Neural tube defects – recent advances, unsolved questions and controversies

PubMed Central

Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E.

2014-01-01

Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

Contemporary Clinical Management of Endometrial Cancer

PubMed Central

Dinkelspiel, Helen E.; Wright, Jason D.; Lewin, Sharyn N.; Herzog, Thomas J.

2013-01-01

Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions. PMID:23864861

Level statistics of disordered spin-1/2 systems and materials with localized Cooper pairs.

PubMed

Cuevas, Emilio; Feigel'man, Mikhail; Ioffe, Lev; Mezard, Marc

2012-01-01

The origin of continuous energy spectra in large disordered interacting quantum systems is one of the key unsolved problems in quantum physics. Although small quantum systems with discrete energy levels are noiseless and stay coherent forever in the absence of any coupling to external world, most large-scale quantum systems are able to produce a thermal bath and excitation decay. This intrinsic decoherence is manifested by a broadening of energy levels, which aquire a finite width. The important question is: what is the driving force and the mechanism of transition(s) between these two types of many-body systems - with and without intrinsic decoherence? Here we address this question via the numerical study of energy-level statistics of a system of interacting spin-1/2 with random transverse fields. We present the first evidence for a well-defined quantum phase transition between domains of discrete and continous many-body spectra in such spin models, implying the appearance of novel insulating phases in the vicinity of the superconductor-insulator transition in InO(x) and similar materials.

[Validation of SHI Claims Data Exemplified by Gender-specific Diagnoses].

PubMed

Hartmann, J; Weidmann, C; Biehle, R

2016-10-01

Aim: Use of statutory health insurance (SHI) data in health services research is increasing steadily and questions of validity are gaining importance. Using gender-specific diagnosis as an example, the aim of this study was to estimate the prevalence of implausible diagnosis and demonstrate an internal validation strategy. Method: The analysis is based on the SHI data from Baden-Württemberg for 2012. Subject of validation are gender-specific outpatient diagnoses that mismatch with the gender of the insured. To uncover this implausibility, it is necessary to clarify whether the diagnosis or the gender is wrong. The validation criteria used were the presence of further gender-specific diagnoses, the presence of gender-specific settlement items, the specialization of the physician in charge and the gender assignment of the first name of the insured. To review the quality of the validation, it was verified if the gender was changed during the following year. Results: Around 5.1% of all diagnoses were gender-specific and there was a mismatch between diagnosis and gender in 0.04% of these cases. All validation criteria were useful to sort out implausibility, whereas the last one was the most effective. Only 14% remained unsolved. From the total of 1 145 insured with implausible gender-specific diagnoses, one year later 128 had a new gender (in the data). 119 of these cases were rightly classified as insured with wrong gender and 9 cases were in the unsolved group. This confirms that the validation works well. Conclusion: Implausibility in SHI data is relatively small and can be solved with appropriate validation criteria. When validating SHI data, it is advisable to question all data used critically, to use multiple validation criteria instead of just one and to abandon the idea that reality and the associated data conform to standardized norms. Keeping these aspects in mind, analysis of SHI data is a good starting point for research in health services. © Georg Thieme Verlag KG Stuttgart · New York.

Everything you always wanted to know about sex ... in flies.

PubMed

Arbeitman, M N; Kopp, Artyom; Siegal, M L; Van Doren, M

2010-01-01

'Everything you always wanted to know about sex' is a workshop organized as part of the annual Drosophila Research Conference of the Genetics Society of America. This workshop provides an intellectual venue for interaction among research groups that study sexual dimorphism from the molecular, evolutionary, genomic, and behavioral perspectives. The speakers summarize the key ideas behind their research for people working in other fields, outline unsolved questions, and offer their opinions about future directions. The 2010 workshop highlighted the power of the Drosophila model for understanding sexual dimorphism at levels ranging from cell biology and gene regulation to population genetics and genome evolution, and demonstrated the importance of cross-disciplinary interactions in the study of sex. In this respect, Drosophila sets a good example for research in other organisms, including humans and their mammalian relatives. Copyright © 2010 S. Karger AG, Basel.

To Be Specific or Not: The Critical Relationship Between Hox And TALE Proteins.

PubMed

Merabet, Samir; Mann, Richard S

2016-06-01

Hox proteins are key regulatory transcription factors that act in different tissues of the embryo to provide specific spatial and temporal coordinates to each cell. These patterning functions often depend on the presence of the TALE-homeodomain class cofactors, which form cooperative DNA-binding complexes with all Hox proteins. How this family of cofactors contributes to the highly diverse and specific functions of Hox proteins in vivo remains an important unsolved question. We review here the most recent advances in understanding the molecular mechanisms underlying Hox-TALE function. In particular, we discuss the role of DNA shape, DNA-binding affinity, and protein-protein interaction flexibility in dictating Hox-TALE specificity. We propose several models to explain how these mechanisms are integrated with each other in the context of the many distinct functions that Hox and TALE factors carry out in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clipping of arginine-methylated histone tails by JMJD5 and JMJD7

PubMed Central

Liu, Haolin; Wang, Chao; Lee, Schuyler; Deng, Yu; Wither, Matthew; Oh, Sangphil; Ning, Fangkun; Dege, Carissa; Zhang, Qianqian; Liu, Xinjian; Johnson, Aaron M.; Zang, Jianye; Janknecht, Ralf; Hansen, Kirk; Marrack, Philippa; Li, Chuan-Yuan; Kappler, John W.; Hagman, James; Zhang, Gongyi

2017-01-01

Two of the unsolved, important questions about epigenetics are: do histone arginine demethylases exist, and is the removal of histone tails by proteolysis a major epigenetic modification process? Here, we report that two orphan Jumonji C domain (JmjC)-containing proteins, JMJD5 and JMJD7, have divalent cation-dependent protease activities that preferentially cleave the tails of histones 2, 3, or 4 containing methylated arginines. After the initial specific cleavage, JMJD5 and JMJD7, acting as aminopeptidases, progressively digest the C-terminal products. JMJD5-deficient fibroblasts exhibit dramatically increased levels of methylated arginines and histones. Furthermore, depletion of JMJD7 in breast cancer cells greatly decreases cell proliferation. The protease activities of JMJD5 and JMJD7 represent a mechanism for removal of histone tails bearing methylated arginine residues and define a potential mechanism of transcription regulation. PMID:28847961

Intrinsic Variability in Multiple Systems and Clusters: Open Questions

NASA Astrophysics Data System (ADS)

Lampens, P.

2006-04-01

It is most interesting and rewarding to probe the stellar structure of stars which belong to a system originating from the same parent cloud as this provides additional and more accurate constraints for the models. New results on pulsating components in multiple systems and clusters are beginning to emerge regularly. Based on concrete studies, I will present still unsolved problems and discuss some of the issues which may affect our understanding of the pulsation physics in such systems but also in general.

Venus: Mysteries Of The "forgotten Planet"

NASA Astrophysics Data System (ADS)

Titov, D. V.

The first phase of Venus spacecraft exploration by the Venera, Pioneer Venus, Vega and Magellan missions and later Galileo and Cassini fly-bys established a basic de- scription of the physical and chemical conditions prevailing in the atmosphere and near-planetary environment. It also expanded considerably our knowledge of VenusS geology and geophysics. At the same time, these studies raised many questions on the physical processes on the planet, most of which remain as of today unsolved. The fundamental mysteries of Venus are related to the global atmospheric circulation, the atmospheric chemical composition and its variations, the surface-atmosphere physical and chemical interactions including volcanism, the physics and chemistry of the cloud layer, the thermal balance and role of trace gases in the greenhouse effect, the origin and evolution of the atmosphere, and the plasma environment and its interaction with the solar wind. Besides, the key issues of the history of Venusian volcanism, the global tectonic structure of Venus, and important characteristics of the planetSs surface are still unresolved. Beyond the specific case of Venus, resolving these issues is of cru- cial importance in a comparative planetology context and notably for understanding the long-term climatic evolution processes on Earth. The above problems can be effi- ciently addressed by an orbiter equipped with a suite of adequate remote sensing and in situ instruments. A combination of spectrometers, spectro-imagers, and imagers covering the UV to thermal IR range, along with other instruments such as a radar and a plasma and neutral atoms analyzer, is able to sound the entire Venus atmosphere from the surface to 200 km, and to address specific questions on the surface. Future in situ investigations by descent probes, balloons, and sample return missions will be required to provide a more detailed insight in the Venus mysteries. For more than 10 years Venus has remained the Sforgotten planetT: none of the worldSs space agencies & cedil; has considered it as a primary target. However, a great number of unsolved funda- mental problems in VenusS physics and availability of observational tools encourages the scientific community to propose missions to the planet. Venus Express in Europe and a set of Discovery missions in USA are being currently considered for inclusion in the programmes of space agencies. The Venus Orbiter mission has been recently approved in Japan.

Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites.

PubMed

Feng, Wenyi; Chakraborty, Arijita

2017-01-01

Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely implicated in a slew of human diseases ranging from neurological disorders to cancer. Yet, the paths leading to these revelations were far from direct, and the number of fragile sites that have been molecularly cloned with known disease-associated genes remains modest. Moreover, as more fragile sites were being discovered, research interests in some of the earliest discovered fragile sites ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this review we attempt to recount some of the early discoveries of fragile sites and highlight those phenomena that have eluded intense scrutiny but remain extremely relevant in our understanding of the mechanisms of chromosome fragility. We then survey the literature for disease association for a comprehensive list of fragile sites. We also review recent studies addressing the underlying cause of chromosome fragility while highlighting some ongoing debates. We report an observed enrichment for R-loop forming sequences in fragile site-associated genes than genomic average. Finally, we will leave the reader with some lingering questions to provoke discussion and inspire further scientific inquiries.

Unsolved problems in biology--The state of current thinking.

PubMed

Dev, Sukhendu B

2015-03-01

Many outstanding problems have been solved in biology and medicine for which scientists have been awarded prestigious prizes including the Nobel Prize, Lasker Award and Breakthrough Prizes in life sciences. These have been the fruits of years of basic research. From time to time, publications have appeared listing "unsolved" problems in biology. In this article, I ask the question whether it is possible to have such a list, if not a unique one, at least one that is analogous to the Millennium Prize in mathematics. My approach to finding an answer to this question was to gather views of leading biologists. I have also included my own views. Analysis of all the responses received over several years has convinced me that it is difficult, but not impossible, to have such a prize. Biology is complex and very interdisciplinary these days at times involving large numbers of teams, unlike mathematics, where Andrew Wiles spent seven years in complete isolation and secrecy solving Fermat's last theorem. Such an approach is simply not possible in biology. Still I would like to suggest that a similar prize can be established by a panel of distinguished scientists. It would be awarded to those who solved one of the listed problems in biology that warrant a verifiable solution. Despite many different opinions, I found that there is some commonality in the responses I received - I go on to discuss what these are and how they may impact future thinking. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lutzomyia longipalpis urbanisation and control

PubMed Central

Salomón, Oscar Daniel; Feliciangeli, María Dora; Quintana, María Gabriela; Afonso, Margarete Martins dos Santos; Rangel, Elizabeth Ferreira

2015-01-01

Since the description of Lutzomyia longipalpis by Lutz and Neiva more than 100 years ago, much has been written in the scientific literature about this phlebotomine species. Soares and Turco (2003) and Lainson and Rangel (2005) have written extensive reviews focused on vector-host-parasite interactions and American visceral leishmaniasis ecology. However, during the last two decades, the success of Lu. longipalpis in colonising urban environments and its simultaneous geographical spreading have led to new theoretical and operational questions. Therefore, this review updates the general information about this species and notes the more challenging topics regarding the new scenario of urbanisation-spreading and its control in America. Here, we summarise the literature on these issues and the remaining unsolved questions, which pose recommendations for operational research. PMID:26517497

Lutzomyia longipalpis urbanisation and control.

PubMed

Salomón, Oscar Daniel; Feliciangeli, María Dora; Quintana, María Gabriela; Afonso, Margarete Martins dos Santos; Rangel, Elizabeth Ferreira

2015-11-01

Since the description of Lutzomyia longipalpis by Lutz and Neiva more than 100 years ago, much has been written in the scientific literature about this phlebotomine species. Soares and Turco (2003) and Lainson and Rangel (2005) have written extensive reviews focused on vector-host-parasite interactions and American visceral leishmaniasis ecology. However, during the last two decades, the success of Lu. longipalpis in colonising urban environments and its simultaneous geographical spreading have led to new theoretical and operational questions. Therefore, this review updates the general information about this species and notes the more challenging topics regarding the new scenario of urbanisation-spreading and its control in America. Here, we summarise the literature on these issues and the remaining unsolved questions, which pose recommendations for operational research.

The Relationship between Video Game Use and a Performance-Based Measure of Persistence

ERIC Educational Resources Information Center

Ventura, Matthew; Shute, Valerie; Zhao, Weinan

2013-01-01

An online performance-based measure of persistence was developed using anagrams and riddles. Persistence was measured by recording the time spent on unsolved anagrams and riddles. Time spent on unsolved problems was correlated to a self-report measure of persistence. Additionally, frequent video game players spent longer times on unsolved problems…

Quantum Quasi-Paradoxes and Quantum Sorites Paradoxes

NASA Astrophysics Data System (ADS)

Smarandache, Florentin

2009-03-01

There can be generated many paradoxes or quasi-paradoxes that may occur from the combination of quantum and non-quantum worlds in physics. Even the passage from the micro-cosmos to the macro-cosmos, and reciprocally, can generate unsolved questions or counter-intuitive ideas. We define a quasi-paradox as a statement which has a prima facie self-contradictory support or an explicit contradiction, but which is not completely proven as a paradox. We present herein four elementary quantum quasi-paradoxes and their corresponding quantum Sorites paradoxes, which form a class of quantum quasi-paradoxes.

What's new on the moon?

NASA Technical Reports Server (NTRS)

1976-01-01

As a result of the Apollo program and other lunar probes, questions that remained unsolved during centuries of speculation and scientific study can now be answered concerning the composition, core, surface, age, and history of the moon. Data obtained from lunar samples and instruments on the lunar surface are being used to gain insight into the history of the earth and the other planets, planetary evolution, the development of planetary magnetic fields, the nature of the solar wind, and how the Sun operates. Projects suggested for using the moon to increase understanding of geophysics are described.

Exposure to Unsolvable Anagrams Impairs Performance on the Iowa Gambling Task

PubMed Central

Starcke, Katrin; Agorku, Janet D.; Brand, Matthias

2017-01-01

Recent research indicates that external manipulations, such as stress or mood induction, can affect decision-making abilities. In the current study, we investigated whether the exposure to an unsolvable task affected subsequent performance on the Iowa Gambling Task. Participants were randomly assigned to a condition in which they were exposed to unsolvable anagrams (n = 20), or a condition in which they worked on solvable anagrams (n = 22). Afterwards, all participants played the Iowa Gambling Task, a prominent task that measures decision making under uncertain conditions with no explicit rules for gains and losses. In this task, it is essential to process feedback from previous decisions. The results demonstrated that participants who worked on unsolvable anagrams made more disadvantageous decisions on the Iowa Gambling Task than the other participants. In addition, a significant gender effect was observed: Males who worked on unsolvable anagrams made a more disadvantageous decisions than the other male participants. Females who worked on unsolvable anagrams also made more disadvantageous decision than the other female participants, but differences were small and not significant. We conclude that the exposure to unsolvable anagrams induced the experience of uncontrollability which can elicit stress and learned helplessness. Stress and learned helplessness might have reduced the ability to learn from the given feedback, particularly in male participants. We assume that in real life, uncontrollable challenges that last longer than a single experimental manipulation can affect decision making severely, at least in males. PMID:28642693

Social selection and peer influence in an online social network.

PubMed

Lewis, Kevin; Gonzalez, Marco; Kaufman, Jason

2012-01-03

Disentangling the effects of selection and influence is one of social science's greatest unsolved puzzles: Do people befriend others who are similar to them, or do they become more similar to their friends over time? Recent advances in stochastic actor-based modeling, combined with self-reported data on a popular online social network site, allow us to address this question with a greater degree of precision than has heretofore been possible. Using data on the Facebook activity of a cohort of college students over 4 years, we find that students who share certain tastes in music and in movies, but not in books, are significantly likely to befriend one another. Meanwhile, we find little evidence for the diffusion of tastes among Facebook friends-except for tastes in classical/jazz music. These findings shed light on the mechanisms responsible for observed network homogeneity; provide a statistically rigorous assessment of the coevolution of cultural tastes and social relationships; and suggest important qualifications to our understanding of both homophily and contagion as generic social processes.

Electron inertia and quasi-neutrality in the Weibel instability

NASA Astrophysics Data System (ADS)

Camporeale, Enrico; Tronci, Cesare

2017-06-01

While electron kinetic effects are well known to be of fundamental importance in several situations, the electron mean-flow inertia is often neglected when length scales below the electron skin depth become irrelevant. This has led to the formulation of different reduced models, where electron inertia terms are discarded while retaining some or all kinetic effects. Upon considering general full-orbit particle trajectories, this paper compares the dispersion relations emerging from such models in the case of the Weibel instability. As a result, the question of how length scales below the electron skin depth can be neglected in a kinetic treatment emerges as an unsolved problem, since all current theories suffer from drawbacks of different nature. Alternatively, we discuss fully kinetic theories that remove all these drawbacks by restricting to frequencies well below the plasma frequency of both ions and electrons. By giving up on the length scale restrictions appearing in previous works, these models are obtained by assuming quasi-neutrality in the full Vlasov-Maxwell system.

Future scientific exploration of Taurus-Littrow

NASA Technical Reports Server (NTRS)

Taylor, G. Jeffrey

1992-01-01

The Apollo 17 site was surveyed with great skill and the collected samples have been studied thoroughly (but not completely) in the 20 years since. Ironically, the success of the field and sample studies makes the site an excellent candidate for a return mission. Rather than solving all the problems, the Apollo 17 mission provided a set of sophisticated questions that can be answered only by returning to the site and exploring further. This paper addresses the major unsolved problems in lunar science and points out the units at the Apollo 17 site that are most suitable for addressing each problem. It then discusses how crucial data can be obtained by robotic rovers and human field work. I conclude that, in general, the most important information can be obtained only by human exploration. The paper ends with some guesses about what we could have learned at the Apollo 17 site from a fairly sophisticated rover capable of in situ analyses, instead of sending people.

Isotope Tales: Remaining Problems, Unsolvable Questions, and Gentle Successes

NASA Astrophysics Data System (ADS)

fogel, marilyn; bradley, christina; newsome, seth; filipp, fabian

2014-05-01

Earth's biomes function and adapt today as climate changes and ecosystems and the organisms within them adapt. Stable isotope biogeochemistry has had a major influence in understanding climate perturbations and continues to be an active area of research on many fronts. Banking on the success of compound specific stable isotope analyses of amino acids, nitrogen, carbon, and hydrogen isotopes continue to reveal subtle shifts in oceanic food webs and metabolic changes in microbes, plants, and animals. A biochemical understanding of exactly how organisms process and partition stable isotopes during metabolism remains unsolved, but is required if this field is to move beyond description to quantitation. Although the patterns of carbon and nitrogen isotopes are fairly well established in the common amino acids, we need to consider specifics: How do shifting metabolic pathways (metabolomics) influence the outcome of stable isotope partitioning? What influence does the gut microflora in animals have on isotopic labeling? What are the intramolecular isotope patterns of common amino acids and what do they tell us? What can be learned with other isotope systems, such as hydrogen? Results and ideas of how to move forward in this field will be presented starting at the molecular level and ending with ecosystems.

Irradiation Design for an Experimental Murine Model

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

Ballesteros-Zebadua, P.; Moreno-Jimenez, S.; Suarez-Campos, J. E.

2010-12-07

In radiotherapy and stereotactic radiosurgery, small animal experimental models are frequently used, since there are still a lot of unsolved questions about the biological and biochemical effects of ionizing radiation. This work presents a method for small-animal brain radiotherapy compatible with a dedicated 6MV Linac. This rodent model is focused on the research of the inflammatory effects produced by ionizing radiation in the brain. In this work comparisons between Pencil Beam and Monte Carlo techniques, were used in order to evaluate accuracy of the calculated dose using a commercial planning system. Challenges in this murine model are discussed.

Investor Outlook: The Unanswered Questions.

PubMed

Schimmer, Joshua; Breazzano, Steven

2017-06-01

The year 2016 was an exciting one for the field, with several notable successes outweighing a few setbacks. As the number of patients treated successfully (and safely) with gene therapy grows, the totality of evidence points to a robust platform with utility in orphan/ultra-orphan diseases as well as broader indications, and with hopefully increasing predictability of results. This year promises to feature more patients treated, more clinical data, and more gene therapy products in registration-enabling studies. For the field to continue to advance and mature into the next great drug delivery platform, a few unsolved and remaining questions need to be addressed, including the business model for cures, a broader safety/efficacy profile once more patients are treated, optimization of delivery (including next-generation approaches), and greater understanding of the impact of competitive dynamics. In this report, we detail the success and setbacks of 2016 and highlight the unanswered questions-and how the answers may shape the field in the years ahead.

Visible rodent brain-wide networks at single-neuron resolution

PubMed Central

Yuan, Jing; Gong, Hui; Li, Anan; Li, Xiangning; Chen, Shangbin; Zeng, Shaoqun; Luo, Qingming

2015-01-01

There are some unsolvable fundamental questions, such as cell type classification, neural circuit tracing and neurovascular coupling, though great progresses are being made in neuroscience. Because of the structural features of neurons and neural circuits, the solution of these questions needs us to break through the current technology of neuroanatomy for acquiring the exactly fine morphology of neuron and vessels and tracing long-distant circuit at axonal resolution in the whole brain of mammals. Combined with fast-developing labeling techniques, efficient whole-brain optical imaging technology emerging at the right moment presents a huge potential in the structure and function research of specific-function neuron and neural circuit. In this review, we summarize brain-wide optical tomography techniques, review the progress on visible brain neuronal/vascular networks benefit from these novel techniques, and prospect the future technical development. PMID:26074784

Faith without answers: the use of religion among cold case homicide survivors.

PubMed

Wellman, Ashley R P

2014-01-01

Through data gathered from interviews with cold case homicide survivors, this article reveals the important role of religion and faith in the aftermath of an unsolved murder. Using qualitative methodology, the author highlights the lived experiences and personal journeys of cold case homicide surviving family members, who are often a forgotten and an overlooked segment of victims. Qualitative data suggests that these cold case homicide survivors found religion to be critical in the aftermath of their loved one's murder. Specifically, survivors indicated their faith was fundamental in coping with the homicide and provided hope for anticipating a resolution in their cases. From these intimate, personal survivor accounts, scholars and practitioners can begin to develop future research and programs that are specifically designed to highlight the role of religion in moving forward after an unsolved murder.

In defense of derivations

NASA Astrophysics Data System (ADS)

Mungan, Carl E.

2016-05-01

At the 2015 AAPT Summer Meeting, I presented four derivations of the formula for motional emf. Such physics derivations involve the construction of explanatory frameworks involving diagrams and mathematical models. Although textbooks devote considerable space to such explanations, many teachers and students spend their time on worksheets, end-of-chapter problems, and the like. The book is reduced to a bank of solved (i.e., example) and unsolved (i.e., homework) questions, along with equations in colored boxes that presumably are to be used to answer those questions. Such an approach encourages fragmentation of knowledge, the view that there is only one right answer to a problem with the goal of physics being to find that answer (neatly boxed of course), and the inability to reason about even a slightly different (much less a novel) situation. If we are to develop scientific literacy, significant course time must be devoted to explaining the structure of and support for the models and equations we use.

KM3NeT - ORCA: measuring the neutrino mass ordering in the Mediterranean

NASA Astrophysics Data System (ADS)

Kouchner, Antoine

2016-05-01

ORCA (Oscillations Research with Cosmics in the Abyss) is the low-energy branch of KM3NeT, the underwater Cherenkov neutrino detector in the Mediterranean. Its primary goal is to resolve the long-standing unsolved question of the neutrino mass ordering by measuring matter oscillation effects in atmospheric neutrinos. To be deployed at the French KM3NeT site, ORCA’s multi-PMT optical modules will exploit the excellent optical properties of deep seawater to reconstruct cascade and track events with a few GeV of energy. This contribution reviews the methods and technology, and discusses the current expected performances.

Wnt-regulated dynamics of positional information in zebrafish somitogenesis

PubMed Central

Bajard, Lola; Morelli, Luis G.; Ares, Saúl; Pécréaux, Jacques; Jülicher, Frank; Oates, Andrew C.

2014-01-01

How signaling gradients supply positional information in a field of moving cells is an unsolved question in patterning and morphogenesis. Here, we ask how a Wnt signaling gradient regulates the dynamics of a wavefront of cellular change in a flow of cells during somitogenesis. Using time-controlled perturbations of Wnt signaling in the zebrafish embryo, we changed segment length without altering the rate of somite formation or embryonic elongation. This result implies specific Wnt regulation of the wavefront velocity. The observed Wnt signaling gradient dynamics and timing of downstream events support a model for wavefront regulation in which cell flow plays a dominant role in transporting positional information. PMID:24595291

Value of 18F-FDG PET and PET/CT for evaluation of pediatric malignancies.

PubMed

Uslu, Lebriz; Donig, Jessica; Link, Michael; Rosenberg, Jarrett; Quon, Andrew; Daldrup-Link, Heike E

2015-02-01

Successful management of solid tumors in children requires imaging tests for accurate disease detection, characterization, and treatment monitoring. Technologic developments aim toward the creation of integrated imaging approaches that provide a comprehensive diagnosis with a single visit. These integrated diagnostic tests not only are convenient for young patients but also save direct and indirect health-care costs by streamlining procedures, minimizing hospitalizations, and minimizing lost school or work time for children and their parents. (18)F-FDG PET/CT is a highly sensitive and specific imaging modality for whole-body evaluation of pediatric malignancies. However, recent concerns about ionizing radiation exposure have led to a search for alternative imaging methods, such as whole-body MR imaging and PET/MR. As we develop new approaches for tumor staging, it is important to understand current benchmarks. This review article will synthesize the current literature on (18)F-FDG PET/CT for tumor staging in children, summarizing questions that have been solved and providing an outlook on unsolved avenues. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Biotrophy at Its Best: Novel Findings and Unsolved Mysteries of the Arabidopsis-Powdery Mildew Pathosystem.

PubMed

Kuhn, Hannah; Kwaaitaal, Mark; Kusch, Stefan; Acevedo-Garcia, Johanna; Wu, Hongpo; Panstruga, Ralph

2016-01-01

It is generally accepted in plant-microbe interactions research that disease is the exception rather than a common outcome of pathogen attack. However, in nature, plants with symptoms that signify colonization by obligate biotrophic powdery mildew fungi are omnipresent. The pervasiveness of the disease and the fact that many economically important plants are prone to infection by powdery mildew fungi drives research on this interaction. The competence of powdery mildew fungi to establish and maintain true biotrophic relationships renders the interaction a paramount example of a pathogenic plant-microbe biotrophy. However, molecular details underlying the interaction are in many respects still a mystery. Since its introduction in 1990, the Arabidopsis-powdery mildew pathosystem has become a popular model to study molecular processes governing powdery mildew infection. Due to the many advantages that the host Arabidopsis offers in terms of molecular and genetic tools this pathosystem has great capacity to answer some of the questions of how biotrophic pathogens overcome plant defense and establish a persistent interaction that nourishes the invader while in parallel maintaining viability of the plant host.

Social selection and peer influence in an online social network

PubMed Central

Lewis, Kevin; Gonzalez, Marco; Kaufman, Jason

2012-01-01

Disentangling the effects of selection and influence is one of social science's greatest unsolved puzzles: Do people befriend others who are similar to them, or do they become more similar to their friends over time? Recent advances in stochastic actor-based modeling, combined with self-reported data on a popular online social network site, allow us to address this question with a greater degree of precision than has heretofore been possible. Using data on the Facebook activity of a cohort of college students over 4 years, we find that students who share certain tastes in music and in movies, but not in books, are significantly likely to befriend one another. Meanwhile, we find little evidence for the diffusion of tastes among Facebook friends—except for tastes in classical/jazz music. These findings shed light on the mechanisms responsible for observed network homogeneity; provide a statistically rigorous assessment of the coevolution of cultural tastes and social relationships; and suggest important qualifications to our understanding of both homophily and contagion as generic social processes. PMID:22184242

Biotrophy at Its Best: Novel Findings and Unsolved Mysteries of the Arabidopsis-Powdery Mildew Pathosystem

PubMed Central

Kuhn, Hannah; Kwaaitaal, Mark; Kusch, Stefan; Acevedo-Garcia, Johanna; Wu, Hongpo; Panstruga, Ralph

2016-01-01

It is generally accepted in plant-microbe interactions research that disease is the exception rather than a common outcome of pathogen attack. However, in nature, plants with symptoms that signify colonization by obligate biotrophic powdery mildew fungi are omnipresent. The pervasiveness of the disease and the fact that many economically important plants are prone to infection by powdery mildew fungi drives research on this interaction. The competence of powdery mildew fungi to establish and maintain true biotrophic relationships renders the interaction a paramount example of a pathogenic plant-microbe biotrophy. However, molecular details underlying the interaction are in many respects still a mystery. Since its introduction in 1990, the Arabidopsis-powdery mildew pathosystem has become a popular model to study molecular processes governing powdery mildew infection. Due to the many advantages that the host Arabidopsis offers in terms of molecular and genetic tools this pathosystem has great capacity to answer some of the questions of how biotrophic pathogens overcome plant defense and establish a persistent interaction that nourishes the invader while in parallel maintaining viability of the plant host. PMID:27489521

Announcing a Hydrogeology Journal theme issue on "The future of hydrogeology"

USGS Publications Warehouse

Voss, Clifford I.

2003-01-01

What is the future of hydrogeology? Are most of the fundamental scientific problems in hydrogeology already solved? Is there really any need for more fundamental research, field measurements, or method development? Have recent scientific advances really added capabilities and tools for our practical needs? Are there any unsolved hydrogeologic questions still remaining that are vital to our optimal use and management of subsurface resources or does the remaining work only fill in some details to a story essentially already told? Will the science of hydrogeology soon become primarily an applied field, where the main task is to use known methods to solve practical problems of water supply and water quality? For other questions involving subsurface fluids, for example, waste isolation, understanding of geological processes and climate changes, are current hydrogeologic capabilities sufficient and is there any possibility for improvement? These are the types of questions that will be dealt with by an upcoming theme issue of Hydrogeology Journal (HJ) to appear in early 2005 [HJ 13(1)]. This issue will contain 10–20 peer-reviewed invited articles on both general topics and specific subject areas of hydrogeology.

A Successful Senior Seminar: Unsolved Problems in Number Theory

ERIC Educational Resources Information Center

Styer, Robert

2014-01-01

The "Unsolved Problems in Number Theory" book by Richard Guy provides nice problems suitable for a typical math major. We give examples of problems that have worked well in our senior seminar course and some nice results that senior math majors can obtain.

Exit channel dynamics in a micro-hydrated SN2 reaction of the hydroxyl anion.

PubMed

Otto, R; Brox, J; Trippel, S; Stei, M; Best, T; Wester, R

2013-08-29

We report on the reaction dynamics of the monosolvated SN2 reaction of cold OH(-)(H2O) with CH3I that have been studied using crossed beam ion imaging. Two SN2 reaction channels are possible for this reaction: Formation of unsolvated I(-) and of solvated I(-)(H2O) products. We find a strong preference for the formation of unsolvated I(-) reaction products with respect to the energetically favored reaction toward solvated I(-)(H2O). Angle differential cross section measurements reveal similar velocity and angular distributions for all solvated and parts of the unsolvated reaction products. We furthermore find that the contribution of these two products to the total product flux can be described by the same collision energy dependence. We interpret our findings in terms of a joint reaction mechanism in which a CH3OH(H2O)···I(-) complex is formed that decays into either solvated or unsolvated products. Quantum chemical calculation are used to support this assumption.

Food Science in Developing Countries: A Selection of Unsolved Problems.

ERIC Educational Resources Information Center

National Academy of Sciences - National Research Council, Washington, DC.

Presented are summaries of 42 unsolved problems in food science which exist in various developing countries throughout the world. Problems deal with new foods, food processing, food composition, nutrition, and health. Each problem presented includes the problem description, background information, possible approaches to solutions, special…

Predicting transport regime and local electrostatic environment from Coulomb blockade diamond sizes

NASA Astrophysics Data System (ADS)

Olsen, Stine T.; Hansen, Thorsten; Mikkelsen, Kurt V.

2017-03-01

Electron transport through a molecule is often described in one of the two regimes: the coherent tunnelling regime or the Coulomb blockade regime. The twilight zone of the two regimes still possesses many unsolved questions. A theoretical analysis of the oligophenylenevinylene OPV3 experiments by Bjørnholm and co-workers is performed. The experiments showed how two OPV3 derivatives performed very differently despite the strong similarity of the molecular structure, hence the experimental data showed two different transport mechanisms. The different transport mechanisms of the two OPV3 derivatives are explained from quantum mechanical calculations of the molecular redox energies and from the experimentally accessible window size.

Cascade debris overlap mechanism of 〈100〉 dislocation loop formation in Fe and FeCr

NASA Astrophysics Data System (ADS)

Granberg, F.; Byggmästar, J.; Sand, A. E.; Nordlund, K.

2017-09-01

Two types of dislocation loops are observed in irradiated α-Fe, the 1/2〈111〉 loop and the 〈100〉 loop. Atomistic simulations consistently predict that only the energetically more favourable 1/2〈111〉 loops are formed directly in cascades, leaving the formation mechanism of 〈100〉 loops an unsolved question. We show how 〈100〉 loops can be formed when cascades overlap with random pre-existing primary radiation damage in Fe and FeCr. This indicates that there are no specific constraints involved in the formation of 〈100〉 loops, and can explain their common occurrence.

Origin of the different color of ruby and emerald

NASA Astrophysics Data System (ADS)

García-Lastra, J. M.; Barriuso, M. T.; Aramburu, J. A.; Moreno, M.

2005-09-01

The different color exhibited by ruby and emerald is a fundamental but still unsolved question. According to recent EXAFS measurements, such a difference can hardly be explained on the basis of a different average distance between Cr3+ and the six oxygen ligands. The puzzling difference in color between the two gemstones is shown in this work to arise essentially from the distinct electrostatic potential imposed by the rest of lattice ions upon the active electrons of the CrO69- unit. Main effects are shown to come from the electric field generated in the neighborhood of the Cr3+ site in ruby which is absent in the case of emerald due to symmetry.

Ligand-free gold atom clusters adsorbed on graphene nano sheets generated by oxidative laser fragmentation in water

NASA Astrophysics Data System (ADS)

Lau, Marcus; Haxhiaj, Ina; Wagener, Philipp; Intartaglia, Romuald; Brandi, Fernando; Nakamura, Junji; Barcikowski, Stephan

2014-08-01

Over three decades after the first synthesis of stabilized Au55-clusters many scientific questions about gold cluster properties are still unsolved and ligand-free colloidal clusters are difficult to fabricate. Here we present a novel route to produce ultra-small gold particles by using a green technique, the laser ablation and fragmentation in water, without using reductive or stabilizing agents at any step of the synthesis. For fabrication only a pulsed laser, a gold-target, pure water, sodium hydroxide and hydrogen peroxide are deployed. The particles are exemplarily hybridized to graphene supports showing that these carbon-free colloidal clusters might serve as versatile building blocks.

Dynamics of cracks in disordered materials

NASA Astrophysics Data System (ADS)

Bonamy, Daniel

2017-05-01

Predicting when rupture occurs or cracks progress is a major challenge in numerous fields of industrial, societal, and geophysical importance. It remains largely unsolved: stress enhancement at cracks and defects, indeed, makes the macroscale dynamics extremely sensitive to the microscale material disorder. This results in giant statistical fluctuations and non-trivial behaviors upon upscaling, difficult to assess via the continuum approaches of engineering.

Hybrid Optical-Magnetic Traps for Studies of 2D Quantum Turbulence in Bose-Einstein Condensates

NASA Astrophysics Data System (ADS)

Myers, Jessica Ann

Turbulence appears in most natural and man-made flows. However, the analysis of turbulence is particularly difficult. Links between microscopic fluid dynamics and statistical signatures of turbulence appear unobtainable from the postulates of fluid dynamics making turbulence one of the most important unsolved theoretical problems in physics. Two-dimensional quantum turbulence (2DQT), an emerging field of study, involves turbulence in two-dimensional (2D) flows in superfluids, such as Bose-Einstein condensates (BECs). In 2D superfluids, a turbulent state can be characterized by a disordered distribution of numerous vortex cores. The question of how to effectively and efficiently generate turbulent states in superfluids is a fundamental question in the field of quantum turbulence. Therefore, experimental studies of vortex nucleation and the onset of turbulence in a superfluid are important for achieving a deeper understanding of the overall problem of turbulence. My PhD dissertation involves the study of vortex nucleation and the onset of turbulence in quasi-2D BECs. First, I discuss experimental apparatus advancements that now enable BECs to be created in a hybrid optical-magnetic trap, an atom trapping configuration conducive to 2DQT experiments. Next, I discuss the design and construction of a quantum vortex microscope and initial vortex detection tests. Finally, I present the first experiments aimed at studying 2DQT carried out in the updated apparatus. Thermal counterflow in superfluid helium, in which the normal and superfluid components flow in opposite directions, is known to create turbulence in the superfluid. However, this phenomenon has not been simulated or studied in dilute-gas BECs as a possible vortex nucleation method. In this dissertation, I present preliminary data from the first experiments aimed at understanding thermal counterflow turbulence in dilute-gas BECs.

(How) Can We Write about Our Patients?

PubMed

Ackerman, Sarah

2018-02-01

The ethical underpinnings of writing about patients are explored, the question of how best to undertake the writing of case reports being subordinated to a more general question about the ethics of choosing how or whether to write. An unsolvable paradox is encountered here: that we need to write or speak about our clinical work in order to conceptualize and understand the work we are doing, but that in the very gesture of doing so, we are breaking a fundamental bond with the patient. This conundrum is viewed from a number of vantage points. The controversy about how best to go about writing clinical accounts is first addressed, after which the literature is reviewed to draw out the ethical conflicts that writing about patients engenders in the patient. Next attention is given to undercurrents in the analyst's motivation to write, again drawing on current literature. Finally, a consideration is provided of how, based on what we might learn from this review, these problems can be addressed.

Costa Rica's Chain of laterally collapsed volcanoes.

NASA Astrophysics Data System (ADS)

Duarte, E.; Fernandez, E.

2007-05-01

From the NW extreme to the SW end of Costa Rica's volcanic backbone, a number of laterally collapsed volcanoes can be observed. Due to several factors, attention has been given to active volcanoes disregarding the importance of collapsed features in terms of assessing volcanic hazards for future generations around inhabited volcanoes. In several cases the typical horseshoe shape amphitheater-like depression can be easily observed. In other cases due to erosion, vegetation, topography, seismic activity or drastic weather such characteristics are not easily recognized. In the order mentioned above appear: Orosi-Cacao, Miravalles, Platanar, Congo, Von Frantzius, Cacho Negro and Turrialba volcanoes. Due to limited studies on these structures it is unknown if sector collapse occurred in one or several phases. Furthermore, in the few studied cases no evidence has been found to relate collapses to actual eruptive episodes. Detailed studies on the deposits and materials composing dome-like shapes will shed light on unsolved questions about petrological and chemical composition. Volume, form and distance traveled by deposits are part of the questions surrounding most of these collapsed volcanoes. Although most of these mentioned structures are extinct, at least Irazú volcano (active volcano) has faced partial lateral collapses recently. It did presented strombolian activity in the early 60s. Collapse scars show on the NW flank show important mass removal in historic and prehistoric times. Moreover, in 1994 a minor hydrothermal explosion provoked the weakening of a deeply altered wall that holds a crater lake (150m diameter, 2.6x106 ). A poster will depict images of the collapsed volcanoes named above with mayor descriptive characteristics. It will also focus on the importance of deeper studies to assess the collapse potential of Irazú volcano with related consequences. Finally, this initiative will invite researchers interested in such topic to join future studies in these Costarrican volcanoes.

ATP-dependent molecular chaperones in plastids--More complex than expected.

PubMed

Trösch, Raphael; Mühlhaus, Timo; Schroda, Michael; Willmund, Felix

2015-09-01

Plastids are a class of essential plant cell organelles comprising photosynthetic chloroplasts of green tissues, starch-storing amyloplasts of roots and tubers or the colorful pigment-storing chromoplasts of petals and fruits. They express a few genes encoded on their organellar genome, called plastome, but import most of their proteins from the cytosol. The import into plastids, the folding of freshly-translated or imported proteins, the degradation or renaturation of denatured and entangled proteins, and the quality-control of newly folded proteins all require the action of molecular chaperones. Members of all four major families of ATP-dependent molecular chaperones (chaperonin/Cpn60, Hsp70, Hsp90 and Hsp100 families) have been identified in plastids from unicellular algae to higher plants. This review aims not only at giving an overview of the most current insights into the general and conserved functions of these plastid chaperones, but also into their specific plastid functions. Given that chloroplasts harbor an extreme environment that cycles between reduced and oxidized states, that has to deal with reactive oxygen species and is highly reactive to environmental and developmental signals, it can be presumed that plastid chaperones have evolved a plethora of specific functions some of which are just about to be discovered. Here, the most urgent questions that remain unsolved are discussed, and guidance for future research on plastid chaperones is given. This article is part of a Special Issue entitled: Chloroplast Biogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence for clonal selection of gamma/delta T cells in response to a human pathogen

PubMed Central

1991-01-01

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens. PMID:1651977

Recent advances in the management of neuropsychiatric symptoms in dementia.

PubMed

Forlenza, Orestes V; Loureiro, Júlia Cunha; Pais, Marcos Vasconcelos; Stella, Florindo

2017-03-01

The present article addresses intriguing questions related to the clinical intervention in distinct neuropsychiatric syndromes of patients with dementia. We reviewed 154 articles published between 2015 and 2016 targeting psychopharmacological and nonpharmacological interventions, and safety-tolerability concerns. We selected 115 articles addressing the purpose of this study. Of these, 33 were chosen because they were dedicated to subtopics: agitation (42), depression (33), apathy (18), sleep disorders/anxiety (8), and psychosis (4). Clinical studies using both pharmacological (70) and nonpharmacological (37) interventions were considered; others were included for theoretical support. Regarding the methodological design, we found double-blind RCTs (17), single-blinded RCTs (4), open-label studies (18), case reports (5), cross-sectional or cohort studies (25), epidemiological papers (2), and expert reviews (44). This observation raises concerns about the overall methodological adequacy of a substantial proportion of studies in this field, which limits the potential of generalization of the findings. Finally, 18 studies were designed to determine safety-tolerability issues of psychotropic medications (6 were discussed). Effective and well tolerated treatment of neuropsychiatric syndromes in dementia remains a critically unsolved challenge. We understand that this is an extremely important area of research, and critically required to guide clinical decisions in geriatric neuropsychiatry.

Some Unsolved Problems, Questions, and Applications of the Brightsen Nucleon Cluster Model

NASA Astrophysics Data System (ADS)

Smarandache, Florentin

2010-10-01

Brightsen Model is opposite to the Standard Model, and it was build on John Weeler's Resonating Group Structure Model and on Linus Pauling's Close-Packed Spheron Model. Among Brightsen Model's predictions and applications we cite the fact that it derives the average number of prompt neutrons per fission event, it provides a theoretical way for understanding the low temperature / low energy reactions and for approaching the artificially induced fission, it predicts that forces within nucleon clusters are stronger than forces between such clusters within isotopes; it predicts the unmatter entities inside nuclei that result from stable and neutral union of matter and antimatter, and so on. But these predictions have to be tested in the future at the new CERN laboratory.

Interventional radiology: a half century of innovation.

PubMed

Baum, Richard A; Baum, Stanley

2014-11-01

The evolution of modern interventional radiology began over half century ago with a simple question. Was it possible to use the same diagnostic imaging tools that had revolutionized the practice of medicine to guide the real-time treatment of disease? This disruptive concept led to rapid treatment advances in every organ system of the body. It became clear that by utilizing imaging some patients could undergo targeted procedures, eliminating the need for major surgery, while others could undergo procedures for previously unsolvable problems. The breadth of these changes now encompasses all of medicine and has forever changed the way we think about disease. In this brief review article, major advances in the field, as chronicled in the pages of Radiology, will be described.

Beyond Problem-Solving: Elementary Students' Mathematical Dispositions When Faced with the Challenge of Unsolved Problems

ERIC Educational Resources Information Center

O'Dell, Jenna R.

2017-01-01

The goal of this study was to document the characteristics of students' dispositions towards mathematics when they engaged in the exploration of parts of unsolved problems: Graceful Tree Conjecture and Collatz Conjecture. Ten students, Grades 4 and 5, from an after-school program in the Midwest participated in the study. I focused on the…

Engineering Geodesy - Definition and Core Competencies

NASA Astrophysics Data System (ADS)

Kuhlmann, Heiner; Schwieger, Volker; Wieser, Andreas; Niemeier, Wolfgang

2014-11-01

This article summarises discussions concerning the definition of "engineering geodesy" within the German Geodetic Commission. It is noted that engineering geodesy by means of its tasks, methods and characteristics is an application-oriented science whose research questions often arise from observed phenomena or from unsolved practical problems. In particular it is characterised by the professional handling of geometry-related problems in a cost-effective manner that includes comprehensive quality assessment at all phases of the problem solution - from planning through measurement to data processing and interpretation. The current methodical developments are primarily characterised by the increasing integration of the measurement and analysis into challenging construction, production and monitoring processes as well as by the transition to spatially continuous methods. A modern definition of engineering geodesy is proposed at the end of this article.

The Invisible Wall Project: Reasoning and Problem Solving Processes of Primary and Lower Secondary Students

ERIC Educational Resources Information Center

Stein, Martin; Burchartz, Birgit

2006-01-01

The Invisible Wall Project analyzes problem-solving processes of children in Grades 3 and 4 and Grades 8 and 9. The central idea of the research is to use sets of tasks that are all unsolvable, which means they have a goal that cannot be reached. The unsolvability, however, is of a kind that can be understood even by younger children. In our case,…

Experimentally-induced learned helplessness in adolescents with type 1 diabetes.

PubMed

McLaughlin, Elizabeth; Lefaivre, Marie-josée; Cummings, Elizabeth

2010-05-01

To determine whether adolescents with type 1 diabetes are more at risk for learned helplessness than their healthy peers. Twenty-three adolescents with diabetes and 25 controls completed a solvable or unsolvable concept formation task. All completed pre- and post-task performance and attribution ratings, and later completed an anagram-solving task to determine if perceived helplessness on the first task would negatively impact performance on the second. Participants in the unsolvable condition solved fewer anagrams; those with diabetes did not show weaker performance than controls. Participants in the solvable condition (diabetes and controls) showed an increase in internal attributions from before the concept formation task to after. In the unsolvable condition, only participants with diabetes made more external attributions for their failure. Contrary to the only other controlled study to use this paradigm in youth with chronic illness, adolescents with diabetes were not more susceptible to learned helplessness.

Radiotracer Technology in Mixing Processes for Industrial Applications

PubMed Central

Othman, N.; Kamarudin, S. K.

2014-01-01

Many problems associated with the mixing process remain unsolved and result in poor mixing performance. The residence time distribution (RTD) and the mixing time are the most important parameters that determine the homogenisation that is achieved in the mixing vessel and are discussed in detail in this paper. In addition, this paper reviews the current problems associated with conventional tracers, mathematical models, and computational fluid dynamics simulations involved in radiotracer experiments and hybrid of radiotracer. PMID:24616642

Development of a new code to solve hydro-mechanical coupling, shear failure and tensile failure due to hydraulic fracturing operations.

NASA Astrophysics Data System (ADS)

María Gómez Castro, Berta; De Simone, Silvia; Carrera, Jesús

2016-04-01

Nowadays, there are still some unsolved relevant questions which must be faced if we want to proceed to the hydraulic fracturing in a safe way. How much will the fracture propagate? This is one of the most important questions that have to be solved in order to avoid the formation of pathways leading to aquifer targets and atmospheric release. Will the fracture failure provoke a microseismic event? Probably this is the biggest fear that people have in fracking. The aim of this work (developed as a part of the EU - FracRisk project) is to understand the hydro-mechanical coupling that controls the shear of existing fractures and their propagation during a hydraulic fracturing operation, in order to identify the key parameters that dominate these processes and answer the mentioned questions. This investigation focuses on the development of a new C++ code which simulates hydro-mechanical coupling, shear movement and propagation of a fracture. The framework employed, called Kratos, uses the Finite Element Method and the fractures are represented with an interface element which is zero thickness. This means that both sides of the element lie together in the initial configuration (it seems a 1D element in a 2D domain, and a 2D element in a 3D domain) and separate as the adjacent matrix elements deform. Since we are working in hard, fragile rocks, we can assume an elastic matrix and impose irreversible displacements in fractures when rock failure occurs. The formulation used to simulate shear and tensile failures is based on the analytical solution proposed by Okada, 1992 and it is part of an iterative process. In conclusion, the objective of this work is to employ the new code developed to analyze the main uncertainties related with the hydro-mechanical behavior of fractures derived from the hydraulic fracturing operations.

Differentiating Burnout from Depression: Personality Matters!

PubMed Central

Melchers, Martin Christoph; Plieger, Thomas; Meermann, Rolf; Reuter, Martin

2015-01-01

Stress-related affective disorders have been identified as a core health problem of the twenty-first century. In the endeavor to identify vulnerability factors, personality has been discussed as a major factor explaining and predicting disorders like depression or burnout. An unsolved question is whether there are specific personality factors allowing differentiation of burnout from depression. The present study tested the relation between one of the most prominent, biological personality theories, Cloninger’s Temperament and Character Inventory, and common measures of burnout (Maslach Burnout Inventory General) and depression (Beck Depression Inventory 2) in a sample of German employees (N = 944) and a sample of inpatients (N = 425). Although the same personality traits (harm avoidance and self-directedness) were predominantly associated with burnout and depression, there was a much stronger association to depression than to burnout in both samples. Besides, we observed specific associations between personality traits and subcomponents of burnout. Our results underline differences in the association of burnout vs. depression to personality, which may mirror differences in scope. While symptoms of depression affect all aspects of life, burnout is supposed to be specifically related to the workplace and its requirements. The much stronger association of personality to depression can be important to select appropriate therapy methods and to develop a more specified treatment for burnout in comparison to depression. PMID:26321963

[Psychiatric patient: the most vulnerable traveller].

PubMed

Felkai, Péter; Kurimay, Tamás; Fülöp, Emoke

2011-01-23

Authors analyse questions of medical evacuation of the psychotic patient from abroad to homeland. This task can be considered the most difficult problem for the attending physician and the escorting medical team as well. The main challenge is to recognise the psychotic patient in a foreign country with a different health-care system and to overcome the language barrier and the different cultural background. The second issue is to prepare the patients - who are usually in a poor condition - for the medical evacuation by commercial aircraft. Another important issue is to take the patient through the strict security control. All of these (partially unsolved) problems make the mentally ill patient defenceless. Although the repatriation of a mentally ill patient is vital and urgent, travel insurance policy mostly excludes to cover the cost of treatment and repatriation. The high cost of treatment and repatriation of the patient should be paid by the patient or the family, who are often in the position of insolvency. In this paper authors present the history of a patient and give a brief review on travel-related mental disorders, the epidemiology of mental alterations during travel as well as the problems of appropriate evacuation. Authors conclude that there is a need for a better approach of the airport authorities and insurance decision makers to the mentally ill patient travelling abroad.

Evolutionary stasis in pollen morphogenesis due to natural selection.

PubMed

Matamoro-Vidal, Alexis; Prieu, Charlotte; Furness, Carol A; Albert, Béatrice; Gouyon, Pierre-Henri

2016-01-01

The contribution of developmental constraints and selective forces to the determination of evolutionary patterns is an important and unsolved question. We test whether the long-term evolutionary stasis observed for pollen morphogenesis (microsporogenesis) in eudicots is due to developmental constraints or to selection on a morphological trait shaped by microsporogenesis: the equatorial aperture pattern. Most eudicots have three equatorial apertures but several taxa have independently lost the equatorial pattern and have microsporogenesis decoupled from aperture pattern determination. If selection on the equatorial pattern limits variation, we expect to see increased variation in microsporogenesis in the nonequatorial clades. Variation of microsporogenesis was studied using phylogenetic comparative analyses in 83 species dispersed throughout eudicots including species with and without equatorial apertures. The species that have lost the equatorial pattern have highly variable microsporogenesis at the intra-individual and inter-specific levels regardless of their pollen morphology, whereas microsporogenesis remains stable in species with the equatorial pattern. The observed burst of variation upon loss of equatorial apertures shows that there are no strong developmental constraints precluding variation in microsporogenesis, and that the stasis is likely to be due principally to selective pressure acting on pollen morphogenesis because of its implication in the determination of the equatorial aperture pattern. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The future of Stardust science

NASA Astrophysics Data System (ADS)

Westphal, A. J.; Bridges, J. C.; Brownlee, D. E.; Butterworth, A. L.; de Gregorio, B. T.; Dominguez, G.; Flynn, G. J.; Gainsforth, Z.; Ishii, H. A.; Joswiak, D.; Nittler, L. R.; Ogliore, R. C.; Palma, R.; Pepin, R. O.; Stephan, T.; Zolensky, M. E.

2017-09-01

Recent observations indicate that >99% of the small bodies in the solar system reside in its outer reaches—in the Kuiper Belt and Oort Cloud. Kuiper Belt bodies are probably the best-preserved representatives of the icy planetesimals that dominated the bulk of the solid mass in the early solar system. They likely contain preserved materials inherited from the protosolar cloud, held in cryogenic storage since the formation of the solar system. Despite their importance, they are relatively underrepresented in our extraterrestrial sample collections by many orders of magnitude ( 1013 by mass) as compared with the asteroids, represented by meteorites, which are composed of materials that have generally been strongly altered by thermal and aqueous processes. We have only begun to scratch the surface in understanding Kuiper Belt objects, but it is already clear that the very limited samples of them that we have in our laboratories hold the promise of dramatically expanding our understanding of the formation of the solar system. Stardust returned the first samples from a known small solar system body, the Jupiter-family comet 81P/Wild 2, and, in a separate collector, the first solid samples from the local interstellar medium. The first decade of Stardust research resulted in more than 142 peer-reviewed publications, including 15 papers in Science. Analyses of these amazing samples continue to yield unexpected discoveries and to raise new questions about the history of the early solar system. We identify nine high-priority scientific objectives for future Stardust analyses that address important unsolved problems in planetary science.

Toward a superconducting quantum computer

PubMed Central

Tsai, Jaw-Shen

2010-01-01

Intensive research on the construction of superconducting quantum computers has produced numerous important achievements. The quantum bit (qubit), based on the Josephson junction, is at the heart of this research. This macroscopic system has the ability to control quantum coherence. This article reviews the current state of quantum computing as well as its history, and discusses its future. Although progress has been rapid, the field remains beset with unsolved issues, and there are still many new research opportunities open to physicists and engineers. PMID:20431256

The geophysical importance of bubbles in the sea

NASA Technical Reports Server (NTRS)

Cirpriano, R. J.

1982-01-01

Present knowledge of the mechanisms for production and enrichment and film drops by bursting bubbles is summarized, with particular emphasis on the unsolved problems. Sea salt is by far the major constituent cycled through the Earth's atmosphere each year. Bursting bubbles in the oceans appear to be primarily responsible. These salt particles play a role in the formation of maritime clouds, which in turn affect the Earth's radiation budget. Along with the salt are carried various chemical pollutants and potentially pathogenic microorganisms, often in highly enriched form.

Ultrafast and nanoscale diodes

NASA Astrophysics Data System (ADS)

Zhang, Peng; Lau, Y. Y.

2016-10-01

Charge carrier transport across interfaces of dissimilar materials (including vacuum) is the essence of all electronic devices. Ultrafast charge transport across a nanometre length scale is of fundamental importance in the miniaturization of vacuum and plasma electronics. With the combination of recent advances in electronics, photonics and nanotechnology, these miniature devices may integrate with solid-state platforms, achieving superior performance. This paper reviews recent modelling efforts on quantum tunnelling, ultrafast electron emission and transport, and electrical contact resistance. Unsolved problems and challenges in these areas are addressed.

Toward a superconducting quantum computer. Harnessing macroscopic quantum coherence.

PubMed

Tsai, Jaw-Shen

2010-01-01

Intensive research on the construction of superconducting quantum computers has produced numerous important achievements. The quantum bit (qubit), based on the Josephson junction, is at the heart of this research. This macroscopic system has the ability to control quantum coherence. This article reviews the current state of quantum computing as well as its history, and discusses its future. Although progress has been rapid, the field remains beset with unsolved issues, and there are still many new research opportunities open to physicists and engineers.

Thermodynamic energy exchange in a moving plate capacitor

NASA Astrophysics Data System (ADS)

Davis, B. R.; Abbott, D.; Parrondo, J. M. R.

2001-09-01

In this paper we describe an apparent paradox concerning a moving plate capacitor driven by thermal noise from a resistor. The plates are attracted together, but a demon restores the plates of the capacitor to their original position when the voltage across the capacitor is small—hence only small forces are present for the demon to work against. The demon has to work harder than this to avoid the situation of perpetual motion, but the open question is how? This is unsolved, however we explore the concept of a moving plate capacitor by examining the case where it is still excited by thermal noise, but where the restoring force on the capacitor plates is provided by a simple spring rather than some unknown demon. We display simulation results with interesting behavior, particularly where the capacitor plates collide with each other.

An Overview of Kinematic and Calibration Models Using Internal/External Sensors or Constraints to Improve the Behavior of Spatial Parallel Mechanisms

PubMed Central

Majarena, Ana C.; Santolaria, Jorge; Samper, David; Aguilar, Juan J.

2010-01-01

This paper presents an overview of the literature on kinematic and calibration models of parallel mechanisms, the influence of sensors in the mechanism accuracy and parallel mechanisms used as sensors. The most relevant classifications to obtain and solve kinematic models and to identify geometric and non-geometric parameters in the calibration of parallel robots are discussed, examining the advantages and disadvantages of each method, presenting new trends and identifying unsolved problems. This overview tries to answer and show the solutions developed by the most up-to-date research to some of the most frequent questions that appear in the modelling of a parallel mechanism, such as how to measure, the number of sensors and necessary configurations, the type and influence of errors or the number of necessary parameters. PMID:22163469

Anisotropy and non-homogeneity of an Allomyrina Dichotoma beetle hind wing membrane.

PubMed

Ha, N S; Jin, T L; Goo, N S; Park, H C

2011-12-01

Biomimetics is one of the most important paradigms as researchers seek to invent better engineering designs over human history. However, the observation of insect flight is a relatively recent work. Several researchers have tried to address the aerodynamic performance of flapping creatures and other natural properties of insects, although there are still many unsolved questions. In this study, we try to answer the questions related to the mechanical properties of a beetle's hind wing, which consists of a stiff vein structure and a flexible membrane. The membrane of a beetle's hind wing is small and flexible to the point that conventional methods cannot adequately quantify the material properties. The digital image correlation method, a non-contact displacement measurement method, is used along with a specially designed mini-tensile testing system. To reduce the end effects, we developed an experimental method that can deal with specimens with as high an aspect ratio as possible. Young's modulus varies over the area in the wing and ranges from 2.97 to 4.5 GPa in the chordwise direction and from 1.63 to 2.24 GPa in the spanwise direction. Furthermore, Poisson's ratio in the chordwise direction is 0.63-0.73 and approximately twice as large as that in the spanwise direction (0.33-0.39). From these results, we can conclude that the membrane of a beetle's hind wing is an anisotropic and non-homogeneous material. Our results will provide a better understanding of the flapping mechanism through the formulation of a fluid-structure interaction analysis or aero-elasticity analysis and meritorious data for biomaterial properties database as well as a creative design concept for a micro aerial flapper that mimics an insect.

Consequences of Learned Helplessness and Recognition of the State of Cognitive Exhaustion in Persons with Mild Intellectual Disability

PubMed Central

Gacek, Michał; Smoleń, Tomasz; Pilecka, Władysława

2017-01-01

Persons with intellectual disability are a group at risk of being exposed to overly demanding problem-solving situations, which may produce learned helplessness. The research was based on the informational model of learned helplessness. The consequences of exposure to an unsolvable task and the ability to recognize the symptoms of cognitive exhaustion were tested in 120 students with mild intellectual disability. After the exposure to the unsolvable task, persons in the experimental group obtained lower results than the control group in the escape/avoidance learning task, but a similar result was found in the divergent thinking fluency task. Also, participants in the experimental group had difficulties recognizing the symptoms of the cognitive exhaustion state. After a week’s time, the difference in escape/avoidance learning performance was still observed. The results indicate that exposure to unsolvable tasks may negatively influence the cognitive performance in persons with intellectual disability, although those persons may not identify the cognitive state related to lowered performance. PMID:28479937

The puzzling unsolved mysteries of liquid water: Some recent progress

NASA Astrophysics Data System (ADS)

Stanley, H. E.; Kumar, P.; Xu, L.; Yan, Z.; Mazza, M. G.; Buldyrev, S. V.; Chen, S.-H.; Mallamace, F.

2007-12-01

Water is perhaps the most ubiquitous, and the most essential, of any molecule on earth. Indeed, it defies the imagination of even the most creative science fiction writer to picture what life would be like without water. Despite decades of research, however, water's puzzling properties are not understood and 63 anomalies that distinguish water from other liquids remain unsolved. We introduce some of these unsolved mysteries, and demonstrate recent progress in solving them. We present evidence from experiments and computer simulations supporting the hypothesis that water displays a special transition point (which is not unlike the “tipping point” immortalized by Malcolm Gladwell). The general idea is that when the liquid is near this “tipping point,” it suddenly separates into two distinct liquid phases. This concept of a new critical point is finding application to other liquids as well as water, such as silicon and silica. We also discuss related puzzles, such as the mysterious behavior of water near a protein.

Consequences of Learned Helplessness and Recognition of the State of Cognitive Exhaustion in Persons with Mild Intellectual Disability.

PubMed

Gacek, Michał; Smoleń, Tomasz; Pilecka, Władysława

2017-01-01

Persons with intellectual disability are a group at risk of being exposed to overly demanding problem-solving situations, which may produce learned helplessness . The research was based on the informational model of learned helplessness. The consequences of exposure to an unsolvable task and the ability to recognize the symptoms of cognitive exhaustion were tested in 120 students with mild intellectual disability. After the exposure to the unsolvable task, persons in the experimental group obtained lower results than the control group in the escape/avoidance learning task, but a similar result was found in the divergent thinking fluency task. Also, participants in the experimental group had difficulties recognizing the symptoms of the cognitive exhaustion state. After a week's time, the difference in escape/avoidance learning performance was still observed. The results indicate that exposure to unsolvable tasks may negatively influence the cognitive performance in persons with intellectual disability, although those persons may not identify the cognitive state related to lowered performance.

Half a century of "the nuclear matrix".

PubMed

Pederson, T

2000-03-01

A cell fraction that would today be termed "the nuclear matrix" was first described and patented in 1948 by Russian investigators. In 1974 this fraction was rediscovered and promoted as a fundamental organizing principle of eukaryotic gene expression. Yet, convincing evidence for this functional role of the nuclear matrix has been elusive and has recently been further challenged. What do we really know about the nonchromatin elements (if any) of internal nuclear structure? Are there objective reasons (as opposed to thinly veiled disdain) to question experiments that use harsh nuclear extraction steps and precipitation-prone conditions? Are the known biophysical properties of the nucleoplasm in vivo consistent with the existence of an extensive network of anastomosing filaments coursing dendritically throughout the interchromatin space? To what extent may the genome itself contribute information for its own quarternary structure in the interphase nucleus? These questions and recent work that bears on the mystique of the nuclear matrix are addressed in this essay. The degree to which gene expression literally depends on nonchromatin nuclear structure as a facilitating organizational format remains an intriguing but unsolved issue in eukaryotic cell biology, and considerable skepticism continues to surround the nuclear matrix fraction as an accurate representation of the in vivo situation.

Retroviral proteases and their roles in virion maturation.

PubMed

Konvalinka, Jan; Kräusslich, Hans-Georg; Müller, Barbara

2015-05-01

Proteolytic processing of viral polyproteins is essential for retrovirus infectivity. Retroviral proteases (PR) become activated during or after assembly of the immature, non-infectious virion. They cleave viral polyproteins at specific sites, inducing major structural rearrangements termed maturation. Maturation converts retroviral enzymes into their functional form, transforms the immature shell into a metastable state primed for early replication events, and enhances viral entry competence. Not only cleavage at all PR recognition sites, but also an ordered sequence of cleavages is crucial. Proteolysis is tightly regulated, but the triggering mechanisms and kinetics and pathway of morphological transitions remain enigmatic. Here, we outline PR structures and substrate specificities focusing on HIV PR as a therapeutic target. We discuss design and clinical success of HIV PR inhibitors, as well as resistance development towards these drugs. Finally, we summarize data elucidating the role of proteolysis in maturation and highlight unsolved questions regarding retroviral maturation. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcriptional bursting is intrinsically caused by interplay between RNA polymerases on DNA

NASA Astrophysics Data System (ADS)

Fujita, Keisuke; Iwaki, Mitsuhiro; Yanagida, Toshio

2016-12-01

Cell-to-cell variability plays a critical role in cellular responses and decision-making in a population, and transcriptional bursting has been broadly studied by experimental and theoretical approaches as the potential source of cell-to-cell variability. Although molecular mechanisms of transcriptional bursting have been proposed, there is little consensus. An unsolved key question is whether transcriptional bursting is intertwined with many transcriptional regulatory factors or is an intrinsic characteristic of RNA polymerase on DNA. Here we design an in vitro single-molecule measurement system to analyse the kinetics of transcriptional bursting. The results indicate that transcriptional bursting is caused by interplay between RNA polymerases on DNA. The kinetics of in vitro transcriptional bursting is quantitatively consistent with the gene-nonspecific kinetics previously observed in noisy gene expression in vivo. Our kinetic analysis based on a cellular automaton model confirms that arrest and rescue by trailing RNA polymerase intrinsically causes transcriptional bursting.

A definition of the degree of controllability - A criterion for actuator placement

NASA Technical Reports Server (NTRS)

Viswanathan, C. N.; Longman, R. W.; Likins, P. W.

1979-01-01

The unsolved problem of how to control the attitude and shape of future very large flexible satellite structures represents a challenging problem for modern control theory. One aspect of this problem is the question of how to choose the number and locations throughout the spacecraft of the control system actuators. Starting from basic physical considerations, this paper develops a concept of the degree of controllability of a control system, and then develops numerical methods to generate approximate values of the degree of controllability for any spacecraft. These results offer the control system designer a tool which allows him to rank the effectiveness of alternative actuator distributions, and hence to choose the actuator locations on a rational basis. The degree of controllability is shown to take a particularly simple form when the satellite dynamics equations are in modal form. Examples are provided to illustrate the use of the concept on a simple flexible spacecraft.

Genetics and Epigenetics of Mating Type Determination in Paramecium and Tetrahymena.

PubMed

Orias, Eduardo; Singh, Deepankar Pratap; Meyer, Eric

2017-09-08

While sex is an ancient and highly conserved eukaryotic invention, self-incompatibility systems such as mating types or sexes appear to be derived limitations that show considerable evolutionary plasticity. Within a single class of ciliates, Paramecium and Tetrahymena species have long been known to present a wide variety of mating type numbers and modes of inheritance, but only recently have the genes involved been identified. Although similar transmembrane proteins mediate self/nonself recognition in both ciliates, the mechanisms of mating type determination differ widely, ranging from Mendelian systems to developmental nuclear differentiation, either stochastic or maternally inherited. The non-Mendelian systems rely on programmed editing of the germline genome that occurs during differentiation of the somatic nucleus, and they have co-opted different DNA recombination mechanisms-some previously unknown. Here we review the recent molecular advances and some remaining unsolved questions and discuss the possible implications of these diverse mechanisms for inbreeding/outbreeding balance regulation.

A study of selected radiation and propagation problems related to antennas and probes in magneto-ionic media

NASA Technical Reports Server (NTRS)

1973-01-01

Research consisted of computations toward the solution of the problem of the current distribution on a cylindrical antenna in a magnetoplasma. The case of an antenna parallel to the applied magnetic field was investigated. A systematic method of asymptotic expansion was found which simplifies the solution in the general case by giving the field of a dipole even at relatively short range. Some useful properties of the dispersion surfaces in a lossy medium have also been found. A laboratory experiment was directed toward evaluating nonlinear effects, such as those due to power level, bias voltage and electron heating. The problem of reflection and transmission of waves in an electron heated plasma was treated theoretically. The profile inversion problem has been pursued. Some results are very encouraging, however, the general question of stability of the solution remains unsolved.

Bioavailability of pollutants in bacterial communities of Rodrigo de Freitas Lagoon, Rio de Janeiro, Brazil

PubMed Central

da Fonseca, E.M.; Neto, J.A. Baptista; McAlister, J.J.; Smith, B.J.; Crapez, M.A.C.

2014-01-01

Processes involving heavy metals and other contaminants continue to present unsolved environmental questions. To advance the understanding of geochemical processes that involve the bioavailability of contaminants, cores where collected in the Rodrigo de Freitas lagoon, and analyzed for bacterial activity and metal concentrations. Results would suggest an extremely reducing environment where organic substances seem to be the predominant agents responsible for this geochemical process. Analytical data showed sulphate reduction to be the main agent driving this process, since this kind of bacteria was found to be active in all of the samples analyzed. Esterase enzyme production did not signal the influence of heavy metals and hydrocarbon concentrations and heavy metals were found to be unavailable for biota. However, correlation between results for bacterial biomass and the potentially mobile percentage of the total Ni concentrations would suggest a negative impact. PMID:25477931

Efficacy of probiotics as an adjuvant agent in eradication of Helicobacter pylori infection and associated side effects.

PubMed

Goli, Y Dasteh; Moniri, R

2016-09-01

The intestinal tract is a host to various types of bacteria that are essential to health. Interactions between intestinal bacteria, i.e. the normal microbiota of the host's intestine, have been a subject of intensive research, as they may influence disease cycles. Recent studies of selected probiotic species and their therapeutic benefits have suggested a potential efficacy in treatment of several gastrointestinal illnesses, including Helicobacter pylori infection. The increasing evidence from these clinical studies supports the promising role of probiotics in improving the treatment of H. pylori by increasing eradication rates as well as decreasing the adverse effects of current medication therapy. However, many unsolved questions remain which require high quality trials on specific probiotic strains in the future. The main part of this review will focus on the effects of supplementary probiotic products during standard triple H. pylori therapy.

PhysioNet: physiologic signals, time series and related open source software for basic, clinical, and applied research.

PubMed

Moody, George B; Mark, Roger G; Goldberger, Ary L

2011-01-01

PhysioNet provides free web access to over 50 collections of recorded physiologic signals and time series, and related open-source software, in support of basic, clinical, and applied research in medicine, physiology, public health, biomedical engineering and computing, and medical instrument design and evaluation. Its three components (PhysioBank, the archive of signals; PhysioToolkit, the software library; and PhysioNetWorks, the virtual laboratory for collaborative development of future PhysioBank data collections and PhysioToolkit software components) connect researchers and students who need physiologic signals and relevant software with researchers who have data and software to share. PhysioNet's annual open engineering challenges stimulate rapid progress on unsolved or poorly solved questions of basic or clinical interest, by focusing attention on achievable solutions that can be evaluated and compared objectively using freely available reference data.

Thermodynamic energy exchange in a moving plate capacitor.

PubMed

Davis, B. R.; Abbott, D.; Parrondo, J. M. R.

2001-09-01

In this paper we describe an apparent paradox concerning a moving plate capacitor driven by thermal noise from a resistor. The plates are attracted together, but a demon restores the plates of the capacitor to their original position when the voltage across the capacitor is small-hence only small forces are present for the demon to work against. The demon has to work harder than this to avoid the situation of perpetual motion, but the open question is how? This is unsolved, however we explore the concept of a moving plate capacitor by examining the case where it is still excited by thermal noise, but where the restoring force on the capacitor plates is provided by a simple spring rather than some unknown demon. We display simulation results with interesting behavior, particularly where the capacitor plates collide with each other. (c) 2001 American Institute of Physics.

Patient responses to Er:YAG laser when used for conservative dentistry.

PubMed

Fornaini, Carlo; Riceputi, David; Lupi-Pegurier, Laurence; Rocca, Jean Paul

2012-11-01

The utilization of laser technology in conservative dentistry offers several advantages compared with traditional instruments, but one of the still unsolved problems is the difficulty in describing and explaining these advantages to patients. The aims of this study were to verify the efficacy of the way patients are informed and to evaluate their satisfaction with laser-assisted treatment. Before treatment, 100 patients were given a brochure that explained the relevant laser-assisted dental procedures, and after dental treatment an 11-item questionnaire was administered to the patients to evaluate their satisfaction with the treatment. Statistical analysis showed high levels of satisfaction for all the questions, especially those regarding the choice between laser therapy and traditional instruments (100%), choosing laser in the future (89%), and recommending it to family and friends (84%). This study may be relevant when determining the overall satisfaction of patients with this new technology.

[Criteria for evaluating the effective work of a tuberculosis hospital, accounting, and software].

PubMed

Lekhliaĭder, M V; Okhtiarkina, V V

2007-01-01

The hospital stage is by right basic in the treatment of patients with tuberculosis. Hospitalization meets two challenges: 1) controlled treatment of a patient and 2) his isolation from healthy individuals. However, the analysis of the efficiency of hospital work only by resource characteristics does not reflect the actual volume and rate of delivered antituberculous care. A check of the work of tuberculosis hospitals in the Chelyabinsk Region has shown a number of unsolved questions requiring a detailed analysis and managerial decision making. At present, there is a need for an exact calculation of the number of specialized tuberculosis beds, their conversion, as well as, to make the most use of all available therapeutic and diagnostic capacities of tuberculosis-controlling service of the subject of the Russian Federation, for the development of a regional route for a tuberculosis patient on the basis of the adopted health care standards.

General Relativity and Cosmology: Unsolved Questions and Future Directions

NASA Astrophysics Data System (ADS)

Debono, Ivan; Smoot, George F.

2016-09-01

For the last 100 years, General Relativity (GR) has taken over the gravitational theory mantle held by Newtonian Gravity for the previous 200 years. This article reviews the status of GR in terms of its self-consistency, completeness, and the evidence provided by observations, which have allowed GR to remain the champion of gravitational theories against several other classes of competing theories. We pay particular attention to the role of GR and gravity in cosmology, one of the areas in which one gravity dominates and new phenomena and effects challenge the orthodoxy. We also review other areas where there are likely conflicts pointing to the need to replace or revise GR to represent correctly observations and consistent theoretical framework. Observations have long been key both to the theoretical liveliness and viability of GR.We conclude with a discussion of the likely developments over the next 100 years.

Maintenance therapy in colon cancer.

PubMed

Giuliani, F; De Vita, F; Colucci, G; Pisconti, S

2010-11-01

In the last decade dramatic improvements have been obtained in the treatment of metastatic colorectal cancer. Thanks to the introduction in the clinical practice of new drugs such as Irinotecan and Oxaliplatin, and modern biological drugs such as Bevacizumab and Cetuximab, the response rate, progression-free and overall survival are about 50-60%, 9-11 and 20-24 months respectively. Despite this progress, many questions remain unsolved especially those related to the optimal duration of treatment and the role of maintenance therapy. To treat until progression (or unacceptable toxicity) is the classical way but in the common clinical practice is frequent to perform an induction therapy (until the maximum response is obtained) followed by a complete stop and restart on progression, or by a maintenance without the drug/s responsible of the major cumulative toxicities. The following report focus on the role of different strategies respect to the classic "treatment until progression". Copyright © 2010 Elsevier Ltd. All rights reserved.

Voice - How humans communicate?

PubMed

Tiwari, Manjul; Tiwari, Maneesha

2012-01-01

Voices are important things for humans. They are the medium through which we do a lot of communicating with the outside world: our ideas, of course, and also our emotions and our personality. The voice is the very emblem of the speaker, indelibly woven into the fabric of speech. In this sense, each of our utterances of spoken language carries not only its own message but also, through accent, tone of voice and habitual voice quality it is at the same time an audible declaration of our membership of particular social regional groups, of our individual physical and psychological identity, and of our momentary mood. Voices are also one of the media through which we (successfully, most of the time) recognize other humans who are important to us-members of our family, media personalities, our friends, and enemies. Although evidence from DNA analysis is potentially vastly more eloquent in its power than evidence from voices, DNA cannot talk. It cannot be recorded planning, carrying out or confessing to a crime. It cannot be so apparently directly incriminating. As will quickly become evident, voices are extremely complex things, and some of the inherent limitations of the forensic-phonetic method are in part a consequence of the interaction between their complexity and the real world in which they are used. It is one of the aims of this article to explain how this comes about. This subject have unsolved questions, but there is no direct way to present the information that is necessary to understand how voices can be related, or not, to their owners.

Healthons: errorless healthcare with bionic hugs and no need for quality control.

PubMed

Bushko, Renata G

2005-01-01

Errorless, invisible, continuous and infrastructure-free healthcare should become our goal. In order to achieve that goal, we need to rapidly move from current episodic and emergency-driven "healthcare delivery system" to an intelligent and extelligent health environment. That requires introduction of distributed affective Intelligent Caring Creatures (ICCs) consisting of healthons. Healthons are tools combining prevention with diagnosis and treatment based on continuous monitoring and analyzing of vital signs and biochemistry. Unlike humans, who posses only two or three dimensions of thinking, healthons can assure errorless health because of their adaptability, flexibility, and multidimensional reasoning capability. ICCs can do "the right thing" based on (1) state-of-art medical knowledge, (2) data about emotional, physiological, and genetic state of a consumer and (3) moral values of a consumer. The transition to the intelligent health environment based on ICCs requires the solutions to many currently unsolved healthcare problems. This paper lists the unsolved problems (by analogy to mathematical unsolved problems list) and explains why errorless healthcare with bionic hugs and no need for quality control is possible.

Introduction: Unsolved Problems on Noise

NASA Astrophysics Data System (ADS)

Oriols, X.; Ciliberto, S.

2016-05-01

This paper is an introduction to the special issue of the 7th Int. Conf. on Unsolved Problems on Noise (UPoN) that took place at Casa Convalescència in Barcelona (Spain) in July 2015. The aim of the UPoN conferences is to provide a forum for researchers working on different fields of noise, fluctuations and variability, where they present their scientific problems which resist solutions. The papers of this Special Issue reflect the interdisciplinary topics (physics, biology, circuits, financial markets, psychology, technology, etc) presented at the UPoN conference. Noise is not only a hindrance to signal detection, but it is indeed a valuable source of information (not present in the signal) that help us to get a deeper understanding on how Nature works. This special issue of the 7th International Conference on Unsolved Problems on Noise (UPoN) is dedicated to Laszlo Kish in the occasion of his 60th birthday. He organized the first edition of these UPoN conferences in Szeged (Hungary) in 1996. Many of us have greatly benefited from his ‘volcanic imagination in tackling new problems from unconventional points of views’.

Entropic stabilization of isolated beta-sheets.

PubMed

Dugourd, Philippe; Antoine, Rodolphe; Breaux, Gary; Broyer, Michel; Jarrold, Martin F

2005-04-06

Temperature-dependent electric deflection measurements have been performed for a series of unsolvated alanine-based peptides (Ac-WA(n)-NH(2), where Ac = acetyl, W = tryptophan, A = alanine, and n = 3, 5, 10, 13, and 15). The measurements are interpreted using Monte Carlo simulations performed with a parallel tempering algorithm. Despite alanine's high helix propensity in solution, the results suggest that unsolvated Ac-WA(n)-NH(2) peptides with n > 10 adopt beta-sheet conformations at room temperature. Previous studies have shown that protonated alanine-based peptides adopt helical or globular conformations in the gas phase, depending on the location of the charge. Thus, the charge more than anything else controls the structure.

Metagenomic Analysis of Viruses in Feces from Unsolved Outbreaks of Gastroenteritis in Humans

PubMed Central

Moore, Nicole E.; Wang, Jing; Hewitt, Joanne; Croucher, Dawn; Williamson, Deborah A.; Paine, Shevaun; Yen, Seiha; Greening, Gail E.

2014-01-01

The etiology of an outbreak of gastroenteritis in humans cannot always be determined, and ∼25% of outbreaks remain unsolved in New Zealand. It is hypothesized that novel viruses may account for a proportion of unsolved cases, and new unbiased high-throughput sequencing methods hold promise for their detection. Analysis of the fecal metagenome can reveal the presence of viruses, bacteria, and parasites which may have evaded routine diagnostic testing. Thirty-one fecal samples from 26 gastroenteritis outbreaks of unknown etiology occurring in New Zealand between 2011 and 2012 were selected for de novo metagenomic analysis. A total data set of 193 million sequence reads of 150 bp in length was produced on an Illumina MiSeq. The metagenomic data set was searched for virus and parasite sequences, with no evidence of novel pathogens found. Eight viruses and one parasite were detected, each already known to be associated with gastroenteritis, including adenovirus, rotavirus, sapovirus, and Dientamoeba fragilis. In addition, we also describe the first detection of human parechovirus 3 (HPeV3) in Australasia. Metagenomics may thus provide a useful audit tool when applied retrospectively to determine where routine diagnostic processes may have failed to detect a pathogen. PMID:25339401

Proceedings of the NASA Conference on Space Telerobotics, volume 3

NASA Technical Reports Server (NTRS)

Rodriguez, Guillermo (Editor); Seraji, Homayoun (Editor)

1989-01-01

The theme of the Conference was man-machine collaboration in space. The Conference provided a forum for researchers and engineers to exchange ideas on the research and development required for application of telerobotics technology to the space systems planned for the 1990s and beyond. The Conference: (1) provided a view of current NASA telerobotic research and development; (2) stimulated technical exchange on man-machine systems, manipulator control, machine sensing, machine intelligence, concurrent computation, and system architectures; and (3) identified important unsolved problems of current interest which can be dealt with by future research.

Deformations of infinite-dimensional Lie algebras, exotic cohomology, and integrable nonlinear partial differential equations

NASA Astrophysics Data System (ADS)

Morozov, Oleg I.

2018-06-01

The important unsolved problem in theory of integrable systems is to find conditions guaranteeing existence of a Lax representation for a given PDE. The exotic cohomology of the symmetry algebras opens a way to formulate such conditions in internal terms of the PDE s under the study. In this paper we consider certain examples of infinite-dimensional Lie algebras with nontrivial second exotic cohomology groups and show that the Maurer-Cartan forms of the associated extensions of these Lie algebras generate Lax representations for integrable systems, both known and new ones.

Surgical treatment of obesity.

PubMed

Bult, Mariëlle J F; van Dalen, Thijs; Muller, Alex F

2008-02-01

More than half of the European population are overweight (body mass index (BMI) > 25 and < 30 kg/m2) and up to 30% are obese (BMI > or = 30 kg/m2). Being overweight and obesity are becoming endemic, particularly because of increasing nourishment and a decrease in physical exercise. Insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cholelithiasis, certain forms of cancer, steatosis hepatis, gastroesophageal reflux, obstructive sleep apnea, degenerative joint disease, gout, lower back pain, and polycystic ovary syndrome are all associated with overweight and obesity. The endemic extent of overweight and obesity with its associated comorbidities has led to the development of therapies aimed at weight loss. The long-term effects of diet, exercise, and medical therapy on weight are relatively poor. With respect to durable weight reduction, bariatric surgery is the most effective long-term treatment for obesity with the greatest chances for amelioration and even resolution of obesity-associated complications. Recent evidence shows that bariatric surgery for severe obesity is associated with decreased overall mortality. However, serious complications can occur and therefore a careful selection of patients is of utmost importance. Bariatric surgery should at least be considered for all patients with a BMI of more than 40 kg/m2 and for those with a BMI of more than 35 kg/m2 with concomitant obesity-related conditions after failure of conventional treatment. The importance of weight loss and results of conventional treatment will be discussed first. Currently used operative treatments for obesity and their effectiveness and complications are described. Proposed criteria for bariatric surgery are given. Also, some attention is devoted to more basic insights that bariatric surgery has provided. Finally we deal with unsolved questions and future directions for research.

Exploring the mechanisms regulating regeneration of deer antlers.

PubMed Central

Price, J; Allen, S

2004-01-01

Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a 'brake', inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues. PMID:15293809

Testing Scientific Software: A Systematic Literature Review.

PubMed

Kanewala, Upulee; Bieman, James M

2014-10-01

Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques.

Current findings, future trends, and unsolved problems in studies of medicinal mushrooms.

PubMed

Wasser, Solomon P

2011-03-01

The target of the present review is to draw attention to many critically important unsolved problems in the future development of medicinal mushroom science in the twenty-first century. Special attention is paid to mushroom polysaccharides. Many, if not all, higher Basidiomycetes mushrooms contain biologically active polysaccharides in fruit bodies, cultured mycelium, and cultured broth. The data on mushroom polysaccharides are summarized for approximately 700 species of higher Hetero- and Homobasidiomycetes. The chemical structure of polysaccharides and its connection to antitumor activity, including possible ways of chemical modification, experimental testing and clinical use of antitumor or immunostimulating polysaccharides, and possible mechanisms of their biological action, are discussed. Numerous bioactive polysaccharides or polysaccharide-protein complexes from medicinal mushrooms are described that appear to enhance innate and cell-mediated immune responses and exhibit antitumor activities in animals and humans. Stimulation of host immune defense systems by bioactive polymers from medicinal mushrooms has significant effects on the maturation, differentiation, and proliferation of many kinds of immune cells in the host. Many of these mushroom polymers were reported previously to have immunotherapeutic properties by facilitating growth inhibition and destruction of tumor cells. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom polymers appears central. Particularly and most importantly for modern medicine are polysaccharides with antitumor and immunostimulating properties. Several of the mushroom polysaccharide compounds have proceeded through phases I, II, and III clinical trials and are used extensively and successfully in Asia to treat various cancers and other diseases. A total of 126 medicinal functions are thought to be produced by medicinal mushrooms and fungi including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemia, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects.

Group work as an incentive for learning – students’ experiences of group work

PubMed Central

Hammar Chiriac, Eva

2014-01-01

Group work is used as a means for learning at all levels in educational systems. There is strong scientific support for the benefits of having students learning and working in groups. Nevertheless, studies about what occurs in groups during group work and which factors actually influence the students’ ability to learn is still lacking. Similarly, the question of why some group work is successful and other group work results in the opposite is still unsolved. The aim of this article is to add to the current level of knowledge and understandings regarding the essence behind successful group work in higher education. This research is focused on the students’ experiences of group work and learning in groups, which is an almost non-existing aspect of research on group work prior to the beginning of the 21st century. A primary aim is to give university students a voice in the matter by elucidating the students’ positive and negative points of view and how the students assess learning when working in groups. Furthermore, the students’ explanations of why some group work ends up being a positive experience resulting in successful learning, while in other cases, the result is the reverse, are of interest. Data were collected through a study-specific questionnaire, with multiple choice and open-ended questions. The questionnaires were distributed to students in different study programs at two universities in Sweden. The present result is based on a reanalysis and qualitative analysis formed a key part of the study. The results indicate that most of the students’ experiences involved group work that facilitated learning, especially in the area of academic knowledge. Three important prerequisites (learning, study-social function, and organization) for group work that served as an effective pedagogy and as an incentive for learning were identified and discussed. All three abstractions facilitate or hamper students’ learning, as well as impact their experiences with group work. PMID:24926282

High fidelity kinetic modeling of magnetic reconnection in laboratory plasma

NASA Astrophysics Data System (ADS)

Stanier, A.; Daughton, W. S.

2017-12-01

Over the past decade, a great deal of progress has been made towards understanding the physics of magnetic reconnection in weakly collisional regimes of relevance to both fusion devices, and to space and astrophysical plasmas. However, there remain some outstanding unsolved problems in reconnection physics, such as the generation and influence of plasmoids (flux ropes) within reconnection layers, the development of magnetic turbulence, the role of current driven and streaming instabilities, and the influence of electron pressure anisotropy on the layer structure. Due to the importance of these questions, new laboratory reconnection experiments are being built to allow controlled and reproducible study of such questions with the simultaneous acquisition of high time resolution measurements at a large number of spatial points. These experiments include the FLARE facility at Princeton University and the T-REX experiment at the University of Wisconsin. To guide and interpret these new experiments, and to extrapolate the results to space applications, new investments in kinetic modeling tools are required. We have recently developed a cylindrical version of the VPIC Particle-In-Cell code with the capability to perform first-principles kinetic simulations that approach experimental device size with more realistic geometry and drive coils. This cylindrical version inherits much of the optimization work that has been done recently for the next generation many-cores architectures with wider vector registers, and achieves comparable conservation properties as the Cartesian code. Namely it features exact discrete charge conservation, and a so-called "energy-conserving" scheme where the energy is conserved in the limit of continuous time, i.e. without contribution from spatial discretization (Lewis, 1970). We will present initial results of modeling magnetic reconnection in the experiments mentioned above. Since the VPIC code is open source (https://github.com/losalamos/vpic), this new cylindrical version will also be freely available to the community.

Isolated thoughts and feelings and unsolved concerns: adolescents' and parents' perspectives on living with type 1 diabetes - a qualitative study using visual storytelling.

PubMed

Castensøe-Seidenfaden, Pernille; Teilmann, Grete; Kensing, Finn; Hommel, Eva; Olsen, Birthe Susanne; Husted, Gitte Reventlov

2017-10-01

To explore and describe the experiences of adolescents and their parents living with type 1 diabetes, to identify their needs for support to improve adolescents' self-management skills in the transition from child- to adulthood. Adolescents with type 1 diabetes often experience deteriorating glycaemic control and distress. Parents are important in adolescents' ability to self-manage type 1 diabetes, but they report anxiety and frustrations. A better understanding of the challenges adolescents and parents face, in relation to the daily self-management of type 1 diabetes, is important to improve clinical practice. A qualitative explorative study using visual storytelling as part of individual interviews. A purposive sample of nine adolescents and their parents (seven mothers, six fathers) took photographs illustrating their experiences living with type 1 diabetes. Subsequently, participants were interviewed individually guided by participants' photographs and a semistructured interview guide. Interviews were analysed using thematic analysis. Four major themes were consistent across adolescents and their parents: (1) striving for safety, (2) striving for normality, (3) striving for independence and (4) worrying about future. Although adolescents and parents had same concerns and challenges living with type 1 diabetes, they were experienced differently. Their thoughts and feelings mostly remained isolated and their concerns and challenges unsolved. The concerns and challenges adolescents and their parents face in the transition from child- to adulthood are still present despite new treatment modalities. Parents are fundamental in supporting the adolescents' self-management-work; however, the parties have unspoken concerns and challenges. Healthcare providers should address the parties' challenges and concerns living with type 1 diabetes to diminish worries about future including fear of hypoglycaemia, the burden of type 1 diabetes and the feeling of being incompetent in diabetes self-management. It is important to focus on supporting both adolescents and their parents, and to provide a shared platform for communication. © 2016 John Wiley & Sons Ltd.

Ancient marine hunter-gatherers from Patagonia and Tierra Del Fuego: Diversity and differentiation using uniparentally inherited genetic markers.

PubMed

de la Fuente, Constanza; Galimany, Jacqueline; Kemp, Brian M; Judd, Kathleen; Reyes, Omar; Moraga, Mauricio

2015-12-01

The human population history from Patagonia and Tierra del Fuego has been of great interest in the context of the American peopling. Different sources of evidence have contributed to the characterization of the local populations, but some main questions about their history remain unsolved. Among the native populations, two marine hunter-gatherers groups inhabited the Patagonian channels below the 478S: Kawéskar and Yámana. Regardless of their geographical proximity and cultural resemblance, their languages were mutually unintelligible. In this study we aim to evaluate the genetic diversity of uniparental genetic markers in both groups and to test if there is a high genetic differentiation between them, mirroring their linguistic differences. Ancient DNA was extracted from 37 samples from both populations. We compared their genetic variability of their mitochondrial lineages and Y-STR as well as with other modern native populations from the area and further north. We observed an important differentiation in their maternal lineages: while Kawéskar shows a high frequency of D (80%), Yámana shows a high frequency of C (90%). The analysis of paternal lineages reveals the presence of only Q1a2a1a1 and little variation was found between individuals. Both groups show very low levels of genetic diversity compared with modern populations. We also notice shared and unique mitochondrial DNA variants between modern and ancient samples of Kawéskar and Yámana. © 2015 Wiley Periodicals, Inc.

The concept of function in modern physiology.

PubMed

Roux, Etienne

2014-06-01

An overview of the scientific literature shows that the concept of function is central in physiology. However, the concept itself is not defined by physiologists. On the other hand, the teleological, namely, the 'goal-directed' dimension of function, and its subsequent explanatory relevance, is a philosophical problem. Intuitively, the function of a trait in a system explains why this trait is present, but, in the early 1960s, Ernest Nagel and Carl Hempel have shown that this inference cannot be logically founded. However, they showed that self-regulated systems are teleological. According to the selectionist theories, the function of an item is its effect that has been selected by natural selection, a process that explains its presence. As they restrict the functional attribution of a trait to its past selective value and not its current properties, these theories are inconsistent with the concept of function in physiology. A more adequate one is the causal role theory, for which a function of a trait in a system is its causal contribution to the functional capacity of the system. However, this leaves unsolved the question of the 'surplus meaning' of the teleological dimension of function. The significance of considering organisms as 'purpose-like' (teleological) systems may reside not in its explanatory power but in its methodological fruitfulness in physiology. In this view, the teleological dimension of physiological functions is convergent to but not imported from, the teleological dimension of evolutionary biology. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum.

PubMed

van Lith, Marcel; Hartigan, Nichola; Hatch, Jennifer; Benham, Adam M

2005-01-14

Protein disulfide isomerase (PDI) is the archetypal enzyme involved in the formation and reshuffling of disulfide bonds in the endoplasmic reticulum (ER). PDI achieves its redox function through two highly conserved thioredoxin domains, and PDI can also operate as an ER chaperone. The substrate specificities and the exact functions of most other PDI family proteins remain important unsolved questions in biology. Here, we characterize a new and striking member of the PDI family, which we have named protein disulfide isomerase-like protein of the testis (PDILT). PDILT is the first eukaryotic SXXC protein to be characterized in the ER. Our experiments have unveiled a novel, glycosylated PDI-like protein whose tissue-specific expression and unusual motifs have implications for the evolution, catalytic function, and substrate selection of thioredoxin family proteins. We show that PDILT is an ER resident glycoprotein that liaises with partner proteins in disulfide-dependent complexes within the testis. PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family proteins to ER oxidoreductases. The expression of PDILT, in addition to PDI in the testis, suggests that PDILT performs a specialized chaperone function in testicular cells. PDILT is an unusual PDI relative that highlights the adaptability of chaperone and redox function in enzymes of the endoplasmic reticulum.

Learning what to expect (in visual perception)

PubMed Central

Seriès, Peggy; Seitz, Aaron R.

2013-01-01

Expectations are known to greatly affect our experience of the world. A growing theory in computational neuroscience is that perception can be successfully described using Bayesian inference models and that the brain is “Bayes-optimal” under some constraints. In this context, expectations are particularly interesting, because they can be viewed as prior beliefs in the statistical inference process. A number of questions remain unsolved, however, for example: How fast do priors change over time? Are there limits in the complexity of the priors that can be learned? How do an individual’s priors compare to the true scene statistics? Can we unlearn priors that are thought to correspond to natural scene statistics? Where and what are the neural substrate of priors? Focusing on the perception of visual motion, we here review recent studies from our laboratories and others addressing these issues. We discuss how these data on motion perception fit within the broader literature on perceptual Bayesian priors, perceptual expectations, and statistical and perceptual learning and review the possible neural basis of priors. PMID:24187536

Probing Strong Interaction with Kaonic Atoms — from DAΦNE to J-PARC

NASA Astrophysics Data System (ADS)

Zmeskal, J.; Sato, M.; Bazzi, M.; Beer, G.; Berucci, C.; Bosnar, D.; Bragadireanu, M.; Buehler, P.; Cargnelli, M.; Clozza, A.; Curceanu, C.; D'uffizi, A.; Fabbietti, L.; Fiorini, C.; Ghio, F.; Golser, R.; Guaraldo, C.; Hashimoto, T.; Hayano, R. S.; Iliescu, M.; Itahashi, K.; Iwasaki, M.; Levi Sandri, P.; Marton, J.; Moskal, P.; Ohnishi, H.; Okada, S.; Outa, H.; Pietreanu, D.; Piscicchia, K.; Poli Lener, M.; Romero Vidal, A.; Sakuma, F.; Sbardella, E.; Scordo, A.; Shi, H.; Sirghi, D.; Sirghi, F.; Suzuki, K.; Tucakovic, I.; Vazquez Doce, O.; Widmann, E.

The study of the antikaon nucleon system at very low energies plays a key role to study strong interaction with strangeness, touching one of the fundamental problems in hadron physic today — the still unsolved question of how hadron masses are generated. Exotic atoms offer a unique possibility to determine s-wave kaon-nucleon scattering lengths at vanishing energy. At the DAΦNE electron positron collider of Laboratori Nazionali di Frascati in the SIDDHARTA experiment kaonic atoms were formed with Z = 1 (K-p) and Z = 2 (K-He), which were measured with up to now unrivalled precision. This experiment is taking advantage of the low-energy charged kaons from ϕ-mesons decaying nearly at rest. Finally, using the experience gained with SIDDHARTA, a proposal to measure kaonic deuterium for the first time was submitted to J-PARC with the goal to determine the isospin dependent scattering lengths, which is only possible by combining the K-p and the upcoming K-d results.

Congenital myopathy associated with the triadin knockout syndrome

PubMed Central

Redhage, Keeley R.; Tester, David J.; Ackerman, Michael J.; Selcen, Duygu

2017-01-01

Objective: Triadin is a component of the calcium release complex of cardiac and skeletal muscle. Our objective was to analyze the skeletal muscle phenotype of the triadin knockout syndrome. Methods: We performed clinical evaluation, analyzed morphologic features by light and electron microscopy, and immunolocalized triadin in skeletal muscle. Results: A 6-year-old boy with lifelong muscle weakness had a triadin knockout syndrome caused by compound heterozygous null mutations in triadin. Light microscopy of a deltoid muscle specimen shows multiple small abnormal spaces in all muscle fibers. Triadin immunoreactivity is absent from type 1 fibers and barely detectable in type 2 fibers. Electron microscopy reveals focally distributed dilation and degeneration of the lateral cisterns of the sarcoplasmic reticulum and loss of the triadin anchors from the preserved lateral cisterns. Conclusions: Absence of triadin in humans can result in a congenital myopathy associated with profound pathologic alterations in components of the sarcoplasmic reticulum. Why only some triadin-deficient patients develop a skeletal muscle phenotype remains an unsolved question. PMID:28202702

Genetics and epigenetics of rheumatoid arthritis

PubMed Central

Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

2013-01-01

Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

Social penalty promotes cooperation in a cooperative society.

PubMed

Ito, Hiromu; Yoshimura, Jin

2015-08-04

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

Cosmic Topology

NASA Astrophysics Data System (ADS)

Luminet, Jean-Pierre

2015-08-01

Cosmic Topology is the name given to the study of the overall shape of the universe, which involves both global topological features and more local geometrical properties such as curvature. Whether space is finite or infinite, simply-connected or multi-connected like a torus, smaller or greater than the portion of the universe that we can directly observe, are questions that refer to topology rather than curvature. A striking feature of some relativistic, multi-connected "small" universe models is to create multiples images of faraway cosmic sources. While the most recent cosmological data fit the simplest model of a zero-curvature, infinite space model, they are also consistent with compact topologies of the three homogeneous and isotropic geometries of constant curvature, such as, for instance, the spherical Poincaré Dodecahedral Space, the flat hypertorus or the hyperbolic Picard horn. After a "dark age" period, the field of Cosmic Topology has recently become one of the major concerns in cosmology, not only for theorists but also for observational astronomers, leaving open a number of unsolved issues.

Metabolic engineering of yeast for lignocellulosic biofuel production.

PubMed

Jin, Yong-Su; Cate, Jamie Hd

2017-12-01

Production of biofuels from lignocellulosic biomass remains an unsolved challenge in industrial biotechnology. Efforts to use yeast for conversion face the question of which host organism to use, counterbalancing the ease of genetic manipulation with the promise of robust industrial phenotypes. Saccharomyces cerevisiae remains the premier host for metabolic engineering of biofuel pathways, due to its many genetic, systems and synthetic biology tools. Numerous engineering strategies for expanding substrate ranges and diversifying products of S. cerevisiae have been developed. Other yeasts generally lack these tools, yet harbor superior phenotypes that could be exploited in the harsh processes required for lignocellulosic biofuel production. These include thermotolerance, resistance to toxic compounds generated during plant biomass deconstruction, and wider carbon consumption capabilities. Although promising, these yeasts have yet to be widely exploited. By contrast, oleaginous yeasts such as Yarrowia lipolytica capable of producing high titers of lipids are rapidly advancing in terms of the tools available for their metabolic manipulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social penalty promotes cooperation in a cooperative society

PubMed Central

Ito, Hiromu; Yoshimura, Jin

2015-01-01

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

Ontogenetic effects on gazing behaviour: a case study of kennel dogs (Labrador Retrievers) in the impossible task paradigm.

PubMed

D'Aniello, Biagio; Scandurra, Anna

2016-05-01

Life experiences and living conditions can influence the problem-solving strategies and the communicative abilities of dogs with humans. The goals of this study were to determine any behavioural differences between Labrador Retrievers living in a kennel and those living in a house as pets and to assess whether kennel dogs show preferences in social behaviours for their caretaker relative to a stranger when they are faced with an unsolvable task. Nine Labrador Retrievers living in a kennel from birth and ten Labrador Retrievers living in a family as pets were tested. The experimental procedure consisted of three "solvable" tasks in which the dogs could easily retrieve food from a container followed by an "unsolvable" task in which the container was hermetically locked. Dogs of both groups spent the same amount of time interacting with the experimental apparatus. Kennel dogs gazed towards people for less time and with higher latency than pet dogs; however, there were no significant preferences in gazing towards the stranger versus the caretaker in both groups. These findings demonstrated that kennel dogs are less prone to use human-directed gazing behaviour when they are faced with an unsolvable problem, taking the humans into account to solve a task less than do the pet dogs.

The role of domestication and experience in 'looking back' towards humans in an unsolvable task.

PubMed

Marshall-Pescini, Sarah; Rao, Akshay; Virányi, Zsófia; Range, Friederike

2017-04-19

A key element thought to have changed during domestication is dogs' propensity to communicate with humans, particularly their inclination to gaze at them. A classic test to measure this is the 'unsolvable task', where after repeated successes in obtaining a reward by object-manipulation, the animal is confronted with an unsolvable version of the task. 'Looking back' at humans has been considered an expression of dogs seeking help. While it occurs more in dogs than in socialized wolves, the level of exposure to human communication also appears to play a role. We tested similarly raised adult wolves and mixed breed dogs, pet dogs and free-ranging dogs. Unlike previous studies, as well as species and levels of socialization, we included 'persistence' in trying to solve the task as a potential explanatory factor. Wolves were more persistent than all dog groups. Regardless of socialization or species, less persistent animals looked back sooner and longer. Free-ranging dogs, despite little exposure to dog-human communication, behaved similarly to other dogs. Together, results suggest that basic wolf-dog differences in motivation and exploration may override differences in human-directed behaviour when animals are equally socialized, and that once the human is considered a social partner, looking behaviour occurs easily.

The role of domestication and experience in ‘looking back’ towards humans in an unsolvable task

PubMed Central

Marshall-Pescini, Sarah; Rao, Akshay; Virányi, Zsófia; Range, Friederike

2017-01-01

A key element thought to have changed during domestication is dogs’ propensity to communicate with humans, particularly their inclination to gaze at them. A classic test to measure this is the ‘unsolvable task’, where after repeated successes in obtaining a reward by object-manipulation, the animal is confronted with an unsolvable version of the task. ‘Looking back’ at humans has been considered an expression of dogs seeking help. While it occurs more in dogs than in socialized wolves, the level of exposure to human communication also appears to play a role. We tested similarly raised adult wolves and mixed breed dogs, pet dogs and free-ranging dogs. Unlike previous studies, as well as species and levels of socialization, we included ‘persistence’ in trying to solve the task as a potential explanatory factor. Wolves were more persistent than all dog groups. Regardless of socialization or species, less persistent animals looked back sooner and longer. Free-ranging dogs, despite little exposure to dog-human communication, behaved similarly to other dogs. Together, results suggest that basic wolf-dog differences in motivation and exploration may override differences in human-directed behaviour when animals are equally socialized, and that once the human is considered a social partner, looking behaviour occurs easily. PMID:28422169

The near-symmetry of proteins.

PubMed

Bonjack-Shterengartz, Maayan; Avnir, David

2015-04-01

The majority of protein oligomers form clusters which are nearly symmetric. Understanding of that imperfection, its origins, and perhaps also its advantages requires the conversion of the currently used vague qualitative descriptive language of the near-symmetry into an accurate quantitative measure that will allow to answer questions such as: "What is the degree of symmetry deviation of the protein?," "how do these deviations compare within a family of proteins?," and so on. We developed quantitative methods to answer this type of questions, which are capable of analyzing the whole protein, its backbone or selected portions of it, down to comparison of symmetry-related specific amino-acids, and which are capable of visualizing the various levels of symmetry deviations in the form of symmetry maps. We have applied these methods on an extensive list of homomers and heteromers and found that apparently all proteins never reach perfect symmetry. Strikingly, even homomeric protein clusters are never ideally symmetric. We also found that the main burden of symmetry distortion is on the amino-acids near the symmetry axis; that it is mainly the more hydrophilic amino-acids that take place in symmetry-distortive interactions; and more. The remarkable ability of heteromers to preserve near-symmetry, despite the different sequences, was also shown and analyzed. The comprehensive literature on the suggested advantages symmetric oligomerizations raises a yet-unsolved key question: If symmetry is so advantageous, why do proteins stop shy of perfect symmetry? Some tentative answers to be tested in further studies are suggested in a concluding outlook. © 2014 Wiley Periodicals, Inc.

Homo- and Heterometallic Bis(Pentafluorobenzoyl)Methanide Complexes of Copper(II) and Cobalt(II)

NASA Astrophysics Data System (ADS)

Crowder, Janell M.

beta-Diketones are well known to form metal complexes with practically every known metal and metalloid. Metal complexes of fluorinated beta-diketones generally exhibit increased volatility and thermal stability compared to the non-fluorinated analogues, and thus are used extensively in various chemical vapor deposition (CVD) processes for the deposition of metal, simple or mixed metal oxides, and fluorine-doped metal oxide thin films. Furthermore, the electron-withdrawing nature of the fluorinated ligand enhances the Lewis acidity of a coordinatively unsaturated metal center which facilitates additional coordination reactions. The physical and structural properties of fluorinated beta-diketonate complexes are discussed in Chapter 1 and a few key application examples are given. The focus of this work is the synthesis and single crystal X-ray structural characterization of unsolvated and coordinatively unsaturated metal complexes of bis(pentafluorobenzoyl)- methanide (L, C6F5COCHCOC 6F5-). In Chapter 2, we present the preparation and isolation of the unsolvated complex [Cu(L)2] in pure crystalline form for the first time. We subsequently investigated the reaction of unsolvated [Cu(L)2] with sodium hexafluoroacetylacetonate [Na(hfac)] in a solvent-free environment. This reaction allowed the isolation of the first heterometallic Na-Cu diketonate [Na2Cu2(L) 4(hfac)2] structurally characterized by single crystal X-ray crystallography. Thermal decomposition of [Na2Cu2(L) 4(hfac)2] was investigated for its potential application in MOCVD processes. In the final chapter, we present the first exploration of the anhydrous synthesis of Co(II) complexed with bis(pentafluorobenzoyl)methanide in order to produce a complex without ligated water. Single crystal X-ray crystallographic investigations revealed the isolation of the ethanol adduct, [Co2(L)4(C2H5OH)2], and following the removal of ethanol, a 1,4-dioxane adduct, [{Co 2(L)4}2(C4H8O2)]. In this work, we have provided the first investigation of the synthesis, isolation and single crystal X-ray structural characterization of unsolvated and coordinatively unsaturated Cu(II) and Co(II) complexes of bis(pentafluorobenzoyl)methanide ligand. These studies demonstrate how the electrophilicity of a coordinatively unsaturated metal complexed to highly-fluorinated â-diketone ligands can be utilized for the formation of new adducts or new and interesting heterometallic complexes. This body of work provides a basis upon which future research into unsolvated and unligated bis(pentafluorobenzoyl)methanide metal complexes can expand.

Metabolic syndrome and obesity in peritoneal dialysis.

PubMed

Lo, Wai Kei

2016-03-01

Metabolic syndrome (MS) refers to clustering of features related to increased risk of cardiovascular disease, which include obesity or central obesity, dyslipidemia, diabetes mellitus or insulin resistance, together with hypertension. The prevalence of MS in end-stage renal failure patients on peritoneal dialysis is quite common, ranging from 40% to 60%, depending on the population studied and the definition used. However, there are controversies about the clinical outcome of patients with MS, particularly in the area of obesity. Whether peritoneal dialysis predisposes patients to MS is another unsolved issue. Despite these controversies, preventing patients from developing MS is important, at least from a theoretical point of view.

Polyphyly of Arundinoideae (Poaceae) and evolution of the twisted geniculate lemma awn.

PubMed

Teisher, J K; McKain, M R; Schaal, B A; Kellogg, E A

2017-11-10

Subfamily Arundinoideae represents one of the last unsolved taxonomic mysteries in the grass family (Poaceae) due to the narrow and remote distributions of many of its 19 morphologically and ecologically heterogeneous genera. Resolving the phylogenetic relationships of these genera could have substantial implications for understanding character evolution in the grasses, for example the twisted geniculate awn - a hygroscopic awn that has been shown to be important in seed germination for some grass species. In this study, the phylogenetic positions of most arundinoid genera were determined using DNA from herbarium specimens, and their placement affects interpretation of this ecologically important trait. A phylogenetic analysis was conducted on a matrix of full-plastome sequences from 123 species in 107 genera representing all grass subfamilies, with 15 of the 19 genera in subfamily Arundinoideae. Parsimony and maximum likelihood mapping approaches were used to estimate ancestral states for presence of a geniculate lemma awn with a twisted column across Poaceae. Lastly, anatomical characters were examined for former arundinoid taxa using light microscopy and scanning electron microscopy. Four genera traditionally included in Arundinoideae fell outside the subfamily in the plastome phylogeny, with the remaining 11 genera forming Arundinoideae sensu stricto . The twisted geniculate awn has originated independently at least five times in the PACMAD grasses, in the subfamilies Panicoideae, Danthonioideae/Chloridoideae and Arundinoideae. Morphological and anatomical characters support the new positions of the misplaced arundinoid genera in the phylogeny, but also highlight convergent and parallel evolution in the grasses. In placing the majority of arundinoid genera in a phylogenetic framework, our study answers one of the last remaining big questions in grass taxonomy while highlighting examples of convergent evolution in an ecologically important trait, the hygroscopic, twisted geniculate awn. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Teacher Research Programs: An Effective Form of Professional Development to Increase Student Achievement and Benefit the Economy

NASA Astrophysics Data System (ADS)

Dubner, J.

2008-12-01

U.S. high school students perform markedly less well in science, technology, engineering and math (STEM) than students in other economically advanced countries. This low level of STEM performance endangers our democracy and economy. The President's Council of Advisors in Science and Technology's 2004 report attributed the shortfall of students attracted to the sciences is a result of the dearth of teachers sufficiently conversant with science and scientists to enable them to communicate to their students the excitement of scientific exploration and discovery, and the opportunities science provides for highly rewarding and remunerative careers. Nonetheless, the United States has made little progress in correcting these deficiencies. Studies have shown that high-quality teaching matters more to student achievement than anything else schools do. This belief is buttressed by evidence from Columbia University's Summer Research Program for Science Teachers (SRP) that highly motivated, in-service science teachers require professional development to enable them and their students to perform up to their potential. Columbia's Summer Research Program is based on the premise that to teach science effectively requires experience in using the tools of contemporary science to answer unsolved questions. From its inception, SRP's goal has been to enhance interest and improve performance in science of students. It seeks to achieve this goal by increasing the professional competence of teachers. The reports of Elmore, Sanders and Rivers, and our own studies, show that professional development is a "key lever for improving student outcomes." While most middle and high school science teachers have taken college science courses that include cookbook laboratory exercises, the vast majority of them have never attempted to answer an unsolved question. Just as student learning depends on the expertise of teachers, the expertise of teachers depends on the quality of their professional development. Columbia University's teacher research program is a very effective form of professional development for pre- college science teachers and has a direct correlation to increased student motivation and achievement in science. The Program is premised on the beliefs that hands-on experience in the practice of science improves the quality and authenticity of science teaching, and that improved science teaching is correlated with increased student interest and achievement in science. The author will present the methodology of the program's evaluation citing statistically significant findings. The author will also show the economic benefits of teacher participation in a well-designed research program.

Space Drive Physics: Introduction and Next Steps

NASA Astrophysics Data System (ADS)

Millis, M. G.

Research toward the visionary goal of propellantless ``space drives'' is introduced, covering key physics issues and a listing of roughly 2-dozen approaches. The targeted advantage of a space drive is to circumvent the propellant constraints of rockets and the maneuvering limits of light sails by using the interactions between the spacecraft and its surrounding space for propulsion. At present, the scientific foundations from which to engineer a space drive have not been discovered and, objectively, might be impossible. Although no propulsion breakthroughs appear imminent, the subject has matured to where the relevant questions have been broached and are beginning to be answered. The critical make-break issues include; conservation of momentum, uncertain sources of reaction mass, and the net-external thrusting requirement. Note: space drives are not necessarily faster- than-light devices. Speed limits are a separate, unanswered issue. Relevant unsolved physics includes; the sources and mechanisms of inertial frames, coupling of gravitation and electromagnetism, and the nature of the quantum vacuum. The propulsion approaches span mostly stages 1 through 3 of the scientific method (defining the problem, collecting data, and articulating hypotheses), while some have matured to stage 4 (testing hypotheses). Nonviable approaches include `stiction drives,' `gyroscopic antigravity,' and `lifters.' No attempt is made to gauge the prospects of the remaining approaches. Instead, a list of next-step research questions is derived from the examination of these goals, unknowns, and concepts.

Reconstructing Climate Change: The Model-Data Ping-Pong

NASA Astrophysics Data System (ADS)

Stocker, T. F.

2017-12-01

When Cesare Emiliani, the father of paleoceanography, made the first attempts at a quantitative reconstruction of Pleistocene climate change in the early 1950s, climate models were not yet conceived. The understanding of paleoceanographic records was therefore limited, and scientists had to resort to plausibility arguments to interpret their data. With the advent of coupled climate models in the early 1970s, for the first time hypotheses about climate processes and climate change could be tested in a dynamically consistent framework. However, only a model hierarchy can cope with the long time scales and the multi-component physical-biogeochemical Earth System. There are many examples how climate models have inspired the interpretation of paleoclimate data on the one hand, and conversely, how data have questioned long-held concepts and models. In this lecture I critically revisit a few examples of this model-data ping-pong, such as the bipolar seesaw, the mid-Holocene greenhouse gas increase, millennial and rapid CO2 changes reconstructed from polar ice cores, and the interpretation of novel paleoceanographic tracers. These examples also highlight many of the still unsolved questions and provide guidance for future research. The combination of high-resolution paleoceanographic data and modeling has never been more relevant than today. It will be the key for an appropriate risk assessment of impacts on the Earth System that are already underway in the Anthropocene.

Cystic fibrosis research topics featured at the 14th ECFS Basic Science Conference: Chairman's summary.

PubMed

Mall, Marcus A; Hwang, Tzyh-Chang; Braakman, Ineke

2018-03-01

In recent years, tremendous progress has been made in the development of novel drugs targeting the basic defect in patients with cystic fibrosis (CF). This breakthrough is based on a solid foundation of knowledge on CFTR's function in health and how mutations in CFTR cause CF multi-organ disease. This knowledge has been collected and continuously expanded by an active and persistent CF research community and has paved the way for precision medicine for CF. Since 2004, the European Cystic Fibrosis Society (ECFS) has held an annual Basic Science Conference that has evolved as an international forum for interdisciplinary discussion of hot topics and unsolved questions related to CF research. This Special Issue reviews CF research topics featured at the 14th ECFS Basic Science Conference and provides an up-to-date overview of recent progress in our understanding of CFTR structure and function, disease mechanisms implicated in airway mucus plugging, inflammation and abnormal host-pathogen interactions, and advancements with enhanced cell and animal model systems and breakthrough therapies directed at mutant CFTR or alternative targets. In addition, this Special Issue also identifies a number of fundamental questions and hurdles that still have to be overcome to realize the full potential of precision medicine and develop transformative therapies for all patients with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Testing Scientific Software: A Systematic Literature Review

PubMed Central

Kanewala, Upulee; Bieman, James M.

2014-01-01

Context Scientific software plays an important role in critical decision making, for example making weather predictions based on climate models, and computation of evidence for research publications. Recently, scientists have had to retract publications due to errors caused by software faults. Systematic testing can identify such faults in code. Objective This study aims to identify specific challenges, proposed solutions, and unsolved problems faced when testing scientific software. Method We conducted a systematic literature survey to identify and analyze relevant literature. We identified 62 studies that provided relevant information about testing scientific software. Results We found that challenges faced when testing scientific software fall into two main categories: (1) testing challenges that occur due to characteristics of scientific software such as oracle problems and (2) testing challenges that occur due to cultural differences between scientists and the software engineering community such as viewing the code and the model that it implements as inseparable entities. In addition, we identified methods to potentially overcome these challenges and their limitations. Finally we describe unsolved challenges and how software engineering researchers and practitioners can help to overcome them. Conclusions Scientific software presents special challenges for testing. Specifically, cultural differences between scientist developers and software engineers, along with the characteristics of the scientific software make testing more difficult. Existing techniques such as code clone detection can help to improve the testing process. Software engineers should consider special challenges posed by scientific software such as oracle problems when developing testing techniques. PMID:25125798

Information flow in the pharmaceutical supply chain.

PubMed

Yousefi, Nazila; Alibabaei, Ahmad

2015-01-01

Managing the supply chain plays an important role in creating competitive advantages for companies. Adequate information flow in supply chain is one of the most important issues in SCM. Therefore, using certain Information Systems can have a significant role in managing and integrating data and information within the supply chain. Pharmaceutical supply chain is more complex than many other supply chains, in the sense that it can affect social and political perspectives. On the other hand, managing the pharmaceutical supply chain is difficult because of its complexity and also government regulations in this field. Although, Iran has progressed a lot in pharmaceutical manufacturing, still there are many unsolved issues in managing the information flow in the pharmaceutical supply chain. In this study, we reviewed the benefits of using different levels of an integrated information system in the supply chain and the possible challenges ahead.

Studies of the atmosphere of Venus by means of spacecraft: Solved and unsolved problems

NASA Astrophysics Data System (ADS)

Moroz, V. I.

Many spacecraft were used for exploration of the atmosphere of Venus. Their list consists of 25 items, including fly-by missions, orbiters, descent and landing probes and even balloons. VENERA-4 (1967) was near the beginning of this list, providing the first time in situ experiments on other planet. It started a long sequence of successful Soviet Venera missions. However after the year 1985 there were no missions to Venus in Russia. It probably was a strategic error. Now several groups of scientists in other countries work on proposals for new missions to Venus. The goal of this paper is to present a brief review of already solved and still unsolved problems in the studies of the Venus' atmosphere and to possible future aims in this field.

[Psychosomatic symptoms in somatic diseases - open-angle glaucoma for example].

PubMed

Emmerich, G M

2010-08-01

Psychological aspects exist in somatic diseases like tumours and even fractures, not only in the beginning but also in the management of disease. Somatic diseases give rise to signs of a special constellation of life and management of these diseases is important for the psychological constellation of the individual. Studies on open-angle glaucoma have shown that many patients suffering from this disease are anxious, hypochondric, perfectionist and emotional instable. Chronic diseases are demanding processes of flexibility and defense, and define how the individual can deal with the diseases and what place in life the disease will occupy in the future. In the holistic view of medicine even psychological conflicts should be treated. In many situations, these conflicts are not consciously experienced by the individual. Therapeutically, 2 different tools can be used: symbolic stories can bring forces to manage the conflict and to solve the conflict (2 examples in the text). The method of positive psychotherapy describes the reasons for psychosomatic diseases in three parts: psychosomatic in the traditional understanding, in further and comprehensive understanding. Especially the psychosomatic effects in comprehensive understanding are embedded in the individual's sociocultural environment and provide tips on reasons for the diseases in those parts of life. The "positive balance model" gives an example of life-management and conflict-therapy. In ophthalmology, fear is often more important for the patient than pain. To avoid this, the patients develop techniques to deny, to cover or to suppress the fear. In the article questions are presented like those the ophthalmologist should be able to ask patients in the office concerning open-angle glaucoma. Tips for the therapy and management for neurotic stress are offered and some special anamnestic questions for the ophthalmologist are presented. Unsolved conflicts and denied desires as neurotic symptoms can be focused in symptoms of eye diseases. Macrotraumata and microtraumata may be reason for changes of the hormonal situation and subsequent destabilisation of the metabolism, hypertonic disease and variation of the intraocular pressure. This article gives an example of the therapeutic possibilities in somatic diseases, to discuss the psychic situation with the patient and to be able to give tips for self-help. Finally, the therapeutic procedere in patients with somatic and psychosomatic diseases is discussed and a 5-step model is presented. Georg Thieme Verlag KG Stuttgart, New York.

Proceedings of the NASA Conference on Space Telerobotics, volume 2

NASA Technical Reports Server (NTRS)

Rodriguez, Guillermo (Editor); Seraji, Homayoun (Editor)

1989-01-01

These proceedings contain papers presented at the NASA Conference on Space Telerobotics held in Pasadena, January 31 to February 2, 1989. The theme of the Conference was man-machine collaboration in space. The Conference provided a forum for researchers and engineers to exchange ideas on the research and development required for application of telerobotics technology to the space systems planned for the 1990s and beyond. The Conference: (1) provided a view of current NASA telerobotic research and development; (2) stimulated technical exchange on man-machine systems, manipulator control, machine sensing, machine intelligence, concurrent computation, and system architectures; and (3) identified important unsolved problems of current interest which can be dealt with by future research.

Towards HIV-1 remission: potential roles for broadly neutralizing antibodies.

PubMed

Halper-Stromberg, Ariel; Nussenzweig, Michel C

2016-02-01

Current antiretroviral drug therapies do not cure HIV-1 because they do not eliminate a pool of long-lived cells harboring immunologically silent but replication-competent proviruses - termed the latent reservoir. Eliminating this reservoir and stimulating the immune response to control infection in the absence of therapy remain important but unsolved goals of HIV-1 cure research. Recently discovered broadly neutralizing antibodies (bNAbs) exhibit remarkable breadth and potency in their ability to neutralize HIV-1 in vitro, and recent studies have demonstrated new therapeutic applications for passively administered bNAbs in vivo. This Review discusses the roles bNAbs might play in HIV-1 treatment regimens, including prevention, therapy, and cure.

Non-technical Issues in Design and Development of Personal Portable Devices.

PubMed

Lhotska, Lenka; Cheshire, Paul; Pharow, Peter; Macku, David

2016-01-01

Mobile technologies are constantly evolving and with the development of Internet of Things we can expect continuous increase of various applications. Mobile technologies have undeniable opportunities to play an important role in health services. Concerning purely technical aspects, almost every problem can be solved. However, there are still many unsolved and unclear issues related with ethics and governance mechanisms for mobile phone applications. These issues are even more critical in medical and health care applications of mobile technologies. This paper tries to analyse ethical, and privacy-related challenges that may occur when introducing Personal Portable Devices (PPD) to collect and record personal health data in health care and welfare environment.

[What Surgeons Need to Know About Forensic Medicine].

PubMed

Beck, N; Meyer, F

2017-02-01

Background: Forensic medicine finds more and more resonance due to requests and queries from clinicians and acts as a mediator between the individual medical disciplines, in particular with regard to legal issues, and as an interface between the fields of medicine, police and judiciary. The aim of this short narrative overview is to make surgeons aware of the forensic aspects of their work, which is usually focused on clinical and curative aspects. Crucial points: Traditionally, the basic work in forensic medicine comprises sudden and unexpected deaths, for which it is important to definitely clarify the mode of death based on the detected cause of death. In addition to violent and unnatural deaths, there are sudden natural deaths, which are natural, but also unsolved. Clinical forensic medicine basically concentrates on the examination of victims of violence, which may comprise various types of bodily harm including sexual crime, child maltreatment and traffic accidents. The investigational results (autopsy findings, injury patterns, results from the investigation of traces) need to be presented and interpreted in public procedures at court by forensic medicine specialists, who act as experts answering questions while retaining a neutral position. Conclusion: Specialists in forensic medicine should not only be consulted for issues related to the inspection of corpses and to issue a death certification. Much rather, they should also be consulted as specialised partners of surgeons and other clinicians, e.g. for the documentation of specific findings and the description of injury patterns in injured persons who are still alive. Georg Thieme Verlag KG Stuttgart · New York.

Flare Observations

NASA Astrophysics Data System (ADS)

Benz, Arnold O.

2017-12-01

Solar flares are observed at all wavelengths from decameter radio waves to gamma-rays beyond 1 GeV. This review focuses on recent observations in EUV, soft and hard X-rays, white light, and radio waves. Space missions such as RHESSI, Yohkoh, TRACE, SOHO, and more recently Hinode and SDO have enlarged widely the observational base. They have revealed a number of surprises: Coronal sources appear before the hard X-ray emission in chromospheric footpoints, major flare acceleration sites appear to be independent of coronal mass ejections, electrons, and ions may be accelerated at different sites, there are at least 3 different magnetic topologies, and basic characteristics vary from small to large flares. Recent progress also includes improved insights into the flare energy partition, on the location(s) of energy release, tests of energy release scenarios and particle acceleration. The interplay of observations with theory is important to deduce the geometry and to disentangle the various processes involved. There is increasing evidence supporting magnetic reconnection as the basic cause. While this process has become generally accepted as the trigger, it is still controversial how it converts a considerable fraction of the energy into non-thermal particles. Flare-like processes may be responsible for large-scale restructuring of the magnetic field in the corona as well as for its heating. Large flares influence interplanetary space and substantially affect the Earth's ionosphere. Flare scenarios have slowly converged over the past decades, but every new observation still reveals major unexpected results, demonstrating that solar flares, after 150 years since their discovery, remain a complex problem of astrophysics including major unsolved questions.

Does an inter-flaw length control the accuracy of rupture forecasting in geological materials?

NASA Astrophysics Data System (ADS)

Vasseur, Jérémie; Wadsworth, Fabian B.; Heap, Michael J.; Main, Ian G.; Lavallée, Yan; Dingwell, Donald B.

2017-10-01

Multi-scale failure of porous materials is an important phenomenon in nature and in material physics - from controlled laboratory tests to rockbursts, landslides, volcanic eruptions and earthquakes. A key unsolved research question is how to accurately forecast the time of system-sized catastrophic failure, based on observations of precursory events such as acoustic emissions (AE) in laboratory samples, or, on a larger scale, small earthquakes. Until now, the length scale associated with precursory events has not been well quantified, resulting in forecasting tools that are often unreliable. Here we test the hypothesis that the accuracy of the forecast failure time depends on the inter-flaw distance in the starting material. We use new experimental datasets for the deformation of porous materials to infer the critical crack length at failure from a static damage mechanics model. The style of acceleration of AE rate prior to failure, and the accuracy of forecast failure time, both depend on whether the cracks can span the inter-flaw length or not. A smooth inverse power-law acceleration of AE rate to failure, and an accurate forecast, occurs when the cracks are sufficiently long to bridge pore spaces. When this is not the case, the predicted failure time is much less accurate and failure is preceded by an exponential AE rate trend. Finally, we provide a quantitative and pragmatic correction for the systematic error in the forecast failure time, valid for structurally isotropic porous materials, which could be tested against larger-scale natural failure events, with suitable scaling for the relevant inter-flaw distances.

The role of syntax in complex networks: Local and global importance of verbs in a syntactic dependency network

NASA Astrophysics Data System (ADS)

Čech, Radek; Mačutek, Ján; Žabokrtský, Zdeněk

2011-10-01

Syntax of natural language has been the focus of linguistics for decades. The complex network theory, being one of new research tools, opens new perspectives on syntax properties of the language. Despite numerous partial achievements, some fundamental problems remain unsolved. Specifically, although statistical properties typical for complex networks can be observed in all syntactic networks, the impact of syntax itself on these properties is still unclear. The aim of the present study is to shed more light on the role of syntax in the syntactic network structure. In particular, we concentrate on the impact of the syntactic function of a verb in the sentence on the complex network structure. Verbs play the decisive role in the sentence structure (“local” importance). From this fact we hypothesize the importance of verbs in the complex network (“global” importance). The importance of verb in the complex network is assessed by the number of links which are directed from the node representing verb to other nodes in the network. Six languages (Catalan, Czech, Dutch, Hungarian, Italian, Portuguese) were used for testing the hypothesis.

Surface science in hernioplasty: The role of plasma treatments

NASA Astrophysics Data System (ADS)

Nisticò, Roberto; Magnacca, Giuliana; Martorana, Selanna

2017-10-01

The aim of this review is to clarify the importance of surface modifications induced in biomaterials for hernia-repair application. Starting from the pioneering experiences involving proto-materials as ancient prosthesis, a historical excursus between the biomaterials used in hernioplasty was realized. Subsequently, after the revolutionary discovery of stereoregular polymerization followed by the PP application in the biomedical field performed by the surgeon F. Usher, a comparative study on different hernia-repair meshes available was realized in order to better understand all the outstanding problems and possible future developments. Furthermore, since many unsolved problems on prosthetic devices implantation are linked to phenomena occurring at the interface between the biomaterials surface and the body fluids, the importance of surface science in hernioplasty was highlighted and case studies of new surface-modified generations of prosthesis presented. The results discussed in the following evidence how the surface study are becoming increasingly important for a proper knowledge of issues related to the interaction between the living matter and the artificial prostheses.

Chromatin reprogramming in breast cancer.

PubMed

Swinstead, Erin E; Paakinaho, Ville; Hager, Gordon

2018-04-24

Reprogramming of the chromatin landscape is a critical component to the transcriptional response in breast cancer. Effects of sex hormones such as estrogens and progesterone have been well described to have a critical impact on breast cancer proliferation. However, the complex network of the chromatin landscape, enhancer regions, and mode of function of steroid receptors (SRs) and other transcription factors (TFs), is an intricate web of signaling and functional processes that is still largely misunderstood at the mechanistic level. In this review, we describe what is currently known about the dynamic interplay between TFs with chromatin and the reprogramming of enhancer elements. Emphasis has been placed on characterizing the different modes of action of TFs in regulating enhancer activity, specifically, how different SRs target enhancer regions and reprogram chromatin in breast cancer cells. In addition, we discuss current techniques employed to study enhancer function at a genome-wide level. Further, we have noted recent advances in live cell imaging technology. These single cell approaches enable the coupling of population based assays with real-time studies to address many unsolved questions about SRs and chromatin dynamics in breast cancer.

Four types of ensemble coding in data visualizations.

PubMed

Szafir, Danielle Albers; Haroz, Steve; Gleicher, Michael; Franconeri, Steven

2016-01-01

Ensemble coding supports rapid extraction of visual statistics about distributed visual information. Researchers typically study this ability with the goal of drawing conclusions about how such coding extracts information from natural scenes. Here we argue that a second domain can serve as another strong inspiration for understanding ensemble coding: graphs, maps, and other visual presentations of data. Data visualizations allow observers to leverage their ability to perform visual ensemble statistics on distributions of spatial or featural visual information to estimate actual statistics on data. We survey the types of visual statistical tasks that occur within data visualizations across everyday examples, such as scatterplots, and more specialized images, such as weather maps or depictions of patterns in text. We divide these tasks into four categories: identification of sets of values, summarization across those values, segmentation of collections, and estimation of structure. We point to unanswered questions for each category and give examples of such cross-pollination in the current literature. Increased collaboration between the data visualization and perceptual psychology research communities can inspire new solutions to challenges in visualization while simultaneously exposing unsolved problems in perception research.

Failures no More: The Radical Consequences of Realistic Stellar Feedback for Dwarf Galaxies, the Milky Way, and Reionization

NASA Astrophysics Data System (ADS)

Hopkins, Philip F.

2016-06-01

Many of the most fundamental unsolved questions in star and galaxy formation revolve around star formation and "feedback" from massive stars, in-extricably linking galaxy formation and stellar evolution. I'll present simulations with un-precedented resolution of Milky-Way (MW) mass galaxies, followed cosmologically to redshift zero. For the first time, these simulations resolve the internal structure of small dwarf satellites around a MW-like host, with detailed models for stellar evolution including radiation pressure, supernovae, stellar winds, and photo-heating. I'll show that, without fine-tuning, these feedback processes naturally resolve the "missing satellites," "too big to fail," and "cusp-core" problems, and produce realistic galaxy populations. At high redshifts however, the realistic ISM structure predicted, coupled to standard stellar population models, naively leads to the prediction that only ~1-2% of ionizing photons can ever escape galaxies, insufficient to ionize the Universe. But these models assume all stars are single: if we account for binary evolution, the escape fraction increases dramatically to ~20% for the small, low-metallicity galaxies believed to ionize the Universe.

Domestic horses send signals to humans when they face with an unsolvable task.

PubMed

Ringhofer, Monamie; Yamamoto, Shinya

2017-05-01

Some domestic animals are thought to be skilled at social communication with humans due to the process of domestication. Horses, being in close relationship with humans, similar to dogs, might be skilled at communication with humans. Previous studies have indicated that they are sensitive to bodily signals and the attentional state of humans; however, there are few studies that investigate communication with humans and responses to the knowledge state of humans. Our first question was whether and how horses send signals to their potentially helpful but ignorant caretakers in a problem-solving situation where a food item was hidden in a bucket that was accessible only to the caretakers. We then examined whether horses alter their behaviours on the basis of the caretakers' knowledge of where the food was hidden. We found that horses communicated to their caretakers using visual and tactile signals. The signalling behaviour of the horses significantly increased in conditions where the caretakers had not seen the hiding of the food. These results suggest that horses alter their communicative behaviour towards humans in accordance with humans' knowledge state.

Toward characterization of Huber's ball-bearing motor

NASA Astrophysics Data System (ADS)

Choo, Joo Liang; Soong, Wen Liang; Abbott, Derek

2005-02-01

A motor that can be powered up by either a DC or AC supply and rotates in either direction, based on the so-called Huber effect, is investigated. For the first time, this paper examines the motor characteristics under both DC and AC conditions, for quantitative comparisons. Earlier work has not examined, in detail, the effect of an AC supply on the Huber motor operation. Previous work on the Huber or ball-bearing motor suffered from alignment problems and here we describe a new methodology to address this. The new construction is also a step toward a micromotor realization. The motor, with its reduced dimensions, also has the advantage of reduced operating current. Since 1959, the principle of operation of this motor has remained an unsolved mystery and various theories exist in the literature. We show various empirical findings that shed some light on the hotly contested debate. The discovery of carbon on the bearings, under AC supply conditions, reported here creates a new open question. Motor acceleration versus torque characteristics are obtained, using a data acquisition system to facilitate dynamic real-time recording.

Capping spheres with scarry crystals: Organizing principles of multi-dislocation, ground-state patterns

NASA Astrophysics Data System (ADS)

Azadi, Amir; Grason, Gregory M.

2014-03-01

Predicting the ground state ordering of curved crystals remains an unsolved, century-old challenge, beginning with the classic Thomson problem to more recent studies of particle-coated droplets. We study the structural features and underlying principles of multi-dislocation ground states of a crystalline cap adhered to a spherical substrate. In the continuum limit, vanishing lattice spacing, a --> 0 , dislocations proliferate and we show that ground states approach a characteristic sequence of patterns of n-fold radial grain boundary ``scars,'' extending from the boundary and terminating in the bulk. A combination of numerical and asymptotic analysis reveals that energetic hierarchy gives rise to a structural hierarchy, whereby the number of dislocation and scars diverge as a --> 0 while the scar length and number of dislocations per scar become remarkably independent of lattice spacing. We show the that structural hierarchy remains intact when n-fold symmetry becomes unstable to polydispersed forked-scar morphologies. We expect this analysis to resolve previously open questions about the optimal symmetries of dislocation patterns in Thomson-like problems, both with and without excess 5-fold defects.

What matters matter? P values, H values, leadership, and us.

PubMed

Granai, C O

2003-08-01

Framed by the question "What matters matter?," this essay considers today's physicians' need for leadership, the principled road they embarked on, and the reasons to continue. Taken as a whole, the vast problems of health care seem unsolvable. Approached in small tangible steps, if not cure, could direction, even inspiration, appear? When people are sick, they look to physicians. By actually caring for patients, physicians have earned trust and learned, scientifically and artfully, about life in ways others cannot. Meaningful patient-centered care occurs at the junction of logical science and tenuous human needs: "p values" and "h values." Along with the privileged understanding gained from patients comes the responsibility to stand publicly for the rights of all patients to private moments. Standing up in these ways can never be easy; then again, it never was. It is the continued journey toward historic ideals. It is an imprecise place of struggle, where caring "leadership" has always been most needed, fulfilling and truly defining physicians. Despite today's seemingly insurmountable obstacles, in this place each physician can find ways to reenergize around what matters matter.

ST5 Observations of the Imbalance of Region 1 and 2 Field-Aligned Currents and its Implication to Ionospheric Closure Currents

NASA Technical Reports Server (NTRS)

Le, G.

2008-01-01

A major unsolved question in the physics of ionosphere-magnetosphere coupling is how field-aligned currents (FACs) close. In order to maintain the divergence free condition, overall downward FACs (carried mainly by upward electrons) must eventually balance the overall upward FACs associated with the precipitating electrons through ionospheric Pedersen currents. Although much of the current closure may take place via local Pedersen currents flowing between Region 1 (R1) and Region 2 (R2) FACs, there is a generally an imbalance, i.e., more currents in R1 than in R2, in total currents between them. The net currents may be closed within R1 via cross-polar cap Pedersen currents. In this study, we use the magnetic field observations from Space Technology 5 mission to quantify the imbalance of R1 and R2 currents. We will determine the net R1-R2 currents under various solar wind conditions and discuss the implication of such imbalance to the ionospheric closure currents.

Fluoxetine and the mitochondria: A review of the toxicological aspects.

PubMed

de Oliveira, Marcos Roberto

2016-09-06

Fluoxetine (a selective serotonin reuptake inhibitor (SSRI)) is used as an antidepressant by modulating the levels of serotonin in the synaptic cleft. Nevertheless, fluoxetine also induces undesirable effects, such as anxiety, sexual dysfunction, sleep disturbances, and gastrointestinal impairments. Fluoxetine has been viewed as an agent that may interfere with cell fate by triggering apoptosis. On the other hand, fluoxetine intake has been associated with increased cancer risk. Nonetheless, data remain contradictory and no conclusions were taken. Several studies demonstrated that fluoxetine interacts with mitochondria triggering apoptosis and/or altering mitochondrial function by modulating the activity of respiratory chain components and enzymes of the Krebs cycle. Furthermore, fluoxetine affects mitochondria-related redox parameters in different experimental models. In this review, data demonstrating the effects of fluoxetine upon mammalian mitochondria are described and discussed, as well as several unsolved questions in this field of research are addressed. A separate section deals with future needs regarding the research involving the impact of fluoxetine treatment upon mitochondria and mitochondria-related signaling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aeronomy of the Venus Upper Atmosphere

NASA Astrophysics Data System (ADS)

Gérard, J.-C.; Bougher, S. W.; López-Valverde, M. A.; Pätzold, M.; Drossart, P.; Piccioni, G.

2017-11-01

We present aeronomical observations collected using remote sensing instruments on board Venus Express, complemented with ground-based observations and numerical modeling. They are mostly based on VIRTIS and SPICAV measurements of airglow obtained in the nadir mode and at the limb above 90 km. They complement our understanding of the behavior of Venus' upper atmosphere that was largely based on Pioneer Venus observations mostly performed over thirty years earlier. Following a summary of recent spectral data from the EUV to the infrared, we examine how these observations have improved our knowledge of the composition, thermal structure, dynamics and transport of the Venus upper atmosphere. We then synthesize progress in three-dimensional modeling of the upper atmosphere which is largely based on global mapping and observations of time variations of the nitric oxide and O2 nightglow emissions. Processes controlling the escape flux of atoms to space are described. Results based on the VeRA radio propagation experiment are summarized and compared to ionospheric measurements collected during earlier space missions. Finally, we point out some unsolved and open questions generated by these recent datasets and model comparisons.

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

Two-dimensional phase separated structures of block copolymers on solids

NASA Astrophysics Data System (ADS)

Sen, Mani; Jiang, Naisheng; Endoh, Maya; Koga, Tadanori; Ribbe, Alexander

The fundamental, yet unsolved question in block copolymer (BCP) thin films is the self-organization process of BCPs at the solid-polymer melt interface. We here focus on the self-organization processes of cylinder-forming polystyrene-block-poly (4-vinylpyridine) diblock copolymer and lamellar-forming poly (styrene-block-butadiene-block-styrene) triblock copolymer on Si substrates as model systems. In order to reveal the buried interfacial structures, the following experimental protocols were utilized: the BCP monolayer films were annealed under vacuum at T>Tg of the blocks (to equilibrate the melts); vitrification of the annealed BCP films via rapid quench to room temperature; subsequent intensive solvent leaching (to remove unadsorbed chains) with chloroform, a non-selective good solvent for the blocks. The strongly bound BCP layers were then characterized by using atomic force microscopy, scanning electron microscopy, grazing incidence small angle X-ray scattering, and X-ray reflectivity. The results showed that both blocks lie flat on the substrate, forming the two-dimensional, randomly phase-separated structure irrespective of their microdomain structures and interfacial energetics. Acknowledgement of financial support from NSF Grant (CMMI -1332499).

Unsolved Mysteries of Science: A Mind-Expanding Journey through a Universe of Big Bangs, Particle Waves, and Other Perplexing Concepts

NASA Astrophysics Data System (ADS)

Malone, John

2001-08-01

A LIVELY EXPLORATION OF THE BIGGEST QUESTIONS IN SCIENCE How Did the Universe Begin? The Big Bang has been the accepted theory for decades, but does it explain everything? How Did Life on Earth Get Started? What triggered the cell division that started the evolutionary chain? Did life come from outer space, buried in a chunk of rock? What is Gravity? Newton's apple just got the arguments started, Einstein made things more complicated. Just how does gravity fit in with quantum theory? What Is the Inside of the Earth Like? What exactly is happening beneath our feet, and can we learn enough to help predict earthquakes and volcanic eruptions? How Do We Learn Language? Is language acquisition an inborn biological ability, or does every child have to start from scratch? Is There a Missing Link? The story of human evolution is not complete. In addition to hoaxes such as "Piltdown Man" and extraordinary finds such as "Lucy," many puzzles remain. What, in the end, do we mean by a "missing link"?

The rising tide of ocean diseases: Unsolved problems and research priorities

USGS Publications Warehouse

Harvell, Drew; Aronson, Richard; Baron, Nancy; Connell, Joseph; Dobson, Andrew P.; Ellner, Steve; Gerber, Leah R.; Kim, Kiho; Kuris, Armand M.; McCallum, Hamish; Lafferty, Kevin D.; McKay, Bruce; Porter, James; Pascual, Mercedes; Smith, Garriett; Sutherland, Katherine; Ward, Jessica

2004-01-01

New studies have detected a rising number of reports of diseases in marine organisms such as corals, molluscs, turtles, mammals, and echinoderms over the past three decades. Despite the increasing disease load, microbiological, molecular, and theoretical tools for managing disease in the world's oceans are under-developed. Review of the new developments in the study of these diseases identifies five major unsolved problems and priorities for future research: (1) detecting origins and reservoirs for marine diseases and tracing the flow of some new pathogens from land to sea; (2) documenting the longevity and host range of infectious stages; (3) evaluating the effect of greater taxonomic diversity of marine relative to terrestrial hosts and pathogens; (4) pinpointing the facilitating role of anthropogenic agents as incubators and conveyors of marine pathogens; (5) adapting epidemiological models to analysis of marine disease.

The riddle of Tasmanian languages

PubMed Central

Bowern, Claire

2012-01-01

Recent work which combines methods from linguistics and evolutionary biology has been fruitful in discovering the history of major language families because of similarities in evolutionary processes. Such work opens up new possibilities for language research on previously unsolvable problems, especially in areas where information from other sources may be lacking. I use phylogenetic methods to investigate Tasmanian languages. Existing materials are so fragmentary that scholars have been unable to discover how many languages are represented in the sources. Using a clustering algorithm which identifies admixture, source materials representing more than one language are identified. Using the Neighbor-Net algorithm, 12 languages are identified in five clusters. Bayesian phylogenetic methods reveal that the families are not demonstrably related; an important result, given the importance of Tasmanian Aborigines for information about how societies have responded to population collapse in prehistory. This work provides insight into the societies of prehistoric Tasmania and illustrates a new utility of phylogenetics in reconstructing linguistic history. PMID:23015621

Information flow in the pharmaceutical supply chain

PubMed Central

Yousefi, Nazila; Alibabaei, Ahmad

2015-01-01

Managing the supply chain plays an important role in creating competitive advantages for companies. Adequate information flow in supply chain is one of the most important issues in SCM. Therefore, using certain Information Systems can have a significant role in managing and integrating data and information within the supply chain. Pharmaceutical supply chain is more complex than many other supply chains, in the sense that it can affect social and political perspectives. On the other hand, managing the pharmaceutical supply chain is difficult because of its complexity and also government regulations in this field. Although, Iran has progressed a lot in pharmaceutical manufacturing, still there are many unsolved issues in managing the information flow in the pharmaceutical supply chain. In this study, we reviewed the benefits of using different levels of an integrated information system in the supply chain and the possible challenges ahead. PMID:26664401

Computational complexity in entanglement transformations

NASA Astrophysics Data System (ADS)

Chitambar, Eric A.

In physics, systems having three parts are typically much more difficult to analyze than those having just two. Even in classical mechanics, predicting the motion of three interacting celestial bodies remains an insurmountable challenge while the analogous two-body problem has an elementary solution. It is as if just by adding a third party, a fundamental change occurs in the structure of the problem that renders it unsolvable. In this thesis, we demonstrate how such an effect is likewise present in the theory of quantum entanglement. In fact, the complexity differences between two-party and three-party entanglement become quite conspicuous when comparing the difficulty in deciding what state changes are possible for these systems when no additional entanglement is consumed in the transformation process. We examine this entanglement transformation question and its variants in the language of computational complexity theory, a powerful subject that formalizes the concept of problem difficulty. Since deciding feasibility of a specified bipartite transformation is relatively easy, this task belongs to the complexity class P. On the other hand, for tripartite systems, we find the problem to be NP-Hard, meaning that its solution is at least as hard as the solution to some of the most difficult problems humans have encountered. One can then rigorously defend the assertion that a fundamental complexity difference exists between bipartite and tripartite entanglement since unlike the former, the full range of forms realizable by the latter is incalculable (assuming P≠NP). However, similar to the three-body celestial problem, when one examines a special subclass of the problem---invertible transformations on systems having at least one qubit subsystem---we prove that the problem can be solved efficiently. As a hybrid of the two questions, we find that the question of tripartite to bipartite transformations can be solved by an efficient randomized algorithm. Our results are obtained by encoding well-studied computational problems such as polynomial identity testing and tensor rank into questions of entanglement transformation. In this way, entanglement theory provides a physical manifestation of some of the most puzzling and abstract classical computation questions.

The Propagation of Cosmic Rays from the Galactic Wind Termination Shock: Back to the Galaxy?

NASA Astrophysics Data System (ADS)

Merten, Lukas; Bustard, Chad; Zweibel, Ellen G.; Becker Tjus, Julia

2018-05-01

Although several theories exist for the origin of cosmic rays (CRs) in the region between the spectral “knee” and “ankle,” this problem is still unsolved. A variety of observations suggest that the transition from Galactic to extragalactic sources occurs in this energy range. In this work, we examine whether a Galactic wind that eventually forms a termination shock far outside the Galactic plane can contribute as a possible source to the observed flux in the region of interest. Previous work by Bustard et al. estimated that particles can be accelerated to energies above the “knee” up to R max = 1016 eV for parameters drawn from a model of a Milky Way wind. A remaining question is whether the accelerated CRs can propagate back into the Galaxy. To answer this crucial question, we simulate the propagation of the CRs using the low-energy extension of the CRPropa framework, based on the solution of the transport equation via stochastic differential equations. The setup includes all relevant processes, including three-dimensional anisotropic spatial diffusion, advection, and corresponding adiabatic cooling. We find that, assuming realistic parameters for the shock evolution, a possible Galactic termination shock can contribute significantly to the energy budget in the “knee” region and above. We estimate the resulting produced neutrino fluxes and find them to be below measurements from IceCube and limits by KM3NeT.

Rigorous RG Algorithms and Area Laws for Low Energy Eigenstates in 1D

NASA Astrophysics Data System (ADS)

Arad, Itai; Landau, Zeph; Vazirani, Umesh; Vidick, Thomas

2017-11-01

One of the central challenges in the study of quantum many-body systems is the complexity of simulating them on a classical computer. A recent advance (Landau et al. in Nat Phys, 2015) gave a polynomial time algorithm to compute a succinct classical description for unique ground states of gapped 1D quantum systems. Despite this progress many questions remained unsolved, including whether there exist efficient algorithms when the ground space is degenerate (and of polynomial dimension in the system size), or for the polynomially many lowest energy states, or even whether such states admit succinct classical descriptions or area laws. In this paper we give a new algorithm, based on a rigorously justified RG type transformation, for finding low energy states for 1D Hamiltonians acting on a chain of n particles. In the process we resolve some of the aforementioned open questions, including giving a polynomial time algorithm for poly( n) degenerate ground spaces and an n O(log n) algorithm for the poly( n) lowest energy states (under a mild density condition). For these classes of systems the existence of a succinct classical description and area laws were not rigorously proved before this work. The algorithms are natural and efficient, and for the case of finding unique ground states for frustration-free Hamiltonians the running time is {\\tilde{O}(nM(n))} , where M( n) is the time required to multiply two n × n matrices.

The evolution of tumour phylogenetics: principles and practice

PubMed Central

Schwartz, Russell; Schäffer, Alejandro A.

2018-01-01

Rapid advances in high-throughput sequencing and a growing realization of the importance of evolutionary theory to cancer genomics have led to a proliferation of phylogenetic studies of tumour progression. These studies have yielded not only new insights but also a plethora of experimental approaches, sometimes reaching conflicting or poorly supported conclusions. Here, we consider this body of work in light of the key computational principles underpinning phylogenetic inference, with the goal of providing practical guidance on the design and analysis of scientifically rigorous tumour phylogeny studies. We survey the range of methods and tools available to the researcher, their key applications, and the various unsolved problems, closing with a perspective on the prospects and broader implications of this field. PMID:28190876

Qualitative content analysis in nursing research: concepts, procedures and measures to achieve trustworthiness.

PubMed

Graneheim, U H; Lundman, B

2004-02-01

Qualitative content analysis as described in published literature shows conflicting opinions and unsolved issues regarding meaning and use of concepts, procedures and interpretation. This paper provides an overview of important concepts (manifest and latent content, unit of analysis, meaning unit, condensation, abstraction, content area, code, category and theme) related to qualitative content analysis; illustrates the use of concepts related to the research procedure; and proposes measures to achieve trustworthiness (credibility, dependability and transferability) throughout the steps of the research procedure. Interpretation in qualitative content analysis is discussed in light of Watzlawick et al.'s [Pragmatics of Human Communication. A Study of Interactional Patterns, Pathologies and Paradoxes. W.W. Norton & Company, New York, London] theory of communication.

Dehydration Polymerization for Poly(hetero)arene Conjugated Polymers.

PubMed

Mirabal, Rafael A; Vanderzwet, Luke; Abuadas, Sara; Emmett, Michael R; Schipper, Derek

2018-02-18

The lack of scalable and sustainable methods to prepare conjugated polymers belies their importance in many enabling technologies. Accessing high-performance poly(hetero)arene conjugated polymers by dehydration has remained an unsolved problem in synthetic chemistry and has historically required transitional-metal coupling reactions. Herein, we report a dehydration method that allows access to conjugated heterocyclic materials. By using the technique, we have prepared a series of small molecules and polymers. The reaction avoids using transition metals, proceeds at room temperature, the only required reactant is a simple base and water is the sole by-product. The dehydration reaction is technically simple and provides a sustainable and straightforward method to prepare conjugated heteroarene motifs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The evolution of tumour phylogenetics: principles and practice.

PubMed

Schwartz, Russell; Schäffer, Alejandro A

2017-04-01

Rapid advances in high-throughput sequencing and a growing realization of the importance of evolutionary theory to cancer genomics have led to a proliferation of phylogenetic studies of tumour progression. These studies have yielded not only new insights but also a plethora of experimental approaches, sometimes reaching conflicting or poorly supported conclusions. Here, we consider this body of work in light of the key computational principles underpinning phylogenetic inference, with the goal of providing practical guidance on the design and analysis of scientifically rigorous tumour phylogeny studies. We survey the range of methods and tools available to the researcher, their key applications, and the various unsolved problems, closing with a perspective on the prospects and broader implications of this field.

Geoscience and a Lunar Base: A Comprehensive Plan for Lunar Exploration

NASA Technical Reports Server (NTRS)

Taylor, G. Jeffrey (Editor); Spudis, Paul D. (Editor)

1990-01-01

This document represents the proceedings of the Workshop on Geoscience from a Lunar Base. It describes a comprehensive plan for the geologic exploration of the Moon. The document begins by explaining the scientific importance of studying the Moon and outlines the many unsolved problems in lunar science. Subsequent chapters detail different, complementary approaches to geologic studies: global surveys, including orbiting spacecraft such as Lunar Observer and installation of a global geophysical network; reconnaissance sample return mission, by either automated rovers or landers, or by piloted forays; detailed field studies, which involve astronauts and teleoperated robotic field geologists. The document then develops a flexible scenario for exploration and sketches the technological developments needed to carry out the exploration scenario.

Rhodium(II) metallopeptide catalyst design enables fine control in selective functionalization of natural SH3 domains.

PubMed

Vohidov, Farrukh; Coughlin, Jane M; Ball, Zachary T

2015-04-07

Chemically modified proteins are increasingly important for use in fundamental biophysical studies, chemical biology, therapeutic protein development, and biomaterials. However, chemical methods typically produce heterogeneous labeling and cannot approach the exquisite selectivity of enzymatic reactions. While bioengineered methods are sometimes an option, selective reactions of natural proteins remain an unsolved problem. Here we show that rhodium(II) metallopeptides combine molecular recognition with promiscuous catalytic activity to allow covalent decoration of natural SH3 domains, depending on choice of catalyst but independent of the specific residue present. A metallopeptide catalyst succeeds in modifying a single SH3-containing kinase at endogenous concentrations in prostate cancer (PC-3) cell lysate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Shapes of the Future

ERIC Educational Resources Information Center

Klee, Victor

1971-01-01

This article presents some easily stated but unsolved geometric problems. The three sections are entitled: Housemoving, Manholes and Fermi Surfaces" (convex figures of constant width), Angels, Pollen Grains and Misanthropes" (packing problems), and The Four-Color Conjecture and Organic Chemistry." (MM)

Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules.

PubMed

Langer, Dominik; Wicher, Barbara; Szczołko, Wojciech; Gdaniec, Maria; Tykarska, Ewa

2016-08-01

The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds.

Juvenile onset depression alters cardiac autonomic balance in response to psychological and physical challenges

PubMed Central

Bylsma, Lauren M.; Yaroslavsky, Ilya; Rottenberg, Jonathan; Jennings, J. Richard; George, Charles J.; Kiss, Enikő; Kapornai, Krisztina; Halas, Kitti; Dochnal, Roberta; Lefkovics, Eszter; Benák, István; Baji, Ildikó; Vetró, Ágnes; Kovacs, Maria

2015-01-01

Cardiac autonomic balance (CAB) indexes the ratio of parasympathetic to sympathetic activation (Berntson, Norman, Hawkley, & Cacioppo, 2008), and is believed to reflect overall autonomic flexibility in the face of environmental challenges. However, CAB has not been examined in depression. We examined changes in CAB and other physiological variables in 179 youth with a history of juvenile onset depression (JOD) and 161 healthy controls, in response to two psychological (unsolvable puzzle, sad film) and two physical (handgrip, and forehead cold pressor) challenges. In repeated measures analyses, controls showed expected reductions in CAB for both the handgrip and unsolvable puzzle, reflecting a shift to sympathetic relative to parasympathetic activation. By contrast, JOD youth showed increased CAB from baseline for both tasks (ps<.05). No effects were found for the forehead cold pressor or sad film tasks, suggesting that CAB differences may arise under conditions requiring greater attentional control or sustained effort. PMID:26225465

Attributional processes in the learned helplessness paradigm: behavioral effects of global attributions.

PubMed

Mikulincer, M

1986-12-01

Following the learned helplessness paradigm, I assessed in this study the effects of global and specific attributions for failure on the generalization of performance deficits in a dissimilar situation. Helplessness training consisted of experience with noncontingent failures on four cognitive discrimination problems attributed to either global or specific causes. Experiment 1 found that performance in a dissimilar situation was impaired following exposure to globally attributed failure. Experiment 2 examined the behavioral effects of the interaction between stable and global attributions of failure. Exposure to unsolvable problems resulted in reduced performance in a dissimilar situation only when failure was attributed to global and stable causes. Finally, Experiment 3 found that learned helplessness deficits were a product of the interaction of global and internal attribution. Performance deficits following unsolvable problems were recorded when failure was attributed to global and internal causes. Results were discussed in terms of the reformulated learned helplessness model.

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M. tuberculosis? 2. How does M. tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M. tuberculosis? 4. What is the mechanism of "endogenous reactivation" of dormant M. tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-alpha. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.

Biochemical activity and multiple locations of particulate guanylate cyclase in Rhyacophila dorsalis acutidens (Insecta: Trichoptera) provide insights into the cGMP signalling pathway in Malpighian tubules.

PubMed

Secca, T; Sciaccaluga, M; Marra, A; Barberini, L; Bicchierai, M C

2011-04-01

In insect renal physiology, cGMP and cAMP have important regulatory roles. In Drosophila melanogaster, considered a good model for molecular physiology studies, and in other insects, cGMP and cAMP act as signalling molecules in the Malpighian tubules (MTs). However, many questions related to cyclic nucleotide functions are unsolved in principal cells (PC) and stellate cells (SC), the two cell types that compose the MT. In PC, despite the large body of information available on soluble guanylate cyclase (sGC) in the cGMP pathway, the functional circuit of particulate guanylate cyclase (pGC) remains obscure. In SC, on the other side, the synthesis and physiological role of the cGMP are still unknown. Our biochemical data regarding the presence of cyclic nucleotides in the MTs of Rhyacophila dorsalis acutidens revealed a cGMP level above the 50%, in comparison with the cAMP. The specific activity values for the membrane-bound guanylate cyclase were also recorded, implying that, besides the sGC, pGC is a physiologically relevant source of cGMP in MTs. Cytochemical studies showed ultrastructurally that there was a great deal of pGC on the basolateral membranes of both the principal and stellate cells. In addition, pGC was also detected in the contact zone between the two cell types and in the apical microvillar region of the stellate cells bordering the tubule lumen. The pGC signal is so well represented in PC and, unexpectedly in SC of MTs, that it is possible to hypothesize the existence of still uncharacterized physiological processes regulated by the pGC-cGMP system. Copyright © 2011 Elsevier Ltd. All rights reserved.

To Model Chemical Reactivity in Heterogeneous Emulsions, Think Homogeneous Microemulsions.

PubMed

Bravo-Díaz, Carlos; Romsted, Laurence Stuart; Liu, Changyao; Losada-Barreiro, Sonia; Pastoriza-Gallego, Maria José; Gao, Xiang; Gu, Qing; Krishnan, Gunaseelan; Sánchez-Paz, Verónica; Zhang, Yongliang; Dar, Aijaz Ahmad

2015-08-25

Two important and unsolved problems in the food industry and also fundamental questions in colloid chemistry are how to measure molecular distributions, especially antioxidants (AOs), and how to model chemical reactivity, including AO efficiency in opaque emulsions. The key to understanding reactivity in organized surfactant media is that reaction mechanisms are consistent with a discrete structures-separate continuous regions duality. Aggregate structures in emulsions are determined by highly cooperative but weak organizing forces that allow reactants to diffuse at rates approaching their diffusion-controlled limit. Reactant distributions for slow thermal bimolecular reactions are in dynamic equilibrium, and their distributions are proportional to their relative solubilities in the oil, interfacial, and aqueous regions. Our chemical kinetic method is grounded in thermodynamics and combines a pseudophase model with methods for monitoring the reactions of AOs with a hydrophobic arenediazonium ion probe in opaque emulsions. We introduce (a) the logic and basic assumptions of the pseudophase model used to define the distributions of AOs among the oil, interfacial, and aqueous regions in microemulsions and emulsions and (b) the dye derivatization and linear sweep voltammetry methods for monitoring the rates of reaction in opaque emulsions. Our results show that this approach provides a unique, versatile, and robust method for obtaining quantitative estimates of AO partition coefficients or partition constants and distributions and interfacial rate constants in emulsions. The examples provided illustrate the effects of various emulsion properties on AO distributions such as oil hydrophobicity, emulsifier structure and HLB, temperature, droplet size, surfactant charge, and acidity on reactant distributions. Finally, we show that the chemical kinetic method provides a natural explanation for the cut-off effect, a maximum followed by a sharp reduction in AO efficiency with increasing alkyl chain length of a particular AO. We conclude with perspectives and prospects.

Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Nonsynonymous Variant at SLC39A8 in Europeans.

PubMed

Li, Ming; Wu, Dong-Dong; Yao, Yong-Gang; Huo, Yong-Xia; Liu, Jie-Wei; Su, Bing; Chasman, Daniel I; Chu, Audrey Y; Huang, Tao; Qi, Lu; Zheng, Yan; Luo, Xiong-Jian

2016-01-01

Natural selection has played important roles in optimizing complex human adaptations. However, schizophrenia poses an evolutionary paradox during human evolution, as the illness has strongly negative effects on fitness, but persists with a prevalence of ~0.5% across global populations. Recent studies have identified numerous risk variations in diverse populations, which might be able to explain the stable and high rate of schizophrenia morbidity in different cultures and regions, but the questions about why the risk alleles derived and maintained in human gene pool still remain unsolved. Here, we studied the evolutionary pattern of a schizophrenia risk variant rs13107325 (P < 5.0 × 10(-8) in Europeans) in the SLC39A8 gene. We found the SNP is monomorphic in Asians and Africans with risk (derived) T-allele totally absent, and further evolutionary analyses showed the T-allele has experienced recent positive selection in Europeans. Subsequent exploratory analyses implicated that the colder environment in Europe was the likely selective pressures, ie, when modern humans migrated "out of Africa" and moved to Europe mainland (a colder and cooler continent than Africa), new alleles derived due to positive selection and protected humans from risk of hypertension and also helped them adapt to the cold environment. The hypothesis was supported by our pleiotropic analyses with hypertension and energy intake as well as obesity in Europeans. Our data thus provides an intriguing example to illustrate a possible mechanism for maintaining schizophrenia risk alleles in the human gene pool, and further supported that schizophrenia is likely a product caused by pleiotropic effect during human evolution. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Police close unsolved 'climategate' investigation

NASA Astrophysics Data System (ADS)

Lavender, Gemma

2012-09-01

Police in Norfolk in the UK have closed an investigation into the hacking of e-mails at the University of East Anglia's Climate Research Unit (CRU) after admitting that they will not be able to find the hackers who broke into CRU computer servers.

Management of functional dyspepsia: Unsolved problems and new perspectives.

PubMed

Madisch, Ahmed; Miehlke, Stephan; Labenz, Joachim

2005-11-14

The common characteristic criteria of all functional gastrointestinal (GI) disorders are the persistence and recurrence of variable gastrointestinal symptoms that cannot be explained by any structural or biochemical abnormalities. Functional dyspepsia (FD) represents one of the important GI disorders in Western countries because of its remarkably high prevalence in general population and its impact on quality of life. Due to its dependence on both subjective determinants and diverse country-specific circumstances, the definition and management strategies of FD are still variably stated. Clinical trials with several drug classes (e.g., proton pump inhibitors, H2-blockers, prokinetic drugs) have been performed frequently without validated disease-specific test instruments for the outcome measurements. Therefore, the interpretation of such trials remains difficult and controversial with respect to comparability and evaluation of drug efficacy, and definite conclusions can be drawn neither for diagnostic management nor for efficacious drug therapy so far. In view of these unsolved problems, guidelines both on the clinical management of FD and on the performance of clinical trials are needed. In recent years, increasing research work has been done in this area. Clinical trials conducted in adequately diagnosed patients that provided validated outcome measurements may result in better insights leading to more effective treatment strategies. Encouraging perspectives have been recently performed by methodologically well-designed treatment studies with herbal drug preparations. Herbal drugs, given their proven efficacy in clinical trials, offer a safe therapeutic alternative in the treatment of FD which is often favored by both patients and physicians. A fixed combination of peppermint oil and caraway oil in patients suffering from FD could be proven effective by well-designed clinical trials.

Toddler’s Self-Regulation Strategies in a Challenge Context are Nap-Dependent

PubMed Central

Miller, Alison L.; Seifer, Ronald; Crossin, Rebecca; LeBourgeois, Monique K.

2015-01-01

SUMMARY Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one’s behavior, attention, and emotion when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers’ self-regulation. Healthy children (n=12; 4 males; 30–36 months (33.9±1.7) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a Nap and a No-Nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the No-Nap versus the Nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in skepticism (d=0.77; 7% change), negative self-appraisal (d=0.92; 5% change), and increases in physical self-soothing (d=0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d=0.50; 9% change), and insistence on completing the unsolvable puzzle (d=0.91; 10% change). Results suggest sleep serves an important role in the way toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to effectively engage in a difficult task and reverted to less mature self-regulation strategies, than when they were well-rested. Over time, chronically missed sleep may impair young children’s self-regulation abilities, resulting in risk for social-emotional, behavioral, and school problems. PMID:25394169

Toddler's self-regulation strategies in a challenge context are nap-dependent.

PubMed

Miller, Alison L; Seifer, Ronald; Crossin, Rebecca; Lebourgeois, Monique K

2015-06-01

Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers' self-regulation. Healthy children (n = 12; four males; aged 30-36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no-nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the no-nap versus the nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self-appraisal (d = 0.92; 5% change) and increases in physical self-soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self-regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self-regulation abilities, resulting in risk for social-emotional, behavioural and school problems. © 2014 European Sleep Research Society.

Biomedical engineering strategies in system design space.

PubMed

Savageau, Michael A

2011-04-01

Modern systems biology and synthetic bioengineering face two major challenges in relating properties of the genetic components of a natural or engineered system to its integrated behavior. The first is the fundamental unsolved problem of relating the digital representation of the genotype to the analog representation of the parameters for the molecular components. For example, knowing the DNA sequence does not allow one to determine the kinetic parameters of an enzyme. The second is the fundamental unsolved problem of relating the parameters of the components and the environment to the phenotype of the global system. For example, knowing the parameters does not tell one how many qualitatively distinct phenotypes are in the organism's repertoire or the relative fitness of the phenotypes in different environments. These also are challenges for biomedical engineers as they attempt to develop therapeutic strategies to treat pathology or to redirect normal cellular functions for biotechnological purposes. In this article, the second of these fundamental challenges will be addressed, and the notion of a "system design space" for relating the parameter space of components to the phenotype space of bioengineering systems will be focused upon. First, the concept of a system design space will be motivated by introducing one of its key components from an intuitive perspective. Second, a simple linear example will be used to illustrate a generic method for constructing the design space in which qualitatively distinct phenotypes can be identified and counted, their fitness analyzed and compared, and their tolerance to change measured. Third, two examples of nonlinear systems from different areas of biomedical engineering will be presented. Finally, after giving reference to a few other applications that have made use of the system design space approach to reveal important design principles, some concluding remarks concerning challenges and opportunities for further development will be made.

Intranasal oxytocin and a polymorphism in the oxytocin receptor gene are associated with human-directed social behavior in golden retriever dogs.

PubMed

Persson, Mia E; Trottier, Agaia J; Bélteky, Johan; Roth, Lina S V; Jensen, Per

2017-09-01

The oxytocin system may play an important role in dog domestication from the wolf. Dogs have evolved unique human analogue social skills enabling them to communicate and cooperate efficiently with people. Genomic differences in the region surrounding the oxytocin receptor (OXTR) gene have previously been associated with variation in dogs' communicative skills. Here we have utilized the unsolvable problem paradigm to investigate the effects of oxytocin and OXTR polymorphisms on human-directed contact seeking behavior in 60 golden retriever dogs. Human-oriented behavior was quantified employing a previously defined unsolvable problem paradigm. Behaviors were tested twice in a repeated, counterbalanced design, where dogs received a nasal dose of either oxytocin or saline 45min before each test occasion. Buccal DNA was analysed for genotype on three previously identified SNP-markers associated with OXTR. The same polymorphisms were also genotyped in 21 wolf blood samples to explore potential genomic differences between the species. Results showed that oxytocin treatment decreased physical contact seeking with the experimenter and one of the three polymorphisms was associated with degree of physical contact seeking with the owner. Dogs with the AA-genotype at this locus increased owner physical contact seeking in response to oxytocin while the opposite effect was found in GG-genotype individuals. Hence, intranasal oxytocin treatment, an OXTR polymorphism and their interaction are associated with dogs' human-directed social skills, which can explain previously described breed differences in oxytocin response. Genotypic variation at the studied locus was also found in wolves indicating that it was present even at the start of dog domestication. Copyright © 2017 Elsevier Inc. All rights reserved.

Mass transfer of large molecules through collagen and collagen-silica hybrid membranes

NASA Astrophysics Data System (ADS)

Jofre-Lora, Pedro

Diabetes is a growing concern in the United States and around the world that must be addressed through new treatment options. Current standard treatment options of diabetes are limiting and have tremendous impacts on patient's lives. Emerging therapies, such as the implantation of encapsulated islets, are promising treatment options, but have not yet materialized due to unsolved problems with material properties. Hybrid silica-collagen membranes address some of these unsolved problems and are a promising material for cell encapsulation. However, the mass transfer properties of large molecules, such as insulin, TNF-alpha, IL1beta, and other important proteins in the etiology of diabetes, through these hybrid membranes are poorly characterized. In order to begin characterizing these properties, a device was constructed to accurately and efficiently measure the mass transfer of other similar large molecules, fluorescein isothiocyanate dextrans (FITC-dextran), through collagen-silica hybrid membranes. The device was used to measure diffusion coefficients of 4, 20, 40, and 150 kDa FITC-dextrans through non-silicified and silicified samples of 200 and 1000 Pa porcine skin collagen. Diffusion coefficients were found to be in the 10-7-10-6 cm2s -1 range, which is in agreement with previously published data for similar molecules through similar hydrogels. The effects of collagen stiffness, FITC-dextran molecular weight, and silicification treatment on diffusion were investigated. It was found that collagen stiffness and FITC-dextran molecular weight had a negative correlation with diffusion, whereas silicification treatment had no global impact on diffusion. The device created, and the results of this preliminary investigation, can be used to develop collagen-silica hybrid membranes as an alternative material for cell encapsulation in a forward-design manner.

Coronary artery disease in women: an unsolved dilemma.

PubMed

Aziz, Fahad

2014-04-01

Cardiovascular disease (CVD) is the leading cause of death in women, as well as an important cause of disability, although many women and their physicians underestimate the risk. The pathogenesis, presentation and diagnosis of CVDs are different in women than men, which make the women prone to under-treatment for these diseases. More gender-based research regarding the management of coronary artery disease (CAD) in women needs to be done. Exercise, hypertension treatment, smoking cessation and aspirin therapy are effective measures for the primary prevention of CAD in women. The roles of hormone replacement therapy in primary prevention are not well established. Hormone replacement therapy has not been effective in lowering the risk of recurrent myocardial infarction. Cardiologists and family physicians should emphasize the use of proven treatments, with particular attention given to underserved populations.

Enhanced, targeted sampling of high-dimensional free-energy landscapes using variationally enhanced sampling, with an application to chignolin

PubMed Central

Shaffer, Patrick; Valsson, Omar; Parrinello, Michele

2016-01-01

The capabilities of molecular simulations have been greatly extended by a number of widely used enhanced sampling methods that facilitate escaping from metastable states and crossing large barriers. Despite these developments there are still many problems which remain out of reach for these methods which has led to a vigorous effort in this area. One of the most important problems that remains unsolved is sampling high-dimensional free-energy landscapes and systems that are not easily described by a small number of collective variables. In this work we demonstrate a new way to compute free-energy landscapes of high dimensionality based on the previously introduced variationally enhanced sampling, and we apply it to the miniprotein chignolin. PMID:26787868

Multi-dimensional simulations of core-collapse supernova explosions with CHIMERA

NASA Astrophysics Data System (ADS)

Messer, O. E. B.; Harris, J. A.; Hix, W. R.; Lentz, E. J.; Bruenn, S. W.; Mezzacappa, A.

2018-04-01

Unraveling the core-collapse supernova (CCSN) mechanism is a problem that remains essentially unsolved despite more than four decades of effort. Spherically symmetric models with otherwise high physical fidelity generally fail to produce explosions, and it is widely accepted that CCSNe are inherently multi-dimensional. Progress in realistic modeling has occurred recently through the availability of petascale platforms and the increasing sophistication of supernova codes. We will discuss our most recent work on understanding neutrino-driven CCSN explosions employing multi-dimensional neutrino-radiation hydrodynamics simulations with the Chimera code. We discuss the inputs and resulting outputs from these simulations, the role of neutrino radiation transport, and the importance of multi-dimensional fluid flows in shaping the explosions. We also highlight the production of 48Ca in long-running Chimera simulations.

The moon illusion: II. A reference theory.

PubMed

Baird, J C

1982-09-01

The present theory provides explanations for the moon illusion and related issues involving size and distance perception in natural, outdoor settings. Although some assumptions of previous theories are rejected, other pivotal aspects are retained in this formulation. In particular, the present theory states that both the sky and ground are important referents in judging the spatial extent of the moon. Neither factor alone can account for all the available data, but quantitative models incorporating both factors do quite well when applied to the parametric findings of Holway and Boring, as well as to the results obtained by Kaufman and Rock. The reference theory and its associated class of specific models suggest new theoretical directions and experimental tests to narrow yet further the selection of appropriate explanations for one of visual perception's oldest unsolved puzzles.

Proceedings of the Workshop on Space Telerobotics, volume 1

NASA Technical Reports Server (NTRS)

Rodriguez, G. (Editor)

1987-01-01

These proceedings report the results of a workshop on space telerobotics, which was held at the Jet Propulsion Laboratory, January 20-22, 1987. Sponsored by the NASA Office of Aeronautics and Space Technology (OAST), the Workshop reflected NASA's interest in developing new telerobotics technology for automating the space systems planned for the 1990s and beyond. The workshop provided a window into NASA telerobotics research, allowing leading researchers in telerobotics to exchange ideas on manipulation, control, system architectures, artificial intelligence, and machine sensing. One of the objectives was to identify important unsolved problems of current interest. The workshop consisted of surveys, tutorials, and contributed papers of both theoretical and practical interest. Several sessions were held on the themes of sensing and perception, control execution, operator interface, planning and reasoning, and system architecture.

Language, Migrants, and Power.

ERIC Educational Resources Information Center

Davis, D. F.

After three decades of diverse and intense immigration accompanied by a range of well intentioned initiatives by the Australian government to meet the needs of immigrants, there remain unsolved problems. An Australian Institute of Multicultural Affairs evaluation (1982) found major achievements in establishing intensive programs of English…

Russian Military Reform: Problems and Challenges

DTIC Science & Technology

2010-03-25

RUSSIAN MILITARY REFORM : PROBLEMS AND CHALLENGES BY LIEUTENANT COLONEL ZURAB AGLADZE Georgian Army...USAWC STRATEGIC REASERCH PROJECT RUSSIAN MILITARY REFORM : PROBLEMS AND CHALLENGES by Lieutenant Colonel...noncommissioned officers still continue to be unsolved. Despite some successes, Russian military reform still faces many challenges that will

Unravelling the Complexity of Teams via a Thermodynamics Perspective

DTIC Science & Technology

2014-10-01

potentially irrational behaviors. Multitasking (MT) is an unsolved but key theoretical problem for organizing teams, organizations and systems...While individuals multitask (MT) poorly (Wickens, 1992), multitasking is the function of groups as they pool skills to accomplish goals they are unable

The Nightingale murder.

PubMed

Trueland, Jennifer

Queen's Nursing Institute director Rosemary Cook has published a book on the unsolved murder of Florence Nightingale Shore, an eminent early 20th century nurse and god-daughter of her famous namesake. Ms Shore's remarkable nursing career provides an insight into the profession during the Victorian/Edwardian era.

UNSOLVED PROBLEMS WITH CORROSION AND DISTRIBUTION SYSTEM INORGANICS

EPA Science Inventory

This presentation provides an overview of new research results and remaining research needs with respect to both corrosion control issues (lead, copper, iron) and to issues of inorganic contaminants that can form or accumulate in distribution system water, pipe scales and distrib...

Positron emission tomography and gene therapy: basic concepts and experimental approaches for in vivo gene expression imaging.

PubMed

Peñuelas, Iván; Boán, JoséF; Martí-Climent, Josep M; Sangro, Bruno; Mazzolini, Guillermo; Prieto, Jesús; Richter, José A

2004-01-01

More than two decades of intense research have allowed gene therapy to move from the laboratory to the clinical setting, where its use for the treatment of human pathologies has been considerably increased in the last years. However, many crucial questions remain to be solved in this challenging field. In vivo imaging with positron emission tomography (PET) by combination of the appropriate PET reporter gene and PET reporter probe could provide invaluable qualitative and quantitative information to answer multiple unsolved questions about gene therapy. PET imaging could be used to define parameters not available by other techniques that are of substantial interest not only for the proper understanding of the gene therapy process, but also for its future development and clinical application in humans. This review focuses on the molecular biology basis of gene therapy and molecular imaging, describing the fundamentals of in vivo gene expression imaging by PET, and the application of PET to gene therapy, as a technology that can be used in many different ways. It could be applied to avoid invasive procedures for gene therapy monitoring; accurately diagnose the pathology for better planning of the most adequate therapeutic approach; as treatment evaluation to image the functional effects of gene therapy at the biochemical level; as a quantitative noninvasive way to monitor the location, magnitude and persistence of gene expression over time; and would also help to a better understanding of vector biology and pharmacology devoted to the development of safer and more efficient vectors.

An Unsolved Mystery: The Target-Recognizing RNA Species of MicroRNA Genes

PubMed Central

Chen, Chang-Zheng

2013-01-01

MicroRNAs (miRNAs) are an abundant class of endogenous ~ 21-nucleotide (nt) RNAs. These small RNAs are produced from long primary miRNA transcripts — pri-miRNAs — through sequential endonucleolytic maturation steps that yield precursor miRNA (pre-miRNA) intermediates and then the mature miRNAs. The mature miRNAs are loaded into the RNA-induced silencing complexes (RISC), and guide RISC to target mRNAs for cleavage and/or translational repression. This paradigm, which represents one of major discoveries of modern molecular biology, is built on the assumption that mature miRNAs are the only species produced from miRNA genes that recognize targets. This assumption has guided the miRNA field for more than a decade and has led to our current understanding of the mechanisms of target recognition and repression by miRNAs. Although progress has been made, fundamental questions remain unanswered with regard to the principles of target recognition and mechanisms of repression. Here I raise questions about the assumption that mature miRNAs are the only target-recognizing species produced from miRNA genes and discuss the consequences of working under an incomplete or incorrect assumption. Moreover, I present evolution-based and experimental evidence that support the roles of pri-/pre-miRNAs in target recognition and repression. Finally, I propose a conceptual framework that integrates the functions of pri-/pre-miRNAs and mature miRNAs in target recognition and repression. The integrated framework opens experimental enquiry and permits interpretation of fundamental problems that have so far been precluded. PMID:23685275

Multi-species coexistence in Lotka-Volterra competitive systems with crowding effects.

PubMed

Gavina, Maica Krizna A; Tahara, Takeru; Tainaka, Kei-Ichi; Ito, Hiromu; Morita, Satoru; Ichinose, Genki; Okabe, Takuya; Togashi, Tatsuya; Nagatani, Takashi; Yoshimura, Jin

2018-01-19

Classical Lotka-Volterra (LV) competition equation has shown that coexistence of competitive species is only possible when intraspecific competition is stronger than interspecific competition, i.e., the species inhibit their own growth more than the growth of the other species. Note that density effect is assumed to be linear in a classical LV equation. In contrast, in wild populations we can observed that mortality rate often increases when population density is very high, known as crowding effects. Under this perspective, the aggregation models of competitive species have been developed, adding the additional reduction in growth rates at high population densities. This study shows that the coexistence of a few species is promoted. However, an unsolved question is the coexistence of many competitive species often observed in natural communities. Here, we build an LV competition equation with a nonlinear crowding effect. Our results show that under a weak crowding effect, stable coexistence of many species becomes plausible, unlike the previous aggregation model. An analysis indicates that increased mortality rate under high density works as elevated intraspecific competition leading to the coexistence. This may be another mechanism for the coexistence of many competitive species leading high species diversity in nature.

Necessary condition for local distinguishability of maximally entangled states: Beyond orthogonality preservation

NASA Astrophysics Data System (ADS)

Singal, Tanmay; Rahaman, Ramij; Ghosh, Sibasish; Kar, Guruprasad

2017-10-01

The (im)possibility of local distinguishability of orthogonal multipartite quantum states still remains an intriguing question. Beyond C3⊗C3 , the problem remains unsolved even for maximally entangled states (MESs). So far, the only known condition for the local distinguishability of states is the well-known orthogonality preservation (OP). Using an upper bound on the locally accessible information for bipartite states, we derive a very simple necessary condition for any set of pairwise orthogonal MESs in Cd⊗Cd to be perfectly locally distinguishable. It is seen that particularly when the number of pairwise orthogonal MES states in Cd⊗Cd is equal to d , then this necessary condition, along with the OP condition, imposes more constraints (for said states to be perfectly locally distinguishable) than the OP condition does. When testing this condition for the local distinguishability of all sets of four generalized Bell states in C4⊗C4 , we find that it is not only necessary but also sufficient to determine their local distinguishability. This demonstrates that the aforementioned upper bound may play a significant role in the general scenario of local distinguishability of bipartite states.

Systematic review on strength training in Parkinson’s disease: an unsolved question

PubMed Central

Ramazzina, Ileana; Bernazzoli, Benedetta; Costantino, Cosimo

2017-01-01

The purpose of this study was to investigate the effectiveness of strength training, performed against a different resistance from body weight, in improving motor and nonmotor symptoms in patients with Parkinson’s disease (PD). The following electronic databases were searched: PubMed, Physiotherapy Evidence Database, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science. The review was conducted and reported in accordance with the PRISMA statement. Thirteen high-quality randomized controlled trials were included. Strength training performed against external resistance is well tolerated and appears to be a suitable physical activity to improve both physical parameters and quality of life parameters of PD subjects. However, although the study intervention included strength training, only a few selected studies assessed the improvement of muscle strength. Despite the encouraging results, it is difficult to establish a correlation between strength training and the improvements made. Our review highlights the lack of common intent in terms of study design and the presence of different primary and secondary outcomes. Accordingly, further studies are needed to support the beneficial effects of different types of strength training in PD subjects and to underline the superiority of strength training in PD patients with respect to other training. PMID:28408811

On the Problems of Cracking and the Question of Structural Integrity of Engineering Composite Materials

NASA Astrophysics Data System (ADS)

Beaumont, Peter W. R.

2014-02-01

Predicting precisely where a crack will develop in a material under stress and exactly when in time catastrophic fracture of the component will occur is one the oldest unsolved mysteries in the design and building of large engineering structures. Where human life depends upon engineering ingenuity, the burden of testing to prove a "fracture safe design" is immense. For example, when human life depends upon structural integrity as an essential design requirement, it takes ten thousand material test coupons per composite laminate configuration to evaluate an airframe plus loading to ultimate failure tails, wing boxes, and fuselages to achieve a commercial aircraft airworthiness certification. Fitness considerations for long-life implementation of aerospace composites include understanding phenomena such as impact, fatigue, creep, and stress corrosion cracking that affect reliability, life expectancy, and durability of structure. Structural integrity analysis treats the design, the materials used, and figures out how best components and parts can be joined. Furthermore, SI takes into account service duty. However, there are conflicting aims in the complete design process of designing simultaneously for high efficiency and safety assurance throughout an economically viable lifetime with an acceptable level of risk.

IYPT problems teach high school students about teamwork and the scientific method

NASA Astrophysics Data System (ADS)

Kochanski, K.; Klishin, A.

2015-12-01

Laboratory work is often STEM students' primary exposure to key creative and communicative skills in the sciences, including experimental design, trouble shooting, team work, and oral presentations. The International Young Physicists' Tournament (IYPT) teaches these skills by inviting high school students to investigate simple unsolved systems instead of reproducing familiar results. Students work in teams to form hypotheses, gather data, and present their results orally in a tournament format. The IYPT has published 17 questions yearly since 1988, and its archives are an efficient source of experimental problems for outreach programs and have also been used for first-year undergraduate project classes (Planisic, 2009). We present insights and outcomes from two schools in which we introduced a new extracurricular program based on the IYPT model. Twenty-four students worked in small teams for three hours per day for six weeks. Surprisingly, most teams chose problems in unfamiliar subject areas such as fluid dynamics, and tailored their approaches to take advantage of individual skills including soldering, photography, and theoretical analysis. As the program progressed, students developed an increasingly intuitive understanding of the scientific method. They began to discuss the repeatability of their experiments without prompting, and were increasingly willing to describe alternative hypotheses.

Social stimuli increase physiological reactivity but not defensive responses.

PubMed

Kosonogov, Vladimir; Sanchez-Navarro, Juan Pedro; Martinez-Selva, Jose Maria; Torrente, Ginesa; Carrillo-Verdejo, Eduvigis

2016-10-01

Emotional reactions are crucial in survival because they provide approach and withdrawal behaviors. However, an unsolved question is whether the social content of the affective stimuli has a specific effect on emotional responses. We studied whether the social content of affective pictures influenced the defensive response and response mobilization. For this purpose, we recorded startle blink reflex (a defensive response) and skin conductance responses (a measure of unspecific physiological reactivity or arousal) in 73 participants while they viewed a series of 81 pictures of varying affective valence and social content. Our results revealed that defense response, as indicated by increases in the magnitude of the startle blink reflex, was mainly dependent on threatening or unpleasant cues, but was unrelated to the social content of the pictures. The social content, however, had an influence on pleasant stimuli, provoking an increase in resource mobilization, as reflected by changes in electrodermal activity. Hence, the social content of the affective stimuli may increase the physiological arousal elicited by pleasant stimuli, and it appears to be unrelated to the defense reactivity provoked by unpleasant stimuli. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Top Mysteries of the Mind: Insights From the Default Space Model of Consciousness

PubMed Central

Jerath, Ravinder; Beveridge, Connor

2018-01-01

Aside from the nature of consciousness itself, there are still many unsolved problems in the neurosciences. Despite the vast and quickly growing body of work in this field, we still find ourselves perplexed at seemingly simple qualities of our mental being such as why we need to sleep. The neurosciences are at least beginning to take a hold on these mysteries and are working toward solving them. We hold a perspective that metastable consciousness models, specifically the Default Space Model (DSM), provide insights into these mysteries. In this perspective article, we explore some of these curious questions in order to elucidate the interesting points they bring up. The DSM is a dynamic, global theory of consciousness that involves the maintenance of an internal, 3D simulation of the external, physical world which is the foundation and structure of consciousness. This space is created and filled by multiple frequencies of membrane potential oscillations throughout the brain and body which are organized, synchronized and harmonized by the thalamus. The veracity of the DSM is highlighted here in its ability to further understanding of some of the most puzzling problems in neuroscience.

[Homocysteine metabolism disorders as a potential predictor of preeclamsia].

PubMed

Kajdy, Anna; Niemiec, Tomasz

2008-11-01

Preeclampsia is one of the main causes of maternal and fetal mortality. We lack a reliable test that would identify the "at risk" group of pregnant women, thus allowing us to implement a specific prevention, management and treatment program. Recently, a number of theories regarding the pathophysiology of preeclampsia has been published. The role of vascular pathology as a result of an increase in homocysteine level is often mentioned. The aim of this paper is to review the current literature related to the pathology of preeclampsia and to evaluate the usefulness of assessment of homocysteine level and homocysteine metabolism disorders as a potential predictor of preeclamsia. Hiperhomocysteinemia is a known risk factor of cardiovascular diseases and hypertension. Different sources report a similar correlation between an increase in homocysteine level and the incidence of preeclampsia. As far as the topic of homocysteine in pregnancy is concerned, numerous questions and problems remain unanswered and unsolved. Although there exists a relationship between an increased values of homocysteine and the incidence of preeclampsia, there is not enough information about what group of patients should be included in the screening test to increase the rate of diagnosis and prevention of the most dangerous sequele.

Top Mysteries of the Mind: Insights From the Default Space Model of Consciousness.

PubMed

Jerath, Ravinder; Beveridge, Connor

2018-01-01

Aside from the nature of consciousness itself, there are still many unsolved problems in the neurosciences. Despite the vast and quickly growing body of work in this field, we still find ourselves perplexed at seemingly simple qualities of our mental being such as why we need to sleep. The neurosciences are at least beginning to take a hold on these mysteries and are working toward solving them. We hold a perspective that metastable consciousness models, specifically the Default Space Model (DSM), provide insights into these mysteries. In this perspective article, we explore some of these curious questions in order to elucidate the interesting points they bring up. The DSM is a dynamic, global theory of consciousness that involves the maintenance of an internal, 3D simulation of the external, physical world which is the foundation and structure of consciousness. This space is created and filled by multiple frequencies of membrane potential oscillations throughout the brain and body which are organized, synchronized and harmonized by the thalamus. The veracity of the DSM is highlighted here in its ability to further understanding of some of the most puzzling problems in neuroscience.

Feelings of helplessness increase ERN amplitudes in healthyindividuals

PubMed Central

Pfabigan, D.M.; Pintzinger, N.M.; Siedek, D.R.; Lamm, C.; Derntl, B.; Sailer, U.

2013-01-01

Experiencing feelings of helplessness has repeatedly been reported to contribute to depressive symptoms and negative affect. In turn, depression and negative affective states are associated, among others, with impairments in performance monitoring. Thus, the question arises whether performance monitoring is also affected by feelings of helplessness. To this end, after the induction of feelings of helplessness via an unsolvable reasoning task, 37 participants (20 females) performed a modified version of a Flanker task. Based on a previously validated questionnaire, 17 participants were classified as helpless and 20 as not-helpless. Behavioral measures revealed no differences between helpless and not-helpless individuals. However, we observed enhanced Error-Related Negativity (ERN) amplitude differences between erroneous and correct responses in the helpless compared to the not-helpless group. Furthermore, correlational analysis revealed that higher scores of helplessness were associated with increased ERN difference scores. No influence of feelings of helplessness on later stages of performance monitoring was observed as indicated by Error-Positivity (Pe) amplitude. The present study is the first to demonstrate that feelings of helplessness modulate the neuronal correlates of performance monitoring. Thus, even a short-lasting subjective state manipulation can lead to ERN amplitude variation, probably via modulation of mesencephalic dopamine activity. PMID:23267824

Open chromatin structures regulate the efficiencies of pre-RC formation and replication initiation in Epstein-Barr virus

PubMed Central

Papior, Peer; Arteaga-Salas, José M.; Günther, Thomas; Grundhoff, Adam

2012-01-01

Whether or not metazoan replication initiates at random or specific but flexible sites is an unsolved question. The lack of sequence specificity in origin recognition complex (ORC) DNA binding complicates genome-scale chromatin immunoprecipitation (ChIP)-based studies. Epstein-Barr virus (EBV) persists as chromatinized minichromosomes that are replicated by the host replication machinery. We used EBV to investigate the link between zones of pre-replication complex (pre-RC) assembly, replication initiation, and micrococcal nuclease (MNase) sensitivity at different cell cycle stages in a genome-wide fashion. The dyad symmetry element (DS) of EBV’s latent origin, a well-established and very efficient pre-RC assembly region, served as an internal control. We identified 64 pre-RC zones that correlate spatially with 57 short nascent strand (SNS) zones. MNase experiments revealed that pre-RC and SNS zones were linked to regions of increased MNase sensitivity, which is a marker of origin strength. Interestingly, although spatially correlated, pre-RC and SNS zones were characterized by different features. We propose that pre-RCs are formed at flexible but distinct sites, from which only a few are activated per single genome and cell cycle. PMID:22891264

Mitigating Mitochondrial Genome Erosion Without Recombination.

PubMed

Radzvilavicius, Arunas L; Kokko, Hanna; Christie, Joshua R

2017-11-01

Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle promote recombination, but it would also compromise the purifying selection benefits of uniparental inheritance. We assess this tradeoff using a stochastic population-genetic model. In the absence of recombination, uniparental inheritance of freely-segregating genomes mitigates mutational erosion, while paternal leakage exacerbates the ratchet effect. Mitochondrial fusion-fission cycles ensure independent genome segregation, improving purifying selection. Paternal leakage provides opportunity for recombination to slow down the mutation accumulation, but always at a cost of increased steady-state mutation load. Our findings indicate that random segregation of mitochondrial genomes under uniparental inheritance can effectively combat the mutational meltdown, and that homologous recombination under paternal leakage might not be needed. Copyright © 2017 by the Genetics Society of America.

Hemorheological changes in ischemia-reperfusion: an overview on our experimental surgical data.

PubMed

Nemeth, Norbert; Furka, Istvan; Miko, Iren

2014-01-01

Blood vessel occlusions of various origin, depending on the duration and extension, result in tissue damage, causing ischemic or ischemia-reperfusion injuries. Necessary surgical clamping of vessels in vascular-, gastrointestinal or parenchymal organ surgery, flap preparation-transplantation in reconstructive surgery, as well as traumatological vascular occlusions, all present special aspects. Ischemia and reperfusion have effects on hemorheological state by numerous ways: besides the local metabolic and micro-environmental changes, by hemodynamic alterations, free-radical and inflammatory pathways, acute phase reactions and coagulation changes. These processes may be harmful for red blood cells, impairing their deformability and influencing their aggregation behavior. However, there are still many unsolved or non-completely answered questions on relation of hemorheology and ischemia-reperfusion. How do various organ (liver, kidney, small intestine) or limb ischemic-reperfusionic processes of different duration and temperature affect the hemorheological factors? What is the expected magnitude and dynamics of these alterations? Where is the border of irreversibility? How can hemorheological investigations be applied to experimental models using laboratory animals in respect of inter-species differences? This paper gives a summary on some of our research data on organ/tissue ischemia-reperfusion, hemorheology and microcirculation, related to surgical research and experimental microsurgery.

Carbonaceous Dye‐Sensitized Solar Cell Photoelectrodes

PubMed Central

Batmunkh, Munkhbayar

2015-01-01

High photovoltaic efficiency is one of the most important keys to the commercialization of dye sensitized solar cells (DSSCs) in the quickly growing renewable electricity generation market. The heart of the DSSC system is a wide bandgap semiconductor based photoelectrode film that helps to adsorb dye molecules and transport the injected electrons away into the electrical circuit. However, charge recombination, poor light harvesting efficiency and slow electron transport of the nanocrystalline oxide photoelectrode film are major issues in the DSSC's performance. Recently, semiconducting composites based on carbonaceous materials (carbon nanoparticles, carbon nanotubes (CNTs), and graphene) have been shown to be promising materials for the photoelectrode of DSSCs due to their fascinating properties and low cost. After a brief introduction to development of nanocrystalline oxide based films, this Review outlines advancements that have been achieved in the application of carbonaceous‐based materials in the photoelectrode of DSSCs and how these advancements have improved performance. In addition, several of the unsolved issues in this research area are discussed and some important future directions are also highlighted. PMID:27980926

New trends in articular cartilage repair.

PubMed

Cucchiarini, Magali; Henrionnet, Christel; Mainard, Didier; Pinzano, Astrid; Madry, Henning

2015-12-01

Damage to the articular cartilage is an important, prevalent, and unsolved clinical issue for the orthopaedic surgeon. This review summarizes innovative basic research approaches that may improve the current understanding of cartilage repair processes and lead to novel therapeutic options. In this regard, new aspects of cartilage tissue engineering with a focus on the choice of the best-suited cell source are presented. The importance of non-destructive cartilage imaging is highlighted with the recent availability of adapted experimental tools such as Second Harmonic Generation (SHG) imaging. Novel insights into cartilage pathophysiology based on the involvement of the infrapatellar fat pad in osteoarthritis are also described. Also, recombinant adeno-associated viral vectors are discussed as clinically adapted, efficient tools for potential gene-based medicines in a variety of articular cartilage disorders. Taken as a whole, such advances in basic research in diverse fields of articular cartilage repair may lead to the development of improved therapies in the clinics for an improved, effective treatment of cartilage lesions in a close future.

Hydrogen bonds and heat diffusion in α-helices: a computational study.

PubMed

Miño, German; Barriga, Raul; Gutierrez, Gonzalo

2014-08-28

Recent evidence has shown a correlation between the heat diffusion pathways and the known allosteric communication pathways in proteins. Allosteric communication in proteins is a central, yet unsolved, problem in biochemistry, and the study and characterization of the structural determinants that mediate energy transfer among different parts of proteins is of major importance. In this work, we characterized the role of hydrogen bonds in diffusivity of thermal energy for two sets of α-helices with different abilities to form hydrogen bonds. These hydrogen bonds can be a constitutive part of the α-helices or can arise from the lateral chains. In our in vacuo simulations, it was observed that α-helices with a higher possibility of forming hydrogen bonds also had higher rates of thermalization. Our simulations also revealed that heat readily flowed through atoms involved in hydrogen bonds. As a general conclusion, according to our simulations, hydrogen bonds fulfilled an important role in heat diffusion in structural patters of proteins.

Influence of DNA sequence on the structure of minicircles under torsional stress

PubMed Central

Wang, Qian; Irobalieva, Rossitza N.; Chiu, Wah; Schmid, Michael F.; Fogg, Jonathan M.; Zechiedrich, Lynn

2017-01-01

Abstract The sequence dependence of the conformational distribution of DNA under various levels of torsional stress is an important unsolved problem. Combining theory and coarse-grained simulations shows that the DNA sequence and a structural correlation due to topology constraints of a circle are the main factors that dictate the 3D structure of a 336 bp DNA minicircle under torsional stress. We found that DNA minicircle topoisomers can have multiple bend locations under high torsional stress and that the positions of these sharp bends are determined by the sequence, and by a positive mechanical correlation along the sequence. We showed that simulations and theory are able to provide sequence-specific information about individual DNA minicircles observed by cryo-electron tomography (cryo-ET). We provided a sequence-specific cryo-ET tomogram fitting of DNA minicircles, registering the sequence within the geometric features. Our results indicate that the conformational distribution of minicircles under torsional stress can be designed, which has important implications for using minicircle DNA for gene therapy. PMID:28609782

Simulation-Based Evaluation of Learning Sequences for Instructional Technologies

ERIC Educational Resources Information Center

McEneaney, John E.

2016-01-01

Instructional technologies critically depend on systematic design, and learning hierarchies are a commonly advocated tool for designing instructional sequences. But hierarchies routinely allow numerous sequences and choosing an optimal sequence remains an unsolved problem. This study explores a simulation-based approach to modeling learning…

Scaffolding in Complex Modelling Situations

ERIC Educational Resources Information Center

Stender, Peter; Kaiser, Gabriele

2015-01-01

The implementation of teacher-independent realistic modelling processes is an ambitious educational activity with many unsolved problems so far. Amongst others, there hardly exists any empirical knowledge about efficient ways of possible teacher support with students' activities, which should be mainly independent from the teacher. The research…

Clue Insensitivity in Remote Associates Test Problem Solving

ERIC Educational Resources Information Center

Smith, Steven M.; Sifonis, Cynthia M.; Angello, Genna

2012-01-01

Does spreading activation from incidentally encountered hints cause incubation effects? We used Remote Associates Test (RAT) problems to examine effects of incidental clues on impasse resolution. When solution words were seen incidentally 3-sec before initially unsolved problems were retested, more problems were resolved (Experiment 1). When…

Internet Investigations: Mixing Talent with Teachers and Telecommunications.

ERIC Educational Resources Information Center

Brown, Mark E.; Riley, Tracy L.

1998-01-01

Describes how teams of grade 4-9 gifted students investigated unsolved mysteries like Bigfoot, aliens and UFOs, the Loch Ness Monster, and Stonehenge to develop Internet and research skills. Highlights student observations on difficulties encountered using the Internet for research, notes student evaluation of the workshop, and provides addresses…

Thirteen Billion Years in Half AN Hour

NASA Astrophysics Data System (ADS)

Bassett, Bruce A.

2005-10-01

We take a high-speed tour of the approximately thirteen billion-year history of our universe focusing on unsolved mysteries and the key events that have sculpted and shaped it - from inflation in the first split second to the dark energy which is currently causing the expansion of the cosmos to accelerate.

CONFERENCES AND SYMPOSIA: Long-lived light phenomena in the atmosphere

NASA Astrophysics Data System (ADS)

Smirnov, Boris M.

1994-05-01

The state of knowledge of long-lived light phenomena in the atmosphere is reviewed in the light of contributions to the International Interdisciplinary Congress on Unsolved Problems of Atmospheric Electricity, September 1993, Salzburg, Austria; and the First International Workshop on Unidentified Atmospheric Light Phenomena, March 1994, Hessdalen, Norway.

Teaching and Learning Mathematics with Technology. 1997 Yearbook.

ERIC Educational Resources Information Center

Blume, Glendon W., Ed.; Heid, M. Kathleen, Ed.

This yearbook focuses on the role of technology in school mathematics. Chapters are replete with classroom-tested ideas for using technology to teach new mathematical ideas and to teach familiar mathematical ideas better. Chapters included: (1) "Using the Graphing Calculator in the Classroom: Helping Students Solve the "Unsolvable" (Eric Milou,…

Prostitute Homicides: A Descriptive Study

ERIC Educational Resources Information Center

Salfati, C. Gabrielle; James, Alison R.; Ferguson, Lynn

2008-01-01

It has been estimated that women involved in street prostitution are 60 to 100 times more likely to be murdered than are nonprostitute females. In addition, homicides of prostitutes are notoriously difficult to investigate and, as such, many cases remain unsolved. Despite this large risk factor, little literature exists on homicides of…

Guards, Galleries, Fortresses, and the Octoplex

ERIC Educational Resources Information Center

Michael, T. S.

2011-01-01

The art gallery problem asks for the maximum number of stationary guards required to protect the interior of a polygonal art gallery with "n" walls. This article explores solutions to this problem and several of its variants. In addition, some unsolved problems involving the guarding of geometric objects are presented.

The Animal Model of Spinal Cord Injury as an Experimental Pain Model

PubMed Central

Nakae, Aya; Nakai, Kunihiro; Yano, Kenji; Hosokawa, Ko; Shibata, Masahiko; Mashimo, Takashi

2011-01-01

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models. PMID:21436995

Risk assessment and patient stratification using implantable medical devices. The funding for personal health programs.

PubMed

Guillén, Alejandra; Colás, Javier; Gutiérrez, Germán

2011-01-01

Chronic diseases are currently recognized as one of the leading causes of mortality and morbidity worldwide. On top of this, these diseases represent a major burden for the healthcare systems in terms of costs and resources, which is driving them to define and adopt novel programs for prevention and chronic disease management. Still, many aspects of the processes of care and follow up of these patients remain unsolved and there is yet uncertainty on how technology can provide an added value to the current processes of care. This paper addresses the importance of the adoption of strategies for the anticipation to acute events within the disease management programs and suggests a holistic approach to embrace the healthcare organizations in the design development and implementation of the new personal health systems.

Understanding the Accretion Engine in Pre-main Sequence Stars

NASA Astrophysics Data System (ADS)

Gómez de Castro, Ana I.

2009-05-01

Planetary systems are angular momentum reservoirs generated during star formation as a result of the joint action of gravity and angular momentum conservation. The accretion process drives to the generation of powerful engines able to drive the optical jets and the molecular outflows. A fraction of the engine energy is released into heating the circumstellar plasma to temperatures between 3000 K to 10 MK depending on the plasma location and density. There are very important unsolved problems concerning the nature of the engine, its evolution and its impact in the chemical evolution of the disk. Of special relevance is the understanding of the shear layer between the stellar photosphere and the disk; this layer controls a significant fraction of the magnetic field building up and the subsequent dissipative processes ought to be studied in the UV.

Bees brought to their knees: microbes affecting honey bee health.

PubMed

Evans, Jay D; Schwarz, Ryan S

2011-12-01

The biology and health of the honey bee Apis mellifera has been of interest to human societies for centuries. Research on honey bee health is surging, in part due to new tools and the arrival of colony-collapse disorder (CCD), an unsolved decline in bees from parts of the United States, Europe, and Asia. Although a clear understanding of what causes CCD has yet to emerge, these efforts have led to new microbial discoveries and avenues to improve our understanding of bees and the challenges they face. Here we review the known honey bee microbes and highlight areas of both active and lagging research. Detailed studies of honey bee-pathogen dynamics will help efforts to keep this important pollinator healthy and will give general insights into both beneficial and harmful microbes confronting insect colonies. Copyright © 2011. Published by Elsevier Ltd.

Constraining the evolution of the Hubble Parameter using cosmic chronometers

NASA Astrophysics Data System (ADS)

Dickinson, Hugh

2017-08-01

Substantial investment is being made in space- and ground-based missions with the goal of revealing the nature of the observed cosmic acceleration. This is one of the most important unsolved problems in cosmology today.We propose here to constrain the evolution of the Hubble parameter [H(z)] between 1.3 < z < 2, using the cosmic chronometer method, based on differential age measurements for passively evolving galaxies. Existing WFC3-IR G102 and G141 grisms data obtained by the WISP, 3D-HST+AGHAST, FIGS, and CLEAR surveys will yield a sample of 140 suitable standard clocks, expanding existing samples by a factor of five. These additional data will enable us to improve existing constraints on the evolution of H at high redshift, and insodoing to better understand the fundamental nature of dark energy.

Integration of planar cell polarity and ECM signaling in elongation of the vertebrate body plan.

PubMed

Skoglund, Paul; Keller, Ray

2010-10-01

The shaping of the vertebrate embryonic body plan depends heavily on the narrowing and lengthening (convergence and extension) of embryonic tissues by cell intercalation, a process by which cells actively crawl between one another along the axis of convergence to produce a narrower, longer array. We discuss recent evidence that the vertebrate non-canonical Wnt/Planar Cell Polarity (PCP) pathway, known to directly function in polarizing the movements of intercalating cells, is also involved in the localized assembly of extracellular matrix (ECM). These cell-ECM interactions, in turn, are necessary for expression of the oriented, polarized cell intercalation. The mechanism of PCP/ECM interactions, their molecular signaling, and their mechanical consequences for morphogenesis are discussed with the goal of identifying important unsolved issues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Multi-dimensional simulations of core-collapse supernova explosions with CHIMERA

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

Messer, Bronson; Harris, James Austin; Hix, William Raphael

Unraveling the core-collapse supernova (CCSN) mechanism is a problem that remains essentially unsolved despite more than four decades of effort. Spherically symmetric models with otherwise high physical fidelity generally fail to produce explosions, and it is widely accepted that CCSNe are inherently multi-dimensional. Progress in realistic modeling has occurred recently through the availability of petascale platforms and the increasing sophistication of supernova codes. We will discuss our most recent work on understanding neutrino-driven CCSN explosions employing multi-dimensional neutrino-radiation hydrodynamics simulations with the Chimera code. We discuss the inputs and resulting outputs from these simulations, the role of neutrino radiation transport,more » and the importance of multi-dimensional fluid flows in shaping the explosions. We also highlight the production of 48Ca in long-running Chimera simulations.« less

Multi-spectral temperature measurement method for gas turbine blade

NASA Astrophysics Data System (ADS)

Gao, Shan; Feng, Chi; Wang, Lixin; Li, Dong

2016-02-01

One of the basic methods to improve both the thermal efficiency and power output of a gas turbine is to increase the firing temperature. However, gas turbine blades are easily damaged in harsh high-temperature and high-pressure environments. Therefore, ensuring that the blade temperature remains within the design limits is very important. There are unsolved problems in blade temperature measurement, relating to the emissivity of the blade surface, influences of the combustion gases, and reflections of radiant energy from the surroundings. In this study, the emissivity of blade surfaces has been measured, with errors reduced by a fitting method, influences of the combustion gases have been calculated for different operational conditions, and a reflection model has been built. An iterative computing method is proposed for calculating blade temperatures, and the experimental results show that this method has high precision.

African trypanosomes and brain infection - the unsolved question.

PubMed

Mogk, Stefan; Boßelmann, Christian M; Mudogo, Celestin N; Stein, Jasmin; Wolburg, Hartwig; Duszenko, Michael

2017-08-01

African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier. It is known that some immune cells are able to cross this barrier, but this requires a sophisticated mechanism and highly specific cell-cell interactions that have not been observed for trypanosomes within the mammalian host. Interestingly, trypanosomes injected directly into the brain parenchyma did not induce an infection. Likewise, after an intraperitoneal infection of rats, Trypanosoma brucei brucei was not observed within the brain, but appeared readily within the cerebrospinal fluid (CSF) and the meninges. Therefore, the parasite did not cross the blood-brain barrier, but the blood-CSF barrier, which is formed by the choroid plexus, i.e. the part of the ventricles where CSF is produced from blood. While there is no question that trypanosomes are able to invade the brain to induce a deadly encephalopathy, controversy exists about the pathway involved. This review lists experimental results that support crossing of the blood-brain barrier and of the blood-CSF barrier and discuss the implications that either pathway would have on infection progress and on the survival strategy of the parasite. For reasons discussed below, we prefer the latter pathway and suggest the existence of an additional distinct meningeal stage, from which trypanosomes could invade the brain via the Virchow-Robin space thereby bypassing the blood-brain barrier. We also consider healthy carriers, i.e. people living symptomless with the disease for up to several decades, and discuss implications the proposed meningeal stage would have for new anti-trypanosomal drug development. Considering the re-infection of blood, a process called relapse, we discuss the likely involvement of the newly described glymphatic connection between the meningeal space and the lymphatic system, that seems also be important for other infectious diseases. © 2016 Cambridge Philosophical Society.

MIS 5e sea levels and `superstorms': what the integration of field data and modelling can tell us?

NASA Astrophysics Data System (ADS)

Rovere, A.; Raymo, M. E.; O'Leary, M.; Stocchi, P.; Vacchi, M.; Lorscheid, T.; Harris, D. L.; Casella, E.; Nandasena, N. A. K.; Sandstrom, R. M.; D'Andrea, W. J.; Dyer, B.

2016-12-01

The Last Interglacial (MIS 5e, 128-116 ka) is among the most studied past periods in Earth's history. The climate at that time was warmer than today, primarily due to different orbital conditions, with smaller ice sheets and higher sea level. Understanding the climate system, and in particular sea level, during MIS 5e is essential to understand the behavior of ice sheets in a warmer world. Two questions in particular remain unsolved: was there a meltwater pulse towards the end of the interglacial? Was the same period characterized by superstorms? Thousands of studies spanning more than a century report information on MIS 5e RSL indicators. Despite the large quantity of field data available, the two questions formulated above remain unanswered. This is due to different reasons. In first instance, relative sea-level (RSL) indicators and field interpretations may carry large uncertainties. Second, processes such as tectonics are difficult to isolate and quantify independently. In this presentation, we will describe the strategies that can be adopted to minimize the uncertainties associated with paleo RSL calculations, and we show the limits of `tectonic stability' assumptions based on the position of MIS 5e shorelines. We then show that the combination of high-resolution topographic methods (e.g. GPS, photogrammetry from UAVs and detailed bathymetry) with scenarios dictated by GIA and coastal hydrodynamic models is essential to gather insights not only on the indicative meaning of RSL indicators, but also on the hypothesis that the last period of MIS 5e was characterized by `superstorms' (as defined by Hansen, J. et al. Atmos. Chem. Phys. Discuss. 15, 2015).

Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes.

PubMed

Deponte, Marcel

2013-05-01

Glutathione-dependent catalysis is a metabolic adaptation to chemical challenges encountered by all life forms. In the course of evolution, nature optimized numerous mechanisms to use glutathione as the most versatile nucleophile for the conversion of a plethora of sulfur-, oxygen- or carbon-containing electrophilic substances. This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms of glutathione-dependent enzymes, including glutathione reductase, glutaredoxins, glutathione peroxidases, peroxiredoxins, glyoxalases 1 and 2, glutathione transferases and MAPEG. Moreover, open mechanistic questions, evolutionary aspects and the physiological relevance of glutathione catalysis are discussed for each enzyme family. It is surprising how little is known about many glutathione-dependent enzymes, how often reaction geometries and acid-base catalysts are neglected, and how many mechanistic puzzles remain unsolved despite almost a century of research. On the one hand, several enzyme families with non-related protein folds recognize the glutathione moiety of their substrates. On the other hand, the thioredoxin fold is often used for glutathione catalysis. Ancient as well as recent structural changes of this fold did not only significantly alter the reaction mechanism, but also resulted in completely different protein functions. Glutathione-dependent enzymes are excellent study objects for structure-function relationships and molecular evolution. Notably, in times of systems biology, the outcome of models on glutathione metabolism and redox regulation is more than questionable as long as fundamental enzyme properties are neither studied nor understood. Furthermore, several of the presented mechanisms could have implications for drug development. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.

Spectral characterization of V-type asteroids - I. Space weathering effects and implications for V-type NEAs

NASA Astrophysics Data System (ADS)

Fulvio, Daniele; Perna, Davide; Ieva, Simone; Brunetto, Rosario; Kanuchova, Zuzana; Blanco, Carlo; Strazzulla, Giovanni; Dotto, Elisabetta

2016-01-01

Among main belt asteroids, V-types belonging to Vesta's dynamical family are known as `Vestoids' while those lying outside Vesta's family as `non-Vestoids'. V-types have also been found within the population of Near Earth Asteroids (NEAs). Several questions on Vesta, the V-types, and the Howardite-Eucrite-Diogenite meteorites are still unsolved, such as the genesis of each class/subclass, their evolution and mutual relationship, and the existence of other basaltic parent bodies. We present new NIR (0.8-2.4 μm) spectroscopic observations of seven non-Vestoids, carried out at the Telescopio Nazionale Galileo (TNG - INAF). We derived a number of spectral parameters (BI and BII centres, band separations, and BI slopes) and compared them with available spectra of V-types belonging to different subclasses (102 V-types in total), to highlight possible spectral differences useful to shed light on the questions mentioned above. We also considered the data from ion irradiation experiments performed on different samples of eucrites, simulating space weathering effects. Net discrepancies are seen for the BI slope distributions: NEAs show a distribution strongly different from all other V-type subclasses. Ion irradiation experiments induce strong effects on BI slope values and, as irradiation proceeds, the BI slope of eucrites quickly increases, changing the overall aspect of their VIS-NIR spectra (0.4-2.5 μm). Space weathering may explain the whole range of spectral slopes observed for all V-type subclasses. An exception is represented by NEAs, where moderate space weathering effects are evidenced. We propose that this is due to tidal perturbations exposing `fresh' unweathered surface grains during close encounters with the Earth, as previously found for Q-type NEAs.

Legionnaires disease: historical perspective.

PubMed Central

Winn, W C

1988-01-01

In the summer of 1976, a mysterious epidemic of fatal respiratory disease in Philadelphia launched an intensive investigation that resulted in the definition of a new family of pathogenic bacteria, the Legionellaceae. In retrospect, members of the family had been isolated from clinical specimens as early as 1943. Unsolved epidemics of acute respiratory disease dating to the 1950s were subsequently attributed to the newly described pathogens. In the intervening years, the Legionellaceae have been firmly established as important causes of sporadic and epidemic respiratory disease. The sources of the infecting bacteria are environmental, and geographic variation in the frequency of infection has been documented. Airborne dissemination of bacteria from cooling towers and evaporative condensers has been responsible for some epidemics, but potable water systems are perhaps more important sources. The mode of transmission from drinking water is unclear. The Legionellaceae are gram-negative, facultative, intracellular pathogens. The resident alveolar macrophage, usually an effective antibacterial defense, is the primary site of growth. Cell-mediated immunity appears to be the most important immunological defense; the role of humoral immunity is less clear. Erythromycin remains the antibiotic of choice for therapy of infected patients, but identification and eradication of environmental sources are also essential for the control of infection. Images PMID:3060246

The current situation and development of medical device testing institutes in China.

PubMed

Yang, Xiaofang; Mu, Ruihong; Fan, Yubo; Wang, Chunren; Li, Deyu

2017-04-01

This article analyses the current situation and development of Chinese medical device testing institutes from the perspectives of the two most important functions - testing functions and medical device standardization functions. Areas Covered: The objective of the Chinese government regulations for medical device industry is to ensure the safety and effectiveness of medical devices for Chinese patients. To support the regulation system, the Chinese government has established medical device testing institutes at different levels for example, the national, provincial, and municipal levels. These testing institutes also play an important role in technical support during medical device premarket registration and post market surveillance, they are also the vital practitioners of Chinese medical device standardization. Expert Commentary: Chinese medical device testing institutes are technical departments established by government, and serve the regulatory functions of government agency. In recent years, with the rapid development of medical device industry as well as constantly increasing international and domestic medical device market, the importance of medical device testing institute is more prominent, However, there are still some problems unsolved, such as their overall capacity remains to be improved, construction of standardization is to be strengthened, etc.

Investigating School-Wide Antecedents of Good Practice Dissemination from Individual Subject Projects

ERIC Educational Resources Information Center

Christophersen, Knut-Andreas; Elstad, Eyvind; Turmo, Are

2012-01-01

Good practice dissemination is an unsolved problem in education. This article describes how clear and "soft" leadership and perceptions of social and economic exchange operate in the bottom-up processes of school reforms and examines the relative impact of these factors on school-wide good practice dissemination and discusses how…

Statistical Inference in the Learning of Novel Phonetic Categories

ERIC Educational Resources Information Center

Zhao, Yuan

2010-01-01

Learning a phonetic category (or any linguistic category) requires integrating different sources of information. A crucial unsolved problem for phonetic learning is how this integration occurs: how can we update our previous knowledge about a phonetic category as we hear new exemplars of the category? One model of learning is Bayesian Inference,…

Le Chatelier's Principle: The Effect of Temperature on the Solubility of Solids in Liquids.

ERIC Educational Resources Information Center

Brice, L. K.

1983-01-01

Provides a rigorous but straightforward thermodynamic treatment of the temperature dependence of the solubility of solids in liquids that is suitable for presentation to undergraduates, suggesting how to approach the qualitative aspects of the subject for freshmen. Considers unsolvated/solvated solutes and Le Chatelier's principle. (JN)

Ugandan Mathematics: An Unsolvable Problem?

ERIC Educational Resources Information Center

Eveleigh, Tobias

2011-01-01

This author is on a journey--hoping that his expertise might have some small local impact. He shares his experiences that might relate to those who are thinking about volunteering abroad, or trying to modernise a system that is cemented in place. Creating change, developing teaching styles, and working for a charity are some of the challenges he…

Children with Autism Spectrum Disorder Have an Exceptional Explanatory Drive

ERIC Educational Resources Information Center

Rutherford, M. D.; Subiaul, Francys

2016-01-01

An "explanatory drive" motivates children to explain ambiguity. Individuals with autism spectrum disorders are interested in how systems work, but it is unknown whether they have an explanatory drive. We presented children with and without autism spectrum disorder unsolvable problems in a physical and in a social context and evaluated…

Urban Education: Past, Present and Future.

ERIC Educational Resources Information Center

Watson, Bernard C.

In spite of the efforts of the Ford Foundation's Great Cities School Improvement Program in ten large city school systems to provide quality education to children and youth from the ghettos of America's cities, this problem remains unsolved. Cities have never been able to do an adequate job of educating the poor, the immigrants, and the…

A time-series approach to estimating soil moisture from vegetated surfaces using L-band radar backscatter

USDA-ARS?s Scientific Manuscript database

Many previous studies have shown the sensitivity of radar backscatter to surface soil moisture content, particularly at L-band. Moreover, the estimation of soil moisture from radar for bare soil surfaces is well-documented, but estimation underneath a vegetation canopy remains unsolved. Vegetation s...

Some Philosophical Paradigms in Education of Modeling and Control

ERIC Educational Resources Information Center

Keviczky, László; Bányász, Csilla

2017-01-01

The paper discusses some interesting, mainly philosophical paradigms of the modeling and control areas, which are still partly unsolved and/or only partially studied. First the possible introduction of a prejudice free control--similar to the term for the modeling introduced by Rudi Kalman--is investigated. Next the real constraints in real…

Predicting Premature Termination within a Randomized Controlled Trial for Binge-Eating Patients

ERIC Educational Resources Information Center

Fluckiger, Christoph; Meyer, Andrea; Wampold, Bruce E.; Gassmann, Daniel; Messerli-Burgy, Nadine; Munsch, Simone

2011-01-01

Understanding the dropout rates of efficacious forms of psychotherapy for patients with binge eating disorder (BED) is an unsolved problem within this increasing population. Up until now the role of psychotherapy process characteristics as predictors of premature termination has not been investigated in the BED literature. Within a randomized…

A Computer Model of Simple Forms of Learning.

ERIC Educational Resources Information Center

Jones, Thomas L.

A basic unsolved problem in science is that of understanding learning, the process by which people and machines use their experience in a situation to guide future action in similar situations. The ideas of Piaget, Pavlov, Hull, and other learning theorists, as well as previous heuristic programing models of human intelligence, stimulated this…

Recent advances in PV systems technology development in Europe

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

Imamura, M.; Grottke, M.; Weiss, I.

1995-11-01

The objectives of the photovoltaics (PV) systems technology development were to study several aspects of plant design, monitoring, control, operation, and management of different types of photovoltaic plants. Unsolved problems were to be identified and analysed, and guidelines to improve the monitoring system were to be developed. Principal studies are summarized.

Latin America: The Revolution of Hope.

ERIC Educational Resources Information Center

Salcedo, Jose Joaquin; And Others

Latin America is a continent with a great deal of poverty, ignorance, and violence. This book describes the problems that plague the region and explains how and why they have gone unsolved. Change can come about only through real and effective participation by men and women in the political and economic activities of their nations. Organized into…

Kirkham’s legacy and contemporary challenges in soil physics research

USDA-ARS?s Scientific Manuscript database

This paper, written by the winners of the Don and Betty Kirkham Award in Soil Physics, is dedicated to the legacy of Don Kirkham. It describes eight longstanding or emerging research areas in soil physics that contain key unsolved problems. All are field-oriented with applications to a number of imp...

The collation of forensic DNA case data into a multi-dimensional intelligence database.

PubMed

Walsh, S J; Moss, D S; Kliem, C; Vintiner, G M

2002-01-01

The primary aim of any DNA Database is to link individuals to unsolved offenses and unsolved offenses to each other via DNA profiling. This aim has been successfully realised during the operation of the New Zealand (NZ) DNA Databank over the past five years. The DNA Intelligence Project (DIP), a collaborative project involving NZ forensic and law enforcement agencies, interrogated the forensic case data held on the NZ DNA databank and collated it into a functional intelligence database. This database has been used to identify significant trends which direct Police and forensic personnel towards the most appropriate use of DNA technology. Intelligence is being provided in areas such as the level of usage of DNA techniques in criminal investigation, the relative success of crime scene samples and the geographical distribution of crimes. The DIP has broadened the dimensions of the information offered through the NZ DNA Databank and has furthered the understanding and investigative capability of both Police and forensic scientists. The outcomes of this research fit soundly with the current policies of 'intelligence led policing', which are being adopted by Police jurisdictions locally and overseas.

Dog Breed Differences in Visual Communication with Humans.

PubMed

Konno, Akitsugu; Romero, Teresa; Inoue-Murayama, Miho; Saito, Atsuko; Hasegawa, Toshikazu

2016-01-01

Domestic dogs (Canis familiaris) have developed a close relationship with humans through the process of domestication. In human-dog interactions, eye contact is a key element of relationship initiation and maintenance. Previous studies have suggested that canine ability to produce human-directed communicative signals is influenced by domestication history, from wolves to dogs, as well as by recent breed selection for particular working purposes. To test the genetic basis for such abilities in purebred dogs, we examined gazing behavior towards humans using two types of behavioral experiments: the 'visual contact task' and the 'unsolvable task'. A total of 125 dogs participated in the study. Based on the genetic relatedness among breeds subjects were classified into five breed groups: Ancient, Herding, Hunting, Retriever-Mastiff and Working). We found that it took longer time for Ancient breeds to make an eye-contact with humans, and that they gazed at humans for shorter periods of time than any other breed group in the unsolvable situation. Our findings suggest that spontaneous gaze behavior towards humans is associated with genetic similarity to wolves rather than with recent selective pressure to create particular working breeds.

Blind prediction of noncanonical RNA structure at atomic accuracy.

PubMed

Watkins, Andrew M; Geniesse, Caleb; Kladwang, Wipapat; Zakrevsky, Paul; Jaeger, Luc; Das, Rhiju

2018-05-01

Prediction of RNA structure from nucleotide sequence remains an unsolved grand challenge of biochemistry and requires distinct concepts from protein structure prediction. Despite extensive algorithmic development in recent years, modeling of noncanonical base pairs of new RNA structural motifs has not been achieved in blind challenges. We report a stepwise Monte Carlo (SWM) method with a unique add-and-delete move set that enables predictions of noncanonical base pairs of complex RNA structures. A benchmark of 82 diverse motifs establishes the method's general ability to recover noncanonical pairs ab initio, including multistrand motifs that have been refractory to prior approaches. In a blind challenge, SWM models predicted nucleotide-resolution chemical mapping and compensatory mutagenesis experiments for three in vitro selected tetraloop/receptors with previously unsolved structures (C7.2, C7.10, and R1). As a final test, SWM blindly and correctly predicted all noncanonical pairs of a Zika virus double pseudoknot during a recent community-wide RNA-Puzzle. Stepwise structure formation, as encoded in the SWM method, enables modeling of noncanonical RNA structure in a variety of previously intractable problems.

Why wind-farm developers should care about measuring atmospheric turbulence? [Chaos in the Air: Unraveling the Complex Relationship Between Wind Power and Atmospheric turbulence

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

Wharton, Sonia; Newman, Jennifer F.

The role of atmospheric turbulence in influencing wind-turbine power production remains an unsolved mystery despite a growing number of researchers who have attempted to make sense of this issue. Turbulence, a term for short-term deviations around the average wind speed, can cause fluctuations in turbine power production and structural loads. While research strongly suggests that ignoring atmospheric turbulence can result in significant errors in power-curve measurements and annual energy production, it appears that there may be no universal relationship between turbulence and power production. Typically when we think of a wind farm operating in a turbulent atmosphere, we picture amore » waked turbine, battered by vortex eddies (circular wind flow) shed from turbine blades upwind. However, turbulence is present nearly everywhere, and is constantly produced and diminished over a wide range of temporal and spatial scales. This article aims to unravel some of the complex factors that remain unsolved regarding turbulence and wind power« less

Why wind-farm developers should care about measuring atmospheric turbulence? [Chaos in the Air: Unraveling the Complex Relationship Between Wind Power and Atmospheric turbulence

DOE PAGES

Wharton, Sonia; Newman, Jennifer F.

2017-09-11

The role of atmospheric turbulence in influencing wind-turbine power production remains an unsolved mystery despite a growing number of researchers who have attempted to make sense of this issue. Turbulence, a term for short-term deviations around the average wind speed, can cause fluctuations in turbine power production and structural loads. While research strongly suggests that ignoring atmospheric turbulence can result in significant errors in power-curve measurements and annual energy production, it appears that there may be no universal relationship between turbulence and power production. Typically when we think of a wind farm operating in a turbulent atmosphere, we picture amore » waked turbine, battered by vortex eddies (circular wind flow) shed from turbine blades upwind. However, turbulence is present nearly everywhere, and is constantly produced and diminished over a wide range of temporal and spatial scales. This article aims to unravel some of the complex factors that remain unsolved regarding turbulence and wind power« less

Unsolved mysteries of Rag GTPase signaling in yeast.

PubMed

Hatakeyama, Riko; De Virgilio, Claudio

2016-10-01

The target of rapamycin complex 1 (TORC1) plays a central role in controlling eukaryotic cell growth by fine-tuning anabolic and catabolic processes to the nutritional status of organisms and individual cells. Amino acids represent essential and primordial signals that modulate TORC1 activity through the conserved Rag family GTPases. These assemble, as part of larger lysosomal/vacuolar membrane-associated complexes, into heterodimeric sub-complexes, which typically comprise two paralogous Rag GTPases of opposite GTP-/GDP-loading status. The TORC1-stimulating/inhibiting states of these heterodimers are controlled by various guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) complexes, which are remarkably conserved in various eukaryotic model systems. Among the latter, the budding yeast Saccharomyces cerevisiae has been instrumental for the elucidation of basic aspects of Rag GTPase regulation and function. Here, we discuss the current state of the respective research, focusing on the major unsolved issues regarding the architecture, regulation, and function of the Rag GTPase containing complexes in yeast. Decoding these mysteries will undoubtedly further shape our understanding of the conserved and divergent principles of nutrient signaling in eukaryotes.

Unsolved mysteries of Rag GTPase signaling in yeast

PubMed Central

Hatakeyama, Riko; De Virgilio, Claudio

2016-01-01

ABSTRACT The target of rapamycin complex 1 (TORC1) plays a central role in controlling eukaryotic cell growth by fine-tuning anabolic and catabolic processes to the nutritional status of organisms and individual cells. Amino acids represent essential and primordial signals that modulate TORC1 activity through the conserved Rag family GTPases. These assemble, as part of larger lysosomal/vacuolar membrane-associated complexes, into heterodimeric sub-complexes, which typically comprise two paralogous Rag GTPases of opposite GTP-/GDP-loading status. The TORC1-stimulating/inhibiting states of these heterodimers are controlled by various guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) complexes, which are remarkably conserved in various eukaryotic model systems. Among the latter, the budding yeast Saccharomyces cerevisiae has been instrumental for the elucidation of basic aspects of Rag GTPase regulation and function. Here, we discuss the current state of the respective research, focusing on the major unsolved issues regarding the architecture, regulation, and function of the Rag GTPase containing complexes in yeast. Decoding these mysteries will undoubtedly further shape our understanding of the conserved and divergent principles of nutrient signaling in eukaryotes. PMID:27400376

Transcranial magnetic stimulation: no effect on mood with single pulse during learned helplessness.

PubMed

Habel, U; Wild, B; Topka, H; Kircher, T; Salloum, J B; Schneider, F

2001-04-01

1. Transcranial Magnetic Stimulation (TMS) is suggested to be an effective tool in the treatment of depression. However, the methodology most suitable for clinical application remains unclear. 2. The effect of TMS was tested in a double-blind and placebo-controlled setting on 18 healthy subjects. At the same time an established learned helplessness paradigm was applied to induce dysphoria, which consisted of unsolvable anagrams. 3. Sixty 0.5 Hz stimuli were administered at an intensity of 130% of the subject's motor threshold after the subjects were exposed to the learned helplessness situation. Using a vertically positioned coil, the stimuli were applied to the right or to the left frontal cortex, or on the occipital cortex as a placebo condition. 4. Although dysphoria was successfully induced by unsolvable anagrams, TMS on either of the two frontal locations did not influence mood. This lack of effect may be due to the stimulation characteristics employed here (low TMS intensity, and low frequency). On the other hand, the findings may reflect the neurobiological difference between experimentally induced sad mood and clinical depression.

Germline recessive mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis

PubMed Central

Pagnamenta, Alistair T.; Howard, Malcolm F.; Wisniewski, Eva; Popitsch, Niko; Knight, Samantha J.L.; Keays, David A.; Quaghebeur, Gerardine; Cox, Helen; Cox, Phillip; Balla, Tamas; Taylor, Jenny C.; Kini, Usha

2015-01-01

Polymicrogyria (PMG) is a structural brain abnormality involving the cerebral cortex that results from impaired neuronal migration and although several genes have been implicated, many cases remain unsolved. In this study, exome sequencing in a family where three fetuses had all been diagnosed with PMG and cerebellar hypoplasia allowed us to identify regions of the genome for which both chromosomes were shared identical-by-descent, reducing the search space for causative variants to 8.6% of the genome. In these regions, the only plausibly pathogenic mutations were compound heterozygous variants in PI4KA, which Sanger sequencing confirmed segregated consistent with autosomal recessive inheritance. The paternally transmitted variant predicted a premature stop mutation (c.2386C>T; p.R796X), whereas the maternally transmitted variant predicted a missense substitution (c.5560G>A; p.D1854N) at a conserved residue within the catalytic domain. Functional studies using expressed wild-type or mutant PI4KA enzyme confirmed the importance of p.D1854 for kinase activity. Our results emphasize the importance of phosphoinositide signalling in early brain development. PMID:25855803

Human interface to large multimedia databases

NASA Astrophysics Data System (ADS)

Davis, Ben; Marks, Linn; Collins, Dave; Mack, Robert; Malkin, Peter; Nguyen, Tam

1994-04-01

The emergence of high-speed networking for multimedia will have the effect of turning the computer screen into a window on a very large information space. As this information space increases in size and complexity, providing users with easy and intuitive means of accessing information will become increasingly important. Providing access to large amounts of text has been the focus of work for hundreds of years and has resulted in the evolution of a set of standards, from the Dewey Decimal System for libraries to the recently proposed ANSI standards for representing information on-line: KIF, Knowledge Interchange Format, and CG's, Conceptual Graphs. Certain problems remain unsolved by these efforts, though: how to let users know the contents of the information space, so that they know whether or not they want to search it in the first place, how to facilitate browsing, and, more specifically, how to facilitate visual browsing. These issues are particularly important for users in educational contexts and have been the focus of much of our recent work. In this paper we discuss some of the solutions we have prototypes: specifically, visual means, visual browsers, and visual definitional sequences.

Breeding synchrony in colonial birds: from local stress to global harmony.

PubMed

Jovani, Roger; Grimm, Volker

2008-07-07

Why and how birds in colonies often breed in striking synchrony is an unsolved question. In colonies, conspecific birds often destroy eggs and kill chicks, either intentionally or not. We propose that social tranquillity at the time of laying can be achieved if a bird's stress level is partly determined by the agitation of its neighbours. Moreover, we propose that this local process, together with environmental cues, can synchronize breeding between neighbours and through a whole colony. We tested our hypotheses using a generic individual-based model where the breeding predisposition of females was updated daily depending on an increase in the photoperiod (positively) and the stress level of neighbours: negatively if they were agitated, and positively otherwise. A female laid her eggs when her stress level fell to a critical value. Even giving only a low relevance to the neighbour's stress level was enough to synchronize the laying date of neighbours and also of a huge colony. Moreover, females bred in a safer environment, which is known from field studies to increase fitness. Our study highlights the power of local adaptive (individual) behaviour to create global (colony) patterns. We argue that collective patterns such as breeding synchrony in colonial birds could have simple adaptive individual-level explanations.

What is the minimum number of water molecules required to dissolve a potassium chloride molecule?

PubMed

Sen, Anik; Ganguly, Bishwajit

2010-12-01

This work answers an unsolved question that consists of determining the least number of water molecules necessary to separate a potassium chloride molecule. The answer based on accurate quantum chemical calculations suggests that tetramers are the smallest clusters necessary to dissociate KCl molecules. The study was made with Møller-Plesset second-order perturbation theory modified with the cluster theory having single, double, and perturbative triple excitations. With this extensive study, the dissociation of KCl molecule in different water clusters was evaluated. The calculated results show that four water molecules stabilize a solvent separated K(+)/Cl(-) ion-pair in prismatic structure and with six water molecules further dissociation was observed. Attenuated total reflection infrared spectroscopy of KCl dissolved in water establishes that clusters are made of closely bound ions with a mean of five water molecules per ion-pair [K(+)(H(2)O)(5)Cl(-)]. (Max and Chapados, Appl Spectrosc 1999, 53, 1601; Max and Chapados, J Chem Phys 2001, 115, 2664.) The calculated results tend to support that five water molecules leads toward the formation of contact ion-pair. The structures, energies, and infrared spectra of KCl molecules in different water clusters are also discussed. © 2010 Wiley Periodicals, Inc.

Genetic and Epigenetic Events Generate Multiple Pathways in Colorectal Cancer Progression

PubMed Central

Pancione, Massimo; Remo, Andrea; Colantuoni, Vittorio

2012-01-01

Colorectal cancer (CRC) is one of the most common causes of death, despite decades of research. Initially considered as a disease due to genetic mutations, it is now viewed as a complex malignancy because of the involvement of epigenetic abnormalities. A functional equivalence between genetic and epigenetic mechanisms has been suggested in CRC initiation and progression. A hallmark of CRC is its pathogenetic heterogeneity attained through at least three distinct pathways: a traditional (adenoma-carcinoma sequence), an alternative, and more recently the so-called serrated pathway. While the alternative pathway is more heterogeneous and less characterized, the traditional and serrated pathways appear to be more homogeneous and clearly distinct. One unsolved question in colon cancer biology concerns the cells of origin and from which crypt compartment the different pathways originate. Based on molecular and pathological evidences, we propose that the traditional and serrated pathways originate from different crypt compartments explaining their genetic/epigenetic and clinicopathological differences. In this paper, we will discuss the current knowledge of CRC pathogenesis and, specifically, summarize the role of genetic/epigenetic changes in the origin and progression of the multiple CRC pathways. Elucidation of the link between the molecular and clinico-pathological aspects of CRC would improve our understanding of its etiology and impact both prevention and treatment. PMID:22888469

Single microfilaments mediate the early steps of microtubule bundling during preprophase band formation in onion cotyledon epidermal cells

PubMed Central

Takeuchi, Miyuki; Karahara, Ichirou; Kajimura, Naoko; Takaoka, Akio; Murata, Kazuyoshi; Misaki, Kazuyo; Yonemura, Shigenobu; Staehelin, L. Andrew; Mineyuki, Yoshinobu

2016-01-01

The preprophase band (PPB) is a cytokinetic apparatus that determines the site of cell division in plants. It originates as a broad band of microtubules (MTs) in G2 and narrows to demarcate the future division site during late prophase. Studies with fluorescent probes have shown that PPBs contain F-actin during early stages of their development but become actin depleted in late prophase. Although this suggests that actins contribute to the early stages of PPB formation, how actins contribute to PPB-MT organization remains unsolved. To address this question, we used electron tomography to investigate the spatial relationship between microfilaments (MFs) and MTs at different stages of PPB assembly in onion cotyledon epidermal cells. We demonstrate that the PPB actins observed by fluorescence microscopy correspond to short, single MFs. A majority of the MFs are bound to MTs, with a subset forming MT-MF-MT bridging structures. During the later stages of PPB assembly, the MF-mediated links between MTs are displaced by MT-MT linkers as the PPB MT arrays mature into tightly packed MT bundles. On the basis of these observations, we propose that the primary function of actins during PPB formation is to mediate the initial bundling of the PPB MTs. PMID:27053663

Identification of minor inner-membrane components of the Shigella type III secretion system 'needle complex'.

PubMed

Zenk, Sebastian F; Stabat, David; Hodgkinson, Julie L; Veenendaal, Andreas K J; Johnson, Steven; Blocker, Ariel J

2007-08-01

Type III secretion systems (T3SSs or secretons) are central virulence factors of many Gram-negative bacteria, used to inject protein effectors of virulence into eukaryotic host cells. Their overall morphology, consisting of a cytoplasmic region, an inner- and outer-membrane section and an extracellular needle, is conserved in various species. A portion of the secreton, containing the transmembrane regions and needle, has been isolated biochemically and termed the 'needle complex' (NC). However, there are still unsolved questions concerning the nature and relative arrangement of the proteins assembling the NC. Until these are resolved, the mode of function of the NC cannot be clarified. This paper describes an affinity purification method that enables highly efficient purification of Shigella NCs under near-physiological conditions. Using this method, three new minor components of the NC were identified by mass spectrometry: IpaD, a known component of the needle tip complex, and two predicted components of its central inner-membrane export apparatus, Spa40 and Spa24. A further minor component of the NC, MxiM, is only detected by immunoblotting. MxiM is a 'pilotin'-type protein for the outer-membrane 'secretin' ring formed of MxiD. As expected, it localized to the outer rim of the upper ring of NCs, validating the other findings.

No evidence for β cell neogenesis in murine adult pancreas

PubMed Central

Xiao, Xiangwei; Chen, Zean; Shiota, Chiyo; Prasadan, Krishna; Guo, Ping; El-Gohary, Yousef; Paredes, Jose; Welsh, Carey; Wiersch, John; Gittes, George K.

2013-01-01

Whether facultative β cell progenitors exist in the adult pancreas is a major unsolved question. To date, lineage-tracing studies have provided conflicting results. To track β cell neogenesis in vivo, we generated transgenic mice that transiently coexpress mTomato and GFP in a time-sensitive, nonconditional Cre-mediated manner, so that insulin-producing cells express GFP under control of the insulin promoter, while all other cells express mTomato (INSCremTmG mice). Newly differentiated β cells were detected by flow cytometry and fluorescence microscopy, taking advantage of their transient coexpression of GFP and mTomato fluorescent proteins. We found that β cell neogenesis predominantly occurs during embryogenesis, decreases dramatically shortly after birth, and is completely absent in adults across various models of β cell loss, β cell growth and regeneration, and inflammation. Moreover, we demonstrated upregulation of neurogenin 3 (NGN3) in both proliferating ducts and preexisting β cells in the ligated pancreatic tail after pancreatic ductal ligation. These results are consistent with some recent reports, but argue against the widely held belief that NGN3 marks cells undergoing endocrine neogenesis in the pancreas. Our data suggest that β cell neogenesis in the adult pancreas occurs rarely, if ever, under either normal or pathological conditions. PMID:23619362

Postcollapse Evolution of Globular Clusters

NASA Astrophysics Data System (ADS)

Makino, Junichiro

1996-11-01

A number of globular clusters appear to have undergone core collapse, in the sense that their predicted collapse times are much shorter than their current ages. Simulations with gas models and the Fokker-Planck approximation have shown that the central density of a globular cluster after the collapse undergoes nonlinear oscillation with a large amplitude (gravothermal oscillation). However, the question whether such an oscillation actually takes place in real N-body systems has remained unsolved because an N-body simulation with a sufficiently high resolution would have required computing resources of the order of several GFLOPS-yr. In the present paper, we report the results of such a simulation performed on a dedicated special-purpose computer, GRAPE-4. We have simulated the evolution of isolated point-mass systems with up to 32,768 particles. The largest number of particles reported previously is 10,000. We confirm that gravothermal oscillation takes place in an N-body system. The expansion phase shows all the signatures that are considered to be evidence of the gravothermal nature of the oscillation. At the maximum expansion, the core radius is ˜1% of the half-mass radius for the run with 32,768 particles. The maximum core size, rc, depends on N as ∝ N-1/3.

Characterization of microcracks by application of digital image correlation to SPM images

NASA Astrophysics Data System (ADS)

Keller, Juergen; Gollhardt, Astrid; Vogel, Dietmar; Michel, Bernd

2004-07-01

With the development of micro- and nanotechnological products such as sensors, MEMS/NEMS and their broad application in a variety of market segments new reliability issues will arise. The increasing interface-to-volume ratio in highly integrated systems and nanoparticle filled materials and unsolved questions of size effect of nanomaterials are challenges for experimental reliability evaluation. To fulfill this needs the authors developed the nanoDAC method (nano Deformation Analysis by Correlation), which allows the determination and evaluation of 2D displacement fields based on scanning probe microscopy (SPM) data. In-situ SPM scans of the analyzed object are carried out at different thermo-mechanical load states. The obtained topography-, phase- or error-images are compared utilizing grayscale cross correlation algorithms. This allows the tracking of local image patterns of the analyzed surface structure. The measurement results of the nanoDAC method are full-field displacement and strain fields. Due to the application of SPM equipment deformations in the micro-, nanometer range can be easily detected. The method can be performed on bulk materials, thin films and on devices i.e microelectronic components, sensors or MEMS/NEMS. Furthermore, the characterization and evaluation of micro- and nanocracks or defects in bulk materials, thin layers and at material interfaces can be carried out.

Direct measurement of the free energy of aging hard sphere colloidal glasses.

PubMed

Zargar, Rojman; Nienhuis, Bernard; Schall, Peter; Bonn, Daniel

2013-06-21

The nature of the glass transition is one of the most important unsolved problems in condensed matter physics. The difference between glasses and liquids is believed to be caused by very large free energy barriers for particle rearrangements; however, so far it has not been possible to confirm this experimentally. We provide the first quantitative determination of the free energy for an aging hard sphere colloidal glass. The determination of the free energy allows for a number of new insights in the glass transition, notably the quantification of the strong spatial and temporal heterogeneity in the free energy. A study of the local minima of the free energy reveals that the observed variations are directly related to the rearrangements of the particles. Our main finding is that the probability of particle rearrangements shows a power law dependence on the free energy changes associated with the rearrangements similar to the Gutenberg-Richter law in seismology.

Suppressing Ice Nucleation of Supercooled Condensate with Biphilic Topography

NASA Astrophysics Data System (ADS)

Hou, Youmin; Yu, Miao; Shang, Yuhe; Zhou, Peng; Song, Ruyuan; Xu, Xiaonan; Chen, Xuemei; Wang, Zuankai; Yao, Shuhuai

2018-02-01

Preventing or minimizing ice formation in supercooled water is of prominent importance in many infrastructures, transportation, and cooling systems. The overall phase change heat transfer on icephobic surfaces, in general, is intentionally sacrificed to suppress the nucleation of water and ice. However, in a condensation frosting process, inhibiting freezing without compromising the water condensation has been an unsolved challenge. Here we show that this conflict between anti-icing and efficient condensation cooling can be resolved by utilizing biphilic topography with patterned high-contrast wettability. By creating a varying interfacial thermal barrier underneath the supercooled condensate, the biphilic structures tune the nucleation rates of water and ice in the sequential condensation-to-freezing process. Our experimental and theoretical investigation of condensate freezing dynamics further unravels the correlation between the onset of droplet freezing and its characteristic radius, offering a new insight for controlling the multiphase transitions among vapor, water, and ice in supercooled conditions.

Suppressing Ice Nucleation of Supercooled Condensate with Biphilic Topography.

PubMed

Hou, Youmin; Yu, Miao; Shang, Yuhe; Zhou, Peng; Song, Ruyuan; Xu, Xiaonan; Chen, Xuemei; Wang, Zuankai; Yao, Shuhuai

2018-02-16

Preventing or minimizing ice formation in supercooled water is of prominent importance in many infrastructures, transportation, and cooling systems. The overall phase change heat transfer on icephobic surfaces, in general, is intentionally sacrificed to suppress the nucleation of water and ice. However, in a condensation frosting process, inhibiting freezing without compromising the water condensation has been an unsolved challenge. Here we show that this conflict between anti-icing and efficient condensation cooling can be resolved by utilizing biphilic topography with patterned high-contrast wettability. By creating a varying interfacial thermal barrier underneath the supercooled condensate, the biphilic structures tune the nucleation rates of water and ice in the sequential condensation-to-freezing process. Our experimental and theoretical investigation of condensate freezing dynamics further unravels the correlation between the onset of droplet freezing and its characteristic radius, offering a new insight for controlling the multiphase transitions among vapor, water, and ice in supercooled conditions.

A Technological Comparison of Six Processes for the Production of Reduction-Grade Alumina from Non-Bauxitic Raw Materials

NASA Astrophysics Data System (ADS)

Bengtson, K. B.

The U. S. Bureau of Mines, by means of a contract with Kaiser Engineers and with Kaiser Aluminum & Chemical Corporation as a subcontractor, has sponsored a technological and an economic evaluation of six candidate processes for the manufacture of alumina from certain U. S. raw materials other than bauxite. This paper describes each process. Flow diagrams and the total energy requirement for each process are included. Important characteristics affecting the economics of producing alumina by each process are discussed, and some presently unsolved technical problems are identified. The extraction of alumina from clay via hydrochloric acid with iron separation by solvent extraction, and the crystallization of intermediate AlCl3·6H2O through the introduction of HCl gas into the pregnant mother liquor, appears to be technically feasible and the most attractive of the six raw material/process combinations.

Ships and Maritime Targets Observation Campaigns Using Available C- and X-Band SAR Satellite

NASA Astrophysics Data System (ADS)

Velotto, Domenico; Bentes, Carlos; Lehner, Susanne

2015-04-01

Obviously, radar resolution and swath width are two very important factors when it comes to synthetic aperture radar (SAR) maritime targets detections. The dilemma of using single polarization SAR imagery with higher resolution and coverage or quad- (or dual- polarimetric) imagery with its richness of information, is still unsolved when it comes to this application.In the framework of ESA project MARISS and EU project DOLPHIN, in situ campaigns aimed at solving this dilemma have been carried out. Single and multi- polarimetric SAR data acquired by TerraSAR-X, RADARSAT-2 and COSMO-SkyMed have been acquired with close time gaps and partial coverage overlap. In this way several moving and non-moving maritime targets have been imaged with different polarization, geometry and working frequency. Available ground truth reports provided by Automatic Identification System (AIS) data, nautical chart and wind farm location are used to validate the different types of maritime targets.

Enantioselective aldol reactions with masked fluoroacetates

NASA Astrophysics Data System (ADS)

Saadi, Jakub; Wennemers, Helma

2016-03-01

Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long-standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds.

A quantum spin-probe molecular microscope

NASA Astrophysics Data System (ADS)

Perunicic, V. S.; Hill, C. D.; Hall, L. T.; Hollenberg, L. C. L.

2016-10-01

Imaging the atomic structure of a single biomolecule is an important challenge in the physical biosciences. Whilst existing techniques all rely on averaging over large ensembles of molecules, the single-molecule realm remains unsolved. Here we present a protocol for 3D magnetic resonance imaging of a single molecule using a quantum spin probe acting simultaneously as the magnetic resonance sensor and source of magnetic field gradient. Signals corresponding to specific regions of the molecule's nuclear spin density are encoded on the quantum state of the probe, which is used to produce a 3D image of the molecular structure. Quantum simulations of the protocol applied to the rapamycin molecule (C51H79NO13) show that the hydrogen and carbon substructure can be imaged at the angstrom level using current spin-probe technology. With prospects for scaling to large molecules and/or fast dynamic conformation mapping using spin labels, this method provides a realistic pathway for single-molecule microscopy.

The Influence of Open Goals on the Acquisition of Problem-Relevant Information

ERIC Educational Resources Information Center

Moss, Jarrod; Kotovsky, Kenneth; Cagan, Jonathan

2007-01-01

There have been a number of recent findings indicating that unsolved problems, or open goals more generally, influence cognition even when the current task has no relation to the task in which the goal was originally set. It was hypothesized that open goals would influence what information entered the problem-solving process. Three studies were…

Partly versus Completely out of Your Mind: Effects of Incubation and Distraction on Resolving Fixation

ERIC Educational Resources Information Center

Kohn, Nicholas; Smith, Steven M.

2009-01-01

Incubation has long been proposed as a mechanism in creative problem solving (Wallas, 1926). A new trial-by-trial method for observing incubation effects was used to compare the forgetting fixation hypothesis with the conscious work hypothesis. Two experiments examined the effects of incubation on initially unsolved Remote Associates Test (RAT)…

Language of Physics, Language of Math: Disciplinary Culture and Dynamic Epistemology

ERIC Educational Resources Information Center

Redish, Edward F.; Kuo, Eric

2015-01-01

Mathematics is a critical part of much scientific research. Physics in particular weaves math extensively into its instruction beginning in high school. Despite much research on the learning of both physics and math, the problem of how to effectively include math in physics in a way that reaches most students remains unsolved. In this paper, we…

Water Pollution, A Scientists' Institute for Public Information Workbook.

ERIC Educational Resources Information Center

Berg, George G.

Analyzed are the reasons why present mechanisms for the control of water purity are inadequate. The control of waterborne epidemics is discussed to illustrate a problem which has been solved, then degradation of the environment is presented as an unsolved problem. Case histories are given of pollution and attempts at control in rivers, lakes,…

Difference rule-a new thermodynamic principle: prediction of standard thermodynamic data for inorganic solvates.

PubMed

Jenkins, H Donald Brooke; Glasser, Leslie

2004-12-08

We present a quite general thermodynamic "difference" rule, derived from thermochemical first principles, quantifying the difference between the standard thermodynamic properties, P, of a solid n-solvate (or n-hydrate), n-S, containing n molecules of solvate, S (water or other) and the corresponding solid parent (unsolvated) salt: [P[n-solvate] - P[parent

Enhancing in situ hydrogen peroxide generation of greige cotton nonwoven wound dressings via ascorbate stabilized copper micro- and nano-particles

USDA-ARS?s Scientific Manuscript database

Understanding how wound dressings may be designed to address critical unsolved issues in wound repair and treatment influences the development of dressings and new concepts of promoting healing. The vast majority of commercial dressing materials focus on the physical aspects of wounds, e.g., acting ...

A method for improved visual landscape compatibility of mobile home park

Treesearch

Daniel R. Jones

1979-01-01

This paper is a description of a research effort directed to improving the visual image of mobile home parks in the landscape. The study is an application of existing methodologies for measuring scenic quality and visual landscape compatibility to an unsolved problem. The paper summarizes two major areas of investigation: regional location factors based on visual...

Alcoholism and the Family. Unit for Child Studies Selected Papers Number 34.

ERIC Educational Resources Information Center

Wilson, G. C.

Alcoholism, and particularly alcoholism in the family, is an unsolved medical and social problem. Addictive drinking results in several social and psychological problems, most of which are caused by a change in brain function. Excessive drinking of alcoholic beverages operates as a stressor and produces alkaloids at the base of the brain that are…

How to?Identify Fingerprints and Animal Tracks

ERIC Educational Resources Information Center

Lindroth, Linda

2005-01-01

Caught by a fingerprint - or is it an animal track? This paper suggests investigating with these science projects for Earth Day. Students love spy mysteries, and the popularity of TV shows such as CSI and Unsolved Mysteries indicates the fascination is not only limited to our students. Why not capture this fascination for your science classroom.…

Developing Design and Management Skills for Senior Industrial Engineering Students

ERIC Educational Resources Information Center

Urbanic, R. J.

2011-01-01

In Canadian engineering institutions, a significant design experience must occur in the final year of study. In the Department of Industrial and Manufacturing Systems at the University of Windsor, unsolved, open ended projects sponsored by industrial partners from a variety of sectors are provided to the student teams in order for them to apply…

Gender, Order, and Femicide: Reading the Popular Culture of Murder in Ciudad Juarez

ERIC Educational Resources Information Center

Volk, Steven S.; Schlotterbeck, Marian E.

2007-01-01

More than 400 women have been murdered in and around Ciudad Juarez, Mexico, over the past decade. As the murders continue unabated and unsolved, and with the likely complicity of state authorities, they have triggered a dynamic cultural response from writers, filmmakers, singers, and others who deplore the murders while suggesting the underlying…

The Unsolved Challenge of System Reform: The Condition of the Frontline Human Services Workforce.

ERIC Educational Resources Information Center

Annie E. Casey Foundation, Baltimore, MD.

Frontline social services workers are the heart and soul of our nation's publicly funded human services system. Conservatively estimated at about 3 million, these workers have a tremendous impact on the life chances of vulnerable children and families. This vital role prompted Casey Foundation staff to conduct an in-depth exploration of job…

An Unsolved Electric Circuit: A Common Misconception

ERIC Educational Resources Information Center

Harsha, N. R. Sree; Sreedevi, A.; Prakash, Anupama

2015-01-01

Despite a number of theories in circuit analysis, little is known about the behaviour of ideal equal voltage sources in parallel, connected across a resistive load. We neither have any theory that can predict the voltage source that provides the load current, nor is there any method to test it experimentally. In a series of experiments performed…

Contact dermatitis: facts and controversies.

PubMed

Wolf, Ronni; Orion, Edith; Ruocco, Eleonora; Baroni, Adone; Ruocco, Vincenzo

2013-01-01

The history of contact dermatitis (CD) is inseparable from the history of the patch test, and the patch test is inseparable from the pioneer in the field, Josef Jadassohn (1860-1936). Despite the fact that we have been diagnosing, treating, and investigating the condition for more than 100 years, there are still many unsolved questions and controversies, which show no signs of coming to an end in the foreseeable future. This contribution reviews and highlights some of the disagreements and discrepancies associated with CD. For example: • What is the real sensitizer in balsam of Peru, one of the most common allergens, and what, if any, is the value of a low-balsam diet? • Is benzalkonium chloride, which has well-known and undisputed irritant properties, a contact allergen as well? • Is cocamidopropyl betaine (CABP) a common contact allergen and what is the actual sensitizer in CABP allergy the molecule itself, or impurities, or intermediaries in its synthesis? • How can the significant differences in the prevalence of sensitization of formaldehyde (FA, a common cause of contact allergy) between the United States (8%-9%) and Europe (2%-3%) be explained? • What is the relationship between formaldehyde releasers (FRs) allergy and an FA allergy? Should we recommend that FA-allergic patients also avoid FRs, and, if so, to what extent? • What is the true frequency of lanolin allergy? This issue remains enigmatic despite the expenditure of thousands of dollars and the innumerable hours spent investigating this subject. • What is the basis behind the so-called "lanolin paradox"? This label was coined in 1996 and is still a matter of controversy. • Is there such a thing as systemic CD from nickel, and, if so, to what extent? Is there a cross-reactivity or concomitant sensitization between nickel and cobalt?These are some of the controversial problems discussed. We have selected the ones that we consider to be of special interest and importance to the practicing dermatologist. Copyright © 2013 Elsevier Inc. All rights reserved.

A Renewed Look at the Planetary Nebula Luminosity Function: Circumstellar Extinction and Contamination From Compact Supernova Remnants

NASA Astrophysics Data System (ADS)

Davis, Brian; Ciardullo, Robin; Feldmeier, John; Jacoby, George H.; McCarron, Adam; Herrmann, Kimberly

2018-01-01

The planetary nebula luminosity function (PNLF) has been used as an extragalactic distance indicator since 1988, but there are still unsolved problems associated with its use. The two most serious involve PNLF distances beyond ~ 10 Mpc, which tend to be slightly smaller than those of other methods, and the lack of a theoretical explanation for the technique. We investigate these questions using a combination of narrow-band imaging data from the KPNO 4-m telescope, and recent LRS2 spectroscopy from the Hobby-Eberly Telescope.For the first project, we consider the implications of spectroscopic investigations by Kreckel et al. (2017), who found that in M74, several of the brightest planetary nebula (PN) candidates found by Herrmann et al. (2008) are actually compact supernova remnants (SNRs). First, we measure the [O III] and H-alpha fluxes of all the known SNRs in M31 and M33, and test whether those objects could be misidentified as bright PNe at distances beyond ~ 8 Mpc. We also obtain spectroscopy of bright PN candidates in the Fireworks Galaxy, NGC 6946, to test for PN/SNR confusion via the strengths of the [N II] and [S II] emission lines. Both experiments suggest that compact supernova remnants are not an important source of contamination in photometric surveys for extragalactic PNe.For the second project, we, for the first time, determine the de-reddened PNLF of an old stellar population. By performing spectroscopy of the brightest PN in M31’s bulge and measuring the objects’ Balmer decrements, we remove the effects of circumstellar extinction and derive the true location of the PNLF’s bright-end cutoff. In future studies, these data can be used to directly test the latest PNLF models, which combine modern post-AGB stellar evolutionary tracks with the physics of expanding nebulae.

A spatio-temporal evaluation of the WRF physical parameterisations for numerical rainfall simulation in semi-humid and semi-arid catchments of Northern China

NASA Astrophysics Data System (ADS)

Tian, Jiyang; Liu, Jia; Wang, Jianhua; Li, Chuanzhe; Yu, Fuliang; Chu, Zhigang

2017-07-01

Mesoscale Numerical Weather Prediction systems can provide rainfall products at high resolutions in space and time, playing an increasingly more important role in water management and flood forecasting. The Weather Research and Forecasting (WRF) model is one of the most popular mesoscale systems and has been extensively used in research and practice. However, for hydrologists, an unsolved question must be addressed before each model application in a different target area. That is, how are the most appropriate combinations of physical parameterisations from the vast WRF library selected to provide the best downscaled rainfall? In this study, the WRF model was applied with 12 designed parameterisation schemes with different combinations of physical parameterisations, including microphysics, radiation, planetary boundary layer (PBL), land-surface model (LSM) and cumulus parameterisations. The selected study areas are two semi-humid and semi-arid catchments located in the Daqinghe River basin, Northern China. The performance of WRF with different parameterisation schemes is tested for simulating eight typical 24-h storm events with different evenness in space and time. In addition to the cumulative rainfall amount, the spatial and temporal patterns of the simulated rainfall are evaluated based on a two-dimensional composed verification statistic. Among the 12 parameterisation schemes, Scheme 4 outperforms the other schemes with the best average performance in simulating rainfall totals and temporal patterns; in contrast, Scheme 6 is generally a good choice for simulations of spatial rainfall distributions. Regarding the individual parameterisations, Single-Moment 6 (WSM6), Yonsei University (YSU), Kain-Fritsch (KF) and Grell-Devenyi (GD) are better choices for microphysics, planetary boundary layers (PBL) and cumulus parameterisations, respectively, in the study area. These findings provide helpful information for WRF rainfall downscaling in semi-humid and semi-arid areas. The methodologies to design and test the combination schemes of parameterisations can also be regarded as a reference for generating ensembles in numerical rainfall predictions using the WRF model.

RELATIVISTIC HEAVY ION PHYSICS: A THEORETICAL OVERVIEW.

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

KHARZEEV,D.

2004-03-28

This is a mini-review of recent theoretical work in the field of relativistic heavy ion physics. The following topics are discussed initial conditions and the Color Glass Condensate; approach to thermalization and the hydrodynamic evolution; hard probes and the properties of the Quark-Gluon Plasma. Some of the unsolved problems and potentially promising directions for future research are listed as well.

How Can Agricultural and Extension Educators Contribute to a Successful New Green Revolution?

ERIC Educational Resources Information Center

Navarro, Maria

2006-01-01

In the middle of the 20th century, many in the world were predicting catastrophic starvation that was halted by the Green Revolution. To address continued population growth and the unsolved problems of the Green Revolution, many hope for a new and different Green Revolution. Supporters of a biotechnology-based revolution claim that it could…

Relatively Recursive Rational Choice.

DTIC Science & Technology

1981-11-01

for the decision procedure of recursively representable rational choice. Alternatively phrased, we wish to inquire into its degrees of unsolvability. We...may first make the observation that there are three classic notions of reducibility of decision procedures for subsets of the natural numbers... rational choice function defined as an effectively computable represent- ation of Richter’s [1971] concept of rational choice, attains by means of an

Celestial mechanics during the last two decades

NASA Technical Reports Server (NTRS)

Szebehely, V.

1978-01-01

The unprecedented progress in celestial mechanics (orbital mechanics, astrodynamics, space dynamics) is reviewed from 1957 to date. The engineering, astronomical and mathematical aspects are synthesized. The measuring and computational techniques developed parallel with the theoretical advances are outlined. Major unsolved problem areas are listed with proposed approaches for their solutions. Extrapolations and predictions of the progress for the future conclude the paper.

Relationship Satisfaction and Risk Factors for Suicide.

PubMed

Till, Benedikt; Tran, Ulrich S; Niederkrotenthaler, Thomas

2017-01-01

Previous studies suggest that troubled romantic relationships are associated with higher risk factors for mental health. However, studies examining the role of relationship satisfaction in suicide risk factors are scarce. We investigated differences in risk factors for suicide between individuals with high relationship satisfaction, individuals with low relationship satisfaction, and singles. Furthermore, we explored patterns of experiencing, and dealing with, conflicts in the relationship and examined associations with suicide risk factors. In this cross-sectional study, we assessed relationship status, relationship satisfaction, specific types of relationship conflicts, and suicide risk factors (i.e., suicidal ideation, hopelessness, depression) with questionnaires among 382 individuals in Austria. Risk factors for suicide were higher among singles than among individuals in happy relationships, but highest among those with low relationship satisfaction [corrected]. Participants reporting a high number of unsolved conflicts in their relationship had higher levels of suicidal ideation, hopelessness, and depression than individuals who tend to solve issues with their partner amicably or report no conflicts. Relationship satisfaction and relationship conflicts reflect risk factors for suicide, with higher levels of suicidal ideation, hopelessness, and depression reported by individuals who mentioned unsolved conflicts with their partner and experienced low satisfaction with their relationship.

Dog Breed Differences in Visual Communication with Humans

PubMed Central

Konno, Akitsugu; Romero, Teresa; Inoue-Murayama, Miho; Saito, Atsuko; Hasegawa, Toshikazu

2016-01-01

Domestic dogs (Canis familiaris) have developed a close relationship with humans through the process of domestication. In human-dog interactions, eye contact is a key element of relationship initiation and maintenance. Previous studies have suggested that canine ability to produce human-directed communicative signals is influenced by domestication history, from wolves to dogs, as well as by recent breed selection for particular working purposes. To test the genetic basis for such abilities in purebred dogs, we examined gazing behavior towards humans using two types of behavioral experiments: the ‘visual contact task’ and the ‘unsolvable task’. A total of 125 dogs participated in the study. Based on the genetic relatedness among breeds subjects were classified into five breed groups: Ancient, Herding, Hunting, Retriever-Mastiff and Working). We found that it took longer time for Ancient breeds to make an eye-contact with humans, and that they gazed at humans for shorter periods of time than any other breed group in the unsolvable situation. Our findings suggest that spontaneous gaze behavior towards humans is associated with genetic similarity to wolves rather than with recent selective pressure to create particular working breeds. PMID:27736990

West Europe Report

DTIC Science & Technology

1987-04-15

themselves to the main task. Civil-Military Cooperation in the WINTEX- CIMEX Exercise? The exercises of the WINTEX- CIMEX series are considered a prime...out successes and improvements resulting from WINTEX- CIMEX . Even the constant demonstration of continuous def icienies and unsolved problems can be...chalked up as a success for this two-year exercise series. From a critical military viewpoint, however, the WINTEX- CIMEX exercise shows clear signs

Planetary atmospheric physics and solar physics research

NASA Technical Reports Server (NTRS)

1973-01-01

An overview is presented on current and planned research activities in the major areas of solar physics, planetary atmospheres, and space astronomy. The approach to these unsolved problems involves experimental techniques, theoretical analysis, and the use of computers to analyze the data from space experiments. The point is made that the research program is characterized by each activity interacting with the other activities in the laboratory.

Nonlinear Multidimensional Assignment Problems Efficient Conic Optimization Methods and Applications

DTIC Science & Technology

2015-06-24

WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Arizona State University School of Mathematical & Statistical Sciences 901 S...SUPPLEMENTARY NOTES 14. ABSTRACT The major goals of this project were completed: the exact solution of previously unsolved challenging combinatorial optimization... combinatorial optimization problem, the Directional Sensor Problem, was solved in two ways. First, heuristically in an engineering fashion and second, exactly

JPRS Report, West Europe.

DTIC Science & Technology

1987-07-31

Sees Earlier Elections 24 Setback for Privitization Movement, by Egon Balsby 25 Many Economic Problems Unsolved, by Lasse Ellegaard 28 First...Geisler, Inuit Ataqatigiit. Setback For Privitization Movement Copenhagen BERLINGSKE AFTEN in Danish 29 May - 4 Jun 87 pp lr 2 [Article by Egon Balsby...34Yes to Socialism — No to Privitization "! [Text] The two large parties in Greenland politics, Ätassut and Siumut, both suffered defeats in an

The implementation of AI technologies in computer wargames

NASA Astrophysics Data System (ADS)

Tiller, John A.

2004-08-01

Computer wargames involve the most in-depth analysis of general game theory. The enumerated turns of a game like chess are dwarfed by the exponentially larger possibilities of even a simple computer wargame. Implementing challenging AI is computer wargames is an important goal in both the commercial and military environments. In the commercial marketplace, customers demand a challenging AI opponent when they play a computer wargame and are frustrated by a lack of competence on the part of the AI. In the military environment, challenging AI opponents are important for several reasons. A challenging AI opponent will force the military professional to avoid routine or set-piece approaches to situations and cause them to think much deeper about military situations before taking action. A good AI opponent would also include national characteristics of the opponent being simulated, thus providing the military professional with even more of a challenge in planning and approach. Implementing current AI technologies in computer wargames is a technological challenge. The goal is to join the needs of AI in computer wargames with the solutions of current AI technologies. This talk will address several of those issues, possible solutions, and currently unsolved problems.

Magnetoresistance Behavior of Conducting Filaments in Resistive-Switching NiO with Different Resistance States.

PubMed

Zhao, Diyang; Qiao, Shuang; Luo, Yuxiang; Chen, Aitian; Zhang, Pengfei; Zheng, Ping; Sun, Zhong; Guo, Minghua; Chiang, Fu-Kuo; Wu, Jian; Luo, Jianlin; Li, Jianqi; Kokado, Satoshi; Wang, Yayu; Zhao, Yonggang

2017-03-29

The resistive switching (RS) effect in various materials has attracted much attention due to its interesting physics and potential for applications. NiO is an important system and its RS effect has been generally explained by the formation/rupture of Ni-related conducting filaments. These filaments are unique since they are formed by an electroforming process, so it is interesting to explore their magnetoresistance (MR) behavior, which can also shed light on unsolved issues such as the nature of the filaments and their evolution in the RS process, and this behavior is also important for multifunctional devices. Here, we focus on MR behavior in NiO RS films with different resistance states. Rich and interesting MR behaviors have been observed, including the normal and anomalous anisotropic magnetoresistance and tunneling magnetoresistance, which provide new insights into the nature of the filaments and their evolution in the RS process. First-principles calculation reveals the essential role of oxygen migration into the filaments during the RESET process and can account for the experimental results. Our work provides a new avenue for exploration of the conducting filaments in resistive switching materials and is significant for understanding the mechanism of RS effect and multifunctional devices.

The Janus Face of Stress on Reproduction: From Health to Disease

PubMed Central

Zelena, Dóra

2015-01-01

Parenthood is a fundamental feature of all known life. However, infertility has been recognized as a public health issue worldwide. But even when the offspring are conceived, in utero problems can lead to immediate (abortion), early (birth), and late (adulthood) consequences. One of the most studied factors is stress. However, stress response is, per se, of adaptive nature allowing the organism to cope with challenges. Stressors lead to deterioration if one is faced with too long lasting, too many, and seemingly unsolvable situations. In stress adaptation the hypothalamus-pituitary-adrenocortical axis and the resulting glucocorticoid elevation are one of the most important mechanisms. At cellular level stress can be defined as an unbalance between production of free radicals and antioxidant defenses. Oxidative stress is widely accepted as an important pathogenic mechanism in different diseases including infertility. On the other hand, the goal of free radical production is to protect the cells from infectious entities. This review aims to summarize the negative and positive influence of stress on reproduction as a process leading to healthy progeny. Special emphasis was given to the balance at the level of the organism and cells. PMID:25945091

Goats display audience-dependent human-directed gazing behaviour in a problem-solving task.

PubMed

Nawroth, Christian; Brett, Jemma M; McElligott, Alan G

2016-07-01

Domestication is an important factor driving changes in animal cognition and behaviour. In particular, the capacity of dogs to communicate in a referential and intentional way with humans is considered a key outcome of how domestication as a companion animal shaped the canid brain. However, the lack of comparison with other domestic animals makes general conclusions about how domestication has affected these important cognitive features difficult. We investigated human-directed behaviour in an 'unsolvable problem' task in a domestic, but non-companion species: goats. During the test, goats experienced a forward-facing or an away-facing person. They gazed towards the forward-facing person earlier and for longer and showed more gaze alternations and a lower latency until the first gaze alternation when the person was forward-facing. Our results provide strong evidence for audience-dependent human-directed visual orienting behaviour in a species that was domesticated primarily for production, and show similarities with the referential and intentional communicative behaviour exhibited by domestic companion animals such as dogs and horses. This indicates that domestication has a much broader impact on heterospecific communication than previously believed. © 2016 The Author(s).

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

Santos-Villalobos, Hector J; Barstow, Del R; Karakaya, Mahmut

Iris recognition has been proven to be an accurate and reliable biometric. However, the recognition of non-ideal iris images such as off angle images is still an unsolved problem. We propose a new biometric targeted eye model and a method to reconstruct the off-axis eye to its frontal view allowing for recognition using existing methods and algorithms. This allows for existing enterprise level algorithms and approaches to be largely unmodified by using our work as a pre-processor to improve performance. In addition, we describe the `Limbus effect' and its importance for an accurate segmentation of off-axis irides. Our method usesmore » an anatomically accurate human eye model and ray-tracing techniques to compute a transformation function, which reconstructs the iris to its frontal, non-refracted state. Then, the same eye model is used to render a frontal view of the reconstructed iris. The proposed method is fully described and results from synthetic data are shown to establish an upper limit on performance improvement and establish the importance of the proposed approach over traditional linear elliptical unwrapping methods. Our results with synthetic data demonstrate the ability to perform an accurate iris recognition with an image taken as much as 70 degrees off-axis.« less

Gaps in Current Knowledge and Priorities for Future Research in Dry Eye.

PubMed

Saldanha, Ian J; Dickersin, Kay; Hutfless, Susan T; Akpek, Esen K

2017-12-01

Dry eye, a common yet underrecognized and evolving field, has few recommended treatment algorithms, mostly based on expert consensus rather than robust research evidence. There are high costs associated with managing dry eye and conducting research to identify effective and safe long-term treatments. To support evidence-based management of dry eye, our purpose was to identify and prioritize important clinical research questions for future clinical research. We translated recommendations from the American Academy of Ophthalmology's 2013 Preferred Practice Patterns for dry eye into answerable clinical research questions about treatment effectiveness. Clinicians around the world who manage patients with dry eye rated each question's importance from 0 (not important) to 10 (very important) using a 2-round online Delphi survey. We considered questions as "important" if ≥75% of respondents assigned a rating of 6 or more in round 2. We mapped the identified important clinical research questions to reliable systematic reviews published up to March 2016. Seventy-five clinicians from at least 21 countries completed both Delphi rounds. Among the 58 questions, 24 met our definition of "important": 9/24 and 7/24 addressed topical and systemic treatments, respectively. All 4 questions with the highest 25th percentiles addressed topical treatments. Although 6/24 "important" questions were associated with 4 existing reliable systematic reviews, none of these reviews came to a definitive conclusion about treatment effectiveness. We identified gaps pertaining to treatment options for dry eye. Future clinical research on the management of dry eye should strongly consider these prioritized questions.

Entracking as a Brain Stem Code for Pitch: The Butte Hypothesis.

PubMed

Joris, Philip X

2016-01-01

The basic nature of pitch is much debated. A robust code for pitch exists in the auditory nerve in the form of an across-fiber pooled interspike interval (ISI) distribution, which resembles the stimulus autocorrelation. An unsolved question is how this representation can be "read out" by the brain. A new view is proposed in which a known brain-stem property plays a key role in the coding of periodicity, which I refer to as "entracking", a contraction of "entrained phase-locking". It is proposed that a scalar rather than vector code of periodicity exists by virtue of coincidence detectors that code the dominant ISI directly into spike rate through entracking. Perfect entracking means that a neuron fires one spike per stimulus-waveform repetition period, so that firing rate equals the repetition frequency. Key properties are invariance with SPL and generalization across stimuli. The main limitation in this code is the upper limit of firing (~ 500 Hz). It is proposed that entracking provides a periodicity tag which is superimposed on a tonotopic analysis: at low SPLs and fundamental frequencies > 500 Hz, a spectral or place mechanism codes for pitch. With increasing SPL the place code degrades but entracking improves and first occurs in neurons with low thresholds for the spectral components present. The prediction is that populations of entracking neurons, extended across characteristic frequency, form plateaus ("buttes") of firing rate tied to periodicity.

RADIO-WEAK BL LAC OBJECTS IN THE FERMI ERA

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

Massaro, F.; Marchesini, E. J.; D’Abrusco, R.

2017-01-10

The existence of “radio-weak BL Lac objects” (RWBLs) has been an open question, and has remained unsolved since the discovery that quasars could be radio-quiet or radio-loud. Recently, several groups identified RWBL candidates, mostly found while searching for low-energy counterparts of the unidentified or unassociated gamma-ray sources listed in the Fermi catalogs. Confirming RWBLs is a challenging task since they could be confused with white dwarfs (WDs) or weak emission line quasars (WELQs) when there are not sufficient data to precisely draw their broadband spectral energy distribution, and their classification is mainly based on a featureless optical spectra. Motivated bymore » the recent discovery that Fermi BL Lacs appear to have very peculiar mid-IR emission, we show that it is possible to distinguish between WDs, WELQs, and BL Lacs using the [3.4]–[4.6]–[12] μ m color–color plot built using the WISE magnitudes when the optical spectrum is available. On the basis of this analysis, we identify WISE J064459.38+603131 and WISE J141046.00+740511.2 as the first two genuine RWBLs, both potentially associated with Fermi sources. Finally, to strengthen our identification of these objects as true RWBLs, we present multifrequency observations for these two candidates to show that their spectral behavior is indeed consistent with that of the BL Lac population.« less

Biomarkers in Pediatric Community-Acquired Pneumonia.

PubMed

Principi, Nicola; Esposito, Susanna

2017-02-19

Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended.

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

PubMed

Kotlan, Beatrix; Plotar, Vanda; Eles, Klara; Horvath, Szabolcs; Balatoni, Timea; Csuka, Orsolya; Újhelyi, Mihaly; Sávolt, Ákos; Szollar, Andras; Vamosi-Nagy, Istvan; Toth, Laszlo; Farkas, Emil; Toth, Jozsef; Kasler, Miklos; Liszkay, Gabriella

2018-03-01

The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized. We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology. We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics.

Colloquium: Toward living matter with colloidal particles

NASA Astrophysics Data System (ADS)

Zeravcic, Zorana; Manoharan, Vinothan N.; Brenner, Michael P.

2017-07-01

A fundamental unsolved problem is to understand the differences between inanimate matter and living matter. Although this question might be framed as philosophical, there are many fundamental and practical reasons to pursue the development of synthetic materials with the properties of living ones. There are three fundamental properties of living materials that we seek to reproduce: The ability to spontaneously assemble complex structures, the ability to self-replicate, and the ability to perform complex and coordinated reactions that enable transformations impossible to realize if a single structure acted alone. The conditions that are required for a synthetic material to have these properties are currently unknown. This Colloquium examines whether these phenomena could emerge by programming interactions between colloidal particles, an approach that bootstraps off of recent advances in DNA nanotechnology and in the mathematics of sphere packings. The argument is made that the essential properties of living matter could emerge from colloidal interactions that are specific—so that each particle can be programmed to bind or not bind to any other particle—and also time dependent—so that the binding strength between two particles could increase or decrease in time at a controlled rate. There is a small regime of interaction parameters that gives rise to colloidal particles with lifelike properties, including self-assembly, self-replication, and metabolism. The parameter range for these phenomena can be identified using a combinatorial search over the set of known sphere packings.

Radio-weak BL Lac Objects in the Fermi Era

NASA Astrophysics Data System (ADS)

Massaro, F.; Marchesini, E. J.; D'Abrusco, R.; Masetti, N.; Andruchow, I.; Smith, Howard A.

2017-01-01

The existence of “radio-weak BL Lac objects” (RWBLs) has been an open question, and has remained unsolved since the discovery that quasars could be radio-quiet or radio-loud. Recently, several groups identified RWBL candidates, mostly found while searching for low-energy counterparts of the unidentified or unassociated gamma-ray sources listed in the Fermi catalogs. Confirming RWBLs is a challenging task since they could be confused with white dwarfs (WDs) or weak emission line quasars (WELQs) when there are not sufficient data to precisely draw their broadband spectral energy distribution, and their classification is mainly based on a featureless optical spectra. Motivated by the recent discovery that Fermi BL Lacs appear to have very peculiar mid-IR emission, we show that it is possible to distinguish between WDs, WELQs, and BL Lacs using the [3.4]-[4.6]-[12] μm color-color plot built using the WISE magnitudes when the optical spectrum is available. On the basis of this analysis, we identify WISE J064459.38+603131 and WISE J141046.00+740511.2 as the first two genuine RWBLs, both potentially associated with Fermi sources. Finally, to strengthen our identification of these objects as true RWBLs, we present multifrequency observations for these two candidates to show that their spectral behavior is indeed consistent with that of the BL Lac population.

The character of sleep disturbances produced by multiple administrations of atropine the antagonist of brain muscarinic cholinergic system.

PubMed

Maglakelidze, N T; Chkhartishvili, E V; Mchedlidze, O M; Dzadzamiia, Sh Sh; Nachkebiia, N G

2012-03-01

Modification of brain muscarinic cholinergic system normal functioning can be considered as an appropriate strategy for the study of its role in sleep-wakefulness cycle basic mechanisms in general and in the course/maintenance of PS in particular. For this aim systemic application of muscarinic cholinoreceptors antagonists is significant because it gives possibility to modify functioning all of known five sub-types of muscarinic cholinoreceptors and to study the character of sleep disturbances in these conditions. Problem is very topical because the question about the intimate aspects of BMChS involvement in PS maintaining mechanisms still remains unsolved. In cats Atropine systemic administration was made once daily at 10:00 a.m. and continuous EEG registration of sleep-wakefulness cycle ultradian structure, lasting for 10 hour daily, was started immediately. In sum each animal received anti-muscarinic drugs for 12 times. Thereafter drug administrations were ceased and EEG registration of sleep-wakefulness cycle ultradian structure was continued during 10 consecutive days. On the basis of results obtained in these conditions we can conclude that brain muscarinic cholinergic system normal functioning is significant for basic mechanisms of sleep-wakefulness cycle. During wakefulness, at the level of neocortex and hippocampus, MChS supports only EEG activation, while it is one of the main factors in PS triggering and maintaining mechanisms.

THE NEWER PENICILLINS

PubMed Central

Simon, Harold J.

1962-01-01

The newer penicillins give high promise of overcoming some of the few disadvantages of penicillin-G. They fall into three groups: The alpha-phenoxy-penicillins; the penicillinase resistant penicillins; and the penicillins with enhanced activity against gram-negative bacteria. The newer alpha-phenoxy-penicillins offer little over alpha-phenoxy methyl penicillin (penicillin-V). As the length of the side chain is increased, absorption and attainable serum concentration is also increased, but these are questionable benefits and probably not significant for therapeusis. The penicillinase-resistant penicillins have once more brought almost all severe staphylococcal infections within therapeutic range. One of them, methicillin, must be administered parenterally. It is the agent of choice for the treatment of severe, penicillin-G resistant staphylococcal infections, and this is its only clinical indication. Another, oxacillin, which may be administered orally, is partially resistant to gastric acid degradation, but must be given on an empty stomach. It is most useful as prolonged therapy following methicillin, in the treatment of mixed hemolytic streptococcal-penicillin-G resistant staphylococcal infections, and as primary therapy for moderately severe penicillin-G resistant staphylococcal infections. The third group is still mostly in the experimental stage, but some strains of Proteus, E. coli, Salmonella and Shigella are highly vulnerable to their action. Toxic and allergic reactions to the newer penicillins, and crossed allergic reactions with penicillin-G, present unsolved problems. PMID:13913108

Redox control of plant growth and development.

PubMed

Kocsy, Gábor; Tari, Irma; Vanková, Radomíra; Zechmann, Bernd; Gulyás, Zsolt; Poór, Péter; Galiba, Gábor

2013-10-01

Redox changes determined by genetic and environmental factors display well-organized interactions in the control of plant growth and development. Diurnal and seasonal changes in the environmental conditions are important for the normal course of these physiological processes and, similarly to their mild irregular alterations, for stress adaptation. However, fast or large-scale environmental changes may lead to damage or death of sensitive plants. The spatial and temporal redox changes influence growth and development due to the reprogramming of metabolism. In this process reactive oxygen and nitrogen species and antioxidants are involved as components of signalling networks. The control of growth, development and flowering by reactive oxygen and nitrogen species and antioxidants in interaction with hormones at organ, tissue, cellular and subcellular level will be discussed in the present review. Unsolved problems of the field, among others the need for identification of new components and interactions in the redox regulatory network at various organization levels using systems biology approaches will be also indicated. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Learned helplessness in chess players: the importance of task similarity and the role of skill.

PubMed

Gobet, F R

1992-01-01

The effects of noncontingency between subjects' responses and outcomes were examined with respect to treatment-and-posttest similarity and skill in the task. The experimental design consisted of three groups. The first group had to solve chess problems with objective solutions and received veridical feedback; each member of the second group faced problems with no objective solutions, and received the same feedback as the member of the first group he was yoked with, but without any control on it; the control group received a waiting task. It was found at the end of the experiment that the group with unsolvable problems was more depressed than the two other groups. The mid-strength players were the most sensitive to the manipulation, and the weakest players showed little effect of learned helplessness. It was also found that the effects were proportional to the degree of similarity between the treatment and the posttest. The results limit the domain of applicability of the learned-helplessness model.

Combined pituitary hormone deficiency: current and future status.

PubMed

Castinetti, F; Reynaud, R; Quentien, M-H; Jullien, N; Marquant, E; Rochette, C; Herman, J-P; Saveanu, A; Barlier, A; Enjalbert, A; Brue, T

2015-01-01

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

Pigmentary and photonic coloration mechanisms reveal taxonomic relationships of the Cattlehearts (Lepidoptera: Papilionidae: Parides)

PubMed Central

2014-01-01

Background The colorful wing patterns of butterflies, a prime example of biodiversity, can change dramatically within closely related species. Wing pattern diversity is specifically present among papilionid butterflies. Whether a correlation between color and the evolution of these butterflies exists so far remained unsolved. Results We here investigate the Cattlehearts, Parides, a small Neotropical genus of papilionid butterflies with 36 members, the wings of which are marked by distinctly colored patches. By applying various physical techniques, we investigate the coloration toolkit of the wing scales. The wing scales contain two different, wavelength-selective absorbing pigments, causing pigmentary colorations. Scale ridges with multilayered lamellae, lumen multilayers or gyroid photonic crystals in the scale lumen create structural colors that are variously combined with these pigmentary colors. Conclusions The pigmentary and structural traits strongly correlate with the taxonomical distribution of Parides species. The experimental findings add crucial insight into the evolution of butterfly wing scales and show the importance of morphological parameter mapping for butterfly phylogenetics. PMID:25064167

Emergent loop-nodal s(±)-wave superconductivity in CeCu(2)Si(2): similarities to the iron-based superconductors.

PubMed

Ikeda, Hiroaki; Suzuki, Michi-To; Arita, Ryotaro

2015-04-10

Heavy-fermion superconductors are prime candidates for novel electron-pairing states due to the spin-orbital coupled degrees of freedom and electron correlations. Superconductivity in CeCu_{2}Si_{2} discovered in 1979, which is a prototype of unconventional (non-BCS) superconductors in strongly correlated electron systems, still remains unsolved. Here we provide the first report of superconductivity based on the advanced first-principles theoretical approach. We find that the promising candidate is an s_{±}-wave state with loop-shaped nodes on the Fermi surface, different from the widely expected line-nodal d-wave state. The dominant pairing glue is magnetic but high-rank octupole fluctuations. This system shares the importance of multiorbital degrees of freedom with the iron-based superconductors. Our findings reveal not only the long-standing puzzle in this material, but also urge us to reconsider the pairing states and mechanisms in all heavy-fermion superconductors.

Quality of herbal medicines: challenges and solutions.

PubMed

Zhang, Junhua; Wider, Barbara; Shang, Hongcai; Li, Xuemei; Ernst, Edzard

2012-01-01

The popularity of herbal medicines has risen worldwide. This increase in usage renders safety issues important. Many adverse events of herbal medicines can be attributed to the poor quality of the raw materials or the finished products. Different types of herbal medicines are associated with different problems. Quality issues of herbal medicines can be classified into two categories: external and internal. In this review, external issues including contamination (e.g. toxic metals, pesticides residues and microbes), adulteration and misidentification are detailed. Complexity and non-uniformity of the ingredients in herbal medicines are the internal issues affecting the quality of herbal medicines. Solutions to the raised problems are discussed. The rigorous implementation of Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practices (GMP) would undoubtedly reduce the risk of external issues. Through the use of modern analytical methods and pharmaceutical techniques, previously unsolved internal issues have become solvable. Standard herbal products can be manufactured from the standard herbal extracts. Copyright © 2011 Elsevier Ltd. All rights reserved.

Unsolved problems in observational astronomy. II. Focus on rapid response - mining the sky with ``thinking" telescopes

NASA Astrophysics Data System (ADS)

Vestrand, W. T.; Theiler, J.; Woznia, P. R.

2004-10-01

The existence of rapidly slewing robotic telescopes and fast alert distribution via the Internet is revolutionizing our capability to study the physics of fast astrophysical transients. But the salient challenge that optical time domain surveys must conquer is mining the torrent of data to recognize important transients in a scene full of normal variations. Humans simply do not have the attention span, memory, or reaction time required to recognize fast transients and rapidly respond. Autonomous robotic instrumentation with the ability to extract pertinent information from the data stream in real time will therefore be essential for recognizing transients and commanding rapid follow-up observations while the ephemeral behavior is still present. Here we discuss how the development and integration of three technologies: (1) robotic telescope networks; (2) machine learning; and (3) advanced database technology, can enable the construction of smart robotic telescopes, which we loosely call ``thinking'' telescopes, capable of mining the sky in real time.

Black-Hole Binaries, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

Kelly, Bernard J.; Centrella, Joan; Baker, John G.; Kelly, Bernard J.; vanMeter, James R.

2010-01-01

Understanding the predictions of general relativity for the dynamical interactions of two black holes has been a long-standing unsolved problem in theoretical physics. Black-hole mergers are monumental astrophysical events ' releasing tremendous amounts of energy in the form of gravitational radiation ' and are key sources for both ground- and spacebased gravitational wave detectors. The black-hole merger dynamics and the resulting gravitational waveforms can only he calculated through numerical simulations of Einstein's equations of general relativity. For many years, numerical relativists attempting to model these mergers encountered a host of problems, causing their codes to crash after just a fraction of a binary orbit cnuld be simulated. Recently ' however, a series of dramatic advances in numerical relativity has ' for the first time, allowed stable / robust black hole merger simulations. We chronicle this remarkable progress in the rapidly maturing field of numerical relativity, and the new understanding of black-hole binary dynamics that is emerging. We also discuss important applications of these fundamental physics results to astrophysics, to gravitationalwave astronomy, and in other areas.

A machine vision system for micro-EDM based on linux

NASA Astrophysics Data System (ADS)

Guo, Rui; Zhao, Wansheng; Li, Gang; Li, Zhiyong; Zhang, Yong

2006-11-01

Due to the high precision and good surface quality that it can give, Electrical Discharge Machining (EDM) is potentially an important process for the fabrication of micro-tools and micro-components. However, a number of issues remain unsolved before micro-EDM becomes a reliable process with repeatable results. To deal with the difficulties in micro electrodes on-line fabrication and tool wear compensation, a micro-EDM machine vision system is developed with a Charge Coupled Device (CCD) camera, with an optical resolution of 1.61μm and an overall magnification of 113~729. Based on the Linux operating system, an image capturing program is developed with the V4L2 API, and an image processing program is exploited by using OpenCV. The contour of micro electrodes can be extracted by means of the Canny edge detector. Through the system calibration, the micro electrodes diameter can be measured on-line. Experiments have been carried out to prove its performance, and the reasons of measurement error are also analyzed.

Restaurant oil and grease management in Hong Kong.

PubMed

Yau, Yiu-Hung; Rudolph, Victor; Lo, Cat Chui-Man; Wu, Kam-Chau

2018-06-24

Oil and grease (O&G) in wastewater can be considered as two parts or proportion contained in emulsion which exceeded O&G standard. Most of oil becomes emulsified with water when they pass through grease trap and discharged in the effluents. Thus, it may indicate that either treatment of grease traps or standards for O&G content stipulated in technical memorandum of Water Pollution Control Ordinance (WPCO) do not reflect the actual situation. Existing grease traps should be upgraded to meet the requirements of WPCO. Alternative technologies need to be developed to tackle this unsolved problem. Good management and practices are also important to ensure proper collection and waste recycling rather than just disposing effluent into drains. Collected O&G content can be recycled as valuable products such as biofuel, flotation agent, or other derivatives. This approach not only protects the environment by improving water quality, it also encourages large flow restaurant operators to recycle oil and grease content towards cleaner production.

Neuroendocrine tumors and fibrosis: An unsolved mystery?

PubMed

Laskaratos, Faidon-Marios; Rombouts, Krista; Caplin, Martyn; Toumpanakis, Christos; Thirlwell, Christina; Mandair, Dalvinder

2017-12-15

Neuroendocrine tumors are a heterogeneous group of slow-growing neoplasms arising mainly from the enterochromaffin cells of the digestive and respiratory tract. Although they are relatively rare, their incidence is rising. It has long been observed that they often are associated with the development of fibrosis, both local and distant. Fibrotic complications, such as carcinoid heart disease and mesenteric desmoplasia, may lead to considerable morbidity or even affect prognosis. The elucidation of the pathophysiology of fibrosis would be of critical importance for the development of targeted therapeutic strategies. In this article, the authors review the available evidence regarding the biological basis of fibrosis in neuroendocrine tumors. They explore the role of the tumor microenvironment and the interplay between tumor cells and fibroblasts as a key factor in fibrogenesis and tumor development/progression. They also review the role of serotonin, growth factors, and other peptides in the development of carcinoid-related fibrotic reactions. Cancer 2017;123:4770-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

Directional, stabilizing, and disruptive trait selection as alternative mechanisms for plant community assembly.

PubMed

Rolhauser, Andrés G; Pucheta, Eduardo

2017-03-01

How plant functional traits (e.g., seed mass) drive species abundance within communities remains an unsolved question. Borrowing concepts from natural selection theory, we propose that trait-abundance relationships can generally correspond to one of three modes of trait selection: directional (a rectilinear relationship, where species at one end of a trait axis are most abundant), stabilizing (an n-shaped relationship), and disruptive (a u-shaped relationship). Stabilizing selection (i.e., the functional convergence of abundant species) would result from positive density-dependent interactions (e.g., facilitation) or due to generalized trade-offs in resource acquisition/use, while disruptive selection (i.e., the divergence of abundant species) would result from negative density-dependent interactions (e.g., competition) or due to environmental heterogeneity. These selection modes can be interpreted as proxies for community-level trait-fitness functions, which establish the degree to which traits are truly "functional". We searched for selection modes in a desert annual-plant community in Argentina (which was divided into winter and summer guilds) to test the hypothesis that the relative importance of disruptive mechanisms (competition, disturbances) decreases with the increase of abiotic stress, a stabilizing agent. Average density was analyzed as a function of eight traits generally linked to resource acquisition and competitive ability (maximum plant height, leaf size, specific leaf area, specific root length), resource retention and stress tolerance (leaf dissection, leaf dry matter content, specific root volume), and regeneration (seed mass) using multiple quadratic-regression models. Trait selection was stabilizing and/or directional when the environment was harshest (winter) and disruptive and/or directional when conditions were milder (summer). Selection patterns differed between guilds for two important traits: plant height and seed mass. These results suggest that abiotic stress may drive within-community functional convergence independently of the trait considered, opposing the view that some traits may be inherently convergent while others divergent. Our quadratic model-based approach provides standardized metrics of both linear and nonlinear selection that may allow simple comparisons among communities subjected to contrasting environmental conditions. These concepts, rooted in natural selection theory, may clarify the functional link between traits and species abundance, and thus help untangle the contributions of deterministic and stochastic processes on community assembly. © 2017 by the Ecological Society of America.

Global SO(3) x SO(3) x U(1) symmetry of the Hubbard model on bipartite lattices

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

Carmelo, J.M.P., E-mail: carmelo@fisica.uminho.p; Ostlund, Stellan; Sampaio, M.J.

2010-08-15

In this paper the global symmetry of the Hubbard model on a bipartite lattice is found to be larger than SO(4). The model is one of the most studied many-particle quantum problems, yet except in one dimension it has no exact solution, so that there remain many open questions about its properties. Symmetry plays an important role in physics and often can be used to extract useful information on unsolved non-perturbative quantum problems. Specifically, here it is found that for on-site interaction U {ne} 0 the local SU(2) x SU(2) x U(1) gauge symmetry of the Hubbard model on amore » bipartite lattice with N{sub a}{sup D} sites and vanishing transfer integral t = 0 can be lifted to a global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry in the presence of the kinetic-energy hopping term of the Hamiltonian with t > 0. (Examples of a bipartite lattice are the D-dimensional cubic lattices of lattice constant a and edge length L = N{sub a}a for which D = 1, 2, 3,... in the number N{sub a}{sup D} of sites.) The generator of the new found hidden independent charge global U(1) symmetry, which is not related to the ordinary U(1) gauge subgroup of electromagnetism, is one half the rotated-electron number of singly occupied sites operator. Although addition of chemical-potential and magnetic-field operator terms to the model Hamiltonian lowers its symmetry, such terms commute with it. Therefore, its 4{sup N}{sub a}{sup D} energy eigenstates refer to representations of the new found global [SU(2) x SU(2) x U(1)]/Z{sub 2}{sup 2} = SO(3) x SO(3) x U(1) symmetry. Consistently, we find that for the Hubbard model on a bipartite lattice the number of independent representations of the group SO(3) x SO(3) x U(1) equals the Hilbert-space dimension 4{sup N}{sub a}{sup D}. It is confirmed elsewhere that the new found symmetry has important physical consequences.« less

Workshop on the Growth of Continental Crust

NASA Technical Reports Server (NTRS)

Ashwal, Lewis D. (Editor)

1988-01-01

Constraints and observations were discussed on a fundamental unsolved problem of global scale relating to the growth of planetary crusts. All of the terrestrial planets were considered, but emphasis was placed on the Earth's continental crust. The title of each session is: (1) Extraterrestrial crustal growth and destruction; (2) Constraints for observations and measurements of terrestrial rocks; (3) Models of crustal growth and destruction; and (4) Process of crustal growth and destruction.

[Inflammatory granulomas in the pathology of the nervous system. General remarks].

PubMed

Tommasi, M

1976-01-01

The "gliogenic" participation in the edification of granulomas may produce peculiar morphological features especially in the central nervous system, and perhaps more than elsewhere, pseudotumoral features. Moreover, the concept of "granuloma" is perhaps not as well defined as in the other tissues. There are also some still unsolved problems concerning the histogenesis of the cells of the "granuloma". Some examples taken among the different etiologies illustrate these notions.

Multi-functional Extreme Environment Surfaces: Nanotribology for Air and Space

DTIC Science & Technology

2010-09-14

SPANNING THE PHYSICAL SCALES OF MODERN TRIBOLOGY ( QCM ) (STM) Fundamental Challenges and Unsolved Issues How do adsorbed and tribo-generated films impact...Space Applications Satellite bearings, InfraRed sensor mechanisms Jet engine bearings 2 mm NCD MCD 300 mm Thrust II: Cryotribology and...Nanocrystalline Diamond for Space Applications Satellite bearings, InfraRed sensor mechanisms Jet engine bearings 2 mm NCD MCD 300 mm Five Years ago: Three

Kinematic and Dynamic Analysis of High-Speed Intermittent-Motion Mechanisms.

DTIC Science & Technology

1984-01-16

intermittent-motion mechanisms which -"have potential application to the high-speed automatic weapon system , and an investigation on the workspace of a robotic...manipulator system . The problems of this investigation belong to a selected group of unsolved or partially solved problems which are relevant and...design of high-speed machinery and automated manufacturing systems . Accession For IiTIS GRA&I DTIC TAB Unamounced 0 Justificatio By_, Distribut ion

Experimental study of nuclear fusion reactions in muonic molecular systems

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

Bogdanova, L. N., E-mail: ludmila@itep.ru

2013-03-15

Since the pioneering discovery of the muon catalysis by Alvarez [L. W. Alvarez, K. Brander, F. S. Crawford, et al., Phys. Rev. 105, 1127 (1957)], considerable efforts were aimed at observation of various fusion processes. Results of these studies facilitated understanding the properties of lightest nuclei and dynamics of low-energy fusion reactions. There still remain unsolved theoretical and experimental problems, especially in case of pt fusion.

Looking back at 'looking back': operationalising referential gaze for dingoes in an unsolvable task.

PubMed

Smith, Bradley Philip; Litchfield, Carla Anita

2013-11-01

This paper examined the performance of dingoes (Canis dingo) on the rope-pulling task, previously used by Miklósi et al. (Curr Biol 13:763-766, 2003) to highlight a key distinction in the problem-solving behaviour of wolves compared to dogs when in the company of humans. That is, when dogs were confronted with an unsolvable task, following a solvable version of the task they looked back or gazed at the human, whereas, wolves did not. We replicated the rope-pulling task using 12 sanctuary-housed dingoes and used the Miklósi et al. (Curr Biol 13:763-766, 2003) definition of looking back behaviour to analyse the data. However, at least three different types of look backs were observed in our study. We, then developed a more accurate operational definition of looking back behaviour that was task specific and reanalysed the data. We found that the operational definition employed greatly influences the results, with vague definitions potentially overestimating the prevalence of looking back behaviour. Thus, caution must be taken when interpreting the results of studies utilising looking back as behaviour linked to assistance seeking during problem solving. We present a more stringent definition and make suggestions for future research.

Comprehensive analysis of Stargardt macular dystrophy patients reveals new genotype-phenotype correlations and unexpected diagnostic revisions

PubMed Central

Zaneveld, Jacques; Siddiqui, Sorath; Li, Huajin; Wang, Xia; Wang, Hui; Wang, Keqing; Li, Hui; Ren, Huanan; Lopez, Irma; Dorfman, Allison; Khan, Ayesha; Wang, Feng; Salvo, Jason; Gelowani, Violet; Li, Yumei; Sui, Ruifang; Koenekoop, Robert; Chen, Rui

2014-01-01

Purpose Stargardt macular dystrophy (STGD) results in early central vision loss. We sought to explain the genetic cause of STGD in a cohort of 88 patients from three different cultural backgrounds. Methods Next Generation Sequencing using a novel capture panel was used to search for disease causing mutations. Unsolved patients were clinically re-examined and tested for copy number variations (CNVs) as well as intronic mutations. Results We determined the cause of disease in 67% of our patients. Our analysis identified 35 novel ABCA4 alleles. Eleven patients had mutations in genes not previously reported to cause STGD. Finally, 45% of our unsolved patients had single deleterious mutations in ABCA4, a recessive disease gene. No likely pathogenic CNVs were identified. Conclusions This study expands our knowledge of STGD by identifying dozens of novel STGD causing alleles. The frequency of patients with single mutations in ABCA4 is higher than controls, indicating these mutations contribute to disease. Eleven patients were explained by mutations outside ABCA4 underlining the need to genotype all retinal disease genes to maximize genetic diagnostic rates. Few ABCA4 mutations were observed in our French Canadian patients. This population may contain an unidentified founder mutation. Our results indicate that CNVs are unlikely to be a major cause of STGD. PMID:25474345

Effects of microsolvation on a SN2 reaction: indirect atomistic dynamics and weakened suppression of reactivity.

PubMed

Yang, Li; Liu, Xu; Zhang, Jiaxu; Xie, Jing

2017-04-12

Systematic studies of microsolvation in the gas phase have enriched our knowledge of solvent effects. Here, the dynamics of a prototype S N 2 reaction of a hydrated fluoride ion with methyl iodide is uncovered employing direct dynamics simulations that show strikingly distinct features from those determined for an unsolvated system. An indirect scattering is found to prevail, which occurs dominantly by forming hydrated F - (H 2 O)-HCH 2 I and F - (H 2 O)-CH 3 I pre-reaction complexes at low energies, but proceeds through their water-free counterparts at higher energies. This finding is in strong contrast to a general evolution from indirect to direct dynamics with enhancing energy for the unsolvated substitution reactions, and this discrepancy is understood by the substantial steric hindrance introduced by a water molecule. As established in experiments, solvation suppresses the reactivity, whereas we find that this depression is remarkably frustrated upon raising the energy given that collision-induced dehydration essentially diminishes the water block for reactive collisions. The present study sheds light on how solute-solvent interactions affect the underlying dynamics at a deeper atomic level, thereby promoting our understanding of the fundamental solvent effects on chemical reactions in solution.

Periodontal Healing Distally to Second Mandibular Molar After Third Molar Coronectomy.

PubMed

Vignudelli, Elisabetta; Monaco, Giuseppe; Gatto, Maria Rosaria Antonella; Franco, Simonetta; Marchetti, Claudio; Corinaldesi, Giuseppe

2017-01-01

Coronectomy of mandibular third molars is a procedure that still raises a number of questions. The aim of the present study was to answer one unsolved question: the periodontal healing distal to the mandibular second molar after third molar coronectomy. A prospective cohort study was performed of 30 patients treated at the Unit of Oral and Maxillofacial Surgery of the Department of Biomedical and Neuromotor Science of the University of Bologna. The predictor variables were the probing pocket depth (PPD), the distance between the marginal crest (MC) and the bottom of the osseous defect (BOD), and the distance between the cementum enamel junction (CEJ) and the BOD. These clinical indexes were recorded on 3 points of the distal surface of second molar: the distobuccal (DB), distomedial (DM), and distolingual (DL) sites. The other variables evaluated included root migration and postoperative complications. The Wilcoxon test for paired data and Kendall's tau-b correlation coefficient was used to evaluate all variables. The significance level was set at P = .05. The cohort was composed of 30 patients with 34 high-risk mandibular third molars (9 men and 21 women), with a mean age of 28 ± 7 years. At 9 months, a statistically significant reduction in the PPD of 2 ± 3, 1 ± 2, and 2 ± 2 mm and a statistically significant reduction in the MC-BOD distance of 4 ± 4, 4 ± 4, and 4 ± 5 mm for the DB, DM, and DL sites, respectively, was observed (P = .001). Also, the intraoperative CEJ-BOD distance showed a statistically significant reduction for the DB, DM, and DL sites. After coronectomy, restoration of a clinical healthy periodontium distal to the second molar was observed. However, further studies are necessary to confirm these preliminary clinical results and to compare periodontal healing between coronectomy and complete extraction. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Should we ask our Children about Sex, Drugs and Rock & Roll?: Potentially Harmful Effects of Asking Questions About Risky Behaviors

PubMed Central

Fitzsimons, Gavan J.; Moore, Sarah G.

2009-01-01

Research shows that asking questions can fundamentally change behavior. We review literature on this question-behavior effect, which demonstrates that asking questions changes both normal and risky behaviors. We discuss potential explanations for the effect and review recent findings that reveal interesting moderators of the influence of questions on behavior. We then highlight the potential impact of the question-behavior effect in an important public health context: screening adolescents for risky behavior. While medical guidelines emphasize the importance of asking adolescents questions about substance (drug, alcohol) use and sexual behaviors, research on the question-behavior effect suggests that asking adolescents about risky behaviors has the potential to increase the frequency with which they engage in these behaviors. We argue that the act of screening or measuring risky behavior is potentially counterproductive. We emphasize the importance of interventions beyond screening, and suggest ways in which screening can be carried out to minimize its impact. In short, asking questions about behaviors can change behavior, and asking questions about risky behaviors may itself be a risky undertaking. PMID:23750098

Magnetic Resonance Imaging Quantification of Liver Iron

PubMed Central

Sirlin, Claude B.; Reeder, Scott B.

2011-01-01

Iron overload is the histological hallmark of genetic hemochromatosis and transfusional hemosiderosis but also may occur in chronic hepatopathies. This article provides an overview of iron deposition and diseases where liver iron overload is clinically relevant. Next, this article reviews why quantitative non-invasive biomarkers of liver iron would be beneficial. Finally, we describe current state of the art methods for quantifying iron with MRI and review remaining challenges and unsolved problems, PMID:21094445

Social work role in developing and managing employee assistance programs in health care settings.

PubMed

Foster, Z; Hirsch, S; Zaske, K

1991-01-01

The hospital setting presents special needs for an Employee Assistance Program and special complications for sponsorship, development, and maintenance. What has been learned, how certain problems can be solved or avoided, how responsibility and accountability can be negotiated are presented by a team that has successfully established such a program at a large metropolitan medical center. In addition to successes, some unsolved problems are identified for further study.

Multi-functional Extreme Environment Surfaces: Nanotribology for Air and Space

DTIC Science & Technology

2010-09-14

TRIBOLOGY ( QCM ) (STM) Fundamental Challenges and Unsolved Issues How do adsorbed and tribo-generated films impact friction and wear? How is heat dissipated...InfraRed sensor mechanisms Jet engine bearings 2 mm NCD MCD 300 mm Thrust II: Cryotribology and Nanocrystalline Diamond for Space Applications...Satellite bearings, InfraRed sensor mechanisms Jet engine bearings 2 mm NCD MCD 300 mm Five Years ago: Three publications in the area of vacuum

Assessing the Perceived Importance of Skin Cancer: How Question-Order Effects Are Influenced by Issue Involvement

ERIC Educational Resources Information Center

Rimal, Rajiv N.; Real, Kevin

2005-01-01

Question-order effects refer to systematic differences in responses that can be attributed to the manner in which questions assessing attitudes and cognitions are asked. This article hypothesized that question-order effects in assessing the perceived importance of skin cancer would be moderated by the extent to which people are involved with the…

Three critical questions for future research on lesbian relationships.

PubMed

Diamond, Lisa M

2017-01-02

In this article I discuss three questions that should be priorities for future research on lesbian love and relationships. The first question concerns the very definition of "lesbian relationship," given how many women may be engaged in same-sex relationships without identifying as lesbian. The second question concerns the potential influence of childhood neglect and abuse on adult women's same-sex relationships, a topic that has important implications for both psychological well-being and relationship functioning. The third question concerns the potential downsides of legal marriage for women's same-sex relationships, a topic that is particularly important in light of the newfound legal recognition of same-sex marriage in all 50 states. Although there are many understudied questions in the domain of women's same-sex relationships, research on these three questions has particularly strong potential to advance our understanding of lesbian love and relationships in important ways.

Research on injury prevention: topics for systematic review.

PubMed

Rivara, F P; Johansen, J M; Thompson, D C

2002-06-01

Duplication should be avoided in research and only effective intervention programs should be implemented. To arrive at a consensus among injury control investigators and practitioners on the most important research questions for systematic review in the area of injury prevention. Delphi survey. A total of 34 injury prevention experts were asked to submit questions for systematic review. These were then collated; experts then ranked these on importance and availability of research. Twenty one experts generated 79 questions. The prevention areas with the most number of questions generated were fires and burns, motor vehicle, and violence (other than intimate partner), and the least were other interventions (which included Safe Communities), and risk compensation. These were ranked by mean score. There was good agreement between the mean score and the proportion of experts rating questions as important or very important. Nine of the top 24 questions were rated as having some to a substantial amount of research available, and 15 as having little research available. The Delphi technique provided a useful means to develop consensus on injury prevention research needs and questions for systematic review.

Lessons learned from additional research analyses of unsolved clinical exome cases.

PubMed

Eldomery, Mohammad K; Coban-Akdemir, Zeynep; Harel, Tamar; Rosenfeld, Jill A; Gambin, Tomasz; Stray-Pedersen, Asbjørg; Küry, Sébastien; Mercier, Sandra; Lessel, Davor; Denecke, Jonas; Wiszniewski, Wojciech; Penney, Samantha; Liu, Pengfei; Bi, Weimin; Lalani, Seema R; Schaaf, Christian P; Wangler, Michael F; Bacino, Carlos A; Lewis, Richard Alan; Potocki, Lorraine; Graham, Brett H; Belmont, John W; Scaglia, Fernando; Orange, Jordan S; Jhangiani, Shalini N; Chiang, Theodore; Doddapaneni, Harsha; Hu, Jianhong; Muzny, Donna M; Xia, Fan; Beaudet, Arthur L; Boerwinkle, Eric; Eng, Christine M; Plon, Sharon E; Sutton, V Reid; Gibbs, Richard A; Posey, Jennifer E; Yang, Yaping; Lupski, James R

2017-03-21

Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts.

Identification of a novel oxidative stress induced cell death by Sorafenib and oleanolic acid in human hepatocellular carcinoma cells.

PubMed

Lange, Matthias; Abhari, Behnaz Ahangarian; Hinrichs, Tobias M; Fulda, Simone; Liese, Juliane

2016-10-15

The lack of effective chemotherapies in hepatocellular carcinoma (HCC) is still an unsolved problem and underlines the need for new strategies in liver cancer treatment. In this study, we present a novel approach to improve the efficacy of Sorafenib, today's only routinely used chemotherapeutic drug for HCC, in combination with triterpenoid oleanolic acid (OA). Our data show that cotreatment with subtoxic concentrations of Sorafenib and OA leads to highly synergistic induction of cell death. Importantly, Sorafenib/OA cotreatment triggers cell damage in a sustained manner and suppresses long-term clonogenic survival. Sorafenib/OA cotreatment induces DNA fragmentation and caspase-3/7 cleavage and the addition of the pan-caspase inhibitor zVAD.fmk shows the requirement of caspase activation for Sorafenib/OA-triggered cell death. Furthermore, Sorafenib/OA co-treatment stimulates a significant increase in reactive oxygen species (ROS) levels. Most importantly, the accumulation of intracellular ROS is required for cell death induction, since the addition of ROS scavengers (i.e. α-tocopherol, MnTBAP) that prevent the increase of intracellular ROS levels completely rescues cells from Sorafenib/OA-triggered cell death. In conclusion, OA represents a novel approach to increase the sensitivity of HCC cells to Sorafenib via oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Organic compounds in fluid inclusions of Archean quartz-Analogues of prebiotic chemistry on early Earth.

PubMed

Schreiber, Ulrich; Mayer, Christian; Schmitz, Oliver J; Rosendahl, Pia; Bronja, Amela; Greule, Markus; Keppler, Frank; Mulder, Ines; Sattler, Tobias; Schöler, Heinz F

2017-01-01

The origin of life is still an unsolved mystery in science. Hypothetically, prebiotic chemistry and the formation of protocells may have evolved in the hydrothermal environment of tectonic fault zones in the upper continental crust, an environment where sensitive molecules are protected against degradation induced e.g. by UV radiation. The composition of fluid inclusions in minerals such as quartz crystals which have grown in this environment during the Archean period might provide important information about the first organic molecules formed by hydrothermal synthesis. Here we present evidence for organic compounds which were preserved in fluid inclusions of Archean quartz minerals from Western Australia. We found a variety of organic compounds such as alkanes, halocarbons, alcohols and aldehydes which unambiguously show that simple and even more complex prebiotic organic molecules have been formed by hydrothermal processes. Stable-isotope analysis confirms that the methane found in the inclusions has most likely been formed from abiotic sources by hydrothermal chemistry. Obviously, the liquid phase in the continental Archean crust provided an interesting choice of functional organic molecules. We conclude that organic substances such as these could have made an important contribution to prebiotic chemistry which might eventually have led to the formation of living cells.

GPER-1/GPR30 a novel estrogen receptor sited in the cell membrane: therapeutic coupling to breast cancer.

PubMed

Molina, Luis; Figueroa, Carlos D; Bhoola, Kanti D; Ehrenfeld, Pamela

2017-08-01

Breast cancer is clinically classified as 'estrogen-positive' when at least 1% of cancer cells stain for the estrogen receptor alpha (ERα). However, recent research on both basic and clinical aspects of breast cancer suggests that GPER-1 (G protein-coupled estrogen receptor-1) may have an important role in breast cancer. Areas covered: This review provides a comprehensive and systematic literature search on GPER-1. We have focused on the role of GPER-1 in breast cancer and on resistance to endocrine therapy, an unsolved clinical issue still under discussion. Expert opinion: The discovery of GPER-1 as a novel estrogen receptor is unique and the signaling pathways activated by its stimulation, when compared to the classical nuclear ERα, indicate a potential role of GPER-1 in the genesis and mechanisms of drug resistance in breast cancer. Tumors expressing ERα represent the largest group of breast cancer patients indicating that more women eventually die from ERα-positive breast tumors than from other more malignant breast cancer subtypes such as HER2-positive and the triple negative groups. It is important to develop new strategies on endocrine therapy with regard to ERα and GPER-1 receptors to achieve innovative successful therapeutic tools.

Towards A Comprehensive Consideration of Epistemic Questions in Software System Safety

NASA Technical Reports Server (NTRS)

Holloway, C. M.; Johnson, Chris W.

2009-01-01

For any software system upon which lives depend, the most important question one can ask about it is, 'How do we know the system is safe?' Despite the critical importance of this question, no widely accepted, generally applicable answer exists. Instead, debate continues to rage over the question, with theorists and practitioners quarrelling with each other and amongst themselves. This paper suggests a possible way forward towards quelling the quarrels, based on refining the critical safety question into additional questions, which may be more likely to have answers on which a consensus can be reached.

What matters most? The content and concordance of patients' and providers' information priorities for contraceptive decision making.

PubMed

Donnelly, Kyla Z; Foster, Tina C; Thompson, Rachel

2014-09-01

The objective of this study was to identify women's and health care providers' information priorities for contraceptive decision making and counseling, respectively. Cross-sectional surveys were administered online to convenience samples of 417 women and 188 contraceptive care providers residing in the United States. Participants were provided with a list of 34 questions related to the features of contraceptive options and rated the importance of each. Participants also ranked the questions in descending order of importance. For both women and providers, we calculated the mean importance rating for each question and the proportion that ranked each question in their three most important questions. The average importance ratings given by women and providers were similar for 18 questions, but dissimilar for the remaining 16 questions. The question rated most important for women was "How does it work to prevent pregnancy?" whereas, for providers, "How often does a patient need to remember to use it?" and "How is it used?" were rated equally. The eight questions most frequently selected in the top three by women and/or providers were related to the safety of the method, mechanism of action, mode of use, side effects, typical- and perfect-use effectiveness, frequency of administration and when it begins to prevent pregnancy. Although we found considerable concordance between women's and provider's information priorities, the presence of some inconsistencies highlights the importance of patient-centered contraceptive counseling and, in particular, shared contraceptive decision making. This study provides insights into the information priorities of women for their contraceptive decision making and health care providers for contraceptive counseling. These insights are critical both to inform the development of decision support tools for implementation in contraceptive care and to guide the delivery of patient-centered care. Copyright © 2014 Elsevier Inc. All rights reserved.

Systems cell biology

PubMed Central

Mast, Fred D.; Ratushny, Alexander V.

2014-01-01

Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology. PMID:25225336

Unsolved Problems in Evolutionary Theory

DTIC Science & Technology

1967-01-01

finding the probability of survival of a single new mutant). Most natural populations probably satisfy these conditions , as is illustrated by the...Ykl) of small quantities adding to zero. Then under suitable conditions on the function f(x), (3) xi + Yi,t+i = fi(x) + YE yjfi(tf) + O(y yt...It is clear that a sufficient condition for the point x to be locally stable is that all the roots of the matrix, (4) (a j) = ____ should have moduli

Digital communications: Microwave applications

NASA Astrophysics Data System (ADS)

Feher, K.

Transmission concepts and techniques of digital systems are presented; and practical state-of-the-art implementation of digital communications systems by line-of-sight microwaves is described. Particular consideration is given to statistical methods in digital transmission systems analysis, digital modulation methods, microwave amplifiers, system gain, m-ary and QAM microwave systems, correlative techniques and applications to digital radio systems, hybrid systems, digital microwave systems design, diversity and protection switching techniques, measurement techniques, and research and development trends and unsolved problems.

Condensed Matter Physics: Does Quantum Mechanics Matter?

NASA Astrophysics Data System (ADS)

Fisher, Michael E.

Herman Feshbach, the organizer of this Symposium in honor of Niels Bohr, asked me, in his original invitation, for a review of the present state of condensed matter physics, with emphasis on major unsolved problems and comments on any overlap with Bohr's ideas regarding the fundamentals of quantum mechanics. That is surely a difficult assignment and, indeed, goes well beyond what is attempted here; nevertheless, I will take the liberty of raising one issue of a philosophical or metaphysical flavor.

Conformational dynamics of L-lysine, L-arginine, L-ornithine binding protein reveals ligand-dependent plasticity.

PubMed

Silva, Daniel-Adriano; Domínguez-Ramírez, Lenin; Rojo-Domínguez, Arturo; Sosa-Peinado, Alejandro

2011-07-01

The molecular basis of multiple ligand binding affinity for amino acids in periplasmic binding proteins (PBPs) and in the homologous domain for class C G-protein coupled receptors is an unsolved question. Here, using unrestrained molecular dynamic simulations, we studied the ligand binding mechanism present in the L-lysine, L-arginine, L-ornithine binding protein. We developed an analysis based on dihedral angles for the description of the conformational changes upon ligand binding. This analysis has an excellent correlation with each of the two main movements described by principal component analysis (PCA) and it's more convenient than RMSD measurements to describe the differences in the conformational ensembles observed. Furthermore, an analysis of hydrogen bonds showed specific interactions for each ligand studied as well as the ligand interaction with the aromatic residues Tyr-14 and Phe-52. Using uncharged histidine tautomers, these interactions are not observed. On the basis of these results, we propose a model in which hydrogen bond interactions place the ligand in the correct orientation to induce a cation-π interaction with Tyr-14 and Phe-52 thereby stabilizing the closed state. Our results also show that this protein adopts slightly different closed conformations to make available specific hydrogen bond interactions for each ligand thus, allowing a single mechanism to attain multiple ligand specificity. These results shed light on the experimental evidence for ligand-dependent conformational plasticity not explained by the previous crystallographic data. Copyright © 2011 Wiley-Liss, Inc.

Quantitative evolutionary design

PubMed Central

Diamond, Jared

2002-01-01

The field of quantitative evolutionary design uses evolutionary reasoning (in terms of natural selection and ultimate causation) to understand the magnitudes of biological reserve capacities, i.e. excesses of capacities over natural loads. Ratios of capacities to loads, defined as safety factors, fall in the range 1.2-10 for most engineered and biological components, even though engineered safety factors are specified intentionally by humans while biological safety factors arise through natural selection. Familiar examples of engineered safety factors include those of buildings, bridges and elevators (lifts), while biological examples include factors of bones and other structural elements, of enzymes and transporters, and of organ metabolic performances. Safety factors serve to minimize the overlap zone (resulting in performance failure) between the low tail of capacity distributions and the high tail of load distributions. Safety factors increase with coefficients of variation of load and capacity, with capacity deterioration with time, and with cost of failure, and decrease with costs of initial construction, maintenance, operation, and opportunity. Adaptive regulation of many biological systems involves capacity increases with increasing load; several quantitative examples suggest sublinear increases, such that safety factors decrease towards 1.0. Unsolved questions include safety factors of series systems, parallel or branched pathways, elements with multiple functions, enzyme reaction chains, and equilibrium enzymes. The modest sizes of safety factors imply the existence of costs that penalize excess capacities. Those costs are likely to involve wasted energy or space for large or expensive components, but opportunity costs of wasted space at the molecular level for minor components. PMID:12122135

Aging-related impairments of hippocampal mossy fibers synapses on CA3 pyramidal cells.

PubMed

Villanueva-Castillo, Cindy; Tecuatl, Carolina; Herrera-López, Gabriel; Galván, Emilio J

2017-01-01

The network interaction between the dentate gyrus and area CA3 of the hippocampus is responsible for pattern separation, a process that underlies the formation of new memories, and which is naturally diminished in the aged brain. At the cellular level, aging is accompanied by a progression of biochemical modifications that ultimately affects its ability to generate and consolidate long-term potentiation. Although the synapse between dentate gyrus via the mossy fibers (MFs) onto CA3 neurons has been subject of extensive studies, the question of how aging affects the MF-CA3 synapse is still unsolved. Extracellular and whole-cell recordings from acute hippocampal slices of aged Wistar rats (34 ± 2 months old) show that aging is accompanied by a reduction in the interneuron-mediated inhibitory mechanisms of area CA3. Several MF-mediated forms of short-term plasticity, MF long-term potentiation and at least one of the critical signaling cascades necessary for potentiation are also compromised in the aged brain. An analysis of the spontaneous glutamatergic and gamma-aminobutyric acid-mediated currents on CA3 cells reveal a dramatic alteration in amplitude and frequency of the nonevoked events. CA3 cells also exhibited increased intrinsic excitability. Together, these results demonstrate that aging is accompanied by a decrease in the GABAergic inhibition, reduced expression of short- and long-term forms of synaptic plasticity, and increased intrinsic excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

Teaching DSM-III to clinicians. Some problems of the DSM-III system reducing reliability, using the diagnosis and classification of depressive disorders as an example.

PubMed

Malt, U F

1986-01-01

Experiences from teaching DSM-III to more than three hundred Norwegian psychiatrists and clinical psychologists suggest that reliable DSM-III diagnoses can be achieved within a few hours training with reference to the decision trees and the diagnostic criteria only. The diagnoses provided are more reliable than the corresponding ICD diagnoses which the participants were more familiar with. The three main sources of reduced reliability of the DSM-III diagnoses are related to: poor knowledge of the criteria which often is connected with failure of obtaining diagnostic key information during the clinical interview; unfamiliar concepts and vague or ambiguous criteria. The two first issues are related to the quality of the teaching of DSM-III. The third source of reduced reliability reflects unsolved validity issues. By using the classification of five affective case stories as examples, these sources of diagnostic pitfalls, reducing reliability and ways to overcome these problems when teaching the DSM-III system, are discussed. It is concluded that the DSM-III system of classification is easy to teach and that the system is superior to other classification systems available from a reliability point of view. The current version of the DSM-III system, however, partly owes a high degree of reliability to broad and heterogeneous diagnostic categories like the concept major depression, which may have questionable validity. Thus, the future revisions of the DSM-III system should, above all, address the issue of validity.

Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

NASA Astrophysics Data System (ADS)

Nath Chatterjee, Amar; Roy, Priti Kumar

2012-02-01

Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

Broad phenotypes in heterozygous NR5A1 46,XY patients with a disorder of sex development: an oligogenic origin?

PubMed

Camats, Núria; Fernández-Cancio, Mónica; Audí, Laura; Schaller, André; Flück, Christa E

2018-06-11

SF-1/NR5A1 is a transcriptional regulator of adrenal and gonadal development. NR5A1 disease-causing variants cause disorders of sex development (DSD) and adrenal failure, but most affected individuals show a broad DSD/reproductive phenotype only. Most NR5A1 variants show in vitro pathogenic effects, but not when tested in heterozygote state together with wild-type NR5A1 as usually seen in patients. Thus, the genotype-phenotype correlation for NR5A1 variants remains an unsolved question. We analyzed heterozygous 46,XY SF-1/NR5A1 patients by whole exome sequencing and used an algorithm for data analysis based on selected project-specific DSD- and SF-1-related genes. The variants detected were evaluated for their significance in literature, databases and checked in silico using webtools. We identified 19 potentially deleterious variants (one to seven per patient) in 18 genes in four 46,XY DSD subjects carrying heterozygous NR5A1 disease-causing variants. We constructed a scheme of all these hits within the landscape of currently known genes involved in male sex determination and differentiation. Our results suggest that the broad phenotype in these heterozygous NR5A1 46,XY DSD subjects may well be explained by an oligogenic mode of inheritance, in which multiple hits, individually non-deleterious, may contribute to a DSD phenotype unique to each heterozygous SF-1/NR5A1 individual.

Chemical Impact of Solar Energetic Particle Event From The Young Sun: Implications for the Origin of Prebiotic Chemistry and the Fain Young Sun Paradox

NASA Astrophysics Data System (ADS)

Airapetian, V.; Gronoff, G.; Hébrard, E.; Danchi, W.

2015-12-01

Understanding how the simple molecules present on the early Earth and possibly Mars may have set a path for complex biological molecules, the building blocks of life, represents one of greatest unsolved questions. Here we present a new model of the rise of the abiotic nitrogen fixation and associated pre-biotic chemistry in the early Earth and Mars atmosphere mediated by solar eruptive events. Our physical models of interaction of magnetic clouds ejected from the young Sun with magnetospheres of the early Earth show significant perturbations of geomagnetic fields that produce extended polar caps. These polar caps provide pathways for energetic particles associated with magnetic clouds to penetrate into the nitrogen-rich weakly reducing atmosphere and initiate the reactive chemistry by breaking molecular nitrogen, carbon dioxide, methane and producing hydrogen cyanide, the essential compound for life. The model also shows that contrary to the current models of warming of early Earth and Mars, major atmospheric constituents, CO2 and CH4 will be destroyed due to collisional dissociation with energetic particles. Instead, efficient formation of the potent greenhouse gas, nitrous oxide, as a by-product of these processes is expected. This mechanism can consistently explain the Faint Young Sun's paradox for the early atmospheres of Earth and Mars. Our new model provides insight into how life may have initiated on Earth and Mars and how to search for the spectral signatures on planets "pregnant" with the potential for life.

Rare earth elements in human and animal health: State of art and research priorities.

PubMed

Pagano, Giovanni; Aliberti, Francesco; Guida, Marco; Oral, Rahime; Siciliano, Antonietta; Trifuoggi, Marco; Tommasi, Franca

2015-10-01

A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessing protein conformational sampling methods based on bivariate lag-distributions of backbone angles

PubMed Central

Maadooliat, Mehdi; Huang, Jianhua Z.

2013-01-01

Despite considerable progress in the past decades, protein structure prediction remains one of the major unsolved problems in computational biology. Angular-sampling-based methods have been extensively studied recently due to their ability to capture the continuous conformational space of protein structures. The literature has focused on using a variety of parametric models of the sequential dependencies between angle pairs along the protein chains. In this article, we present a thorough review of angular-sampling-based methods by assessing three main questions: What is the best distribution type to model the protein angles? What is a reasonable number of components in a mixture model that should be considered to accurately parameterize the joint distribution of the angles? and What is the order of the local sequence–structure dependency that should be considered by a prediction method? We assess the model fits for different methods using bivariate lag-distributions of the dihedral/planar angles. Moreover, the main information across the lags can be extracted using a technique called Lag singular value decomposition (LagSVD), which considers the joint distribution of the dihedral/planar angles over different lags using a nonparametric approach and monitors the behavior of the lag-distribution of the angles using singular value decomposition. As a result, we developed graphical tools and numerical measurements to compare and evaluate the performance of different model fits. Furthermore, we developed a web-tool (http://www.stat.tamu.edu/∼madoliat/LagSVD) that can be used to produce informative animations. PMID:22926831

Naturalness and a light Z'

NASA Astrophysics Data System (ADS)

Zhu, Bin; Staub, Florian; Ding, Ran

2017-08-01

Models with a light, additional gauge boson are attractive extensions of the standard model. Often these models are only considered as an effective low-energy theory without any assumption about an UV completion. This not only leaves the hierarchy problem of the SM unsolved, but also introduces a copy of it because of the new fundamental scalars responsible for breaking the new gauge group. A possible solution is to embed these models into a supersymmetric framework. However, this gives rise to an additional source of fine-tuning compared to the MSSM and poses a question about how natural such a setup is. One might expect that the additional fine-tuning is huge, namely, O (MSUSY2/mZ'2). In this paper, we point out that this is not necessarily the case. We show that it is possible to find a focus point behavior also in the new sector in coexistence with the MSSM focus point. We call this the "double focus point supersymmetry." Moreover, we stress the need for a proper inclusion of radiative corrections in the fine-tuning calculation: a tree-level estimate would lead to predictions for the tuning which can be wrong by many orders of magnitude. As a showcase, we use the U (1 )B -L extended MSSM and discuss possible consequences of the observed 8Be anomaly. However, similar features are expected for other models with an extended gauge group which involve potentially large Yukawa-like interactions of the new scalars.

Hypophosphatasia: the patient's and patient's family's point of view.

PubMed

Ursprung, S

2017-05-01

Today, public opinion and the French authorities are more aware of rare diseases, in particular due to the implementation of national plans for rare diseases (PNMR I: 2005-2008 and PNMR II: 2011-2016), the existence of national networks and the current organization of the reference expert centers for rare diseases. While the management of rare diseases is now better structured, it remains long for the patients to be diagnosed. It is not always easy for physicians to clearly identify one of the 7,000 rare diseases even though they increasingly ask themselves the question: is this a rare disease? A person diagnosed with a rare disease lives in a familial, social and professional environment that has not prepared him or her, suddenly or after years of uncertainty, for such an experience. It may be temptng to take refuge in isolation. The patient's pathway is a real challenge and include the recognition to his/her 'difference' and the right to benefit from the expert medical and social care. Patients affected with hypophosphatasia, a very rare bone and dental disease, are not exceptions to the rule, despite the dynamic support of Hypophosphatasie Europe, the first patient association, created in 2004. In twelve years, the overall understanding of hypophosphatasia has dramatically improved, including through the discovery of novel therapies. Yet, diagnostic errance, transition between childhood and adulthood and management and care of affected adults remain unsolved issues. © 2017 Elsevier Masson SAS. All rights reserved.

Two-Coordinate Magnesium(I) Dimers Stabilized by Super Bulky Amido Ligands.

PubMed

Boutland, Aaron J; Dange, Deepak; Stasch, Andreas; Maron, Laurent; Jones, Cameron

2016-08-01

A variety of very bulky amido magnesium iodide complexes, LMgI(solvent)0/1 and [LMg(μ-I)(solvent)0/1 ]2 (L=-N(Ar)(SiR3 ); Ar=C6 H2 {C(H)Ph2 }2 R'-2,6,4; R=Me, Pr(i) , Ph, or OBu(t) ; R'=Pr(i) or Me) have been prepared by three synthetic routes. Structurally characterized examples of these materials include the first unsolvated amido magnesium halide complexes, such as [LMg(μ-I)]2 (R=Me, R'=Pr(i) ). Reductions of several such complexes with KC8 in the absence of coordinating solvents have afforded the first two-coordinate magnesium(I) dimers, LMg-MgL (R=Me, Pr(i) or Ph; R'=Pr(i) , or Me), in low to good yields. Reductions of two of the precursor complexes in the presence of THF have given the related THF adduct complexes, L(THF)Mg-Mg(THF)L (R=Me; R'=Pr(i) ) and LMg-Mg(THF)L (R=Pr(i) ; R'=Me) in trace yields. The X-ray crystal structures of all magnesium(I) complexes were obtained. DFT calculations on the unsolvated examples reveal their Mg-Mg bonds to be covalent and of high s-character, while Ph⋅⋅⋅Mg bonding interactions in the compounds were found to be weak at best. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Council for International Organizations of Medical Sciences (CIOMS) Ethical Guidelines: advancements and unsolved topics in 2016 upgrade.

PubMed

Borgeat Meza, Marjorie; Luengo-Charath, Ximena; Arancibia, Marcelo; Madrid, Eva

2018-04-25

In 2016, the new edition of the Council for International Organizations of Medical Sciences (CIOMS) Ethical Guidelines was released, which are universally acknowledged as ethical standards in biomedical research. In this article, we critically analyze the improvements and shortcomings of the CIOMS Ethical Guidelines 2016. Among the improvements are the relevance assigned to the social value of research and its effects on decision-making and the creation of public policies; the research development in low-resources scenarios; the communities’ involvement in the research process; the determination of participants’ vulnerability and changes on informed consent related proceedings. Despite the improved harmonization with scientific, technologic and social changes, and that the guidelines provide a tool for researchers and members of research ethics committees alike, some topics remain unsolved, namely the management of participants’ minimal risk and conflicts of interest involved in research, and the development of research in low-incomes scenarios. Nonetheless, we recognize that these new guidelines constitute a progress regarding the context and needs of populations in which research will be conducted, with greater community involvement in the different phases of the investigation project, thus allowing them to access the potential benefits. The impact of the CIOMS Ethical Guidelines 2016, should be appraised over time, particularly in socio-sanitary inequities scenarios and in the context of commercial interests of industry on biomedical research.

The α-Effect and Competing Mechanisms: The Gas-Phase Reactions of Microsolvated Anions with Methyl Formate

NASA Astrophysics Data System (ADS)

Thomsen, Ditte L.; Nichols, Charles M.; Reece, Jennifer N.; Hammerum, Steen; Bierbaum, Veronica M.

2014-02-01

The enhanced reactivity of α-nucleophiles, which contain an electron lone pair adjacent to the reactive site, has been demonstrated in solution and in the gas phase and, recently, for the gas-phase SN2 reactions of the microsolvated HOO-(H2O) ion with methyl chloride. In the present work, we continue to explore the significance of microsolvation on the α-effect as we compare the gas-phase reactivity of the microsolvated α-nucleophile HOO-(H2O) with that of microsolvated normal alkoxy nucleophiles, RO-(H2O), in reactions with methyl formate, where three competing reactions are possible. The results reveal enhanced reactivity of HOO-(H2O) towards methyl formate, and clearly demonstrate the presence of an overall α-effect for the reactions of the microsolvated α-nucleophile. The association of the nucleophiles with a single water molecule significantly lowers the degree of proton abstraction and increases the SN2 and BAC2 reactivity compared with the unsolvated analogs. HOO-(H2O) reacts with methyl formate exclusively via the BAC2 channel. While microsolvation lowers the overall reaction efficiency, it enhances the BAC2 reaction efficiency for all anions compared with the unsolvated analogs. This may be explained by participation of the solvent water molecule in the BAC2 reaction in a way that continuously stabilizes the negative charge throughout the reaction.

Defining the Medical Library Association research agenda: methodology and final results from a consensus process

PubMed Central

Eldredge, Jonathan D.; Harris, Martha R.; Ascher, Marie T.

2009-01-01

Objective: Using a group consensus methodology, the research sought to generate a list of the twelve to fifteen most important and answerable research questions in health sciences librarianship as part of a broader effort to implement the new Medical Library Association (MLA) research policy. Methods: The delphi method was used. The committee distributed a brief survey to all estimated 827 MLA leaders and 237 MLA Research Section members, requesting they submit what they considered to be the most important and answerable research questions facing the profession. The submitted questions were then subjected to 2 rounds of voting to produce a short list of top-ranked questions. Results: The survey produced 62 questions from 54 MLA leaders and MLA Research Section members, who responded from an estimated potential population of 1,064 targeted colleagues. These questions were considered by the process participants to be the most important and answerable research questions facing the profession. Through 2 rounds of voting, these 62 questions were reduced to the final 12 highest priority questions. Conclusion: The modified delphi method accomplished its desired survey and consensus goals. Future survey and consensus processes will be revised to generate more initial questions and to distill a larger number of ranked prioritized research questions. PMID:19626143

Crystal Structure of the Marburg Virus Nucleoprotein Core Domain Chaperoned by a VP35 Peptide Reveals a Conserved Drug Target for Filovirus.

PubMed

Zhu, Tengfei; Song, Hao; Peng, Ruchao; Shi, Yi; Qi, Jianxun; Gao, George F

2017-09-15

Filovirus nucleoprotein (NP), viral protein 35 (VP35), and polymerase L are essential for viral replication and nucleocapsid formation. Here, we identify a 28-residue peptide (NP binding peptide [NPBP]) from Marburg virus (MARV) VP35 through sequence alignment with previously identified Ebola virus (EBOV) NPBP, which bound to the core region (residues 18 to 344) of the N-terminal portion of MARV NP with high affinity. The crystal structure of the MARV NP core/NPBP complex at a resolution of 2.6 Å revealed that NPBP binds to the C-terminal region of the NP core via electrostatic and nonpolar interactions. Further structural analysis revealed that the MARV and EBOV NP cores hold a conserved binding pocket for NPBP, and this pocket could serve as a promising target for the design of universal drugs against filovirus infection. In addition, cross-binding assays confirmed that the NP core of MARV or EBOV can bind the NPBP from the other virus, although with moderately reduced binding affinities that result from termini that are distinct between the MARV and EBOV NPBPs. IMPORTANCE Historically, Marburg virus (MARV) has caused severe disease with up to 90% lethality. Among the viral proteins produced by MARV, NP and VP35 are both multifunctional proteins that are essential for viral replication. In its relative, Ebola virus (EBOV), an N-terminal peptide from VP35 binds to the NP N-terminal region with high affinity. Whether this is a common mechanism among filoviruses is an unsolved question. Here, we present the crystal structure of a complex that consists of the core domain of MARV NP and the NPBP peptide from VP35. As we compared MARV NPBP with EBOV NPBP, several different features at the termini were identified. Although these differences reduce the affinity of the NP core for NPBPs across genera, a conserved pocket in the C-terminal region of the NP core makes cross-species binding possible. Our results expand our knowledge of filovirus NP-VP35 interactions and provide more details for therapeutic intervention. Copyright © 2017 American Society for Microbiology.

Application of field geophysics in geomorphology: Advances and limitations exemplified by case studies

NASA Astrophysics Data System (ADS)

Schrott, Lothar; Sass, Oliver

2008-01-01

During the last decade, the use of geophysical techniques has become popular in many geomorphological studies. However, the correct handling of geophysical instruments and the subsequent processing of the data they yield are difficult tasks. Furthermore, the description and interpretation of geomorphological settings to which they apply can significantly influence the data gathering and subsequent modelling procedure ( e.g. achieving a maximum depth of 30 m requires a certain profile length and geophone spacing or a particular frequency of antenna). For more than three decades geophysical techniques have been successfully applied, for example, in permafrost studies. However, in many cases complex or more heterogeneous subsurface structures could not be adequately interpreted due to limited computer facilities and time consuming calculations. As a result of recent technical improvements, geophysical techniques have been applied to a wider spectrum of geomorphological and geological settings. This paper aims to present some examples of geomorphological studies that demonstrate the powerful integration of geophysical techniques and highlight some of the limitations of these techniques. A focus has been given to the three most frequently used techniques in geomorphology to date, namely ground-penetrating radar, seismic refraction and DC resistivity. Promising applications are reported for a broad range of landforms and environments, such as talus slopes, block fields, landslides, complex valley fill deposits, karst and loess covered landforms. A qualitative assessment highlights suitable landforms and environments. The techniques can help to answer yet unsolved questions in geomorphological research regarding for example sediment thickness and internal structures. However, based on case studies it can be shown that the use of a single geophysical technique or a single interpretation tool is not recommended for many geomorphological surface and subsurface conditions as this may lead to significant errors in interpretation. Because of changing physical properties of the subsurface material ( e.g. sediment, water content) in many cases only a combination of two or sometimes even three geophysical methods gives sufficient insight to avoid serious misinterpretation. A "good practice guide" has been framed that provides recommendations to enable the successful application of three important geophysical methods in geomorphology and to help users avoid making serious mistakes.

Centers for Disease Control and Prevention injury research agenda: identification of acute care research topics of interest to the Centers for disease Control and Prevention--National Center for Injury Prevention and Control.

PubMed

Jurkovich, Gregory J; Rivara, Frederick P; Johansen, Jennifer M; Maier, Ronald V

2004-05-01

The purpose of this report is to identify the most important research questions pertaining to the acute care of the injured patient using a Web-based Delphi technique to achieve expert opinion consensus. Experts in trauma care from the United States and Canada (n =39) generated structured research questions and then ranked these questions in order of importance, using a Web-based survey for question generation, question ranking, and a Delphi technique of consensus. Guidelines for question construction and ranking specified that participants considered questions that fall within the interest and domain of the Centers for Disease Control (CDC)-National Center for Injury Prevention and Control (NCIPC). One hundred thirty-seven questions in 18 distinct categories of interest were initially generated. After two rounds of merging, collating, reassessing, and ranking by significance and importance, 25 research questions were deemed most important and significant in the care of the injured patient. Ten of these (40%) were considered to be appropriate issues for the CDC-NCIPC to address and fund, dealing with injury prevention strategies, trauma systems design and funding, the epidemiology of injury, and global outcome determinants. These 25 questions were also reviewed with consideration given to the most likely source of federal funding of investigations. This report identifies the areas of trauma care in which research efforts might best be directed. Fully 40% of the key research questions could be considered to fall under the interest and auspices of the CDC-NCIPC. The remaining questions cover a broad range of topics and likely funding sources, emphasizing the need for a coordinated oversight of research funding in trauma care.

The 150 most important questions in cancer research and clinical oncology series: Questions 25-30 : Edited by Chinese Journal of Cancer.

PubMed

2017-05-04

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8 + T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?

What Variables Appear Important in Changing Traditional Inservice Training Procedures.

ERIC Educational Resources Information Center

Sobol, Francis Thomas

Herein are discussed descriptive findings from the educational literature on the question of what variables appear important in changing traditional in-service training procedures. The question of the content versus the process of in-service training, important problems in in-service training programs, and implications of the important problems…

On Formative Assessment in Math: How Diagnostic Questions Can Help

ERIC Educational Resources Information Center

Barton, Craig

2018-01-01

In this article, the author asserts that asking and responding to diagnostic questions is the single most important part of teaching secondary school mathematics. He notes the importance of formative assessment and recommends a formative assessment strategy that requires students to be public about their answers to questions, displaying their…

Light Chemical Elements in Stars: Mysteries and Unsolved Problems

NASA Astrophysics Data System (ADS)

Lyubimkov, L. S.

2018-06-01

The first eight elements of the periodic table are discussed: H, He, Li, Be, B, C, N, and O. They are referred to as key elements, given their important role in stellar evolution. It is noteworthy that all of them were initially synthesized in the Big Bang. The primordial abundances of these elements calculated using the Standard Model of the Big Bang (SMBB) are presented in this review. The good agreement between the SMBB and observations of the primordial abundances of the isotopes of hydrogen and helium, D, 3He, and 4He, is noted, but there is a difference of 0.5 dex for lithium (the isotope 7Li) between the SMBB and observations of old stars in the galactic halo that has not yet been explained. The abundances of light elements in stellar atmospheres depends on the initial rotation velocity, so the typical rotation velocities of young Main Sequence (MS) stars are examined. Since the data on the abundances of light elements in stars are very extensive, the main emphasis in this review is on several unsolved problems. The helium abundance He/H in early B-type of the MS stars shows an increment with age; in particular, for the most massive B stars with masses M = 12-19M ⊙, He/H increases by more than a factor of two toward the end of the MS. Theoretical models of stars with rotation cannot explain such a large increase in He/H. For early B- and late O-type MS stars that are components of close binary systems, He/H undergoes a sharp jump in the middle of the MS stage that is a mystery for the theory. The anomalous abundance of helium (and lithium) in the atmospheres of chemically peculiar stars (types He-s, He-w, HgMn, Ap, and Am) is explained in terms of the diffusion of atoms in surface layers of the stars, but this hypothesis cannot yet explain all the features of the chemical composition of these stars. The abundances of lithium, beryllium, and boron in FGK-dwarfs manifest a trend with decreasing effective temperature T eff as well as a dip at T eff 6600 K in the Hyades and other old clusters. The two effects are among the unsolved problems. In the case of lithium, there is special interest in FGK-giants and supergiants that are rich in lithium (they have logɛ(Li)≥ 2). Most of them cannot be explained in terms of the standard theory of stellar evolution, so nonstandard hypotheses are invoked: the recent synthesis of lithium in a star and the engulfment by a star of a giant planet with mass equal to that of Jupiter or greater. An analysis of the abundances of carbon, nitrogen, and oxygen in early B- and late O-stars of the MS indicates that the C II, N II, and O II ions are overionized in their atmospheres. For early B-type MS stars, good agreement is found between observations of the N/O ratio and model calculations for rotating stars. A quantitative explanation of the well-known "nitrogen-oxygen" anticorrelation in FGK-giants and supergiants is found. It reflects the dependence of the anomalies in N and C on the initial rotation velocity V 0. The stellar rotation models which yield successful explanations for C, N. and O cannot, however, explain the observed helium enrichment in early B-type MS stars.

Question Classification Taxonomies as Guides to Formulating Questions for Use in Chemistry Classrooms

ERIC Educational Resources Information Center

Festo, Kayima

2016-01-01

Teacher questions play an important role in facilitating classroom discourse. Using appropriate question types and proper questioning techniques help to create reflective-active learners. Teacher questions can elicit students' explanations, elaboration of their ideas and thinking, and they can be used to disclose students' misconceptions. Despite…

Hydrogen anion and subgap states in amorphous In-Ga-Zn-O thin films for TFT applications

NASA Astrophysics Data System (ADS)

Bang, Joonho; Matsuishi, Satoru; Hosono, Hideo

2017-06-01

Hydrogen is an impurity species having an important role in the physical properties of semiconductors. Despite numerous studies, the role of hydrogen in oxide semiconductors remains an unsolved puzzle. This situation arises from insufficient information about the chemical state of the impurity hydrogen. Here, we report direct evidence for anionic hydrogens bonding to metal cations in amorphous In-Ga-Zn-O (a-IGZO) thin films for thin-film transistors (TFT) applications and discuss how the hydrogen impurities affect the electronic structure of a-IGZO. Infrared absorption spectra of self-standing a-IGZO thin films prepared by sputtering reveal the presence of hydrogen anions as a main hydrogen species (concentration is ˜1020 cm-3) along with the hydrogens in the form of the hydroxyl groups (˜1020 cm-3). Density functional theory calculations show that bonds between these hydride ions with metal centers give rise to subgap states above the top of the valence band, implying a crucial role of anionic hydrogen in the negative bias illumination stress instability commonly observed in a-IGZO TFTs.

Software System Safety and the NASA Aeronautics Blueprint

NASA Technical Reports Server (NTRS)

Holloway, C. Michael; Hayhurst, Kelly J.

2002-01-01

NASA's Aeronautics Blueprint lays out a research agenda for the Agency s aeronautics program. The word software appears only four times in this Blueprint, but the critical importance of safe and correct software to the fulfillment of the proposed research is evident on almost every page. Most of the technology solutions proposed to address challenges in aviation are software dependent technologies. Of the fifty-two specific technology solutions described in the Blueprint, forty-one depend, at least in part, on software for success. For thirty-five of these forty-one, software is not only critical to success, but also to human safety. That is, implementing the technology solutions will require using software in such a way that it may, if not specified, designed, and implemented properly, lead to fatal accidents. These results have at least two implications for the research based on the Blueprint: (1) knowledge about the current state-of-the-art and state-of-the-practice in software engineering and software system safety is essential, and (2) research into current unsolved problems in these software disciplines is also essential.

A combination of feature extraction methods with an ensemble of different classifiers for protein structural class prediction problem.

PubMed

Dehzangi, Abdollah; Paliwal, Kuldip; Sharma, Alok; Dehzangi, Omid; Sattar, Abdul

2013-01-01

Better understanding of structural class of a given protein reveals important information about its overall folding type and its domain. It can also be directly used to provide critical information on general tertiary structure of a protein which has a profound impact on protein function determination and drug design. Despite tremendous enhancements made by pattern recognition-based approaches to solve this problem, it still remains as an unsolved issue for bioinformatics that demands more attention and exploration. In this study, we propose a novel feature extraction model that incorporates physicochemical and evolutionary-based information simultaneously. We also propose overlapped segmented distribution and autocorrelation-based feature extraction methods to provide more local and global discriminatory information. The proposed feature extraction methods are explored for 15 most promising attributes that are selected from a wide range of physicochemical-based attributes. Finally, by applying an ensemble of different classifiers namely, Adaboost.M1, LogitBoost, naive Bayes, multilayer perceptron (MLP), and support vector machine (SVM) we show enhancement of the protein structural class prediction accuracy for four popular benchmarks.

HOPPING CONDUCTIVITY AND MAGNETIC TRANSITIONS OF THE Cu2+ SPINS IN SINGLE-CRYSTAL La2CuO4+y

NASA Astrophysics Data System (ADS)

Thio, Tineke; Birgeneau, R. J.; Chen, C. Y.; Freer, B. S.; Gabbe, D. R.; Jenssen, H. P.; Kastner, M. A.; Picone, P. J.; Preyer, N. W.

Measurements are reported of the magnetoresistance (MR) for fields up to 23T in La2CuO4+y single crystals in which the Cu2+ spins order antiferromagnetically at TN˜240K, and in which the conductivity at low temperature is characterised by hopping between localised states. Using the MR, we map out the phase diagram of the spin flop transition, observed when the magnetic field is applied parallel to the zero-field staggered magnetisation, and that of the weak-ferromagnetic transition, observed with the field perpendicular to the CuO planes. In both transitions the antiferromagnetic propagation vector changes from the ěca direction at zero field to the ěcc direction at the highest fields. This rather subtle change of the Cu spin ordering is accompanied by a large increase in the interlayer hopping conductivity: up to a factor 2. We show that the magnetoconductance is proportional to the three-dimensional staggered moment with propagation vector in the orthorhombic ěcc direction. The origin of this unusual behaviour is an important unsolved problem.

Whole Genome Sequencing Identifies a 78 kb Insertion from Chromosome 8 as the Cause of Charcot-Marie-Tooth Neuropathy CMTX3

PubMed Central

Brewer, Megan H.; Chaudhry, Rabia; Qi, Jessica; Kidambi, Aditi; Drew, Alexander P.; Ryan, Monique M.; Subramanian, Gopinath M.; Young, Helen K.; Zuchner, Stephan; Reddel, Stephen W.; Nicholson, Garth A.; Kennerson, Marina L.

2016-01-01

With the advent of whole exome sequencing, cases where no pathogenic coding mutations can be found are increasingly being observed in many diseases. In two large, distantly-related families that mapped to the Charcot-Marie-Tooth neuropathy CMTX3 locus at chromosome Xq26.3-q27.3, all coding mutations were excluded. Using whole genome sequencing we found a large DNA interchromosomal insertion within the CMTX3 locus. The 78 kb insertion originates from chromosome 8q24.3, segregates fully with the disease in the two families, and is absent from the general population as well as 627 neurologically normal chromosomes from in-house controls. Large insertions into chromosome Xq27.1 are known to cause a range of diseases and this is the first neuropathy phenotype caused by an interchromosomal insertion at this locus. The CMTX3 insertion represents an understudied pathogenic structural variation mechanism for inherited peripheral neuropathies. Our finding highlights the importance of considering all structural variation types when studying unsolved inherited peripheral neuropathy cases with no pathogenic coding mutations. PMID:27438001

The formation of planetary disks and winds: an ultraviolet view

NASA Astrophysics Data System (ADS)

Gómez de Castro, Ana I.

2009-04-01

Planetary systems are angular momentum reservoirs generated during star formation. This accretion process produces very powerful engines able to drive the optical jets and the molecular outflows. A fraction of the engine energy is released into heating thus the temperature of the engine ranges from the 3000 K of the inner disk material to the 10 MK in the areas where magnetic reconnection occurs. There are important unsolved problems concerning the nature of the engine, its evolution and the impact of the engine in the chemical evolution of the inner disk. Of special relevance is the understanding of the shear layer between the stellar photosphere and the disk; this layer controls a significant fraction of the magnetic field building up and the subsequent dissipative processes ougth to be studied in the UV. This contribution focus on describing the connections between 1 Myr old suns and the Sun and the requirements for new UV instrumentation to address their evolution during this period. Two types of observations are shown to be needed: monitoring programmes and high resolution imaging down to, at least, milliarsecond scales.

Abnormal patterns of displacement activities: a review and reinterpretation.

PubMed

Anselme, Patrick

2008-09-01

A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model.

The Role of Task-Related Learned Representations in Explaining Asymmetries in Task Switching

PubMed Central

Barutchu, Ayla; Becker, Stefanie I.; Carter, Olivia; Hester, Robert; Levy, Neil L.

2013-01-01

Task switch costs often show an asymmetry, with switch costs being larger when switching from a difficult task to an easier task. This asymmetry has been explained by difficult tasks being represented more strongly and consequently requiring more inhibition prior to switching to the easier task. The present study shows that switch cost asymmetries observed in arithmetic tasks (addition vs. subtraction) do not depend on task difficulty: Switch costs of similar magnitudes were obtained when participants were presented with unsolvable pseudo-equations that did not differ in task difficulty. Further experiments showed that neither task switch costs nor switch cost asymmetries were due to perceptual factors (e.g., perceptual priming effects). These findings suggest that asymmetrical switch costs can be brought about by the association of some tasks with greater difficulty than others. Moreover, the finding that asymmetrical switch costs were observed (1) in the absence of a task switch proper and (2) without differences in task difficulty, suggests that present theories of task switch costs and switch cost asymmetries are in important ways incomplete and need to be modified. PMID:23613919

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

Goriely, S.; Bauswein, A.; Janka, H.-T.

About half of the nuclei heavier than iron observed in nature are produced by the so-called rapid neutron capture process, or r-process, of nucleosynthesis. The identification of the astrophysics site and the specific conditions in which the r-process takes place remains, however, one of the still-unsolved mysteries of modern astrophysics. Another underlying difficulty associated with our understanding of the r-process concerns the uncertainties in the predictions of nuclear properties for the few thousands exotic neutron-rich nuclei involved, for which essentially no experimental data exist. The present paper emphasizes some important future challenges faced by nuclear physics in this problem, particularlymore » in the determination of the nuclear structure properties of exotic neutron-rich nuclei as well as their radiative neutron capture rates and their fission probabilities. These quantities are particularly relevant to determine the composition of the matter resulting from the r-process. Both the astrophysics and the nuclear physics difficulties are critically reviewed with special attention paid to the r-process taking place during the decompression of neutron star matter following the merging of two neutron stars.« less

Quiet-sun and non-flaring active region measurements from the FOXSI-2 sounding rocket

NASA Astrophysics Data System (ADS)

Buitrago-Casas, J. C.; Glesener, L.; Christe, S.; Ishikawa, S. N.; Narukage, N.; Krucker, S.; Bale, S. D.

2016-12-01

Solar hard X-ray (HXR) emissions are a cornerstone for understanding particle acceleration and energy release in the corona. These phenomena are present at different size scales and intensities, from large eruptive events down to the smallest flares. The presence of HXRs in small, unresolved flares would provide direct evidence of small reconnection events, i.e. nano-flares, that are thought to be be important for the unsolved coronal heating problem. Currently operating solar-dedicated instruments that observe HXRs from the Sun do not have the dynamic range, nor the sensitivity, crucial to observe the faintest solar HXRs. The Focusing Optics X-ray Solar Imager (FOXSI) sounding rocket payload is a novel experiment that develops and applies direct focusing optics coupled with semiconductor detectors to observe faint HXRs from the Sun. The FOXSI rocket has successfully completed two flights, observing areas of the quiet-Sun, active regions and micro-flares. We present recent data analysis to test the presence of hot plasma in and outside of active regions observed during the two flights, focusing on the differential emission measure distribution of the non-flaring corona.

Friction falls towards zero in quartz rock as slip velocity approaches seismic rates.

PubMed

Di Toro, Giulio; Goldsby, David L; Tullis, Terry E

2004-01-29

An important unsolved problem in earthquake mechanics is to determine the resistance to slip on faults in the Earth's crust during earthquakes. Knowledge of coseismic slip resistance is critical for understanding the magnitude of shear-stress reduction and hence the near-fault acceleration that can occur during earthquakes, which affects the amount of damage that earthquakes are capable of causing. In particular, a long-unresolved problem is the apparently low strength of major faults, which may be caused by low coseismic frictional resistance. The frictional properties of rocks at slip velocities up to 3 mm s(-1) and for slip displacements characteristic of large earthquakes have been recently simulated under laboratory conditions. Here we report data on quartz rocks that indicate an extraordinary progressive decrease in frictional resistance with increasing slip velocity above 1 mm s(-1). This reduction extrapolates to zero friction at seismic slip rates of approximately 1 m s(-1), and appears to be due to the formation of a thin layer of silica gel on the fault surface: it may explain the low strength of major faults during earthquakes.

Nonlinear data assimilation: towards a prediction of the solar cycle

NASA Astrophysics Data System (ADS)

Svedin, Andreas

The solar cycle is the cyclic variation of solar activity, with a span of 9-14 years. The prediction of the solar cycle is an important and unsolved problem with implications for communications, aviation and other aspects of our high-tech society. Our interest is model-based prediction, and we present a self-consistent procedure for parameter estimation and model state estimation, even when only one of several model variables can be observed. Data assimilation is the art of comparing, combining and transferring observed data into a mathematical model or computer simulation. We use the 3DVAR methodology, based on the notion of least squares, to present an implementation of a traditional data assimilation. Using the Shadowing Filter — a recently developed method for nonlinear data assimilation — we outline a path towards model based prediction of the solar cycle. To achieve this end we solve a number of methodological challenges related to unobserved variables. We also provide a new framework for interpretation that can guide future predictions of the Sun and other astrophysical objects.

Flexible and stretchable electronics for wearable healthcare devices and minimally invasive surgical tools

NASA Astrophysics Data System (ADS)

Kim, Dae-Hyeong; Lee, Mincheol; Lee, Hyunjae

2016-05-01

Recent advances in soft electronics have attracted great attention, largely due to their potential applications in personalized, bio-integrated healthcare devices. The mechanical mismatch between conventional electronic/optoelectronic devices and soft human tissues/organs have presented many challenges, such as the low signalto- noise ratio of biosensors because of the incomplete integration of rigid devices with the body, inflammation and excessive immune responses of implanted stiff devices originated from friction and their foreign nature to biotic systems, and the considerable discomfort and consequent stress experienced by users when wearing/implanting these devices. Ultra-flexible and stretchable electronic devices are being highlighted due to their low system modulus and the intrinsic system-level softness that are important to solve these issues. Here, we describe our unique strategies for the nanomaterial synthesis and fabrication, their seamless assembly and integration, and the design and development of corresponding wearable healthcare devices and minimally invasive surgical tools. These bioelectronic systems fully utilize recent breakthroughs in unconventional soft electronics based on nanomaterials to address unsolved issues in clinical medicine and to provide new opportunities in the personalized healthcare.

Challenges of ligand identification for the second wave of orphan riboswitch candidates.

PubMed

Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M; Brewer, Kenneth I; Harris, Kimberly A; Malkowski, Sarah N; Mirihana Arachchilage, Gayan; Perkins, Kevin R; Sherlock, Madeline E; Breaker, Ronald R

2018-03-04

Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn 2+ , and the metabolites guanidine and PRPP. Such studies also yield useful linkages between the ligands sensed by the riboswitches and numerous biochemical pathways. In the current report, we describe the known characteristics of 30 distinct classes of orphan riboswitch candidates - some of which have remained unsolved for over a decade. We also discuss the prospects for uncovering novel biological insights via focused studies on these RNAs. Lastly, we make recommendations for experimental objectives along the path to finding ligands for these mysterious RNAs.

Novel rolling circle amplification and DNA origami-based DNA belt-involved signal amplification assay for highly sensitive detection of prostate-specific antigen (PSA).

PubMed

Yan, Juan; Hu, Chongya; Wang, Ping; Liu, Rui; Zuo, Xiaolei; Liu, Xunwei; Song, Shiping; Fan, Chunhai; He, Dannong; Sun, Gang

2014-11-26

Prostate-specific antigen (PSA) is one of the most important biomarkers for the early diagnosis and prognosis of prostate cancer. Although many efforts have been made to achieve significant progress for the detection of PSA, challenges including relative low sensitivity, complicated operation, sophisticated instruments, and high cost remain unsolved. Here, we have developed a strategy combining rolling circle amplification (RCA)-based DNA belts and magnetic bead-based enzyme-linked immunosorbent assay (ELISA) for the highly sensitive and specific detection of PSA. At first, a 96-base circular DNA template was designed and prepared for the following RCA. Single stranded DNA (ssDNA) products from RCA were used as scaffold strand for DNA origami, which was hybridized with three staple strands of DNA. The resulting DNA belts were conjugated with multiple enzymes for signal amplification and then employed to magnetic bead based ELISA for PSA detection. Through our strategy, as low as 50 aM of PSA can be detected with excellent specificity.

A methyltransferase gene from arbuscular mycorrhizal fungi involved in arsenic methylation and volatilization.

PubMed

Li, Jinglong; Sun, Yuqing; Zhang, Xin; Hu, Yajun; Li, Tao; Zhang, Xuemeng; Wang, Zhi; Wu, Songlin; Wu, Zhaoxiang; Chen, Baodong

2018-06-20

Arbuscular mycorrhizal fungi (AMF), ubiquitous symbiotic fungi associated with the majority of terrestrial plants, were demonstrated to play important roles in arsenic (As) translocation and transformation in the plant-soil continuum, and substantially influence plant As tolerance. However, the direct involvement of AMF in As methylation and volatilization and their molecular mechanisms remain unsolved. Here, an arsenite methyltransferase gene RiMT-11 was identified and characterized from AM fungus Rhizophagus irregularis. Heterologous expression of RiMT-11 enhanced arsenite resistance of E. coli (Δars) through methylating As into monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and ultimately volatile trimethyl arsine (TMAs). In a two-compartment in vitro monoxenic cultivation system, methylated and volatile As were also detected from AM symbioses with arsenate addition, accompanied by strong up-regulation of RiMT-11 expression in extraradical hyphae. The present study provided direct evidence and illustrated an underlying mechanism of As methylation and volatilization by AMF, leading to a deeper insight into the role of AMF in As biogeochemical cycling. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cross-industry Performance Modeling: Toward Cooperative Analysis

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

Reece, Wendy Jane; Blackman, Harold Stabler

One of the current unsolved problems in human factors is the difficulty in acquiring information from lessons learned and data collected among human performance analysts in different domains. There are several common concerns and generally accepted issues of importance for human factors, psychology and industry analysts of performance and safety. Among these are the need to incorporate lessons learned in design, to carefully consider implementation of new designs and automation, and the need to reduce human performance-based contributions to risk. In spite of shared concerns, there are several roadblocks to widespread sharing of data and lessons learned from operating experiencemore » and simulation, including the fact that very few publicly accessible data bases exist (Gertman & Blackman, 1994, and Kirwan, 1997). There is a need to draw together analysts and analytic methodologies to comprise a centralized source of data with sufficient detail to be meaningful while ensuring source anonymity. We propose that a generic source of performance data and a multi-domain data store may provide the first steps toward cooperative performance modeling and analysis across industries.« less

Cross-Industry Performance Modeling: Toward Cooperative Analysis

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

H. S. Blackman; W. J. Reece

One of the current unsolved problems in human factors is the difficulty in acquiring information from lessons learned and data collected among human performance analysts in different domains. There are several common concerns and generally accepted issues of importance for human factors, psychology and industry analysts of performance and safety. Among these are the need to incorporate lessons learned in design, to carefully consider implementation of new designs and automation, and the need to reduce human performance-based contributions to risk. In spite of shared concerns, there are several road blocks to widespread sharing of data and lessons learned from operatingmore » experience and simulation, including the fact that very few publicly accessible data bases exist(Gertman & Blackman, 1994, and Kirwan, 1997). There is a need to draw together analysts and analytic methodologies to comprise a centralized source of data with sufficient detail to be meaningful while ensuring source anonymity. We propose that a generic source of performance data and a multi-domain data store may provide the first steps toward cooperative performance modeling and analysis across industries.« less

A Computational Study of the Effect of Winglets on the Performance of Micro-Aerial Vehicles

NASA Astrophysics Data System (ADS)

Mönttinen, Jarmo T.; Reed, Helen L.; Squires, Kyle D.; Saric, William S.

2003-11-01

Since mid-1990's an increased interest in developing Micro-Aerial Vehicles (MAVs) has been expressed by military and civilian entities. An MAV is required to have a nominal maximum dimension of 6 inches and to fly at 5 to 20 m/s, which leads to chord Reynolds numbers of 50,000 to 200,000. Despite a wide variety of research projects in universities, companies, and government agencies, the MAV-design problem remains unsolved to a satisfactory manner. The current study uses the Finite Volume solver Cobalt to computationally investigate the effect of winglets on the performance of MAVs. Historically the effectiveness of winglets is addressed in terms of drag reduction. For MAVs, the increase in lift obtained through the addition of winglets is more important as this increase is required to enable low-speed flight. The current results show that winglets can lead to an increase in lift that is sufficiently large to improve the lift-to-drag-ratio as well despite the increased form drag that is typically larger than the decrease in the induced drag.

The unsolved cyclosporine-induced kidney injury: is paricalcitol a feasible new renoprotective option?

PubMed

Reis, Flávio N F

2010-06-01

The management of cyclosporine A (CsA)-induced nephrotoxicity remains one of the main challenges in kidney transplantation. The animal study by Park et al. proposes that paricalcitol, a vitamin D analog with renoprotective actions reported in other conditions, attenuates CsA-induced kidney injury via the suppression of inflammatory, fibrotic, and apoptotic factors. Before paricalcitol can be considered a feasible new therapeutic option for post-transplantation nephropathy, these interesting data require further studies assessing other mechanisms of CsA-induced nephrotoxicity.

Systems cell biology.

PubMed

Mast, Fred D; Ratushny, Alexander V; Aitchison, John D

2014-09-15

Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology. © 2014 Mast et al.

Analytical Solution of a Generalized Hirota-Satsuma Equation

NASA Astrophysics Data System (ADS)

Kassem, M.; Mabrouk, S.; Abd-el-Malek, M.

A modified version of generalized Hirota-Satsuma is here solved using a two parameter group transformation method. This problem in three dimensions was reduced by Estevez [1] to a two dimensional one through a Lie transformation method and left unsolved. In the present paper, through application of symmetry transformation the Lax pair has been reduced to a system of ordinary equations. Three transformations cases are investigated. The obtained analytical solutions are plotted and show a profile proper to deflagration processes, well described by Degasperis-Procesi equation.

Turbulence in nature and in the laboratory

PubMed Central

Warhaft, Z.

2002-01-01

Fluid turbulence has attracted the attention of physicists, mathematicians, and engineers for over 100 years, yet it remains an unsolved problem. The reasons for the difficulties are outlined and recent advances in describing its small-scale statistical structure are described. Contrary to traditional notions, new experimental evidence indicates that the small scales are anisotropic, reflecting the overall character of the flow. The consequences of this finding with regard to the long-held postulate of the universality of the small-scale turbulence structure are discussed. PMID:11875199

Advancement of High Resolution Radar Polarimetry in Target Verses Clutter Detection, Discrimination, Classification: A. Basic Theory and Modeling of Polarimetric Clutter Phenomenology.

DTIC Science & Technology

1988-07-15

the interim period, polarimetLic measurement data collected at other DOD/NATO/Industrial R/D/M facilities will be used. These basic studies will be...the polarization sphere and its spread can he related either to the coherency factor or the depolarization factor plus descriptive parameters of the...careful study of the concluding sections outlining the overall scenario of solved and unsolved problems. Here, we also refer to the recent report (Dec

Enhancing learning using questions, adjunct to science charts

NASA Astrophysics Data System (ADS)

Holliday, William G.; Benson, Garth

This study supported two hypotheses. First, adjunct questions interacted with a science chart so powerfully that content established as difficult to learn in the pilot and in this study's control groups became easier to learn when charted. Second, students familiar with the chart test before instruction (test exposure) were better prepared to take this test after instruction. This adjunct-question study examined the generalizability of selective-attention and academic-studying hypotheses to a modified science chart medium. About 300 high school students were randomly assigned to four conditions each including a vitamin chart (chart only, test exposure, importance of questions emphasized to students by teachers, and combinational conditions - test exposure and question importance) across 16 biology classrooms. Then these same students were again randomly assigned within each classroom to a control and to four question treatments no questions, questions focusing on easy-to-learn charted content, questions focusing on difficult-to-learn charted content, and a combinational treatment.

Enhancing learning using questions adjunct to science charts

NASA Astrophysics Data System (ADS)

Holliday, William G.; Benson, Garth

This study supported two hypotheses. First, adjunct questions interacted with a science chart so powerfully that content established as difficult to learn in the pilot and in this study's control groups became easier to learn when charted. Second, students familiar with the chart test before instruction (test exposure) were better prepared to take this test after instruction. This adjunct-question study examined the generalizability of selective-attention and academic-studying hypotheses to a modified science chart medium. About 300 high school students were randomly assigned to four conditions each including a vitamin chart (chart only, test exposure, importance of questions emphasized to students by teachers, and combinational conditions--test exposure and question importance) across 16 biology classrooms. Then these same students were again randomly assigned within each classroom to a control and to four question treatments (no questions, questions focusing on easy-to-learn charted content, questions focusing on difficult-to-learn charted content, and a combinational treatment).

Developing a research agenda for the American Society of Colon and Rectal Surgeons: results of a delphi approach.

PubMed

Burt, Caroline G; Cima, Robert R; Koltun, Walter A; Littlejohn, Charles E; Ricciardi, Rocco; Temple, Larissa K; Rothenberger, David A; Baxter, Nancy N

2009-05-01

By use of a systematic approach, the aim of this project was to survey a group of colorectal specialists and reach a consensus on the research questions of highest importance in terms of clinical care. A modified Delphi process was performed. In Round 1 research questions were solicited from members of The American Society of Colon and Rectal Surgeons. A review group categorized the results, combined similar questions, and presented them to The American Society of Colon and Rectal Surgeons membership in Round 2 for prioritizing according to importance. In Round 3 the 50 questions with the highest scores in Round 2 were reranked by The American Society of Colon and Rectal Surgeons membership to produce the 20 highest-priority research questions. A total of 203 respondents in Round 1 submitted 746 questions. The review team reduced these to 105 individual questions encompassing 21 topics in colorectal surgical practice. In Rounds 2 and 3, 399 and 360 respondents, respectively, prioritized the questions presented. The final 20 items included 14 questions related to colorectal cancer, and 6 were on benign disease topics. The research agenda produced by this study reflects the clinical issues of greatest importance to colorectal surgeons. The results are of potential benefit to researchers, funding organizations, medical journals, and ultimately, patients.

Automatic Chinese Factual Question Generation

ERIC Educational Resources Information Center

Liu, Ming; Rus, Vasile; Liu, Li

2017-01-01

Question generation is an emerging research area of artificial intelligence in education. Question authoring tools are important in educational technologies, e.g., intelligent tutoring systems, as well as in dialogue systems. Approaches to generate factual questions, i.e., questions that have concrete answers, mainly make use of the syntactical…

Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México

PubMed Central

2010-01-01

Background In 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems. Methods From 2003 to 2006, four nation-wide cross-sectional probabilistic population based surveys were conducted using a four stage sampling design. Thirty thousand households were visited in each survey. The number of IMSS members interviewed ranged from 79,797 respondents in 2003 to 117,036 respondents in 2006. Results The four surveys showed a substantial increase in coverage indicators for each age group: children, completed schemes of vaccination (> 90%), iron supplementation (17.8% to 65.5%), newborn screening for metabolic disorders (60.3% to 81.6%). Adolescents, measles - rubella vaccine (52.4% to 71.4%), hepatitis vaccine (9.3% to 46.2%), use of condoms (17.9% to 59.9%). Women, measles-rubella vaccine (28.5% to 59-2%), cervical cancer screening (66.7% to 75%), breast cancer screening (> 2.1%). Men, type 2 diabetes screening (38.6% to 57.8%) hypertension screening (48-4% to 64.0%). Older adults, pneumococcal vaccine (13.2% to 24.9%), influenza vaccine (12.6% to 52.9) Regarding the unmet needs, the prevalence of anemia in children was 30% and a growing prevalence of overweight and obesity, type 2 diabetes, and hypertension was found in men, women and older adults. Conclusion PREVENIMSS showed an important increase in the coverage of preventive services and stressed the magnitude of the old and new challenges that this healthcare system faces. The unsolved problems such as anemia, and the emerging ones such as overweight, obesity, among others, point out the need to strength preventive care through designing and implementing innovative programs aimed to attain effective coverage for those conditions in which prevention obtains substandard results. PMID:20626913

Setting Priorities for Diabetic Retinopathy Clinical Research and Identifying Evidence Gaps.

PubMed

Le, Jimmy T; Hutfless, Susan; Li, Tianjing; Bressler, Neil M; Heyward, James; Bittner, Ava K; Glassman, Adam; Dickersin, Kay

2017-01-01

Prioritizing comparative effectiveness research may contribute to obtaining answers that clinicians perceive they need and may minimize research that could be considered wasteful. Our objective was to identify evidence gaps and set priorities for new systematic reviews and randomized controlled trials for managing diabetic retinopathy (DR), including diabetic macular edema (DME). Cross-sectional study. Diabetic Retinopathy Clinical Research Network (DRCR.net) investigators. We provided recommendations from the American Academy of Ophthalmology's 2012 Preferred Practice Patterns for Diabetic Retinopathy as 91 answerable clinical research questions about intervention effectiveness to 410 DRCR.net investigators to rate each question's importance from 0 (not important) to 10 (very important) using a 2-round Delphi survey and to suggest additional questions. We considered questions as high priority if at least 75% of respondents to both rounds assigned an importance rating of 5 or more in round 2. We also extracted outcome measures relevant to DR and asked respondents to identify those that must be measured in all studies. We mapped Cochrane reviews published up to March 2016 to high-priority clinical research questions. Ranking of importance of each clinical question. Thirty-two individuals completed rounds 1 and 2 and suggested 15 questions. Among the final list of 106 clinical research questions, 22 questions met our definition of high priority: 9 of 22 concerned the effectiveness of anti-VEGF therapy, and 13 of 22 focused on how often patients should be followed up (re-examination) and treatment effectiveness in patients with specific characteristics (e.g., DME). Outcomes that 75% or more of respondents marked as "must be measured in all studies" included visual acuity and visual loss, death of participants, and intraocular pressure. Only 1 prioritized question was associated with conclusive evidence from a Cochrane systematic review. A limited response rate among DRCR.net members identified 22 comparative effectiveness research questions as high priority for the management of DR, including DME, but few were associated with Cochrane reviews. These results support the need of systematic reviews and randomized controlled trials to address evidence gaps.

Inertial frames and breakthrough propulsion physics

NASA Astrophysics Data System (ADS)

Millis, Marc G.

2017-09-01

The term ;Breakthrough Propulsion Physics; comes from the NASA project by that name which examined non-rocket space drives, gravity control, and faster-than-light travel. The focus here is on space drives and the related unsolved physics of inertial frames. A ;space drive; is a generic term encompassing any concept for using as-yet undiscovered physics to move a spacecraft instead of existing rockets, sails, or tethers. The collective state of the art spans mostly steps 1-3 of the scientific method: defining the problem, collecting data, and forming hypotheses. The key issues include (1) conservation of momentum, (2) absence of obvious reaction mass, and (3) the net-external thrusting requirement. Relevant open problems in physics include: (1) the sources and mechanisms of inertial frames, (2) coupling of gravitation to the other fundamental forces, and (3) the nature of the quantum vacuum. Rather than following the assumption that inertial frames are an immutable, intrinsic property of space, this paper revisits Mach's Principle, where it is posited that inertia is relative to the distant surrounding matter. This perspective allows conjectures that a space drive could impart reaction forces to that matter, via some as-yet undiscovered interaction with the inertial frame properties of space. Thought experiments are offered to begin a process to derive new hypotheses. It is unknown if this line of inquiry will be fruitful, but it is hoped that, by revisiting unsolved physics from a propulsion point of view, new insights will be gained.

Thinking aloud influences perceived time.

PubMed

Hertzum, Morten; Holmegaard, Kristin Due

2015-02-01

We investigate whether thinking aloud influences perceived time. Thinking aloud is widely used in usability evaluation, yet it is debated whether thinking aloud influences thought and behavior. If thinking aloud is restricted to the verbalization of information to which a person is already attending, there is evidence that thinking aloud does not influence thought and behavior. In an experiment, 16 thinking-aloud participants and 16 control participants solved a code-breaking task 24 times each. Participants estimated task duration. The 24 trials involved two levels of time constraint (timed, untimed) and resulted in two levels of success (solved, unsolved). The ratio of perceived time to clock time was lower for thinking-aloud than control participants. Participants overestimated time by an average of 47% (thinking aloud) and 94% (control). The effect of thinking aloud on time perception also held separately for timed, untimed, solved, and unsolved trials. Thinking aloud (verbalization at Levels 1 and 2) influences perceived time. Possible explanations of this effect include that thinking aloud may require attention, cause a processing shift that overshadows the perception of time, or increase mental workload. For usability evaluation, this study implies that time estimates made while thinking aloud cannot be compared with time estimates made while not thinking aloud, that ratings of systems experienced while thinking aloud may be inaccurate (because the experience of time influences other experiences), and that it may therefore be considered to replace concurrent thinking aloud with retrospective thinking aloud when evaluations involve time estimation.

Decellularized scaffold of cryopreserved rat kidney retains its recellularization potential.

PubMed

Chani, Baldeep; Puri, Veena; Sobti, Ranbir C; Jha, Vivekanand; Puri, Sanjeev

2017-01-01

The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.

Physical activity improves cognition: possible explanations.

PubMed

Koščak Tivadar, Blanka

2017-08-01

Good cognitive abilities (CA) enable autonomy, improve social inclusion and act preventively. Regular physical activity (PA) reduces the risk of developing Alzheimer's disease (AD) and, at the same time, it reduces the decline of CA and stimulates neurogenesis. So PA in connection with cognitive training, nutrition and social interaction has a positive effect on general CA and the central nervous system, the central executor, memory and attention, and reduces the likelihood of developing dementia. Our objective was to examine which sort and intensity of PA is preferred. We did a review, restricted only to human studies, of transparent scientific articles and sample surveys carried out and published in the period between 2001 and 2016 based on the keywords: age, aging, physical activity, physical abilities, cognitive abilities, memory and Alzheimer's disease. According to results CA and PA interact, as an increasing PA of only 10% reduces the risk of dementia and AD significantly. However, there is a question of appropriate intensity of exercise. Low-intensity aerobic exercise has a positive effect on the visual spatial perception and attention, whereas moderate PA has a positive impact on general CA, working memory and attention, verbal memory and attention and vice versa. While the majority of experts recommends vigorous or moderate exercise, many of them warn that higher intensity requires more attention to PA and less to cognitive processes, particularly in terms of reducing reactions, selective attention and flexibility to tasks. There is also a further question what PA should be like. Although some experts believe that the best combination is aerobic PA and exercises against resistance, it is not entirely clear whether the improvement in CA is a result of cardiac vascular fitness. On the other hand, for most elderly it is more suitable to perform an alternative form (not anaerobic) of PA due to comorbidity and actual fragility. We can conclude that PA has a positive effect on CA, but an appropriate intensity and the type of exercise remain unsolved. For the relevant findings it is absolutely necessary to have an interdisciplinary approach.

Engaging High School Youth in Paleobiology Research

NASA Astrophysics Data System (ADS)

Saltzman, J.; Heim, N. A.; Payne, J.

2013-12-01

The chasm between classroom science and scientific research is bridged by the History of Life Internships at Stanford University. Nineteen interns recorded more than 25,500 linear body size measurements of fossil echinoderms and ostracods spanning more than 11,000 species. The interns were selected from a large pool of applicants, and well-established relationships with local teachers at schools serving underrepresented groups in STEM fields were leveraged to ensure a diverse mix of applicants. The lead investigator has been hosting interns in his research group for seven years, in the process measuring over 36,000 foraminfera species as well as representatives from many other fossil groups. We (faculty member, researcher, and educators) all find this very valuable to engage youth in novel research projects. We are able to create an environment where high school students can make genuine contributions to jmportant and unsolved scientific problems, not only through data collection but also through original data analysis. Science often involves long intervals of data collection, which can be tedious, and big questions often require big datasets. Body size evolution is ideally suited to this type of program, as the data collection process requires substantial person-power but not deep technical expertise or expensive equipment. Students are therefore able to engage in the full scientific process, posing previously unanswered questions regarding the evolution of animal size, compiling relevant data, and then analyzing the data in order to test their hypotheses. Some of the projects students developed were truly creative and fun to see come together. Communicating is a critical step in science yet is often lost in the science classroom. The interns submitted seven abstracts to this meeting for the youth session entitled Bright STaRS based on their research projects. To round out the experience, students also learn about the broad field of earth sciences through traditional lectures, active learning exercises, discussions of primary and secondary literature, guest speakers, lab tours and field trips (including to the UC Museum of Paleontology, Hayward fault, fossiliferous Pliocene outcrops, and tidepools). We will use a survey to assess the impact of the History of Life Internships on participant attitudes toward science and careers in science.

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

PubMed Central

Tomé-Carneiro, Joao; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos

2013-01-01

Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol-based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of ‘potential’ benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called ‘Resveratrol Paradox’, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently available evidence regarding resveratrol’s effects on humans obtained from randomized clinical trials. In addition, we will provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug. PMID:23448440

Investigating Consistency of Questions in Primary and Middle School Science Textbooks with Objectives in Science Curriculum

ERIC Educational Resources Information Center

Yaman, Süleyman

2017-01-01

Due to problems related their content and use; textbooks do not achieve the expected effect in learning although they are one of the most important elements of the science curriculum. Questions in textbooks are also important criteria in determining the effect of textbooks. In this study, it was aimed to compare questions in four different science…

The 150 most important questions in cancer research and clinical oncology series: questions 40-49.

PubMed

2017-07-13

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 10 more questions are presented as followed. Question 40. Why do mice being used as tumorigenesis models raised in different places or different conditions possess different tumor formation rate? Question 41. How could we generate more effective anti-metastasis drugs? Question 42. What is the molecular mechanism underlying heterogeneity of cancer cachexia in patients with the same pathologic type? Question 43. Will patients with oligo-metastatic disease be curable by immunotherapy plus stereotactic body radiotherapy? Question 44. Can the Warburg effect regulation be targeted for cancer treatment? Question 45. Why do adenocarcinomas seldom occur in the small intestine? Question 46. Is Epstein-Barr virus infection a causal factor for nasal natural killer/T cell lymphoma formation? Question 47. Why will not all but very few human papillomavirus-infected patients eventually develop cervical cancer? Question 48. Why do cervical carcinomas induced by human papilloma virus have a low mutation rate in tumor suppressor genes? Question 49. Can viral infection trigger lung cancer relapse?

A targeted resequencing gene panel for focal epilepsy.

PubMed

Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

2016-04-26

We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

Medicinal mushroom science: Current perspectives, advances, evidences, and challenges.

PubMed

Wasser, Solomon P

2014-01-01

The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

What causes alopecia areata?

PubMed Central

McElwee, K. J.; Gilhar, A.; Tobin, D. J.; Ramot, Y.; Sundberg, J. P.; Nakamura, M.; Bertolini, M.; Inui, S.; Tokura, Y.; Jr, L. E. King; Duque-Estrada, B.; Tosti, A; Keren, A.; Itami, S.; Shoenfeld, Y.; Zlotogorski, A.; Paus, R.

2014-01-01

The pathobiology of alopecia areata (AA), one of the most frequent autoimmune diseases and a major unsolved clinical problem, has intrigued dermatologists, hair biologists and immunologists for decades. Simultaneously, both affected patients and the physicians who take care of them are increasingly frustrated that there is still no fully satisfactory treatment. Much of this frustration results from the fact that the pathobiology of AA remains unclear, and no single AA pathogenesis concept can claim to be universally accepted. In fact, some investigators still harbour doubts whether this even is an autoimmune disease, and the relative importance of CD8+ T cells, CD4+ T cells and NKGD2+ NK or NKT cells and the exact role of genetic factors in AA pathogenesis remain bones of contention. Also, is AA one disease, a spectrum of distinct disease entities or only a response pattern of normal hair follicles to immunologically mediated damage? During the past decade, substantial progress has been made in basic AA-related research, in the development of new models for translationally relevant AA research and in the identification of new therapeutic agents and targets for future AA management. This calls for a re-evaluation and public debate of currently prevalent AA pathobiology concepts. The present Controversies feature takes on this challenge, hoping to attract more skin biologists, immunologists and professional autoimmunity experts to this biologically fascinating and clinically important model disease. PMID:23947678

Modeling Core Collapse Supernovae

NASA Astrophysics Data System (ADS)

Mezzacappa, Anthony

2017-01-01

Core collapse supernovae, or the death throes of massive stars, are general relativistic, neutrino-magneto-hydrodynamic events. The core collapse supernova mechanism is still not in hand, though key components have been illuminated, and the potential for multiple mechanisms for different progenitors exists. Core collapse supernovae are the single most important source of elements in the Universe, and serve other critical roles in galactic chemical and thermal evolution, the birth of neutron stars, pulsars, and stellar mass black holes, the production of a subclass of gamma-ray bursts, and as potential cosmic laboratories for fundamental nuclear and particle physics. Given this, the so called ``supernova problem'' is one of the most important unsolved problems in astrophysics. It has been fifty years since the first numerical simulations of core collapse supernovae were performed. Progress in the past decade, and especially within the past five years, has been exponential, yet much work remains. Spherically symmetric simulations over nearly four decades laid the foundation for this progress. Two-dimensional modeling that assumes axial symmetry is maturing. And three-dimensional modeling, while in its infancy, has begun in earnest. I will present some of the recent work from the ``Oak Ridge'' group, and will discuss this work in the context of the broader work by other researchers in the field. I will then point to future requirements and challenges. Connections with other experimental, observational, and theoretical efforts will be discussed, as well.

Direct volume estimation without segmentation

NASA Astrophysics Data System (ADS)

Zhen, X.; Wang, Z.; Islam, A.; Bhaduri, M.; Chan, I.; Li, S.

2015-03-01

Volume estimation plays an important role in clinical diagnosis. For example, cardiac ventricular volumes including left ventricle (LV) and right ventricle (RV) are important clinical indicators of cardiac functions. Accurate and automatic estimation of the ventricular volumes is essential to the assessment of cardiac functions and diagnosis of heart diseases. Conventional methods are dependent on an intermediate segmentation step which is obtained either manually or automatically. However, manual segmentation is extremely time-consuming, subjective and highly non-reproducible; automatic segmentation is still challenging, computationally expensive, and completely unsolved for the RV. Towards accurate and efficient direct volume estimation, our group has been researching on learning based methods without segmentation by leveraging state-of-the-art machine learning techniques. Our direct estimation methods remove the accessional step of segmentation and can naturally deal with various volume estimation tasks. Moreover, they are extremely flexible to be used for volume estimation of either joint bi-ventricles (LV and RV) or individual LV/RV. We comparatively study the performance of direct methods on cardiac ventricular volume estimation by comparing with segmentation based methods. Experimental results show that direct estimation methods provide more accurate estimation of cardiac ventricular volumes than segmentation based methods. This indicates that direct estimation methods not only provide a convenient and mature clinical tool for cardiac volume estimation but also enables diagnosis of cardiac diseases to be conducted in a more efficient and reliable way.

Challenge of biomechanics.

PubMed

Volokh, K Y

2013-06-01

The application of mechanics to biology--biomechanics--bears great challenges due to the intricacy of living things. Their dynamism, along with the complexity of their mechanical response (which in itself involves complex chemical, electrical, and thermal phenomena) makes it very difficult to correlate empirical data with theoretical models. This difficulty elevates the importance of useful biomechanical theories compared to other fields of engineering. Despite inherent imperfections of all theories, a well formulated theory is crucial in any field of science because it is the basis for interpreting observations. This is all-the-more vital, for instance, when diagnosing symptoms, or planning treatment to a disease. The notion of interpreting empirical data without theory is unscientific and unsound. This paper attempts to fortify the importance of biomechanics and invigorate research efforts for those engineers and mechanicians who are not yet involved in the field. It is not aimed here, however, to give an overview of biomechanics. Instead, three unsolved problems are formulated to challenge the readers. At the micro-scale, the problem of the structural organization and integrity of the living cell is presented. At the meso-scale, the enigma of fingerprint formation is discussed. At the macro-scale, the problem of predicting aneurysm ruptures is reviewed. It is aimed here to attract the attention of engineers and mechanicians to problems in biomechanics which, in the author's opinion, will dominate the development of engineering and mechanics in forthcoming years.

The 50 Most Important Questions Relating to the Maintenance and Restoration of an Ecological Continuum in the European Alps

PubMed Central

Walzer, Chris; Kowalczyk, Christine; Alexander, Jake M.; Baur, Bruno; Bogliani, Giuseppe; Brun, Jean-Jacques; Füreder, Leopold; Guth, Marie-Odile; Haller, Ruedi; Holderegger, Rolf; Kohler, Yann; Kueffer, Christoph; Righetti, Antonio; Spaar, Reto; Sutherland, William J.; Ullrich-Schneider, Aurelia; Vanpeene-Bruhier, Sylvie N.; Scheurer, Thomas

2013-01-01

The European Alps harbour a unique and species-rich biodiversity, which is increasingly impacted by habitat fragmentation through land-use changes, urbanization and expanding transport infrastructure. In this study, we identified the 50 most important questions relating to the maintenance and restoration of an ecological continuum – the connectedness of ecological processes across many scales including trophic relationship and disturbance processes and hydro-ecological flows in the European Alps. We initiated and implemented a trans-national priority setting exercise, inviting 48 institutions including researchers, conservation practitioners, NGOs, policymakers and administrators from the Alpine region. The exercise was composed of an initial call for pertinent questions, a first online evaluation of the received questions and a final discussion and selection process during a joint workshop. The participating institutions generated 484 initial questions, which were condensed to the 50 most important questions by 16 workshop participants. We suggest new approaches in tackling the issue of an ecological continuum in the Alps by analysing and classifying the characteristics of the resulting questions in a non-prioritized form as well as in a visual conceptualisation of the inter-dependencies among these questions. This priority setting exercise will support research and funding institutions in channelling their capacities and resources towards questions that need to be urgently addressed in order to facilitate significant progress in biodiversity conservation in the European Alps. PMID:23341928

Widening and Deepening Questions in Web-Based Investigative Learning

ERIC Educational Resources Information Center

Kashihara, Akihiro; Akiyama, Naoto

2016-01-01

Web allows learners to investigate any question with a great variety of Web resources, in which they could construct a wider, and deeper knowledge. In such investigative learning process, it is important for them to deepen and widen the question, which involves decomposing the question into the sub-questions to be further investigated. This…

A Patient-centered Approach to Evaluate the Information Needs of Women With Ductal Carcinoma In Situ.

PubMed

Lo, Andrea C; Olson, Robert; Feldman-Stewart, Deb; Truong, Pauline T; Aquino-Parsons, Christina; Bottorff, Joan L; Carolan, Hannah

2017-12-01

To evaluate the information needs of ductal carcinoma in situ (DCIS) patients. Four focus groups involving 24 previously treated DCIS patients were conducted to develop a comprehensive list of questions they felt were important to have answered at the time of diagnosis. Using a survey, a separate group of patients treated for DCIS then rated the importance of having each of these questions addressed before treatment decision making. Response options were "essential," "desired," "not important," "no opinion," and "avoid." For each essential/desired question, respondents specified how addressing it would help them: "understand," "decide," "plan," "not sure," or "other." Focus group participants generated 117 questions used in the survey. Fifty-seven patients completed the survey (55% response rate). Respondents rated a median of 66 questions as essential. The most commonly cited reason for rating a question essential was to "understand," followed by to "decide." The top questions women deemed essential to help them understand were disease specific, whereas the top questions deemed essential to help women decide were predominantly treatment specific, pertaining to available options, recurrence and survival outcomes, and timelines to decide and start treatment. DCIS patients want a large number of questions answered, mostly for understanding, and also for deciding and planning. A core set of questions that most patients consider essential for decision making has been formulated and may be used in the clinical setting and in research to develop educational resources and decision-making tools specific to DCIS.

Important questions asked by family members of intensive care unit patients.

PubMed

Peigne, Vincent; Chaize, Marine; Falissard, Bruno; Kentish-Barnes, Nancy; Rusinova, Katerina; Megarbane, Bruno; Bele, Nicolas; Cariou, Alain; Fieux, Fabienne; Garrouste-Orgeas, Maite; Georges, Hugues; Jourdain, Merce; Kouatchet, Achille; Lautrette, Alexandre; Legriel, Stephane; Regnier, Bernard; Renault, Anne; Thirion, Marina; Timsit, Jean-Francois; Toledano, Dany; Chevret, Sylvie; Pochard, Frédéric; Schlemmer, Benoît; Azoulay, Elie

2011-06-01

Relatives often lack important information about intensive care unit patients. High-quality information is crucial to help relatives overcome the often considerable situational stress and to acquire the ability to participate in the decision-making process, most notably regarding the appropriate level of care. We aimed to develop a list of questions important for relatives of patients in the intensive care unit. This was a multicenter study. Questions asked by relatives of intensive care unit patients were collected from five different sources (literature, panel of 28 intensive care unit nurses and physicians, 1-wk survey of nurses and 1-wk survey of physicians in 14 intensive care units, and in-depth interviews with 14 families). After a qualitative analysis (framework approach and thematic analysis), questions were rated by 22 relatives and 14 intensive care unit physicians, and the ratings were analyzed using principal component analysis and hierarchical clustering. The five sources produced 2,135 questions. Removal of duplicates and redundancies left 443 questions, which were distributed among nine predefined domains using a framework approach ("diagnosis," "treatment," "prognosis," "comfort," "interaction," "communication," "family," "end of life," and "postintensive care unit management"). Thematic analysis in each domain led to the identification of 46 themes, which were reworded as 46 different questions. Ratings by relatives and physicians showed that 21 of these questions were particularly important for relatives of intensive care unit patients. This study increases knowledge about the informational needs of relatives of intensive care unit patients. This list of questions may prove valuable for both relatives and intensive care unit physicians as a tool for improving communication in the intensive care unit.

Signs of Bullying: Important Questions for Parents to Ask

MedlinePlus

... Español Text Size Email Print Share Signs of Bullying: Important Questions for Parents to Ask Page Content ... messages to disappear after a period of time. Bullying Signs Kids who bully often learn the behavior ...

Full-wave modeling of EMIC waves near the He + gyrofrequency

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

Kim, Eun -Hwa; Johnson, Jay R.

Electromagnetic ion cyclotron (EMIC) waves are known to be excited by the cyclotron instability associated with hot and anisotropic ion distributions in the equatorial region of the magnetosphere and are thought to play a key role in radiation belt losses. Although detection of these waves at the ground can provide a global view of the EMIC wave environment, it is not clear what signatures, if any, would be expected. One of the significant scientific issues concerning EMIC waves is to understand how these waves are detected at the ground. In order to solve this puzzle, it is necessary to understandmore » the propagation characteristics of the field-aligned EMIC waves, which include polarization reversal, cutoff, resonance, and mode coupling between different wave modes, in a dipolar magnetic field. However, the inability of ray tracing to adequately describe wave propagation near the crossover cutoff-resonance frequencies in multi-ion plasmas is one of reasons why these scientific questions remain unsolved. Using a recently developed 2-D full-wave code that solves the full-wave equations in global magnetospheric geometry, we demonstrate how EMIC waves propagate from the equatorial region to higher magnetic latitude in an electron-proton-He+ plasma. We find that polarization reversal occurs at the crossover frequency from left-hand polarization (LHP) to right-hand (RHP) polarization and such RHP EMIC waves can either propagate to the inner magnetosphere or reflect to the outer magnetosphere at the Buchsbaum resonance location. Lastly, we also find that mode coupling from guided LHP EMIC waves to unguided RHP or LHP waves (i.e., fast mode) occurs.« less

Translational research in infectious disease: current paradigms and challenges ahead

PubMed Central

Fontana, Judith M.; Alexander, Elizabeth; Salvatore, Mirella

2012-01-01

In recent years, the biomedical community has witnessed a rapid scientific and technological evolution following the development and refinement of high-throughput methodologies. Concurrently and consequentially, the scientific perspective has changed from the reductionist approach of meticulously analyzing the fine details of a single component of biology, to the “holistic” approach of broadmindedly examining the globally interacting elements of biological systems. The emergence of this new way of thinking has brought about a scientific revolution in which genomics, proteomics, metabolomics and other “omics” have become the predominant tools by which large amounts of data are amassed, analyzed and applied to complex questions of biology that were previously unsolvable. This enormous transformation of basic science research and the ensuing plethora of promising data, especially in the realm of human health and disease, have unfortunately not been followed by a parallel increase in the clinical application of this information. On the contrary, the number of new potential drugs in development has been steadily decreasing, suggesting the existence of roadblocks that prevent the translation of promising research into medically relevant therapeutic or diagnostic application. In this paper we will review, in a non-inclusive fashion, several recent scientific advancements in the field of translational research, with a specific focus on how they relate to infectious disease. We will also present a current picture of the limitations and challenges that exist for translational research, as well as ways that have been proposed by the National Institutes of Health to improve the state of this field. PMID:22633095

Global health and orthopaedic surgery—A call for international morbidity and mortality conferences

PubMed Central

Sheth, Neil P.; Donegan, Derek J.; Foran, Jared R.H.; Sugarman, Jeremy

2014-01-01

Introduction There is a large discrepancy between supply and demand of surgical services in developing countries. This inequality holds true in orthopaedic surgery and the delivery of musculoskeletal care. Intertwined amongst the decision to perform surgical procedures in the developing world are the ethics of doing so – just because one is capable of performing a procedure, should it be done? Presentation of case A 31 year-old female with end-stage joint destruction underwent a left total hip replacement by a foreign orthopaedic team in Tanzania. She had a favorable outcome for 8 months, but is now diagnosed with tuberculosis and a deep space infection in her prosthetic left hip – an unsolvable problem in the developing world. Discussion This case demonstrates the ethical challenges that can be created from performing surgical procedures in the developing world without concomitant access to appropriate patient follow-up or resources for treating post-operative complications. While the current system is inadequate to manage the burden of disease, these inadequacies may be exacerbated at times by post-operative complications resulting from well-intentioned surgical missions. Conclusion This case illustrates many difficulties in caring for individuals in the developing world, raising several questions: (1) How can complications be prevented in the future? (2) What are possible ways of managing complications with resources at hand once it occurs? (3) What resources are needed to minimize patient? Ideally an international forum can help provide descriptions of issues and problems that are encountered so as to increase awareness and identify potential solutions. PMID:25524304

Using Stochastic Spiking Neural Networks on SpiNNaker to Solve Constraint Satisfaction Problems

PubMed Central

Fonseca Guerra, Gabriel A.; Furber, Steve B.

2017-01-01

Constraint satisfaction problems (CSP) are at the core of numerous scientific and technological applications. However, CSPs belong to the NP-complete complexity class, for which the existence (or not) of efficient algorithms remains a major unsolved question in computational complexity theory. In the face of this fundamental difficulty heuristics and approximation methods are used to approach instances of NP (e.g., decision and hard optimization problems). The human brain efficiently handles CSPs both in perception and behavior using spiking neural networks (SNNs), and recent studies have demonstrated that the noise embedded within an SNN can be used as a computational resource to solve CSPs. Here, we provide a software framework for the implementation of such noisy neural solvers on the SpiNNaker massively parallel neuromorphic hardware, further demonstrating their potential to implement a stochastic search that solves instances of P and NP problems expressed as CSPs. This facilitates the exploration of new optimization strategies and the understanding of the computational abilities of SNNs. We demonstrate the basic principles of the framework by solving difficult instances of the Sudoku puzzle and of the map color problem, and explore its application to spin glasses. The solver works as a stochastic dynamical system, which is attracted by the configuration that solves the CSP. The noise allows an optimal exploration of the space of configurations, looking for the satisfiability of all the constraints; if applied discontinuously, it can also force the system to leap to a new random configuration effectively causing a restart. PMID:29311791

Meaningful coping with chronic pain: Exploring the interplay between goal violation, meaningful coping strategies and life satisfaction in chronic pain patients.

PubMed

Dezutter, Jessie; Dewitte, Laura; Thauvoye, Evalyne; Vanhooren, Siebrecht

2017-02-01

Trying to cope with chronic pain is a highly demanding and challenging task and pain patients often need to reformulate goals or aspirations due to their pain condition. This goal violation is often related with experienced distress and requires coping processes in order to decrease the distress and stimulate a healthy adaptation. Some scholars, however, argued that in so-called unsolvable or irreparable stressors such as chronic pain, conventional coping strategies like problem-focused coping might not be the most adaptive option. In these situations, meaningful coping strategies attempting to transform the meaning of the stressful experience would be more accurate. In this study, we aim to test if goal violation triggers meaningful coping strategies over time and whether engagement in these meaningful coping strategies result in improved life satisfaction, as an indicator of adaptation. A longitudinal three wave study in a sample of paint patients (n = 125) tests whether goal violation triggers positive reappraisal and downward comparison, two possible meaningful coping strategies. The study furthermore tests if engagement in these strategies results in a better adaptation to the pain condition, reflected in higher life satisfaction. Results partially supported our hypotheses by pointing to the benevolent role of downward comparison on life satisfaction via decreased goal violation of pain patients. Our findings however did also show that positive reappraisal predicted lower life satisfaction via increased levels of appraised goal violation which questions the role of positive reappraisal as a genuine meaningful coping strategy. Implications and limitations are discussed. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors

PubMed Central

Dienstmann, R.; Rodon, J.; Prat, A.; Perez-Garcia, J.; Adamo, B.; Felip, E.; Cortes, J.; Iafrate, A. J.; Nuciforo, P.; Tabernero, J.

2014-01-01

The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1–4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1–4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors. PMID:24265351

Can cloud point-based enrichment, preservation, and detection methods help to bridge gaps in aquatic nanometrology?

PubMed

Duester, Lars; Fabricius, Anne-Lena; Jakobtorweihen, Sven; Philippe, Allan; Weigl, Florian; Wimmer, Andreas; Schuster, Michael; Nazar, Muhammad Faizan

2016-11-01

Coacervate-based techniques are intensively used in environmental analytical chemistry to enrich and extract different kinds of analytes. Most methods focus on the total content or the speciation of inorganic and organic substances. Size fractionation is less commonly addressed. Within coacervate-based techniques, cloud point extraction (CPE) is characterized by a phase separation of non-ionic surfactants dispersed in an aqueous solution when the respective cloud point temperature is exceeded. In this context, the feature article raises the following question: May CPE in future studies serve as a key tool (i) to enrich and extract nanoparticles (NPs) from complex environmental matrices prior to analyses and (ii) to preserve the colloidal status of unstable environmental samples? With respect to engineered NPs, a significant gap between environmental concentrations and size- and element-specific analytical capabilities is still visible. CPE may support efforts to overcome this "concentration gap" via the analyte enrichment. In addition, most environmental colloidal systems are known to be unstable, dynamic, and sensitive to changes of the environmental conditions during sampling and sample preparation. This delivers a so far unsolved "sample preparation dilemma" in the analytical process. The authors are of the opinion that CPE-based methods have the potential to preserve the colloidal status of these instable samples. Focusing on NPs, this feature article aims to support the discussion on the creation of a convention called the "CPE extractable fraction" by connecting current knowledge on CPE mechanisms and on available applications, via the uncertainties visible and modeling approaches available, with potential future benefits from CPE protocols.

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

NASA Astrophysics Data System (ADS)

Wang, Jun-Song; Wang, Mei-Li; Li, Xiao-Li; Ernst, Niebur

2015-03-01

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model (NPM). We propose that a proportional-derivative (PD) type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM. Project supported by the National Natural Science Foundation of China (Grant Nos. 61473208, 61025019, and 91132722), ONR MURI N000141010278, and NIH grant R01EY016281.

Full-wave modeling of EMIC waves near the He + gyrofrequency

DOE PAGES

Kim, Eun -Hwa; Johnson, Jay R.

2016-01-06

Electromagnetic ion cyclotron (EMIC) waves are known to be excited by the cyclotron instability associated with hot and anisotropic ion distributions in the equatorial region of the magnetosphere and are thought to play a key role in radiation belt losses. Although detection of these waves at the ground can provide a global view of the EMIC wave environment, it is not clear what signatures, if any, would be expected. One of the significant scientific issues concerning EMIC waves is to understand how these waves are detected at the ground. In order to solve this puzzle, it is necessary to understandmore » the propagation characteristics of the field-aligned EMIC waves, which include polarization reversal, cutoff, resonance, and mode coupling between different wave modes, in a dipolar magnetic field. However, the inability of ray tracing to adequately describe wave propagation near the crossover cutoff-resonance frequencies in multi-ion plasmas is one of reasons why these scientific questions remain unsolved. Using a recently developed 2-D full-wave code that solves the full-wave equations in global magnetospheric geometry, we demonstrate how EMIC waves propagate from the equatorial region to higher magnetic latitude in an electron-proton-He+ plasma. We find that polarization reversal occurs at the crossover frequency from left-hand polarization (LHP) to right-hand (RHP) polarization and such RHP EMIC waves can either propagate to the inner magnetosphere or reflect to the outer magnetosphere at the Buchsbaum resonance location. Lastly, we also find that mode coupling from guided LHP EMIC waves to unguided RHP or LHP waves (i.e., fast mode) occurs.« less

A new conceptual model of coral biomineralisation: hypoxia as the physiological driver of skeletal extension

NASA Astrophysics Data System (ADS)

Wooldridge, S. A.

2012-09-01

That corals skeletons are built of aragonite crystals with taxonomy-linked ultrastructure has been well understood since the 19th century. Yet, the way by which corals control this crystallization process remains an unsolved question. Here, I outline a new conceptual model of coral biominerationsation that endeavours to relate known skeletal features with homeostatic functions beyond traditional growth (structural) determinants. In particular, I propose that the dominant physiological driver of skeletal extension is night-time hypoxia, which is exacerbated by the respiratory oxygen demands of the coral's algal symbionts (= zooxanthellae). The model thus provides a new narrative to explain the high growth rate of symbiotic corals, by equating skeletal deposition with the "work-rate" of the coral host needed to maintain a stable and beneficial symbiosis. In this way, coral skeletons are interpreted as a continuous (long-run) recording unit of the stability and functioning of the coral-algae endosymbiosis. After providing supportive evidence for the model across multiple scales of observation, I use coral core data from the Great Barrier Reef (Australia) to highlight the disturbed nature of the symbiosis in recent decades, but suggest that its onset is consistent with a trajectory that has been followed since at least the start of the 1900's. In concluding, I explain how the evolved capacity of the cnidarians (which now includes modern reef corals) to overcome the metabolic limitation of hypoxia via skeletogenesis, may underpin the sudden appearance in the fossil record of calcified skeletons at the Precambrian-Cambrian transition - and the ensuing rapid appearance of most major animal phyla.

A new conceptual model of coral biomineralisation: hypoxia as the physiological driver of skeletal extension

NASA Astrophysics Data System (ADS)

Wooldridge, S.

2013-05-01

That corals skeletons are built of aragonite crystals with taxonomy-linked ultrastructure has been well understood since the 19th century. Yet, the way by which corals control this crystallization process remains an unsolved question. Here, I outline a new conceptual model of coral biomineralisation that endeavours to relate known skeletal features with homeostatic functions beyond traditional growth (structural) determinants. In particular, I propose that the dominant physiological driver of skeletal extension is night-time hypoxia, which is exacerbated by the respiratory oxygen demands of the coral's algal symbionts (= zooxanthellae). The model thus provides a new narrative to explain the high growth rate of symbiotic corals, by equating skeletal deposition with the "work-rate" of the coral host needed to maintain a stable and beneficial symbiosis. In this way, coral skeletons are interpreted as a continuous (long-run) recording unit of the stability and functioning of the coral-algae endosymbiosis. After providing supportive evidence for the model across multiple scales of observation, I use coral core data from the Great Barrier Reef (Australia) to highlight the disturbed nature of the symbiosis in recent decades, but suggest that its onset is consistent with a trajectory that has been followed since at least the start of the 1900s. In concluding, I outline how the proposed capacity of cnidarians (which includes modern reef corals) to overcome the metabolic limitation of hypoxia via skeletogenesis also provides a new hypothesis to explain the sudden appearance in the fossil record of calcified skeletons at the Precambrian-Cambrian transition - and the ensuing rapid appearance of most major animal phyla.

Computer-assisted handwriting style identification system for questioned document examination

NASA Astrophysics Data System (ADS)

Cha, Sung-Hyuk; Yoon, Sungsoo; Tappert, Charles C.; Lee, Yillbyung

2005-03-01

Handwriting originates from a particular copybook style such as Palmer or Zaner-Bloser that one learns in childhood. Since questioned document examination plays an important investigative and forensic role in many types of crime, it is important to develop a system that helps objectively identify a questioned document"s handwriting style. Here, we propose a computer vision system that can assist a document examiner in the identification of a writer"s handwriting style and therefore the origin or nationality of an unknown writer of a questioned document. We collected 33 Roman alphabet copybook styles from 18 countries. Each character in a questioned document is segmented and matched against all of the 33 handwriting copybook styles. The more characters present in the questioned document, the higher the accuracy observed.

Main information requests of family members of patients in Intensive Care Units.

PubMed

Velasco Bueno, J M; Alonso-Ovies, A; Heras La Calle, G; Zaforteza Lallemand, C

2017-11-03

To compile an inventory of information requests prioritized by the family members, to find out which professionals them consider able to respond these requests, and to explore the differences in perception between family members and professionals. Qualitative analysis of content validation and descriptive cross-sectional study. 41 Spanish ICU. Relatives, physicians and nurses of critical patients. From an initial list of questions extracted from literature review, physicians, nurses, and relatives of critical patients incorporated issues that they considered not included. After analyzing content validity, a new list was obtained, which was again submitted to the participants' assessment to evaluate the level of importance that they assigned to each question and which professional they considered appropriate to answer it. most important questions for the relatives: concern about the clinical situation, measures to be taken, prognosis and information. There was a coincidence between relatives and professionals in the priority issues for families. There were significant differences in the importance given to each question: between doctors and relatives (72/82 questions), and between nurses and relatives (66/82 questions) (P<.05). For the relatives, 63% of the questions could be answered by doctors or nurses, 27% preferably by doctors and 10% by nurses. The most relevant issues for families were prognosis and severity, but also the need for information. Healthcare professionals tend to underestimate the importance of many of the questions that concern families. Relatives feel that most of their concerns can be resolved either by doctors or nurses. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

[Substance abuse and toxicity. Fetal drug syndrome].

PubMed

Rodé, Magdolna

2003-08-10

24% of the 16 years old adolescents have already consumed so called substances suitable for abuse. We must make children, teachers, parents, lawyers, priests, physicians and family aware of the effects and outcomes of drug use. This is just one of the many similar unsolved problems of society like AIDS and smoking. It is imperative that education for healthy lifestyle should be thought at every level of social life. Fighting against the hard problems emerging from drug abuse must be continuously kept on the right place in teaching medicine and in our everyday activity.

Riddles about the origin and thermal history of the moon

NASA Technical Reports Server (NTRS)

Levin, B. Y.; Mayeva, S. V.

1977-01-01

Magmatic differentiation of the moon's interior, confirmed through calculations of thermal history, was studied. It appears that differentiation was a result of the moon's initial temperature whose origin remains unknown. In solving this problem, convective models of the moon were considered as well as a two layered differentiated model of the moon, operative over the past 3.5 billion years. The high content of long lived radioactive elements present was investigated in explaining the moon's current thermal properties. The controversy concerning the true nature of magmatic differentiation continues to be unsolved.

Military Implications of a Possible World Order Crisis in the 1980s

DTIC Science & Technology

1977-11-01

for "the tardy growth of stable inde- pendent combinations among hired journeymen" in England. They found it "in the prospects of economic...P^^W^WW^: I™T"™ ...»jjiiijiiinwiiiiimnpni —mmumimK 11 ,�ŕ ’ "ll’liH-^B^W^piWI -31- Presldent Ferdinand E. Marcos of the Philippines , who... Philippines (mimeo). 2 Dial Torgerson, "U.N. Economic Talks Close With Most Conference Problems Still Unsolved," The Los Angeles Times, June 1, 1976

Autonomy in the Industrial R&D Lab

DTIC Science & Technology

1984-10-01

engineers. Organizational Behavior and Human Performance, 18, 1977, 329-345. Kubie , L. S. Some unsolved problems of the scientific career. American...MtNS DTK 0U4-2 SE;.EC!I3V k raELIMIVARf . :«I»LDCJIMC SiCTlOV CSMfROM SI«TI3M Mrxa^DPIA. V« 2Z3H JlFt^Jr.1 TtCHMtCSL...iCriill IICH. INFORMATION CTR. » TIN: 3TIC DU«-2 JELECTICIi k . PF(rLlr’ItJAr<Y ; MALUGJl JGSSELT ICN :,\\MEPn^ SIATICN ALEXA’>3RIA

Classical integrable many-body systems disconnected with semi-simple Lie algebras

NASA Astrophysics Data System (ADS)

Inozemtsev, V. I.

2017-05-01

The review of the results in the theory of integrable many-body systems disconnected with semisimple Lie algebras is done. The one-dimensional systems of light Calogero-Sutherland-Moser particles interacting with one particle of infinite mass located at the origin are described in detail. In some cases the exact solutions of the equations of motion are obtained. The general theory of integration of the equations of motion needs the methods of algebraic geometry. The Lax pairs with spectral parameter are constructed for this purpose. The theory still contains many unsolved problems.

Organ donation: a significant marketing challenge.

PubMed

Clarke, Roberta N

2007-01-01

Unlike most health care markets, the organ donation market is one where patients are the marketers, prospective donors are the customers, and no payment is allowed in the exchange process. The assumption that altruistic behavior by donors would satisfy the need for organs has proven woefully untrue. As a result, those needing organs have resorted to relying on unwilling or impoverished donors, to having to promote themselves on websites which have achieved success for only small numbers of patients, or to waiting for organs which they may never receive. This remains a still unsolved marketing challenge.

Scenario Decomposition for 0-1 Stochastic Programs: Improvements and Asynchronous Implementation

DOE PAGES

Ryan, Kevin; Rajan, Deepak; Ahmed, Shabbir

2016-05-01

We recently proposed scenario decomposition algorithm for stochastic 0-1 programs finds an optimal solution by evaluating and removing individual solutions that are discovered by solving scenario subproblems. In our work, we develop an asynchronous, distributed implementation of the algorithm which has computational advantages over existing synchronous implementations of the algorithm. Improvements to both the synchronous and asynchronous algorithm are proposed. We also test the results on well known stochastic 0-1 programs from the SIPLIB test library and is able to solve one previously unsolved instance from the test set.

Exploring the anomaly in the interaction cross section and matter radius of (23)O

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

Kanungo, R.; Uchida, M.; Perro, C.

New measurements of the interaction cross sections of {sup 22,23}O at 900A MeV performed at the GSI, Darmstadt are reported that address the unsolved puzzle of the large cross section previously observed for {sup 23}O. The matter radii for these oxygen isotopes extracted through a Glauber model analysis are in good agreement with the new predictions of the ab initio coupled-cluster theory reported here. They are consistent with a {sup 22}O + neutron description of {sup 23}O as well.

Has modern perinatal practice caused the fall in perinatal mortality? The experience of a district maternity hospital.

PubMed

Shepherd, R C; Ridley, W; Struthers, J O

1983-07-01

During the first 12 years of operation the perinatal mortality rate in Paisley Maternity Hospital fell steadily from 27 per 1,000 in 1970 to 10 per 1,000 in 1981. During this period the nulliparous birth rate remained constant, but the parous birth rate fell. Improved survival of premature babies, falling numbers of babies with neural tube defects and reduction in intrapartum asphyxia are identified as responsible for this fall. Unexplained intra-uterine death remains an unsolved problem.

On the relativistic micro-canonical ensemble and relativistic kinetic theory for N relativistic particles in inertial and non-inertial rest frames

NASA Astrophysics Data System (ADS)

Alba, David; Crater, Horace W.; Lusanna, Luca

2015-03-01

A new formulation of relativistic classical mechanics allows a reconsideration of old unsolved problems in relativistic kinetic theory and in relativistic statistical mechanics. In particular a definition of the relativistic micro-canonical partition function is given strictly in terms of the Poincaré generators of an interacting N-particle system both in the inertial and non-inertial rest frames. The non-relativistic limit allows a definition of both the inertial and non-inertial micro-canonical ensemble in terms of the Galilei generators.

Types and Cognitive Levels of Questions Asked by Professors during College of Agriculture Class Sessions

ERIC Educational Resources Information Center

Ewing, John C.; Whittington, M. Susie

2007-01-01

One common teacher behavior exhibited in college of agriculture class sessions is oral questioning of students. Belland, Belland, and Price (1971) believed that if questioning was a noted teacher behavior, then it was important to evaluate and analyze questions asked by professors. Professors use questions to control classroom interactions,…

A Risk Assessment Methodology and Excel Tool for Acquisition Programs

DTIC Science & Technology

2013-01-01

Importance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11...readily available to an assessor at the OSD level. Questions that measure these standards are assigned (1) an importance (i.e., mag- nitude of the negative...i.e., the level to which it has been ensured that the question-related standard has been met). The sum product of the importance and completeness

Setting priorities for comparative effectiveness research on management of primary angle closure: a survey of Asia-Pacific clinicians.

PubMed

Yu, Tsung; Li, Tianjing; Lee, Kinbo J; Friedman, David S; Dickersin, Kay; Puhan, Milo A

2015-01-01

To set priorities for new systematic reviews (SRs) and randomized clinical trials on the management of primary angle closure (PAC) using clinical practice guidelines and a survey of Asia-Pacific clinicians. We restated the American Academy of Ophthalmology's Preferred Practice Patterns recommendations for management of PAC into answerable clinical questions. We asked participants at the Asia-Pacific Joint Glaucoma Congress 2010 in Taipei to rate the importance of having an answer to each question for providing effective patient care, using a Likert-type scale and scoring from 0 (not important at all) to 10 (highly important). We identified relevant SRs and mapped the evidence to clinical questions to identify evidence gaps. We generated 42 clinical questions. One hundred seventy-five individuals agreed to participate in the survey, 132 responded (75.4% response rate) and 96 completed the questionnaire (54.9% usable response rate). Questions rated important include laser iridotomy for the prevention of angle closure in primary angle-closure suspects, further therapies in eyes with plateau iris syndrome after laser iridotomy, and evaluation of the fellow eye in acute angle-closure patients for improving prognosis. Up-to-date and conclusive SR evidence was not available for any of the 42 clinical questions. We identified high priority clinical questions on the management of PAC, none of which had reliable SR evidence available. New SRs and randomized clinical trials can be initiated to address these evidence gaps.

75 FR 1620 - Agency Information Collection Activities: Final Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... the survey: 1. Added question--Years in Business in Part 1, Question 1. 2. Removed ``Medium-term Loan... mandate (Export-Import Act of 1945, as amended, 12 U.S.C. 635) which directs the Export-Import Bank to...

Fatty Acid Profile of Neutral and Polar Lipid Fraction of Wild Eggs and Hatchlings from Wild and Captive Reared Broodstock of Octopus vulgaris

PubMed Central

Estefanell, Juan; Mesa-Rodríguez, Antonio; Ramírez, Besay; La Barbera, Antonio; Socorro, Juan; Hernandez-Cruz, Carmen María; Izquierdo, María Soledad

2017-01-01

The culture of Octopus vulgaris is constrained by unsolved problems in paralarvae rearing, mainly associated to the unknown nutritional requirements of this species in early stages. In this article we studied the fatty acid profile (total, neutral, and polar lipid fractions) in wild eggs and wild hatchlings, collected in Gran Canaria (SW) (Spain) with artificial dens, in comparison to hatchlings obtained in captivity from broodstock fed on trash fish species. Total lipids were 11.5–13.5% dw, with the polar fraction representing a 70.6–75.5% of total lipid, with lower values in wild hatchling in comparison with captive ones. Docosahexaenoic acid (DHA) was the main component in neutral and polar fatty acid profile in all samples, underlying its importance in this species. Decreasing levels of saturates and arachidonic acid (ARA) from wild eggs to hatchlings, mainly associated to the polar fraction, suggest their use during embryonic development. In hatchlings, increasing levels of oleic acid in the neutral fraction and eicosapentaenoic acid (EPA) in the polar fraction, suggests their importance in hatchlings quality. Wild hatchlings showed in the polar fraction higher oleic acid and ARA, and lower DHA/ARA and EPA/ARA ratios in comparison with captive hatchlings, suggesting a difference in paralarvae nutritional status. These results suggest the importance of n-3 highly unsaturated fatty acids (HUFA), oleic acid, and ARA, presented in the adequate lipid fraction, in the diet of broodstock and paralarvae of O. vulgaris. PMID:28790921

Connecting LHC signals with deep physics at the TeV scale and baryogenesis

NASA Astrophysics Data System (ADS)

Shu, Jing

We address in this dissertation two primary questions aimed at deciphering collider signals at the Large Hadron Collider (LHC) to give a deep and concrete understanding of the TeV scale physics and to interpret the origin of baryon asymmetry in our universe. We are at a stage of exploring new physics at the terascale which is responsible for the electroweak symmetry breaking (EWSB) in the Standard Model (SM) of particle physics. The LHC, which begins its operation this year, will break us into such a new energy frontier and seek for the possible signals of new physics. Theorists have come up with many possible models beyond SM to explain the origin of EWSB. However, how we will determine the underlying physics from LHC data is still an open question. In the first part of this dissertation, we consider several examples to connect the expected LHC signals to the underlying physics in a completely model independent way. We first explore the Randall-Sundrum (RS) scenario, and use the collider signals of first Kaluza-Klein (KK) excitations of gluons to discriminate several commonly considered theories which attempt to render RS consistent with precision electroweak data. We then investigate top compositeness. We derive a bound for the energy scale of right handed top compositeness from top pair production at the Tevatron, and we find that the cross section to produce four tops will be greatly amplified by 3 orders of magnitude. We next consider the possibilities that the gauge symmetry in the underlying theory is violated in the incomplete theory that we can reconstruct from the LHC observables. We derive a model independent bound on the scale of new physics from unitarity of the S-matrix if we observe a new massive vector boson with nonzero axial couplings to fermions at LHC. Finally, we derive a generalized Landau-Yang theorem and apply it to the Z' decay into two Z bosons. We show that there is a phase shift in the azimuthal angle distribution in the normalized differential cross section and the anomalous coupling of Z'-Z-Z can be discriminated from the regular one at the 3s level when both Z bosons decay leptonically at the LHC. The origin of baryon asymmetry of the Universe (BAU) remains an important, unsolved problem for particle physics and cosmology, and is one of the motivations to search for possible new physics beyond SM. In the second part of this dissertation, we attempt to account for the baryon number generation in our universe through some novel mechanisms. We first systematically investigate models of baryogenesis from spontaneously Lorentz violating background (SLVB). We find that the sphaleron transitions will generate a nonzero B+L asymmetry in the presence of SLVB and we identify two scenarios of interest. We then consider the possibilities to generate a baryon asymmetry through an earlier time phase transition and address the question whether or not we can still test the baryogenesis mechanism at LHC/ILC if the electroweak phase transition is not strongly first order. We find a general framework and realize this idea in the top flavor model. We show that the realistic baryon density can be achieved in the natural parameter space of topflavor model.

Optograms and criminology: science, news reporting, and fanciful novels.

PubMed

Lanska, Douglas J

2013-01-01

A persistent nineteenth-century urban legend was the notion that photograph-like images of the last-seen object or person would be preserved in the eyes of the dead. This popular notion followed technological developments (the daguerreotype and ophthalmoscope) that antedated by decades a basic understanding of retinal physiology. From 1876 to 1877, Boll described photochemical bleaching of the retina and produced a crude retinal image that remained briefly visible after death in an experimental animal. From 1877 to 1881, Kühne elaborated the processes involved in photochemical transduction, and created more complex retinal images, or "optograms," that were visible after the death of experimental animals under special laboratory circumstances. In 1880, Kühne reported the first human "optogram" when he examined the eyes following the state execution of a convicted murderer. Although the work of these physiologists increased public interest in "optography" as a potential tool in forensic investigations, Kühne and his student, Ayres, concluded after an extensive series of investigations that optography would never be useful for this purpose. Nevertheless, because of the prior tantalizing results, optography became a frequent consideration in speculative news reports of sensational unsolved murders, and as a plot device in works of fiction, some quite fantastical. Fictional portrayals included works by Rudyard Kipling and Jules Verne. Despite denouncement of optography for forensic investigations by Kühne, and by numerous physicians, the general public and mass media continued to press for examination of the retinae of murder victims well into the twentieth century, particularly in high-profile unsolved cases. © 2013 Elsevier B.V. All rights reserved.

Gene identification in the congenital disorders of glycosylation type I by whole-exome sequencing.

PubMed

Timal, Sharita; Hoischen, Alexander; Lehle, Ludwig; Adamowicz, Maciej; Huijben, Karin; Sykut-Cegielska, Jolanta; Paprocka, Justyna; Jamroz, Ewa; van Spronsen, Francjan J; Körner, Christian; Gilissen, Christian; Rodenburg, Richard J; Eidhof, Ilse; Van den Heuvel, Lambert; Thiel, Christian; Wevers, Ron A; Morava, Eva; Veltman, Joris; Lefeber, Dirk J

2012-10-01

Congenital disorders of glycosylation type I (CDG-I) form a growing group of recessive neurometabolic diseases. Identification of disease genes is compromised by the enormous heterogeneity in clinical symptoms and the large number of potential genes involved. Until now, gene identification included the sequential application of biochemical methods in blood samples and fibroblasts. In genetically unsolved cases, homozygosity mapping has been applied in consanguineous families. Altogether, this time-consuming diagnostic strategy led to the identification of defects in 17 different CDG-I genes. Here, we applied whole-exome sequencing (WES) in combination with the knowledge of the protein N-glycosylation pathway for gene identification in our remaining group of six unsolved CDG-I patients from unrelated non-consanguineous families. Exome variants were prioritized based on a list of 76 potential CDG-I candidate genes, leading to the rapid identification of one known and two novel CDG-I gene defects. These included the first X-linked CDG-I due to a de novo mutation in ALG13, and compound heterozygous mutations in DPAGT1, together the first two steps in dolichol-PP-glycan assembly, and mutations in PGM1 in two cases, involved in nucleotide sugar biosynthesis. The pathogenicity of the mutations was confirmed by showing the deficient activity of the corresponding enzymes in patient fibroblasts. Combined with these results, the gene defect has been identified in 98% of our CDG-I patients. Our results implicate the potential of WES to unravel disease genes in the CDG-I in newly diagnosed singleton families.

Somatic APC mosaicism and oligogenic inheritance in genetically unsolved colorectal adenomatous polyposis patients.

PubMed

Ciavarella, Michele; Miccoli, Sara; Prossomariti, Anna; Pippucci, Tommaso; Bonora, Elena; Buscherini, Francesco; Palombo, Flavia; Zuntini, Roberta; Balbi, Tiziana; Ceccarelli, Claudio; Bazzoli, Franco; Ricciardiello, Luigi; Turchetti, Daniela; Piazzi, Giulia

2018-03-01

Germline variants in the APC gene cause familial adenomatous polyposis. Inherited variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism have been reported as alternative causes of polyposis. However, ~30-50% of cases of polyposis remain genetically unsolved. Thus, the aim of this study was to investigate the genetic causes of unexplained adenomatous polyposis. Eight sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous polyps by 55 years of age, and no causative germline variants in APC and/or MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal polyposis. APC gene mosaicism was investigated on DNA from colonic adenomas by Sanger sequencing or Whole Exome Sequencing (WES). Mosaicism extension to other tissues (peripheral blood, saliva, hair follicles) was evaluated using Sanger sequencing and/or digital PCR. APC second hit was investigated in adenomas from mosaic patients. WES was performed on DNA from peripheral blood to identify additional polyposis candidate variants. We identified APC mosaicism in 50% of patients. In three cases mosaicism was restricted to the colon, while in one it also extended to the duodenum and saliva. One patient without APC mosaicism, carrying an APC in-frame deletion of uncertain significance, was found to harbor rare germline variants in OGG1, POLQ, and EXO1 genes. In conclusion, our restrictive selection criteria improved the detection of mosaic APC patients. In addition, we showed for the first time that an oligogenic inheritance of rare variants might have a cooperative role in sporadic colorectal polyposis onset.

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

PubMed

Carss, Keren J; Arno, Gavin; Erwood, Marie; Stephens, Jonathan; Sanchis-Juan, Alba; Hull, Sarah; Megy, Karyn; Grozeva, Detelina; Dewhurst, Eleanor; Malka, Samantha; Plagnol, Vincent; Penkett, Christopher; Stirrups, Kathleen; Rizzo, Roberta; Wright, Genevieve; Josifova, Dragana; Bitner-Glindzicz, Maria; Scott, Richard H; Clement, Emma; Allen, Louise; Armstrong, Ruth; Brady, Angela F; Carmichael, Jenny; Chitre, Manali; Henderson, Robert H H; Hurst, Jane; MacLaren, Robert E; Murphy, Elaine; Paterson, Joan; Rosser, Elisabeth; Thompson, Dorothy A; Wakeling, Emma; Ouwehand, Willem H; Michaelides, Michel; Moore, Anthony T; Webster, Andrew R; Raymond, F Lucy

2017-01-05

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease. Copyright © 2017. Published by Elsevier Inc.

A Selective Group Authentication Scheme for IoT-Based Medical Information System.

PubMed

Park, YoHan; Park, YoungHo

2017-04-01

The technology of IoT combined with medical systems is expected to support advanced medical services. However, unsolved security problems, such as misuse of medical devices, illegal access to the medical server and so on, make IoT-based medical systems not be applied widely. In addition, users have a high burden of computation to access Things for the explosive growth of IoT devices. Because medical information is critical and important, but users have a restricted computing power, IoT-based medical systems are required to provide secure and efficient authentication for users. In this paper, we propose a selective group authentication scheme using Shamir's threshold technique. The property of selectivity gives the right of choice to users to form a group which consists of things users select and access. And users can get an access authority for those Things at a time. Thus, our scheme provides an efficient user authentication for multiple Things and conditional access authority for safe IoT-based medical information system. To the best of our knowledge, our proposed scheme is the first in which selectivity is combined with group authentication in IoT environments.

How to pass information and deliver energy to a network of implantable devices within the human body.

PubMed

Sun, Mingui; Hackworth, Steven A; Tang, Zhide; Gilbert, Gary; Cardin, Sylvain; Sclabassi, Robert J

2007-01-01

It has been envisioned that a body network can be built to collect data from, and transport information to, implanted miniature devices at multiple sites within the human body. Currently, two problems of utmost importance remain unsolved: 1) how to link information between a pair of implants at a distance? and 2) how to provide electric power to these implants allowing them to function and communicate? In this paper, we present new solutions to these problems by minimizing the intra-body communication distances. We show that, based on a study of human anatomy, the maximum distance from the body surface to the deepest point inside the body is approximately 15 cm. This finding provides an upper bound for the lengths of communication pathways required to reach the body's interior. We also show that these pathways do not have to cross any joins within the body. In order to implement the envisioned body network, we present the design of a new device, called an energy pad. This small-size, light-weight device can easily interface with the skin to perform data communication with, and supply power to, miniature implants.

The meaning of work in people with severe mental illness (SMI) in Iran.

PubMed

Khalaf Beigi, Mitra; Mohammadi Shahbolaghi, Farahnaz; Rassafiani, Mehdi; Haghgoo, Hojjat-Allah; Taherkhani, Hamid

2015-01-01

Work is the key component for most people in regard to financial, social and wellbeing matters. Employment is an important factor underpinning mental health disorders. However, unemployment remains an unsolved issue worldwide. Numerous studies have focused on employment outcomes in people with severe mental illness (SMI) but, only a few have explored their perspective on employment. Therefore, this study aimed to clarify the meaning of work among clients with SMI in Iran. A qualitative research approach was used to conduct this research. Ten participants who were consumers of mental health services took part in this study. Data were analyzed by inductive content analysis approach. Four themes emerged from data including: acquiring identity, work as a drive, passing the time and financial independence. Meaning of work in studied people with SMI was probably similar to the general population. The different finding in this study refers to the dominancy of family relationships and spiritual believes which could cover some problems and in turn affect the meaning of work. Highlighting these meanings could direct mental health professionals to better planning for their clients have better understanding of their clients' work future and in turn provide more precise plan for them.

Sexual dimorphism of gonadotropin-releasing hormone type-III (GnRH3) neurons and hormonal sex reversal of male reproductive behavior in Mozambique tilapia.

PubMed

Kuramochi, Asami; Tsutiya, Atsuhiro; Kaneko, Toyoji; Ohtani-Kaneko, Ritsuko

2011-10-01

In tilapia, hormone treatment during the period of sexual differentiation can alter the phenotype of the gonads, indicating that endocrine factors can cause gonadal sex reversal. However, the endocrine mechanism underlying sex reversal of reproductive behaviors remains unsolved. In the present study, we detected sexual dimorphism of gonadotropin-releasing hormone type III (GnRH3) neurons in Mozambique tilapia Oreochromis mossambicus. Our immunohistochemical observations showed sex differences in the number of GnRH3 immunoreactive neurons in mature tilapia; males had a greater number of GnRH3 neurons in the terminal ganglion than females. Treatment with androgen (11-ketotestosterone (11-KT) or methyltestosterone), but not that with 17β-estradiol, increased the number of GnRH3 neurons in females to a level similar to that in males. Furthermore, male-specific nest-building behavior was induced in 70% of females treated with 11-KT within two weeks after the onset of the treatment. These results indicate androgen-dependent regulation of GnRH3 neurons and nest-building behavior, suggesting that GnRH3 is importantly involved in sex reversal of male-specific reproductive behavior.

A selection of biomechanical research problems: From modeling to experimentation

NASA Astrophysics Data System (ADS)

Abbasi, Cyrus Omid

The research undertakings within this manuscript illustrate the importance of biomechanics in today's science. Without doubt, biomechanics can be utilized to obtain a better understanding of many unsolved mysteries involved in the field of medicine. Moreover, biomechanics can be used to develop better prosthetic or surgical devices as well. Chapter 2 represents a medical problem, which has not been solved for more than a century. With the use of fundamental principles of biomechanics', a better insight of this problem and its possible causes were obtained. Chapter 3 investigates the mechanical interaction between the human teeth and some processed food products during mastication, which is a routine but crucial daily activity of a human being. Chapter 4 looks at a problem within the field of surgery. In this chapter the stability and reliability of two different Suturing-Techniques are explored. Chapters 5 and 6 represent new patent designs as a result of the investigations made in Chapter 4. Chapter 7 studies the impact and load transfer patterns during the collision between a child's head and the ground. All of the above mentioned chapters show the significance of biomechanics in solving a range of different medical problems that involve physical and or mechanical characters.

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

Chen, Qi; Cheng, Xiaolin; Univ. of Tennessee, Knoxville, TN

Although Elvitegravir (EVG) is a newly developed antiretrovirals drug to treat the acquired immunodeficiency syndrome (AIDS), drug resistance has already been found in clinic, such as E92Q/N155H and Q148H/G140S. Several structural investigations have already been reported to reveal the molecular mechanism of the drug resistance. As full length crystal structure for HIV-1 integrase is still unsolved, we use in this paper the crystal structure of the full length prototype foamy virus (PFV) in complex with virus DNA and inhibitor Elvitegravir as a template to construct the wild type and E92Q/N155H mutant system of HIV-1 integrase. Molecular dynamic simulations was usedmore » to revel the binding mode and the drug resistance of the EVG ligand in E92Q/N155H. Several important interactions were discovered between the mutated residues and the residues in the active site of the E92Q/N155H double mutant pattern, and cross correlation and clustering methods were used for detailed analysis. The results from the MD simulation studies will be used to guide the experimental efforts of developing novel inhibitors against drug-resistant HIV integrase mutants.« less

Origin of the concept of the quiescent centre of plant roots.

PubMed

Barlow, Peter W

2016-09-01

Concepts in biology feed into general theories of growth, development and evolution of organisms and how they interact with the living and non-living components of their environment. A well-founded concept clarifies unsolved problems and serves as a focus for further research. One such example of a constructive concept in the plant sciences is that of the quiescent centre (QC). In anatomical terms, the QC is an inert group of cells maintained within the apex of plant roots. However, the evidence that established the presence of a QC accumulated only gradually, making use of strands of different types of observations, notably from geometrical-analytical anatomy, radioisotope labelling and autoradiography. In their turn, these strands contributed to other concepts: those of the mitotic cell cycle and of tissue-related cell kinetics. Another important concept to which the QC contributed was that of tissue homeostasis. The general principle of this last-mentioned concept is expressed by the QC in relation to the recovery of root growth following a disturbance to cell proliferation; the resulting activation of the QC provides new cells which not only repair the root meristem but also re-establish a new QC.

Community response to noise: research in Central, Eastern and South-Eastern Europe and Newly Independent States.

PubMed

Jeram, Sonja; Lekaviciute, Jurgita; Krukle, Zanda; Argalasova-Sobotova, Lubica; Ristovska, Gordana; Paunovic, Katarina; Pawlaczyk-Luszczynska, Malgorzata

2013-01-01

The systems of public complaints on environmental noise were reviewed in seven countries of Central and Eastern Europe (CEE), South-East Europe (SEE), and Newly Independent States (NIS). Public complaints remain an important issue due to differences in public sensitivity to noise and due to several cases where a measurement of noise intensity does not give a satisfying solution to the problem. The unresolved problem remaining in the residential neighborhoods is the noise from pubs and restaurants that are open until late in the night. In our review, we compiled information on the institutions responsible for the implementation of environmental noise legislation and organizations that are responsible for dealing with public complaints. Information on activities for increasing public awareness on hazards rising from environmental noise and the role of civil initiative was explored. In seven countries, and among them, Slovenia, Lithuania, Latvia, Slovakia, The Former Yugoslav Republic of Macedonia, Serbia, and Poland, the responsibilities and duties are shared among different institutions at national and regional levels, depending on the noise source. The problem of gathering information on complaints and using it for improving the wellbeing and health of citizens remains often difficult and unsolved.

Novel synergistic mechanism for sst2 somatostatin and TNFalpha receptors to induce apoptosis: crosstalk between NF-kappaB and JNK pathways.

PubMed

Guillermet-Guibert, J; Saint-Laurent, N; Davenne, L; Rochaix, P; Cuvillier, O; Culler, M D; Pradayrol, L; Buscail, L; Susini, C; Bousquet, C

2007-02-01

Somatostatin is a multifunctional hormone that modulates cell proliferation, differentiation and apoptosis. Mechanisms for somatostatin-induced apoptosis are at present mostly unsolved. Therefore, we investigated whether somatostatin receptor subtype 2 (sst2) induces apoptosis in the nontransformed murine fibroblastic NIH3T3 cells. Somatostatin receptor subtype 2 expression induced an executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B (NF-kappaB) activity and subsequent inhibition of the mitogen-activated protein kinase JNK. Tumor necrosis factor alpha (TNFalpha) stimulated both NF-kappaB and c-Jun NH2-terminal kinase (JNK) activities, which had opposite action on cell survival. Importantly, sst2 sensitized NIH3T3 cells to TNFalpha-induced apoptosis by (1) upregulating TNFalpha receptor protein expression, and sensitizing to TNFalpha-induced caspase-8 activation; (2) enhancing TNFalpha-mediated activation of NF-kappaB, resulting in JNK inhibition and subsequent executioner caspase activation and cell death. We have here unraveled a novel signaling mechanism for a G protein-coupled receptor, which directly triggers apoptosis and crosstalks with a death receptor to enhance death ligand-induced apoptosis.

Evaluation of uncertainty for regularized deconvolution: A case study in hydrophone measurements.

PubMed

Eichstädt, S; Wilkens, V

2017-06-01

An estimation of the measurand in dynamic metrology usually requires a deconvolution based on a dynamic calibration of the measuring system. Since deconvolution is, mathematically speaking, an ill-posed inverse problem, some kind of regularization is required to render the problem stable and obtain usable results. Many approaches to regularized deconvolution exist in the literature, but the corresponding evaluation of measurement uncertainties is, in general, an unsolved issue. In particular, the uncertainty contribution of the regularization itself is a topic of great importance, because it has a significant impact on the estimation result. Here, a versatile approach is proposed to express prior knowledge about the measurand based on a flexible, low-dimensional modeling of an upper bound on the magnitude spectrum of the measurand. This upper bound allows the derivation of an uncertainty associated with the regularization method in line with the guidelines in metrology. As a case study for the proposed method, hydrophone measurements in medical ultrasound with an acoustic working frequency of up to 7.5 MHz are considered, but the approach is applicable for all kinds of estimation methods in dynamic metrology, where regularization is required and which can be expressed as a multiplication in the frequency domain.

Synthetic-Aperture Silhouette Imaging (SASI)

NASA Astrophysics Data System (ADS)

Paxman, R.

2016-09-01

The problem of ground-based fine-resolution imaging of geosynchronous satellites continues to be an important unsolved space-surveillance problem. We are investigating a passive-illumination approach that is radically different from amplitude, intensity, or heterodyne interferometry approaches. The approach, called Synthetic-Aperture Silhouette Imaging (SASI), produces a fine-resolution image of the satellite silhouette. When plane-wave radiation emanating from a bright star is occluded by a GEO satellite, then the light is diffracted and a moving diffraction pattern (shadow) is cast on the surface of the earth. With prior knowledge of the satellite orbit and star location, the track of the moving shadow can be predicted with high precision. A linear array of inexpensive hobby telescopes can be deployed roughly perpendicular to the shadow track to collect a time history of the star intensity as the shadow passes by. A phase-retrieval algorithm, using the strong constraint that the occlusion of the satellite is a binary-valued silhouette, allows us to retrieve the missing phase and reconstruct a fine-resolution image of the silhouette. Silhouettes are highly informative, providing diagnostic information about deployment of antennas and solar panels, enabling satellite pose estimation, and revealing the presence and orientation of neighboring satellites in rendezvous and proximity operations.

Spontaneous water filtration of bio-inspired membrane

NASA Astrophysics Data System (ADS)

Kim, Kiwoong; Kim, Hyejeong; Lee, Sang Joon

2016-11-01

Water is one of the most important elements for plants, because it is essential for various metabolic activities. Thus, water management systems of vascular plants, such as water collection and water filtration have been optimized through a long history. In this view point, bio-inspired technologies can be developed by mimicking the nature's strategies for the survival of the fittest. However, most of the underlying biophysical features of the optimized water management systems remain unsolved In this study, the biophysical characteristics of water filtration phenomena in the roots of mangrove are experimentally investigated. To understand water-filtration features of the mangrove, the morphological structures of its roots are analyzed. The electrokinetic properties of the root surface are also examined. Based on the quantitatively analyzed information, filtration of sodium ions in the roots are visualized. Motivated by this mechanism, spontaneous desalination mechanism in the root of mangrove is proposed by combining the electrokinetics and hydrodynamic transportation of ions. This study would be helpful for understanding the water-filtration mechanism of the roots of mangrove and developing a new bio-inspired desalination technology. This research was financially supported by the National Research Foundation (NRF) of Korea (Contract Grant Number: 2008-0061991).

Identification of Manganese Superoxide Dismutase from Sphingobacterium sp. T2 as a Novel Bacterial Enzyme for Lignin Oxidation.

PubMed

Rashid, Goran M M; Taylor, Charles R; Liu, Yangqingxue; Zhang, Xiaoyang; Rea, Dean; Fülöp, Vilmos; Bugg, Timothy D H

2015-10-16

The valorization of aromatic heteropolymer lignin is an important unsolved problem in the development of a biomass-based biorefinery, for which novel high-activity biocatalysts are needed. Sequencing of the genomic DNA of lignin-degrading bacterial strain Sphingobacterium sp. T2 revealed no matches to known lignin-degrading genes. Proteomic matches for two manganese superoxide dismutase proteins were found in partially purified extracellular fractions. Recombinant MnSOD1 and MnSOD2 were both found to show high activity for oxidation of Organosolv and Kraft lignin, and lignin model compounds, generating multiple oxidation products. Structure determination revealed that the products result from aryl-Cα and Cα-Cβ bond oxidative cleavage and O-demethylation. The crystal structure of MnSOD1 was determined to 1.35 Å resolution, revealing a typical MnSOD homodimer harboring a five-coordinate trigonal bipyramidal Mn(II) center ligated by three His, one Asp, and a water/hydroxide in each active site. We propose that the lignin oxidation reactivity of these enzymes is due to the production of a hydroxyl radical, a highly reactive oxidant. This is the first demonstration that MnSOD is a microbial lignin-oxidizing enzyme.

Molecular dynamics simulations with electronic stopping can reproduce experimental sputtering yields of metals impacted by large cluster ions

NASA Astrophysics Data System (ADS)

Tian, Jiting; Zhou, Wei; Feng, Qijie; Zheng, Jian

2018-03-01

An unsolved problem in research of sputtering from metals induced by energetic large cluster ions is that molecular dynamics (MD) simulations often produce sputtering yields much higher than experimental results. Different from the previous simulations considering only elastic atomic interactions (nuclear stopping), here we incorporate inelastic electrons-atoms interactions (electronic stopping, ES) into MD simulations using a friction model. In this way we have simulated continuous 45° impacts of 10-20 keV C60 on a Ag(111) surface, and found that the calculated sputtering yields can be very close to the experimental results when the model parameter is appropriately assigned. Conversely, when we ignore the effect of ES, the yields are much higher, just like the previous studies. We further expand our research to the sputtering of Au induced by continuous keV C60 or Ar100 bombardments, and obtain quite similar results. Our study indicates that the gap between the experimental and the simulated sputtering yields is probably induced by the ignorance of ES in the simulations, and that a careful treatment of this issue is important for simulations of cluster-ion-induced sputtering, especially for those aiming to compare with experiments.

Patriotism and Parochialism: Why Teach American Jewish History, and How?

ERIC Educational Resources Information Center

Levisohn, Jon A.

2004-01-01

In this article, the author focuses on these questions: why is American Jewish history worthy of being "taught"? And what purpose should such teaching serve? Philosophical questions such as these are important because topics of study are not self-justifying, and asking the questions--questions that must be pursued through conceptual inquiry,…

Trustworthiness and relevance in web-based clinical question answering.

PubMed

Cruchet, Sarah; Boyer, Célia; van der Plas, Lonneke

2012-01-01

Question answering systems try to give precise answers to a user's question posed in natural language. It is of utmost importance that the answers returned are relevant to the user's question. For clinical QA, the trustworthiness of answers is another important issue. Limiting the document collection to certified websites helps to improve the trustworthiness of answers. On the other hand, limited document collections are known to harm the relevancy of answers. We show, however, in a comparative evaluation, that promoting trustworthiness has no negative effect on the relevance of the retrieved answers in our clinical QA system. On the contrary, the answers found are in general more relevant.

Antimicrobial activity of fluoride and its in vivo importance: identification of research questions.

PubMed

Van Loveren, C

2001-01-01

This manuscript discusses the antimicrobial activity of fluoride and its in vivo importance in order to identify research questions. There is a lot of information on mechanisms by which fluoride may interfere with bacterial metabolism and dental plaque acidogenicity. The antimicrobial activity of fluoride products is enhanced when fluoride is associated with antimicrobial cations like Sn(2+) and amine. It is not clear whether the antimicrobial mechanisms of fluoride are operating in vivo or even to what extent antimicrobial activity can contribute to caries prevention. This latter question may be the most important one in research. Copyright 2001 S. Karger AG, Basel.

Patients' perceptions of their "most" and "least" important medications: a retrospective cohort study.

PubMed

Linsky, Amy; Simon, Steven R

2012-11-02

Despite benefits of adherence, little is known about the degree to which patients will express their perceptions of medications as more or less important to take as prescribed. We determined the frequency with which Veteran patients would explicitly identify one of their medications as "most important" or "least important." We conducted a retrospective cohort study of patients from ambulatory clinics at VA Boston from April 2010-July 2011. Patients answered two questions: "Which one of your medicines, if any, do you think is the most important? (if none, please write 'none')" and "Which one of your medicines, if any, do you think is the least important? (if none, please write 'none')." We determined the prevalence of response categories for each question. Our cohort of 104 patients was predominantly male (95%), with a mean of 9 medications (SD 5.7). Regarding their most important medication, 41 patients (39%) identified one specific medication; 26 (25%) selected more than one; 21 (20%) wrote "none"; and 16 (15%) did not answer the question. For their least important medication, 31 Veterans (30%) chose one specific medication; two (2%) chose more than one; 51 (49%) wrote "none"; and 20 (19%) did not directly answer the question. Thirty-five percent of patients did not identify a most important medication, and 68% did not identify a least important medication. Better understanding of how patients prioritize medications and how best to elicit this information will improve patient-provider communication, which may in turn lead to better adherence.

An Important Question for Student Journalists: Must Freedom, Rules/Law Inevitably Conflict?

ERIC Educational Resources Information Center

Martinson, David L.

2001-01-01

Considers the importance of developing a well constructed publications policy and notes that a carefully designed policy will provide some mechanism for addressing questions regarding the inevitable conflicts that will arise when students express a desire to publish certain controversial material. (SC)

Frequent Questions about the Hazardous Waste Export-Import Revisions Final Rule

EPA Pesticide Factsheets

Answers questions such as: What new requirements did EPA finalize in the Hazardous Waste Export-Import Revisions Final Rule? Why did EPA implement these changes now? What are the benefits of the final rule? What are the compliance dates for the final rule?

HOW PEOPLE RESPOND TO CONTINGENT VALUATION QUESTIONS

EPA Science Inventory

The purpose of the project is to understand better how individuals interpret and respond to contingent valuation (CV) questions. The research will address three issues: the reliability of the referendum questions format, the importance of reminding respondents about subst...

Impression formation of tests: retrospective judgments of performance are higher when easier questions come first.

PubMed

Jackson, Abigail; Greene, Robert L

2014-11-01

Four experiments are reported on the importance of retrospective judgments of performance (postdictions) on tests. Participants answered general knowledge questions and estimated how many questions they answered correctly. They gave higher postdictions when easy questions preceded difficult questions. This was true when time to answer each question was equalized and constrained, when participants were instructed not to write answers, and when questions were presented in a multiple-choice format. Results are consistent with the notion that first impressions predominate in overall perception of test difficulty.

On the morphological characteristics of overdeepenings in high-mountain glacier beds W. Haeberli1, A. Cochachin2, U.H. Fischer3, A. Linsbauer1, C. Salazar2 1Geography Department, University of Zurich, Switzerland 2Glaciology and Water Resources Unit, Huaraz, Peru 3Nagra, Wettingen, Switzerland

NASA Astrophysics Data System (ADS)

Haeberli, W.; Cochachin, A.; Fischer, U. H.; Linsbauer, A.; Salazar Checa, C. J.

2013-12-01

Overdeepenings, i.e. closed topographic depressions with adverse slopes in the flow direction, are characteristic for glacier beds and glacially sculpted landscapes. Besides their importance as geomorphological landforms, groundwater bodies and sedimentary archives, they are of increasing interest in relation to climate-induced lake formation in de-glaciating landscapes and depth erosion under ice age conditions in connection with the long-term safety of radioactive waste repositories in some mid-latitude countries. Quantitative predictions of their shape, distribution and conditions of occurrence remain difficult. One major problem thereby relates to the still unsatisfactory treatment in glacier erosion theory of sediment evacuation at glacier beds, especially by subglacial meltwater. An alternative way of searching for realistic/empirical quantitative estimates is, therefore, to analyse the geometry of well-documented overdeepenings. The present study attempts to do this by combining statistical analyses of (a) detailed bathymetries from recently exposed lakes in the Peruvian Andes, (b) numerous bed overdeepenigs below still existing glaciers of the Swiss Alps modelled with a robust shear stress approximation linking surface slope to ice thickness at high resolution, and (c, for comparison) reconstructed overdeepenings produced by ice age glaciers in the Swiss Plateau. The sample of (a) has the advantage that geometries are exactly measured and are only subject to young/small sedimentation effects. Sample (b) allows for a comparison with a modern model calculation and with known glacier characteristics. Sample (c) may provide some insights into the question how safely results from high mountain topography can be transferred to sites with markedly different topographic, climatic and glaciological controls (cold-arid lowland). Where possible, mean and maximum values of the parameters surface area, length, width, depth, volume, adverse slope and their statistical interrelations are determined with their corresponding uncertainty ranges. For sample (b) basal shear stress (as used in the model), thermal ice types, glacier size/type, relation to flow characteristics (position along flow, confined-unconfined, confluence-diffluence-channel-forefield) are also included. As principal problem thereby remains the unsolved question of when exactly the overdeepenings had formed (present-day conditions, Holocene maximum stages, ice ages?). Some results nevertheless remain safe. Marked overdeepenings can, for instance, exist under very small cirque glaciers flowing under low shear stresses and having low melt-water input. They can form at confluences but also often occur under conditions of confined flow in rather straight channel configurations. Corresponding lakes can be dammed by huge (terminal) moraines or may form in beautifully polished pure rock beds. The full results of the study are hoped to improve the knowledge basis for practical applications (unmeasured and future lakes, depth erosion by glaciers).

31 CFR 9.5 - Applications for investigation.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., both past and current. (c) Statistical material presented should be on a calendar-year basis for... domestic industry concerned with the article in question. (4) Pertinent statistics showing the quantities... competition created by imports of the article in question. (6) The effect, if any, of imports of the article...

Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis.

PubMed

Zhou, Xinyu; Cipriani, Andrea; Furukawa, Toshi A; Cuijpers, Pim; Zhang, Yuqing; Hetrick, Sarah E; Pu, Juncai; Yuan, Shuai; Del Giovane, Cinzia; Xie, Peng

2018-01-05

Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents. We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children's Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies. Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care. CRD42016051657. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Stacking and metamorphism of continuous segments of subducted lithosphere in a high-pressure wedge: The example of Alpine Corsica (France)

NASA Astrophysics Data System (ADS)

Vitale Brovarone, Alberto; Beyssac, Olivier; Malavieille, Jacques; Molli, Giancarlo; Beltrando, Marco; Compagnoni, Roberto

2013-01-01

Alpine Corsica consists of a stack of variably metamorphosed units of continental and Tethys-derived rocks. It represents an excellent example of high-pressure (HP) orogenic belt, such as the Western Alps, exposed over a small and accessible area. Compared to the Western Alps, the geology of Alpine Corsica is poorly unraveled. During the 1970s-80s, based on either lithostratigraphic or metamorphic field observations, various classifications of the belt have been proposed, but these classifications have been rarely matched together. Furthermore, through time, the internal complexity of large domains has been progressively left aside in the frame of large-scale geodynamic reconstructions. As a consequence, major open questions on the internal structure of the belt have remained unsolved. Apart from a few local studies, Alpine Corsica has not benefited of modern developments in petrology and basin research. This feature results in several uncertainties when combining lithostratigraphic and metamorphic patterns and, consequently, in the definition of an exhaustive architecture of the belt. In this paper we provide a review on the geology of Alpine Corsica, paying particular attention to the available lithostratigraphic and metamorphic classifications of the metamorphic terranes. These data are completed by a new and exhaustive metamorphic dataset obtained by means of thermometry based on Raman Spectroscopy of Carbonaceous Material (RSCM). This technique provides reliable insights on the peak temperature of the metamorphic history for CM-bearing metasediments. A detailed metamorphic characterization of metasediments, which have been previously largely ignored due to retrogression or to the lack of diagnostic mineralogy, is thus obtained and fruitfully coupled with the available lithostratigraphic data. Nine main tectono-metamorphic units are defined, from subgreenschist (ca. 280-300 °C) to the lawsonite-eclogite-facies (ca. 500-550 °C) condition. These units are homogeneous in metamorphism, laterally continuous and have characteristic lithostratigraphic features. This study also suggests a direct link between the pre-orogenic extensional setting and the present-day compressional structure of Alpine Corsica, indicating that large sections of subducted lithosphere were subducted and exhumed as coherent domains. These features provide important insight on the mechanism of stacking and exhumation of HP rocks, and make Alpine Corsica a unique reference for mountain-building processes in Tethyan-type orogens.

Yes-No Questions that Convey a Critical Stance in the Language Classroom

ERIC Educational Resources Information Center

Waring, Hansun Zhang

2012-01-01

Despite certain important critiques, much of the work on teacher questions has centered on the distinction between referential and display questions as well as their roles in creating more or less communicative classrooms. With some notable exceptions, few have delved into the specificity of how questions work in the details of classroom…

What Are the "Right" Questions and the "Right" Answers in Teaching Practice Supervision?

ERIC Educational Resources Information Center

Jyrhama, Riitta

This paper links the problem of questioning and answering in student teacher supervision with teachers' pedagogical thinking. The first section discusses whether asking the right questions or giving the right answers is more important and what is actually involved when the questions and answers are correct. The second section discusses the…

[Consequences learned from the use of chemical weapons during the First World War for the modern military medicine].

PubMed

Belskikh, A N; Basharin, V A; Chepur, S V; Khalimov, Yu Sh; Markizova, N F

2015-08-01

The article describes the way medical service dealed with problems resulted from the use of chemical weapons during the First World War (1914-1918). It was revealed that many of the abovementioned problems remain unsolved up to the present moment. It is stated the existence of the threat of use of chemical weapons in modem military conflicts, which expands the area of responsibility for medical chemical protection. The authors proved necessity and algorithm of the training system, considered as a part of medical protection in case of adverse factors of chemical nature.

Radio Photosphere and Mass-Loss Envelope of VY Canis Majoris

NASA Astrophysics Data System (ADS)

Lipscy, S. J.; Jura, M.; Reid, M. J.

2005-06-01

We have used the VLA to detect emission from the supergiant VY CMa at radio wavelengths and have constructed 3000-4500 K isothermal outer atmospheres constrained by the data. These models produce a radio photosphere at 1.5-2 R*. An extrapolation of the model can account for the observed total mass-loss rate of the star. We also present mid-infrared imaging of the supergiant which suggests that warm dust is extended in the same direction as the near-infrared reflection nebula around VY CMa. The origin of the asymmetries in the outflow remains an unsolved problem.

Putting the Aero Back into Aeroelasticity

NASA Technical Reports Server (NTRS)

Bousman, William G.

2000-01-01

The lack of progress in understanding the physics of rotorcraft loads and vibration over the last 30 years is addressed in this paper. As befits this extraordinarily difficult problem, the reasons for the lack of progress are complicated and difficult to ascertain. It is proposed here that the difficulty lies within at least three areas: 1) a loss of perspective as to what are the key factors in rotor loads and vibration, 2) the overlooking of serious unsolved problems in the field, and 3) cultural barriers that impede progress. Some criteria are suggested for future research to provide a more concentrated focus on the problem.

Interactions between nitric oxide and plant hormones in aluminum tolerance.

PubMed

He, Huyi; He, Longfei; Gu, Minghua

2012-04-01

Nitric oxide (NO) is involved, together with plant hormones, in the adaptation to Al stress in plants. However, the mechanism by which NO and plant hormones interplay to improve Al tolerance are still unclear. We have recently shown that patterns of plant hormones alteration differ between rye and wheat under Al stress. NO may enhance Al tolerance by regulating hormonal equilibrium in plants, as a regulator of plant hormones signaling. In this paper, some unsolved issues are discussed based on recent studies and the complex network of NO and plant hormones in inducing Al tolerance of plants are proposed.

Recent Progress on PEDOT-Based Thermoelectric Materials

PubMed Central

Wei, Qingshuo; Mukaida, Masakazu; Kirihara, Kazuhiro; Naitoh, Yasuhisa; Ishida, Takao

2015-01-01

The thermoelectric properties of poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials have attracted attention recently because of their remarkable electrical conductivity, power factor, and figure of merit. In this review, we summarize recent efforts toward improving the thermoelectric properties of PEDOT-based materials. We also discuss thermoelectric measurement techniques and several unsolved problems with the PEDOT system such as the effect of water absorption from the air and the anisotropic thermoelectric properties. In the last part, we describe our work on improving the power output of thermoelectric modules by using PEDOT, and we outline the potential applications of polymer thermoelectric generators. PMID:28787968

On Frequency Combs in Monolithic Resonators

NASA Astrophysics Data System (ADS)

Savchenkov, A. A.; Matsko, A. B.; Maleki, L.

2016-06-01

Optical frequency combs have become indispensable in astronomical measurements, biological fingerprinting, optical metrology, and radio frequency photonic signal generation. Recently demonstrated microring resonator-based Kerr frequency combs point the way towards chip scale optical frequency comb generator retaining major properties of the lab scale devices. This technique is promising for integrated miniature radiofrequency and microwave sources, atomic clocks, optical references and femtosecond pulse generators. Here we present Kerr frequency comb development in a historical perspective emphasizing its similarities and differences with other physical phenomena. We elucidate fundamental principles and describe practical implementations of Kerr comb oscillators, highlighting associated solved and unsolved problems.

Diffraction of a plane wave on two-dimensional conductive structures and a surface wave

NASA Astrophysics Data System (ADS)

Davidovich, Mikhael V.

2018-04-01

We consider the structures type of two-dimensional electron gas in the form of a thin conductive, in particular, graphene films described by tensor conductivity, which are isolated or located on the dielectric layers. The dispersion equation for hybrid modes, as well as scattering parameters. We show that free wave (eigenwaves) problem follow from the problem of diffraction when linking the amplitude of the current of the linear equations are unsolvable, i.e., the determinant of this system is zero. As a particular case the dispersion equation follow from the conditions of matching (with zero reflection coefficient).