tuned to give a more realistic shape of γ(ρ). Our results indicate that the finite size of molecules is an important factor to take into account when modeling liquids over a large density......Many liquids have curves (isomorphs) in their phase diagrams along which structure, dynamics, and some thermodynamic quantities are invariant in reduced units. A substantial part of their phase diagrams is thus effectively one dimensional. The shapes of these isomorphs are described by a material...

  1. Serological, molecular detection and potential risk factors associated with camel brucellosis in Pakistan.

    Science.gov (United States)

    Fatima, Sana; Khan, Iahtasham; Nasir, Amar; Younus, Muhammad; Saqib, Muhammad; Melzer, Falk; Neubauer, Heinrich; El-Adawy, Hosny

    2016-12-01

    Brucellosis is one of the most important zoonoses in developing countries and was considered the most widespread zoonosis in the world. Brucellosis was reported in camels and has been reported from all camel-keeping countries.The present study was performed in three districts (Jhang, Chiniot, and Bhakkar) of Punjab province of Pakistan. A total of 200 camel (Camelus bactrianus) sera were collected using random and multistage cluster sampling from different areas. Fifty samples were collected from one organized governmental farm. One hundred fifty samples were collected randomly from nomadic/pastoral production systems. All sera were tested with Rose Bengal plate agglutination test (RBPT) and confirmed by ELISA. Genomic DNA was extracted from all serum samples and tested by real-time PCR. Various potential risk factors (season, rearing with other animals, and abortion or orchitis history) recorded through questionnaires were statistically analyzed by Chi-square test.In total, 5 % of investigated sera were positive by RBPT. Only 2 % of the camel sera were CELISA positive. Brucella abortus DNA was detected in 1.5 % of the investigated animals. Season, rearing of camels with other ruminants, abortion, and orchitis history were found to be statistically significant (p brucellosis is a zoonotic disease in the Pakistani Punjab with various risk factors maintaining and perpetuating its spread. Therefore, there is a need for implementing control measures and raising public health awareness in prevention of brucellosis in Pakistan.

  2. Molecular detection of toxigenic potential of fungi in peanut samples collected in retail shops in Maringá/PR, Brazil

    Directory of Open Access Journals (Sweden)

    Alessandra Valéria de Oliveira

    2015-02-01

    Full Text Available Many foods are susceptible to fungal contamination. Grains, such as peanuts, are commonly affected, with consequences including compromised integrity and infeasibility for human and animal consumption. Furthermore, some fungi may pose a health risk, largely due the production of mycotoxins. Among these, aflatoxins produced by Aspergillus flavus and A. parasiticus produce various carcinogenic, teratogenic, immunosuppressive, hepatotoxic and nephrotoxic effects. Molecular techniques have been used to identify and distinguish fungal species in foods. The objective of this study was molecular detection of Aspergillus species in peanut samples collected in stores in Maringá-PR, by amplification of fungal genetic material with specific primers for the intergenic spacer aflR-aflJ and later cutting with restriction enzymes. Of the 50 peanut samples analyzed, 27 were positive for the intergenic spacer aflR-aflJ, seven of which were identified as Aspergillus flavus. Our results demonstrate that peanuts sold in retail stores in this region have potential for contamination with toxigenic fungi.

  3. An update on potential molecular mechanisms underlying the actions of snake venom L-amino acid oxidases (LAAOs).

    Science.gov (United States)

    Paloschi, Mauro Valentino; Pontes, Adriana Silva; Soares, Andreimar Martins; Zuliani, Juliana Pavan

    2017-11-08

    LAAOs (EC 1.4.3.2) are found in concentrations that vary according to each species of snakes; Viperidae, Crotalidae and Elapidae contain 1-9% of this enzyme in their venoms. This review focuses on an update on molecular mechanisms, platelet activities, antimicrobial, antiprotozoal, induction of apoptosis and inflammatory potential underlying the actions of SV-LAAOs. Snake venom LAAOs (SV-LAAOs) have become an interesting subject for pharmacological, structural and molecular studies. Although the mechanisms of action of these enzymes are not well understood they are a subject of a variety of studies, because LAAOs are multifunctional enzymes exhibiting a wide range of pharmacological effects, including the inhibition or induction of platelet aggregation, hemolysis and hemorrhage, in addition to the stimulation of apoptosis, the activation of leukocytes and the formation of edema. Moreover, SV-LAAOs play an important role in bactericidal, cytotoxic, anti-parasitic, anti-tumor, and antiviral activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

    Directory of Open Access Journals (Sweden)

    Hasan Kweder

    2015-01-01

    Full Text Available Subacute Sclerosing Panencephalitis (SSPE, a rare lethal disease of children and young adults due to persistence of measles virus (MeV in the brain, is caused by wild type (wt MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23 that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.

  5. Comprehensive Transcriptome Study to Develop Molecular Resources of the Copepod Calanus sinicus for Their Potential Ecological Applications

    Science.gov (United States)

    Yang, Qing; Sun, Fanyue; Yang, Zhi; Li, Hongjun

    2014-01-01

    Calanus sinicus Brodsky (Copepoda, Crustacea) is a dominant zooplanktonic species widely distributed in the margin seas of the Northwest Pacific Ocean. In this study, we utilized an RNA-Seq-based approach to develop molecular resources for C. sinicus. Adult samples were sequenced using the Illumina HiSeq 2000 platform. The sequencing data generated 69,751 contigs from 58.9 million filtered reads. The assembled contigs had an average length of 928.8 bp. Gene annotation allowed the identification of 43,417 unigene hits against the NCBI database. Gene ontology (GO) and KEGG pathway mapping analysis revealed various functional genes related to diverse biological functions and processes. Transcripts potentially involved in stress response and lipid metabolism were identified among these genes. Furthermore, 4,871 microsatellites and 110,137 single nucleotide polymorphisms (SNPs) were identified in the C. sinicus transcriptome sequences. SNP validation by the melting temperature (T m)-shift method suggested that 16 primer pairs amplified target products and showed biallelic polymorphism among 30 individuals. The present work demonstrates the power of Illumina-based RNA-Seq for the rapid development of molecular resources in nonmodel species. The validated SNP set from our study is currently being utilized in an ongoing ecological analysis to support a future study of C. sinicus population genetics. PMID:24982883

  6. Molecular simulation of CO chemisorption on Co(0001) in presence of supercritical fluid solvent: A potential of mean force study

    Energy Technology Data Exchange (ETDEWEB)

    Asiaee, Alireza; Benjamin, Kenneth M., E-mail: kenneth.benjamin@sdsmt.edu [Department of Chemical and Biological Engineering, South Dakota School of Mines and Technology, 501 E. Saint Joseph St., Rapid City, South Dakota 57701 (United States)

    2016-08-28

    For several decades, heterogeneous catalytic processes have been improved through utilizing supercritical fluids (SCFs) as solvents. While numerous experimental studies have been established across a range of chemistries, such as oxidation, pyrolysis, amination, and Fischer-Tropsch synthesis, still there is little fundamental, molecular-level information regarding the role of the SCF on elementary heterogeneous catalytic steps. In this study, the influence of hexane solvent on the adsorption of carbon monoxide on Co(0001), as the first step in the reaction mechanism of many processes involving syngas conversion, is probed. Simulations are performed at various bulk hexane densities, ranging from ideal gas conditions (no SCF hexane) to various near- and super-critical hexane densities. For this purpose, both density functional theory and molecular dynamics simulations are employed to determine the adsorption energy and free energy change during CO chemisorption. Potential of mean force calculations, utilizing umbrella sampling and the weighted histogram analysis method, provide the first commentary on SCF solvent effects on the energetic aspects of the chemisorption process. Simulation results indicate an enhanced stability of CO adsorption on the catalyst surface in the presence of supercritical hexane within the reduced pressure range of 1.0–1.5 at a constant temperature of 523 K. Furthermore, it is shown that the maximum stability of CO in the adsorbed state as a function of supercritical hexane density at 523 K nearly coincides with the maximum isothermal compressibility of bulk hexane at this temperature.

  7. A small-molecule compound inhibits a collagen-specific molecular chaperone and could represent a potential remedy for fibrosis.

    Science.gov (United States)

    Ito, Shinya; Ogawa, Koji; Takeuchi, Koh; Takagi, Motoki; Yoshida, Masahito; Hirokawa, Takatsugu; Hirayama, Shoshiro; Shin-Ya, Kazuo; Shimada, Ichio; Doi, Takayuki; Goshima, Naoki; Natsume, Tohru; Nagata, Kazuhiro

    2017-12-08

    Fibrosis can disrupt tissue structure and integrity and impair organ function. Fibrosis is characterized by abnormal collagen accumulation in the extracellular matrix. Pharmacological inhibition of collagen secretion therefore represents a promising strategy for the management of fibrotic disorders, such as liver and lung fibrosis. Hsp47 is an endoplasmic reticulum (ER)-resident collagen-specific molecular chaperone essential for correct folding of procollagen in the ER. Genetic deletion of Hsp47 or inhibition of its interaction with procollagen interferes with procollagen triple helix production, which vastly reduces procollagen secretion from fibroblasts. Thus, Hsp47 could be a potential and promising target for the management of fibrosis. In this study, we screened small-molecule compounds that inhibit the interaction of Hsp47 with collagen from chemical libraries using surface plasmon resonance (BIAcore), and we found a molecule AK778 and its cleavage product Col003 competitively inhibited the interaction and caused the inhibition of collagen secretion by destabilizing the collagen triple helix. Structural information obtained with NMR analysis revealed that Col003 competitively binds to the collagen-binding site on Hsp47. We propose that these structural insights could provide a basis for designing more effective therapeutic drugs for managing fibrosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Diagnostic potential of low molecular weight excretory secretory proteins of Paramphistomum epiclitum for caprine amphistomosis.

    Science.gov (United States)

    Jaiswal, Amit Kumar; Shanker, Daya; Sudan, Vikrant; Singh, Amit

    2018-06-15

    In the present study, the 75% alcoholic fractionation of excretory-secretory (ES) antigen isolated from 200 to 300 live P. epiclitum was assessed for its diagnostic potential for the detection of caprine amphistomosis by using antibody detection enzyme immunoassay. Prior to enzyme immunoassay, 75% alcoholic fractionation of excretory-secretory (ES) antigen was subjected to SDS- PAGE and western blot analysis for the presence of immunoreactive polypeptides. SDS-PAGE analysis of ES antigen resolved a total 7 polypeptides bands of size 56, 27, 25, 22.5, 12, 11 and 10 kDa. Western blot analysis revealed only two immunoreactive polypeptides (11 kDa and 12 kDa) when polypeptides resolved in SDS-PAGE were probed with known positive pooled serum. None of the polypeptides showed reactions with pooled known negative serum. The working dilutions of antigen, sera and conjugates were determined by checkerboard titration for employing ELISA and cut-off O.D. was calculated 0.616 by using the mean absorbance value of 11 negative kid sera. The sensitivity and specificity of ELISA was found to be 100% and 86.76%, respectively. As per kappa value estimation, the strength of agreement was found to be good. Antibodies to 75% alcoholic fractionation of ES antigen was detected in 20% goats (n = 160) of either sex, although faecal examination detected 10.6% goats to be infected with amphistomosis. The study confirmed that 75% alcoholic fractionation of ES antigen of P. epiclitum based ELISA had good value for serodiagnosis of caprine amphistomosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Assessing the bioconfinement potential of a Nicotiana hybrid platform for use in plant molecular farming applications.

    Science.gov (United States)

    Rice, J Hollis; Mundell, Richard E; Millwood, Reginald J; Chambers, Orlando D; Stewart, C Neal; Davies, H Maelor

    2013-08-06

    The introduction of pharmaceutical traits in tobacco for commercial production could benefit from the utilization of a transgene bioconfinement system. It has been observed that interspecific F1Nicotiana hybrids (Nicotiana tabacum × Nicotiana glauca) are sterile and thus proposed that hybrids could be suitable bioconfined hosts for biomanufacturing. We genetically tagged hybrids with green fluorescent protein (GFP), which was used as a visual marker to enable gene flow tracking and quantification for field and greenhouse studies. GFP was used as a useful proxy for pharmaceutical transgenes. Analysis of DNA content revealed significant genomic downsizing of the hybrid relative to that of N. tabacum. Hybrid pollen was capable of germination in vitro, albeit with a very low frequency and with significant differences between plants. In two field experiments, one each in Tennessee and Kentucky, we detected outcrossing at only one location (Tennessee) at 1.4%. Additionally, from 50 hybrid plants at each field site, formation of 84 and 16 seed was observed, respectively. Similar conclusions about hybrid fertility were drawn from greenhouse crosses. In terms of above-ground biomass, the hybrid yield was not significantly different than that of N. tabacum in the field. N. tabacum × N. glauca hybrids show potential to contribute to a bioconfinement- and biomanufacturing host system. Hybrids exhibit extremely low fertility with no difference of green biomass yields relative to N. tabacum. In addition, hybrids are morphologically distinguishable from tobacco allowing for identity preservation. This hybrid system for biomanufacturing would optimally be used where N. glauca is not present and in physical isolation of N. tabacum production to provide total bioconfinement.

  10. Mechanisms of Zr surface corrosion determined via molecular dynamics simulations with charge-optimized many-body (COMB) potentials

    International Nuclear Information System (INIS)

    Noordhoek, Mark J.; Liang, Tao; Chiang, Tsu-Wu; Sinnott, Susan B.; Phillpot, Simon R.

    2014-01-01

    Highlights: • An interatomic potential for zirconium–zirconium oxide–zirconium hydride is presented. • Diffusion of oxygen and hydrogen into Zr (0 0 0 1). • Deposition of O 2 and H 2 O on low-index Zr surfaces. • Surface structure affects resulting corrosion behavior. - Abstract: A charge-optimized many-body (COMB) potential is proposed for the zirconium–zirconium oxide–zirconium hydride system. This potential is developed to describe the energetics of the interactions of oxygen and hydrogen with zirconium metal. We perform classical molecular dynamics simulations showing the initial corrosion behavior of three low-index zirconium surfaces via the deposition of O 2 and H 2 O molecules. The basal (0 0 0 1) surface shows greater resistance to oxygen diffusion than the prism (101 ¯ 0) and (112 ¯ 0) surfaces. We suggest ways in which the surface structure has a unique role in the experimentally observed enhanced corrosion of the prism surfaces

  11. Molecular characterization of gluten hydrolysing Bacillus sp. and their efficacy and biotherapeutic potential as probiotics using Caco-2 cell line.

    Science.gov (United States)

    Rashmi, B S; Gayathri, D

    2017-09-01

    To isolate and characterize indigenous gluten hydrolysing bacteria from wheat sourdough and curd samples and further evaluation of their probiotic potentiality. Indigenous gluten hydrolysing isolates GS 33, GS 143, GS 181 and GS 188 were identified as Bacillus sp. by molecular-typing methods and studied extensively for their functional and probiotic attributes. All the tested isolates could survive at pH 2 and toxicity of 0·3% bile and also exhibited cell surface hydrophobicity and autoaggregation phenotype. The isolates were adhered strongly to Caco-2 cells and coaggregated with Escherichia coli MTCC 433 and Listeria monocytogenes MTCC 1143 preventing pathogen invasion into Caco-2 cells in vitro. In addition, the minimum inhibitory concentration of selected antibiotics for all the investigated gluten hydrolysing isolates was within the breakpoint values as recommended by the European Food Safety Authority. The indigenous high intensity gluten hydrolysing bacteria exhibited high resistance to gastric and pancreatic stress and possessed antibacterial, aggregation, adhesion and pathogen exclusion properties, and as a potential probiotics, either alone or in consortium would be useful in the development of gluten-free wheat foods. Exploring new indigenous gluten hydrolysing bacteria from wheat sourdough and curd samples would be beneficial in developing gluten-free wheat foods using potential indigenous probiotics. © 2017 The Society for Applied Microbiology.

  12. Synthesis of bis-indolylmethanes as new potential inhibitors of β-glucuronidase and their molecular docking studies.

    Science.gov (United States)

    Taha, Muhammad; Ullah, Hayat; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Muhammad Naseem; Rahim, Fazal; Ahmat, Norizan; Ali, Muhammad; Perveen, Shahnaz

    2018-01-01

    Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by 1 HNMR, 13 CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d-saccharic acid-1,4-lactone (IC 50 value 48.30 ± 1.20 μM). Derivatives 1-32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Transport coefficients of liquid CF4 and SF6 computed by molecular dynamics using polycenter Lennard-Jones potentials

    Science.gov (United States)

    Hoheisel, C.

    1989-01-01

    For several liquid states of CF4 and SF4, the shear and the bulk viscosity as well as the thermal conductivity were determined by equilibrium molecular dynamics (MD) calculations. Lennard-Jones four- and six-center pair potentials were applied, and the method of constraints was chosen for the MD. The computed Green-Kubo integrands show a steep time decay, and no particular longtime behavior occurs. The molecule number dependence of the results is found to be small, and 3×105 integration steps allow an accuracy of about 10% for the shear viscosity and the thermal conductivity coefficient. Comparison with experimental data shows a fair agreement for CF4, while for SF6 the transport coefficients fall below the experimental ones by about 30%.

  14. Transport coefficients of liquid CF4 and SF6 computed by molecular dynamics using polycenter Lennard-Jones potentials

    International Nuclear Information System (INIS)

    Hoheisel, C.

    1989-01-01

    For several liquid states of CF 4 and SF 6 , the shear and the bulk viscosity as well as the thermal conductivity were determined by equilibrium molecular dynamics (MD) calculations. Lennard-Jones four- and six-center pair potentials were applied, and the method of constraints were chosen for the MD. The computed Green-Kubo integrands show a steep time decay, and no particular longtime behavior occurs. The molecule number dependence of the results is found to be small, and 3 x 10 5 integration steps allow an accuracy of about 10% for the shear viscosity and the thermal conductivity coefficient. Comparison with experimental data shows a fair agreement for CF 4 , while for SF 6 the transport coefficients fall below the experimental ones by about 30%

  15. Applicability of effective fragment potential version 2 - Molecular dynamics (EFP2-MD) simulations for predicting excess properties of mixed solvents

    Science.gov (United States)

    Kuroki, Nahoko; Mori, Hirotoshi

    2018-02-01

    Effective fragment potential version 2 - molecular dynamics (EFP2-MD) simulations, where the EFP2 is a polarizable force field based on ab initio electronic structure calculations were applied to water-methanol binary mixture. Comparing EFP2s defined with (aug-)cc-pVXZ (X = D,T) basis sets, it was found that large sets are necessary to generate sufficiently accurate EFP2 for predicting mixture properties. It was shown that EFP2-MD could predict the excess molar volume. Since the computational cost of EFP2-MD are far less than ab initio MD, the results presented herein demonstrate that EFP2-MD is promising for predicting physicochemical properties of novel mixed solvents.

  16. Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine

    Science.gov (United States)

    Yasui, Yuko; Su, Tsung-Ping

    2016-01-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance. PMID:27088037

  17. Exploring the potential of fulvalene dimetals as platforms for molecular solar thermal energy storage: computations, syntheses, structures, kinetics, and catalysis.

    Science.gov (United States)

    Börjesson, Karl; Ćoso, Dušan; Gray, Victor; Grossman, Jeffrey C; Guan, Jingqi; Harris, Charles B; Hertkorn, Norbert; Hou, Zongrui; Kanai, Yosuke; Lee, Donghwa; Lomont, Justin P; Majumdar, Arun; Meier, Steven K; Moth-Poulsen, Kasper; Myrabo, Randy L; Nguyen, Son C; Segalman, Rachel A; Srinivasan, Varadharajan; Tolman, Willam B; Vinokurov, Nikolai; Vollhardt, K Peter C; Weidman, Timothy W

    2014-11-17

    A study of the scope and limitations of varying the ligand framework around the dinuclear core of FvRu2 in its function as a molecular solar thermal energy storage framework is presented. It includes DFT calculations probing the effect of substituents, other metals, and CO exchange for other ligands on ΔHstorage . Experimentally, the system is shown to be robust in as much as it tolerates a number of variations, except for the identity of the metal and certain substitution patterns. Failures include 1,1',3,3'-tetra-tert-butyl (4), 1,2,2',3'-tetraphenyl (9), diiron (28), diosmium (24), mixed iron-ruthenium (27), dimolybdenum (29), and ditungsten (30) derivatives. An extensive screen of potential catalysts for the thermal reversal identified AgNO3 -SiO2 as a good candidate, although catalyst decomposition remains a challenge. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. First molecular evidence of potentially zoonotic Babesia microti and Babesia sp. EU1 in Ixodes ricinus ticks in Belgium.

    Science.gov (United States)

    Lempereur, Laetitia; De Cat, Ann; Caron, Yannick; Madder, Maxime; Claerebout, Edwin; Saegerman, Claude; Losson, Bertrand

    2011-02-01

    We report the first molecular evidence of the presence of Babesia sp. EU1 and Babesia microti in Ixodes ricinus ticks in Belgium. A 1-year national survey collected 1005 ticks from cats and dogs. A polymerase chain reaction technique amplifying a part of the 18S rRNA gene detected Babesia spp. in 11 out of 841 selected and validated tick extracts. Subsequent sequencing identified Ba. microti (n=3) and Babesia sp. EU1 (n=6). This study has demonstrated a low infection rate (1.31% with 95% CI: 0.65-2.33) of Babesia spp. carriage in I. ricinus ticks in Belgium but, for the first time, reports two potentially zoonotic species belonging to this genus. Coinfection with Ba. microti and Borrelia burgdorferi sensu stricto also was demonstrated. In addition, this study clearly demonstrates that inhibitors of polymerase chain reaction amplification are present in engorged ticks.

  19. Molecular and Material Approaches to Overcome Kinetic and Energetic Constraints in Dye-Sensitized Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hamann, Thomas [Michigan State Univ., East Lansing, MI (United States)

    2016-08-14

    Dye-sensitized solar cells (DSSCs) have attracted a lot of interest as they proffer the possibility of extremely inexpensive and efficient solar energy conversion. The excellent performance of the most efficient DSSCs relies on two main features: 1) a high surface area nanoparticle semiconductor photoanode to allow for excellent light absorption with moderate extinction molecular dyes and 2) slow recombination rates from the photoanode to I3- allowing good charge collection. The I3-/I- couple, however, has some disadvantages, notably the redox potential limits the maximum open-circuit voltage, and the dye regeneration requires a large driving force which constrains the light harvesting ability. Thus, the design features that allow DSSCs to perform as well as they do also prevent further significant improvements in performance. As a consequence, the most efficient device configuration, and the maximum efficiency, has remained essentially unchanged over the last 16 years. Significant gains in performance are possible; however it will likely require a substantial paradigm shift. The general goal of this project is to understand the fundamental role of dye-sensitized solar cell, DSSC, components (sensitizer, redox shuttle, and photoanode) involved in key processes in order to overcome the kinetic and energetic constraints of current generation DSSCs. For example, the key to achieving high energy conversion efficiency DSSCs is the realization of a redox shuttle which fulfills the dual requirements of 1) efficient dye regeneration with a minimal driving force and 2) efficient charge collection. In current generation DSSCs, however, only one or the other of these requirements is met. We are currently primarily interested in understanding the physical underpinnings of the regeneration and recombination reactions. Our approach is to systematically vary the components involved in reactions and interrogate them with a

  20. Synthesis and In Vitro and In Vivo Evaluation of Iodine-131-Labeled Folates: Potential Molecular Diagnostic and Therapeutic Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Al Jammaz, I.

    2009-01-01

    Molecular targeting imaging has a great potential to be able to image molecular changes that are currently defined as predisease states which facilitate earlier detection of cancer and consequently, the greatest chance of cure. Advancement of scintigraphic imaging and radiotherapy is highly determined by development of more specific radiotracers. The Membrane-associated-folic acid receptor is a glycosylphospstidylinositol protein that overexpressed in approximately 100% of serious ovarian adenocarcinomas and various epithelial cancers including cervical, colorectal and renal cancers. Meanwhile, this receptor is highly restricted in most normal tissues which make these tumors as an excellent candidates for molecular targeting imaging and therapy through the folate receptor system. As part of our on-going research effort to develop prosthetic precursors for radiohalogenation of bioactive molecules, we have previously reported the synthesis and biological characterization of [ 18 F]- fluorobenzene and pyridine carbohydrazide-folate conjugates ([ 18 F]-SFB and [ 18 F]-SFP-folates). We here report the synthesis and biological characterization of [ 131 I]-iodobenzenecarbohydrazide-folate conjugate ([ 131 I]-SIB-folate) as a potential therapeutic radiopharmaceutical. The synthetic approaches for preparation of [ 131 I]iodobenzene carbohydrazide-folates ([ 131 I]-SIB-folate) entailed sequence of reactions. Hydrazide-folate was reacted with N-succinimidyl-m-[131I]-iodobenzoate-carboxylate ([ 131 I]-SIB) to give [ 131 I]-SIB-folate conjugate. Radiochemical yield was greater than 80% and synthesis times were ranging between 40-45 min. Radiochemical purity was also greater than 97% without HPLC purification. These synthetic approaches hold considerable promise as rapid and simple method for the radiohalogenation of folate in high radiochemical yield in short time. In vitro tests on KB cell line has shown that significant amount of the radioconjugate associated with cell

  1. Molecular Detection of Two Potential Probiotic Lactobacilli Strains and Evaluation of Their Performance as Starter Adjuncts in Yogurt Production.

    Science.gov (United States)

    Saxami, Georgia; Papadopoulou, Olga S; Chorianopoulos, Nikos; Kourkoutas, Yiannis; Tassou, Chrysoula C; Galanis, Alex

    2016-05-04

    A molecular method for efficient and accurate detection and identification of two potential probiotic lactobacilli strains isolated from fermented olives, namely Lactobacillus pentosus B281 and Lb. plantarum B282, was developed in the present study. Random Amplified Polymorphic DNA (RAPD) analysis was performed, and strain specific primers were designed and applied in a multiplex polymerase chain reaction (PCR) assay. The specificity of the assay was tested and successfully confirmed in 27 and 22 lactobacilli strains for Lb. pentosus B281 and Lb. plantarum B282, respectively. Moreover, the two strains were used as starter cultures in yogurt production. Cell enumeration followed by multiplex PCR analysis demonstrated that the two strains were present in yogurt samples at levels ≥6 log CFU/g even after 35 days of storage at 4 °C. Microbiological analysis showed that lactobacilli and streptococci were present within usual levels, whereas enterobacteriaceae and yeast/mold counts were not detected as expected. Although the pH values of the novel products were slightly lower than the control ones, the yogurt containing the probiotic cultures scored similar values compared to the control in a series of sensory tests. Overall, these results demonstrated the possible use of the two strains as starter adjuncts in the production of yogurt with potential probiotic properties.

  2. Robust Denaturation of Villin Headpiece by MoS2 Nanosheet: Potential Molecular Origin of the Nanotoxicity

    Science.gov (United States)

    Gu, Zonglin; Yang, Zaixing; Kang, Seung-Gu; Yang, Jerry R.; Luo, Judong; Zhou, Ruhong

    2016-06-01

    MoS2 nanosheet, a new two-dimensional transition metal dichalcogenides nanomaterial, has attracted significant attentions lately due to many potential promising biomedical applications. Meanwhile, there is also a growing concern on its biocompatibility, with little known on its interactions with various biomolecules such as proteins. In this study, we use all-atom molecular dynamics simulations to investigate the interaction of a MoS2 nanosheet with Villin Headpiece (HP35), a model protein widely used in protein folding studies. We find that MoS2 exhibits robust denaturing capability to HP35, with its secondary structures severely destroyed within hundreds of nanosecond simulations. Both aromatic and basic residues are critical for the protein anchoring onto MoS2 surface, which then triggers the successive protein unfolding process. The main driving force behind the adsorption process is the dispersion interaction between protein and MoS2 monolayer. Moreover, water molecules at the interface between some key hydrophobic residues (e.g. Trp-64) and MoS2 surface also help to accelerate the process driven by nanoscale drying, which provides a strong hydrophobic force. These findings might have shed new light on the potential nanotoxicity of MoS2 to proteins with atomic details, which should be helpful in guiding future biomedical applications of MoS2 with its nanotoxicity mitigated.

  3. Development of empirical potential functions for the study of molecular geometry, and applications to chlorophyll a dimers

    Energy Technology Data Exchange (ETDEWEB)

    Oie, Tetsuro [Univ. of Rochester, NY (United States); Univ. of Kansas, Lawrence, KS (United States). Dept. of Chemistry

    1980-07-28

    A purpose of the present studies is twofold: (1) development of an empirical potential function (EPF) and (2) application of it to the studies of photoreaction center chlorophyll a dimer. The reliable estimate of geometric structures and energies of large molecules by quantum mechanical methods is not possible at the present time. An alternative method is, therefore, needed for the studies of large molecular systems, and Chapter I is dedicated to the development of this tool, i.e., an empirical potential function, which could suffice this purpose. Because of a large number of variable chemical compositions and functional groups characteristically present in a large molecule, it is important to include a large number of structurally diverse molecules in the development of the EPF. In Chapter II, the EPF is applied to study the geometrical structure of a chlorophyll a (Chl a) dimer, which is believed to exist at the photoreaction center of green plants and is known to play an essential role in photosynthetic energy conversion. Although various models have been proposed for this dimer structure, there is still a great need for information concerning the detailed geometric structure of this dimer. Therefore, in this chapter the structural stabilities of various dimer models are examined by the EPF, and detailed and quantitative information on the structure and stability of these models is provided.

  4. Molecular Detection of Two Potential Probiotic Lactobacilli Strains and Evaluation of Their Performance as Starter Adjuncts in Yogurt Production

    Directory of Open Access Journals (Sweden)

    Georgia Saxami

    2016-05-01

    Full Text Available A molecular method for efficient and accurate detection and identification of two potential probiotic lactobacilli strains isolated from fermented olives, namely Lactobacillus pentosus B281 and Lb. plantarum B282, was developed in the present study. Random Amplified Polymorphic DNA (RAPD analysis was performed, and strain specific primers were designed and applied in a multiplex polymerase chain reaction (PCR assay. The specificity of the assay was tested and successfully confirmed in 27 and 22 lactobacilli strains for Lb. pentosus B281 and Lb. plantarum B282, respectively. Moreover, the two strains were used as starter cultures in yogurt production. Cell enumeration followed by multiplex PCR analysis demonstrated that the two strains were present in yogurt samples at levels ≥6 log CFU/g even after 35 days of storage at 4 °C. Microbiological analysis showed that lactobacilli and streptococci were present within usual levels, whereas enterobacteriaceae and yeast/mold counts were not detected as expected. Although the pH values of the novel products were slightly lower than the control ones, the yogurt containing the probiotic cultures scored similar values compared to the control in a series of sensory tests. Overall, these results demonstrated the possible use of the two strains as starter adjuncts in the production of yogurt with potential probiotic properties.

  5. Apoptosis induced by low-intensity ultrasound in vitro: Alteration of protein profile and potential molecular mechanism

    Science.gov (United States)

    Feng, Yi; Wan, Mingxi

    2017-03-01

    To analyze the potential mechanism related to the apoptosis induced by low intensity focused ultrasound, comparative proteomic method was introduced in the study. After ultrasound irradiation (3.0 W/cm2, 1 minute, 6 hours incubation post-irradiation), the human SMMC-7721 hepatocarcinoma cells were stained by trypan blue to detect the morphologic changes, and then the percentage of early apoptosis were tested by the flow cytometry with double staining of FITC-labelled Annexin V/Propidium iodide. Two-dimensional SDS polyacrylamide gel electrophoresis was used to get the protein profile and some proteins differently expressed after ultrasound irradiation were identified by MALDI-TOF mass spectrometry. It's proved early apoptosis of cells were induced by low intentisy focused ultrasound. After ultrasound irradiation, the expressing characteristics of several proteins changed, in which protein p53 and heat shock proteins are associated with apoptosis initiation. It is suggested that the low-intensity ultrasound-induced apoptotic cancer therapy has the potential application via understanding its relevant molecular signaling and key proteins. Moreover, the comparative proteomic method is proved to be useful to supply information about the protein expression to analyze the metabolic processes related to bio-effects of biomedical ultrasound.

  6. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    Dayan, Dan; Salo, Tuula; Salo, Sirpa; Nyberg, Pia; Nurmenniemi, Sini; Costea, Daniela Elena; Vered, Marilena

    2012-01-01

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  7. Structural Insights into the Quadruplex-Duplex 3' Interface Formed from a Telomeric Repeat: A Potential Molecular Target.

    Science.gov (United States)

    Russo Krauss, Irene; Ramaswamy, Sneha; Neidle, Stephen; Haider, Shozeb; Parkinson, Gary N

    2016-02-03

    We report here on an X-ray crystallographic and molecular modeling investigation into the complex 3' interface formed between putative parallel stranded G-quadruplexes and a duplex DNA sequence constructed from the human telomeric repeat sequence TTAGGG. Our crystallographic approach provides a detailed snapshot of a telomeric 3' quadruplex-duplex junction: a junction that appears to have the potential to form a unique molecular target for small molecule binding and interference with telomere-related functions. This unique target is particularly relevant as current high-affinity compounds that bind putative G-quadruplex forming sequences only rarely have a high degree of selectivity for a particular quadruplex. Here DNA junctions were assembled using different putative quadruplex-forming scaffolds linked at the 3' end to a telomeric duplex sequence and annealed to a complementary strand. We successfully generated a series of G-quadruplex-duplex containing crystals, both alone and in the presence of ligands. The structures demonstrate the formation of a parallel folded G-quadruplex and a B-form duplex DNA stacked coaxially. Most strikingly, structural data reveals the consistent formation of a TAT triad platform between the two motifs. This triad allows for a continuous stack of bases to link the quadruplex motif with the duplex region. For these crystal structures formed in the absence of ligands, the TAT triad interface occludes ligand binding at the 3' quadruplex-duplex interface, in agreement with in silico docking predictions. However, with the rearrangement of a single nucleotide, a stable pocket can be produced, thus providing an opportunity for the binding of selective molecules at the interface.

  8. Modeling, molecular dynamics, and docking assessment of transcription factor rho: a potential drug target in Brucella melitensis 16M

    Directory of Open Access Journals (Sweden)

    Pradeepkiran JA

    2015-03-01

    24934545 and ZINC72319544 – that showed high binding affinity among 2,829 drug analogs that bind with key active-site residues; these residues are considered for protein-ligand binding and unbinding pathways via steered molecular dynamics simulations. Arg215 in the model plays an important role in the stability of the protein-ligand complex via a hydrogen bonding interaction by aromatic-π contacts, and the ADMET (absorption, distribution, metabolism, and excretion analysis of best leads indicate nontoxic in nature with good potential for drug development. Keywords: brucellosis, rho proteins, transcription inhibitors, SMD simulations, ADMET analysis, therapeutics 

  9. Voltage-Gated Potassium Channels Kv1.3--Potentially New Molecular Target in Cancer Diagnostics and Therapy.

    Science.gov (United States)

    Teisseyre, Andrzej; Gąsiorowska, Justyna; Michalak, Krystyna

    2015-01-01

    Voltage-gated potassium channels, Kv1.3, which were discovered in 1984, are integral membrane proteins which are activated ("open") upon change of the cell membrane potential, enabling a passive flux of potassium ions across the cell membrane. The channels are expressed in many different tissues, both normal and cancer. Since 2005 it has been known that the channels are expressed not only in the plasma membrane, but also in the inner mitochondrial membrane. The activity of Kv1.3 channels plays an important role, among others, in setting the cell resting membrane potential, cell proliferation, apoptosis and volume regulation. For some years, these channels have been considered a potentially new molecular target in both the diagnostics and therapy of some cancer diseases. This review article focuses on: 1) changes of expression of the channels in cancer disorders with special regard to correlations between the channels' expression and stage of the disease, 2) influence of inhibitors of Kv1.3 channels on proliferation and apoptosis of cancer cells, 3) possible future applications of Kv1.3 channels' inhibitors in therapy of some cancer diseases. In the last section, the results of studies performed in our Laboratory of Bioelectricity on the influence of selected biologically active plant-derived compounds from the groups of flavonoids and stilbenes and their natural and synthetic derivatives on the activity of Kv1.3 channels in normal and cancer cells are reviewed. A possible application of some compounds from these groups to support therapy of cancer diseases, such as breast, colon and lymph node cancer, and melanoma or chronic lymphocytic leukemia (B-CLL), is announced.

  10. Spectroscopic and molecular docking studies on N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine: A potential bioactive agent for lung cancer treatment

    Science.gov (United States)

    Mohamed Asath, R.; Premkumar, R.; Mathavan, T.; Milton Franklin Benial, A.

    2017-09-01

    Potential energy surface scan was performed and the most stable molecular structure of the N,N-di-tert-butoxycarbonyl (Boc)-2-amino pyridine (DBAP) molecule was predicted. The most stable molecular structure of the molecule was optimized using B3LYP method with cc-pVTZ basis set. Anticancer activity of the DBAP molecule was evaluated by molecular docking analysis. The structural parameters and vibrational wavenumbers were calculated for the optimized molecular structure. The experimental and theoretical wavenumbers were assigned and compared. Ultraviolet-Visible spectrum was simulated and validated experimentally. The molecular electrostatic potential surface was simulated and Fukui function calculations were also carried out to investigate the reactive nature of the DBAP molecule. The natural bond orbital analysis was also performed to probe the intramolecular interactions and confirm the bioactivity of the DBAP molecule. The molecular docking analysis reveals the better inhibitory nature of the DBAP molecule against the epidermal growth factor receptor (EGFR) protein which causes lung cancer. Hence, the present study unveils the structural and bioactive nature of the title molecule. The DBAP molecule was identified as a potential inhibitor against the lung cancer which may be useful in further development of drug designing in the treatment of lung cancer.

  11. Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches

    Science.gov (United States)

    Almutairi, Maha S.; Zakaria, Azza S.; Ignasius, P. Primsa; Al-Wabli, Reem I.; Joe, Isaac Hubert; Attia, Mohamed I.

    2018-02-01

    Indole-isatin molecular hybrids 5a-i have been synthesized and characterized by different spectroscopic methods to be evaluated as new antimicrobial agents against a panel of Gram positive bacteria, Gram negative bacteria, and moulds. Compound 5h was selected as a representative example of the prepared compounds 5a-i to perform computational investigations. Its vibrational properties have been studied using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal target protein.

  12. Prediction of phonon thermal transport in thin GaAs, InAs and InP nanowires by molecular dynamics simulations: influence of the interatomic potential

    Energy Technology Data Exchange (ETDEWEB)

    Carrete, J; Longo, R C; Gallego, L J, E-mail: jesus.carrete@usc.es [Departamento de Fisica de la Materia Condensada, Facultad de Fisica, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela (Spain)

    2011-05-06

    A number of different potentials are currently being used in molecular dynamics simulations of semiconductor nanostructures. Confusion can arise if an inappropriate potential is used. To illustrate this point, we performed direct molecular dynamics simulations to predict the room temperature lattice thermal conductivity {lambda} of thin GaAs, InAs and InP nanowires. In each case, simulations performed using the classical Harrison potential afforded values of {lambda} about an order of magnitude smaller than those obtained using more elaborate potentials (an Abell-Tersoff, as parameterized by Hammerschmidt et al for GaAs and InAs, and a potential of Vashishta type for InP). These results will be a warning to those wishing to use computer simulations to orient the development of quasi-one-dimensional systems as heat sinks or thermoelectric devices.

  13. Molecular profiling and bioactive potential of an endophytic fungus Aspergillus sulphureus isolated from Sida acuta: a medicinal plant.

    Science.gov (United States)

    Murali, M; Mahendra, C; Hema, P; Rajashekar, N; Nataraju, A; Sudarshana, M S; Amruthesh, K N

    2017-12-01

    Sida acuta Burm.f. (Malvaceae) extracts are reported to have applications against malaria, diuretic, antipyretic, nervous and urinary diseases. No fungal endophytes of S. acuta are reported. Isolation, identification and evaluation of antibacterial, antioxidant, anticancer and haemolytic potential of fungal endophytes from the ethnomedcinal plant S. acuta. Sida acuta stem segments were placed on PDA medium to isolate endophytic fungi. The fungus was identified by genomic DNA analysis and phylogenetic tree was constructed using ITS sequences (GenBank) to confirm species. The antibacterial efficacy of Aspergillus sulphureus MME12 ethyl acetate extract was tested against Gram-positive and Gram-negative pathogenic bacteria. DPPH free radical scavenging activity, anticancer and DNA fragmentation against EAC cells, and direct haemolytic activity (100-500 μg/mL) using human erythrocytes were determined. The ethyl acetate extract of A. sulphureus (Fresen.) Wehmer (Trichocomaceae) demonstrated significant antibacterial potential against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi compared to streptomycin. MIC against test pathogens was in the range of 15.6-62.5 μg/mL. The antioxidant results revealed significant RSA from 12.43% to 62.02% (IC 50  = 350.4 μg/mL, p ≤ 0.05). MME12 offered considerable inhibition of EAC proliferation (23% to 84%, IC 50  = 216.7 μg/mL, p ≤ 0.05) supported by DNA fragmentation studies. The extract also offered insignificant haemolysis (5.6%) compared to Triton X-100. A single endophytic fungus, A. sulphureus MME12 was isolated and identified using molecular profiling. The above-mentioned findings support the pharmacological application of A. sulphureus MME12 extract and demand for purification of the active principle(s).

  14. Molecular identification and potential of an isolate of white rot fungi in bioremediation of petroleum contaminated soils

    Directory of Open Access Journals (Sweden)

    Maryam Mohammadi-sichani

    2017-06-01

    Full Text Available Introduction:Elimination or reduction of petroleum hydrocarbons from natural resources such as water and soil is a serious problem of countries, particularly oil-rich countries of the world. Using white rotting fungi compost for bioremediation of soils contaminated by petroleum hydrocarbons is effective. The aim of this study is molecular identification and potential of anisolate of white rot fungi in bioremediation of petroleum contaminated soils. Materials and methods: Spent compost of white rotting fungi was inoculated with petroleum contaminated soil into 3%, 5% and 10% (w/w. Treatments were incubated at 25-23 °C for 3 months. Reduction of petroleum hydrocarbons in treated soil was determined by gas chromatography. Ecotoxicity of soil was evaluated by seed germination test. Results: Based on the genome sequence of 18s rRNA, it is revealed that this isolate is Ganoderma lucidum and this isolate is deposited as accession KX525204 in the Gene Bank database. Reduction of petroleum hydrocarbons in soil treated with compost (3, 5 and 10% ranged from 42% to 71%. The germination index (% in ecotoxicity tests ranged from 20.8% to 70.8%. Gas chromatography results also showed a decrease in soil Hydrocarbons compounds. Discussion and conclusion: The compost of Ganoderma lucidum, a white rot fungus, has a potential ability to remove petroleum hydrocarbons in contaminated soil. Removal of hydrocarbons was increased with increase in compost mixed with contaminated soil. Petroleum contaminated soil amended with spent compost of G.lucidum 10% during three months is appropriate to remove this pollutant.

  15. Free energy profiles of cocaine esterase-cocaine binding process by molecular dynamics and potential of mean force simulations.

    Science.gov (United States)

    Zhang, Yuxin; Huang, Xiaoqin; Han, Keli; Zheng, Fang; Zhan, Chang-Guo

    2016-11-25

    The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profile of the CocE)-(+)-cocaine binding process in comparison with that of the corresponding CocE-(-)-cocaine binding process. According to the MD simulations, the equilibrium CocE-(+)-cocaine binding mode is similar to the CocE-(-)-cocaine binding mode. However, based on the simulated free energy profiles, a significant free energy barrier (∼5 kcal/mol) exists in the CocE-(+)-cocaine binding process whereas no obvious free energy barrier exists in the CocE-(-)-cocaine binding process, although the free energy barrier of ∼5 kcal/mol is not high enough to really slow down the CocE-(+)-cocaine binding process. In addition, the obtained free energy profiles also demonstrate that (+)-cocaine and (-)-cocaine have very close binding free energies with CocE, with a negligible difference (∼0.2 kcal/mol), which is qualitatively consistent with the nearly same experimental K M values of the CocE enzyme for (+)-cocaine and (-)-cocaine. The consistency between the computational results and available experimental data suggests that the mechanistic insights obtained from this study are reasonable. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Relativistic four-component potential energy curves for the lowest 23 covalent states of molecular bromine (Br2).

    Science.gov (United States)

    Gomes, José da Silva; Gargano, Ricardo; Martins, João B L; M de Macedo, Luiz Guilherme

    2014-08-07

    The covalent excited states and ground state of the Br2 molecule has been investigated by using four-component relativistic COSCI and MRCISD methods. These methods were performed for all covalent states in the representation Ω((±)). Calculated potential energy curves (PECs) were obtained at the four-component COSCI level, and spectroscopic constants (R(e), D(e), D0, ω(e), ω(e)x(e), ω(e)y(e), B(e), α(e), γ(e), Te, Dv) for bounded states are reported. The vertical excitations for all covalent states are reported at COSCI, MRCISD, and MRCISD+Q levels. We also present spectroscopic constants for two weakly bounded states (A':(1)2u and B':(1)0(-)u) not yet reported in the literature, as well as accurate analytical curves for all five relativistic molecular bounded sates [the ground state X:0 g(+) and the excited states A:(1)1(u), B:(1)0(u)(+), C:(2)1(u), and B':(1)0(u)(-)] found in this work.

  17. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    Science.gov (United States)

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  18. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology(1.).

    Science.gov (United States)

    Robarts, Daniel W H; Wolfe, Andrea D

    2014-07-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance.

  19. Therapeutic potential of brain-derived neurotrophic factor (BDNF and a small molecular mimics of BDNF for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mary Wurzelmann

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF, a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  20. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

    Science.gov (United States)

    Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

    2017-01-01

    Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  1. Impact assessment of mercury accumulation and biochemical and molecular response of Mentha arvensis: a potential hyperaccumulator plant.

    Science.gov (United States)

    Manikandan, R; Sahi, S V; Venkatachalam, P

    2015-01-01

    The present study was focused on examining the effect of Hg oxidative stress induced physiochemical and genetic changes in M. arvensis seedlings. The growth rate of Hg treated seedlings was decreased to 56.1% and 41.5% in roots and shoots, respectively, compared to the control. Accumulation of Hg level in both roots and shoots was increased with increasing the concentration of Hg. Superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) activities were found to be increased with increasing the Hg concentration up to 20 mg/L; however, it was decreased at 25 mg/L Hg concentration. The POX enzyme activity was positively correlated with Hg dose. The changes occurring in the random amplification of ploymorphic DNA (RAPD) profiles generated from Hg treated seedlings included variations in band intensity, disappearance of bands, and appearance of new bands compared with the control seedlings. It was concluded that DNA polymorphisms observed with RAPD profile could be used as molecular marker for the evaluation of heavy metal induced genotoxic effects in plant species. The present results strongly suggested that Mentha arvensis could be used as a potential phytoremediator plant in mercury polluted environment.

  2. Molecular-based approaches to characterize coastal microbial community and their potential relation to the trophic state of Red Sea

    KAUST Repository

    Ansari, Mohd Ikram

    2015-03-11

    Molecular-based approaches were used to characterize the coastal microbiota and to elucidate the trophic state of Red Sea. Nutrient content and enterococci numbers were monitored, and used to correlate with the abundance of microbial markers. Microbial source tracking revealed the presence of >1 human-associated Bacteroides spp. at some of the near-shore sampling sites and at a heavily frequented beach. Water samples collected from the beaches had occasional exceedances in enterococci numbers, higher total organic carbon (TOC, 1.48-2.18 mg/L) and nitrogen (TN, 0.15-0.27 mg/L) than that detected in the near-shore waters. Enterococci abundances obtained from next-generation sequencing did not correlate well with the cultured enterococci numbers. The abundance of certain genera, for example Arcobacter, Pseudomonas and unclassified Campylobacterales, was observed to exhibit slight correlation with TOC and TN. Low abundance of functional genes accounting for up to 41 copies/L of each Pseudomonas aeruginosa and Campylobacter coli were detected. Arcobacter butzleri was also detected in abundance ranging from 111 to 238 copies/L. Operational taxonomic units (OTUs) associated with cyanobacteria, Prochlorococcus, Ostreococcus spp. and Gramella were more prevalent in waters that were likely impacted by urban runoffs and recreational activities. These OTUs could potentially serve as quantifiable markers indicative of the water quality.

  3. The Potential Role of Lycopene for the Prevention and Therapy of Prostate Cancer: From Molecular Mechanisms to Clinical Evidence

    Science.gov (United States)

    Holzapfel, Nina Pauline; Holzapfel, Boris Michael; Champ, Simon; Feldthusen, Jesper; Clements, Judith; Hutmacher, Dietmar Werner

    2013-01-01

    Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. PMID:23857058

  4. Molecular detection and characterization of potentially new Babesia and Theileria species/variants in wild felids from Kenya.

    Science.gov (United States)

    Githaka, Naftaly; Konnai, Satoru; Kariuki, Edward; Kanduma, Esther; Murata, Shiro; Ohashi, Kazuhiko

    2012-10-01

    Piroplasms frequently infect domestic and wild carnivores. At present, there is limited information on the occurrence and molecular identity of these tick-borne parasites in wild felids in Kenya. In 2009, a pair of captive lions (Panthare leo) was diagnosed with suspected babesiosis and mineral deficiency at an animal orphanage on the outskirts of Nairobi, Kenya. Blood smears indicated presences of haemoparasites in the erythrocytes, however, no further investigations were conducted to identify the infecting agent. The animals recovered completely following diet supplementation and treatment with anti-parasite drug. In this report, we extracted and detected parasite DNA from the two lions and seven other asymptomatic feline samples; two leopards (Panthera pardus) and five cheetahs (Acinonyx jubatus). Reverse line blot with probes specific for Babesia spp. of felines indicated the presence of new Babesia species or genotypes in the lions and leopards, and unknown Theileria sp. in the cheetahs. Phylogenetic analyses using partial sequences of 18S ribosomal RNA (18S rRNA) gene showed that the parasite infecting the lions belong to the Babesia canis complex, and the parasite variant detected in the leopards clusters in a clade bearing other Babesia spp. reported in wild felids from Africa. The cheetah isolates falls in the Theileria sensu stricto group. Our findings indicate the occurrence of potentially new species or genotypes of piroplams in all three feline species. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. CADRE-SS, an in Silico Tool for Predicting Skin Sensitization Potential Based on Modeling of Molecular Interactions.

    Science.gov (United States)

    Kostal, Jakub; Voutchkova-Kostal, Adelina

    2016-01-19

    Using computer models to accurately predict toxicity outcomes is considered to be a major challenge. However, state-of-the-art computational chemistry techniques can now be incorporated in predictive models, supported by advances in mechanistic toxicology and the exponential growth of computing resources witnessed over the past decade. The CADRE (Computer-Aided Discovery and REdesign) platform relies on quantum-mechanical modeling of molecular interactions that represent key biochemical triggers in toxicity pathways. Here, we present an external validation exercise for CADRE-SS, a variant developed to predict the skin sensitization potential of commercial chemicals. CADRE-SS is a hybrid model that evaluates skin permeability using Monte Carlo simulations, assigns reactive centers in a molecule and possible biotransformations via expert rules, and determines reactivity with skin proteins via quantum-mechanical modeling. The results were promising with an overall very good concordance of 93% between experimental and predicted values. Comparison to performance metrics yielded by other tools available for this endpoint suggests that CADRE-SS offers distinct advantages for first-round screenings of chemicals and could be used as an in silico alternative to animal tests where permissible by legislative programs.

  6. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc.

    Science.gov (United States)

    Takada, Toru; Nishida, Kotaro; Doita, Minoru; Kurosaka, Masahiro

    2002-07-15

    Rat and human intervertebral disc specimens were examined immunohistochemically. Reverse transcription polymerase chain reaction (RT-PCR) analysis was also performed on rat disc tissue to demonstrate the existence of Fas ligand. To clarify the existence of Fas ligand on intact intervertebral disc cells. The nucleus pulposus has been reported to be an immune-privileged site. The immune-privileged characteristic in other tissues such as the retina and testis has been attributed to the local expression of Fas ligand, which acts by inducing apoptosis of invading Fas-positive T-cells. The existence of Fas ligand in normal disc cells has not yet been addressed. Skeletally mature SD male rats were killed, and the coccygeal discs were harvested. Human disc specimens were obtained from idiopathic scoliosis patients during surgical procedures. Immunohistochemical staining for Fas ligand was performed for cross-sections of the discs by standard procedures. Reverse transcription polymerase chain reaction analysis was also carried out to demonstrate Fas ligand mRNA expression on rat intervertebral discs. Testes of the rats were used for positive controls, and muscles were used for negative controls. The sections were observed by light microscopy. The nucleus pulposus cells exhibited intense positive immune staining for Fas ligand. The outer anulus fibrosus cells and notochordal cells exhibited little immunopositivity. The positive controls exhibited positive immune staining, and the negative control showed no immunopositivity. The result of RT-PCR confirmed the existence of Fas ligand in disc cells. The human nucleus pulposus cells showed a similar predilection to rat disc cells. We demonstrated the existence of Fas ligand on disc cells, which should play a key role in the potential molecular mechanism to maintain immune privilege of the disc. Immune privilege and Fas ligand expression of the intervertebral disc may provide a new insight for basic science research as well as

  7. Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

    Directory of Open Access Journals (Sweden)

    Jielu Wei

    2017-10-01

    Full Text Available Celangulin V (CV, one of dihydroagarofuran sesquiterpene polyesters isolated from Chinese bittersweet (Celastrus angulatus Maxim, is famous natural botanical insecticide. Decades of research suggests that is displays excellent insecticidal activity against some insects, such as Mythimna separata Walker. Recently, it has been validated that the H subunit of V-ATPase is one of the target proteins of the insecticidal dihydroagarofuran sesquiterpene polyesters. As a continuation of the development of new pesticides from these natural products, a series of β-dihydroagarofuran derivatives have been designed and synthesized. The compound JW-3, an insecticidal derivative of CV with a p-fluorobenzyl group, exhibits higher insecticidal activity than CV. In this study, the potential inhibitory effect aused by the interaction of JW-3 with the H subunit of V-ATPase c was verified by confirmatory experiments at the molecular level. Both spectroscopic techniques and isothermal titration calorimetry measurements showed the binding of JW-3 to the subunit H of V-ATPase was specific and spontaneous. In addition, the possible mechanism of action of the compound was discussed. Docking results indicated compound JW-3 could bind well in ‘the interdomain cleft’ of the V-ATPase subunit H by the hydrogen bonding and make conformation of the ligand–protein complex become more stable. All results are the further validations of the hypothesis, that the target protein of insecticidal dihydroagarofuran sesquiterpene polyesters and their β-dihydroagarofuran derivatives is the subunit H of V-ATPase. The results also provide new ideas for developing pesticides acting on V-ATPase of insects.

  8. A molecular study on the prevalence and virulence potential of Aeromonas spp. recovered from patients suffering from diarrhea in Israel.

    Directory of Open Access Journals (Sweden)

    Yigal Senderovich

    Full Text Available BACKGROUND: Species of the genus Aeromonas are native inhabitants of aquatic environments and have recently been considered emerging human pathogens. Although the gastrointestinal tract is by far the most common anatomic site from which aeromonads are recovered, their role as etiologic agents of bacterial diarrhea is still disputed. Aeromonas-associated diarrhea is a phenomenon occurring worldwide; however, the exact prevalence of Aeromonas infections on a global scale is unknown. METHODOLOGY/PRINCIPAL FINDINGS: The prevalence and virulence potential of Aeromonas in patients suffering from diarrhea in Israel was studied using molecular methods. 1,033 diarrheal stools were sampled between April and September 2010 and Aeromonas species were identified in 17 (∼2% patients by sequencing the rpoD gene. Aeromonas species identity and abundance was: A. caviae (65%, A. veronii (29% and Aeromonas taiwanensis (6%. This is the first clinical record of A. taiwanensis as a diarrheal causative since its recent discovery from a wound infection in a patient in Taiwan. Most of the patients (77% from which Aeromonas species were isolated were negative for any other pathogens. The patients ranged from 1 to 92 years in age. Aeromonas isolates were found to possess different virulence-associated genes: ahpB (88%, pla/lip/lipH3/apl-1 (71%, act/hlyA/aerA (35%, alt (18%, ast (6%, fla (65%, lafA (41%, TTSS ascV (12%, TTSS ascF-ascG (12%, TTSS-dependent ADP-ribosylating toxins aexU (41% and aexT (6% in various combinations. Most of the identified strains were resistant to beta-lactam antibiotics but susceptible to third-generation cephalosporin antibiotics. CONCLUSIONS: Aeromonas may be a causative agent of diarrhea in patients in Israel and therefore should be included in routine bacteriological screenings.

  9. Potential of Central, Eastern and Western Africa Medicinal Plants for Cancer Therapy: Spotlight on Resistant Cells and Molecular Targets

    Directory of Open Access Journals (Sweden)

    Armelle T. Mbaveng

    2017-06-01

    Full Text Available Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp, multi drug-resistance-related proteins (MRPs, breast cancer resistance protein (BCRP, ABCG2 as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1, human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways. Plants with the ability to preferentially kills resistant cancer cells were also reported. Data compiled in the present document were retrieved from scientific websites such as PubMed, Scopus, Sciencedirect, Web-of-Science, and Scholar Google. In summary, plant extracts from CEWA and isolated compounds thereof exert cytotoxic effects by several modes of action including caspases activation, alteration of mitochondrial membrane potential (MMP, induction of reactive oxygen species (ROS in cancer cells and inhibition of angiogenesis. Ten strongest cytotoxic plants from CEWA recorded following in vitro screening assays are: Beilschmiedia acuta Kosterm, Echinops giganteus var. lelyi (C. D. Adams A. Rich., Erythrina sigmoidea Hua (Fabaceae, Imperata cylindrical Beauv. var. koenigii Durand et Schinz, Nauclea pobeguinii (Pobég. ex Pellegr. Merr. ex E.M.A., Piper capense L.f., Polyscias fulva (Hiern Harms., Uapaca togoensis Pax., Vepris soyauxii Engl. and Xylopia aethiopica (Dunal A. Rich. Prominent antiproliferative compounds include: isoquinoline alkaloid isotetrandrine (51

  10. Potential of Central, Eastern and Western Africa Medicinal Plants for Cancer Therapy: Spotlight on Resistant Cells and Molecular Targets

    Science.gov (United States)

    Mbaveng, Armelle T.; Kuete, Victor; Efferth, Thomas

    2017-01-01

    Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA) regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp), multi drug-resistance-related proteins (MRPs), breast cancer resistance protein (BCRP, ABCG2) as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1), human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways. Plants with the ability to preferentially kills resistant cancer cells were also reported. Data compiled in the present document were retrieved from scientific websites such as PubMed, Scopus, Sciencedirect, Web-of-Science, and Scholar Google. In summary, plant extracts from CEWA and isolated compounds thereof exert cytotoxic effects by several modes of action including caspases activation, alteration of mitochondrial membrane potential (MMP), induction of reactive oxygen species (ROS) in cancer cells and inhibition of angiogenesis. Ten strongest cytotoxic plants from CEWA recorded following in vitro screening assays are: Beilschmiedia acuta Kosterm, Echinops giganteus var. lelyi (C. D. Adams) A. Rich., Erythrina sigmoidea Hua (Fabaceae), Imperata cylindrical Beauv. var. koenigii Durand et Schinz, Nauclea pobeguinii (Pobég. ex Pellegr.) Merr. ex E.M.A., Piper capense L.f., Polyscias fulva (Hiern) Harms., Uapaca togoensis Pax., Vepris soyauxii Engl. and Xylopia aethiopica (Dunal) A. Rich. Prominent antiproliferative compounds include: isoquinoline alkaloid isotetrandrine (51), two

  11. Surface potential, charging and local current transport of individual Ge quantum dots grown by molecular beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Singha, R.K. [Department of Physics, Visva-Bharati, Santiniketan 731235 (India); Manna, S.; Bar, R.; Das, S. [Department of Physics, Indian Institute of Technology-Kharagpur, Kharagpur 721302 (India); Ray, S.K., E-mail: physkr@phy.iitkgp.ernet.in [Department of Physics, Indian Institute of Technology-Kharagpur, Kharagpur 721302 (India)

    2017-06-15

    Highlights: We have elaborately explained the individual Ge QD charging phenomena and current transport, which is very important to understand the Ge/Si nano devices. This paper will give a flavor to properly understand these phenomena linked together along with the photocurrent mechanism which is related to the Ge/Si valence band offset. • Both the CAFM and KPFM techniques point out the functionality of doping nature of the underneath Si substrate on the aforementioned characteristics of Ge QDs. • Analysis of the surface potential mapping using KPFM technique yields an approximate valence band offset measurement which is required to understand the intra-valence transition of holes for the realization of long wavelength infrared photodetector. • KPFM and CAFM can be utilized to explore the charging/discharging phenomena of dots and their composition variations. • Current-voltage (I–V) characteristics of the individual Ge QD strongly depends on the individual QD size. • Energy band diagrams for diamond tip and Ge QD shows the higher barrier for electrons and lower barrier for holes allowing the easy tunneling for holes to dominate the transport. - Abstract: It is fundamentally important to understand the nanoscale electronic properties of a single quantum dot (QD) contrary to an ensemble of QDs. Kelvin probe force microscopy (KPFM) and conductive atomic force microscopy (CAFM) are two important tools, which could be employed to probe surface potential, charging phenomena, and current transport mechanism of individual QD. We demonstrate the aforementioned characteristics of self-assembled Ge QDs, which was grown on Si substrates by solid source molecular beam epitaxy driven by the Stranski-Krastanov method. Study reveals that each Ge QD acts as charge storage node even at zero applied bias. The shape, size and density of QDs could be well probed by CAFM and KPFM, whereas QD facets could be better resolved by the conductive tip. The CAFM investigation

  12. Roles of N-methyl-d-aspartate receptors during the sensory stimulation-evoked field potential responses in mouse cerebellar cortical molecular layer.

    Science.gov (United States)

    Xu, Yin-Hua; Zhang, Guang-Jian; Zhao, Jing-Tong; Chu, Chun-Ping; Li, Yu-Zi; Qiu, De-Lai

    2017-11-01

    The functions of N-methyl-d-aspartate receptors (NMDARs) in cerebellar cortex have been widely studied under in vitro condition, but their roles during the sensory stimulation-evoked responses in the cerebellar cortical molecular layer in living animals are currently unclear. We here investigated the roles of NMDARs during the air-puff stimulation on ipsilateral whisker pad-evoked field potential responses in cerebellar cortical molecular layer in urethane-anesthetized mice by electrophysiological recording and pharmacological methods. Our results showed that cerebellar surface administration of NMDA induced a dose-dependent decrease in amplitude of the facial stimulation-evoked inhibitory responses (P1) in the molecular layer, accompanied with decreases in decay time, half-width and area under curve (AUC) of P1. The IC 50 of NMDA induced inhibition in amplitude of P1 was 46.5μM. In addition, application of NMDA induced significant increases in the decay time, half-width and AUC values of the facial stimulation-evoked excitatory responses (N1) in the molecular layer. Application of an NMDAR blocker, D-APV (250μM) abolished the facial stimulation-evoked P1 in the molecular layer. These results suggested that NMDARs play a critical role during the sensory information processing in cerebellar cortical molecular layer in vivo in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Molecular interaction studies of acetylcholinesterase with potential acetylcholinesterase inhibitors from the root of Rhodiola crenulata using molecular docking and isothermal titration calorimetry methods.

    Science.gov (United States)

    Li, Fa-Jie; Liu, Yuan; Yuan, Yuan; Yang, Bin; Liu, Zhen-Ming; Huang, Lu-Qi

    2017-11-01

    (-)-Epicatechin gallate ((-)-ECG), 1,2,3,4,6-O-pentagalloylglucose (PGG), rhodionin, herbacetin and rhodiosin isolated from the root of Rhodiola crenulata exhibited potent, dose-dependent inhibitory effects on acetylcholinesterase (AChE) with IC 50 ranged from 57.50±5.83 to 2.43±0.34μg/mL. With the aim of explaining the differences in activity of these active ingredients and clarifying how they inhibit AChE, the AChE-inhibitor interactions were further explored using molecular docking and isothermal titration calorimetry (ITC) methods in the present study. Molecular docking studies revealed that all compounds except PGG showed binding energy values ranging from -10.30 to -8.00kcal/mol while the binding energy of galantamine, a known AChE inhibitor, was -9.53kcal/mol; they inhibited the AChE by binding into the ligand pocket with the similar binding pattern to that of galantamine by interacting with Glu199 of AChE. Inhibition constant of these active ingredients had a positive correlation with binding energy. The interaction between AChE and PGG was further evaluated with the ITC method and the results indicated that the PGG-AChE interaction was relevant to AChE concentration. The results revealed a possible mechanism for the AChE inhibition activity of these bioactive ingredients, which may provide some help in lead compounds optimization in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Potential Energy and Free Energy Surfaces of the Formic Acid Dimer: Correlared ab initio Calculations and Molecular Dynamics Simulations

    Czech Academy of Sciences Publication Activity Database

    Chocholoušová, Jana; Vacek, Jaroslav; Hobza, Pavel

    2002-01-01

    Roč. 4, - (2002), s. 2119-2122 ISSN 1463-9076 R&D Projects: GA MŠk LN00A032 Institutional research plan: CEZ:AV0Z4040901 Keywords : formic acid dimer * ab initio calculations * molecular dynamics simulations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.838, year: 2002

  15. CpG Methylation Analysis—Current Status of Clinical Assays and Potential Applications in Molecular Diagnostics

    Science.gov (United States)

    Sepulveda, Antonia R.; Jones, Dan; Ogino, Shuji; Samowitz, Wade; Gulley, Margaret L.; Edwards, Robin; Levenson, Victor; Pratt, Victoria M.; Yang, Bin; Nafa, Khedoudja; Yan, Liying; Vitazka, Patrick

    2009-01-01

    Methylation of CpG islands in gene promoter regions is a major molecular mechanism of gene silencing and underlies both cancer development and progression. In molecular oncology, testing for the CpG methylation of tissue DNA has emerged as a clinically useful tool for tumor detection, outcome prediction, and treatment selection, as well as for assessing the efficacy of treatment with the use of demethylating agents and monitoring for tumor recurrence. In addition, because CpG methylation occurs early in pre-neoplastic tissues, methylation tests may be useful as markers of cancer risk in patients with either infectious or inflammatory conditions. The Methylation Working Group of the Clinical Practice Committee of the Association of Molecular Pathology has reviewed the current state of clinical testing in this area. We report here our summary of both the advantages and disadvantages of various methods, as well as the needs for standardization and reporting. We then conclude by summarizing the most promising areas for future clinical testing in cancer molecular diagnostics. PMID:19541921

  16. Density functional calculations of potential energy surface and charge transfer integrals in molecular triphenylene derivative HAT6

    NARCIS (Netherlands)

    Zbiri, M.; Johnson, M.R.; Kearley, G.J.; Mulder, F.M.

    2009-01-01

    We investigate the effect of structural fluctuations on charge transfer integrals, overlap integrals, and site energies in a system of two stacked molecular 2,3,6,7,10,11-hexakishexyloxytriphenylene (HAT6), which is a model system for conducting devices in organic photocell applications. A density

  17. Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.; Choy, Hak; Dicker, Adam P.; Saha, Debabrata; Simko, Jeff; Story, Michael D.; Torossian, Artour; Lu, Bo

    2012-01-01

    Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

  18. Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

    Science.gov (United States)

    Shen, Lin; Yang, Weitao

    2016-04-12

    We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

  19. Parameter-free one-center model potential for an effective one-electron description of molecular hydrogen

    DEFF Research Database (Denmark)

    Lühr, Armin Christian; Vanne, Yulian; Saenz, Alejandro

    2008-01-01

    For the description of an H2 molecule, an effective one-electron model potential is proposed which is fully determined by the exact ionization potential of the H2 molecule. In order to test the model potential and examine its properties, it is employed to determine excitation energies, transition...

  20. Getting the Right Answers for the Right Reasons: Toward Predictive Molecular Simulations of Water with Many-Body Potential Energy Functions.

    Science.gov (United States)

    Paesani, Francesco

    2016-09-20

    The central role played by water in fundamental processes relevant to different disciplines, including chemistry, physics, biology, materials science, geology, and climate research, cannot be overemphasized. It is thus not surprising that, since the pioneering work by Stillinger and Rahman, many theoretical and computational studies have attempted to develop a microscopic description of the unique properties of water under different thermodynamic conditions. Consequently, numerous molecular models based on either molecular mechanics or ab initio approaches have been proposed over the years. However, despite continued progress, the correct prediction of the properties of water from small gas-phase clusters to the liquid phase and ice through a single molecular model remains challenging. To large extent, this is due to the difficulties encountered in the accurate modeling of the underlying hydrogen-bond network in which both number and strength of the hydrogen bonds vary continuously as a result of a subtle interplay between energetic, entropic, and nuclear quantum effects. In the past decade, the development of efficient algorithms for correlated electronic structure calculations of small molecular complexes, accompanied by tremendous progress in the analytical representation of multidimensional potential energy surfaces, opened the doors to the design of highly accurate potential energy functions built upon rigorous representations of the many-body expansion (MBE) of the interaction energies. This Account provides a critical overview of the performance of the MB-pol many-body potential energy function through a systematic analysis of energetic, structural, thermodynamic, and dynamical properties as well as of vibrational spectra of water from the gas to the condensed phase. It is shown that MB-pol achieves unprecedented accuracy across all phases of water through a quantitative description of each individual term of the MBE, with a physically correct representation

  1. Exploring the molecular mechanisms underlying the potentiation of exogenous growth hormone on alcohol-induced fatty liver diseases in mice

    Directory of Open Access Journals (Sweden)

    Tian Ya-ping

    2010-11-01

    Full Text Available Abstract Background Growth hormone (GH is an essential regulator of intrahepatic lipid metabolism by activating multiple complex hepatic signaling cascades. Here, we examined whether chronic exogenous GH administration (via gene therapy could ameliorate liver steatosis in animal models of alcoholic fatty liver disease (AFLD and explored the underlying molecular mechanisms. Methods Male C57BL/6J mice were fed either an alcohol or a control liquid diet with or without GH therapy for 6 weeks. Biochemical parameters, liver histology, oxidative stress markers, and serum high molecular weight (HMW adiponectin were measured. Quantitative real-time PCR and western blotting were also conducted to determine the underlying molecular mechanism. Results Serum HMW adiponectin levels were significantly higher in the GH1-treated control group than in the control group (3.98 ± 0.71 μg/mL vs. 3.07 ± 0.55 μg/mL; P P P P P Conclusions GH therapy had positive effects on AFLD and may offer a promising approach to prevent or treat AFLD. These beneficial effects of GH on AFLD were achieved through the activation of the hepatic adiponectin-SIRT1-AMPK and PPARα-AMPK signaling systems.

  2. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.

    Science.gov (United States)

    Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

    2014-12-01

    Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  3. Molecular Docking Simulation of Neuraminidase Influenza A Subtype H1N1 with Potential Inhibitor of Disulfide Cyclic Peptide (DNY, NNY, LRL)

    Science.gov (United States)

    Putra, R. P.; Imaniastuti, R.; Nasution, M. A. F.; Kerami, Djati; Tambunan, U. S. F.

    2018-04-01

    Oseltamivir resistance as an inhibitor of neuraminidase influenza A virus subtype H1N1 has been reported lately. Therefore, to solve this problem, several kinds of research has been conducted to design and discover disulfide cyclic peptide ligands through molecular docking method, to find the potential inhibitors for neuraminidase H1N1 which then can disturb the virus replication. This research was studied and evaluated the interaction of ligands toward enzyme using molecular docking simulation, which was performed on three disulfide cyclic peptide inhibitors (DNY, LRL, and NNT), along with oseltamivir and zanamivir as the standard ligands using MOE 2008.10 software. The docking simulation shows that all disulfide cyclic peptide ligands have lower Gibbs free binding energies (ΔGbinding) than the standard ligands, with DNY ligand has the lowest ΔGbinding at -7.8544 kcal/mol. Furthermore, these ligands were also had better molecular interactions with neuraminidase than the standards, owing by the hydrogen bonds that were formed during the docking simulation. In the end, we concluded that DNY, LRL and NNT ligands have the potential to be developed as the inhibitor of neuraminidase H1N1.

  4. In silico molecular docking studies of new potential 4-phthalazinyl-hydrazones on selected Trypanosoma cruzi and Leishmania enzyme targets.

    Science.gov (United States)

    Romero, Angel H; López, Simón E

    2017-09-01

    Recently, a series of 4-phthalazinyl-hydrazones under its E-configuration have exhibited excellent in vitro antichagasic and antileishmanial profiles. Preliminary assays on both parasites suggested that the most active derivatives act through oxidative and nitrosative stress mechanisms; however, their exact mode of actions as anti-trypanosomal and anti-leishmanial agents have not been completely elucidated. This motivated to perform a molecular docking study on essential trypanosomatid enzymes such as superoxide dismutase (SOD), trypanothione reductase (TryR), cysteine-protease (CP) and pteridine reductase 1 (PTR1). In addition, to understand the experimental results of nitric oxide production obtained for infected macrophages with Leishmania parasite, a molecular docking was evaluated on nitric oxide synthase (iNOS) enzyme of Rattus norvegicus. Both diastereomers (E and Z) of the 4-phthalazinyl-hydrazones were docked on the mentioned targets. In general, molecular docking on T. cruzi enzymes revealed that the E-diastereomers exhibited lower binding energies than Z-diastereomers on the Fe-SOD and CP enzymes, while Z-diastereomers showed lower docking energies than E-isomers on TryR enzyme. For the Leishmania docking studies, the Z-isomers exhibited the best binding affinities on the PTR1 and iNOS enzymes, while the TryR enzyme showed a minor dependence with the stereoselectivity of the tested phthalazines. However, either the structural information of the ligand-enzyme complexes or the experimental data suggest that the significant antitrypanosomatid activity of the most active derivatives is not associated to the inhibition of the SOD, CP and PTR1 enzymes, while the TryR inhibition and nitric oxide generation in host cells emerge as interesting antitrypanosomatid therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Linear and nonlinear relationships between biodegradation potential and molecular descriptors/fragments for organic pollutants and a theoretical interpretation

    International Nuclear Information System (INIS)

    He, Jia; Qin, Weichao; Zhang, Xujia; Wen, Yang; Su, Limin; Zhao, Yuanhui

    2013-01-01

    Prediction of the biodegradability of organic pollutants is an ecologically desirable and economically feasible tool for estimating the environmental fate of chemicals. In this paper, linear and nonlinear relationships between biological oxygen demand (BOD) and molecular descriptors/fragments have been investigated for 1130 organic chemicals. Significant relationships have been observed between the simple molecular descriptors and %BOD for some homologous compounds, but not for the whole set of compounds. Electronic parameters, such as E HOMO and E LUMO , are the dominant factors affecting the biodegradability for some homologous chemicals. However, other descriptors, such as molecular weight, acid dissociation constant and polarity still have a significant impact on the biodegradation. The best global model for %BOD prediction is that developed from a chain-based fragmentation scheme. At the same time, the theoretical relationship between %BOD and molecular descriptors/fragments has been investigated, based on a first-order kinetic process. The %BOD is nonlinearly, rather than linearly, related to the descriptors. The coefficients of determination can be significantly improved by using nonlinear models for the homologous compounds and the whole data set. After analysing 1130 ready and not ready biodegradable compounds using 23 simple descriptors and various fragmentation schemes, it was revealed that biodegradation could be well predicted from a chain-based fragmentation scheme, a decision tree and a %BOD model. The models were capable of separating NRB and RB with an overall accuracy of 87.2%, 83.0% and 82.5%, respectively. The best classification model developed was a chain-based model but it used 155 fragments. The simplest model was a decision tree which only used 10 structural fragments. The effect of structures on the biodegradation has been analysed and the biodegradation pathway and mechanisms have been discussed based on activating and inactivating

  6. First molecular evidence of potentially zoonotic Babesia microti and Babesia sp. EU1 in Ixodes ricinus ticks in Belgium

    OpenAIRE

    Lempereur, L.; De Cat, A.; Caron, Y.; Madder, M.; Claerebout, E.; Saegerman, C.; Losson, B.

    2011-01-01

    We report the first molecular evidence of the presence of Babesia sp. EU1 and Babesia microti in Ixodes ricinus ticks in Belgium. A 1-year national survey collected 1005 ticks from cats and dogs. A polymerase chain reaction technique amplifying a part of the 18S rRNA gene detected Babesia spp. in 11 out of 841 selected and validated tick extracts. Subsequent sequencing identified Ba. microti (n = 3) and Babesia sp. EU1 (n = 6). This study has demonstrated a low infection rate (1.31% with 95% ...

  7. Spectroscopic investigation (FT-IR, FT-Raman), HOMO-LUMO, NBO, and molecular docking analysis of N-ethyl-N-nitrosourea, a potential anticancer agent

    Science.gov (United States)

    Singh, Priyanka; Islam, S. S.; Ahmad, Hilal; Prabaharan, A.

    2018-02-01

    Nitrosourea plays an important role in the treatment of cancer. N-ethyl-N-nitrosourea, also known as ENU, (chemical formula C3H7N3O2), is a highly potent mutagen. The chemical is an alkylating agent and acts by transferring the ethyl group of ENU to nucleobases (usually thymine) in nucleic acids. The molecular structure of N-ethyl-N-nitrosourea has been elucidated using experimental (FT-IR and FT-Raman) and theoretical (DFT) techniques. APT charges, Mulliken atomic charges, Natural bond orbital, Electrostatic potential, HOMO-LUMO and AIM analysis were performed to identify the reactive sites and charge transfer interactions. Furthermore, to evaluate the anticancer activity of ENU molecular docking studies were carried out against 2JIU protein.

  8. Scattering of thermal He beams by crossed atomic and molecular beams. II. The He--Ar van der Waals potential

    International Nuclear Information System (INIS)

    Keilb, M.; Slankas, J.T.; Kuppermann, A.

    1979-01-01

    Differential cross sections for He--Ar scattering at room temperature have been measured. The experimental consistency of these measurements with others performed in different laboratories is demonstrated. Despite this consistency, the present van der Waals well depth of 1.78 meV, accurate to 10%, is smaller by 20% to 50% than the experimental values obtained previously. These discrepancies are caused by differences between the assumed mathematical forms or between the assumed dispersion coefficients of the potentials used in the present paper and those of previous studies. Independent investigations have shown that the previous assumptions are inappropriate for providing accurate potentials from fits to experimental differential cross section data for He--Ar. We use two forms free of this inadequacy in the present analysis: a modified version of the Simons--Parr--Finlan--Dunham (SPFD) potential, and a double Morse--van der Waals (M 2 SV) type of parameterization. The resulting He--Ar potentials are shown to be equal to with experimental error, throughout the range of interatomic distances to which the scattering data are sensitive. The SPFD or M 2 SV potentials are combined with a repulsive potential previously determined exclusively from fits to gas phase bulk properties. The resulting potentials, valid over the extended range of interatomic distances r> or approx. =2.4 A, are able to reproduce all these bulk properties quite well, without adversely affecting the quality of the fits to the DCS

  9. BRCA1, FANCD2 and Chk1 are potential molecular targets for the modulation of a radiation-induced DNA damage response in bystander cells.

    Science.gov (United States)

    Burdak-Rothkamm, Susanne; Rothkamm, Kai; McClelland, Keeva; Al Rashid, Shahnaz T; Prise, Kevin M

    2015-01-28

    Radiotherapy is an important treatment option for many human cancers. Current research is investigating the use of molecular targeted drugs in order to improve responses to radiotherapy in various cancers. The cellular response to irradiation is driven by both direct DNA damage in the targeted cell and intercellular signalling leading to a broad range of bystander effects. This study aims to elucidate radiation-induced DNA damage response signalling in bystander cells and to identify potential molecular targets to modulate the radiation induced bystander response in a therapeutic setting. Stalled replication forks in T98G bystander cells were visualised via bromodeoxyuridine (BrdU) nuclear foci detection at sites of single stranded DNA. γH2AX co-localised with these BrdU foci. BRCA1 and FANCD2 foci formed in T98G bystander cells. Using ATR mutant F02-98 hTERT and ATM deficient GM05849 fibroblasts it could be shown that ATR but not ATM was required for the recruitment of FANCD2 to sites of replication associated DNA damage in bystander cells whereas BRCA1 bystander foci were ATM-dependent. Phospho-Chk1 foci formation was observed in T98G bystander cells. Clonogenic survival assays showed moderate radiosensitisation of directly irradiated cells by the Chk1 inhibitor UCN-01 but increased radioresistance of bystander cells. This study identifies BRCA1, FANCD2 and Chk1 as potential targets for the modulation of radiation response in bystander cells. It adds to our understanding of the key molecular events propagating out-of-field effects of radiation and provides a rationale for the development of novel molecular targeted drugs for radiotherapy optimisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Global transcriptomic profiling of aspen trees under elevated [CO2] to identify potential molecular mechanisms responsible for enhanced radial growth.

    Science.gov (United States)

    Wei, Hairong; Gou, Jiqing; Yordanov, Yordan; Zhang, Huaxin; Thakur, Ramesh; Jones, Wendy; Burton, Andrew

    2013-03-01

    Aspen (Populus tremuloides) trees growing under elevated [CO(2)] at a free-air CO(2) enrichment (FACE) site produced significantly more biomass than control trees. We investigated the molecular mechanisms underlying the observed increase in biomass by producing transcriptomic profiles of the vascular cambium zone (VCZ) and leaves, and then performed a comparative study to identify significantly changed genes and pathways after 12 years exposure to elevated [CO(2)]. In leaves, elevated [CO(2)] enhanced expression of genes related to Calvin cycle activity and linked pathways. In the VCZ, the pathways involved in cell growth, cell division, hormone metabolism, and secondary cell wall formation were altered while auxin conjugation, ABA synthesis, and cytokinin glucosylation and degradation were inhibited. Similarly, the genes involved in hemicellulose and pectin biosynthesis were enhanced, but some genes that catalyze important steps in lignin biosynthesis pathway were inhibited. Evidence from systemic analysis supported the functioning of multiple molecular mechanisms that underpin the enhanced radial growth in response to elevated [CO(2)].

  11. Morphological and molecular characterization of lymnaeid snails and their potential role in transmission of Fasciola spp. in Vietnam.

    Science.gov (United States)

    Dung, Bui Thi; Doanh, Pham Ngoc; The, Dang Tat; Loan, Ho Thi; Losson, Bertrand; Caron, Yannick

    2013-12-01

    Freshwater snails of the family Lymnaeidae play an important role in the transmission of fascioliasis worldwide. In Vietnam, 2 common lymnaeid species, Lymnaea swinhoei and Lymnaea viridis, can be recognized on the basis of morphology, and a third species, Lymnaea sp., is known to exist. Recent studies have raised controversy about their role in transmission of Fasciola spp. because of confusion in identification of the snail hosts. The aim of this study is, therefore, to clarify the identities of lymnaeid snails in Vietnam by a combination of morphological and molecular approaches. The molecular analyses using the second internal transcribed spacer (ITS2) of the nuclear ribosomal DNA clearly showed that lymnaeids in Vietnam include 3 species, Austropeplea viridis (morphologically identified as L. viridis), Radix auricularia (morphologically identified as L. swinhoei) and Radix rubiginosa (morphologically identified as Lymnaea sp.). R. rubiginosa is a new record for Vietnam. Among them, only A. viridis was found to be infected with Fasciola spp. These results provide a new insight into lymnaeid snails in Vietnam. Identification of lymnaeid snails in Vietnam and their role in the liver fluke transmission should be further investigated.

  12. MOLECULAR MODELING OF 1-OCTADECYL-2-METHOXYPROPYL-(N,N-DIMETHYL- beta-HYDROXYETHYLAMMONIUM IODIDE ANALOGS AS POTENTIAL ANTITUMOR COMPOUNDS

    Directory of Open Access Journals (Sweden)

    Sophie Rodriguez de L.

    2010-08-01

    Full Text Available En nuestra búsqueda de nuevos compuestos con actividad antitumoral y/o anti- HIV, estudiamos nuevos análogos del Yoduro de l-Octadecil-2-Metoxipropil- (N,N - dimetil - P - hidroxietilamonio, un éter lipídico de conocida actividad antitumoral y antiHIV. Se modelaron los compuestos propuestos, substituyendo la cadena bidrofóbica por cadenas similares a los lípidos de la membrana celular. Para el análisis conformacional se utilizaron cálculos de Mecánica Molecular y Dinámica Molecular. Las conformaciones de mínima energía obtenidas ftieron superpuestas con el compuesto de referencia, obteniéndose una buena superposición, concluyéndose que podrían presentar propiedades similares a los éteres lipidíeos en la membrana celular y por tanto son buenos candidatos para ser sintetizados.

  13. Internal molecular dynamics of LaI3. I. Potential energy function of vibrational modes in harmonic and anharmonic approximations

    International Nuclear Information System (INIS)

    Giricheva, N.I.; Girichev, G.V.; Smorodin, S.V.

    2007-01-01

    Scanning of potential energy surface in the LaI 3 molecule along normal coordinates are realized using the B3LYP/SDD,SDD method. The most anharmonicity is shown to have a potential function of non-planar oscillation ν 2 (A 2 ''). Effect of anharmonicity on the value of mean-square oscillation amplitudes and oscillation spectrum of the molecule is established. It is noted that the account of anharmonicity of potential functions leads to decreasing mean-square oscillation amplitudes [ru

  14. The anisotropic potential of molecular hydrogen determined from the scattering of oriented H2 on inert gases

    International Nuclear Information System (INIS)

    Zandee, A.P.L.M.

    1977-01-01

    This thesis deals with an experiment aimed at determining the angle dependence of an intermolecular potential between H 2 molecule and a rare gas atom. The small relative difference in total collision cross section for beams of differently oriented H 2 molecules colliding with inert gas atoms in a scattering box is measured (anisotropy A). Through variation of the orientation and by studying its influence on the total collision cross sections, the angle dependence of the intermolecular potential can be arrived at

  15. Biochemical, structural and molecular dynamics analyses of the potential virulence factor RipA from Yersinia pestis.

    Directory of Open Access Journals (Sweden)

    Rodrigo Torres

    Full Text Available Human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. A subset of these pathogens has developed mechanisms to survive in human macrophages. Yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. A previous study has shown that a novel rip (required for intracellular proliferation operon (ripA, ripB and ripC is essential for replication and survival of Y. pestis in postactivated macrophages, by playing a role in lowering macrophage-produced nitric oxide (NO levels. A bioinformatics analysis indicates that the rip operon is conserved among a distally related subset of macrophage-residing pathogens, including Burkholderia and Salmonella species, and suggests that this previously uncharacterized pathway is also required for intracellular survival of these pathogens. The focus of this study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate-CoA transferase; however, biochemical analysis suggests that RipA functions as a butyryl-CoA transferase. The 1.9 Å X-ray crystal structure reveals that RipA belongs to the class of Family I CoA transferases and exhibits a unique tetrameric state. Molecular dynamics simulations are consistent with RipA tetramer formation and suggest a possible gating mechanism for CoA binding mediated by Val227. Together, our structural characterization and molecular dynamic simulations offer insights into acyl-CoA specificity within the active site binding pocket, and support biochemical results that RipA is a butyryl-CoA transferase. We hypothesize that the end product of the rip operon is butyrate, a known anti-inflammatory, which has been shown to lower NO levels in macrophages. Thus, the results of this molecular study of Y. pestis RipA provide a structural platform for rational inhibitor design, which may lead to a greater understanding of the

  16. Interaction between ropinirole hydrochloride and aspirin with human serum albumin as binary and ternary systems by multi-spectroscopic, molecular modeling and zeta potential

    International Nuclear Information System (INIS)

    Mahaki, Hanie; Memarpoor-Yazdi, Mina; Chamani, Jamshidkhan; Reza Saberi, Mohammad

    2013-01-01

    The aim of the present study was to describe the competition of ropinirole hydrochloride (RP) and aspirin (ASA) in binding to human serum albumin (HSA) in physiological buffer (pH=7.4) using multi-spectroscopic, molecular modeling and zeta-potential measurements. Fluorescence analysis was used to define the binding and quenching properties of drug-HSA complexes in binary and ternary systems. Fluorescence spectroscopy showed that in the presence of RP, the binding constant of HSA–ASA was increased. Static quenching was confirmed to result in the fluorescence quenching and FRET. The effect of drugs on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy, three-dimensional fluorescence spectra and circular dichroism (CD). The RLS method determined the critical aggregation concentration of drugs on HSA in binary and ternary systems that confirmed the zeta potential results. Structural modeling showed that the affinity of each of the drugs to HSA in binary and ternary systems confirms the spectroscopic results. - Highlights: ► We studied the interaction of ropinirole hydrochloride and aspirin with HSA. ► Molecular modeling and zeta-potential used to describe competitive interaction. ► We determined the critical induced aggregation concentration of both drugs on HSA. ► The binding mechanism of drugs as separate and simultaneous to HSA has been compared. ► The binding site of both drugs as simultaneous effects on HSA has been determined.

  17. Interaction between ropinirole hydrochloride and aspirin with human serum albumin as binary and ternary systems by multi-spectroscopic, molecular modeling and zeta potential

    Energy Technology Data Exchange (ETDEWEB)

    Mahaki, Hanie, E-mail: hanieh.mahaki@gmail.com [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Memarpoor-Yazdi, Mina; Chamani, Jamshidkhan [Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Reza Saberi, Mohammad [Medical Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

    2013-02-15

    The aim of the present study was to describe the competition of ropinirole hydrochloride (RP) and aspirin (ASA) in binding to human serum albumin (HSA) in physiological buffer (pH=7.4) using multi-spectroscopic, molecular modeling and zeta-potential measurements. Fluorescence analysis was used to define the binding and quenching properties of drug-HSA complexes in binary and ternary systems. Fluorescence spectroscopy showed that in the presence of RP, the binding constant of HSA-ASA was increased. Static quenching was confirmed to result in the fluorescence quenching and FRET. The effect of drugs on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy, three-dimensional fluorescence spectra and circular dichroism (CD). The RLS method determined the critical aggregation concentration of drugs on HSA in binary and ternary systems that confirmed the zeta potential results. Structural modeling showed that the affinity of each of the drugs to HSA in binary and ternary systems confirms the spectroscopic results. - Highlights: Black-Right-Pointing-Pointer We studied the interaction of ropinirole hydrochloride and aspirin with HSA. Black-Right-Pointing-Pointer Molecular modeling and zeta-potential used to describe competitive interaction. Black-Right-Pointing-Pointer We determined the critical induced aggregation concentration of both drugs on HSA. Black-Right-Pointing-Pointer The binding mechanism of drugs as separate and simultaneous to HSA has been compared. Black-Right-Pointing-Pointer The binding site of both drugs as simultaneous effects on HSA has been determined.

  18. NSAIDs as potential treatment option for preventing amyloid β toxicity in Alzheimer's disease: an investigation by docking, molecular dynamics, and DFT studies.

    Science.gov (United States)

    Azam, Faizul; Alabdullah, Nada Hussin; Ehmedat, Hadeel Mohammed; Abulifa, Abdullah Ramadan; Taban, Ismail; Upadhyayula, Sreedevi

    2018-06-01

    Aggregation of amyloid beta (Aβ) protein considered as one of contributors in development of Alzheimer's disease (AD). Several investigations have identified the importance of non-steroidal anti-inflammatory drugs (NSAIDs) as Aβ aggregation inhibitors. Here, we have examined the binding interactions of 24 NSAIDs belonging to eight different classes, with Aβ fibrils by exploiting docking and molecular dynamics studies. Minimum energy conformation of the docked NSAIDs were further optimized by density functional theory (DFT) employing Becke's three-parameter hybrid model, Lee-Yang-Parr (B3LYP) correlation functional method. DFT-based global reactivity descriptors, such as electron affinity, hardness, softness, chemical potential, electronegativity, and electrophilicity index were calculated to inspect the expediency of these descriptors for understanding the reactive nature and sites of the molecules. Few selected NSAID-Aβ fibrils complexes were subjected to molecular dynamics simulation to illustrate the stability of these complexes and the most prominent interactions during the simulated trajectory. All of the NSAIDs exhibited potential activity against Aβ fibrils in terms of predicted binding affinity. Sulindac was found to be the most active compound underscoring the contribution of indene methylene substitution, whereas acetaminophen was observed as least active NSAID. General structural requirements for interaction of NSAIDs with Aβ fibril include: aryl/heteroaryl aromatic moiety connected through a linker of 1-2 atoms to a distal aromatic group. Considering these structural requirements and electronic features, new potent agents can be designed and developed as potential Aβ fibril inhibitors for the treatment of AD.

  19. Potential bacterial core species associated with digital dermatitis in cattle herds identified by molecular profiling of interdigital skin samples

    DEFF Research Database (Denmark)

    Weiss Nielsen, Martin; Strube, Mikael Lenz; Isbrand, Anastasia

    2016-01-01

    of different molecular methods. Deep sequencing of the 16S rRNA gene variable regions V1–V2 showed that Treponema, Mycoplasma, Fusobacterium and Porphyromonas were the genera best differentiating the DD samples from the controls. Additional deep sequencing analysis of the most abundant genus, Treponema...... in the epidermal lesions and were present in only a subset of samples. RT-qPCR analysis showed that treponemes were also actively expressing a panel of virulence factors at the site of infection. Our results further support the hypothesis that species belonging to the genus Treponema are major pathogens of DD...... and also provide sufficient clues to motivate additional research into the role of M. fermentans, F. necrophorum and P. levii in the etiology of DD....

  20. Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

    Science.gov (United States)

    Hariono, Maywan; Abdullah, Nurshariza; Damodaran, K. V.; Kamarulzaman, Ezatul E.; Mohamed, Nornisah; Hassan, Sharifah Syed; Shamsuddin, Shaharum; Wahab, Habibah A.

    2016-12-01

    We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.