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.

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

Cabrera-Palmer, Belkis

Predicting the performance of radiation detection systems at field sites based on measured performance acquired under controlled conditions at test locations, e.g., the Nevada National Security Site (NNSS), remains an unsolved and standing issue within DNDO’s testing methodology. Detector performance can be defined in terms of the system’s ability to detect and/or identify a given source or set of sources, and depends on the signal generated by the detector for the given measurement configuration (i.e., source strength, distance, time, surrounding materials, etc.) and on the quality of the detection algorithm. Detector performance is usually evaluated in the performance and operationalmore » testing phases, where the measurement configurations are selected to represent radiation source and background configurations of interest to security applications.« less

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.

An assessment of non-stationarity in physiological cognitive state assessment using artificial neural networks.

PubMed

Estepp, Justin R; Klosterman, Samantha L; Christensen, James C

2011-01-01

With increased attention toward physiological cognitive state assessment as a component in the larger field of applied neuroscience, the need to develop methods for robust, stable assessment of cognitive state has been expressed as critical to designing effective augmented human-machine systems. The technique of cognitive state assessment, as well as its benefits, has been demonstrated by many research groups. In an effort to move closer toward a realized system, efforts must now be focused on critical issues that remain unsolved, namely instability of pattern classifiers over the course of hours and days. This work, as part of the Cognitive State Assessment Competition 2011, seeks to explore methods for 'learning' non-stationarity as a mitigation for more generalized patterns that are stable over time courses that are not widely discussed in the literature.

Resource Allocation in Healthcare: Implications of Models of Medicine as a Profession

PubMed Central

Kluge, Eike-Henner W.

2007-01-01

For decades, the problem of how to allocate healthcare resources in a just and equitable fashion has been the subject of concerted discussion and analysis, yet the issue has stubbornly resisted resolution. This article suggests that a major reason for this is that the discussion has focused exclusively on the nature and status of the material resources, and that the nature and role of the medical profession have been entirely ignored. Because physicians are gatekeepers to healthcare resources, their role in allocation is central from a process perspective. This article identifies 3 distinct interpretations of the nature of medicine, shows how each mandates a different method of allocation, and argues that unless an appropriate model of medicine is developed that acknowledges the valid points contained in each of the 3 approaches, the allocation problem will remain unsolvable. PMID:17435657

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…

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…

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.

[Teleradiology - update 2014].

PubMed

Pinto dos Santos, D; Hempel, J-M; Kloeckner, R; Düber, C; Mildenberger, P

2014-05-01

Due to economic considerations and thanks to technological advances there is a growing interest in the integration of teleradiological applications into the regular radiological workflow. The legal and technical hurdles which are still to be overcome are being discussed in politics as well as by national and international radiological societies. The European Commission as well as the German Federal Ministry of Health placed a focus on telemedicine with their recent eHealth initiatives. The European Society of Radiology (ESR) recently published a white paper on teleradiology. In Germany §3 section 4 of the Röntgenverordnung (RöV, X-ray regulations) and DIN 6868-159 set a framework in which teleradiology can also be used for primary reads. These possibilities are already being used by various networks and some commercial providers across Germany. With regards to cross-border teleradiology, which currently stands in contrast to the RöV, many issues remain unsolved.

Whole-Brain Microscopy Meets In Vivo Neuroimaging: Techniques, Benefits, and Limitations.

PubMed

Aswendt, Markus; Schwarz, Martin; Abdelmoula, Walid M; Dijkstra, Jouke; Dedeurwaerdere, Stefanie

2017-02-01

Magnetic resonance imaging, positron emission tomography, and optical imaging have emerged as key tools to understand brain function and neurological disorders in preclinical mouse models. They offer the unique advantage of monitoring individual structural and functional changes over time. What remained unsolved until recently was to generate whole-brain microscopy data which can be correlated to the 3D in vivo neuroimaging data. Conventional histological sections are inappropriate especially for neuronal tracing or the unbiased screening for molecular targets through the whole brain. As part of the European Society for Molecular Imaging (ESMI) meeting 2016 in Utrecht, the Netherlands, we addressed this issue in the Molecular Neuroimaging study group meeting. Presentations covered new brain clearing methods, light sheet microscopes for large samples, and automatic registration of microscopy to in vivo imaging data. In this article, we summarize the discussion; give an overview of the novel techniques; and discuss the practical needs, benefits, and limitations.

Genomic big data hitting the storage bottleneck.

PubMed

Papageorgiou, Louis; Eleni, Picasi; Raftopoulou, Sofia; Mantaiou, Meropi; Megalooikonomou, Vasileios; Vlachakis, Dimitrios

2018-01-01

During the last decades, there is a vast data explosion in bioinformatics. Big data centres are trying to face this data crisis, reaching high storage capacity levels. Although several scientific giants examine how to handle the enormous pile of information in their cupboards, the problem remains unsolved. On a daily basis, there is a massive quantity of permanent loss of extensive information due to infrastructure and storage space problems. The motivation for sequencing has fallen behind. Sometimes, the time that is spent to solve storage space problems is longer than the one dedicated to collect and analyse data. To bring sequencing to the foreground, scientists have to slide over such obstacles and find alternative ways to approach the issue of data volume. Scientific community experiences the data crisis era, where, out of the box solutions may ease the typical research workflow, until technological development meets the needs of Bioinformatics.

Recurrent Pericarditis.

PubMed

Imazio, Massimo; Gribaudo, Elena; Gaita, Fiorenzo

Recurrent pericarditis is the most common and troublesome complication of pericarditis affecting 20% to 50% of patients. Its pathogenesis is often presumed to be immune-mediated, but additional investigations are needed to clarify the pathogenesis in order to develop etiology-oriented therapies. Imaging with computed tomography and especially cardiac magnetic resonance holds promise to help in the identification of more difficult cases and improve their management. Refractory recurrent pericarditis with corticosteroid dependence and colchicine resistance remain still an unsolved issue in search of new therapies, although old drugs such as azathioprine, intravenous immunoglobulins, and biological agents seem promising, but new randomized clinical trials are needed to confirm their role. Despite compromising the quality of life, idiopathic recurrent pericarditis has an overall good long-term outcome without mortality and significant risk of constrictive pericarditis evolution. The risk of constriction, the most feared complication, is related to the etiology and not the number of recurrences. Copyright © 2016 Elsevier Inc. All rights reserved.

The secret of life

NASA Astrophysics Data System (ADS)

Jenkins, David; Kirsebom, Oliver

2013-02-01

Life as we know it would not be possible were it not for a particular nuclear energy level of carbon-12 predicted 60 years ago by Fred Hoyle. But the true nature of this energy level remains one of the biggest unsolved questions in nuclear physics, say David Jenkins and Oliver Kirsebom.

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…

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

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 ...

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.

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...

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.

Accurate palm vein recognition based on wavelet scattering and spectral regression kernel discriminant analysis

NASA Astrophysics Data System (ADS)

Elnasir, Selma; Shamsuddin, Siti Mariyam; Farokhi, Sajad

2015-01-01

Palm vein recognition (PVR) is a promising new biometric that has been applied successfully as a method of access control by many organizations, which has even further potential in the field of forensics. The palm vein pattern has highly discriminative features that are difficult to forge because of its subcutaneous position in the palm. Despite considerable progress and a few practical issues, providing accurate palm vein readings has remained an unsolved issue in biometrics. We propose a robust and more accurate PVR method based on the combination of wavelet scattering (WS) with spectral regression kernel discriminant analysis (SRKDA). As the dimension of WS generated features is quite large, SRKDA is required to reduce the extracted features to enhance the discrimination. The results based on two public databases-PolyU Hyper Spectral Palmprint public database and PolyU Multi Spectral Palmprint-show the high performance of the proposed scheme in comparison with state-of-the-art methods. The proposed approach scored a 99.44% identification rate and a 99.90% verification rate [equal error rate (EER)=0.1%] for the hyperspectral database and a 99.97% identification rate and a 99.98% verification rate (EER=0.019%) for the multispectral database.

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…

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.

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

Geometric Data Perturbation-Based Personal Health Record Transactions in Cloud Computing

PubMed Central

Balasubramaniam, S.; Kavitha, V.

2015-01-01

Cloud computing is a new delivery model for information technology services and it typically involves the provision of dynamically scalable and often virtualized resources over the Internet. However, cloud computing raises concerns on how cloud service providers, user organizations, and governments should handle such information and interactions. Personal health records represent an emerging patient-centric model for health information exchange, and they are outsourced for storage by third parties, such as cloud providers. With these records, it is necessary for each patient to encrypt their own personal health data before uploading them to cloud servers. Current techniques for encryption primarily rely on conventional cryptographic approaches. However, key management issues remain largely unsolved with these cryptographic-based encryption techniques. We propose that personal health record transactions be managed using geometric data perturbation in cloud computing. In our proposed scheme, the personal health record database is perturbed using geometric data perturbation and outsourced to the Amazon EC2 cloud. PMID:25767826

Geometric data perturbation-based personal health record transactions in cloud computing.

PubMed

Balasubramaniam, S; Kavitha, V

2015-01-01

Cloud computing is a new delivery model for information technology services and it typically involves the provision of dynamically scalable and often virtualized resources over the Internet. However, cloud computing raises concerns on how cloud service providers, user organizations, and governments should handle such information and interactions. Personal health records represent an emerging patient-centric model for health information exchange, and they are outsourced for storage by third parties, such as cloud providers. With these records, it is necessary for each patient to encrypt their own personal health data before uploading them to cloud servers. Current techniques for encryption primarily rely on conventional cryptographic approaches. However, key management issues remain largely unsolved with these cryptographic-based encryption techniques. We propose that personal health record transactions be managed using geometric data perturbation in cloud computing. In our proposed scheme, the personal health record database is perturbed using geometric data perturbation and outsourced to the Amazon EC2 cloud.

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.

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.

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.

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.

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.

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.

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

Self-Formed Hybrid Interphase Layer on Lithium Metal for High-Performance Lithium-Sulfur Batteries.

PubMed

Li, Guoxing; Huang, Qingquan; He, Xin; Gao, Yue; Wang, Daiwei; Kim, Seong H; Wang, Donghai

2018-02-27

Lithium-sulfur (Li-S) batteries are promising candidates for high-energy storage devices due to high theoretical capacities of both the sulfur cathode and lithium (Li) metal anode. Considerable efforts have been devoted to improving sulfur cathodes. However, issues associated with Li anodes, such as low Coulombic efficiency (CE) and growth of Li dendrites, remain unsolved due to unstable solid-electrolyte interphase (SEI) and lead to poor capacity retention and a short cycling life of Li-S batteries. In this work, we demonstrate a facile and effective approach to fabricate a flexible and robust hybrid SEI layer through co-deposition of aromatic-based organosulfides and inorganic Li salts using poly(sulfur-random-1,3-diisopropenylbenzene) as an additive in an electrolyte. The aromatic-based organic components with planar backbone conformation and π-π interaction in the SEI layers can improve the toughness and flexibility to promote stable and high efficient Li deposition/dissolution. The as-formed durable SEI layer can inhibit dendritic Li growth, enhance Li deposition/dissolution CE (99.1% over 420 cycles), and in turn enable Li-S batteries with good cycling stability (1000 cycles) and slow capacity decay. This work demonstrates a route to address the issues associated with Li metal anodes and promote the development of high-energy rechargeable Li metal batteries.

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

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…

[Conversations on the "good death": the bioethical debate on euthanasia].

PubMed

Siqueira-Batista, Rodrigo; Schramm, Fermin Roland

2005-01-01

Despite extensive current debate on euthanasia, many open and apparently unsolvable issues persist, awaiting a better conceptual treatment. The area includes "prejudices and fundamentalisms" in relation to the theme, still viewed as taboo by a major share of society, specifically in the case of Brazil, while semantic imprecision in the term and argumentative tensions surround the issue, focusing on the principles of sacredness of life, quality of life, and autonomy and the so-called "slippery slope" argument. The purpose of the current essay is thus to serve as a sphere of inquiry concerning euthanasia, moving from historical antecedents towards a better solution to the problem and the demarcation of necessary future perspectives for enhanced understanding of the issue.

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.

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

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.

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

Molecular aspects of eye evolution and development: from the origin of retinal cells to the future of regenerative medicine.

PubMed

Ohuchi, Hideyo

2013-01-01

A central issue of evolutionary developmental biology is how the eye is diverged morphologically and functionally. However, the unifying mechanisms or schemes that govern eye diversification remain unsolved. In this review, I first introduce the concept of evolutionary developmental biology of the eye with a focus on photoreception, the fundamental property of retinal cells. Second, I summarize the early development of vertebrate eyes and the role of a homeobox gene, Lhx1, in subdivision of the retina into 2 domains, the neural retina and retinal pigmented epithelium of the optic primordium. The 2 retinal domains are essential components of the eye as they are found in such prototypic eyes as the extant planarian eye. Finally, I propose the presence of novel retinal cell subtypes with photosensory functions based on our recent work on atypical photopigments (opsins) in vertebrates. Since human diseases are attributable to the aberration of various types of cells due to alterations in gene expression, understanding the precise mechanisms of cellular diversification and unraveling the molecular profiles of cellular subtypes are essential to future regenerative medicine.

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.

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.

Self-consistent discharge growing model of helicon plasma

NASA Astrophysics Data System (ADS)

Isayama, Shogo; Hada, Tohru; Shinohara, Shunjiro; Tanikawa, Takao

2015-11-01

Helicon plasma is a high-density and low-temperature plasma generated by the electromagnetic (Helicon) wave excited in the plasma. It is thought to be useful for various applications including electric thrusters. Physics of helicon plasma production involves such fundamental processes as the wave propagation (dispersion relation), collisional and non-collisional wave damping, plasma heating, ionization/recombination of neutral particles, and modification of the dispersion relation by newly ionized plasma. There remain a number of unsolved physical issues such as, how the Helicon and the TG modes influence the plasma density, electron temperature and their spatial profiles. While the Helicon mode is absorbed in the bulk plasma, the TG mode is mostly absorbed near the edge of the plasma. The local power deposition in the helicon plasma is mostly balanced by collisional loss. This local power balance can give rise to the inhomogeneous electron temperature profile that leads to time evolution of density profile and dispersion relation. In our study, we construct a self-consistent model of the discharge evolution that includes the wave excitation, electron heat transfer, and diffusion of charged particles.

Pattern Recognition Using Artificial Neural Network: A Review

NASA Astrophysics Data System (ADS)

Kim, Tai-Hoon

Among the various frameworks in which pattern recognition has been traditionally formulated, the statistical approach has been most intensively studied and used in practice. More recently, artificial neural network techniques theory have been receiving increasing attention. The design of a recognition system requires careful attention to the following issues: definition of pattern classes, sensing environment, pattern representation, feature extraction and selection, cluster analysis, classifier design and learning, selection of training and test samples, and performance evaluation. In spite of almost 50 years of research and development in this field, the general problem of recognizing complex patterns with arbitrary orientation, location, and scale remains unsolved. New and emerging applications, such as data mining, web searching, retrieval of multimedia data, face recognition, and cursive handwriting recognition, require robust and efficient pattern recognition techniques. The objective of this review paper is to summarize and compare some of the well-known methods used in various stages of a pattern recognition system using ANN and identify research topics and applications which are at the forefront of this exciting and challenging field.

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.

GeoSegmenter: A statistically learned Chinese word segmenter for the geoscience domain

NASA Astrophysics Data System (ADS)

Huang, Lan; Du, Youfu; Chen, Gongyang

2015-03-01

Unlike English, the Chinese language has no space between words. Segmenting texts into words, known as the Chinese word segmentation (CWS) problem, thus becomes a fundamental issue for processing Chinese documents and the first step in many text mining applications, including information retrieval, machine translation and knowledge acquisition. However, for the geoscience subject domain, the CWS problem remains unsolved. Although a generic segmenter can be applied to process geoscience documents, they lack the domain specific knowledge and consequently their segmentation accuracy drops dramatically. This motivated us to develop a segmenter specifically for the geoscience subject domain: the GeoSegmenter. We first proposed a generic two-step framework for domain specific CWS. Following this framework, we built GeoSegmenter using conditional random fields, a principled statistical framework for sequence learning. Specifically, GeoSegmenter first identifies general terms by using a generic baseline segmenter. Then it recognises geoscience terms by learning and applying a model that can transform the initial segmentation into the goal segmentation. Empirical experimental results on geoscience documents and benchmark datasets showed that GeoSegmenter could effectively recognise both geoscience terms and general terms.

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.

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 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

Definition of a visuospatial dimension as a step forward in the diagnostic puzzle of nonverbal learning disability.

PubMed

Poletti, Michele

2017-01-01

Although clinically recognized for almost 50 years, the categorical distinction of specific learning disabilities due to an impairment of the nonverbal domain (nonverbal learning disability [NLD]) is still debated and controversial. Unsolved issues involve theoretical models, diagnostic criteria, rehabilitative interventions, and moderator factors. These issues are briefly overviewed to sustain the need for a shift toward dimensional approaches, as suggested by research domain criteria, as a step forward in the diagnostic puzzle of NLD. With this aim, a visuospatial dimension, or spectrum, is proposed, and then clinical conditions that may fit with its impaired side are systemized, while specifying in which conditions a visuospatial impairment may be considered an NLD.

Spectroscopic Studies of the Chan-Lam Amination: A Mechanism-Inspired Solution to Boronic Ester Reactivity.

PubMed

Vantourout, Julien C; Miras, Haralampos N; Isidro-Llobet, Albert; Sproules, Stephen; Watson, Allan J B

2017-04-05

We report an investigation of the Chan-Lam amination reaction. A combination of spectroscopy, computational modeling, and crystallography has identified the structures of key intermediates and allowed a complete mechanistic description to be presented, including off-cycle inhibitory processes, the source of amine and organoboron reactivity issues, and the origin of competing oxidation/protodeboronation side reactions. Identification of key mechanistic events has allowed the development of a simple solution to these issues: manipulating Cu(I) → Cu(II) oxidation and exploiting three synergistic roles of boric acid has allowed the development of a general catalytic Chan-Lam amination, overcoming long-standing and unsolved amine and organoboron limitations of this valuable transformation.

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

Self-Formed Hybrid Interphase Layer on Lithium Metal for High-Performance Lithium–Sulfur Batteries

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

Li, Guoxing; Huang, Qingquan; He, Xin

Lithium–sulfur (Li–S) batteries are promising candidates for high-energy storage devices due to high theoretical capacities of both the sulfur cathode and lithium (Li) metal anode. Considerable efforts have been devoted to improving sulfur cathodes. However, issues associated with Li anodes, such as low Coulombic efficiency (CE) and growth of Li dendrites, remain unsolved due to unstable solid-electrolyte interphase (SEI) and lead to poor capacity retention and a short cycling life of Li–S batteries. In this paper, we demonstrate a facile and effective approach to fabricate a flexible and robust hybrid SEI layer through co-deposition of aromatic-based organosulfides and inorganic Limore » salts using poly(sulfur-random-1,3-diisopropenylbenzene) as an additive in an electrolyte. The aromatic-based organic components with planar backbone conformation and π–π interaction in the SEI layers can improve the toughness and flexibility to promote stable and high efficient Li deposition/dissolution. The as-formed durable SEI layer can inhibit dendritic Li growth, enhance Li deposition/dissolution CE (99.1% over 420 cycles), and in turn enable Li–S batteries with good cycling stability (1000 cycles) and slow capacity decay. Finally, this work demonstrates a route to address the issues associated with Li metal anodes and promote the development of high-energy rechargeable Li metal batteries.« less

Self-Formed Hybrid Interphase Layer on Lithium Metal for High-Performance Lithium–Sulfur Batteries

DOE PAGES

Li, Guoxing; Huang, Qingquan; He, Xin; ...

2018-01-29

Lithium–sulfur (Li–S) batteries are promising candidates for high-energy storage devices due to high theoretical capacities of both the sulfur cathode and lithium (Li) metal anode. Considerable efforts have been devoted to improving sulfur cathodes. However, issues associated with Li anodes, such as low Coulombic efficiency (CE) and growth of Li dendrites, remain unsolved due to unstable solid-electrolyte interphase (SEI) and lead to poor capacity retention and a short cycling life of Li–S batteries. In this paper, we demonstrate a facile and effective approach to fabricate a flexible and robust hybrid SEI layer through co-deposition of aromatic-based organosulfides and inorganic Limore » salts using poly(sulfur-random-1,3-diisopropenylbenzene) as an additive in an electrolyte. The aromatic-based organic components with planar backbone conformation and π–π interaction in the SEI layers can improve the toughness and flexibility to promote stable and high efficient Li deposition/dissolution. The as-formed durable SEI layer can inhibit dendritic Li growth, enhance Li deposition/dissolution CE (99.1% over 420 cycles), and in turn enable Li–S batteries with good cycling stability (1000 cycles) and slow capacity decay. Finally, this work demonstrates a route to address the issues associated with Li metal anodes and promote the development of high-energy rechargeable Li metal batteries.« less

Planet Earth, Humans, Gravity and Their Connection to Natural Medicine-Essence from a 5000 Yrs Old Ancient Pedagogy

NASA Astrophysics Data System (ADS)

Lakshmanan, S.; Monsanto, C.; Radjendirane, B.

2015-12-01

According to the Ancient Indian Science, the fundamental constituents of planet earth are the five elements (Solid, Liquid, Heat, Air and Akash (subtlest energy field)). The same five elements constitute the human body. The Chinese and many other native traditions have used their deep understanding of these elements to live in balance with the planet. David Suzuki has elaborated on this key issue in his classic book, The Legacy: "Today we are in a state of crisis, and we must join together to respond to that crisis. If we do so, Suzuki envisions a future in which we understand that we are the Earth and live accordingly. All it takes is imagination and a determination to live within our, and the planet's, means". Gravity, the common force that connects both the body and earth plays a major role in the metabolism as well as the autonomous function of different organs in the body. Gravity has a direct influence on the fruits and vegetables that are grown on the planet as well. As a result, there is a direct relationship among gravity, food and human health. My talk will cover the missing link between the Earth's Gravity and the human health. A new set of ancient axioms will be used to address this and many other issues that are remain as "major unsolved problems" linking modern Geophysical and Health sciences.

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.

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.

A linear programming model for protein inference problem in shotgun proteomics.

PubMed

Huang, Ting; He, Zengyou

2012-11-15

Assembling peptides identified from tandem mass spectra into a list of proteins, referred to as protein inference, is an important issue in shotgun proteomics. The objective of protein inference is to find a subset of proteins that are truly present in the sample. Although many methods have been proposed for protein inference, several issues such as peptide degeneracy still remain unsolved. In this article, we present a linear programming model for protein inference. In this model, we use a transformation of the joint probability that each peptide/protein pair is present in the sample as the variable. Then, both the peptide probability and protein probability can be expressed as a formula in terms of the linear combination of these variables. Based on this simple fact, the protein inference problem is formulated as an optimization problem: minimize the number of proteins with non-zero probabilities under the constraint that the difference between the calculated peptide probability and the peptide probability generated from peptide identification algorithms should be less than some threshold. This model addresses the peptide degeneracy issue by forcing some joint probability variables involving degenerate peptides to be zero in a rigorous manner. The corresponding inference algorithm is named as ProteinLP. We test the performance of ProteinLP on six datasets. Experimental results show that our method is competitive with the state-of-the-art protein inference algorithms. The source code of our algorithm is available at: https://sourceforge.net/projects/prolp/. zyhe@dlut.edu.cn. Supplementary data are available at Bioinformatics Online.

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.

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

Cutaneous Scarring: A Clinical Review

PubMed Central

Baker, Richard; Urso-Baiarda, Fulvio; Linge, Claire; Grobbelaar, Adriaan

2009-01-01

Cutaneous scarring can cause patients symptoms ranging from the psychological to physical pain. Although the process of normal scarring is well described the ultimate cause of pathological scarring remains unknown. Similarly, exactly how early gestation fetuses can heal scarlessly remains unsolved. These questions are crucial in the search for a preventative or curative antiscarring agent. Such a discovery would be of enormous medical and commercial importance, not least because it may have application in other tissues. In the clinical context the assessment of scars is becoming more sophisticated and new physical, medical and surgical therapies are being introduced. This review aims to summarise some of the recent developments in scarring research for non-specialists and specialists alike. PMID:20585482

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.

[On practicability of implementing the speciality "podiatry" in traumatology and orthopedics].

PubMed

2011-01-01

The absence of single opinion concerning the classification of foot and ankle joint pathology does not permit to formulate universal and practical approach to the identification of pathological syndromes in case of patient foot lesion. The situation is aggravated by the unsolved issues related to the terminological definition of podiatry as a direction in orthopedics to solve the issues of foot and ankle joint pathology. In actual conditions the implementation of new technologies into the structure of traumatological orthopedics care is needed. This approach permits to combine the qualities of models of effective and optimized care to patients with foot and ankle joint pathology. The study of issue related to the systematization of podiatric pathology revealed that actually no single universal classification easy-to-use in practice exists. Hence the development of original applied working scheme of foot and ankle joint pathology is proposed.

An accuracy measurement method for star trackers based on direct astronomic observation

PubMed Central

Sun, Ting; Xing, Fei; Wang, Xiaochu; You, Zheng; Chu, Daping

2016-01-01

Star tracker is one of the most promising optical attitude measurement devices and it is widely used in spacecraft for its high accuracy. However, how to realize and verify such an accuracy remains a crucial but unsolved issue until now. The authenticity of the accuracy measurement method of a star tracker will eventually determine the satellite performance. A new and robust accuracy measurement method for a star tracker based on the direct astronomical observation is proposed here. In comparison with the conventional method with simulated stars, this method utilizes real navigation stars as observation targets which makes the measurement results more authoritative and authentic. Transformations between different coordinate systems are conducted on the account of the precision movements of the Earth, and the error curves of directional vectors are obtained along the three axes. Based on error analysis and accuracy definitions, a three-axis accuracy evaluation criterion has been proposed in this paper, which could determine pointing and rolling accuracy of a star tracker directly. Experimental measurements confirm that this method is effective and convenient to implement. Such a measurement environment is close to the in-orbit conditions and it can satisfy the stringent requirement for high-accuracy star trackers. PMID:26948412

Prospects for hydrogen storage in graphene.

PubMed

Tozzini, Valentina; Pellegrini, Vittorio

2013-01-07

Hydrogen-based fuel cells are promising solutions for the efficient and clean delivery of electricity. Since hydrogen is an energy carrier, a key step for the development of a reliable hydrogen-based technology requires solving the issue of storage and transport of hydrogen. Several proposals based on the design of advanced materials such as metal hydrides and carbon structures have been made to overcome the limitations of the conventional solution of compressing or liquefying hydrogen in tanks. Nevertheless none of these systems are currently offering the required performances in terms of hydrogen storage capacity and control of adsorption/desorption processes. Therefore the problem of hydrogen storage remains so far unsolved and it continues to represent a significant bottleneck to the advancement and proliferation of fuel cell and hydrogen technologies. Recently, however, several studies on graphene, the one-atom-thick membrane of carbon atoms packed in a honeycomb lattice, have highlighted the potentialities of this material for hydrogen storage and raise new hopes for the development of an efficient solid-state hydrogen storage device. Here we review on-going efforts and studies on functionalized and nanostructured graphene for hydrogen storage and suggest possible developments for efficient storage/release of hydrogen under ambient conditions.

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.

An accuracy measurement method for star trackers based on direct astronomic observation.

PubMed

Sun, Ting; Xing, Fei; Wang, Xiaochu; You, Zheng; Chu, Daping

2016-03-07

Star tracker is one of the most promising optical attitude measurement devices and it is widely used in spacecraft for its high accuracy. However, how to realize and verify such an accuracy remains a crucial but unsolved issue until now. The authenticity of the accuracy measurement method of a star tracker will eventually determine the satellite performance. A new and robust accuracy measurement method for a star tracker based on the direct astronomical observation is proposed here. In comparison with the conventional method with simulated stars, this method utilizes real navigation stars as observation targets which makes the measurement results more authoritative and authentic. Transformations between different coordinate systems are conducted on the account of the precision movements of the Earth, and the error curves of directional vectors are obtained along the three axes. Based on error analysis and accuracy definitions, a three-axis accuracy evaluation criterion has been proposed in this paper, which could determine pointing and rolling accuracy of a star tracker directly. Experimental measurements confirm that this method is effective and convenient to implement. Such a measurement environment is close to the in-orbit conditions and it can satisfy the stringent requirement for high-accuracy star trackers.

Modeling of helicon wave propagation and the physical process of helicon plasma production

NASA Astrophysics Data System (ADS)

Isayama, Shogo; Hada, Tohru; Shinohara, Shunjiro; Tanikawa, Takao

2014-10-01

Helicon plasma is a high-density and low-temperature plasma generated by the helicon wave, and is expected to be useful for various applications. On the other hand, there still remain a number of unsolved physical issues regarding how the plasma is generated using the helicon wave. The generation involves such physical processes as wave propagation, mode conversion, and collisionless as well as collisional wave damping that leads to ionization/recombination of neutral particles. In this study, we attempt to construct a model for the helicon plasma production using numerical simulations. In particular, we will make a quantitative argument on the roles of the mode conversion from the helicon to the electrostatic Trivelpiece-Gould (TG) wave, as first proposed by Shamrai. According to his scenario, the long wavelength helicon wave linearly mode converts to the TG wave, which then dissipates rapidly due to its large wave number. On the other hand, the efficiency of the mode conversion depends strongly on the magnitudes of dissipation parameters. Particularly when the dissipation is dominant, the TG wave is no longer excited and the input helicon wave directly dissipates. In the presentation, we will discuss the mode conversion and the plasma heating using numerical simulations.

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.

Assessing FAÇADE Visibility in 3d City Models for City Marketing

NASA Astrophysics Data System (ADS)

Albrecht, F.; Moser, J.; Hijazi, I.

2013-08-01

In city marketing, different applications require the evaluation of the visual impression of displays in the urban environment on people that visit the city. Therefore, this research focuses on the way how visual displays on façades for movie performances are perceived during a cultural event triggered by city marketing. We describe the different visibility analysis methods that are applicable to the analysis of façades. The methods advanced from the domains of Geographic Information Science, architecture and computer graphics. A detailed scenario is described in order to perform a requirements analysis for identifying the requirements to visibility information. This visibility information needs to describe the visual perception of displays on façades adequately. The requirements are compared to the visibility information that can be provided by the visibility methods. A discussion of the comparison summarizes the advantages and disadvantages of existing visibility analysis methods for describing the visibility of façades. The results show that part of the researched approaches is able to support the requirements to visibility information. But they also show that for a complete support of the entire analysis workflow, there remain unsolved workflow integration issues.

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.

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.

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.

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.

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.

What is memory? The present state of the engram.

PubMed

Poo, Mu-Ming; Pignatelli, Michele; Ryan, Tomás J; Tonegawa, Susumu; Bonhoeffer, Tobias; Martin, Kelsey C; Rudenko, Andrii; Tsai, Li-Huei; Tsien, Richard W; Fishell, Gord; Mullins, Caitlin; Gonçalves, J Tiago; Shtrahman, Matthew; Johnston, Stephen T; Gage, Fred H; Dan, Yang; Long, John; Buzsáki, György; Stevens, Charles

2016-05-19

The mechanism of memory remains one of the great unsolved problems of biology. Grappling with the question more than a hundred years ago, the German zoologist Richard Semon formulated the concept of the engram, lasting connections in the brain that result from simultaneous "excitations", whose precise physical nature and consequences were out of reach of the biology of his day. Neuroscientists now have the knowledge and tools to tackle this question, however, and this Forum brings together leading contemporary views on the mechanisms of memory and what the engram means today.

The hair follicle enigma.

PubMed

Bernard, Bruno A

2017-06-01

The hair follicle is a mini-organ endowed with a unique structure and cyclic behaviour. Despite the intense research efforts which have been devoted at deciphering the hair follicle biology over the past 70 years, one must admit that hair follicle remains an enigma. In this brief review, various aspects of hair follicle biology will be addressed, and more importantly, unsolved questions and new possible research tracks will be highlighted, including hair follicle glycobiology and exosome-mediated cell-cell interactions. Even though bricks of knowledge are solidly being acquired, an integrative picture remains to emerge. One can predict that computer science, algorithms and bioinformatics will assist in fostering our understanding hair biology. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

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…

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.

PML Nuclear Bodies

PubMed Central

Lallemand-Breitenbach, Valérie; de Thé, Hugues

2010-01-01

PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma. PMID:20452955

PML nuclear bodies.

PubMed

Lallemand-Breitenbach, Valérie; de Thé, Hugues

2010-05-01

PML nuclear bodies are matrix-associated domains that recruit an astonishing variety of seemingly unrelated proteins. Since their discovery in the early 1960s, PML bodies have fascinated cell biologists because of their beauty and their tight association with cellular disorders. The identification of PML, a gene involved in an oncogenic chromosomal translocation, as the key organizer of these domains drew instant interest onto them. The multiple levels of PML body regulation by a specific posttranslational modification, sumoylation, have raised several unsolved issues. Functionally, PML bodies may sequester, modify or degrade partner proteins, but in many ways, PML bodies still constitute an enigma.

[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.

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.

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

[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.

Statins and myositis: the role of anti-HMGCR antibodies.

PubMed

Selva-O'Callaghan, Albert; Alvarado-Cardenas, Marcelo; Marin, Ana; Pinal-Fernandez, Iago

2015-01-01

Muscle toxicity is a recognized adverse effect of statin use. Recently, a new myositis syndrome was described in association with antibodies directed against the pharmacologic target of statins, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR antibody). The patient's genetic background, characteristic histologic patterns (immune-mediated necrotizing myopathy), and presence of anti-HMGCR antibodies define the syndrome. In most patients, statin discontinuation is insufficient to reverse the myositis symptoms, and immunosuppressive therapy is needed. The mechanisms by which these antibodies may lead to disease are not fully elucidated. Several important questions remain unsolved and warrant further research.

New results on water in bulk, nanoconfined, and biological environments

NASA Astrophysics Data System (ADS)

Stanley, H. E.; Kumar, Pradeep; Xu, Limei; Yan, Zhenyu; Mazza, Marco 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. Despite decades of research, however, water's puzzling properties are not understood and 63 anomalies that distinguish water from other liquids remain unsolved. We present evidence from experiments and computer simulations supporting the hypothesis that water displays polyamorphism, i.e., water separates into two distinct liquid phases. This concept of a new liquid-liquid 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 biomolecule.

The meaning of work in people with severe mental illness (SMI) in Iran

PubMed Central

Khalaf beigi, Mitra; Mohammadi Shahbolaghi, Farahnaz; Rassafiani, Mehdi; Haghgoo, Hojjat-Allah; Taherkhani, Hamid

2015-01-01

Background: 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. Methods: 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. Results: Four themes emerged from data including: acquiring identity, work as a drive, passing the time and financial independence. Conclusion: 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. PMID:26034732

Is There a Risk of Yellow Fever Virus Transmission in South Asian Countries with Hyperendemic Dengue?

PubMed Central

Agampodi, Suneth B.; Wickramage, Kolitha

2013-01-01

The fact that yellow fever (YF) has never occurred in Asia remains an “unsolved mystery” in global health. Most countries in Asia with high Aedes aegypti mosquito density are considered “receptive” for YF transmission. Recently, health officials in Sri Lanka issued a public health alert on the potential spread of YF from a migrant group from West Africa. We performed an extensive review of literature pertaining to the risk of YF in Sri Lanka/South Asian region to understand the probability of actual risk and assist health authorities to form evidence informed public health policies/practices. Published data from epidemiological, historical, biological, molecular, and mathematical models were harnessed to assess the risk of YF in Asia. Using this data we examine a number of theories proposed to explain lack of YF in Asia. Considering the evidence available, we conclude that the probable risk of local transmission of YF is extremely low in Sri Lanka and for other South Asian countries despite a high Aedes aegypti density and associated dengue burden. This does not however exclude the future possibility of transmission in Asia, especially considering the rapid influx travelers from endemic areas, as we report, arriving in Sri Lanka. PMID:24367789

Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

PubMed Central

Choi, Seung-In; Lim, Ji Yeon; Yoo, Sungjae; Kim, Hyun; Hwang, Sun Wook

2016-01-01

TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. PMID:26885404

Multiconstrained gene clustering based on generalized projections

PubMed Central

2010-01-01

Background Gene clustering for annotating gene functions is one of the fundamental issues in bioinformatics. The best clustering solution is often regularized by multiple constraints such as gene expressions, Gene Ontology (GO) annotations and gene network structures. How to integrate multiple pieces of constraints for an optimal clustering solution still remains an unsolved problem. Results We propose a novel multiconstrained gene clustering (MGC) method within the generalized projection onto convex sets (POCS) framework used widely in image reconstruction. Each constraint is formulated as a corresponding set. The generalized projector iteratively projects the clustering solution onto these sets in order to find a consistent solution included in the intersection set that satisfies all constraints. Compared with previous MGC methods, POCS can integrate multiple constraints from different nature without distorting the original constraints. To evaluate the clustering solution, we also propose a new performance measure referred to as Gene Log Likelihood (GLL) that considers genes having more than one function and hence in more than one cluster. Comparative experimental results show that our POCS-based gene clustering method outperforms current state-of-the-art MGC methods. Conclusions The POCS-based MGC method can successfully combine multiple constraints from different nature for gene clustering. Also, the proposed GLL is an effective performance measure for the soft clustering solutions. PMID:20356386

Precipitation and Hardening in Magnesium Alloys

NASA Astrophysics Data System (ADS)

Nie, Jian-Feng

2012-11-01

Magnesium alloys have received an increasing interest in the past 12 years for potential applications in the automotive, aircraft, aerospace, and electronic industries. Many of these alloys are strong because of solid-state precipitates that are produced by an age-hardening process. Although some strength improvements of existing magnesium alloys have been made and some novel alloys with improved strength have been developed, the strength level that has been achieved so far is still substantially lower than that obtained in counterpart aluminum alloys. Further improvements in the alloy strength require a better understanding of the structure, morphology, orientation of precipitates, effects of precipitate morphology, and orientation on the strengthening and microstructural factors that are important in controlling the nucleation and growth of these precipitates. In this review, precipitation in most precipitation-hardenable magnesium alloys is reviewed, and its relationship with strengthening is examined. It is demonstrated that the precipitation phenomena in these alloys, especially in the very early stage of the precipitation process, are still far from being well understood, and many fundamental issues remain unsolved even after some extensive and concerted efforts made in the past 12 years. The challenges associated with precipitation hardening and age hardening are identified and discussed, and guidelines are outlined for the rational design and development of higher strength, and ultimately ultrahigh strength, magnesium alloys via precipitation hardening.

Integrating user profile in medical CBIR systems to answer perceptual similarity queries

NASA Astrophysics Data System (ADS)

Bugatti, Pedro H.; Kaster, Daniel S.; Ponciano-Silva, Marcelo; Traina, Agma J. M.; Traina, Caetano, Jr.

2011-03-01

Techniques for Content-Based Image Retrieval (CBIR) have been intensively explored due to the increase in the amount of captured images and the need of fast retrieval of them. The medical field is a specific example that generates a large flow of information, especially digital images employed for diagnosing. One issue that still remains unsolved deals with how to reach the perceptual similarity. That is, to achieve an effective retrieval, one must characterize and quantify the perceptual similarity regarding the specialist in the field. Therefore, the present paper was conceived to fill in this gap creating a consistent support to perform similarity queries over medical images, maintaining the semantics of a given query desired by the user. CBIR systems relying in relevance feedback techniques usually request the users to label relevant images. In this paper, we present a simple but highly effective strategy to survey user profiles, taking advantage of such labeling to implicitly gather the user perceptual similarity. The user profiles maintain the settings desired for each user, allowing tuning the similarity assessment, which encompasses dynamically changing the distance function employed through an interactive process. Experiments using computed tomography lung images show that the proposed approach is effective in capturing the users' perception.

Universal surface-enhanced Raman scattering amplification detector for ultrasensitive detection of multiple target analytes.

PubMed

Zheng, Jing; Hu, Yaping; Bai, Junhui; Ma, Cheng; Li, Jishan; Li, Yinhui; Shi, Muling; Tan, Weihong; Yang, Ronghua

2014-02-18

Up to now, the successful fabrication of efficient hot-spot substrates for surface-enhanced Raman scattering (SERS) remains an unsolved problem. To address this issue, we describe herein a universal aptamer-based SERS biodetection approach that uses a single-stranded DNA as a universal trigger (UT) to induce SERS-active hot-spot formation, allowing, in turn, detection of a broad range of targets. More specifically, interaction between the aptamer probe and its target perturbs a triple-helix aptamer/UT structure in a manner that activates a hybridization chain reaction (HCR) among three short DNA building blocks that self-assemble into a long DNA polymer. The SERS-active hot-spots are formed by conjugating 4-aminobenzenethiol (4-ABT)-encoded gold nanoparticles with the DNA polymer through a specific Au-S bond. As proof-of-principle, we used this approach to quantify multiple target analytes, including thrombin, adenosine, and CEM cancer cells, achieving lowest limit of detection values of 18 pM, 1.5 nM, and 10 cells/mL, respectively. As a universal SERS detector, this prototype can be applied to many other target analytes through the use of suitable DNA-functional partners, thus inspiring new designs and applications of SERS for bioanalysis.

Predicting Electrostatic Forces in RNA Folding

PubMed Central

Tan, Zhi-Jie; Chen, Shi-Jie

2016-01-01

Metal ion-mediated electrostatic interactions are critical to RNA folding. Although considerable progress has been made in mechanistic studies, the problem of accurate predictions for the ion effects in RNA folding remains unsolved, mainly due to the complexity of several potentially important issues such as ion correlation and dehydration effects. In this chapter, after giving a brief overview of the experimental findings and theoretical approaches, we focus on a recently developed new model, the tightly bound ion (TBI) model, for ion electrostatics in RNA folding. The model is unique because it can treat ion correlation and fluctuation effects for realistic RNA 3D structures. For monovalent ion (such as Na+) solutions, where ion correlation is weak, TBI and the Poisson–Boltzmann (PB) theory give the same results and the results agree with the experimental data. For multivalent ion (such as Mg2+) solutions, where ion correlation can be strong, however, TBI gives much improved predictions than the PB. Moreover, the model suggests an ion correlation- induced mechanism for the unusual efficiency of Mg2+ ions in the stabilization of RNA tertiary folds. In this chapter, after introducing the theoretical framework of the TBI model, we will describe how to apply the model to predict ion-binding properties and ion-dependent folding stabilities. PMID:20946803

A Main Sequence For Quasars

NASA Astrophysics Data System (ADS)

Marziani, Paola; Sulentic, J. W.; Dultzin, D.; Negrete, A.; del Olmo, A.; Martínez-Carballo, M. A.; Stirpe, G. M.; D'Onofrio, M.; Perea, J.

2016-10-01

The 4D eigenvector 1 parameter space defined by Sulentic et al. may be seen as a surrogate H-R diagram for quasars. As in the stellar H-R diagram, a source sequence can be easily identified. In the case of quasars, the main sequence appears to be mainly driven by Eddington ratio. A transition Eddington ratio may in part explain the striking observational differences between quasars at opposite ends of the main sequence. The eigenvector-1 approach opens the door towards properly contextualized models of quasar physics, geometry and kinematics. We review some of the progress that has been made over the past 15 years, and point out still unsolved issues.

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.

Short-Term fo F2 Forecast: Present Day State of Art

NASA Astrophysics Data System (ADS)

Mikhailov, A. V.; Depuev, V. H.; Depueva, A. H.

An analysis of the F2-layer short-term forecast problem has been done. Both objective and methodological problems prevent us from a deliberate F2-layer forecast issuing at present. An empirical approach based on statistical methods may be recommended for practical use. A forecast method based on a new aeronomic index (a proxy) AI has been proposed and tested over selected 64 severe storm events. The method provides an acceptable prediction accuracy both for strongly disturbed and quiet conditions. The problems with the prediction of the F2-layer quiet-time disturbances as well as some other unsolved problems are discussed

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…

Report from a consensus conference on antibody-mediated rejection in heart transplantation

PubMed Central

Kobashigawa, Jon; Crespo-Leiro, Maria G.; Ensminger, Stephan M.; Reichenspurner, Hermann; Angelini, Annalisa; Berry, Gerald; Burke, Margaret; Czer, Lawrence; Hiemann, Nicola; Kfoury, Abdallah G.; Mancini, Donna; Mohacsi, Paul; Patel, Jignesh; Pereira, Naveen; Platt, Jeffrey L.; Reed, Elaine F.; Reinsmoen, Nancy; Rodriguez, E. Rene; Rose, Marlene L.; Russell, Stuart D.; Starling, Randy; Suciu-Foca, Nicole; Tallaj, Jose; Taylor, David O.; Van Bakel, Adrian; West, Lori; Zeevi, Adriana; Zuckermann, Andreas

2012-01-01

BACKGROUND The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. METHODS The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. RESULTS A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. CONCLUSIONS The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues. PMID:21300295

Vanishing spin stiffness in the spin-1/2 Heisenberg chain for any nonzero temperature

NASA Astrophysics Data System (ADS)

Carmelo, J. M. P.; Prosen, T.; Campbell, D. K.

2015-10-01

Whether at the zero spin density m =0 and finite temperatures T >0 the spin stiffness of the spin-1 /2 X X X chain is finite or vanishes remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we explicitly compute the stiffness at m =0 and find strong evidence that it vanishes. In particular, we derive an upper bound on the stiffness within a canonical ensemble at any fixed value of spin density m that is proportional to m2L in the thermodynamic limit of chain length L →∞ , for any finite, nonzero temperature, which implies the absence of ballistic transport for T >0 for m =0 . Although our method relies in part on the thermodynamic Bethe ansatz (TBA), it does not evaluate the stiffness through the second derivative of the TBA energy eigenvalues relative to a uniform vector potential. Moreover, we provide strong evidence that in the thermodynamic limit the upper bounds on the spin current and stiffness used in our derivation remain valid under string deviations. Our results also provide strong evidence that in the thermodynamic limit the TBA method used by X. Zotos [Phys. Rev. Lett. 82, 1764 (1999), 10.1103/PhysRevLett.82.1764] leads to the exact stiffness values at finite temperature T >0 for models whose stiffness is finite at T =0 , similar to the spin stiffness of the spin-1 /2 Heisenberg chain but unlike the charge stiffness of the half-filled 1D Hubbard model.

Vaccines and Kawasaki disease.

PubMed

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

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

Quantification of Liver Iron with MRI: State of the Art and Remaining Challenges

PubMed Central

Hernando, Diego; Levin, Yakir S; Sirlin, Claude B; Reeder, Scott B

2015-01-01

Liver iron overload is the histological hallmark of hereditary hemochromatosis and transfusional hemosiderosis, and can also occur in chronic hepatopathies. Iron overload can result in liver damage, with the eventual development of cirrhosis, liver failure and hepatocellular carcinoma. Assessment of liver iron levels is necessary for detection and quantitative staging of iron overload, and monitoring of iron-reducing treatments. This article discusses the need for non-invasive assessment of liver iron, and reviews qualitative and quantitative methods with a particular emphasis on MRI. Specific MRI methods for liver iron quantification include signal intensity ratio as well as R2 and R2* relaxometry techniques. Methods that are in clinical use, as well as their limitations, are described. Remaining challenges, unsolved problems, and emerging techniques to provide improved characterization of liver iron deposition are discussed. PMID:24585403

Some unsolved problems in discrete mathematics and mathematical cybernetics

NASA Astrophysics Data System (ADS)

Korshunov, Aleksei D.

2009-10-01

There are many unsolved problems in discrete mathematics and mathematical cybernetics. Writing a comprehensive survey of such problems involves great difficulties. First, such problems are rather numerous and varied. Second, they greatly differ from each other in degree of completeness of their solution. Therefore, even a comprehensive survey should not attempt to cover the whole variety of such problems; only the most important and significant problems should be reviewed. An impersonal choice of problems to include is quite hard. This paper includes 13 unsolved problems related to combinatorial mathematics and computational complexity theory. The problems selected give an indication of the author's studies for 50 years; for this reason, the choice of the problems reviewed here is, to some extent, subjective. At the same time, these problems are very difficult and quite important for discrete mathematics and mathematical cybernetics. Bibliography: 74 items.

[The social hygiene problems in the operator work of hydroelectric power station workers and the means for enhancing work capacity].

PubMed

Karakashian, A N; Lepeshkina, T R; Ratushnaia, A N; Glushchenko, S S; Zakharenko, M I; Lastovchenko, V B; Diordichuk, T I

1993-01-01

Weight, tension and harmfulness of professional activity, peculiarities of labour conditions and characteristics of work, shift dynamics of operative personnel's working capacity were studied in the course of 8-hour working day currently accepted at hydroelectric power stations (HEPS) and experimental 12-hour schedule. Working conditions classified as "admissible", positive dynamics of operators' state, their social and material contentment were a basis for 12-hour two-shift schedule to be recommended as more appropriate. At the same time, problem of optimal shift schedules for operative personnel of HEPS remains unsolved and needs to be further explored.

A generative, probabilistic model of local protein structure.

PubMed

Boomsma, Wouter; Mardia, Kanti V; Taylor, Charles C; Ferkinghoff-Borg, Jesper; Krogh, Anders; Hamelryck, Thomas

2008-07-01

Despite significant progress in recent years, protein structure prediction maintains its status as one of the prime unsolved problems in computational biology. One of the key remaining challenges is an efficient probabilistic exploration of the structural space that correctly reflects the relative conformational stabilities. Here, we present a fully probabilistic, continuous model of local protein structure in atomic detail. The generative model makes efficient conformational sampling possible and provides a framework for the rigorous analysis of local sequence-structure correlations in the native state. Our method represents a significant theoretical and practical improvement over the widely used fragment assembly technique by avoiding the drawbacks associated with a discrete and nonprobabilistic approach.

Security Measures to Protect Mobile Agents

NASA Astrophysics Data System (ADS)

Dadhich, Piyanka; Govil, M. C.; Dutta, Kamlesh

2010-11-01

The security issues of mobile agent systems have embarrassed its widespread implementation. Mobile agents that move around the network are not safe because the remote hosts that accommodate the agents initiates all kinds of attacks. These hosts try to analyze the agent's decision logic and their accumulated data. So, mobile agent security is the most challenging unsolved problems. The paper analyzes various security measures deeply. Security especially the attacks performed by hosts to the visiting mobile agent (the malicious hosts problem) is a major obstacle that prevents mobile agent technology from being widely adopted. Being the running environment for mobile agent, the host has full control over them and could easily perform many kinds of attacks against them.

Conflicting evidence about long-distance animal navigation.

PubMed

Alerstam, Thomas

2006-08-11

Because of conflicting evidence about several fundamental issues, long-distance animal navigation has yet to be satisfactorily explained. Among the unsolved problems are the nature of genetic spatial control of migration and the relationships between celestial and magnetic compass mechanisms and between different map-related cues in orientation and homing, respectively. In addition, navigation is expected to differ between animal groups depending on sensory capabilities and ecological conditions. Evaluations based on modern long-term tracking techniques of the geometry of migration routes and individual migration history, combined with behavioral experiments and exploration of the sensory and genetic mechanisms, will be crucial for understanding the spatial principles that guide animals on their global journeys.

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,…

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.

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.

Social Experiments in the Mesoscale: Humans Playing a Spatial Prisoner's Dilemma

PubMed Central

Grujić, Jelena; Fosco, Constanza; Araujo, Lourdes; Cuesta, José A.; Sánchez, Angel

2010-01-01

Background The evolutionary origin of cooperation among unrelated individuals remains a key unsolved issue across several disciplines. Prominent among the several mechanisms proposed to explain how cooperation can emerge is the existence of a population structure that determines the interactions among individuals. Many models have explored analytically and by simulation the effects of such a structure, particularly in the framework of the Prisoner's Dilemma, but the results of these models largely depend on details such as the type of spatial structure or the evolutionary dynamics. Therefore, experimental work suitably designed to address this question is needed to probe these issues. Methods and Findings We have designed an experiment to test the emergence of cooperation when humans play Prisoner's Dilemma on a network whose size is comparable to that of simulations. We find that the cooperation level declines to an asymptotic state with low but nonzero cooperation. Regarding players' behavior, we observe that the population is heterogeneous, consisting of a high percentage of defectors, a smaller one of cooperators, and a large group that shares features of the conditional cooperators of public goods games. We propose an agent-based model based on the coexistence of these different strategies that is in good agreement with all the experimental observations. Conclusions In our large experimental setup, cooperation was not promoted by the existence of a lattice beyond a residual level (around 20%) typical of public goods experiments. Our findings also indicate that both heterogeneity and a “moody” conditional cooperation strategy, in which the probability of cooperating also depends on the player's previous action, are required to understand the outcome of the experiment. These results could impact the way game theory on graphs is used to model human interactions in structured groups. PMID:21103058

i3Drefine software for protein 3D structure refinement and its assessment in CASP10.

PubMed

Bhattacharya, Debswapna; Cheng, Jianlin

2013-01-01

Protein structure refinement refers to the process of improving the qualities of protein structures during structure modeling processes to bring them closer to their native states. Structure refinement has been drawing increasing attention in the community-wide Critical Assessment of techniques for Protein Structure prediction (CASP) experiments since its addition in 8(th) CASP experiment. During the 9(th) and recently concluded 10(th) CASP experiments, a consistent growth in number of refinement targets and participating groups has been witnessed. Yet, protein structure refinement still remains a largely unsolved problem with majority of participating groups in CASP refinement category failed to consistently improve the quality of structures issued for refinement. In order to alleviate this need, we developed a completely automated and computationally efficient protein 3D structure refinement method, i3Drefine, based on an iterative and highly convergent energy minimization algorithm with a powerful all-atom composite physics and knowledge-based force fields and hydrogen bonding (HB) network optimization technique. In the recent community-wide blind experiment, CASP10, i3Drefine (as 'MULTICOM-CONSTRUCT') was ranked as the best method in the server section as per the official assessment of CASP10 experiment. Here we provide the community with free access to i3Drefine software and systematically analyse the performance of i3Drefine in strict blind mode on the refinement targets issued in CASP10 refinement category and compare with other state-of-the-art refinement methods participating in CASP10. Our analysis demonstrates that i3Drefine is only fully-automated server participating in CASP10 exhibiting consistent improvement over the initial structures in both global and local structural quality metrics. Executable version of i3Drefine is freely available at http://protein.rnet.missouri.edu/i3drefine/.

[Neurologic complications of subarachnoid hemorrhage due to intracranial aneurysm rupture].

PubMed

Rama-Maceiras, P; Fàbregas Julià, N; Ingelmo Ingelmo, I; Hernández-Palazón, J

2010-12-01

The high rates of morbidity and mortality after subarachnoid hemorrhage due to spontaneous rupture of an intracranial aneurysm are mainly the result of neurologic complications. Sixty years after cerebral vasospasm was first described, this problem remains unsolved in spite of its highly adverse effect on prognosis after aneurysmatic rupture. Treatment is somewhat empirical, given that uncertainties remain in our understanding of the pathophysiology of this vascular complication, which involves structural and biochemical changes in the endothelium and smooth muscle of vessels. Vasospasm that is refractory to treatment leads to cerebral infarction. Prophylaxis, early diagnosis, and adequate treatment of neurologic complications are key elements in the management of vasospasm if neurologic damage, lengthy hospital stays, and increased use of health care resources are to be avoided. New approaches to early treatment of cerebral lesions and cortical ischemia in cases of subarachnoid hemorrhage due to aneurysm rupture should lead to more effective, specific management.

Necrotizing Enterocolitis in the Premature Infant

PubMed Central

Gregory, Katherine E.; DeForge, Christine E.; Natale, Kristan M.; Phillips, Michele; Van Marter, Linda J.

2013-01-01

Necrotizing enterocolitis (NEC) remains one of the most catastrophic comorbidities associated with prematurity. In spite of extensive research, the disease remains unsolved. The aims of this paper are to present the current state of the science on the pathogenesis of NEC, summarize the clinical presentation and severity staging of the disease, and highlight the nursing assessments required for early identification of NEC and ongoing care for infants diagnosed with this gastrointestinal disease. The distributions of systemic and intestinal clinical signs that are most sensitive to nursing assessment and associated with Bell Staging Criteria are presented. This descriptive data is representative of 117 cases of NEC diagnosed in low gestational age infants (<29 weeks gestation). The data highlights the clinical signs most commonly observed in infants with NEC, and thus, provides NICU nurses an evidence-based guide for assessment and care of infants with NEC. PMID:21730907

Medications Used for Cognitive Enhancement in Patients With Schizophrenia, Bipolar Disorder, Alzheimer's Disease, and Parkinson's Disease.

PubMed

Hsu, Wen-Yu; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Cognitive impairment, which frequently occurs in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease, has a significant impact on the daily lives of both patients and their family. Furthermore, since the medications used for cognitive enhancement have limited efficacy, the issue of cognitive enhancement still remains a clinically unsolved challenge. We reviewed the clinical studies (published between 2007 and 2017) that focused on the efficacy of medications used for enhancing cognition in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease. Acetylcholinesterase inhibitors and memantine are the standard treatments for Alzheimer's disease and Parkinson's disease. Some studies have reported selective cognitive improvement in patients with schizophrenia following galantamine treatment. Newer antipsychotics, including paliperidone, lurasidone, aripiprazole, ziprasidone, and BL-1020, have also been reported to exert cognitive benefits in patients with schizophrenia. Dopaminergic medications were found to improve language function in patients with Parkinson's disease. However, no beneficial effects on cognitive function were observed with dopamine agonists in patients with schizophrenia. The efficacies of nicotine and its receptor modulators in cognitive improvement remain controversial, with the majority of studies showing that varenicline significantly improved the cognitive function in schizophrenic patients. Several studies have reported that N -methyl-d-aspartate glutamate receptor (NMDAR) enhancers improved the cognitive function in patients with chronic schizophrenia. NMDAR enhancers might also have cognitive benefits in patients with Alzheimer's disease or Parkinson's disease. Raloxifene, a selective estrogen receptor modulator, has also been demonstrated to have beneficial effects on attention, processing speed, and memory in female patients with schizophrenia. Clinical trials with larger sample sizes evaluating comprehensive cognitive domains are warranted to examine the efficacy of medications in cognitive enhancement in patients with schizophrenia, bipolar disorder, Alzheimer's disease, and Parkinson's disease.

Personality differences in early versus late suicide attempters.

PubMed

Lewitzka, Ute; Denzin, Sebastian; Sauer, Cathrin; Bauer, Michael; Jabs, Burkhard

2016-08-09

Suicidality is an individual behaviour caused by a complex framework of internal and external factors. The predictive values of personality traits for a suicide attempt have been demonstrated, especially in conjunction with Cloninger's TCI and impulsivity. Two issues remain unsolved, namely whether these traits alter over time after a suicide attempt, and how they may be influenced by depressive symptoms. We studied two patient cohorts: one sample of 81 patients after a suicide attempt no longer than 3 months previously (SA early) and another sample of 32 patients whose attempt had taken place more than 6 months previously (SA late). We carried out structured interviews with these subjects addressing diagnosis (MINI), suicidality (Scale for suicide ideation), depression (HAMD-17), temperament and character inventory (TCI), and impulsivity (BIS-10). Data analysis was done using SPSS 16.0. Our two groups did not differ significantly in sociodemographics or suicidality. However, patients in the SA early group were significantly more depressed (p < 0.001), and scored lower in reward dependence (p < 0.001) and persistence (p = 0.005) but higher in harm avoidance (p < 0.001); they did not differ significantly in impulsivity (p < 0.01). Reward dependence, persistence, and harm avoidance remained significantly different between the two groups after controlling for depressive symptoms. Our findings suggest that some personality traits vary after a suicide attempt. Further investigations are necessary to verify our results, ideally in longitudinal studies with larger, carefully-described cohorts. It would be also clinically important to investigate the influence of therapeutic strategies on the variability of personality traits and their impact on suicidal behavior.

Geometric and Colour Data Fusion for Outdoor 3D Models

PubMed Central

Merchán, Pilar; Adán, Antonio; Salamanca, Santiago; Domínguez, Vicente; Chacón, Ricardo

2012-01-01

This paper deals with the generation of accurate, dense and coloured 3D models of outdoor scenarios from scanners. This is a challenging research field in which several problems still remain unsolved. In particular, the process of 3D model creation in outdoor scenes may be inefficient if the scene is digitalized under unsuitable technical (specific scanner on-board camera) and environmental (rain, dampness, changing illumination) conditions. We address our research towards the integration of images and range data to produce photorealistic models. Our proposal is based on decoupling the colour integration and geometry reconstruction stages, making them independent and controlled processes. This issue is approached from two different viewpoints. On the one hand, given a complete model (geometry plus texture), we propose a method to modify the original texture provided by the scanner on-board camera with the colour information extracted from external images taken at given moments and under specific environmental conditions. On the other hand, we propose an algorithm to directly assign external images onto the complete geometric model, thus avoiding tedious on-line calibration processes. We present the work conducted on two large Roman archaeological sites dating from the first century A.D., namely, the Theatre of Segobriga and the Fori Porticus of Emerita Augusta, both in Spain. The results obtained demonstrate that our approach could be useful in the digitalization and 3D modelling fields. PMID:22969327

Uncertainty propagation in orbital mechanics via tensor decomposition

NASA Astrophysics Data System (ADS)

Sun, Yifei; Kumar, Mrinal

2016-03-01

Uncertainty forecasting in orbital mechanics is an essential but difficult task, primarily because the underlying Fokker-Planck equation (FPE) is defined on a relatively high dimensional (6-D) state-space and is driven by the nonlinear perturbed Keplerian dynamics. In addition, an enormously large solution domain is required for numerical solution of this FPE (e.g. encompassing the entire orbit in the x-y-z subspace), of which the state probability density function (pdf) occupies a tiny fraction at any given time. This coupling of large size, high dimensionality and nonlinearity makes for a formidable computational task, and has caused the FPE for orbital uncertainty propagation to remain an unsolved problem. To the best of the authors' knowledge, this paper presents the first successful direct solution of the FPE for perturbed Keplerian mechanics. To tackle the dimensionality issue, the time-varying state pdf is approximated in the CANDECOMP/PARAFAC decomposition tensor form where all the six spatial dimensions as well as the time dimension are separated from one other. The pdf approximation for all times is obtained simultaneously via the alternating least squares algorithm. Chebyshev spectral differentiation is employed for discretization on account of its spectral ("super-fast") convergence rate. To facilitate the tensor decomposition and control the solution domain size, system dynamics is expressed using spherical coordinates in a noninertial reference frame. Numerical results obtained on a regular personal computer are compared with Monte Carlo simulations.

A new nano-engineered hierarchical membrane for concurrent removal of surfactant and oil from oil-in-water nanoemulsion

PubMed Central

Qin, Detao; Liu, Zhaoyang; Bai, Hongwei; Sun, Darren Delai; Song, Xiaoxiao

2016-01-01

Surfactant stabilized oil-in-water nanoemulsions pose a severe threat to both the environment and human health. Recent development of membrane filtration technology has enabled efficient oil removal from oil/water nanoemulsion, however, the concurrent removal of surfactant and oil remains unsolved because the existing filtration membranes still suffer from low surfactant removal rate and serious surfactant-induced fouling issue. In this study, to realize the concurrent removal of surfactant and oil from nanoemulsion, a novel hierarchically-structured membrane is designed with a nanostructured selective layer on top of a microstructured support layer. The physical and chemical properties of the overall membrane, including wettability, surface roughness, electric charge, thickness and structures, are delicately tailored through a nano-engineered fabrication process, that is, graphene oxide (GO) nanosheet assisted phase inversion coupled with surface functionalization. Compared with the membrane fabricated by conventional phase inversion, this novel membrane has four times higher water flux, significantly higher rejections of both oil (~99.9%) and surfactant (as high as 93.5%), and two thirds lower fouling ratio when treating surfactant stabilized oil-in-water nanoemulsion. Due to its excellent performances and facile fabrication process, this nano-engineered membrane is expected to have wide practical applications in the oil/water separation fields of environmental protection and water purification. PMID:27087362

Impact of phenomenological theory of turbulence on pragmatic approach to fluvial hydraulics

NASA Astrophysics Data System (ADS)

Ali, Sk Zeeshan; Dey, Subhasish

2018-04-01

The phenomenological theory of turbulence (PTT) remains a long-standing and fascinating theory in turbulence research. In this review article, we highlight the state-of-the-science of the impact of the PTT on the pragmatic approach to fluvial hydraulics, explored over recent decades, discussing the salient and the subtle roles that the turbulence plays in governing many physical processes. To acquire a theoretical explanation of this pragmatic approach necessitates an intuitive thought that can bring together the background mechanisms of all the physical processes under one law—a thought that is capable of finding their inextricable links with the turbulent energy spectrum. We begin here with emphasizing the spectral and the co-spectral origin of the well-recognized laws of the wall, the resistance equation, and the turbulence intensities by portraying the typical momentum transfer mechanism of eddies in a turbulent flow. Next, we focus on the scaling laws of key fluvial processes derived from the perspective of the PTT, enlightening their physical insight and ability to judge how far the so-called empirical formulas can be used with confidence. The PTT has been able to disclose the origin of several primeval empirical formulas that have been used over many years without having any theoretical clarification and confirmation. Finally, we make an effort to describe some unsolved issues to be resolved as a future scope of research.

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.

'Einselection' of pointer observables: The new H-theorem?

NASA Astrophysics Data System (ADS)

Kastner, Ruth E.

2014-11-01

In attempting to derive irreversible macroscopic thermodynamics from reversible microscopic dynamics, Boltzmann inadvertently smuggled in a premise that assumed the very irreversibility he was trying to prove: 'molecular chaos'. The program of 'einselection' (environmentally induced superselection) within Everettian approaches faces a similar 'Loschmidt's Paradox': the universe, according to the Everettian picture, is a closed system obeying only unitary dynamics, and it therefore contains no distinguishable environmental subsystems with the necessary 'phase randomness' to effect einselection of a pointer observable. The theoretically unjustified assumption of distinguishable environmental subsystems is the hidden premise that makes the derivation of einselection circular. In effect, it presupposes the 'emergent' structures from the beginning. Thus the problem of basis ambiguity remains unsolved in Everettian interpretations.

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.

Reconstructing galaxy histories from globular clusters.

PubMed

West, Michael J; Côté, Patrick; Marzke, Ronald O; Jordán, Andrés

2004-01-01

Nearly a century after the true nature of galaxies as distant 'island universes' was established, their origin and evolution remain great unsolved problems of modern astrophysics. One of the most promising ways to investigate galaxy formation is to study the ubiquitous globular star clusters that surround most galaxies. Globular clusters are compact groups of up to a few million stars. They generally formed early in the history of the Universe, but have survived the interactions and mergers that alter substantially their parent galaxies. Recent advances in our understanding of the globular cluster systems of the Milky Way and other galaxies point to a complex picture of galaxy genesis driven by cannibalism, collisions, bursts of star formation and other tumultuous events.

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

Targeting the Cerebellum by Noninvasive Neurostimulation: a Review.

PubMed

van Dun, Kim; Bodranghien, Florian; Manto, Mario; Mariën, Peter

2017-06-01

Transcranial magnetic and electric stimulation of the brain are novel and highly promising techniques currently employed in both research and clinical practice. Improving or rehabilitating brain functions by modulating excitability with these noninvasive tools is an exciting new area in neuroscience. Since the cerebellum is closely connected with the cerebral regions subserving motor, associative, and affective functions, the cerebello-thalamo-cortical pathways are an interesting target for these new techniques. Targeting the cerebellum represents a novel way to modulate the excitability of remote cortical regions and their functions. This review brings together the studies that have applied cerebellar stimulation, magnetic and electric, and presents an overview of the current knowledge and unsolved issues. Some recommendations for future research are implemented as well.

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.

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

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.

Initiation of Positive Streamers near Uncharged Ice Hydrometeors in the Thundercloud Field

NASA Astrophysics Data System (ADS)

Babich, L. P.; Bochkov, E. I.

2018-05-01

Since the threshold electric field required for breakdown of air is much higher than the maximum field strength measured in thunderstorm clouds, the problem of lightning initiation still remains unsolved. According to the popular hypothesis, lightning can be initiated by a streamer discharge in the field enhanced near a hydrometeor. To verify the adequacy of this hypothesis, the development of a positive streamer propagating along the thunderstorm electric field in the vicinity of an ice needle at an air pressure corresponding to an altitude of 5 km (which is typical of the lightning initiation conditions) was simulated numerically. The hydrometeor dimensions are determined at which streamers can be initiated at different strengths of the thunderstorm electric field.

Bioimage informatics for experimental biology

PubMed Central

Swedlow, Jason R.; Goldberg, Ilya G.; Eliceiri, Kevin W.

2012-01-01

Over the last twenty years there have been great advances in light microscopy with the result that multi-dimensional imaging has driven a revolution in modern biology. The development of new approaches of data acquisition are reportedly frequently, and yet the significant data management and analysis challenges presented by these new complex datasets remains largely unsolved. Like the well-developed field of genome bioinformatics, central repositories are and will be key resources, but there is a critical need for informatics tools in individual laboratories to help manage, share, visualize, and analyze image data. In this article we present the recent efforts by the bioimage informatics community to tackle these challenges and discuss our own vision for future development of bioimage informatics solution. PMID:19416072

Unplugging the callose plug from sieve pores.

PubMed

Xie, Bo; Hong, Zonglie

2011-04-01

The presence of callose in sieve plates has been known for a long time, but how this polysaccharide plug is synthesized has remained unsolved. Two independent laboratories have recently reported the identification of callose synthase 7 (CalS7), also known as glucan synthase-like 7 (GSL7), as the enzyme responsible for callose deposition in sieve plates. Mutant plants defective in this enzyme failed to synthesize callose in developing sieve plates during phloem formation and were unable to accumulate callose in sieve pores in response to stress treatments. The mutant plants developed less open pores per sieve plate and the pores were smaller in diameter. As a result, phloem conductivity was reduced significantly and the mutant plants were shorter and set fewer seeds.

Electronic structures of superionic conductor Li3N

NASA Astrophysics Data System (ADS)

Aoki, Masaru; Ode, Yoshiyuki; Tsumuraya, Kazuo

2011-03-01

Lithium nitride is a superionic conductor with high Li conductivity. The compound has been studied extensively because of its potential utility as electrolyte in solid-state batteries. Though the mobility of the cations within the crystalline solid is high comparable to that of molten salts, the mechanism of the high mobility of the cations remains unsolved. To clarify the origin of the mobility we investigate the electronic states of the Li cations in the Li 3 N crystal with the first principles electronic structure analysis, focusing a correlation between the cations and the ionicities of the constituent atoms. We have found the existence of the covalent bonding between the Li atoms in the Li 3 N crystal in spite of the ionized states of the constituent atoms.

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.

Thymic Fatness and Approaches to Enhance Thymopoietic Fitness in Aging

PubMed Central

Dixit, Vishwa Deep

2010-01-01

Summary With advancing age, the thymus undergoes striking fibrotic and fatty changes that culminate in its transformation into adipose tissue. As the thymus involutes, reduction in thymocytes and thymic epithelial cells precede the emergence of mature lipid-laden adipocytes. Dogma dictates that adipocytes are ‘passive’ cells that occupy non-epithelial thymic space or ‘infiltrate’ the non cellular thymic niches. The provenance and purpose of ectopic thymic adipocytes during aging in an organ that is required for establishment and maintenance of T cell repertoire remains an unsolved puzzle. Nonetheless, tantalizing clues about elaborate reciprocal relationship between thymic fatness and thymopoietic fitness are emerging. Blocking or bypassing the route towards thymic adiposity may complement the approaches to rejuvenate thymopoiesis and immunity in elderly. PMID:20650623

Helicopter-V/STOL dynamic wind and turbulence design methodology

NASA Technical Reports Server (NTRS)

Bailey, J. Earl

1987-01-01

Aircraft and helicopter accidents due to severe dynamic wind and turbulence continue to present challenging design problems. The development of the current set of design analysis tools for a aircraft wind and turbulence design began in the 1940's and 1950's. The areas of helicopter dynamic wind and turbulence modeling and vehicle response to severe dynamic wind inputs (microburst type phenomena) during takeoff and landing remain as major unsolved design problems from a lack of both environmental data and computational methodology. The development of helicopter and V/STOL dynamic wind and turbulence response computation methology is reviewed, the current state of the design art in industry is outlined, and comments on design methodology are made which may serve to improve future flight vehicle design.

Observational Consequences of Coronal Heating Mechanisms

NASA Technical Reports Server (NTRS)

Winebarger, Amy R.; Cirtain, Jonathan C.; Golub, Leon; Kobayashi, Ken

2014-01-01

The coronal heating problem remains unsolved today, 80 years after its discovery, despite 50 years of suborbital and orbital coronal observatories. Tens of theoretical coronal heating mechanisms have been suggested, but only a few have been able to be ruled out. In this talk, we will explore the reasons for the slow progress and discuss the measurements that will be needed for potential breakthrough, including imaging the solar corona at small spatial scales, measuring the chromospheric magnetic fields, and detecting the presence of high temperature, low emission measure plasma. We will discuss three sounding rocket instruments developed to make these measurements: the High resolution Resolution Coronal Imager (Hi-C), the Chromospheric Lyman-Alpha Spectropolarimeter (CLASP), and the Marshall Grazing Incidence X-ray Spectrometer (MaGIXS).

New Instruments to Isolate the Coronal Heating Mechanism

NASA Technical Reports Server (NTRS)

Winebarger, Amy

2014-01-01

The coronal heating problem remains unsolved today, 80 years after its discovery, despite 50 years of suborbital and orbital coronal observatories. Tens of theoretical coronal heating mechanisms have been suggested, but only a few have been able to be ruled out. In this talk, we will explore the reasons for the slow progress and discuss the measurements that will be needed for potential breakthrough, including imaging the solar corona at small spatial scales, measuring the chromospheric magnetic fields, and detecting the presence of high temperature, low-emission measure plasma. We will discuss three sounding rocket instruments developed to make these measurements: the High-resolution Resolution Coronal Imager (Hi-C), the Chromospheric Lyman-Alpha Spectropolarimeter (CLASP), and the Marshall Grazing Incidence X-ray Spectrometer (MaGIXS).

The double copy: gravity from gluons

NASA Astrophysics Data System (ADS)

White, C. D.

2018-04-01

Three of the four fundamental forces in nature are described by so-called gauge theories, which include the effects of both relativity and quantum mechanics. Gravity, on the other hand, is described by General Relativity, and the lack of a well-behaved quantum theory - believed to be relevant at the centre of black holes, and at the Big Bang itself - remains a notorious unsolved problem. Recently a new correspondence, the double copy, has been discovered between scattering amplitudes (quantities related to the probability for particles to interact) in gravity, and their gauge theory counterparts. This has subsequently been extended to other quantities, providing gauge theory analogues of e.g. black holes. We here review current research on the double copy, and describe some possible applications.

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.

Unplugging the callose plug from sieve pores

PubMed Central

Xie, Bo

2011-01-01

The presence of callose in sieve plates has been known for a long time, but how this polysaccharide plug is synthesized has remained unsolved. Two independent laboratories have recently reported the identification of callose synthase 7 (CalS7), also known as glucan synthase-like 7 (GSL7), as the enzyme responsible for callose deposition in sieve plates. Mutant plants defective in this enzyme failed to synthesize callose in developing sieve plates during phloem formation and were unable to accumulate callose in sieve pores in response to stress treatments. The mutant plants developed less open pores per sieve plate and the pores were smaller in diameter. As a result, phloem conductivity was reduced significantly and the mutant plants were shorter and set fewer seeds. PMID:21386663

The evolutionary origin of bilaterian smooth and striated myocytes

PubMed Central

Brunet, Thibaut; Fischer, Antje HL; Steinmetz, Patrick RH; Lauri, Antonella; Bertucci, Paola; Arendt, Detlev

2016-01-01

The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed and nervous control. Our data suggest that both visceral smooth and somatic striated myocytes were present in the protostome-deuterostome ancestor and that smooth myocytes later co-opted the striated contractile module repeatedly – for example, in vertebrate heart evolution. During these smooth-to-striated myocyte conversions, the core regulatory complex of transcription factors conveying myocyte identity remained unchanged, reflecting a general principle in cell type evolution. DOI: http://dx.doi.org/10.7554/eLife.19607.001 PMID:27906129

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.

Unsolved Problems of Intracellular Noise

NASA Astrophysics Data System (ADS)

Paulsson, Johan

2003-05-01

Many molecules are present at so low numbers per cell that significant fluctuations arise spontaneously. Such `noise' can randomize developmental pathways, disrupt cell cycle control or force metabolites away from their optimal levels. It can also be exploited for non-genetic individuality or, surprisingly, for more reliable and deterministic control. However, in spite of the mechanistic and evolutionary significance of noise, both explicit modeling and implicit verbal reasoning in molecular biology are completely dominated by macroscopic kinetics. Here I discuss some particularly under-addressed issues of noise in genetic and metabolic networks: 1) relations between systematic macro- and mesoscopic approaches; 2) order and disorder in gene expression; 3) autorepression for checking fluctuations; 4) noise suppression by noise; 5) phase-transitions in metabolic systems; 6) effects of cell growth and division; and 7) mono- and bistable bimodal switches.

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.

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.

Beware! Uncle Sam has your DNA: legal fallout from its use and misuse in the U.S.

PubMed

Weiss, Marcia J

2004-01-01

Technology has provided state and federal governments with huge collections of DNA samples and identifying profiles stored in databanks. That information can be used to solve crimes by matching samples from convicted felons to unsolved crimes, and has aided law enforcement in investigating and convicting suspects, and exonerating innocent felons, even after lengthy incarceration. Rights surrounding the provision of DNA samples, however, remain unclear in light of the constitutional guarantee against "unreasonable searches and seizures" and privacy concerns. The courts have just begun to consider this issue, and have provided little guidance. It is unclear whether the laws governing protected health information are applicable to the instant situation, and if so, the degree to which they apply. DNA databanks are not uniformly regulated, and it is possible that DNA samples contained in them may be used for purposes unintended by donors of the samples. As people live their lives, they leave bits of their DNA behind. They cannot be assured that these tiny specimens will not be taken or used against their will or without their knowledge for activities such as profiling to measure tendencies such as thrill-seeking, aggressiveness, or crimes with threatening behavior. Existing racial or ethnic discrimination and profiling may also encompass genetic discrimination and profiling, creating societal class distinctions. This article will explore the constitutionality of collecting genetic materials, the ethics of such activities, and balance the social good in solving crime and deterrence against the individual's security, liberty, and privacy.

Kinetic description of rotating Tokamak plasmas with anisotropic temperatures in the collisionless regime

NASA Astrophysics Data System (ADS)

Cremaschini, Claudio; Tessarotto, Massimo

2011-11-01

A largely unsolved theoretical issue in controlled fusion research is the consistent kinetic treatment of slowly-time varying plasma states occurring in collisionless and magnetized axisymmetric plasmas. The phenomenology may include finite pressure anisotropies as well as strong toroidal and poloidal differential rotation, characteristic of Tokamak plasmas. Despite the fact that physical phenomena occurring in fusion plasmas depend fundamentally on the microscopic particle phase-space dynamics, their consistent kinetic treatment remains still essentially unchallenged to date. The goal of this paper is to address the problem within the framework of Vlasov-Maxwell description. The gyrokinetic treatment of charged particles dynamics is adopted for the construction of asymptotic solutions for the quasi-stationary species kinetic distribution functions. These are expressed in terms of the particle exact and adiabatic invariants. The theory relies on a perturbative approach, which permits to construct asymptotic analytical solutions of the Vlasov-Maxwell system. In this way, both diamagnetic and energy corrections are included consistently into the theory. In particular, by imposing suitable kinetic constraints, the existence of generalized bi-Maxwellian asymptotic kinetic equilibria is pointed out. The theory applies for toroidal rotation velocity of the order of the ion thermal speed. These solutions satisfy identically also the constraints imposed by the Maxwell equations, i.e., quasi-neutrality and Ampere's law. As a result, it is shown that, in the presence of nonuniform fluid and EM fields, these kinetic equilibria can sustain simultaneously toroidal differential rotation, quasi-stationary finite poloidal flows and temperature anisotropy.

Content-Adaptive Sketch Portrait Generation by Decompositional Representation Learning.

PubMed

Zhang, Dongyu; Lin, Liang; Chen, Tianshui; Wu, Xian; Tan, Wenwei; Izquierdo, Ebroul

2017-01-01

Sketch portrait generation benefits a wide range of applications such as digital entertainment and law enforcement. Although plenty of efforts have been dedicated to this task, several issues still remain unsolved for generating vivid and detail-preserving personal sketch portraits. For example, quite a few artifacts may exist in synthesizing hairpins and glasses, and textural details may be lost in the regions of hair or mustache. Moreover, the generalization ability of current systems is somewhat limited since they usually require elaborately collecting a dictionary of examples or carefully tuning features/components. In this paper, we present a novel representation learning framework that generates an end-to-end photo-sketch mapping through structure and texture decomposition. In the training stage, we first decompose the input face photo into different components according to their representational contents (i.e., structural and textural parts) by using a pre-trained convolutional neural network (CNN). Then, we utilize a branched fully CNN for learning structural and textural representations, respectively. In addition, we design a sorted matching mean square error metric to measure texture patterns in the loss function. In the stage of sketch rendering, our approach automatically generates structural and textural representations for the input photo and produces the final result via a probabilistic fusion scheme. Extensive experiments on several challenging benchmarks suggest that our approach outperforms example-based synthesis algorithms in terms of both perceptual and objective metrics. In addition, the proposed method also has better generalization ability across data set without additional training.

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.

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.

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.

[A new way of financing the French healthcare system?].

PubMed

Elbaum, Mireille

2010-01-01

Several changes occurred lately in the regulation of the French healthcare system: the public health insurance deficit has been reduced until 2008, the ratio of health expenditure as percentage of GDP has remained fairly stable, activity-based payments have been implemented in public and private hospitals, and the government tried to promote more coordination and better prescriptions among practitioners. These changes have nevertheless limited impacts, and do not concern the "heart" of economic regulation: the system of prices, fees and reimbursement remains unchanged, and health insurance deficits have been repeatedly funded by new specific taxes and decreases in reimbursement. The part of expenses left to complementary insurances and out-of-pocket spending is increasing for ambulatory care, and government policies claiming for more "responsibility" in the use of health care mainly apply to patients. As these problems remain unsolved, the French health system has to tackle major short and medium-term challenges: the consolidation of deficits linked or not to the economic crisis, the long-term trend of health care expenditures resulting from population ageing, and the necessity to improve the efficiency of the system in a way which does not increase inequities in health care access.

Needs assessment for business strategies of anesthesiology groups' practices.

PubMed

Scurlock, Corey; Dexter, Franklin; Reich, David L; Galati, Maria

2011-07-01

Progress has been made in understanding strategic decision making influencing anesthesia groups' operating room business practices. However, there has been little analysis of the remaining gaps in our knowledge. We performed a needs assessment to identify unsolved problems in anesthesia business strategy based on Porter's Five Forces Analysis. The methodology was a narrative literature review. We found little previous investigation for 2 of the 5 forces (threat of new entrants and bargaining power of suppliers), modest understanding for 1 force (threat of substitute products or services), and substantial understanding for 2 forces (bargaining power of customers and jockeying for position among current competitors). Additional research in strategic decisions influencing anesthesia groups should focus on the threat of new entrants, bargaining power of suppliers, and the threat of substitute products or services.

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.

Thymic fatness and approaches to enhance thymopoietic fitness in aging.

PubMed

Dixit, Vishwa Deep

2010-08-01

With advancing age, the thymus undergoes striking fibrotic and fatty changes that culminate in its transformation into adipose tissue. As the thymus involutes, reduction in thymocytes and thymic epithelial cells precede the emergence of mature lipid-laden adipocytes. Dogma dictates that adipocytes are 'passive' cells that occupy non-epithelial thymic space or 'infiltrate' the non-cellular thymic niches. The provenance and purpose of ectopic thymic adipocytes during aging in an organ that is required for establishment and maintenance of T cell repertoire remains an unsolved puzzle. Nonetheless, tantalizing clues about elaborate reciprocal relationship between thymic fatness and thymopoietic fitness are emerging. Blocking or bypassing the route toward thymic adiposity may complement the approaches to rejuvenate thymopoiesis and immunity in elderly. Copyright 2010 Elsevier Ltd. All rights reserved.

The Interplay of Opacities and Rotation in Promoting the Explosion of Core-Collapse Supernovae

NASA Astrophysics Data System (ADS)

Vartanyan, David; Burrows, Adam; Radice, David

2018-01-01

For over five decades, the mechanism of explosion in core-collapse supernovae has been a central unsolved problem in astrophysics, challenging both our computational capabilities and our understanding of relevant physics. Current simulations often produce explosions, but they are at times underenergetic. The neutrino mechanism, wherein a fraction of emitted neutrinos is absorbed in the mantle of the star to reignite the stalled shock, remains the dominant model for reviving explosions in massive stars undergoing core collapse. We present here a diverse suite of 2D axisymmetric simulations produced by FORNAX, a highly parallelizable multidimensional supernova simulation code. We explore the effects of various corrections, including the many-body correction, to neutrino-matter opacities and the possible role of rotation in promoting explosion amongst various core-collapse progenitors.

Asymptotic identity in min-plus algebra: a report on CPNS.

PubMed

Li, Ming; Zhao, Wei

2012-01-01

Network calculus is a theory initiated primarily in computer communication networks, especially in the aspect of real-time communications, where min-plus algebra plays a role. Cyber-physical networking systems (CPNSs) are recently developing fast and models in data flows as well as systems in CPNS are, accordingly, greatly desired. Though min-plus algebra may be a promising tool to linearize any node in CPNS as can be seen from its applications to the Internet computing, there are tough problems remaining unsolved in this regard. The identity in min-plus algebra is one problem we shall address. We shall point out the confusions about the conventional identity in the min-plus algebra and present an analytical expression of the asymptotic identity that may not cause confusions.

Asymptotic Identity in Min-Plus Algebra: A Report on CPNS

PubMed Central

Li, Ming; Zhao, Wei

2012-01-01

Network calculus is a theory initiated primarily in computer communication networks, especially in the aspect of real-time communications, where min-plus algebra plays a role. Cyber-physical networking systems (CPNSs) are recently developing fast and models in data flows as well as systems in CPNS are, accordingly, greatly desired. Though min-plus algebra may be a promising tool to linearize any node in CPNS as can be seen from its applications to the Internet computing, there are tough problems remaining unsolved in this regard. The identity in min-plus algebra is one problem we shall address. We shall point out the confusions about the conventional identity in the min-plus algebra and present an analytical expression of the asymptotic identity that may not cause confusions. PMID:21822446

Direction-dependent arm kinematics reveal optimal integration of gravity cues.

PubMed

Gaveau, Jeremie; Berret, Bastien; Angelaki, Dora E; Papaxanthis, Charalambos

2016-11-02

The brain has evolved an internal model of gravity to cope with life in the Earth's gravitational environment. How this internal model benefits the implementation of skilled movement has remained unsolved. One prevailing theory has assumed that this internal model is used to compensate for gravity's mechanical effects on the body, such as to maintain invariant motor trajectories. Alternatively, gravity force could be used purposely and efficiently for the planning and execution of voluntary movements, thereby resulting in direction-depending kinematics. Here we experimentally interrogate these two hypotheses by measuring arm kinematics while varying movement direction in normal and zero-G gravity conditions. By comparing experimental results with model predictions, we show that the brain uses the internal model to implement control policies that take advantage of gravity to minimize movement effort.

i3Drefine Software for Protein 3D Structure Refinement and Its Assessment in CASP10

PubMed Central

Bhattacharya, Debswapna; Cheng, Jianlin

2013-01-01

Protein structure refinement refers to the process of improving the qualities of protein structures during structure modeling processes to bring them closer to their native states. Structure refinement has been drawing increasing attention in the community-wide Critical Assessment of techniques for Protein Structure prediction (CASP) experiments since its addition in 8th CASP experiment. During the 9th and recently concluded 10th CASP experiments, a consistent growth in number of refinement targets and participating groups has been witnessed. Yet, protein structure refinement still remains a largely unsolved problem with majority of participating groups in CASP refinement category failed to consistently improve the quality of structures issued for refinement. In order to alleviate this need, we developed a completely automated and computationally efficient protein 3D structure refinement method, i3Drefine, based on an iterative and highly convergent energy minimization algorithm with a powerful all-atom composite physics and knowledge-based force fields and hydrogen bonding (HB) network optimization technique. In the recent community-wide blind experiment, CASP10, i3Drefine (as ‘MULTICOM-CONSTRUCT’) was ranked as the best method in the server section as per the official assessment of CASP10 experiment. Here we provide the community with free access to i3Drefine software and systematically analyse the performance of i3Drefine in strict blind mode on the refinement targets issued in CASP10 refinement category and compare with other state-of-the-art refinement methods participating in CASP10. Our analysis demonstrates that i3Drefine is only fully-automated server participating in CASP10 exhibiting consistent improvement over the initial structures in both global and local structural quality metrics. Executable version of i3Drefine is freely available at http://protein.rnet.missouri.edu/i3drefine/. PMID:23894517

NI-60RECURRENT PATTERNS OF BEVACIZUMAB MONOTHERAPY FOR RECURRENT PRIMARY GLIOBLASTOMA AND PERSPECTIVES ON BEVACIZUMAB-BASED THERAPIES

PubMed Central

Nagane, Motoo; Kobayashi, Keiichi; Saito, Kuniaki; Shiokawa, Yoshiaki

2014-01-01

BACKGROUND. Prognosis of patients with recurrent glioblastoma (GBM) remains dismal, their median overall survival (mOS) ranging from 7 to 10 months. Currently, bevacizumab (BEV), a monoclonal antibody against VEGF, has been widely used since it prolonged progression-free survival (PFS) accompanied with symptom relief in BEV trials. However, improvement of OS seems modest at most, and issues regarding short survival after BEV failure, invasive relapse, and difficulty in determining true progression remain unsolved. Here we examined the patterns of radiological BEV failure in relationship with survival of several post-treatment periods. METHODS. Twenty-five patients with primary GBM who were treated with BEV monotherapy at recurrence in Kyorin University hospital since August 2009 were included in this study. Mean age was 53 yo, 13 males/12 females, median KPS was 60 (30-100), and mOS from the initial surgery was 23.2 months. MRI patterns at BEV progression were determined using modified classification by Nowosielsky et al. (Neurology 2014) as follows: 1) T2-diffuse, 2) cT1-flare up, 3) Primary non-responders, 4) T2-circumscribed, and 5) Remote metastasis. RESULTS. mPFS and mOS of BEV monotherapy were 3.4 and 7.6 months, respectively, and post-BEV mOS was 4.7 months. Frequency and BEV-PFS/post-BEV OS were 1) 20%, 3.8/0.8 months; 2) 40%, 3.4/7.1 months, 3) 24%, 0.9/3.3 months, 4) 8%, 3.7/3.9 months, 5) 8%, 2.0/4.2 months. The cT1-flare up recurrent pattern was found most frequently with relatively better survivals, whereas the T2-diffuse recurrence included fatal brain stem invasion in two cases, resulting in poorer prognosis. CONCLUSIONS. BEV monotherapy showed limited survival benefit and the clinical course after BEV failure may differ by patterns of relapse. Although RANO criteria have been a standard method to determine progression, measurement of T2/FLAIR hyperintensity remains critically controversial. Efforts to improve BEV-based therapy for recurrent GBM including longitudinal and combined chemotherapy will be also discussed.

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.

On Quaternary glaciations, observations and theories

NASA Astrophysics Data System (ADS)

Paillard, D.

2015-07-01

In a recent paper, Paillard (2015) presents a rapid overview of both major theoretical and empirical studies of Pleistocene glaciations. In particular, it is explained how, over the last 150 years, astronomical theories were confronted to observational constraints and why the "100-kyr problem" is still the major unsolved issue of Quaternary ice ages. This paper also discusses the main alternative theory, which involves changes in atmospheric carbon dioxide concentration. It is then argued that a synthesis of both theories would better account for empirical evidences, as well as for our current knowledge of climate physics. Indeed, if there is no doubt that ice ages are "paced" by the astronomy as evidenced in Hays et al. (1976), the cause of terminations, and therefore the dynamics of the 100-kyr cycles, appears to be closely linked to Southern Ocean climate and atmospheric pCO2.

Management of immune thrombocytopenia: Korean experts recommendation in 2017.

PubMed

Jang, Jun Ho; Kim, Ji Yoon; Mun, Yeung-Chul; Bang, Soo-Mee; Lim, Yeon Jung; Shin, Dong-Yeop; Choi, Young Bae; Yhim, Ho-Young; Lee, Jong Wook; Kook, Hoon

2017-12-01

Management options for patients with immune thrombocytopenia (ITP) have evolved substantially over the past decades. The American Society of Hematology published a treatment guideline for clinicians referring to the management of ITP in 2011. This evidence-based practice guideline for ITP enables the appropriate treatment of a larger proportion of patients and the maintenance of normal platelet counts. Korean authority operates a unified mandatory national health insurance system. Even though we have a uniform standard guideline enforced by insurance reimbursement, there are several unsolved issues in real practice in ITP treatment. To optimize the management of Korean ITP patients, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and the Korean data on the clinical practices of ITP therapy. Here, we report a Korean expert recommendation guide for the management of ITP.

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.

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.

A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

PubMed Central

Winkler, T.; Sass, F. A.; Schmidt-Bleek, K.

2018-01-01

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Cardiovascular Disease Susceptibility and Resistance in Circumpolar Inuit Populations.

PubMed

Tvermosegaard, Maria; Dahl-Petersen, Inger K; Nielsen, Nina Odgaard; Bjerregaard, Peter; Jørgensen, Marit Eika

2015-09-01

Cardiovascular disease (CVD) is a major public health issue in indigenous populations in the Arctic. These diseases have emerged concomitantly with profound social changes over the past 60 years. The aim of this study was to summarize the literature on CVD risk among Arctic Inuit. Literature on prevalence, incidence, and time trends for CVD and its risk factors in Arctic Inuit populations was reviewed. Most evidence supports a similar incidence of coronary heart disease and a higher incidence of cerebrovascular disease among Arctic Inuit than seen in western populations. Factors that may increase CVD risk include aging of the population, genetic susceptibility, and a rapid increase in obesity, diabetes, and hypertension in parallel with decreasing physical activity and deterioration of the lipid profile. In contrast, and of great importance, there has been a decrease in smoking and alcohol intake (at least documented in Greenland), and contaminant levels are declining. Although there have been marked socioeconomic and dietary changes, it remains unsolved and to some extent controversial how this may have influenced cardiovascular risk among Arctic Inuit. The increase in life expectancy, in combination with improved prognosis for patients with manifest CVD, will inevitably lead to a large increase in absolute numbers of individuals affected by CVD in Arctic Inuit populations, exacerbated by the rise in most CVD risk factors over the past decades. For preventive purposes and for health care planning, it is crucial to carefully monitor disease incidence and trends in risk factors in these vulnerable Arctic populations. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Redish, Edward F.; Kuo, Eric

2015-07-01

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 suggest that a fundamental issue has received insufficient exploration: the fact that in science, we don't just use math, we make meaning with it in a different way than mathematicians do. In this reflective essay, we explore math as a language and consider the language of math in physics through the lens of cognitive linguistics. We begin by offering a number of examples that show how the use of math in physics differs from the use of math as typically found in math classes. We then explore basic concepts in cognitive semantics to show how humans make meaning with language in general. The critical elements are the roles of embodied cognition and interpretation in context. Then, we show how a theoretical framework commonly used in physics education research, resources, is coherent with and extends the ideas of cognitive semantics by connecting embodiment to phenomenological primitives and contextual interpretation to the dynamics of meaning-making with conceptual resources, epistemological resources, and affect. We present these ideas with illustrative case studies of students working on physics problems with math and demonstrate the dynamical nature of student reasoning with math in physics. We conclude with some thoughts about the implications for instruction.

The generation of plate tectonics from mantle convection

NASA Astrophysics Data System (ADS)

Bercovici, David

2003-01-01

In the last decade, significant progress has been made toward understanding how plate tectonics is generated from mantle dynamics. A primary goal of plate-generation studies has been the development of models that allow the top cold thermal boundary layer of mantle convection, i.e. the lithosphere, to develop broad and strong plate-like segments separated by narrow, weak and rapidly deforming boundaries; ideally, such models also permit significant strike-slip (toroidal) motion, passive ridges (i.e. pulled rather than pried apart), and self-consistent initiation of subduction. A major outcome of work so far is that nearly all aspects of plate generation require lithospheric rheologies and shear-localizing feedback mechanisms that are considerably more exotic than rheologies typically used in simple fluid-dynamical models of mantle flow. The search for plate-generating behavior has taken us through investigations of the effects of shear weakening ('stick-slip') and viscoplastic rheologies, of melting at ridges and low-viscosity asthenospheres, and of grain-size dependent rheologies and damage mechanics. Many such mechanisms, either by themselves or in combination, have led to self-consistent fluid-mechanical models of mantle flow that are remarkably plate-like, which is in itself a major accomplishment. However, many other important problems remain unsolved, such as subduction intiation and asymmetry, temporal evolution of plate geometry, rapid changes in plate motion, and the Archaean initiation of the plate-tectonic mode of convection. This paper presents a brief review of progress made in the plate-generation problem over the last decade, and discusses unresolved issues and future directions of research in this important area.

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

CT Perfusion of the Liver: Principles and Applications in Oncology

PubMed Central

Kim, Se Hyung; Kamaya, Aya

2014-01-01

With the introduction of molecularly targeted chemotherapeutics, there is an increasing need for defining new response criteria for therapeutic success because use of morphologic imaging alone may not fully assess tumor response. Computed tomographic (CT) perfusion imaging of the liver provides functional information about the microcirculation of normal parenchyma and focal liver lesions and is a promising technique for assessing the efficacy of various anticancer treatments. CT perfusion also shows promising results for diagnosing primary or metastatic tumors, for predicting early response to anticancer treatments, and for monitoring tumor recurrence after therapy. Many of the limitations of early CT perfusion studies performed in the liver, such as limited coverage, motion artifacts, and high radiation dose of CT, are being addressed by recent technical advances. These include a wide area detector with or without volumetric spiral or shuttle modes, motion correction algorithms, and new CT reconstruction technologies such as iterative algorithms. Although several issues related to perfusion imaging—such as paucity of large multicenter trials, limited accessibility of perfusion software, and lack of standardization in methods—remain unsolved, CT perfusion has now reached technical maturity, allowing for its use in assessing tumor vascularity in larger-scale prospective clinical trials. In this review, basic principles, current acquisition protocols, and pharmacokinetic models used for CT perfusion imaging of the liver are described. Various oncologic applications of CT perfusion of the liver are discussed and current challenges, as well as possible solutions, for CT perfusion are presented. © RSNA, 2014 Online supplemental material is available for this article. PMID:25058132

New analytical model for the ozone electronic ground state potential surface and accurate ab initio vibrational predictions at high energy range.

PubMed

Tyuterev, Vladimir G; Kochanov, Roman V; Tashkun, Sergey A; Holka, Filip; Szalay, Péter G

2013-10-07

An accurate description of the complicated shape of the potential energy surface (PES) and that of the highly excited vibration states is of crucial importance for various unsolved issues in the spectroscopy and dynamics of ozone and remains a challenge for the theory. In this work a new analytical representation is proposed for the PES of the ground electronic state of the ozone molecule in the range covering the main potential well and the transition state towards the dissociation. This model accounts for particular features specific to the ozone PES for large variations of nuclear displacements along the minimum energy path. The impact of the shape of the PES near the transition state (existence of the "reef structure") on vibration energy levels was studied for the first time. The major purpose of this work was to provide accurate theoretical predictions for ozone vibrational band centres at the energy range near the dissociation threshold, which would be helpful for understanding the very complicated high-resolution spectra and its analyses currently in progress. Extended ab initio electronic structure calculations were carried out enabling the determination of the parameters of a minimum energy path PES model resulting in a new set of theoretical vibrational levels of ozone. A comparison with recent high-resolution spectroscopic data on the vibrational levels gives the root-mean-square deviations below 1 cm(-1) for ozone band centres up to 90% of the dissociation energy. New ab initio vibrational predictions represent a significant improvement with respect to all previously available calculations.

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

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.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes.

PubMed

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms.

GATA4 Variants in Individuals With a 46,XY Disorder of Sex Development (DSD) May or May Not Be Associated With Cardiac Defects Depending on Second Hits in Other DSD Genes

PubMed Central

Martinez de LaPiscina, Idoia; de Mingo, Carmen; Riedl, Stefan; Rodriguez, Amaia; Pandey, Amit V.; Fernández-Cancio, Mónica; Camats, Nuria; Sinclair, Andrew; Castaño, Luis; Audi, Laura; Flück, Christa E.

2018-01-01

Disorders of sex development (DSD) consist of a wide range of conditions involving numerous genes. Nevertheless, about half of 46,XY individuals remain genetically unsolved. GATA4 gene variants, mainly related to congenital heart defects (CHD), have also been recently associated with 46,XY DSD. In this study, we characterized three individuals presenting with 46,XY DSD with or without CHD and GATA4 variants in order to understand the phenotypical variability. We studied one patient presenting CHD and 46,XY gonadal dysgenesis, and two patients with a history of genetically unsolved 46,XY DSD, also known as male primary hypogonadism. Mutation analysis was carried out by candidate gene approach or targeted gene panel sequencing. Functional activity of GATA4 variants was tested in vitro on the CYP17 promoter involved in sex development using JEG3 cells. We found two novel and one previously described GATA4 variants located in the N-terminal zinc finger domain of the protein. Cys238Arg variant lost transcriptional activity on the CYP17 promoter reporter, while Trp228Cys and Pro226Leu behaved similar to wild type. These results were in line with bioinformatics simulation studies. Additional DSD variations, in the LRP4 and LHCGR genes, respectively, were identified in the two 46,XY individuals without CHD. Overall, our study shows that human GATA4 mutations identified in patients with 46,XY DSD may or may not be associated with CHD. Possible explanations for phenotypical variability may comprise incomplete penetrance, variable sensitivity of partner genes, and oligogenic mechanisms. PMID:29670578

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

Human mobility prediction from region functions with taxi trajectories.

PubMed

Wang, Minjie; Yang, Su; Sun, Yi; Gao, Jun

2017-01-01

People in cities nowadays suffer from increasingly severe traffic jams due to less awareness of how collective human mobility is affected by urban planning. Besides, understanding how region functions shape human mobility is critical for business planning but remains unsolved so far. This study aims to discover the association between region functions and resulting human mobility. We establish a linear regression model to predict the traffic flows of Beijing based on the input referred to as bag of POIs. By solving the predictor in the sense of sparse representation, we find that the average prediction precision is over 74% and each type of POI contributes differently in the predictor, which accounts for what factors and how such region functions attract people visiting. Based on these findings, predictive human mobility could be taken into account when planning new regions and region functions.

A rapid method of toilet training the institutionalized retarded1

PubMed Central

Azrin, N. H.; Foxx, R. M.

1971-01-01

Incontinence is a major unsolved problem in the institutional care of the profoundly retarded. A reinforcement and social analysis of incontinence was used to develop a procedure that would rapidly toilet train retardates and motivate them to remain continent during the day in their ward setting. Nine profoundly retarded adults were given intensive training (median of four days per patient), the distinctive features of which were artificially increasing the frequency of urinations, positive reinforcement of correct toileting but a delay for “accidents”, use of new automatic apparatus for signalling elimination, shaping of independent toileting, cleanliness training, and staff reinforcement procedures. Incontinence was reduced immediately by about 90% and eventually decreased to near-zero. These results indicate the present procedure is an effective, rapid, enduring, and administratively feasible solution to the problem of incontinence of the institutionalized retarded. PMID:16795291

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.

The radiocarbon budget for Mono Lake: an unsolved mystery

USGS Publications Warehouse

Broecker, W.S.; Wanninkhof, R.; Mathieu, G.; Peng, T.-H.; Stine, S.; Robinson, S.; Herczeg, A.; Stuiver, M.

1988-01-01

Since 1957 the 14C C ratio of the dissolved inorganic carbon in Mono Lake has risen by about 60???. The magnitude of this increase is about four times larger than that expected from the invasion of bomb-produced 14C from the atmosphere. We have eliminated the following explanations: (1) measurement error, (2) an unusually high physical exchange rate for non-reactive gases, (3) inorganic enhancement of the CO2 exchange rate, and (4) biological enhancement of the CO2 exchange rate. Clandestine disposal of waste radiocarbon remains a dark-horse explanation. In the course of our investigations we have uncovered evidence for at least one episodic input of radiocarbon-free carbon to the lake over the last 1000 years. We speculate that this injection was related to a hydrothermal event resulting from sublacustrine volcanic activity. ?? 1988.

Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite

PubMed Central

Seebeck, Thomas; Sterk, Geert Jan; Ke, Hengming

2011-01-01

Protozoan infections remain a major unsolved medical problem in many parts of our world. A major obstacle to their treatment is the blatant lack of medication that is affordable, effective, safe and easy to administer. For some of these diseases, including human sleeping sickness, very few compounds are available, many of them old and all of them fraught with toxic side effects. We explore a new concept for developing new-generation antiprotozoan drugs that are based on phosphodiesterase (PDE) inhibitors. Such inhibitors are already used extensively in human pharmacology. Given the high degree of structural similarity between the human and the protozoan PDEs, the vast expertise available in the human field can now be applied to developing disease-specific PDE inhibitors as new antiprotozoan drugs. PMID:21859303

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.

Unsolved matters in leprosy: a descriptive review and call for further research.

PubMed

Franco-Paredes, Carlos; Rodriguez-Morales, Alfonso J

2016-05-21

Leprosy, a chronic mycobacterial infection caused by Mycobacterium leprae, is an infectious disease that has ravaged human societies throughout millennia. This ancestral pathogen causes disfiguring cutaneous lesions, peripheral nerve injury, ostearticular deformity, limb loss and dysfunction, blindness and stigma. Despite ongoing efforts in interrupting leprosy transmission, large numbers of new cases are persistently identified in many endemic areas. Moreover, at the time of diagnosis, most newly identified cases have considerable neurologic disability. Many challenges remain in our understanding of the epidemiology of leprosy including: (a) the precise mode and route of transmission; (b) the socioeconomic, environmental, and behavioral factors that promote its transmission; and (c) strategies to achieve early diagnosis and prevent neurologic impairment to reduce the large burden of disability among newly identified cases; and among those who endure long-term disability in spite of completing multidrug therapy.

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

Observer-based H∞ resilient control for a class of switched LPV systems and its application

NASA Astrophysics Data System (ADS)

Yang, Dong; Zhao, Jun

2016-11-01

This paper deals with the issue of observer-based H∞ resilient control for a class of switched linear parameter-varying (LPV) systems by utilising a multiple parameter-dependent Lyapunov functions method. First, attention is focused upon the design of a resilient observer, an observer-based resilient controller and a parameter and estimate state-dependent switching signal, which can stabilise and achieve the disturbance attenuation for the given systems. Then, a solvability condition of the H∞ resilient control problem is given in terms of matrix inequality for the switched LPV systems. This condition allows the H∞ resilient control problem for each individual subsystem to be unsolvable. The observer, controller, and switching signal are explicitly computed by solving linear matrix inequalities (LMIs). Finally, the effectiveness of the proposed control scheme is illustrated by its application to a turbofan engine, which can hardly be handled by the existing approaches.

Hidden Order and Dimensional Crossover of the Charge Density Waves in TiSe 2

DOE PAGES

Chen, P.; Chan, Y. -H.; Fang, X. -Y.; ...

2016-11-29

Charge density wave (CDW) formation, a key physics issue for materials, arises from interactions among electrons and phonons that can also lead to superconductivity and other competing or entangled phases. The prototypical system TiSe 2, with a particularly simple (2 × 2 × 2) transition and no Kohn anomalies caused by electron-phonon coupling, is a fascinating but unsolved case after decades of research. Our angle-resolved photoemission measurements of the band structure as a function of temperature, aided by first-principles calculations, reveal a hitherto undetected but crucial feature: a (2 × 2) electronic order in each layer sets in at ~232more » K before the widely recognized three-dimensional structural order at ~205 K. The dimensional crossover, likely a generic feature of such layered materials, involves renormalization of different band gaps in two stages.« less

Secure Publish-Subscribe Protocols for Heterogeneous Medical Wireless Body Area Networks

PubMed Central

Picazo-Sanchez, Pablo; Tapiador, Juan E.; Peris-Lopez, Pedro; Suarez-Tangil, Guillermo

2014-01-01

Security and privacy issues in medical wireless body area networks (WBANs) constitute a major unsolved concern because of the challenges posed by the scarcity of resources in WBAN devices and the usability restrictions imposed by the healthcare domain. In this paper, we describe a WBAN architecture based on the well-known publish-subscribe paradigm. We present two protocols for publishing data and sending commands to a sensor that guarantee confidentiality and fine-grained access control. Both protocols are based on a recently proposed ciphertext policy attribute-based encryption (CP-ABE) scheme that is lightweight enough to be embedded into wearable sensors. We show how sensors can implement lattice-based access control (LBAC) policies using this scheme, which are highly appropriate for the eHealth domain. We report experimental results with a prototype implementation demonstrating the suitability of our proposed solution. PMID:25460814

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

2013-06-01

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

Poly-paper: a sustainable material for packaging, based on recycled paper and recyclable with paper.

PubMed

Del Curto, Barbara; Barelli, Nadia; Profaizer, Mauro; Farè, Silvia; Tanzi, Maria Cristina; Cigada, Alberto; Ognibene, Giulia; Recca, Giuseppe; Cicala, Gianluca

2016-11-02

Until now, environmental sustainability issues are almost entirely unsolved for packaging materials. With the final aim of finding materials with a single recycling channel, cellulose fiber/poly(vinyl)alcohol composites were investigated. After extrusion and injection molding, samples of composite with different cellulose fiber content (30%, 50% and 70% w/w) were tested. Tensile mechanical tests exhibited an improvement in composite stiffness when the reinforcement content was increased together with a decrease in composite elongation. Solubility tests performed at room temperature and 45°C showed different behavior depending on the water-resistant film applied on the composite (50% cellulose fiber content). In particular, the uncoated composite showed complete solubility after 2 hours, whereas at the same time point, no solubility occurred when a non-water-soluble varnish was used. The proposed composites, named Poly-paper, appear to warrant further investigation as highly sustainable packaging.

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.

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.

Synthesizing new types of ultrathin 2D metal oxide nanosheets via half-successive ion layer adsorption and reaction

NASA Astrophysics Data System (ADS)

Gao, Linjie; Li, Yaguang; Xiao, Mu; Wang, Shufang; Fu, Guangsheng; Wang, Lianzhou

2017-06-01

Two-dimensional (2D) metal oxide nanosheets have demonstrated their great potential in a broad range of applications. The existing synthesis strategies are mainly preparing 2D nanosheets from layered and specific transition metal oxides. How to prepare the other types of metal oxides as ultrathin 2D nanosheets remains unsolved, especially for metal oxides containing alkali, alkaline earth metal, and multiple metal elements. Herein, we developed a half-successive ion layer adsorption and reaction (SILAR) method, which could synthesize those types of metal oxides as ultrathin 2D nanosheets. The synthesized 2D metal oxides nanosheets are within 1 nm level thickness and 500 m2 · g-1 level surface area. This method allows us to develop many new types of ultrathin 2D metal oxides nanosheets that have never been prepared before.

Optical Imaging and Control of Neurons

NASA Astrophysics Data System (ADS)

Song, Yoon-Kyu

Although remarkable progress has been made in our understanding of the function, organization, and development of the brain by various approaches of modern science and technology, how the brain performs its marvelous function remains unsolved or incompletely understood. This is mainly attributed to the insufficient capability of currently available research tools and conceptual frameworks to deal with enormous complexity of the brain. Hence, in the last couple of decades, a significant effort has been made to crack the complexity of brain by utilizing research tools from diverse scientific areas. The research tools include the optical neurotechnology which incorporates the exquisite characteristics of optics, such as multi-parallel access and non-invasiveness, in sensing and stimulating the excitable membrane of a neuron, the basic functional unit of the brain. This chapter is aimed to serve as a short introduction to the optical neurotechnology for those who wish to use optical techniques as one of their brain research tools.

The nature of primary consciousness. A new synthesis.

PubMed

Feinberg, Todd E; Mallatt, Jon

2016-07-01

While the philosophical puzzles about "life" that once confounded biology have all been solved by science, much of the "mystery of consciousness" remains unsolved due to multiple "explanatory gaps" between the brain and conscious experience. One reason for this impasse is that diverse brain architectures both within and across species can create consciousness, thus making any single neurobiological feature insufficient to explain it. We propose instead that an array of general biological features that are found in all living things, combined with a suite of special neurobiological features unique to animals with consciousness, evolved to create subjective experience. Combining philosophical, neurobiological and evolutionary approaches to consciousness, we review our theory of neurobiological naturalism that we argue closes the "explanatory gaps" between the brain and subjective experience and naturalizes the "experiential gaps" between subjectivity and third-person observation of the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Human mobility prediction from region functions with taxi trajectories

PubMed Central

Wang, Minjie; Sun, Yi; Gao, Jun

2017-01-01

People in cities nowadays suffer from increasingly severe traffic jams due to less awareness of how collective human mobility is affected by urban planning. Besides, understanding how region functions shape human mobility is critical for business planning but remains unsolved so far. This study aims to discover the association between region functions and resulting human mobility. We establish a linear regression model to predict the traffic flows of Beijing based on the input referred to as bag of POIs. By solving the predictor in the sense of sparse representation, we find that the average prediction precision is over 74% and each type of POI contributes differently in the predictor, which accounts for what factors and how such region functions attract people visiting. Based on these findings, predictive human mobility could be taken into account when planning new regions and region functions. PMID:29190708

Direction-dependent arm kinematics reveal optimal integration of gravity cues

PubMed Central

Gaveau, Jeremie; Berret, Bastien; Angelaki, Dora E; Papaxanthis, Charalambos

2016-01-01

The brain has evolved an internal model of gravity to cope with life in the Earth's gravitational environment. How this internal model benefits the implementation of skilled movement has remained unsolved. One prevailing theory has assumed that this internal model is used to compensate for gravity's mechanical effects on the body, such as to maintain invariant motor trajectories. Alternatively, gravity force could be used purposely and efficiently for the planning and execution of voluntary movements, thereby resulting in direction-depending kinematics. Here we experimentally interrogate these two hypotheses by measuring arm kinematics while varying movement direction in normal and zero-G gravity conditions. By comparing experimental results with model predictions, we show that the brain uses the internal model to implement control policies that take advantage of gravity to minimize movement effort. DOI: http://dx.doi.org/10.7554/eLife.16394.001 PMID:27805566

Space-time wiring specificity supports direction selectivity in the retina

PubMed Central

Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F.; Campos, Michael; Denk, Winfried; Seung, H. Sebastian

2014-01-01

How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, we reconstructed Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of “citizen neuroscientists.” Based on quantitative analyses of contact area and branch depth in the retina, we found evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, while another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such “space-time wiring specificity” could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma. PMID:24805243

Space-time wiring specificity supports direction selectivity in the retina.

PubMed

Kim, Jinseop S; Greene, Matthew J; Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F; Campos, Michael; Denk, Winfried; Seung, H Sebastian

2014-05-15

How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.

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.

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.

Vapor explosions and the blast at Mt. St. Helens

NASA Astrophysics Data System (ADS)

Sturtevant, B.; Kieffer, S. W.

In the study of geophysical phenomena, there are many problems which are of interest to fluid dynamicists, and some of these problems are suited for an investigation with the methods of shock-tube technology. The present paper is concerned with the physical basis of explosive volcanoes and some laboratory-scale experiments which have been initiated to examine the fundamental flow processes which control the eruptions. The main obejctive of the paper is to point out a few of the many problems which remain unsolved in this field. For the proper evaluation of results obtained with jets of model fluids, the behavior of gas jets has to be documented. A brief description is, therefore, provided of observations of transient jets of gases of differing density obtained in experiments using shock-tube techniques. Attention is given to a steady-flow model of the lateral blast related to the eruption of Mt. St. Helens on May 18, 1980.

Identification of structural motifs as tunneling two-level systems in amorphous alumina at low temperatures

NASA Astrophysics Data System (ADS)

Paz, Alejandro Pérez; Lebedeva, Irina V.; Tokatly, Ilya V.; Rubio, Angel

2014-12-01

One of the most accepted models that describe the anomalous thermal behavior of amorphous materials at temperatures below 1 K relies on the quantum mechanical tunneling of atoms between two nearly equivalent potential energy wells forming a two-level system (TLS). Indirect evidence for TLSs is widely available. However, the atomistic structure of these TLSs remains an unsolved topic in the physics of amorphous materials. Here, using classical molecular dynamics, we found several hitherto unknown bistable structural motifs that may be key to understanding the anomalous thermal properties of amorphous alumina at low temperatures. We show through free energy profiles that the complex potential energy surface can be reduced to canonical TLSs. The tunnel splitting predicted from instanton theory, the number density, dipole moment, and coupling to external strain of the discovered motifs are consistent with experiments.

Re-evaluation of ``;The Propagation of Radiation in the Spherical Wave Form''

NASA Astrophysics Data System (ADS)

Joshi, Narahari V.

2012-03-01

It is well accepted that radiation propagates in the free space (without obstacles) in a spherical wave form as well as in a plane wave form. Almost all observed phenomena such as interference, diffraction etc are explained satisfactorily on the basis of spherical wave propagation with a slight alteration in the mathematical treatment. However, one of the fundamental aspects, namely the intensity of the radiation as a function of the distance still remains an unsolved problem as the intensity varies with 1/(distance)2 when one represents the propagation in terms of spherical waves while it is independent of the distance if it is considered as a plane wave. In order to understand this puzzle, the propagation by a spherical wave form is reexamined. It is found that conversion of fields into particle (vice versa), via the field quantization process, explains several dilemma related with the radiation propagation.

The development of supported employment services for people with mental illness: local experience in Hong Kong.

PubMed

Chiu, Frank P.F.

2000-01-01

Before the 1960s in Hong Kong, specialized vocational services for people with mental illness were very limited, and sheltered workshop seemed to be the only option for their future vocational placement at that time. As discussed in the literature, there are still many shortcomings of the sheltered workshop model, that brings us to the emergence of another community-based vocational service: Supported Employment. Unlike traditional vocational services, the concept of supported employment emphasizes the placing of the clients into integrated work environments and then providing on-going support and work-related skills training in the job post. Though supported employment services help many clients to sustain a job in the competitive market, many service barriers and problems still remain unsolved. These service barriers and problems will be discussed in this article, and suggestions will be made.

Synergistic Impacts of Electrolyte Adsorption on the Thermoelectric Properties of Single-Walled Carbon Nanotubes.

PubMed

Nakano, Motohiro; Nakashima, Takuya; Kawai, Tsuyoshi; Nonoguchi, Yoshiyuki

2017-08-01

Single-walled carbon nanotubes are promising candidates for light-weight and flexible energy materials. Recently, the thermoelectric properties of single-walled carbon nanotubes have been dramatically improved by ionic liquid addition; however, controlling factors remain unsolved. Here the thermoelectric properties of single-walled carbon nanotubes enhanced by electrolytes are investigated. Complementary characterization with absorption, Raman, and X-ray photoelectron spectroscopy reveals that shallow hole doping plays a partial role in the enhanced electrical conductivity. The molecular factors controlling the thermoelectric properties of carbon nanotubes are systematically investigated in terms of the ionic functionalities of ionic liquids. It is revealed that appropriate ionic liquids show a synergistic enhancement in conductivity and the Seebeck coefficient. The discovery of significantly precise doping enables the generation of thermoelectric power factor exceeding 460 µW m - 1 K -2 . © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Noroviruses: a challenge for military forces.

PubMed

Delacour, H; Dubrous, P; Koeck, J L

2010-12-01

For military forces, the control of infectious acute gastroenteritis constitutes an old, constant and unsolved concern. Recent epidemiological studies suggest that the common bacterial causes are being overtaken by viruses. Norviruses are the most alarming group and norovirus outbreaks in military forces are regularly reported. Illness is generally mild and characterised by acute vomiting and diarrhoea, which lasts for a few days on average, but may be severe and potentially life-threatening in subjects who are already dehydrated due to daily activity. Moreover, outbreaks may diminish operational effectiveness. Prevention of norovirus infection currently relies on strict application of personal and collective hygiene rules including isolation of the cases, to the greatest possible extent. Although noroviruses are frequently mentioned as the cause of gastroenteritis outbreaks in troops deployed overseas, laboratory diagnosis is rarely done. So their real burden in military forces remains unclear and further epidemiological studies are required to determine the full impact of norovirus gastroenteritis on troops.

Ubiquitous information for ubiquitous computing: expressing clinical data sets with openEHR archetypes.

PubMed

Garde, Sebastian; Hovenga, Evelyn; Buck, Jasmin; Knaup, Petra

2006-01-01

Ubiquitous computing requires ubiquitous access to information and knowledge. With the release of openEHR Version 1.0 there is a common model available to solve some of the problems related to accessing information and knowledge by improving semantic interoperability between clinical systems. Considerable work has been undertaken by various bodies to standardise Clinical Data Sets. Notwithstanding their value, several problems remain unsolved with Clinical Data Sets without the use of a common model underpinning them. This paper outlines these problems like incompatible basic data types and overlapping and incompatible definitions of clinical content. A solution to this based on openEHR archetypes is motivated and an approach to transform existing Clinical Data Sets into archetypes is presented. To avoid significant overlaps and unnecessary effort during archetype development, archetype development needs to be coordinated nationwide and beyond and also across the various health professions in a formalized process.

[Oxidative stress in pathogenesis of COPD].

PubMed

Betsuyaku, Tomoko

2007-04-01

Cigarette smoke and aging are major risk factors of chronic obstructive pulmonary disease(COPD). It remains unsolved how long -term smoking with age affects the molecular responses in the lung. Respiratory tract is the major interface to the environment and is rich in glutathione, which protects lung from oxidative stress. We performed bronchoalveolar lavage for nonsmokers and smokers of various ages, who were further categorized according to the presence of emphysema on high-resolution computed tomography. We thus evaluated glutathione antioxidant system in BAL fluid. Characterization of older smokers with long-term smoking histories, contrasted with young recent smokers, may in part explain the predisposition of the lungs to destructive lung diseases. On the other hands, oxidative stress results from an imbalance in aerobic metabolism and poses a serious threat to cellular apoptosis, leading to emphysematous lung destruction. The therapeutic interference with targeted up-regulation of protective mechanisms might be critical for the success of future COPD therapies.

Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

PubMed

Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

2015-09-01

Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively.

Gastrokines: stomach-specific proteins with putative homeostatic and tumor suppressor roles.

PubMed

Menheniott, Trevelyan R; Kurklu, Bayzar; Giraud, Andrew S

2013-01-15

During the past decade, a new family of stomach-specific proteins has been recognized. Known as "gastrokines" (GKNs), these secreted proteins are products of gastric mucus-producing cell lineages. GKNs are highly conserved in physical structure, and emerging data point to convergent functions in the modulation of gastric mucosal homeostasis and inflammation. While GKNs are highly prevalent in the normal stomach, frequent loss of GKN expression in gastric cancers, coupled with established antiproliferative activity, suggests putative tumor suppressor roles. Conversely, ectopic expression of GKNs in reparative lesions of Crohn's disease alludes to additional activity in epithelial wound healing and/or repair. Modes of action remain unsolved, but the recent demonstration of a GKN2-trefoil factor 1 heterodimer implicates functional interplay with trefoil factors. This review aims to provide a historical account of GKN biology and encapsulate the rapidly accumulating evidence supporting roles in gastric epithelial homeostasis and tumor suppression.

Diverse Formation Mechanisms for Compact Galaxies

NASA Astrophysics Data System (ADS)

Kim, Jin-Ah; Paudel, Sanjaya; Yoon, Suk-Jin

2018-01-01

Compact, quenched galaxies such as M32 are unusual ones located off the mass - size scaling relation defined by normal galaxies. Still, their formation mechanisms remain unsolved. Here we investigate the evolution of ~100 compact, quenched galaxies at z = 0 identified in the Illustris cosmological simulation. We identify three ways for a galaxy to become a compact one and, often, multiple mechanisms operate in a combined manner. First, stripping is responsible for making about a third of compact galaxies. Stripping removes stars from galaxies, usually while keeping their sizes intact. About one third are galaxies that cease their growth early on after entering into more massive, gigantic halos. Finally, about half of compact galaxies, ~ 35 % of which turn out to undergo stripping, experience the compaction due to the highly centrally concentrated star formation. We discuss the evolutionary path of compact galaxies on the mass – size plane for each mechanism in a broader context of dwarf galaxy formation and evolution.

Chiral encoding may provide a simple solution to the origin of life

NASA Astrophysics Data System (ADS)

Brewer, Ashley; Davis, Anthony P.

2014-07-01

The route by which the complex and specific molecules of life arose from the 'prebiotic soup' remains an unsolved problem. Evolution provides a large part of the answer, but this requires molecules that can carry information (that is, exist in many variants) and can replicate themselves. The process is commonplace in living organisms, but not so easy to achieve with simple chemical systems. It is especially difficult to contemplate in the chemical chaos of the prebiotic world. Although popular in many quarters, the notion that RNA was the first self-replicator carries many difficulties. Here, we present an alternative view, suggesting that there may be undiscovered self-replication mechanisms possible in much simpler systems. In particular, we highlight the possibility of information coding through stereochemical configurations of substituents in organic polymers. We also show that this coding system leads naturally to enantiopurity, solving the apparent problem of biological homochirality.

Invisible magnetic sensors

NASA Astrophysics Data System (ADS)

Mach-Batlle, Rosa; Navau, Carles; Sanchez, Alvaro

2018-04-01

Sensing magnetic fields is essential in many applications in biomedicine, transportation, or smart cities. The distortion magnetic sensors create in response to the field they are detecting may hinder their use, for example, in applications requiring dense packaging of sensors or accurately shaped field distributions. For sensing electromagnetic waves, cloaking shells that reduce the scattering of sensors have been introduced. However, the problem of making a magnetic sensor undetectable remains unsolved. Here, we present a general strategy on how to make a sensor magnetically invisible while keeping its ability to sense. The sensor is rendered undetectable by surrounding it with a spherical shell having a tailored magnetic permeability. Our method can be applied to arbitrary shaped magnetic sensors in arbitrary magnetic fields. The invisibility can be made exact when the sensor is spherical and the probed field is uniform. A metasurface composed of superconducting pieces is presented as a practical realization of the ideal invisibility shell.

Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth.

PubMed

Forsythe, Jay G; Yu, Sheng-Sheng; Mamajanov, Irena; Grover, Martha A; Krishnamurthy, Ramanarayanan; Fernández, Facundo M; Hud, Nicholas V

2015-08-17

Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α-amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α-hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α-hydroxy acids and α-amino acids form depsipeptides-oligomers with a combination of ester and amide linkages-in model prebiotic reactions that are driven by wet-cool/dry-hot cycles. Through a combination of ester-amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long-standing hypothesis that peptides might have arisen from ester-based precursors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Establishing the identity of the massacred tigress in a case of wildlife crime.

PubMed

Gupta, Sandeep Kumar; Bhagavatula, Jyotsna; Thangaraj, Kumarasamy; Singh, Lalji

2011-01-01

We report a case study, where we have established the identity from a challenging biological sample of a deceased tigress by parentage analysis. A wildlife crime was committed in one of the zoological parks in India in the year 2000, where one young tigress was killed for its claws. This was of media interest for several days and remained an unsolved case for four years. A framed claw and decomposed tiger hide were seized from the accused in 2005. Biological samples of the victim tigress was not available for further forensics examination, therefore; DNA samples of the biological parents and a male sibling were used to establish the identity of the claw using STRs and mitochondrial DNA markers. Our analysis indicates that the seized claw belongs to the victim tigress. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

An Architecture for Semantically Interoperable Electronic Health Records.

PubMed

Toffanello, André; Gonçalves, Ricardo; Kitajima, Adriana; Puttini, Ricardo; Aguiar, Atualpa

2017-01-01

Despite the increasing adhesion of electronic health records, the challenge of semantic interoperability remains unsolved. The fact that different parties can exchange messages does not mean they can understand the underlying clinical meaning, therefore, it cannot be assumed or treated as a requirement. This work introduces an architecture designed to achieve semantic interoperability, in a way which organizations that follow different policies may still share medical information through a common infrastructure comparable to an ecosystem, whose organisms are exemplified within the Brazilian scenario. Nonetheless, the proposed approach describes a service-oriented design with modules adaptable to different contexts. We also discuss the establishment of an enterprise service bus to mediate a health infrastructure defined on top of international standards, such as openEHR and IHE. Moreover, we argue that, in order to achieve truly semantic interoperability in a wide sense, a proper profile must be published and maintained.

Progress on alternative energy resources

NASA Astrophysics Data System (ADS)

Couch, H. T.

1982-03-01

Progress in the year 1981 toward the development of energy systems suitable for replacing petroleum products combustion and growing in use to fulfill a near term expansion in energy use is reviewed. Coal is noted to be a potentially heavy pollution source, and the presence of environmentally acceptable methods of use such as fluidized-bed combustion and gasification and liquefaction reached the prototype stage in 1981, MHD power generation was achieved in two U.S. plants, with severe corrosion problems remaining unsolved for the electrodes. Solar flat plate collectors sales amounted to 20 million sq ft in 1981, and solar thermal electric conversion systems with central receivers neared completion. Solar cells are progressing toward DOE goals of $.70/peak W by 1986, while wind energy conversion sales were 2000 machines in 1981, and the industry is regarded as maturing. Finally, geothermal, OTEC, and fusion systems are reviewed.

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.

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.

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.

Absence of ballistic charge transport in the half-filled 1D Hubbard model

NASA Astrophysics Data System (ADS)

Carmelo, J. M. P.; Nemati, S.; Prosen, T.

2018-05-01

Whether in the thermodynamic limit of lattice length L → ∞, hole concentration mηz = - 2 Sηz/L = 1 -ne → 0, nonzero temperature T > 0, and U / t > 0 the charge stiffness of the 1D Hubbard model with first neighbor transfer integral t and on-site repulsion U is finite or vanishes and thus whether there is or there is no ballistic charge transport, respectively, remains an unsolved and controversial issue, as different approaches yield contradictory results. (Here Sηz = - (L -Ne) / 2 is the η-spin projection and ne =Ne / L the electronic density.) In this paper we provide an upper bound on the charge stiffness and show that (similarly as at zero temperature), for T > 0 and U / t > 0 it vanishes for mηz → 0 within the canonical ensemble in the thermodynamic limit L → ∞. Moreover, we show that at high temperature T → ∞ the charge stiffness vanishes as well within the grand-canonical ensemble for L → ∞ and chemical potential μ →μu where (μ -μu) ≥ 0 and 2μu is the Mott-Hubbard gap. The lack of charge ballistic transport indicates that charge transport at finite temperatures is dominated by a diffusive contribution. Our scheme uses a suitable exact representation of the electrons in terms of rotated electrons for which the numbers of singly occupied and doubly occupied lattice sites are good quantum numbers for U / t > 0. In contrast to often less controllable numerical studies, the use of such a representation reveals the carriers that couple to the charge probes and provides useful physical information on the microscopic processes behind the exotic charge transport properties of the 1D electronic correlated system under study.

Calculation of the ALMA Risk of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

PubMed

Loforte, Antonio; Montalto, Andrea; Musumeci, Francesco; Amarelli, Cristiano; Mariani, Carlo; Polizzi, Vincenzo; Lilla Della Monica, Paola; Grigioni, Francesco; Di Bartolomeo, Roberto; Marinelli, Giuseppe

2018-05-08

Right ventricular failure after continuous-flow left ventricular assist device (LVAD) implantation is still an unsolved issue and remains a life-threatening event for patients. We undertook this study to determine predictors of the patients who are candidates for isolated LVAD therapy as opposed to biventricular support (BVAD). We reviewed demographic, echocardiographic, hemodynamic, and laboratory variables for 258 patients who underwent both isolated LVAD implantation and unplanned BVAD because of early right ventricular failure after LVAD insertion, between 2006 and 2017 (LVAD = 170 and BVAD = 88). The final study patients were randomly divided into derivation (79.8%, n = 206) and validation (20.1%, n = 52) cohorts. Fifty-seven preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BVAD. Nineteen variables demonstrated statistical significance on univariable analysis. Multivariable logistic regression analysis identified destination therapy (odds ratio [OR] 2.0 [1.7-3.9], p = 0.003), a pulmonary artery pulsatility index <2 (OR 3.3 [1.7-6.1], p = 0.001), a right ventricle/left ventricle end-diastolic diameter ratio >0.75 (OR 2.7 [1.5-5.5], p = 0.001), an right ventricle stroke work index <300 mm Hg/ml/m (OR 4.3 [2.5-7.3], p < 0.001), and a United Network for Organ Sharing modified Model for End-Stage Liver Disease Excluding INR score >17 (OR 3.5 [1.9-6.9], p < 0.001) as the major predictors of the need for BVAD. Using these data, we propose a simple risk calculator to determine the suitability of patients for isolated LVAD support in the era of continuous-flow mechanical circulatory support devices.

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.

Observing Planetary Nebulae with JWST and Extremely Large Telescopes

NASA Astrophysics Data System (ADS)

Sahai, Raghvendra

2015-01-01

Most stars in the Universe that leave the main sequence in a Hubble time will end their lives evolving through the Planetary Nebula (PN) evolutionary phase. The heavy mass loss which occurs during the preceding AGB phase is important across astrophysics, dramatically changing the course of stellar evolution, dominantly contributing to the dust content of the interstellar medium, and influencing its chemical composition. The evolution from the AGB phase to the PN phases remains poorly understood, especially the dramatic transformation that occurs in the morphology of the mass-ejecta as AGB stars and their round circumstellar envelopes evolve into mostly PNe, the majority of which deviate strongly from spherical symmetry. In addition, although the PN [OIII] luminosity function (PNLF) has been used as a standard candle (on par with distance indicators such as Cepheids), we do not understand why it works. It has been argued that the resolution of these issues may be linked to binarity and associated processes such as mass transfer and common envelope evolution.Thus, understanding the formation and evolution of PNe is of wide astrophysical importance. PNe have long been known to emit across a very large span of wavelengths, from the radio to X-rays. Extensive use of space-based observatories at X-ray (Chandra/ XMM-Newton), optical (HST) and far-infrared (Spitzer, Herschel) wavelengths in recent years has produced significant new advances in our knowledge of these objects. Given the expected advent of the James Webb Space Telescope in the near future, and ground-based Extremely Large Telescope(s) somewhat later, this talk will focus on future high-angular-resolution, high-sensitivity observations at near and mid-IR wavelengths with these facilities that can help in addressing the major unsolved problems in the study of PNe.

Absence of high-temperature ballistic transport in the spin-1/2 XXX chain within the grand-canonical ensemble

NASA Astrophysics Data System (ADS)

Carmelo, J. M. P.; Prosen, T.

2017-01-01

Whether in the thermodynamic limit, vanishing magnetic field h → 0, and nonzero temperature the spin stiffness of the spin-1/2 XXX Heisenberg chain is finite or vanishes within the grand-canonical ensemble remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we provide an upper bound on the stiffness and show that within that ensemble it vanishes for h → 0 in the thermodynamic limit of chain length L → ∞, at high temperatures T → ∞. Our approach uses a representation in terms of the L physical spins 1/2. For all configurations that generate the exact spin-S energy and momentum eigenstates such a configuration involves a number 2S of unpaired spins 1/2 in multiplet configurations and L - 2 S spins 1/2 that are paired within Msp = L / 2 - S spin-singlet pairs. The Bethe-ansatz strings of length n = 1 and n > 1 describe a single unbound spin-singlet pair and a configuration within which n pairs are bound, respectively. In the case of n > 1 pairs this holds both for ideal and deformed strings associated with n complex rapidities with the same real part. The use of such a spin 1/2 representation provides useful physical information on the problem under investigation in contrast to often less controllable numerical studies. Our results provide strong evidence for the absence of ballistic transport in the spin-1/2 XXX Heisenberg chain in the thermodynamic limit, for high temperatures T → ∞, vanishing magnetic field h → 0 and within the grand-canonical ensemble.

Towards a Video Passive Content Fingerprinting Method for Partial-Copy Detection Robust against Non-Simulated Attacks

PubMed Central

2016-01-01

Passive content fingerprinting is widely used for video content identification and monitoring. However, many challenges remain unsolved especially for partial-copies detection. The main challenge is to find the right balance between the computational cost of fingerprint extraction and fingerprint dimension, without compromising detection performance against various attacks (robustness). Fast video detection performance is desirable in several modern applications, for instance, in those where video detection involves the use of large video databases or in applications requiring real-time video detection of partial copies, a process whose difficulty increases when videos suffer severe transformations. In this context, conventional fingerprinting methods are not fully suitable to cope with the attacks and transformations mentioned before, either because the robustness of these methods is not enough or because their execution time is very high, where the time bottleneck is commonly found in the fingerprint extraction and matching operations. Motivated by these issues, in this work we propose a content fingerprinting method based on the extraction of a set of independent binary global and local fingerprints. Although these features are robust against common video transformations, their combination is more discriminant against severe video transformations such as signal processing attacks, geometric transformations and temporal and spatial desynchronization. Additionally, we use an efficient multilevel filtering system accelerating the processes of fingerprint extraction and matching. This multilevel filtering system helps to rapidly identify potential similar video copies upon which the fingerprint process is carried out only, thus saving computational time. We tested with datasets of real copied videos, and the results show how our method outperforms state-of-the-art methods regarding detection scores. Furthermore, the granularity of our method makes it suitable for partial-copy detection; that is, by processing only short segments of 1 second length. PMID:27861492

The use of quality-adjusted life-years in the economic evaluation of health technologies in Spain: a review of the 1990-2009 literature.

PubMed

Rodriguez, José Manuel; Paz, Silvia; Lizan, Luis; Gonzalez, Paloma

2011-06-01

To appraise economic evaluations of health technologies that included quality-adjusted life-years (QALYs) as an outcome measure conducted over the past 20 years in Spain. A systematic review of the literature was conducted. Economic evaluations that included QALYs as an outcome measure, conducted in Spain and published between January 1990 and December 2009 were identified. Primary and gray literature sources were reviewed. A total of 60 articles and 4 health technology assessment reports were included. Key findings were 1) the vast majority of articles (77.1%) referred to therapeutic interventions; 2) 63.2% dealt with pharmaceutical products and much fewer with preventive strategies, medical devices, or diagnostic interventions; 3) most evaluations referred to cardiovascular- (19.8%), respiratory- (16.3%), and cancer- (13.0%) related processes; 4) 80.3% were based on a theoretical model, most commonly Markov models (71.4%); 5) 67.3% adopted the National Health System perspective; 6) information on the methods used to describe the health states was given in 45.1% of studies; 7) 40.3% used the EuroQoL-5D to elicit preferences, whereas 66.1% gave no details on the methods applied to determine patients' choices; 8) it was possible to state who completed the questionnaires in only 17.7% of studies; 9) 77.1% of the interventions assessed were below the €30,000/QALY suggested affordable threshold in Spain. An increasing number of economic evaluations using QALYs had been conducted. Most of them relied on theoretical models. Several methodological issues remain unsolved. Great disparity exists regarding the reporting of the methods used to determine health states and utility values. Copyright © 2011. Published by Elsevier Inc.

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.

A mechanical model predicts morphological abnormalities in the developing human brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

Voltage-gated proton channels: what' next?

PubMed Central

DeCoursey, Thomas E

2008-01-01

This review is an attempt to identify and place in context some of the many questions about voltage-gated proton channels that remain unsolved. As the gene was identified only 2 years ago, the situation is very different than in fields where the gene has been known for decades. For the proton channel, most of the obvious and less obvious structure–function questions are still wide open. Remarkably, the proton channel protein strongly resembles the voltage-sensing domain of many voltage-gated ion channels, and thus offers a novel approach to study gating mechanisms. Another surprise is that the proton channel appears to function as a dimer, with two separate conduction pathways. A number of significant biological questions remain in dispute, unanswered, or in some cases, not yet asked. This latter deficit is ascribable to the intrinsic difficulty in evaluating the importance of one component in a complex system, and in addition, to the lack, until recently, of a means of performing an unambiguous lesion experiment, that is, of selectively eliminating the molecule in question. We still lack a potent, selective pharmacological inhibitor, but the identification of the gene has allowed the development of powerful new tools including proton channel antibodies, siRNA and knockout mice. PMID:18801839

A new species of Allodaposuchus (Eusuchia, Crocodylia) from the Maastrichtian (Late Cretaceous) of Spain: phylogenetic and paleobiological implications

PubMed Central

Blanco, Alejandro; Fortuny, Josep; Vicente, Alba; Luján, Àngel H.; García-Marçà, Jordi Alexis

2015-01-01

Background. The Late Cretaceous is a keystone period to understand the origin and early radiation of Crocodylia, the group containing all extant lineages of crocodilians. Among the taxa described from the latest Cretaceous of Europe, the genus Allodaposuchus is one of the most common but also one of the most controversial. However, because of its fragmentary record, several issues regarding its phylogenetic emplacement and its ecology remain unsolved or unknown. The discovery of a single specimen attributed to Allodaposuchus, represented by both cranial and postcranial remains, from the Casa Fabà site (Tremp Basin, NE Spain) in the lower red unit of the Tremp Fm. (early Maastrichtian, Late Cretaceous) offers a unique opportunity to deepen in the phylogenetic relationships of the group and its ecological features. Methods. The specimen is described in detail, and CT scan of the skull is performed in order to study the endocranial morphology as well as paratympanic sinuses configuration. In addition, myological and phylogenetic analyses are also carried out on the specimen for to shed light in ecological and phylogenetic issues, respectively. Results. The specimen described herein represents a new species, Allodaposuchus hulki sp. nov., closely related to the Romanian A. precedens. The CT scan of the skull revealed an unexpected paratympanic sinuses configuration. Allosaposuchus hulki exhibits an “anterodorsal tympanic sinus” not observed in any other extant or extinct crocodilian. The caudal tympanic recesses are extremely enlarged, and the expanded quadratic sinus seems to be connected to the middle-ear channel. Phylogenetic analyses confirm the emplacement of the informal taxonomic group ‘Allodaposuchia’ at the base of Crocodylia, being considered the sister group of Borealosuchus and Planocraniidae. Discussion. Although this is a preliminary hypothesis, the unique paratympanic configuration displayed by A. hulki suggests that it could possess a high-specialized auditory system. Further, the large cranial cavities could help to reduce the weight of the cranium. Concerning the postcranial skeleton, Allodaposuchus hulki shows massive and robust vertebrae and forelimb bones, suggesting it could have a bulky body. The myological study performed on the anterior limb elements supports this interpretation. In addition, several bone and muscular features seem to point at a semi-erected position of the forelimbs during terrestrial locomotion. Taking all the above results into consideration, it seems plausible to suggest that A. hulki could conduct large incursions out of the water and have a semi-terrestrial lifestyle. PMID:26339549

A Generic analytical solution for modelling pumping tests in wells intersecting fractures

NASA Astrophysics Data System (ADS)

Dewandel, Benoît; Lanini, Sandra; Lachassagne, Patrick; Maréchal, Jean-Christophe

2018-04-01

The behaviour of transient flow due to pumping in fractured rocks has been studied for at least the past 80 years. Analytical solutions were proposed for solving the issue of a well intersecting and pumping from one vertical, horizontal or inclined fracture in homogeneous aquifers, but their domain of application-even if covering various fracture geometries-was restricted to isotropic or anisotropic aquifers, whose potential boundaries had to be parallel or orthogonal to the fracture direction. The issue thus remains unsolved for many field cases. For example, a well intersecting and pumping a fracture in a multilayer or a dual-porosity aquifer, where intersected fractures are not necessarily parallel or orthogonal to aquifer boundaries, where several fractures with various orientations intersect the well, or the effect of pumping not only in fractures, but also in the aquifer through the screened interval of the well. Using a mathematical demonstration, we show that integrating the well-known Theis analytical solution (Theis, 1935) along the fracture axis is identical to the equally well-known analytical solution of Gringarten et al. (1974) for a uniform-flux fracture fully penetrating a homogeneous aquifer. This result implies that any existing line- or point-source solution can be used for implementing one or more discrete fractures that are intersected by the well. Several theoretical examples are presented and discussed: a single vertical fracture in a dual-porosity aquifer or in a multi-layer system (with a partially intersecting fracture); one and two inclined fractures in a leaky-aquifer system with pumping either only from the fracture(s), or also from the aquifer between fracture(s) in the screened interval of the well. For the cases with several pumping sources, analytical solutions of flowrate contribution from each individual source (fractures and well) are presented, and the drawdown behaviour according to the length of the pumped screened interval of the well is discussed. Other advantages of this proposed generic analytical solution are also given. The application of this solution to field data should provide additional field information on fracture geometry, as well as identifying the connectivity between the pumped fractures and other aquifers.

Formulation, Quality Control and Safety Issues of Nanocarriers Used for Cancer Treatment.

PubMed

Bianco, Ismael D; Ceballos, Marcelo R; Casado, Cristian; Dabbene, Viviana G; Rizzi, Carolina; Mizutamari, R Kiyomi

2017-01-01

Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few. In this context, nanotechnology with the emerging tools of nanoengineering offers many possibilities to guide the design of new products with improved safety and efficacy. The presence of several reacting groups and the sensitivity of their properties to small changes in composition make nanocarriers tunable not only to modify their stability in a particular environment but also to respond to changes in biological situations in the right place and time frame. This review summarizes the main preparation methods and formulation strategies of nano and microcarriers designed for drug delivery applications for cancer treatment and will attempt to give a glimpse on how their structure, shape, physico-chemical properties and chemical composition may affect their overall stability and interactions with biological systems. We will also cover aspects of nanoengineering that are opening new opportunities for the development of more effective nanomedicines, emphasizing on the challenges that have to be kept in mind when dealing with biological activities of nanocarriers that depend not only on their chemical composition but also on those of the structures formed by them and by their interactions with biological systems. From this, a very important issue that emerges is that nanocarriers frequently display an intrinsic bioactivity (i.e.: immunomodulatory). Therefore, it should be stressed that nanocarriers cannot be considered as inert, biocompatible excipients. Furthermore, their biological activity will mostly depend on the physical and chemical properties of the structures of the nanoparticles that are presented to living systems. As an approach to the rational design of new pharmaceutical products, nanoengineering is providing new tools for the precise control of the properties of nanocarriers for cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Definition of Failed Induction of Labor and Its Predictive Factors: Two Unsolved Issues of an Everyday Clinical Situation.

PubMed

Baños, Núria; Migliorelli, Federico; Posadas, Eduardo; Ferreri, Janisse; Palacio, Montse

2015-01-01

The objectives of this review were to identify the predictive factors of induction of labor (IOL) failure or success as well as to highlight the current heterogeneity regarding the definition and diagnosis of failed IOL. Only studies in which the main or secondary outcome was failed IOL, defined as not entering the active phase of labor after 24 h of prostaglandin administration ± 12 h of oxytocin infusion, were included in the review. The data collected were: study design, definition of failed IOL, induction method, IOL indications, failed IOL rate, cesarean section because of failed IOL and predictors of failed IOL. The database search detected 507 publications. The main reason for exclusion was that the primary or secondary outcomes were not the predetermined definition of failed IOL (not achieving active phase of labor). Finally, 7 studies were eligible. The main predictive factors identified in the review were cervical status, evaluated by the Bishop score or cervical length. Failed IOL should be defined as the inability to achieve the active phase of labor, considering that the definition of IOL is to enter the active phase of labor. A universal definition of failed IOL is an essential requisite to analyze and obtain solid results and conclusions on this issue. An important finding of this review is that only 7 of all the studies reviewed assessed achieving the active phase of labor as a primary or secondary IOL outcome. Another conclusion is that cervical status remains the most important predictor of IOL outcome, although the value of the parameters explored up to now is limited. To find or develop predictive tools to identify those women exposed to IOL who may not reach the active phase of labor is crucial to minimize the risks and costs associated with IOL failure while opening a great opportunity for investigation. Therefore, other predictive tools should be studied in order to improve IOL outcome in terms of health and economic burden. © 2015 S. Karger AG, Basel.

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.

[Current issues, problems and prospects of tension-free hernioplasty (review)].

PubMed

2014-01-01

In the present study there are discussed modern methods of the tension free hernioplastics, the complications associated with them and technical difficulties, up-to-date views and the perspectives of the issue development in terms of avoiding infectious complications, positioning of implants and their fixation. Hernia is one of the widespread surgical pathologies as it is found in 4% of the population and its share among the inpatient surgical diseases is about 18-30%. Consequently annually up to 20-21 mln hernioplasties are carried out worldwide. Despite of many years of experience in the field of hernia surgical treatment there still exist many unsolved problems such as safe closure of defects of abdominal cavity wall. Up to 200 methods of hernioplastics, various implantations and application of synthetic materials refer to lack of the optimal surgical strategy. In modern herniology priorities are given to tension free plastics. The merge of the synthetic implants and "tension free hernioplastics" concepts enabled sharp reduction of the side effects list, making it possible to perform successful surgeries in that contingent whose treatment by the method of tissue-plasty was related with high risk of lethality. Large scale introduction of tension free hernioplastics caused intensification of the associated problems such as migration, dissection and shortening of the net.

[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.

Eosinophilic esophagitis: a bulk of mysteries.

PubMed

Straumann, Alex

2013-01-01

Eosinophilic esophagitis (EoE), which was first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory esophageal disease. The diagnosis is based clinically on the presence of symptoms related to esophageal dysfunction and histologically by an eosinophil-predominant inflammation once other conditions leading to esophageal eosinophilia are excluded. This striking male-prevalent disease has an increasing incidence and prevalence in the Westernized countries. Currently, EoE represents the main cause of dysphagia and bolus impaction in adult patients. Despite the fact that EoE often occurs in atopic patients, the value of allergic testing is still under discussion. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by practical issues. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies have been fully defined. Currently, the list of unsolved issues--or mysteries--is still long and a concerted effort on behalf of clinicians and scientists is required to improve the understanding and the therapeutic management of this mysterious disease. Copyright © 2013 S. Karger AG, Basel.

Setting up a model intercomparison project for the last deglaciation

NASA Astrophysics Data System (ADS)

Ivanovic, R. F.; Gregoire, L. J.; Valdes, P. J.; Roche, D. M.; Kageyama, M.

2014-12-01

The last deglaciation (~ 21-9 ka) presents a series of opportunities to study the underlying mechanisms of abrupt climate changes and long-term trends in the Earth System. Most of the forcings are relatively well constrained and geological archives record responses over a range of timescales. Despite this, large uncertainties remain over the feedback loops that culminated in the collapse of the great Northern Hemisphere ice sheets, and a consensus has yet to be reached on the chains of events that led to rapid surface warming and cooling during this period.Climate models are powerful tools for quantitatively assessing these outstanding issues through their ability to temporally resolve cause and effect, as well as break down the contributions from different forcings. This is well demonstrated by pioneering work; for example by Liu et al. (2009), Roche et al. (2011), Gregoire et al. (2012) and Menviel et al. (2011). However, such work is not without challenges; model-geological data mismatches remain unsolved and it is difficult to compare results from different models with unique experiment designs. Therefore, we have established a multidisciplinary Paleoclimate Model Intercomparison Project working group to coordinate transient climate model simulations and geological archive compilations of the last deglaciation. Here, we present the plans and progress of the working group in its first phase of activity; the investigation of Heinrich Stadial 1 and the lead into the Bolling warming event. We describe the set-up of the core deglacial experiment, explain our approach for dealing with uncertain climate forcings and outline our solutions to challenges posed by this research. By defining a common experiment design, we have built a framework to include models of different speeds, complexities and resolution, maximising the reward of this varied approach. One of the next challenges is to compile transient proxy records and develop a methodology for dealing with uncertainty and error in model-geological data comparisons. Through this global and interdisciplinary initiative, we combine multi-proxy records with a suite of different modelling techniques to test hypotheses for abrupt climate changes and reconstruct the chain of events that deglaciated the Earth 21-9 ka.

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.

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.

Ethical issues in paleopathological and anthropological research experiences.

PubMed

Licata, Marta; Monza, Francesca

2017-10-23

In recent years, archaeologists and anthropologists involved in the study of human remains have had to take into consideration ethical issues, which have come to the fore. The aim of this study is to illustrate the ethical and religious issues involved in relation to the positions of researchers. Ethical issues involve the different study phases of human remains: archaeological excavation, anthropological analysis and, finally, museum display. Osteoarchaeological remains may find a place in museums. However, in recent years, even the display of human remains museum has had to face new important ethical issue involving previously ignored or neglected aspect. The adoption of Native American Grave Protection Act in 1990 in the United States and the Human Tissue Act in 2004 in England, has created new scenarios relating to the storage of human remains in museum. All this caused a series of changes in the study of human remains, but many issues remain open to debate.

Structural integrity of engineering composite materials: a cracking good yarn.

PubMed

Beaumont, Peter W R; Soutis, Costas

2016-07-13

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-scale engineering structures. Where human life depends upon engineering ingenuity, the burden of testing to prove a 'fracture safe design' is immense. Fitness considerations for long-life implementation of large composite structures 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, and takes service duty into account. 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. This article is part of the themed issue 'Multiscale modelling of the structural integrity of composite materials'. © 2016 The Author(s).

The Fate of a Normal Human Cell Traversed by a Single Charged Particle

NASA Astrophysics Data System (ADS)

Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

2012-09-01

The long-term ``fate'' of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability.

The Fate of a Normal Human Cell Traversed by a Single Charged Particle

PubMed Central

Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

2012-01-01

The long-term “fate” of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability. PMID:22966418

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.

Real-world visual statistics and infants' first-learned object names

PubMed Central

Clerkin, Elizabeth M.; Hart, Elizabeth; Rehg, James M.; Yu, Chen

2017-01-01

We offer a new solution to the unsolved problem of how infants break into word learning based on the visual statistics of everyday infant-perspective scenes. Images from head camera video captured by 8 1/2 to 10 1/2 month-old infants at 147 at-home mealtime events were analysed for the objects in view. The images were found to be highly cluttered with many different objects in view. However, the frequency distribution of object categories was extremely right skewed such that a very small set of objects was pervasively present—a fact that may substantially reduce the problem of referential ambiguity. The statistical structure of objects in these infant egocentric scenes differs markedly from that in the training sets used in computational models and in experiments on statistical word-referent learning. Therefore, the results also indicate a need to re-examine current explanations of how infants break into word learning. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’. PMID:27872373

Review of analytical models to stream depletion induced by pumping: Guide to model selection

NASA Astrophysics Data System (ADS)

Huang, Ching-Sheng; Yang, Tao; Yeh, Hund-Der

2018-06-01

Stream depletion due to groundwater extraction by wells may cause impact on aquatic ecosystem in streams, conflict over water rights, and contamination of water from irrigation wells near polluted streams. A variety of studies have been devoted to addressing the issue of stream depletion, but a fundamental framework for analytical modeling developed from aquifer viewpoint has not yet been found. This review shows key differences in existing models regarding the stream depletion problem and provides some guidelines for choosing a proper analytical model in solving the problem of concern. We introduce commonly used models composed of flow equations, boundary conditions, well representations and stream treatments for confined, unconfined, and leaky aquifers. They are briefly evaluated and classified according to six categories of aquifer type, flow dimension, aquifer domain, stream representation, stream channel geometry, and well type. Finally, we recommend promising analytical approaches that can solve stream depletion problem in reality with aquifer heterogeneity and irregular geometry of stream channel. Several unsolved stream depletion problems are also recommended.

Simpson-Golabi-Behmel syndrome in a female: A case report and an unsolved issue.

PubMed

Vaisfeld, Alessandro; Pomponi, Maria Grazia; Pietrobono, Roberta; Tabolacci, Elisabetta; Neri, Giovanni

2017-01-01

Simpson-Golabi-Behmel syndrome is an X-linked recessive overgrowth condition caused by alterations in GPC3 gene, encoding for the cell surface receptor glypican 3, whose clinical manifestations in affected males are well known. Conversely, there is little information regarding affected females, with very few reported cases, and a clinical definition of this phenotype is still lacking. In the present report we describe an additional case, the first to receive a primary molecular diagnosis based on strong clinical suspicion. Possible explanations for full clinical expression of X-linked recessive conditions in females include several mechanisms, such as skewed X inactivation or homozygosity/compound heterozygosity of the causal mutation. Both of these were excluded in our case. Given that the possibility of full expression of SGBS in females is now firmly established, we recommend that GPC3 analysis be performed in all suggestive female cases. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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.

Biodegradable black phosphorus-based nanomaterials in biomedicine: theranostic applications.

PubMed

Wang, Zhen; Liu, Zhiming; Su, Chengkang; Yang, Biwen; Fei, Xixi; Li, Yi; Hou, Yuqing; Zhao, Henan; Guo, Yanxian; Zhuang, Zhengfei; Zhong, Huiqing; Guo, Zhouyi

2017-09-20

Ascribe to the unique two-dimensional planar nanostructure with exceptional physical and chemical properties, black phosphorous (BP) as the emerging inorganic two-dimensional nanomaterial with high biocompatibility and degradability has been becoming one of the most promising materials of great potentials in biomedicine. The exfoliated BP sheets possess ultra-high surface area available for valid bio-conjugation and molecular loading for chemotherapy. Utilizing the intrinsic near-infrared optical absorbance, BP-based photothermal therapy in vivo, photodynamic therapy and biomedical imaging has been realized, achieving unprecedented anti-tumor therapeutic efficacy in animal experiments. Additionally, the BP nanosheets can strongly react with oxygen and water, and finally degrade to non-toxic phosphate and phosphonate in the aqueous solution. This manuscript aimed to summarize the preliminary progresses on theranostic application of BP and its derivatives black phosphorus quantum dots (BPQDs), and discussed the prospects and the state-of-art unsolved critical issues of using BP-based material for theranostic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Investing in European market real property through reits

NASA Astrophysics Data System (ADS)

Adamuscin, A.

2010-03-01

For institutional and private investors, investing in real estate represents an attractive form of the consignment of their money. Real estate provides a regular source of income in the form of the rent from or interest on the credit provided. At the same time, real estate is a good investment instrument, because it provides diversified contributions and security against inflation for investors. In their efforts to diversify risk, investors are expressing growing interest in investing in the whole European Union. The success of Real Estate Investment Trusts (REITs) in the U.S. also opened the door for investing in this market for small investors, which is the reason for the development of this type of investment company in the European arena. One problem concerning the development of European real estate investment funds is the unsolved issue of the harmonization of the legislation and regulatory safety measures, which would enable the creation of a common market for new investment products in Europe.

Interactions between gastro-oesophageal reflux disease and eosinophilic oesophagitis.

PubMed

Molina-Infante, Javier; van Rhijn, Bram D

2015-10-01

Gastro-oesophageal reflux disease (GORD) is the most common oesophageal disorder, whereas eosinophilic oesophagitis (EoE) is an emerging disease unresponsive to PPI therapy. Updated guidelines in 2011 described proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE), a novel phenotype in EoE patients who were responsive to PPIs. This article aims to update the complex interplay between GORD, EoE and PPIs. Oesophageal mucosal integrity is diffusely impaired in EoE and PPI-REE patients. PPI-REE might occur with either normal or pathological pH monitoring. The genetic hallmark of EoE is overlapped in PPI-REE, but not in GORD. PPIs can partially restore epithelial integrity and reverse allergic inflammation gene expression in PPI-REE. Acid hypersensitivity in EoE patients may explain symptomatic but not histological response on PPIs. Unsolved issues with PPI-REE are whether oesophageal barrier impairment is the cause or the effect of oesophageal eosinophilia and whether PPIs primarily targets barrier integrity or oesophageal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of specific immunoglobulins and vaccines for the management of accidental needlestick injury in the child: a practical review in the anti-vaccination movement era.

PubMed

Sollai, Sara; Iacopelli, Jessica; Giovannini, Mattia; Prato, Manuela; Galli, Luisa; de Martino, Maurizio; Chiappini, Elena

2016-10-01

Accidental needle injury is a common but still discussed problem. We discuss possible options to optimize the management of injured children in light of the available literature findings. The risk of viral infection is low. However, blood investigations are mandatory, as well as appropriate counselling. Anti-HBV immunoglobulins are recommended in all unvaccinated subjects exposed to a HBsAg-positive source; however, there is no agreement regarding their administration in unvaccinated children. Use of anti-tetanus immunoglobulins in unvaccinated child with minor and clean wound is well defined; however, wound type classification in the event of needlestick injury may be difficult and subjective. There is no agreement on the routine use of antiretroviral prophylaxis. From a practical point of view, several unsolved issues have emerged regarding the management of the children with needlestick injury, which appear particularly relevant in the anti-vaccination movement era. International guidelines should be encouraged at this regard.

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.

Photogenerated Intrinsic Free Carriers in Small-molecule Organic Semiconductors Visualized by Ultrafast Spectroscopy

PubMed Central

He, Xiaochuan; Zhu, Gangbei; Yang, Jianbing; Chang, Hao; Meng, Qingyu; Zhao, Hongwu; Zhou, Xin; Yue, Shuai; Wang, Zhuan; Shi, Jinan; Gu, Lin; Yan, Donghang; Weng, Yuxiang

2015-01-01

Confirmation of direct photogeneration of intrinsic delocalized free carriers in small-molecule organic semiconductors has been a long-sought but unsolved issue, which is of fundamental significance to its application in photo-electric devices. Although the excitonic description of photoexcitation in these materials has been widely accepted, this concept is challenged by recently reported phenomena. Here we report observation of direct delocalized free carrier generation upon interband photoexcitation in highly crystalline zinc phthalocyanine films prepared by the weak epitaxy growth method using ultrafast spectroscopy. Transient absorption spectra spanning the visible to mid-infrared region revealed the existence of short-lived free electrons and holes with a diffusion length estimated to cross at least 11 molecules along the π−π stacking direction that subsequently localize to form charge transfer excitons. The interband transition was evidenced by ultraviolet-visible absorption, photoluminescence and electroluminescence spectroscopy. Our results suggest that delocalized free carriers photogeneration can also be achieved in organic semiconductors when the molecules are packed properly. PMID:26611323

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.

New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID).

PubMed

Van Gijn, Marielle E; Ceccherini, Isabella; Shinar, Yael; Carbo, Ellen C; Slofstra, Mariska; Arostegui, Juan I; Sarrabay, Guillaume; Rowczenio, Dorota; Omoyımnı, Ebun; Balci-Peynircioglu, Banu; Hoffman, Hal M; Milhavet, Florian; Swertz, Morris A; Touitou, Isabelle

2018-03-29

Hereditary recurrent fevers (HRFs) are rare inflammatory diseases sharing similar clinical symptoms and effectively treated with anti-inflammatory biological drugs. Accurate diagnosis of HRF relies heavily on genetic testing. This study aimed to obtain an experts' consensus on the clinical significance of gene variants in four well-known HRF genes: MEFV , TNFRSF1A , NLRP3 and MVK . We configured a MOLGENIS web platform to share and analyse pathogenicity classifications of the variants and to manage a consensus-based classification process. Four experts in HRF genetics submitted independent classifications of 858 variants. Classifications were driven to consensus by recruiting four more expert opinions and by targeting discordant classifications in five iterative rounds. Consensus classification was reached for 804/858 variants (94%). None of the unsolved variants (6%) remained with opposite classifications (eg, pathogenic vs benign). New mutational hotspots were found in all genes. We noted a lower pathogenic variant load and a higher fraction of variants with unknown or unsolved clinical significance in the MEFV gene. Applying a consensus-driven process on the pathogenicity assessment of experts yielded rapid classification of almost all variants of four HRF genes. The high-throughput database will profoundly assist clinicians and geneticists in the diagnosis of HRFs. The configured MOLGENIS platform and consensus evolution protocol are usable for assembly of other variant pathogenicity databases. The MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis; the specific HRF configuration is available at http://molgenis.org/said/. The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/. © 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.

Development of a DNA Barcoding System for Seagrasses: Successful but Not Simple

PubMed Central

Lucas, Christina; Thangaradjou, Thirunavakkarasu; Papenbrock, Jutta

2012-01-01

Seagrasses, a unique group of submerged flowering plants, profoundly influence the physical, chemical and biological environments of coastal waters through their high primary productivity and nutrient recycling ability. They provide habitat for aquatic life, alter water flow, stabilize the ground and mitigate the impact of nutrient pollution. at the coast region. Although on a global scale seagrasses represent less than 0.1% of the angiosperm taxa, the taxonomical ambiguity in delineating seagrass species is high. Thus, the taxonomy of several genera is unsolved. While seagrasses are capable of performing both, sexual and asexual reproduction, vegetative reproduction is common and sexual progenies are always short lived and epimeral in nature. This makes species differentiation often difficult, especially for non-taxonomists since the flower as a distinct morphological trait is missing. Our goal is to develop a DNA barcoding system assisting also non-taxonomists to identify regional seagrass species. The results will be corroborated by publicly available sequence data. The main focus is on the 14 described seagrass species of India, supplemented with seagrasses from temperate regions. According to the recommendations of the Consortium for the Barcoding of Life (CBOL) rbcL and matK were used in this study. After optimization of the DNA extraction method from preserved seagrass material, the respective sequences were amplified from all species analyzed. Tree- and character-based approaches demonstrate that the rbcL sequence fragment is capable of resolving up to family and genus level. Only matK sequences were reliable in resolving species and partially the ecotype level. Additionally, a plastidic gene spacer was included in the analysis to confirm the identification level. Although the analysis of these three loci solved several nodes, a few complexes remained unsolved, even when constructing a combined tree for all three loci. Our approaches contribute to the understanding of the morphological plasticity of seagrasses versus genetic differentiation. PMID:22253849

[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.

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.

The Caterer's Problem.

ERIC Educational Resources Information Center

Krause, Eugene F.

1983-01-01

An approach to teaching problem solving to preservice and in-service middle school teachers is described. They examined an unsolved question as a class research project. The process of developing the solution is detailed, and difficulties contained within the process are noted. (MP)

Capturing attention is not that simple: different mechanisms for stimulus-driven and contingent capture.

PubMed

Liao, Hsin-I; Yeh, Su-Ling

2013-11-01

Attentional orienting can be involuntarily directed to task-irrelevant stimuli, but it remains unsolved whether such attentional capture is contingent on top-down settings or could be purely stimulus-driven. We propose that attentional capture depends on the stimulus property because transient and static features are processed differently; thus, they might be modulated differently by top-down controls. To test this hybrid account, we adopted a spatial cuing paradigm in which a noninformative onset or color cue preceded an onset or color target with various stimulus onset asynchronies (SOAs). Results showed that the onset cue captured attention regardless of target type at short-but not long-SOAs. In contrast, the color cue captured attention at short and long SOAs, but only with a color target. The overall pattern of results corroborates our hypothesis, suggesting that different mechanisms are at work for stimulus-driven capture (by onset) and contingent capture (by color). Stimulus-driven capture elicits reflexive involuntary orienting, and contingent capture elicits voluntary feature-based enhancement.

Structure of p73 DNA-binding domain tetramer modulates p73 transactivation

PubMed Central

Ethayathulla, Abdul S.; Tse, Pui-Wah; Monti, Paola; Nguyen, Sonha; Inga, Alberto; Fronza, Gilberto; Viadiu, Hector

2012-01-01

The transcription factor p73 triggers developmental pathways and overlaps stress-induced p53 transcriptional pathways. How p53-family response elements determine and regulate transcriptional specificity remains an unsolved problem. In this work, we have determined the first crystal structures of p73 DNA-binding domain tetramer bound to response elements with spacers of different length. The structure and function of the adaptable tetramer are determined by the distance between two half-sites. The structures with zero and one base-pair spacers show compact p73 DNA-binding domain tetramers with large tetramerization interfaces; a two base-pair spacer results in DNA unwinding and a smaller tetramerization interface, whereas a four base-pair spacer hinders tetramerization. Functionally, p73 is more sensitive to spacer length than p53, with one base-pair spacer reducing 90% of transactivation activity and longer spacers reducing transactivation to basal levels. Our results establish the quaternary structure of the p73 DNA-binding domain required as a scaffold to promote transactivation. PMID:22474346

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme

PubMed Central

Bailey, Lucas J; Tan, Yong Zi; Wei, Hui; Wang, Andrew; Farcasanu, Mara; Woods, Virgil A; McCord, Lauren A; Lee, David; Shang, Weifeng; Deprez-Poulain, Rebecca; Deprez, Benoit; Liu, David R; Koide, Akiko; Koide, Shohei; Kossiakoff, Anthony A

2018-01-01

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies. PMID:29596046

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.

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

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.

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

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

New strategy for drug discovery by large-scale association analysis of molecular networks of different species.

PubMed

Zhang, Bo; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Wu, Ziyin; Zhang, Wenjuan; Yang, Xiaoyan; Gong, Fukai; Li, Yuerong; Chen, Xiaoyu; Gao, Shuo; Chen, Xuetong; Li, Yan; Lu, Aiping; Wang, Yonghua

2016-02-25

The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.

Multi-Messenger Astronomy and Dark Matter

NASA Astrophysics Data System (ADS)

Bergström, Lars

This chapter presents the elaborated lecture notes on Multi-Messenger Astronomy and Dark Matter given by Lars Bergström at the 40th Saas-Fee Advanced Course on "Astrophysics at Very High Energies". One of the main problems of astrophysics and astro-particle physics is that the nature of dark matter remains unsolved. There are basically three complementary approaches to try to solve this problem. One is the detection of new particles with accelerators, the second is the observation of various types of messengers from radio waves to gamma-ray photons and neutrinos, and the third is the use of ingenious experiments for direct detection of dark matter particles. After giving an introduction to the particle universe, the author discusses the relic density of particles, basic cross sections for neutrinos and gamma-rays, supersymmetric dark matter, detection methods for neutralino dark matter, particular dark matter candidates, the status of dark matter detection, a detailled calculation on an hypothetical "Saas-Fee Wimp", primordial black holes, and gravitational waves.

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.

Spatial and Time Domain Feature of ERP Speller System Extracted via Convolutional Neural Network.

PubMed

Yoon, Jaehong; Lee, Jungnyun; Whang, Mincheol

2018-01-01

Feature of event-related potential (ERP) has not been completely understood and illiteracy problem remains unsolved. To this end, P300 peak has been used as the feature of ERP in most brain-computer interface applications, but subjects who do not show such peak are common. Recent development of convolutional neural network provides a way to analyze spatial and temporal features of ERP. Here, we train the convolutional neural network with 2 convolutional layers whose feature maps represented spatial and temporal features of event-related potential. We have found that nonilliterate subjects' ERP show high correlation between occipital lobe and parietal lobe, whereas illiterate subjects only show correlation between neural activities from frontal lobe and central lobe. The nonilliterates showed peaks in P300, P500, and P700, whereas illiterates mostly showed peaks in around P700. P700 was strong in both subjects. We found that P700 peak may be the key feature of ERP as it appears in both illiterate and nonilliterate subjects.

Spatial and Time Domain Feature of ERP Speller System Extracted via Convolutional Neural Network

PubMed Central

2018-01-01

Feature of event-related potential (ERP) has not been completely understood and illiteracy problem remains unsolved. To this end, P300 peak has been used as the feature of ERP in most brain–computer interface applications, but subjects who do not show such peak are common. Recent development of convolutional neural network provides a way to analyze spatial and temporal features of ERP. Here, we train the convolutional neural network with 2 convolutional layers whose feature maps represented spatial and temporal features of event-related potential. We have found that nonilliterate subjects' ERP show high correlation between occipital lobe and parietal lobe, whereas illiterate subjects only show correlation between neural activities from frontal lobe and central lobe. The nonilliterates showed peaks in P300, P500, and P700, whereas illiterates mostly showed peaks in around P700. P700 was strong in both subjects. We found that P700 peak may be the key feature of ERP as it appears in both illiterate and nonilliterate subjects.

The origin of workplace bullying: experiences from the perspective of bully victims in the public service sector.

PubMed

K, Margaretha Strandmark; Hallberg, Lillemor R-M

2007-04-01

Workplace bullying has attracted increased attention during the last decade due to its severe consequences on health. However, the origin of bullying has, so far, been insufficiently described. This study investigates the manner in which bullying is initiated at workplaces in the public service sector. Twenty-two bully victims were interviewed in-depth and data were analysed according to grounded theory methodology. The findings of this study demonstrated that bullying was preceded by a long-standing struggle for power. This power struggle emanated from conflicts of values caused by organizational conditions, leadership styles and the involved parties' work expectations. In particular, individuals who perceived themselves as strong and competent or as vulnerable and sensitive persons were targeted in these types of power struggles. In these cases, if values conflicts were solved, the power struggle ebbed. When values conflicts remained unsolved, the gap widened between the targeted individual and that person's opponents. Thereby, the conflict escalated and grew into one characterized by systematic and persistent bullying.

Algae biomass as a precursor for synthesis of nitrogen-and sulfur-co-doped carbon dots: A better probe in Arabidopsis guard cells and root tissues.

PubMed

Zhang, Che; Xiao, Yumei; Ma, Yongqiang; Li, Baoming; Liu, Zhidan; Lu, Cheng; Liu, Xue; Wei, Yao; Zhu, Zhangbing; Zhang, Yuanhui

2017-09-01

The challenge of controlling algal blooms and reusing algal biomass remain unsolved worldwide. We introduce a facile method to reuse Nannochloropsis biocrude oil (NBO) for the synthesis of nitrogen and sulfur co-doped carbon dots (N-S-C-dots). N-S-C-dots can pass through the heavily thickened wall of mature Arabidopsis thaliana (A. thaliana) guard cells because of high solubility and excellent biocompatibility. N-S-C-dots exhibit multicolor luminescence and could effectively reduce the interference of autofluorescence in plant cells by changing filters. Bioimaging of root tissues reveals that 2 major factors affect the transmission of N-S-C-dots: high osmotic pressure and intensity of cellular metabolism. This study highlights the potential application of CDs for bioimaging in plant cells and demonstrates the significance of investigating the reuse of algal biomass. Copyright © 2017. Published by Elsevier B.V.

Evidence for short-range magnetic order in the nematic phase of FeSe from anisotropic in-plane magnetostriction and susceptibility measurements

NASA Astrophysics Data System (ADS)

He, Mingquan; Wang, Liran; Hardy, Frédéric; Xu, Liping; Wolf, Thomas; Adelmann, Peter; Meingast, Christoph

2018-03-01

The nature of the nematic state in FeSe remains one of the major unsolved mysteries in Fe-based superconductors. Both spin and orbital physics have been invoked to explain the origin of this phase. Here we present experimental evidence for frustrated, short-range magnetic order, as suggested by several recent theoretical works, in the nematic state of FeSe. We use a combination of magnetostriction, susceptibility, and resistivity measurements to probe the in-plane anisotropies of the nematic state and its associated fluctuations. Despite the absence of long-range magnetic order in FeSe, we observe a sizable in-plane magnetic susceptibility anisotropy, which is responsible for the field-induced in-plane distortion inferred from magnetostriction measurements. Further we demonstrate that all three anisotropies in FeSe are very similar to those of BaFe2As2 , which strongly suggests that the nematic phase in FeSe is also of magnetic origin.

Membrane fouling control using a rotary disk in a submerged anaerobic membrane sponge bioreactor.

PubMed

Kim, Jungmin; Shin, Jaewon; Kim, Hyemin; Lee, Jung-Yeol; Yoon, Min-Hyuk; Won, Seyeon; Lee, Byung-Chan; Song, Kyung Guen

2014-11-01

Despite significant research efforts over the last few decades, membrane fouling in anaerobic membrane bioreactors (AnMBRs) remains an unsolved problem that increases the overall operational costs and obstructs the industrial applications. Herein, we developed a method for effectively controlling the membrane fouling in a sponge-submerged AnMBRs using an anaerobic rotary disk MBR (ARMBR). The disk rotation led the effective collision between the sponge and membrane surface; thus successfully enhanced the membrane permeability in the ARMBR. The effect of the disk rotational speed and sponge volume fraction on the membrane permeability and the relationship between the water flow direction and membrane permeability were investigated. The long-term feasibility was tested over 100days of synthetic wastewater treatment. As a result, stable and economical performance was observed without membrane replacement and washing. The proposed integrated rotary disk-supporting media appears to be a feasible and even beneficial option in the AnMBR technology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes.

PubMed

Nielsen, H Bjørn; Almeida, Mathieu; Juncker, Agnieszka Sierakowska; Rasmussen, Simon; Li, Junhua; Sunagawa, Shinichi; Plichta, Damian R; Gautier, Laurent; Pedersen, Anders G; Le Chatelier, Emmanuelle; Pelletier, Eric; Bonde, Ida; Nielsen, Trine; Manichanh, Chaysavanh; Arumugam, Manimozhiyan; Batto, Jean-Michel; Quintanilha Dos Santos, Marcelo B; Blom, Nikolaj; Borruel, Natalia; Burgdorf, Kristoffer S; Boumezbeur, Fouad; Casellas, Francesc; Doré, Joël; Dworzynski, Piotr; Guarner, Francisco; Hansen, Torben; Hildebrand, Falk; Kaas, Rolf S; Kennedy, Sean; Kristiansen, Karsten; Kultima, Jens Roat; Léonard, Pierre; Levenez, Florence; Lund, Ole; Moumen, Bouziane; Le Paslier, Denis; Pons, Nicolas; Pedersen, Oluf; Prifti, Edi; Qin, Junjie; Raes, Jeroen; Sørensen, Søren; Tap, Julien; Tims, Sebastian; Ussery, David W; Yamada, Takuji; Renault, Pierre; Sicheritz-Ponten, Thomas; Bork, Peer; Wang, Jun; Brunak, Søren; Ehrlich, S Dusko

2014-08-01

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a largely unsolved problem. Here we present a method, based on binning co-abundant genes across a series of metagenomic samples, that enables comprehensive discovery of new microbial organisms, viruses and co-inherited genetic entities and aids assembly of microbial genomes without the need for reference sequences. We demonstrate the method on data from 396 human gut microbiome samples and identify 7,381 co-abundance gene groups (CAGs), including 741 metagenomic species (MGS). We use these to assemble 238 high-quality microbial genomes and identify affiliations between MGS and hundreds of viruses or genetic entities. Our method provides the means for comprehensive profiling of the diversity within complex metagenomic samples.

[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.

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.

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.

On the cosmic ray spectrum from type II supernovae expanding in their red giant presupernova wind

NASA Astrophysics Data System (ADS)

Cardillo, Martina; Amato, Elena; Blasi, Pasquale

2015-09-01

While from the energetic point of view supernova remnants are viable sources of Galactic cosmic rays (CRs), the issue of whether they can accelerate protons up to a few PeV remains unsolved. Here we discuss particle acceleration at the forward shock of supernovae, and discuss the possibility that the current of escaping particles may excite a non-resonant instability that in turn leads to the formation of resonant modes that confine particles close to the shock, thereby increasing the maximum energy. This mechanism is at work throughout the expansion of the supernova explosion, from the ejecta dominated (ED) phase to the Sedov-Taylor (ST) phase. The transition from one stage to the other reflects in a break in the spectrum of injected particles. Because of their higher explosion rate, we focus our work on type II SNe expanding in the slow, dense wind, produced by the red super-giant progenitor stars. When the explosion occurs in such winds, the transition between the ED and the ST phase is likely to take place within a few tens of years. The highest energies are reached at even earlier times, when, however, a small fraction of the mass of ejecta has been processed. As a result, the spectrum of accelerated particles shows a break in the slope, at an energy that is the maximum energy (EM) achieved at the beginning of the ST phase. Above this characteristic energy, the spectrum becomes steeper but remains a power law rather than developing an exponential cutoff. An exponential cut is eventually present at much higher energies but it does not have a phenomenological relevance. We show that for parameters typical of type II supernovae, EM for protons can easily reach values in the PeV range, confirming that type II SNRs are the best candidate sources for CRs at the knee. From the point of view of implications of this scenario on the measured particle spectra, we have tried to fit KASCADE-Grande, ARGO -YBJ and YAC1-Tibet Array data with our model but we could not find any combination of the parameters that could explain all data sets. Indeed the recent measurement of the proton and helium spectra in the knee region, with the ARGO-YBJ and YAC1-Tibet Array, has made the situation very confused. These measurements suggest that the knee in the light component is at ∼ 650 TeV, appreciably below the knee in the overall spectrum. On one hand this finding would resolve the problem of reaching very high energies in supernovae, but on the other it would open a critical issue in the transition region between Galactic and extragalactic CRs.

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.

Big pharma and health care: unsolvable conflict of interests between private enterprise and public health.

PubMed

Brezis, Mayer

2008-01-01

A landmark paper on Game Theory showed that individual maximization of profit necessarily endangers the public good, and since the problem has no technical solution, "it requires a fundamental extension in morality" (1). We propose here that public health, as a public good, now emerges as a grave example of this problem. Recent events and reports increasingly suggest misalignment between the interests of the pharmaceutical industry and those of public health. Johnson & Johnson illegally and effectively promoted Propulsid off-label for children despite internal company documents raising safety concerns. Death in drug trial has been described as a "trade secret." On Vioxx, Topol wrote: "Sadly, it is clear that Merck's commercial interest exceeded its concern about the drug's toxicity" (2). More and more concerns are raised by scholars and major journal editors about the type and the quality of published evidence, often biased towards efficacy of new products. The industry, funding over 80% of trials, sets up a research agenda guided more by marketing than by clinical considerations. Smart statistical and epidemiological tactics help obtain the desired results. Budget for marketing is by far greater than for research. Massive advertising to physicians and to the public gets increasingly sophisticated: ghost writing, professional guidelines, targeting of consumer groups and manipulating media for disease mongering. Pervasive lobbying and political ties limit the independence of regulatory bodies. Obligation to shareholders overriding public health considerations is not unique to the pharmaceutical industry. The chemical, tobacco and food industries share similar tactics: proclaiming doubts about safety issues, buying researchers, infiltrating universities, boards, media and legislative agencies. By contrast, powerful and cheap health promoting activities, poorly supported by industry because they are too cheap and not patented, are markedly underutilized: technologies for changing behavior (e.g., cardiac rehabilitation), palliative care and use of old, effective and safe drugs - all could benefit from industry's tools of marketing and quality. As those most affected are the sick, the poor and the least educated, free market successes appear to pose unsolvable challenges to social justice in public health.

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…

Instantaneous velocity measurement of AC electroosmotic flows by laser induced fluorescence photobleaching anemometer with high temporal resolution

NASA Astrophysics Data System (ADS)

Zhao, Wei; Yang, Fang; Qiao, Rui; Wang, Guiren; Rui Qiao Collaboration

2015-11-01

Understanding the instantaneous response of flows to applied AC electric fields may help understand some unsolved issues in induced-charge electrokinetics and enhance performance of microfluidic devices. Since currently available velocimeters have difficulty in measuring velocity fluctuations with frequency higher than 1 kHz, most experimental studies so far focus only on the average velocity measurement in AC electrokinetic flows. Here, we present measurements of AC electroosmotic flow (AC-EOF) response time in microchannels by a novel velocimeter with submicrometer spatial resolution and microsecond temporal resolution, i.e. laser-induced fluorescence photobleaching anemometer (LIFPA). Several parameters affecting the AC-EOF response time to the applied electric signal were investigated, i.e. channel length, transverse position and solution conductivity. The experimental results show that the EOF response time under a pulsed electric field decreases with the reduction of the microchannel length, distance between the detection position to the wall and the conductivity of the solution. This work could provide a new powerful tool to measure AC electrokinetics and enhance our understanding of AC electrokinetic flows.

Real-world visual statistics and infants' first-learned object names.

PubMed

Clerkin, Elizabeth M; Hart, Elizabeth; Rehg, James M; Yu, Chen; Smith, Linda B

2017-01-05

We offer a new solution to the unsolved problem of how infants break into word learning based on the visual statistics of everyday infant-perspective scenes. Images from head camera video captured by 8 1/2 to 10 1/2 month-old infants at 147 at-home mealtime events were analysed for the objects in view. The images were found to be highly cluttered with many different objects in view. However, the frequency distribution of object categories was extremely right skewed such that a very small set of objects was pervasively present-a fact that may substantially reduce the problem of referential ambiguity. The statistical structure of objects in these infant egocentric scenes differs markedly from that in the training sets used in computational models and in experiments on statistical word-referent learning. Therefore, the results also indicate a need to re-examine current explanations of how infants break into word learning.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

Moving object detection using dynamic motion modelling from UAV aerial images.

PubMed

Saif, A F M Saifuddin; Prabuwono, Anton Satria; Mahayuddin, Zainal Rasyid

2014-01-01

Motion analysis based moving object detection from UAV aerial image is still an unsolved issue due to inconsideration of proper motion estimation. Existing moving object detection approaches from UAV aerial images did not deal with motion based pixel intensity measurement to detect moving object robustly. Besides current research on moving object detection from UAV aerial images mostly depends on either frame difference or segmentation approach separately. There are two main purposes for this research: firstly to develop a new motion model called DMM (dynamic motion model) and secondly to apply the proposed segmentation approach SUED (segmentation using edge based dilation) using frame difference embedded together with DMM model. The proposed DMM model provides effective search windows based on the highest pixel intensity to segment only specific area for moving object rather than searching the whole area of the frame using SUED. At each stage of the proposed scheme, experimental fusion of the DMM and SUED produces extracted moving objects faithfully. Experimental result reveals that the proposed DMM and SUED have successfully demonstrated the validity of the proposed methodology.

Some thoughts on building, evaluating and constraining hydrologic models from catchment to continental scales

NASA Astrophysics Data System (ADS)

Wagener, Thorsten

2017-04-01

We increasingly build and apply hydrologic models that simulate systems beyond the catchment scale. Such models run at regional, national or even continental scales. They therefore offer opportunities for new scientific insights, for example by enabling comparative hydrology or connectivity studies, and for water management, where we might better understand changes to water resources from larger scale activities like agriculture or from hazards such as droughts. However, these models also require us to rethink how we build and evaluate them given that some of the unsolved problems from the catchment scale have not gone away. So what role should such models play in scientific advancement in hydrology? What problems do we still have to resolve before they can fulfill their role? What opportunities for solving these problems are there, but have not yet been utilized? I will provide some thoughts on these issues in the context of the IAHS Panta Rhei initiative and the scientific challenges it has set out for hydrology (Montanari et al., 2013, Hydrological Sciences Journal; McMillan et al., 2016, Hydrological Sciences Journal).

The "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study: Rationale, design and methods.

PubMed

Calvani, Riccardo; Picca, Anna; Marini, Federico; Biancolillo, Alessandra; Cesari, Matteo; Pesce, Vito; Lezza, Angela Maria Serena; Bossola, Maurizio; Leeuwenburgh, Christiaan; Bernabei, Roberto; Landi, Francesco; Marzetti, Emanuele

2018-05-10

Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

A novel and lightweight system to secure wireless medical sensor networks.

PubMed

He, Daojing; Chan, Sammy; Tang, Shaohua

2014-01-01

Wireless medical sensor networks (MSNs) are a key enabling technology in e-healthcare that allows the data of a patient's vital body parameters to be collected by the wearable or implantable biosensors. However, the security and privacy protection of the collected data is a major unsolved issue, with challenges coming from the stringent resource constraints of MSN devices, and the high demand for both security/privacy and practicality. In this paper, we propose a lightweight and secure system for MSNs. The system employs hash-chain based key updating mechanism and proxy-protected signature technique to achieve efficient secure transmission and fine-grained data access control. Furthermore, we extend the system to provide backward secrecy and privacy preservation. Our system only requires symmetric-key encryption/decryption and hash operations and is thus suitable for the low-power sensor nodes. This paper also reports the experimental results of the proposed system in a network of resource-limited motes and laptop PCs, which show its efficiency in practice. To the best of our knowledge, this is the first secure data transmission and access control system for MSNs until now.

From structure from motion to historical building information modeling: populating a semantic-aware library of architectural elements

NASA Astrophysics Data System (ADS)

Santagati, Cettina; Lo Turco, Massimiliano

2017-01-01

In recent years, we have witnessed a huge diffusion of building information modeling (BIM) approaches in the field of architectural design, although very little research has been undertaken to explore the value, criticalities, and advantages attributable to the application of these methodologies in the cultural heritage domain. Furthermore, the last developments in digital photogrammetry lead to the easy generation of reliable low-cost three-dimensional textured models that could be used in BIM platforms to create semantic-aware objects that could compose a specific library of historical architectural elements. In this case, the transfer between the point cloud and its corresponding parametric model is not so trivial and the level of geometrical abstraction could not be suitable with the scope of the BIM. The aim of this paper is to explore and retrace the milestone works on this crucial topic in order to identify the unsolved issues and to propose and test a unique and simple workflow practitioner centered and based on the use of the latest available solutions for point cloud managing into commercial BIM platforms.

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

Morality Principles for Risk Modelling: Needs and Links with the Origins of Plausible Inference

NASA Astrophysics Data System (ADS)

Solana-Ortega, Alberto; Solana, Vicente

2009-12-01

In comparison with the foundations of probability calculus, the inescapable and controversial issue of how to assign probabilities has only recently become a matter of formal study. The introduction of information as a technical concept was a milestone, but the most promising entropic assignment methods still face unsolved difficulties, manifesting the incompleteness of plausible inference theory. In this paper we examine the situation faced by risk analysts in the critical field of extreme events modelling, where the former difficulties are especially visible, due to scarcity of observational data, the large impact of these phenomena and the obligation to assume professional responsibilities. To respond to the claim for a sound framework to deal with extremes, we propose a metafoundational approach to inference, based on a canon of extramathematical requirements. We highlight their strong moral content, and show how this emphasis in morality, far from being new, is connected with the historic origins of plausible inference. Special attention is paid to the contributions of Caramuel, a contemporary of Pascal, unfortunately ignored in the usual mathematical accounts of probability.

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…

Comparison of mediastinal lymph node status and relapse pattern in clinical stage IIIA non-small cell lung cancer patients treated with neoadjuvant chemotherapy versus upfront surgery: A single center experience.

PubMed

Savic, Milan; Kontic, Milica; Ercegovac, Maja; Stojsic, Jelena; Bascarevic, Slavisa; Moskovljevic, Dejan; Kostic, Marko; Vesovic, Radomir; Popevic, Spasoje; Laban, Marija; Markovic, Jelena; Jovanovic, Dragana

2017-09-01

In spite of the progress made in neoadjuvant therapy for operable non small-cell lung cancer (NSCLC), many issues remain unsolved, especially in locally advanced stage IIIA. Retrospective data of 163 patients diagnosed with stage IIIA NSCLC after surgery was analyzed. The patients were divided into two groups: a preoperative chemotherapy group including 59 patients who received platinum-etoposide doublet treatment before surgery, and an upfront surgery group including 104 patients for whom surgical resection was the first treatment step. Adjuvant chemotherapy or/and radiotherapy was administered to 139 patients (85.3%), while 24 patients (14.7%) were followed-up only. The rate of N2 disease was significantly higher in the upfront surgery group ( P  < 0.001). The one-year relapse rate was 49.5% in the preoperative chemotherapy group compared to 65.4% in the upfront surgery group. There was a significant difference in relapse rate in relation to adjuvant chemotheraphy treatment ( P  = 0.007). The probability of relapse was equal whether radiotherapy was applied or not ( P  = 0.142). There was no statistically significant difference in two-year mortality ( P  = 0.577). The median survival duration after two years of follow-up was 19.6 months in the preoperative chemotherapy group versus 18.8 months in the upfront surgery group ( P  = 0.608 > 0.05). There was significant difference in preoperative chemotherapy group regarding relapse rate and treatment outcomes related to the lymph node status comparing to the upfront surgery group. Neoadjuvant/adjuvant chemo-therapy is a part of treatment for patients with stage IIIA NSCLC, but further investigation is required to determine optimal treatment. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Metabolic control of puberty: roles of leptin and kisspeptins.

PubMed

Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin and putatively related pathways in the concerted control of puberty by energy balance and metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

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 gradient-boosting approach for filtering de novo mutations in parent-offspring trios.

PubMed

Liu, Yongzhuang; Li, Bingshan; Tan, Renjie; Zhu, Xiaolin; Wang, Yadong

2014-07-01

Whole-genome and -exome sequencing on parent-offspring trios is a powerful approach to identifying disease-associated genes by detecting de novo mutations in patients. Accurate detection of de novo mutations from sequencing data is a critical step in trio-based genetic studies. Existing bioinformatic approaches usually yield high error rates due to sequencing artifacts and alignment issues, which may either miss true de novo mutations or call too many false ones, making downstream validation and analysis difficult. In particular, current approaches have much worse specificity than sensitivity, and developing effective filters to discriminate genuine from spurious de novo mutations remains an unsolved challenge. In this article, we curated 59 sequence features in whole genome and exome alignment context which are considered to be relevant to discriminating true de novo mutations from artifacts, and then employed a machine-learning approach to classify candidates as true or false de novo mutations. Specifically, we built a classifier, named De Novo Mutation Filter (DNMFilter), using gradient boosting as the classification algorithm. We built the training set using experimentally validated true and false de novo mutations as well as collected false de novo mutations from an in-house large-scale exome-sequencing project. We evaluated DNMFilter's theoretical performance and investigated relative importance of different sequence features on the classification accuracy. Finally, we applied DNMFilter on our in-house whole exome trios and one CEU trio from the 1000 Genomes Project and found that DNMFilter could be coupled with commonly used de novo mutation detection approaches as an effective filtering approach to significantly reduce false discovery rate without sacrificing sensitivity. The software DNMFilter implemented using a combination of Java and R is freely available from the website at http://humangenome.duke.edu/software. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Heterogeneous sharpness for cross-spectral face recognition

NASA Astrophysics Data System (ADS)

Cao, Zhicheng; Schmid, Natalia A.

2017-05-01

Matching images acquired in different electromagnetic bands remains a challenging problem. An example of this type of comparison is matching active or passive infrared (IR) against a gallery of visible face images, known as cross-spectral face recognition. Among many unsolved issues is the one of quality disparity of the heterogeneous images. Images acquired in different spectral bands are of unequal image quality due to distinct imaging mechanism, standoff distances, or imaging environment, etc. To reduce the effect of quality disparity on the recognition performance, one can manipulate images to either improve the quality of poor-quality images or to degrade the high-quality images to the level of the quality of their heterogeneous counterparts. To estimate the level of discrepancy in quality of two heterogeneous images a quality metric such as image sharpness is needed. It provides a guidance in how much quality improvement or degradation is appropriate. In this work we consider sharpness as a relative measure of heterogeneous image quality. We propose a generalized definition of sharpness by first achieving image quality parity and then finding and building a relationship between the image quality of two heterogeneous images. Therefore, the new sharpness metric is named heterogeneous sharpness. Image quality parity is achieved by experimentally finding the optimal cross-spectral face recognition performance where quality of the heterogeneous images is varied using a Gaussian smoothing function with different standard deviation. This relationship is established using two models; one of them involves a regression model and the other involves a neural network. To train, test and validate the model, we use composite operators developed in our lab to extract features from heterogeneous face images and use the sharpness metric to evaluate the face image quality within each band. Images from three different spectral bands visible light, near infrared, and short-wave infrared are considered in this work. Both error of a regression model and validation error of a neural network are analyzed.

Molecular and isotope constraints on the formation of the insoluble organic matter of carbonaceous meteorites

NASA Astrophysics Data System (ADS)

Derenne, Sylvie; Robert, François

2017-04-01

The origin of the insoluble organic matter (IOM) of the carbonaceous meteorites remains an unsolved issue despite major achievements in the knowledge of its chemical structure. The latter led us to propose a model for its molecular structure. Based on the relationship between the aromatic moieties of the macromolecular structure and their aliphatic linkages, it was recently suggested that, its synthesis has taken place in the gas phase of the disk surrounding the Sun in its early T-Tauri phase and that organic radicals have played a central role in this organo-synthesis. To test experimentally this pathway, we submitted short hydrocarbons (methane, pentane, octane) to a microwave plasma discharge so as to produce in situ CHx radicals. The black organic residue deposited contained both soluble and insoluble OM. The comparison at the molecular level between the thus synthesized IOM and that of meteorite led to strong similarities thus supporting the proposed pathway for its organo-synthesis. Moreover, in the meteorite IOM, systematic deuterium enrichment relative to the protosolar value is observed at the bulk sample scale and micrometer-sized grains exhibit dramatic enrichments in deuterium interpreted as a heritage of the interstellar medium or resulting from ion-molecule reactions taking place in the diffuse part of the solar disk. In the aforementioned synthesized IOM, NanoSIMS analyses revealed large variations at a sub-micrometric spatial resolution. They likely reflect the differences in the D/H ratios of the CHx radicals whose polymerization is at the origin of the IOM. These isotopic heterogeneities are commensurable with those observed in meteorite IOM. As a consequence, the appearance of organic radicals in the ionized regions of the T-Tauri solar disk may have triggered the formation of organic compounds. This laboratory synthesis thus shed a new light on the formation conditions and pathways of the IOM of carbonaceous chondrites.

[Animal feeding and feed legislation after the detection of the first indigenous BSE cases in Germany].

PubMed

Kamphues, J

2002-08-01

In Great Britain, even the earliest tangible signs indicating the epidemiologic significance of meat and bone meal in the spreading of BSE soon gave rise to increasingly rigorous legislative measures regulating animal feedstuffs. In 1994 a ban on the feeding of animal proteins to ruminants was implemented throughout the entire EU. But until the first BSE cases were actually confirmed in locally raised cattle (November 2000), feeding practice and legislation more or less in Germany remained unaffected by the efforts undertaken in Great Britain. This situation was suddenly changed on 1 December, 2000, when the so-called "Verfütterungsverbot" was put into effect, a law which drastically extended bans regarding the feedstuffs (including fishmeal and animal fats) as well as the species concerned (all animals used in food production). In 2001 the "contamination" phenomenon (ingredients of animal origin were detected in mixed feeds) became a vital issue for the feed industry; through the media, the subject "feedstuff safety" gained a previously unseen level of public awareness. Those circles concerned with mixed feed production and animal husbandry were increasingly confronted with the consequences of the "Verfütterungsverbot" (availability and pricing of substitute ingredients; the demand for amino acids and inorganic sources of phosphorus; problems finding adequate substitutes for animal fats; poor digestibility of alternative components such as indigenous legumes or vegetable fats in calf diets; lower utilization rate of original phosphorus in mixed feeds with negative consequences for skeletal development). With the conditional approval of fishmeal (except in feeds for ruminants) the situation has eased again to a certain degree; on the EU level there are increasing signals pointing toward a political intention to reinstate the utilization of by-products of slaughtered animals qualified for human consumption (with the exception of fallen/dead animals and specific risk material) in poultry and swine feeding. In Germany, at least, the question of animal fat utilization for food-producing animals is still unsolved.

The Conference Proceedings of the 1999 Air Transport Research Group (ATRG) of the WCTR Society. Volume 4

NASA Technical Reports Server (NTRS)

Zhang, Anming (Editor); Bowen, Brent D. (Editor)

1999-01-01

Issues around direct flights across Taiwan Strait are always one of the hottest topics in eastern Asia transport market. Although the direct links have not been connected yet, they are still highly concerned by different disciplines of politics, laws, and management. Airlines and related business also watch closely to these issues for policy changes will easily affect their interests in Chinese market which the future of the air transportation in eastern Asia is heavily depending on. In the past decades, Hong Kong was the most important hub in this market; it will still be an important one in the future. It is proved, however, traffic on the link between Hong Kong and Taiwan can be shifted to the link between Macau and Taiwan, so can it be shifted to the links across Taiwan Strait. Moreover, outgoing passengers from China transferred in Hong Kong can also find transit services in Taiwan. These movements will possibly cause a big change in eastern Asian air transport system for there are millions of passengers travelling in this area. The uncertainties of direct links across Taiwan Strait are still leaving, some problems unsolved. Whether the direct links will be defined as international routes or domestic' routes are not clear; the selection of hubs and airlines to provide direct services are not yet made; even the type of freedoms and bilateral agreements can also change the market and network quite a lot. A much bigger volume of passengers can also be found if further travelling deregulation for Chinese to travel across Taiwan Strait can be made. All these variables are making issues around direct flights worthy of continuous observant.

Ethical Issues Surrounding the Use of Modern Human Remains for Research in South Africa.

PubMed

Briers, N; Dempers, J J

2017-02-01

Chapter 8 of the South African National Health Act 61 of 2003 (NHA) that deals with the donation of human tissue was promulgated in 2012. The new Act is perceived to impose restrictions on low-risk research involving human remains. This study aimed to identify the issues raised by a research ethics committee (REC) when reviewing protocols where human remains are used as data source. REC minutes from 2009 to 2014 were reviewed, and issues raised by the committee were categorized. In total, 127 protocols submitted to the committee over 6 years involved human remains. Queries relating to science (22.2%) and administration (18.9%) were the most common, whereas queries relating to legal issues constituted only 10.2%. Ethical issues centered on informed consent regarding sensitive topics such as HIV, DNA, and deceased children. The change in legislation did not change the number or type of legal issues identified by the REC.

Helminths and Cancers From the Evolutionary Perspective.

PubMed

Scholte, Larissa L S; Pascoal-Xavier, Marcelo A; Nahum, Laila A

2018-01-01

Helminths include free-living and parasitic Platyhelminthes and Nematoda which infect millions of people worldwide. Some Platyhelminthes species of blood flukes ( Schistosoma haematobium, Schistosoma japonicum , and Schistosoma mansoni ) and liver flukes ( Clonorchis sinensis and Opisthorchis viverrini ) are known to be involved in human cancers. Other helminths are likely to be carcinogenic. Our main goals are to summarize the current knowledge of human cancers caused by Platyhelminthes, point out some helminth and human biomarkers identified so far, and highlight the potential contributions of phylogenetics and molecular evolution to cancer research. Human cancers caused by helminth infection include cholangiocarcinoma, colorectal hepatocellular carcinoma, squamous cell carcinoma, and urinary bladder cancer. Chronic inflammation is proposed as a common pathway for cancer initiation and development. Furthermore, different bacteria present in gastric, colorectal, and urogenital microbiomes might be responsible for enlarging inflammatory and fibrotic responses in cancers. Studies have suggested that different biomarkers are involved in helminth infection and human cancer development; although, the detailed mechanisms remain under debate. Different helminth proteins have been studied by different approaches. However, their evolutionary relationships remain unsolved. Here, we illustrate the strengths of homology identification and function prediction of uncharacterized proteins from genome sequencing projects based on an evolutionary framework. Together, these approaches may help identifying new biomarkers for disease diagnostics and intervention measures. This work has potential applications in the field of phylomedicine (evolutionary medicine) and may contribute to parasite and cancer research.

On the consistency of the Oppenheimer-Snyder solution for a dust star. Reply to Marshall's criticism

NASA Astrophysics Data System (ADS)

Zakir, Zahid

2018-02-01

The recent alternative to the Oppenheimer-Snyder (OS) solution for a dust star proposed by Marshall in the paper "Gravitational collapse without black holes" (Astrophys. Space Sci. 342:329, 2012) is analyzed. It is shown that this proposal leads to a non-diagonal metric, with which the Einstein equations become practically unsolvable. Any ansatz proposed as their exact solution turns out to be arbitrary and may be unlimited number of the such solutions. This is due to the fact that an auxiliary function y(R,r), introduced by OS as t=M(y), is unambiguously fixed by the diagonality condition and the matching on the surface, and thus in the non-diagonal case it remains arbitrary. It is also shown that the OS solution, as a description in terms of the Schwarzschild coordinates, leads to a frozen star (or frozar) picture not only for the surface, asymptotically freezing outside the gravitational radius, but for interior layers too which also freeze near their own asymptotes. At most of the inner region these asymptotes are located almost equidistantly and only for layers initially close to the surface they become denser. The reason for the such densifying is not "a gravitational repulsion", but their later freezing and higher spatial contractions, while they remain be uniform and free falling in the comoving frames.

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

Improvement of Cell Survival During Human Pluripotent Stem Cell Definitive Endoderm Differentiation

PubMed Central

Wang, Han; Luo, Xie; Yao, Li; Lehman, Donna M.

2015-01-01

Definitive endoderm (DE) is a vital precursor for internal organs such as liver and pancreas. Efficient protocol to differentiate human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) to DE is essential for regenerative medicine and for modeling diseases; yet, poor cell survival during DE differentiation remains unsolved. In this study, our use of B27 supplement in modified differentiation protocols has led to a substantial improvement. We used an SOX17-enhanced green fluorescent protein (eGFP) reporter hESC line to compare and modify established DE differentiation protocols. Both total live cell numbers and the percentages of eGFP-positive cells were used to assess differentiation efficiency. Among tested protocols, three modified protocols with serum-free B27 supplement were developed to generate a high number of DE cells. Massive cell death was avoided during DE differentiation and the percentage of DE cells remained high. When the resulting DE cells were further differentiated toward the pancreatic lineage, the expression of pancreatic-specific markers was significantly increased. Similar high DE differentiation efficiency was observed in H1 hESCs and iPSCs through the modified protocols. In B27 components, bovine serum albumin was found to facilitate DE differentiation and cell survival. Using our modified DE differentiation protocols, satisfactory quantities of quality DE can be produced as primary material for further endoderm lineage differentiation. PMID:26132288

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,…

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.

Understanding plant reproductive diversity.

PubMed

Barrett, Spencer C H

2010-01-12

Flowering plants display spectacular floral diversity and a bewildering array of reproductive adaptations that promote mating, particularly outbreeding. A striking feature of this diversity is that related species often differ in pollination and mating systems, and intraspecific variation in sexual traits is not unusual, especially among herbaceous plants. This variation provides opportunities for evolutionary biologists to link micro-evolutionary processes to the macro-evolutionary patterns that are evident within lineages. Here, I provide some personal reflections on recent progress in our understanding of the ecology and evolution of plant reproductive diversity. I begin with a brief historical sketch of the major developments in this field and then focus on three of the most significant evolutionary transitions in the reproductive biology of flowering plants: the pathway from outcrossing to predominant self-fertilization, the origin of separate sexes (females and males) from hermaphroditism and the shift from animal pollination to wind pollination. For each evolutionary transition, I consider what we have discovered and some of the problems that still remain unsolved. I conclude by discussing how new approaches might influence future research in plant reproductive biology.

Proline dehydrogenase promotes senescence through the generation of reactive oxygen species.

PubMed

Nagano, Taiki; Nakashima, Akio; Onishi, Kengo; Kawai, Kosuke; Awai, Yuto; Kinugasa, Mizuki; Iwasaki, Tetsushi; Kikkawa, Ushio; Kamada, Shinji

2017-04-15

Cellular senescence is a complex stress response characterized by permanent loss of proliferative capacity and is implicated in age-related disorders. Although the transcriptional activity of p53 (encoded by TP53 ) is known to be vital for senescence induction, the downstream effector genes critical for senescence remain unsolved. Recently, we have identified the proline dehydrogenase gene ( PRODH ) to be upregulated specifically in senescent cells in a p53-dependent manner, and the functional relevance of this to senescence is yet to be defined. Here, we conducted functional analyses to explore the relationship between PRODH and the senescence program. We found that genetic and pharmacological inhibition of PRODH suppressed senescent phenotypes induced by DNA damage. Furthermore, ectopic expression of wild-type PRODH, but not enzymatically inactive forms, induced senescence associated with the increase in reactive oxygen species (ROS) and the accumulation of DNA damage. Treatment with N-acetyl-L-cysteine, a ROS scavenger, prevented senescence induced by PRODH overexpression. These results indicate that PRODH plays a causative role in DNA damage-induced senescence through the enzymatic generation of ROS. © 2017. Published by The Company of Biologists Ltd.

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.

Local sensitivities of the gulf stream separation

DOE PAGES

Schoonover, Joseph; Dewar, William K.; Wienders, Nicolas; ...

2016-12-05

Robust and accurate Gulf Stream separation remains an unsolved problem in general circulation modeling whose resolution will positively impact the ocean and climate modeling communities. Oceanographic literature does not face a shortage of plausible hypotheses that attempt to explain the dynamics of the Gulf Stream separation, yet a single theory that the community agrees on is missing. We investigate the impact of the Deep Western Boundary Current, coastline curvature, and continental shelf steepening on the Gulf Stream separation within regional configurations of the MIT General Circulation Model. Artificial modifications to the regional bathymetry are introduced to investigate the sensitivity ofmore » the separation to each of these factors. Metrics for subsurface separation detection confirm the direct link between flow separation and the surface expression of the Gulf Stream in the Mid-Atlantic Bight. Conversely, the Gulf Stream separation exhibits minimal sensitivity to the presence of the DWBC and coastline curvature. The implications of these results to the development of a “separation recipe” for ocean modeling are discussed. Furthermore, we conclude adequate topographic resolution is a necessary, but not sufficient, condition for proper Gulf Stream separation.« less

A homozygous NOP14 variant is likely to cause recurrent pregnancy loss.

PubMed

Suzuki, Toshifumi; Behnam, Mahdiyeh; Ronasian, Firooze; Salehi, Mansoor; Shiina, Masaaki; Koshimizu, Eriko; Fujita, Atsushi; Sekiguchi, Futoshi; Miyatake, Satoko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Ogata, Kazuhiro; Takeda, Satoru; Matsumoto, Naomichi; Miyake, Noriko

2018-04-01

Recurrent pregnancy loss is newly defined as more than two consecutive miscarriages. Recurrent pregnancy loss occurs in <5% of total pregnancies. The cause in approximately 40-60% of recurrent pregnancy loss cases remains elusive and must be determined. We investigated two unrelated Iranian consanguineous families with recurrent pregnancy loss. We performed exome sequencing using DNA from a miscarriage tissue and identified a homozygous NOP14 missense variant (c.[136C>G];[136C>G]) in both families. NOP14 is an evolutionally conserved protein among eukaryotes and is required for 18S rRNA processing and 40S ribosome biogenesis. Interestingly, in zebrafish, homozygous mutation of nop14 (possibly loss of function) resulting from retrovirus-mediated insertional mutagenesis led to embryonic lethality at 5 days after fertilization, mimicking early pregnancy loss in humans. Similarly, it is known that the nop14-null yeast is inviable. These data suggest that the homozygous NOP14 mutation is likely to cause recurrent pregnancy loss. Furthermore, this study shows that exome sequencing is very useful to determine the etiology of unsolved recurrent pregnancy loss.

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

Schoonover, Joseph; Dewar, William K.; Wienders, Nicolas

Robust and accurate Gulf Stream separation remains an unsolved problem in general circulation modeling whose resolution will positively impact the ocean and climate modeling communities. Oceanographic literature does not face a shortage of plausible hypotheses that attempt to explain the dynamics of the Gulf Stream separation, yet a single theory that the community agrees on is missing. We investigate the impact of the Deep Western Boundary Current, coastline curvature, and continental shelf steepening on the Gulf Stream separation within regional configurations of the MIT General Circulation Model. Artificial modifications to the regional bathymetry are introduced to investigate the sensitivity ofmore » the separation to each of these factors. Metrics for subsurface separation detection confirm the direct link between flow separation and the surface expression of the Gulf Stream in the Mid-Atlantic Bight. Conversely, the Gulf Stream separation exhibits minimal sensitivity to the presence of the DWBC and coastline curvature. The implications of these results to the development of a “separation recipe” for ocean modeling are discussed. Furthermore, we conclude adequate topographic resolution is a necessary, but not sufficient, condition for proper Gulf Stream separation.« less

Metamaterials: supra-classical dynamic homogenization

NASA Astrophysics Data System (ADS)

Caleap, Mihai; Drinkwater, Bruce W.

2015-12-01

Metamaterials are artificial composite structures designed for controlling waves or fields, and exhibit interaction phenomena that are unexpected on the basis of their chemical constituents. These phenomena are encoded in effective material parameters that can be electronic, magnetic, acoustic, or elastic, and must adequately represent the wave interaction behavior in the composite within desired frequency ranges. In some cases—for example, the low frequency regime—there exist various efficient ways by which effective material parameters for wave propagation in metamaterials may be found. However, the general problem of predicting frequency-dependent dynamic effective constants has remained unsolved. Here, we obtain novel mathematical expressions for the effective parameters of two-dimensional metamaterial systems valid at higher frequencies and wavelengths than previously possible. By way of an example, random configurations of cylindrical scatterers are considered, in various physical contexts: sound waves in a compressible fluid, anti-plane elastic waves, and electromagnetic waves. Our results point towards a paradigm shift in our understanding of these effective properties, and metamaterial designs with functionalities beyond the low-frequency regime are now open for innovation. Dedicated with gratitude to the memory of Prof Yves C Angel.

Three friendly walkers

NASA Astrophysics Data System (ADS)

Jensen, Iwan

2017-01-01

More than 15 years ago Guttmann and Vöge (2002 J. Stat. Plan. Inference 101 107), introduced a model of friendly walkers. Since then it has remained unsolved. In this paper we provide the exact solution to a closely allied model which essentially only differs in the boundary conditions. The exact solution is expressed in terms of the reciprocal of the generating function for vicious walkers which is a D-finite function. However, ratios of D-finite functions are inherently not D-finite and in this case we prove that the friendly walkers generating function is the solution to a non-linear differential equation with polynomial coefficients, it is in other words D-algebraic. We find using numerically exact calculations a conjectured expression for the generating function of the original model as a ratio of a D-finite function and the generating function for vicious walkers. We obtain an expression for this D-finite function in terms of a {{}2}{{F}1} hypergeometric function with a rational pullback and its first and second derivatives. Dedicated to Tony Guttmann on the occasion of his 70th birthday.

Functional end-arterial circulation of the choroid assessed by using fat embolism and electric circuit simulation.

PubMed

Lee, Ji Eun; Ahn, Ki Su; Park, Keun Heung; Pak, Kang Yeun; Kim, Hak Jin; Byon, Ik Soo; Park, Sung Who

2017-05-30

The discrepancy in the choroidal circulation between anatomy and function has remained unsolved for several decades. Postmortem cast studies revealed extensive anastomotic channels, but angiographic studies indicated end-arterial circulation. We carried out experimental fat embolism in cats and electric circuit simulation. Perfusion defects were observed in two categories. In the scatter perfusion defects suggesting an embolism at the terminal arterioles, fluorescein dye filled the non-perfused lobule slowly from the adjacent perfused lobule. In the segmental perfusion defects suggesting occlusion of the posterior ciliary arteries, the hypofluorescent segment became perfused by spontaneous resolution of the embolism without subsequent smaller infarction. The angiographic findings could be simulated with an electric circuit. Although electric currents flowed to the disconnected lobule, the level was very low compared with that of the connected ones. The choroid appeared to be composed of multiple sectors with no anastomosis to other sectors, but to have its own anastomotic arterioles in each sector. Blood flows through the continuous choriocapillaris bed in an end-arterial nature functionally to follow a pressure gradient due to the drainage through the collector venule.

The Basal Ganglia-Circa 1982

NASA Technical Reports Server (NTRS)

Mehler, William R.

1981-01-01

Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

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

Defending the beauty of the Invariance Principle

NASA Astrophysics Data System (ADS)

Barkana, Itzhak

2014-01-01

Customary stability analysis methods for nonlinear nonautonomous systems seem to require a strict condition of uniform continuity. Although extensions of LaSalle's Invariance Principle to nonautonomous systems that mitigate this condition have been available for a long time, they have remained surprisingly unknown or open to misinterpretations. The large scope of the Principle might have misled the prospective users and its application to Control problems has been received with amazing yet clear uneasiness. Counterexamples have been used in order to claim that the Invariance Principle cannot be applied to nonlinear nonautonomous systems. Because the original formulation of the Invariance Principle still imposes conditions that are not necessarily needed, this paper presents a new Invariance Principle that further mitigates previous conditions and thus further expands the scope of stability analysis. A brief comparative review of various alternatives to stability analysis of nonautonomous nonlinear systems and their implications is also presented in order to illustrate that thorough analysis of same examples may actually confirm the efficiency of the Invariance Principle approach when dealing with stability of nonautonomous nonlinear systems problems that may look difficult or even unsolvable otherwise.

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.

Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring

PubMed Central

Zhu, Kathy Q.; Carrougher, Gretchen J.; Gibran, Nicole S.; Isik, F. Frank; Engrav, Loren H.

2010-01-01

Hypertrophic scarring after burns is an unsolved problem and remains as devastating today as it was in the 40s and it may be that the main reason for this is the lack of an accepted, useful animal model. The female, red Duroc pig was described as a model of hypertrophic scarring nearly 30 years ago but then vanished from the literature. This seemed strange since the authors reported that 12 of 12 pigs developed thick scar. In the mid 90s we explored the model and found that, indeed, the red Duroc pig does make thick scar. Other authors have established that the Yorkshire pig does not heal in this fashion so there is the possibility of a same species control. We have continued to explore the Duroc/Yorkshire model and herein describe our experiences. Is it a perfect model of hypertrophic scarring? No. Is it a useful model of hypertrophic scarring? Time will tell. We have now obtained gene expression data from the Duroc/Yorkshire model and analysis is underway. PMID:17727465

Colchicine in Pericardial Disease: from the Underlying Biology and Clinical Benefits to the Drug-Drug Interactions in Cardiovascular Medicine.

PubMed

Schenone, Aldo L; Menon, Venu

2018-06-14

This is an in-depth review on the mechanism of action, clinical utility, and drug-drug interactions of colchicine in the management of pericardial disease. Recent evidence about therapeutic targets on pericarditis has demonstrated that NALP3 inflammasome blockade is the cornerstone in the clinical benefits of colchicine. Such benefits extend from acute and recurrent pericarditis to transient constriction and post-pericardiotomy syndrome. Despite the increased utilization of colchicine in cardiovascular medicine, safety concerns remains unsolved regarding the long-term use of colchicine in the cardiac patient. Moreover, recent evidence has demonstrated that numerous cardiovascular medications, ranging from antihypertensive medication to antiarrhythmics, are known to interact with the CYP3A4 and/or P-gp system increasing the toxicity potential of colchicine. The use of adjunctive colchicine in the management of inflammatory pericardial diseases is standard of care in current practice. It is advised that a careful medication reconciliation with emphasis on pharmacokinetic is completed before prescribing colchicine in order to avoid harmful interaction by finding an alternative regimen or adjusting colchicine dosing.

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

Exon Shuffling and Origin of Scorpion Venom Biodiversity

PubMed Central

Wang, Xueli; Gao, Bin; Zhu, Shunyi

2016-01-01

Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences. PMID:28035955

Exon Shuffling and Origin of Scorpion Venom Biodiversity.

PubMed

Wang, Xueli; Gao, Bin; Zhu, Shunyi

2016-12-26

Scorpion venom is a complex combinatorial library of peptides and proteins with multiple biological functions. A combination of transcriptomic and proteomic techniques has revealed its enormous molecular diversity, as identified by the presence of a large number of ion channel-targeted neurotoxins with different folds, membrane-active antimicrobial peptides, proteases, and protease inhibitors. Although the biodiversity of scorpion venom has long been known, how it arises remains unsolved. In this work, we analyzed the exon-intron structures of an array of scorpion venom protein-encoding genes and unexpectedly found that nearly all of these genes possess a phase-1 intron (one intron located between the first and second nucleotides of a codon) near the cleavage site of a signal sequence despite their mature peptides remarkably differ. This observation matches a theory of exon shuffling in the origin of new genes and suggests that recruitment of different folds into scorpion venom might be achieved via shuffling between body protein-coding genes and ancestral venom gland-specific genes that presumably contributed tissue-specific regulatory elements and secretory signal sequences.

On the Conditioning of Machine-Learning-Assisted Turbulence Modeling

NASA Astrophysics Data System (ADS)

Wu, Jinlong; Sun, Rui; Wang, Qiqi; Xiao, Heng

2017-11-01

Recently, several researchers have demonstrated that machine learning techniques can be used to improve the RANS modeled Reynolds stress by training on available database of high fidelity simulations. However, obtaining improved mean velocity field remains an unsolved challenge, restricting the predictive capability of current machine-learning-assisted turbulence modeling approaches. In this work we define a condition number to evaluate the model conditioning of data-driven turbulence modeling approaches, and propose a stability-oriented machine learning framework to model Reynolds stress. Two canonical flows, the flow in a square duct and the flow over periodic hills, are investigated to demonstrate the predictive capability of the proposed framework. The satisfactory prediction performance of mean velocity field for both flows demonstrates the predictive capability of the proposed framework for machine-learning-assisted turbulence modeling. With showing the capability of improving the prediction of mean flow field, the proposed stability-oriented machine learning framework bridges the gap between the existing machine-learning-assisted turbulence modeling approaches and the demand of predictive capability of turbulence models in real applications.

Dopamine: Just the Right Medicine for Membranes

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

Yang, Hao-Cheng; Waldman, Ruben Z.; Wu, Ming-Bang

Mussel-inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been achieved in both mussel-inspired chemistry and membrane surface engineering based on mussel-inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel-inspired coatings, dopamine-assisted codeposition technology, and photoinitiated grafting directly on mussel-inspired coatings are presented. Some of these technologies have not yet beenmore » employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel-inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal-organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.« less

From the Nano- to the Macroscale - Bridging Scales for the Moving Contact Line Problem

NASA Astrophysics Data System (ADS)

Nold, Andreas; Sibley, David; Goddard, Benjamin; Kalliadasis, Serafim; Complex Multiscale Systems Team

2016-11-01

The moving contact line problem remains an unsolved fundamental problem in fluid mechanics. At the heart of the problem is its multiscale nature: a nanoscale region close to the solid boundary where the continuum hypothesis breaks down, must be resolved before effective macroscale parameters such as contact line friction and slip can be obtained. To capture nanoscale properties very close to the contact line and to establish a link to the macroscale behaviour, we employ classical density-functional theory (DFT), in combination with extended Navier-Stokes-like equations. Using simple models for viscosity and slip at the wall, we compare our computations with the Molecular Kinetic Theory, by extracting the contact line friction, depending on the imposed temperature of the fluid. A key fluid property captured by DFT is the fluid layering at the wall-fluid interface, which has a large effect on the shearing properties of a fluid. To capture this crucial property, we propose an anisotropic model for the viscosity, which also allows us to scrutinize the effect of fluid layering on contact line friction.

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.

Generalized run-and-turn motions: From bacteria to Lévy walks

NASA Astrophysics Data System (ADS)

Detcheverry, François

2017-07-01

Swimming bacteria exhibit a repertoire of motility patterns, in which persistent motion is interrupted by turning events. What are the statistical properties of such random walks? If some particular instances have long been studied, the general case where turning times do not follow a Poisson process has remained unsolved. We present a generic extension of the continuous time random walks formalism relying on operators and noncommutative calculus. The approach is first applied to a unimodal model of bacterial motion. We examine the existence of a minimum in velocity correlation function and discuss the maximum of diffusivity at an optimal value of rotational diffusion. The model is then extended to bimodal patterns and includes as particular cases all swimming strategies: run-and-tumble, run-stop, run-reverse and run-reverse-flick. We characterize their velocity correlation functions and investigate how bimodality affects diffusivity. Finally, the wider applicability of the method is illustrated by considering curved trajectories and Lévy walks. Our results are relevant for intermittent motion of living beings, be they swimming micro-organisms or crawling cells.

[Development of a new technique to detect the laterality of microscopic hematuria by means of gas cystoscopy].

PubMed

Kamoi, K; Teraski, T; Kojima, M; Uchida, M; Watanabe, H

1996-04-01

We developed a new technique to determine the laterality of microscopic hematuria by means of gas cystoscopy. An originally designed catheter system consisted of two catheters. On the tip of an inner catheter, a urine dipstick for blood was attached, with a cap on the tip of an outer catheter to keep the dipstick dry. In order to react a dipstick with the urine coming out from a ureteral orifice in the bladder, CO2 was insufflated into the bladder through a cystoscope (gas cystoscopy). The laterality of microscopic hematuria was determined in the bladder, based on the color reaction on the dipstick. This technique was performed successfully in 14 (88%) of 16 cases with microscopic hematuria. The laterality of microscopic hematuria was determined to be ipsilateral in 6 patients, which coincided with the side of a urological upper urinary tract disorder. In contract, bilateral microscopic hematuria was confirmed in 8 patients with glomerular disorders. The diagnostic process in patients with microscopic hematuria remains unsolved for urologists and nephrologists. This technique may provide a new approach in diagnosing microscopic hematuria.

Unresolved Problems by Shock Capturing: Taming the Overheating Problem

NASA Technical Reports Server (NTRS)

Liou, Meng-Sing

2012-01-01

The overheating problem, first observed by von Neumann [1] and later studied extensively by Noh [2] using both Eulerian and Lagrangian formulations, remains to be one of the unsolved problems by shock capturing. It is historically well known to occur when a flow is under compression, such as when a shock wave hits and reflects from a wall or when two streams collides with each other. The overheating phenomenon is also found numerically in a smooth flow undergoing rarefaction created by two streams receding from each other. This is in contrary to one s intuition expecting a decrease in internal energy. The excessive amount in the temperature increase does not reduce by refining the mesh size or increasing the order of accuracy. This study finds that the overheating in the receding flow correlates with the entropy generation. By requiring entropy preservation, the overheating is eliminated and the solution is grid convergent. The shock-capturing scheme, as being practiced today, gives rise to the entropy generation, which in turn causes the overheating. This assertion stands up to the convergence test.

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.

The Taming of the Cell Penetrating Domain of the HIV Tat: Myths and Realities

PubMed Central

Chauhan, Ashok; Tikoo, Akshay; Kapur, Arvinder K.; Singh, Mahavir

2007-01-01

Protein transduction with cell penetrating peptides over the past several years has been shown to be an effective way of delivering proteins in vitro and now several reports have also shown valuable in vivo applications in correcting disease states. An impressive bioinspired phenomenon of crossing biological barriers came from HIV transactivator Tat protein. Specifically, the protein transduction domain of HIV-Tat has been shown to be a potent pleiotropic peptide in protein delivery. Various approaches such as molecular modeling, arginine guanidinium head group structural strategy, multimerization of PTD sequence and phage display system have been applied for taming of the PTD. This has resulted in identification of PTD variants which are efficient in cell membrane penetration and cytoplasmic delivery. Inspite of these state of the art technologies, the dilemma of low protein transduction efficiency and target specific delivery of PTD fusion proteins remains unsolved. Moreover, some misconceptions about PTD of Tat in the literature require considerations. We have assembled critical information on secretory, plasma membrane penetration and transcellular properties of Tat and PTD using molecular analysis and available experimental evidences. PMID:17196289

Dopamine: Just the Right Medicine for Membranes

DOE PAGES

Yang, Hao-Cheng; Waldman, Ruben Z.; Wu, Ming-Bang; ...

2018-01-09

Mussel-inspired chemistry has attracted widespread interest in membrane science and technology. Demonstrating the rapid growth of this field over the past several years, substantial progress has been achieved in both mussel-inspired chemistry and membrane surface engineering based on mussel-inspired coatings. At this stage, it is valuable to summarize the most recent and distinctive developments, as well as to frame the challenges and opportunities remaining in this field. In this review, recent advances in rapid and controllable deposition of mussel-inspired coatings, dopamine-assisted codeposition technology, and photoinitiated grafting directly on mussel-inspired coatings are presented. Some of these technologies have not yet beenmore » employed directly in membrane science. Beyond discussing advances in conventional membrane processes, emerging applications of mussel-inspired coatings in membranes are discussed, including as a skin layer in nanofiltration, interlayer in metal-organic framework based membranes, hydrophilic layer in Janus membranes, and protective layer in catalytic membranes. Finally, some critical unsolved challenges are raised in this field and some potential pathways are proposed to address them.« less

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.

The molecular mechanism of SPOROCYTELESS/NOZZLE in controlling Arabidopsis ovule development

PubMed Central

Wei, Baoye; Zhang, Jinzhe; Pang, Changxu; Yu, Hao; Guo, Dongshu; Jiang, Hao; Ding, Mingxin; Chen, Zhuoyao; Tao, Qing; Gu, Hongya; Qu, Li-Jia; Qin, Genji

2015-01-01

Ovules are essential for plant reproduction and develop into seeds after fertilization. SPOROCYTELESS/NOZZLE (SPL/NZZ) has been known for more than 15 years as an essential factor for ovule development in Arabidopsis, but the biochemical nature of SPL function has remained unsolved. Here, we demonstrate that SPL functions as an adaptor-like transcriptional repressor. We show that SPL recruits TOPLESS/TOPLESS-RELATED (TPL/TPR) co-repressors to inhibit the CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors. We reveal that SPL uses its EAR motif at the C-terminal end to recruit TPL/TPRs and its N-terminal part to bind and inhibit the TCPs. We demonstrate that either disruption of TPL/TPRs or overexpression of TCPs partially phenocopies the defects of megasporogenesis in spl. Moreover, disruption of TCPs causes phenotypes that resemble spl-D gain-of-function mutants. These results define the action mechanism for SPL, which along with TPL/TPRs controls ovule development by repressing the activities of key transcription factors. Our findings suggest that a similar gene repression strategy is employed by both plants and fungi to control sporogenesis. PMID:25378179

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.

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.

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"?

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…

Water and Life on Mars: Exploring the Possibilities through an Astronomy Laboratory

ERIC Educational Resources Information Center

Wilhelm, Ronald; Wilhelm, Jennifer

2004-01-01

Nontraditional laboratories can provide primary pathways by which students comprehend and apply modern astronomy. To teach a nontraditional astronomy lab, we must give students opportunities to critically contemplate unsolved questions and evaluate current data sources. In doing so, students can develop their own conjectures that will lead to…

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.

Type II odontoid fractures in the elderly: an evidence-based narrative review of management.

PubMed

Pal, D; Sell, P; Grevitt, M

2011-02-01

Considerable controversy exists regarding the optimal management of elderly patients with type II odontoid fractures. There is uncertainty regarding the consequences of non-union. The best treatment remains unclear because of the morbidity associated with prolonged cervical immobilisation versus the risks of surgical intervention. The objective of the study was to evaluate the published literature and determine the current evidence for the management of type II odontoid fractures in elderly. A search of the English language literature from January 1970 to date was performed using Medline and the following keywords: odontoid, fractures, cervical spine and elderly. The search was supplemented by cross-referencing between articles. Case reports and review articles were excluded although some were referred to in the discussion. Studies in patients aged 65 years with a minimum follow-up of 12 months were selected. One-hundred twenty-six articles were reviewed. No class I study was identified. There were two class II studies and the remaining were class III. Significant variability was found in the literature regarding mortality and morbidity rates in patients treated with and without halo vest immobilisation. In recent years several authors have claimed satisfactory results with anterior odontoid screw fixation while others have argued that this may lead to increased complications in this age group. Lately, the posterior cervical (Goel-Harms) construct has also gained popularity amongst surgeons. There is insufficient evidence to establish a standard or guideline for odontoid fracture management in elderly. While most authors agree that cervical immobilisation yields satisfactory results for type I and III fractures in the elderly, the optimal management for type II fractures remain unsolved. A prospective randomised controlled trial is recommended.

Taking Action on Air Pollution Control in the Beijing-Tianjin-Hebei (BTH) Region: Progress, Challenges and Opportunities

PubMed Central

Wang, Li; Zhang, Fengying; Pilot, Eva; Yu, Jie; Holdaway, Jennifer; Yang, Linsheng; Li, Yonghua; Wang, Wuyi; Vardoulakis, Sotiris; Krafft, Thomas

2018-01-01

Due to rapid urbanization, industrialization and motorization, a large number of Chinese cities are affected by heavy air pollution. In order to explore progress, remaining challenges, and sustainability of air pollution control in the Beijing-Tianjin-Hebei (BTH) region after 2013, a mixed method analysis was undertaken. The quantitative analysis comprised an overview of air quality management in the BTH region. Semi-structured expert interviews were conducted with 12 stakeholders from various levels of government and research institutions who played substantial roles either in decision-making or in research and advising on air pollution control in the BTH region. The results indicated that with the stringent air pollution control policies, the air quality in BTH meets the targets of the Air Pollution Prevention and Control Action Plan. However, improvements vary across the region and for different pollutants. Although implementation has been decisive and was at least in parts effectively enforced, significant challenges remained with regard to industrial and traffic emission control, and national air quality limits continued to be significantly exceeded and competing development interests remained mainly unsolved. There were also concerns about the sustainability of the current air pollution control measures especially for industries due to the top-down enforcement, and the associated large burden of social cost including unemployment and social inequity resulting industrial restructuring. Better mechanisms for ensuring cross-sectoral coordination and for improved central-local government communication were suggested. Further suggestions were provided to improve the conceptual design and effective implementation of respective air pollution control strategies in BTH. Our study highlights some of the major hurdles that need to be addressed to succeed with a comprehensive air pollution control management for the Chinese mega-urban agglomerations. PMID:29425189

Taking Action on Air Pollution Control in the Beijing-Tianjin-Hebei (BTH) Region: Progress, Challenges and Opportunities.

PubMed

Wang, Li; Zhang, Fengying; Pilot, Eva; Yu, Jie; Nie, Chengjing; Holdaway, Jennifer; Yang, Linsheng; Li, Yonghua; Wang, Wuyi; Vardoulakis, Sotiris; Krafft, Thomas

2018-02-09

Due to rapid urbanization, industrialization and motorization, a large number of Chinese cities are affected by heavy air pollution. In order to explore progress, remaining challenges, and sustainability of air pollution control in the Beijing-Tianjin-Hebei (BTH) region after 2013, a mixed method analysis was undertaken. The quantitative analysis comprised an overview of air quality management in the BTH region. Semi-structured expert interviews were conducted with 12 stakeholders from various levels of government and research institutions who played substantial roles either in decision-making or in research and advising on air pollution control in the BTH region. The results indicated that with the stringent air pollution control policies, the air quality in BTH meets the targets of the Air Pollution Prevention and Control Action Plan. However, improvements vary across the region and for different pollutants. Although implementation has been decisive and was at least in parts effectively enforced, significant challenges remained with regard to industrial and traffic emission control, and national air quality limits continued to be significantly exceeded and competing development interests remained mainly unsolved. There were also concerns about the sustainability of the current air pollution control measures especially for industries due to the top-down enforcement, and the associated large burden of social cost including unemployment and social inequity resulting industrial restructuring. Better mechanisms for ensuring cross-sectoral coordination and for improved central-local government communication were suggested. Further suggestions were provided to improve the conceptual design and effective implementation of respective air pollution control strategies in BTH. Our study highlights some of the major hurdles that need to be addressed to succeed with a comprehensive air pollution control management for the Chinese mega-urban agglomerations.

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

Alcohol dehydrogenase of acetic acid bacteria: structure, mode of action, and applications in biotechnology.

PubMed

Yakushi, Toshiharu; Matsushita, Kazunobu

2010-05-01

Pyrroquinoline quinone-dependent alcohol dehydrogenase (PQQ-ADH) of acetic acid bacteria is a membrane-bound enzyme involved in the acetic acid fermentation by oxidizing ethanol to acetaldehyde coupling with reduction of membranous ubiquinone (Q), which is, in turn, re-oxidized by ubiquinol oxidase, reducing oxygen to water. PQQ-ADHs seem to have co-evolved with the organisms fitting to their own habitats. The enzyme consists of three subunits and has a pyrroloquinoline quinone, 4 heme c moieties, and a tightly bound Q as the electron transfer mediators. Biochemical, genetic, and electrochemical studies have revealed the unique properties of PQQ-ADH since it was purified in 1978. The enzyme is unique to have ubiquinol oxidation activity in addition to Q reduction. This mini-review focuses on the molecular properties of PQQ-ADH, such as the roles of the subunits and the cofactors, particularly in intramolecular electron transport of the enzyme from ethanol to Q. Also, we summarize biotechnological applications of PQQ-ADH as to enantiospecific oxidations for production of the valuable chemicals and bioelectrocatalysis for sensors and fuel cells using indirect and direct electron transfer technologies and discuss unsolved issues and future prospects related to this elaborate enzyme.

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.

Phytoceuticals: mighty but ignored weapons against Helicobacter pylori infection.

PubMed

Lee, Sun-Young; Shin, Yong Woon; Hahm, Ki-Baik

2008-08-01

Helicobacter pylori (H. pylori) infection causes peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphomas and gastric adenocarcinomas, for which the pathogenesis of chronic gastric inflammation prevails and provides the pathogenic basis. Since the role of H. pylori infection is promoting carcinogenesis rather than acting as a direct carcinogen, as several publications show, eradication alone cannot be the right answer for preventing H. pylori-associated gastric cancer. Therefore, a non-antimicrobial approach has been suggested to attain microbe-associated cancer prevention through controlling H. pylori-related chronic inflammatory processes and mediators responsible for carcinogenesis. Phytoceutical is a term for plant products that are active on biological systems. Phytoceuticals such as Korean red ginseng, green tea, red wine, flavonoids, broccoli sprouts, garlic, probiotics and flavonoids are known to inhibit H. pylori colonization, decrease gastric inflammation by inhibiting cytokine and chemokine release, and repress precancerous changes by inhibiting nuclear factor-kappa B DNA binding, inducing profuse levels of apoptosis and inhibiting mutagenesis. Even though further unsolved issues are awaited before phytoceuticals are accepted as a standard treatment for H. pylori infection, phytoceuticals can be a mighty weapon for either suppressing or modulating the disease-associated footprints of H. pylori infection.

Transcolonic Perirectal NOTES Access (PNA): A feasibility study with survival in swine model.

PubMed

Oliveira, André L A; Zorron, Ricardo; Oliveira, Flavio M M DE; Santos, Marcelo B Dos; Scheffer, Jussara P; Rios, Marcelo; Antunes, Fernanda

2017-05-01

Transrectal access still has some unsolved issues such as spatial orientation, infection, access and site closure. This study presents a simple technique to perform transcolonic access with survival in a swine model series. A new technique for NOTES perirectal access to perform retroperitoneoscopy, peritoneoscopy, liver and lymphnode biopsies was performed in 6 pigs, using Totally NOTES technique. The specimens were extracted transanally. The flexible endoscope was inserted through a posterior transmural incision and the retrorectal space. Cultures of bacteria were documented for the retroperitoneal space and intra abdominal cavity after 14 days. Rectal site was closed using non-absorbable sutures. There was no bowel cleansing, nor preoperative fasting. The procedures were performed in 6 pigs through transcolonic natural orifice access using available endoscopic flexible instruments. All animals survived 14 days without complications, and cultures were negative. Histopathologic examination of the rectal closure site showed adequate healing of suture line and no micro abscesses. The results of feasibility and safety of experimental Transcolonic NOTES potentially brings new frontiers and future wider applications for minimally invasive surgery. The treatment of colorectal, abdominal and retroperitoneal diseases through a flexible Perirectal NOTES Access (PNA) is a promising new approach.

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.

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)…

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

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…

Preoperative ultrasound still valuable for radio-cephalic arteriovenous fistula creation?

PubMed

Pajek, Jernej; Malovrh, Marko

2017-03-06

Radio-cephalic arteriovenous fistula is a prototype hemodialysis access with small incidences of infection and distal ischemia, it spares proximal veins for future access use and it helps in the maturation of veins that may be used for more proximal access creations. This access type is prone to higher early failure rates compared to more proximal fistulas and there are unsolved uncertainties regarding exact ultrasound parameters predictive of fistula outcome. Evolution of ultrasound use has yielded several functional parameters that can be measured in addition to anatomical lumen sizes, which remain core parameters on which the decision to construct fistula in radio-cephalic forearm position is based. We propose to use arterial hyperemic response and wall morphology to aid in this decision when radial artery diameter falls in the interval with predictive uncertainty of 1.6-1.9 mm and to use venous flow pattern, respiratory variation, radial artery status and possibly venous distensibility when cephalic vein augmented diameter lies in the borderline interval of 2-2.4 mm. Ultrasound preoperative mapping and planning should be followed by expert surgical technique and several technique modifications of the classical end-to-side approach are possible to enhance operation outcome and diminish the incidence of stenosis most often present at juxta-anastomotic location. In our experience radio-cephalic arteriovenous fistula remains the golden standard for hemodialysis access and preoperative ultrasound the single best imaging modality to plan the operation and predict its success.

m-YouTube Mobile UI: Video Selection Based on Social Influence

NASA Astrophysics Data System (ADS)

Marcus, Aaron; Perez, Angel

The ease-of-use of Web-based video-publishing services provided by applications like YouTube has encouraged a new means of asynchronous communication, in which users can post videos not only to make them public for review and criticism, but also as a way to express moods, feelings, or intentions to an ever-growing network of friends. Following the current trend of porting Web applications onto mobile platforms, the authors sought to explore user-interface design issues of a mobile-device-based YouTube, which they call m-YouTube. They first analyzed the elements of success of the current YouTube Web site and observed its functionality. Then, they looked for unsolved issues that could give benefit through information-visualization design for small screens on mobile phones to explore a mobile version of such a product/service. The biggest challenge was to reduce the number of functions and amount information to fit into a mobile phone screen, but still be usable, useful, and appealing within the YouTube context of use and user experience. Borrowing ideas from social research in the area of social influence processes, they made design decisions aiming to help YouTube users to make the decision of what video content to watch and to increase the chances of YouTube authors being evaluated and observed by peers. The paper proposes a means to visualize large amounts of video relevant to YouTube users by using their friendship network as a relevance indicator to help in the decision-making process.

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

From Authoritative Discourse to Internally Persuasive Discourse: Discursive Evolution in Teaching and Learning the Language of Science

ERIC Educational Resources Information Center

Hsu, Pei-Ling; Roth, Wolff-Michael

2014-01-01

Learning science interpreted in existing theoretical frameworks often means that students are assimilated, accommodated or enculturated from the entity of the vernacular world to the entity of the scientific world. However, there are some unsolved questions as to how students can best learn purely a new language or new knowledge of science. The…

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.

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

Radio Frequency Identification (RFID) in Space

NASA Technical Reports Server (NTRS)

Bacon, John B.

2011-01-01

The ISS has some significant inventory management challenges. RFID solves many of these, and was deployed 8/2011. Significant issues (some unique to spacecraft) remain. NASA is interested and investing in technologies that will help to overcome the remaining issues.

Manual removal of the placenta after vaginal delivery: an unsolved problem in obstetrics.

PubMed

Urner, Fiona; Zimmermann, Roland; Krafft, Alexander

2014-01-01

The third stage of labor is associated with considerable maternal morbidity and mortality. The major complication is postpartum hemorrhage (PPH), which is the leading cause of maternal morbidity and mortality worldwide. Whereas in the event of PPH due to atony of the uterus there exist numerous treatment guidelines; for the management of retained placenta the general consensus is more difficult to establish. Active management of the third stage of labour is generally accepted as standard of care as already its duration is contributing to the risk of PPH. Despite scant evidence it is commonly advised that if the placenta has not been expelled 30 minutes after delivery, manual removal of the placenta should be carried out under anaesthesia. Pathologic adhesion of the placenta in the low risk situation usually is diagnosed at the time of delivery; therefore a pre- or intrapartum screening opportunity for placenta accreta would be desirable. But diagnosis of abnormalities of placentation other than placenta previa remains a challenge. Nevertheless the use of ultrasound and doppler sonography might be helpful in the third stage of labor. An improvement might be the implementation of standardized operating procedures for retained placenta which could contribute to a reduction of maternal morbidity.

Initial Binding of Ions to the Interhelical Loops of Divalent Ion Transporter CorA: Replica Exchange Molecular Dynamics Simulation Study

PubMed Central

Zhang, Tong; Mu, Yuguang

2012-01-01

Crystal structures of Thermotoga maritima magnesium transporter CorA, reported in 2006, revealed its homo-pentameric constructions. However, the structure of the highly conserved extracellular interhelical loops remains unsolved, due to its high flexibility. We have explored the configurations of the loops through extensive replica exchange molecular dynamics simulations in explicit solvent model with the presence of either Co(III) Hexamine ions or Mg2+ ions. We found that there are multiple binding sites available on the interhelical loops in which the negatively charged residues, E316 and E320, are located notably close to the positively charged ions during the simulations. Our simulations resolved the distinct binding patterns of the two kinds of ions: Co(III) Hexamine ions were found to bind stronger with the loop than Mg2+ ions with binding free energy −7.3 kJ/mol lower, which is nicely consistent with the previous data. Our study provides an atomic basis description of the initial binding process of Mg2+ ions on the extracellular interhelical loops of CorA and the detailed inhibition mechanism of Co(III) Hexamine ions on CorA ions transportation. PMID:22952795

Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

NASA Astrophysics Data System (ADS)

Howell, Steven C.

Chromatin conformation and dynamics remains unsolved despite the critical role of the chromatin in fundamental genetic functions such as transcription, replication, and repair. At the molecular level, chromatin can be viewed as a linear array of nucleosomes, each consisting of 147 base pairs (bp) of double-stranded DNA (dsDNA) wrapped around a protein core and connected by 10 to 90 bp of linker dsDNA. Using small-angle X-ray scattering (SAXS), we investigated how the conformations of model nucleosome arrays in solution are modulated by ionic condition as well as the effect of linker histone proteins. To facilitate ensemble modeling of these SAXS measurements, we developed a simulation method that treats coarse-grained DNA as a Markov chain, then explores possible DNA conformations using Metropolis Monte Carlo (MC) sampling. This algorithm extends the functionality of SASSIE, a program used to model intrinsically disordered biological molecules, adding to the previous methods for simulating protein, carbohydrates, and single-stranded DNA. Our SAXS measurements of various nucleosome arrays together with the MC generated models provide valuable solution structure information identifying specific differences from the structure of crystallized arrays.

Targeted next-generation sequencing reveals that a compound heterozygous mutation in phosphodiesterase 6a gene leads to retinitis pigmentosa in a Chinese family.

PubMed

Zhang, Shanshan; Li, Jie; Li, Shujin; Yang, Yeming; Yang, Mu; Yang, Zhenglin; Zhu, Xianjun; Zhang, Lin

2018-04-25

Retinitis pigmentosa (RP) is a genetically heterogeneous disease with over 70 causative genes identified to date. However, approximately 40% of RP cases remain genetically unsolved, suggesting that many novel disease-causing mutations are yet to be identified. The purpose of this study is to identify the causative mutations of a Chinese RP family. Targeted next-generation sequencing (NGS) for a total of 163 genes which involved in inherited retinal disorders were used to screen the possible causative mutations. Sanger sequencing was used to verify the mutations. As results, we identified two heterozygous mutations: a splicing site mutation c.1407 + 1G>C and a nonsense mutation c. 1957C>T (p.R653X) in phosphodiesterase 6A (PDE6A) gene in the RP patient. These two mutations are inherited from his father and mother, respectively. Furthermore, these mutations are unique in our in-house database and are rare in human genome databases, implicating that these two mutations are pathological. By using targeted NGS method, we identified a compound heterozygous mutation in PDE6A gene that is associated with RP in a Chinese family.

Robust Real-Time and Rotation-Invariant American Sign Language Alphabet Recognition Using Range Camera

NASA Astrophysics Data System (ADS)

Lahamy, H.; Lichti, D.

2012-07-01

The automatic interpretation of human gestures can be used for a natural interaction with computers without the use of mechanical devices such as keyboards and mice. The recognition of hand postures have been studied for many years. However, most of the literature in this area has considered 2D images which cannot provide a full description of the hand gestures. In addition, a rotation-invariant identification remains an unsolved problem even with the use of 2D images. The objective of the current study is to design a rotation-invariant recognition process while using a 3D signature for classifying hand postures. An heuristic and voxelbased signature has been designed and implemented. The tracking of the hand motion is achieved with the Kalman filter. A unique training image per posture is used in the supervised classification. The designed recognition process and the tracking procedure have been successfully evaluated. This study has demonstrated the efficiency of the proposed rotation invariant 3D hand posture signature which leads to 98.24% recognition rate after testing 12723 samples of 12 gestures taken from the alphabet of the American Sign Language.

An Extracorporeal Artificial Placenta Supports Extremely Premature Lambs for One Week

PubMed Central

Bryner, Benjamin; Gray, Brian; Perkins, Elena; Davis, Ryan; Hoffman, Hayley; Barks, John; Owens, Gabe; Bocks, Martin; Rojas-Peña, Alvaro; Hirschl, Ronald; Bartlett, Robert; Mychaliska, George

2015-01-01

Purpose The treatment of extreme prematurity remains an unsolved problem. We developed an artificial placenta (AP) based on extracorporeal life support (ECLS) that simulates the intrauterine environment and provides gas exchange without mechanical ventilation (MV), and compared it to the current standard of neonatal care. Methods Extremely premature lambs (110-120d; term=145d) were used. AP lambs (n=9) were cannulated (jugular drainage, umbilical vein reinfusion) for ECLS .Control lambs (n=7) were intubated, ventilated, given surfactant, and transitioned to high-frequency oscillatory ventilation. All lambs received parenteral nutrition, antibiotics, and steroids. Hemodynamics, blood gases, hemoglobin, and circuit flows were measured. Results Four premature lambs survived for 1 week on the AP; one survived 6 days. Adequate oxygenation and ventilation were provided by the AP. The MV lambs survived 2-8 hours. Each of these lambs experienced a transient improvement with surfactant, but developed progressive hypercapnea and hypoxia despite high airway pressures and HFOV. Conclusions Extremely premature lambs were supported for 1 week with the AP with hemodynamic stability and adequate gas exchange; mechanically ventilated lambs succumbed within 8 hours. Further studies will assess control of fetal circulation and organ maturation on the AP. PMID:25598091

Learning dynamics explains human behaviour in prisoner's dilemma on networks.

PubMed

Cimini, Giulio; Sánchez, Angel

2014-05-06

Cooperative behaviour lies at the very basis of human societies, yet its evolutionary origin remains a key unsolved puzzle. Whereas reciprocity or conditional cooperation is one of the most prominent mechanisms proposed to explain the emergence of cooperation in social dilemmas, recent experimental findings on networked Prisoner's Dilemma games suggest that conditional cooperation also depends on the previous action of the player-namely on the 'mood' in which the player is currently in. Roughly, a majority of people behave as conditional cooperators if they cooperated in the past, whereas they ignore the context and free ride with high probability if they did not. However, the ultimate origin of this behaviour represents a conundrum itself. Here, we aim specifically to provide an evolutionary explanation of moody conditional cooperation (MCC). To this end, we perform an extensive analysis of different evolutionary dynamics for players' behavioural traits-ranging from standard processes used in game theory based on pay-off comparison to others that include non-economic or social factors. Our results show that only a dynamic built upon reinforcement learning is able to give rise to evolutionarily stable MCC, and at the end to reproduce the human behaviours observed in the experiments.

High-Throughput Synthesis and Structure of Zeolite ZSM-43 with Two-Directional 8-Ring Channels.

PubMed

Willhammar, Tom; Su, Jie; Yun, Yifeng; Zou, Xiaodong; Afeworki, Mobae; Weston, Simon C; Vroman, Hilda B; Lonergan, William W; Strohmaier, Karl G

2017-08-07

The aluminosilicate zeolite ZSM-43 (where ZSM = Zeolite Socony Mobil) was first synthesized more than 3 decades ago, but its chemical structure remained unsolved because of its poor crystallinity and small crystal size. Here we present optimization of the ZSM-43 synthesis using a high-throughput approach and subsequent structure determination by the combination of electron crystallographic methods and powder X-ray diffraction. The synthesis required the use of a combination of both inorganic (Cs + and K + ) and organic (choline) structure-directing agents. High-throughput synthesis enabled a screening of the synthesis conditions, which made it possible to optimize the synthesis, despite its complexity, in order to obtain a material with significantly improved crystallinity. When both rotation electron diffraction and high-resolution transmission electron microscopy imaging techniques are applied, the structure of ZSM-43 could be determined. The structure of ZSM-43 is a new zeolite framework type and possesses a unique two-dimensional channel system limited by 8-ring channels. ZSM-43 is stable upon calcination, and sorption measurements show that the material is suitable for adsorption of carbon dioxide as well as methane.

The unsolved puzzle of neuropathogenesis in glutaric aciduria type I.

PubMed

Jafari, Paris; Braissant, Olivier; Bonafé, Luisa; Ballhausen, Diana

2011-12-01

Glutaric aciduria type I (GA-I) is a cerebral organic aciduria caused by deficiency of glutaryl-Co-A dehydrogenase (GCDH). GCDH deficiency leads to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA), two metabolites that are believed to be neurotoxic, in brain and body fluids. The disorder usually becomes clinically manifest during a catabolic state (e.g. intercurrent illness) with an acute encephalopathic crisis that results in striatal necrosis and in a permanent dystonic-dyskinetic movement disorder. The results of numerous in vitro and in vivo studies have pointed to three main mechanisms involved in the metabolite-mediated neuronal damage: excitotoxicity, impairment of energy metabolism and oxidative stress. There is evidence that during a metabolic crisis GA and its metabolites are produced endogenously in the CNS and accumulate because of limiting transport mechanisms across the blood-brain barrier. Despite extensive experimental work, the relative contribution of the proposed pathogenic mechanisms remains unclear and specific therapeutic approaches have yet to be developed. Here, we review the experimental evidence and try to delineate possible pathogenetic models and approaches for future studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Radiation-enhanced self- and boron diffusion in germanium

NASA Astrophysics Data System (ADS)

Schneider, S.; Bracht, H.; Klug, J. N.; Hansen, J. Lundsgaard; Larsen, A. Nylandsted; Bougeard, D.; Haller, E. E.

2013-03-01

We report experiments on proton radiation-enhanced self- and boron (B) diffusion in germanium (Ge) for temperatures between 515 ∘C and 720 ∘C. Modeling of the experimental diffusion profiles measured by means of secondary ion mass spectrometry is achieved on the basis of the Frenkel pair reaction and the interstitialcy and dissociative diffusion mechanisms. The numerical simulations ascertain concentrations of Ge interstitials and B-interstitial pairs that deviate by several orders of magnitude from their thermal equilibrium values. The dominance of self-interstitial related defects under irradiation leads to an enhanced self- and B diffusion in Ge. Analysis of the experimental profiles yields data for the diffusion of self-interstitials (I) and the thermal equilibrium concentration of BI pairs in Ge. The temperature dependence of these quantities provides the migration enthalpy of I and formation enthalpy of BI that are compared with recent results of atomistic calculations. The behavior of self- and B diffusion in Ge under concurrent annealing and irradiation is strongly affected by the property of the Ge surface to hinder the annihilation of self-interstitials. The limited annihilation efficiency of the Ge surface can be caused by donor-type surface states favored under vacuum annealing, but the physical origin remains unsolved.

Kuramoto model with uniformly spaced frequencies: Finite-N asymptotics of the locking threshold.

PubMed

Ottino-Löffler, Bertrand; Strogatz, Steven H

2016-06-01

We study phase locking in the Kuramoto model of coupled oscillators in the special case where the number of oscillators, N, is large but finite, and the oscillators' natural frequencies are evenly spaced on a given interval. In this case, stable phase-locked solutions are known to exist if and only if the frequency interval is narrower than a certain critical width, called the locking threshold. For infinite N, the exact value of the locking threshold was calculated 30 years ago; however, the leading corrections to it for finite N have remained unsolved analytically. Here we derive an asymptotic formula for the locking threshold when N≫1. The leading correction to the infinite-N result scales like either N^{-3/2} or N^{-1}, depending on whether the frequencies are evenly spaced according to a midpoint rule or an end-point rule. These scaling laws agree with numerical results obtained by Pazó [D. Pazó, Phys. Rev. E 72, 046211 (2005)PLEEE81539-375510.1103/PhysRevE.72.046211]. Moreover, our analysis yields the exact prefactors in the scaling laws, which also match the numerics.

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.

Pinpointing the knee of cosmic rays with diffuse PeV γ-rays and neutrinos

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

Guo, Y. Q.; Hu, H. B.; Yuan, Q.

2014-11-01

The origin of the knee in the cosmic ray spectrum remains to be an unsolved fundamental problem. There are various kinds of models that predict different break positions and the compositions of the knee. In this work, we suggest the use of diffuse γ-rays and neutrinos as probes to test these models. Based on several typical types of composition models, the diffuse γ-ray and neutrino spectra are calculated and show distinctive cutoff behaviors at energies from tens of TeV to multi-PeV. The expected flux will be observable by the newly upgraded Tibet-ASγ+MD (muon detector) experiment as well as more sensitivemore » future projects, such as LHAASO and HiSCORE. By comparing the neutrino spectrum with the recent observations by the IceCube experiment, we find that the diffuse neutrinos from interactions between the cosmic rays and the interstellar medium may not be responsible to the majority of the IceCube events. Future measurements of the neutrinos may be able to identify the Galactic diffuse component and shed further light on the problem of the knee of cosmic rays.« less

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

Pharmacologic Calcitriol Inhibits Osteoclast Lineage Commitment via the BMP-Smad1 and IκB-NF-κB Pathways.

PubMed

Li, Anna; Cong, Qian; Xia, Xuechun; Leong, Wai Fook; Yeh, James; Miao, Dengshun; Mishina, Yuji; Liu, Huijuan; Li, Baojie

2017-07-01

Vitamin D is involved in a range of physiological processes and its active form and analogs have been used to treat diseases such as osteoporosis. Yet how vitamin D executes its function remains unsolved. Here we show that the active form of vitamin D calcitriol increases the peak bone mass in mice by inhibiting osteoclastogenesis and bone resorption. Although calcitriol modestly promoted osteoclast maturation, it strongly inhibited osteoclast lineage commitment from its progenitor monocyte by increasing Smad1 transcription via the vitamin D receptor and enhancing BMP-Smad1 activation, which in turn led to increased IκBα expression and decreased NF-κB activation and NFATc1 expression, with IκBα being a Smad1 target gene. Inhibition of BMP type I receptor or ablation of Bmpr1a in monocytes alleviated the inhibitory effects of calcitriol on osteoclast commitment, bone resorption, and bone mass augmentation. These findings uncover crosstalk between the BMP-Smad1 and RANKL-NF-κB pathways during osteoclastogenesis that underlies the action of active vitamin D on bone health. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

Ultrafast laser ablation for targeted atherosclerotic plaque removal

NASA Astrophysics Data System (ADS)

Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

2015-07-01

Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

A new method for solving reachable domain of spacecraft with a single impulse

NASA Astrophysics Data System (ADS)

Chen, Qi; Qiao, Dong; Shang, Haibin; Liu, Xinfu

2018-04-01

This paper develops a new approach to solve the reachable domain of a spacecraft with a single maximum available impulse. First, the distance in a chosen direction, started from a given position on the initial orbit, is formulated. Then, its extreme value is solved to obtain the maximum reachable distance in this direction. The envelop of the reachable domain in three-dimensional space is determined by solving the maximum reachable distance in all directions. Four scenarios are analyzed, including three typical scenarios (either the maneuver position or impulse direction is fixed, or both are arbitrary) and a new extended scenario (the maneuver position is restricted to an interval and the impulse direction is arbitrary). Moreover, the symmetry and the boundedness of the reachable domain are discussed in detail. The former is helpful to reduce the numerical computation, while the latter decides the maximum eccentricity of the initial orbit for a maximum available impulse. The numerical simulations verify the effectiveness of the proposed method for solving the reachable domain in all four scenarios. Especially, the reachable domain with a highly elliptical initial orbit can be determined successfully, which remains unsolved in the existing papers.

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.

Multiple species of wild tree peonies gave rise to the ‘king of flowers’, Paeonia suffruticosa Andrews

PubMed Central

Zhou, Shi-Liang; Zou, Xin-Hui; Zhou, Zhi-Qin; Liu, Jing; Xu, Chao; Yu, Jing; Wang, Qiang; Zhang, Da-Ming; Wang, Xiao-Quan; Ge, Song; Sang, Tao; Pan, Kai-Yu; Hong, De-Yuan

2014-01-01

The origin of cultivated tree peonies, known as the ‘king of flowers' in China for more than 1000 years, has attracted considerable interest, but remained unsolved. Here, we conducted phylogenetic analyses of explicitly sampled traditional cultivars of tree peonies and all wild species from the shrubby section Moutan of the genus Paeonia based on sequences of 14 fast-evolved chloroplast regions and 25 presumably single-copy nuclear markers identified from RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers was fully resolved and largely congruent with morphology and classification. The incongruence between the nuclear and chloroplast trees suggested that there had been gene flow between the wild species. The comparison of nuclear and chloroplast phylogenies including cultivars showed that the cultivated tree peonies originated from homoploid hybridization among five wild species. Since the origin, thousands of cultivated varieties have spread worldwide, whereas four parental species are currently endangered or on the verge of extinction. The documentation of extensive homoploid hybridization involved in tree peony domestication provides new insights into the mechanisms underlying the origins of garden ornamentals and the way of preserving natural genetic resources through domestication. PMID:25377453

Transcriptome analysis reveals candidate genes involved in luciferin metabolism in Luciola aquatilis (Coleoptera: Lampyridae)

PubMed Central

Vongsangnak, Wanwipa; Chumnanpuen, Pramote

2016-01-01

Bioluminescence, which living organisms such as fireflies emit light, has been studied extensively for over half a century. This intriguing reaction, having its origins in nature where glowing insects can signal things such as attraction or defense, is now widely used in biotechnology with applications of bioluminescence and chemiluminescence. Luciferase, a key enzyme in this reaction, has been well characterized; however, the enzymes involved in the biosynthetic pathway of its substrate, luciferin, remains unsolved at present. To elucidate the luciferin metabolism, we performed a de novo transcriptome analysis using larvae of the firefly species, Luciola aquatilis. Here, a comparative analysis is performed with the model coleopteran insect Tribolium casteneum to elucidate the metabolic pathways in L. aquatilis. Based on a template luciferin biosynthetic pathway, combined with a range of protein and pathway databases, and various prediction tools for functional annotation, the candidate genes, enzymes, and biochemical reactions involved in luciferin metabolism are proposed for L. aquatilis. The candidate gene expression is validated in the adult L. aquatilis using reverse transcription PCR (RT-PCR). This study provides useful information on the bio-production of luciferin in the firefly and will benefit to future applications of the valuable firefly bioluminescence system. PMID:27761329

Extracellular and Intracellular Mechanisms Mediating Metastatic Activity of Exogenous Osteopontin

PubMed Central

Mandelin, Jami; Lin, Emme C. K.; Hu, Dana D.; Knowles, Susan K.; Do, Kim-Anh; Wang, Xuemei; Sage, E. Helene; Smith, Jeffrey W.; Arap, Wadih; Pasqualini, Renata

2009-01-01

BACKGROUND Osteopontin affects several steps of the metastatic cascade. Despite direct correlation with metastasis in experimental systems and in patient studies, the extracellular and intracellular basis for these observations remains unsolved. We used human melanoma and sarcoma cell lines to evaluate the effects of soluble osteopontin on metastasis. METHODS Exogenous osteopontin or negative controls, including a site-directed mutant osteopontin, were used in functional assays in vitro, ex vivo, and in vivo designed to test extracellular and intracellular mechanisms involved in experimental metastasis. RESULTS In the extracellular environment, we confirm that soluble osteopontin is required for its pro-metastatic effects; this phenomenon is specific, RGD-dependent, and evident in experimental models of metastasis. In the intracellular environment, osteopontin initially induces rapid Tyr-418 dephosphorylation of c-Src, with decreases in actin stress fibers and increased binding to the vascular endothelium. This heretofore undescribed Tyr dephosphorylation is followed by a tandem c-Src phosphorylation after tumor cell attachment to the metastatic site. CONCLUSION Our results reveal a complex molecular interaction as well as a dual role for osteopontin in metastasis that is dependent on whether tumor cells are in circulation or attached. Such context-dependent functional insights may contribute to anti-metastasis strategies. PMID:19224553

Toward a Trust Evaluation Mechanism in the Social Internet of Things.

PubMed

Truong, Nguyen Binh; Lee, Hyunwoo; Askwith, Bob; Lee, Gyu Myoung

2017-06-09

In the blooming era of the Internet of Things (IoT), trust has been accepted as a vital factor for provisioning secure, reliable, seamless communications and services. However, a large number of challenges still remain unsolved due to the ambiguity of the concept of trust as well as the variety of divergent trust models in different contexts. In this research, we augment the trust concept, the trust definition and provide a general conceptual model in the context of the Social IoT (SIoT) environment by breaking down all attributes influencing trust. Then, we propose a trust evaluation model called REK, comprised of the triad of trust indicators (TIs) Reputation, Experience and Knowledge. The REK model covers multi-dimensional aspects of trust by incorporating heterogeneous information from direct observation (as Knowledge TI), personal experiences (as Experience TI) to global opinions (as Reputation TI). The associated evaluation models for the three TIs are also proposed and provisioned. We then come up with an aggregation mechanism for deriving trust values as the final outcome of the REK evaluation model. We believe this article offers better understandings on trust as well as provides several prospective approaches for the trust evaluation in the SIoT environment.

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.

Minimally Invasive Surgical Device for Precise Application of Bioadhesives to Prevent iPPROM.

PubMed

Devaud, Yannick Robert; Züger, Silvia; Zimmermann, Roland; Ehrbar, Martin; Ochsenbein-Kölble, Nicole

2018-06-19

The benefits of endoscopic fetal surgery are deteriorated by the high risk of iatrogenic preterm prelabor rupture of fetal membranes (iPPROM). While previous studies have reported good sealing candidates to prevent membrane rupture, the delivery of these materials to the location of membrane puncture remains unsolved. We describe an approach to apply sealing materials onto the amnion through the fetoscopy port. We developed a device composed of an umbrella-shaped polyester coated nitinol mesh and an applicator. The spontaneously unfolding umbrella is pushed through the port, pulled against the amnion, and glued onto the amnion defect site. We tested the adhesion strength of multiple glues and tested the feasibility and reproducibility of this fetal membrane sealing approach in an ex vivo model. The umbrella unfolded and was well positioned in all tests (n = 18). When applied via the fetoscopy port, umbrellas were successfully glued onto the fetal membrane, and all of them completely covered the defect (n = 5). The mean time needed for the whole procedure was 3 min. This study is a proof of concept presenting a potential future solution for the precise local application of bioadhesives for the prevention of iPPROM. © 2018 S. Karger AG, Basel.

The CD20 homologue MS4A4 directs trafficking of KIT toward clathrin-independent endocytosis pathways and thus regulates receptor signaling and recycling

PubMed Central

Cruse, Glenn; Beaven, Michael A.; Music, Stephen C.; Bradding, Peter; Gilfillan, Alasdair M.; Metcalfe, Dean D.

2015-01-01

MS4A family members differentially regulate the cell cycle, and aberrant, or loss of, expression of MS4A family proteins has been observed in colon and lung cancer. However, the precise functions of MS4A family proteins and their mechanistic interactions remain unsolved. Here we report that MS4A4 facilitates trafficking of the receptor tyrosine kinase KIT through endocytic recycling rather than degradation pathways by a mechanism that involves recruitment of KIT to caveolin-1–enriched microdomains. Silencing of MS4A4 in human mast cells altered ligand-induced KIT endocytosis pathways and reduced receptor recycling to the cell surface, thus promoting KIT signaling in the endosomes while reducing that in the plasma membrane, as exemplified by Akt and PLCγ1 phosphorylation, respectively. The altered endocytic trafficking of KIT also resulted in an increase in SCF-induced mast cell proliferation and migration, which may reflect altered signaling in these cells. Our data reveal a novel function for MS4A family proteins in regulating trafficking and signaling, which could have implications in both proliferative and immunological diseases. PMID:25717186

Toward a Trust Evaluation Mechanism in the Social Internet of Things

PubMed Central

Truong, Nguyen Binh; Lee, Hyunwoo; Askwith, Bob; Lee, Gyu Myoung

2017-01-01

In the blooming era of the Internet of Things (IoT), trust has been accepted as a vital factor for provisioning secure, reliable, seamless communications and services. However, a large number of challenges still remain unsolved due to the ambiguity of the concept of trust as well as the variety of divergent trust models in different contexts. In this research, we augment the trust concept, the trust definition and provide a general conceptual model in the context of the Social IoT (SIoT) environment by breaking down all attributes influencing trust. Then, we propose a trust evaluation model called REK, comprised of the triad of trust indicators (TIs) Reputation, Experience and Knowledge. The REK model covers multi-dimensional aspects of trust by incorporating heterogeneous information from direct observation (as Knowledge TI), personal experiences (as Experience TI) to global opinions (as Reputation TI). The associated evaluation models for the three TIs are also proposed and provisioned. We then come up with an aggregation mechanism for deriving trust values as the final outcome of the REK evaluation model. We believe this article offers better understandings on trust as well as provides several prospective approaches for the trust evaluation in the SIoT environment. PMID:28598401

Birth of an oceanic spreading center at a magma-poor rift system.

PubMed

Gillard, Morgane; Sauter, Daniel; Tugend, Julie; Tomasi, Simon; Epin, Marie-Eva; Manatschal, Gianreto

2017-11-08

Oceanic crust is continuously created at mid-oceanic ridges and seafloor spreading represents one of the main processes of plate tectonics. However, if oceanic crust architecture, composition and formation at present-day oceanic ridges are largely described, the processes governing the birth of a spreading center remain enigmatic. Understanding the transition between inherited continental and new oceanic domains is a prerequisite to constrain one of the last major unsolved problems of plate tectonics, namely the formation of a stable divergent plate boundary. In this paper, we present newly released high-resolution seismic reflection profiles that image the complete transition from unambiguous continental to oceanic crusts in the Gulf of Guinea. Based on these high-resolution seismic sections we show that onset of oceanic seafloor spreading is associated with the formation of a hybrid crust in which thinned continental crust and/or exhumed mantle is sandwiched between magmatic intrusive and extrusive bodies. This crust results from a polyphase evolution showing a gradual transition from tectonic-driven to magmatic-driven processes. The results presented in this paper provide a characterization of the domain in which lithospheric breakup occurs and enable to define the processes controlling formation of a new plate boundary.

A New View of Dynamic River Networks

NASA Astrophysics Data System (ADS)

Perron, J. T.; Willett, S.; McCoy, S. W.

2014-12-01

River networks are the main conduits that transport water, sediment, and nutrients from continental interiors to the oceans. They also shape topography as they erode through bedrock. These hierarchical networks are dynamic: there are numerous examples of apparent changes in the topology of river networks through geologic time. But these examples are geographically scattered, the evidence can be ambiguous, and the mechanisms that drive changes in river networks are poorly understood. This makes it difficult to assess how pervasive river network reorganization is, how it operates, and how the interlocking river basins that compose a given landscape are changing through time. Recent progress has improved the situation. We describe three developments that have dramatically advanced our understanding of dynamic river networks. First, new topographic, geophysical and geochronological measurement techniques are revealing the rate and extent of river network adjustment. Second, laboratory experiments and computational models are clarifying how river networks respond to tectonic and climatic perturbations at scales ranging from local to continental. Third, spatial analysis of genetic data is exposing links between landscape evolution, biological evolution, and the development of biodiversity. We highlight key problems that remain unsolved, and suggest ways to build on recent advances that will bring dynamic river networks into even sharper focus.

Low speed hybrid generalized predictive control of a gasoline-propelled car.

PubMed

Romero, M; de Madrid, A P; Mañoso, C; Milanés, V

2015-07-01

Low-speed driving in traffic jams causes significant pollution and wasted time for commuters. Additionally, from the passengers׳ standpoint, this is an uncomfortable, stressful and tedious scene that is suitable to be automated. The highly nonlinear dynamics of car engines at low-speed turn its automation in a complex problem that still remains as unsolved. Considering the hybrid nature of the vehicle longitudinal control at low-speed, constantly switching between throttle and brake pedal actions, hybrid control is a good candidate to solve this problem. This work presents the analytical formulation of a hybrid predictive controller for automated low-speed driving. It takes advantage of valuable characteristics supplied by predictive control strategies both for compensating un-modeled dynamics and for keeping passengers security and comfort analytically by means of the treatment of constraints. The proposed controller was implemented in a gas-propelled vehicle to experimentally validate the adopted solution. To this end, different scenarios were analyzed varying road layouts and vehicle speeds within a private test track. The production vehicle is a commercial Citroën C3 Pluriel which has been modified to automatically act over its throttle and brake pedals. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

[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.

Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation

PubMed Central

Kourtesi, Christina; Ball, Anthony R; Huang, Ying-Ying; Jachak, Sanjay M; Vera, D Mariano A; Khondkar, Proma; Gibbons, Simon; Hamblin, Michael R; Tegos, George P

2013-01-01

Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches. PMID:23569468

Communication: Correct charge transfer in CT complexes from the Becke'05 density functional

NASA Astrophysics Data System (ADS)

Becke, Axel D.; Dale, Stephen G.; Johnson, Erin R.

2018-06-01

It has been known for over twenty years that density functionals of the generalized-gradient approximation (GGA) type and exact-exchange-GGA hybrids with low exact-exchange mixing fraction yield enormous errors in the properties of charge-transfer (CT) complexes. Manifestations of this error have also plagued computations of CT excitation energies. GGAs transfer far too much charge in CT complexes. This error has therefore come to be called "delocalization" error. It remains, to this day, a vexing unsolved problem in density-functional theory (DFT). Here we report that a 100% exact-exchange-based density functional known as Becke'05 or "B05" [A. D. Becke, J. Chem. Phys. 119, 2972 (2003); 122, 064101 (2005)] predicts excellent charge transfers in classic CT complexes involving the electron donors NH3, C2H4, HCN, and C2H2 and electron acceptors F2 and Cl2. Our approach is variational, as in our recent "B05min" dipole moments paper [Dale et al., J. Chem. Phys. 147, 154103 (2017)]. Therefore B05 is not only an accurate DFT for thermochemistry but is promising as a solution to the delocalization problem as well.

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).

Large-scale outflows in luminous QSOs revisited. The impact of beam smearing on AGN feedback efficiencies

NASA Astrophysics Data System (ADS)

Husemann, B.; Scharwächter, J.; Bennert, V. N.; Mainieri, V.; Woo, J.-H.; Kakkad, D.

2016-10-01

Context. Feedback from active galactic nuclei (AGN) is thought to play an important role in quenching star formation in galaxies. However, the efficiency with which AGN dissipate their radiative energy into the ambient medium remains strongly debated. Aims: Enormous observational efforts have been made to constrain the energetics of AGN feedback by mapping the kinematics of the ionized gas on kpc scale. We study how the observed kinematics and inferred energetics are affected by beam smearing of a bright unresolved narrow-line region (NLR) due to seeing. Methods: We re-analyse optical integral-field spectroscopy of a sample of twelve luminous unobscured quasi-stellar objects (QSOs) (0.4

Corkscrew Structures and Precessing Jets

NASA Astrophysics Data System (ADS)

Sahai, Raghvendra

2005-07-01

Collimated jets are one of the most intriguing, yet poorly understood phenomena in astrophysics. Jets have been found in a wide variety of object classes which include AGNs, YSOs, massive X-ray binaries {e.g. SS433}, black hole X-ray transients, symbiotic stars, supersoft X-ray sources, and finally, planetary and preplanetary nebulae {PNs & PPNs}. In the case of PNs and PPNs, we have propsoed that wobbling collimated jets are the universal mechanism which can shape the wide variety of bipolar and multipolar morphologies seen in these objects. Most of our knowledge of post-AGB jets is indirectly inferred from their effects on the circumstellar envelopes of the progenitor AGB stars and, for that reason, these jets remain very poorly understood. Thus the mechanism that powers and collimates these jet-like post-AGB outflows remains as one of the most important, unsolved issues in post-AGB evolution. We propose an archival study of two bipolar PPNs, motivated by two recent discoveries which indicate that precessing jets are likely to be operational in them, and that the properties of the jets and the bipolar lobes produced by them, may be directly measured. One of these is IRAS16342-3814 {IRAS1634}, previously imaged with WPFC2, in which new Adaptive Optics {AO} observations at near-IR wavelengths show a remarkable corkscrew-shaped structure, the tell-tale signature of a precessing jet. Inspection of WFPC2 images of another PPN, OH231.8+4.2 in which we have recently discovered a A-type companion to the central mass-losing star, shows a sinuous nebulosity in a broad-band continuum image, resembling a corkscrew structure. We will use the latter to constrain the phsyical properties of the jet {precession period, opening angle, jet beam diameter, temporal history} in OH231.8. Using the multi-wavelength data on both sources, we will build models of the density distribution of the lobes and their interiors. In the case of IRAS1634, these models will be used to investigate the hypothesis that the HST images do not show the corkscrew structure because of opacity effects. Under the assumption that the jets are driven by an accretion disk around the companion, we will use theoretical relationships between disk precession and binary rotation period to estimate the properties of the binary {period, separation}. The results of this study will provide quantitative constraints for jet-driven shaping of PNs and inspire new models for the launching of jets from accretion disks in dying stars with binary companions.

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

29 CFR 1902.17 - The proceeding.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR STATE... subject or issue concerning the plan, the Assistant Secretary proposes to reject a plan or rejection remains in issue for any reason, he shall follow the procedures prescribed in the remaining sections of...

ACL Return to Sport Guidelines and Criteria.

PubMed

Davies, George J; McCarty, Eric; Provencher, Matthew; Manske, Robert C

2017-09-01

Because of the epidemiological incidence of anterior cruciate ligament (ACL) injuries, the high reinjury rates that occur when returning back to sports, the actual number of patients that return to the same premorbid level of competition, the high incidence of osteoarthritis at 5-10-year follow-ups, and the effects on the long-term health of the knee and the quality of life for the patient, individualizing the return to sports after ACL reconstruction (ACL-R) is critical. However, one of the challenging but unsolved dilemmas is what criteria and clinical decision making should be used to return an athlete back to sports following an ACL-R. This article describes an example of a functional testing algorithm (FTA) as one method for clinical decision making based on quantitative and qualitative testing and assessment utilized to make informed decisions to return an athlete to their sports safely and without compromised performance. The methods were a review of the best current evidence to support a FTA. In order to evaluate all the complicated domains of the clinical decision making for individualizing the return to sports after ACL-R, numerous assessments need to be performed including the biopsychosocial concepts, impairment testing, strength and power testing, functional testing, and patient-reported outcomes (PROs). The optimum criteria to use for individualizing the return to sports after ACL-R remain elusive. However, since this decision needs to be made on a regular basis with the safety and performance factors of the patient involved, this FTA provides one method of quantitatively and qualitatively making the decisions. Admittedly, there is no predictive validity of this system, but it does provide practical guidelines to facilitate the clinical decision making process for return to sports. The clinical decision to return an athlete back into competition has significant implications ranging from the safety of the athlete, to performance factors and actual litigation issues. By using a multifactorial FTA, such as the one described, provides quantitative and qualitatively criteria to make an informed decision in the best interests of the athlete.

Observations and simulations of the western United States' hydroclimate

NASA Astrophysics Data System (ADS)

Guirguis, Kristen

While very important from an economical and societal point of view, estimating precipitation in the western United States remains an unsolved and challenging problem. This is due to difficulties in observing and modeling precipitation in complex terrain. This research examines this issue by (i) providing a systematic evaluation of precipitation observations to quantify data uncertainty; and (ii) investigating the ability of the Ocean-Land-Atmosphere Model (OLAM) to simulate the winter hydroclimate in this region. This state-of-the-art, non-hydrostatic model has the capability of simulating simultaneously all scales of motions at various resolutions. This research intercompares nine precipitation datasets commonly used in hydrometeorological research in two ways. First, using principal component analysis, a precipitation climatology is conducted for the western U.S. from which five unique precipitation climates are identified. From this analysis, data uncertainty is shown to be primarily due to differences in (i) precipitation over the Rocky Mountains, (ii) the eastward wet-to-dry precipitation gradient during the cold season, (iii) the North American Monsoon signal, and (iv) precipitation in the desert southwest during spring and summer. The second intercomparison uses these five precipitation regions to provide location-specific assessments of uncertainty, which is shown to be dependent on season, location. Long-range weather forecasts on the order of a season are important for water-scarce regions such as the western U.S. The modeling component of this research looks at the ability of the OLAM to simulate the hydroclimate in the western U.S. during the winter of 1999. Six global simulations are run, each with a different spatial resolution over the western U.S. (360 km down to 11 km). For this study, OLAM is configured as for a long-range seasonal hindcast but with observed sea surface temperatures. OLAM precipitation compares well against observations, and is generally within the range of data uncertainty. Observed and simulated synoptic meteorological conditions are examined during the wettest and driest events. OLAM is shown to reproduce the appropriate anomaly fields, which is encouraging since it demonstrates the capability of a global climate model, driven only by SSTs and initial conditions, to represent meteorological features associated with daily precipitation variability.

National regulations for diagnostics in health surveillance, therapy and compensation of hand-transmitted vibration injury in Japan.

PubMed

Yamada, Shin'ya

2002-01-01

During the period of technological innovation and rapid economic development, portable power tools were introduced on a large scale in Japan. Vibration disease from the operation of those tools and its prevention and therapy became urgent social problems in the 1970s. This paper aims to introduce national regulations in Japan for diagnostics in the health surveillance, certification, therapy and compensation of vibration disease and evaluates them in the present perspective. Relevant laws, regulations and administrative directives were described in chronological order. Effect of those laws, regulations and directives were evaluated by statistics. Relevant regulations were established in 1947 and were revised in the 1960s and 1970s. According to those regulations, administrative directives were issued. Relevant vibration-disease statistics improved from the 1970s to 1990s. The annual ratio of workers examined was 95% to 100% in national forests (NFs), 47.3% in 1980 and 40.8% in 1990 in private industry (PI). The number of workers certified in NFs was 1,796 from 1971-1975, with a decrease to nine from 1991-1995, while in PI there were 9,783 from 1976-1980, decreasing to 2,331 from 1991-1995. However, in the construction industry the number increased again in the 1990s. The top four workers certified by the type of tool from 1994-1997 were operators of rock drills, chainsaws, pick hammers and concrete vibrators. The annual number of workers under treatment (at highest level) was 3,605 (1982; NFs) and 13,501 (1987; PI), with a decrease to 3,481 (1997; NFs) and 8,958 (1997; PI). Regulations for compensation covered 3,670 workers from 1965 to 1997 (NFs) and 22,723 from 1976 to 1997 (PI) in medical treatment benefits, and 189 (NFs) and 15,448 (PI) in disability benefits during the same term. The national regulations developed in Japan since 1965 for health surveillance, certification, therapy and compensation of hand-transmitted vibration disease have proven effective for prevention and compensation of vibration disease in many industries, but unsolved problems remain in the construction industry.

Advanced Tie Feature Matching for the Registration of Mobile Mapping Imaging Data and Aerial Imagery

NASA Astrophysics Data System (ADS)

Jende, P.; Peter, M.; Gerke, M.; Vosselman, G.

2016-06-01

Mobile Mapping's ability to acquire high-resolution ground data is opposing unreliable localisation capabilities of satellite-based positioning systems in urban areas. Buildings shape canyons impeding a direct line-of-sight to navigation satellites resulting in a deficiency to accurately estimate the mobile platform's position. Consequently, acquired data products' positioning quality is considerably diminished. This issue has been widely addressed in the literature and research projects. However, a consistent compliance of sub-decimetre accuracy as well as a correction of errors in height remain unsolved. We propose a novel approach to enhance Mobile Mapping (MM) image orientation based on the utilisation of highly accurate orientation parameters derived from aerial imagery. In addition to that, the diminished exterior orientation parameters of the MM platform will be utilised as they enable the application of accurate matching techniques needed to derive reliable tie information. This tie information will then be used within an adjustment solution to correct affected MM data. This paper presents an advanced feature matching procedure as a prerequisite to the aforementioned orientation update. MM data is ortho-projected to gain a higher resemblance to aerial nadir data simplifying the images' geometry for matching. By utilising MM exterior orientation parameters, search windows may be used in conjunction with a selective keypoint detection and template matching. Originating from different sensor systems, however, difficulties arise with respect to changes in illumination, radiometry and a different original perspective. To respond to these challenges for feature detection, the procedure relies on detecting keypoints in only one image. Initial tests indicate a considerable improvement in comparison to classic detector/descriptor approaches in this particular matching scenario. This method leads to a significant reduction of outliers due to the limited availability of putative matches and the utilisation of templates instead of feature descriptors. In our experiments discussed in this paper, typical urban scenes have been used for evaluating the proposed method. Even though no additional outlier removal techniques have been used, our method yields almost 90% of correct correspondences. However, repetitive image patterns may still induce ambiguities which cannot be fully averted by this technique. Hence and besides, possible advancements will be briefly presented.

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

Historical earthquakes studies in Eastern Siberia: State-of-the-art and plans for future

NASA Astrophysics Data System (ADS)

Radziminovich, Ya. B.; Shchetnikov, A. A.

2013-01-01

Many problems in investigating historical seismicity of East Siberia remain unsolved. A list of these problems may refer particularly to the quality and reliability of data sources, completeness of parametric earthquake catalogues, and precision and transparency of estimates for the main parameters of historical earthquakes. The main purpose of this paper is to highlight the current status of the studies of historical seismicity in Eastern Siberia, as well as analysis of existing macroseismic and parametric earthquake catalogues. We also made an attempt to identify the main shortcomings of existing catalogues and to clarify the reasons for their appearance in the light of the history of seismic observations in Eastern Siberia. Contentious issues in the catalogues of earthquakes are considered by the example of three strong historical earthquakes, important for assessing seismic hazard in the region. In particular, it was found that due to technical error the parameters of large M = 7.7 earthquakes of 1742 were transferred from the regional catalogue to the worldwide database with incorrect epicenter coordinates. The way some stereotypes concerning active tectonics influences on the localization of the epicenter is shown by the example of a strong М = 6.4 earthquake of 1814. Effect of insufficient use of the primary data source on completeness of earthquake catalogues is illustrated by the example of a strong M = 7.0 event of 1859. Analysis of the state-of-the-art of historical earthquakes studies in Eastern Siberia allows us to propose the following activities in the near future: (1) database compilation including initial descriptions of macroseismic effects with reference to their place and time of occurrence; (2) parameterization of the maximum possible (magnitude-unlimited) number of historical earthquakes on the basis of all the data available; (3) compilation of an improved version of the parametric historical earthquake catalogue for East Siberia with detailed consideration of each event and distinct logic schemes for data interpretation. Thus, we can make the conclusion regarding the necessity of a large-scale revision in historical earthquakes catalogues for the area of study.

Different uptake of 123I-MIBG in the two main liver lobes: A persistant unsolved mistery.

PubMed

Bonacina, M; Albano, D; Steimberg, N; Bosio, G; Camoni, L; Bertagna, F; Giubbini, R; Mazzoleni, G

2018-05-10

After radiopharmaceutical injection, a heightened 123 I-MIBG concentration is frequently observed in the left hepatic lobe compared to the right one, but the reason of this finding remains unknown. Our aim was to retrospectively analyze the different 123 I-MIBG uptake pattern between the two hepatic lobes and correlate our results with some epidemiological/clinical features. Ninety-four 123 I-MIBG scintigraphies from 71 patients were selected. Regions of interest were drawn in the right and left lobes using transverse tomographic sections and left to right activity ratios (L/R ratio) were calculated at 6 and 24h after radiotracer administration. Twenty-seven examinations were positive for hypermetabolic lesions while the remaining 67 were negative. In all cases mean early and delayed L/R ratios were greater than 1.00; average early L/R ratio was 1.37 and delayed L/R ratio 1.52. The delayed L/R ratio was significantly higher than the early one. There was no difference in the L/R ratios with regard to age, gender, primary disease and result of scintigraphy. 123 I-MIBG uptake was higher in left hepatic lobe compared to right and this ratio did not correlate with any epidemiological or clinical feature. The reason of this metabolic is not yet explained and some biomolecular hypotheses could be tested in 3D dynamic in vitro models. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

Correction of lobule-type microtia: I. The first stage of costal cartilage grafting.

PubMed

Yotsuyanagi, Takatoshi; Yamashita, Ken; Yamauchi, Makoto; Sugai, Asuka; Kayama, Musashi; Gonda, Ayako; Kita, Arisa

2014-01-01

Recently, auriculoplasty with costal cartilage grafting has been successfully used for correcting microtia and creating a clearly refined contour and a natural appearance of the ear. However, several important problems remain unsolved in these techniques. The authors describe an improved technique for harvesting costal cartilage with minimal morbidity and a new procedure for fabricating a cartilage frame that ensures a refined shape and rigid structure of the constructed ear. Costal cartilage is harvested directly with a chisel. This technique enables some of the cartilage at the chest wall to remain intact. The base frame is fabricated by two cartilage blocks partly overlapped on the area of the antihelix. The thickness in the overlapping area emphasizes the contour between the antihelix and the helical crus. To prevent absorption of the cartilage, helical and antihelical parts are created using the outer rigid layer of the harvested cartilage and are covered as much as possible by perichondrium. A total of 137 ears in 121 patients were corrected with the authors' technique and followed up for at least 3 years. Almost all of the patients could walk within 2 days after the operation. The structure and contour of the constructed ear were well maintained. Attention should be given not only to successful outcomes of construction of the ear but also to minimal morbidity for the patients. Our technique made it possible to construct a cosmetically refined ear that could be maintained for a long period and minimize the pain and deformity of the donor's chest.

Heart lesion after the first attack of the rheumatic Fever 22 years experience in single centre.

PubMed

Bejiqi, Ramush A; Retkoceri, Ragip; Zeka, Naim; Bejiqi, Hana; Retkoceri, Arber

2015-02-01

Acute rheumatic fever and its sequels, rheumatic heart diseases, remain major unsolved preventable health problems in Kosovo population, particularly among the disadvantages indigenous Albanian and Egyptians people. In Kosovo, despite of performing secondary prophylaxis with benzathine penicillin, acute rheumatic fever hospitalization rates have remained essentially unchanged for the last 20 years. The role of echocardiography in the diagnosis of acute rheumatic carditis was established over the last 20 years. In this study we aimed to determine the prevalence of rheumatic heart disease in children from Kosovo population with first attack of acute rheumatic fever. Also, we presented that echocardiography examination detects a greater prevalence of rheumatic heart disease than other diagnostic procedures. We aimed to compare the sensitivity and specificity of cardiac auscultation, ECG record, lab analysis to echocardiography and to determine the feasibility of specific age in this setting. To optimize accurate diagnosis of rheumatic fever and rheumatic heart disease, we utilized two group models. In the first group of 388 children, hospitalized and treated before 1999, diagnosis of rheumatic fever was decided basing on the clinical and laboratory findings whereas in second group (221 children treated from1999 to 2010) clinical and lab diagnosis were amplified also on the detection by echocardiography. In second group, using echocardiography as a method of diagnosis and assessment children with rheumatic fever, we found high rates of undetected rheumatic heart disease in this high-risk group population. Echocardiographic examination of children with rheumatic fever for rheumatic heart disease may over diagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded.

The mixed alkali effect in ionically conducting glasses revisited: a study by molecular dynamics simulation.

PubMed

Habasaki, Junko; Ngai, Kia L

2007-09-07

When more than two kinds of mobile ions are mixed in ionic conducting glasses and crystals, there is a non-linear decrease of the transport coefficients of either type of ion. This phenomenon is known as the mixed mobile ion effect or Mixed Alkali Effect (MAE), and remains an unsolved problem. We use molecular dynamics simulation to study the complex ion dynamics in ionically conducting glasses including the MAE. In the mixed alkali lithium-potassium silicate glasses and related systems, a distinct part of the van Hove functions reveals that jumps from one kind of site to another are suppressed. Although, consensus for the existence of preferential jump paths for each kind of mobile ions seems to have been reached amongst researchers, the role of network formers and the number of unoccupied ion sites remain controversial in explaining the MAE. In principle, these factors when incorporated into a theory can generate the MAE, but in reality they are not essential for a viable explanation of the ion dynamics and the MAE. Instead, dynamical heterogeneity and "cooperativity blockage" originating from ion-ion interaction and correlation are fundamental for the observed ion dynamics and the MAE. Suppression of long range motion with increased back-correlated motions is shown to be a cause of the large decrease of the diffusivity especially in dilute foreign alkali regions. Support for our conclusion also comes from the fact that these features of ion dynamics are common to other ionic conductors, which have no glassy networks, and yet they all exhibit the MAE.

Iraq Reconstruction: Lessons from Auditing U.S.-funded Stabilization and Reconstruction Activities

DTIC Science & Technology

2012-10-01

Emergency Response Program: Hotel Construction Successfully Completed, but Project Management Issues Remain 09-025 7/26/2009 Commander’s Emergency...Emergency Response Pro- gram: Hotel Construction Completed, but Project Management Issues Remain,” 7/26/2009. 47. SIGIR Audit 11-003, “Iraqi Security Forces

Coxiella burnetii DNA in goat milk after vaccination with Coxevac(®).

PubMed

Hermans, Mirjam H A; Huijsmans, C Ronald J J; Schellekens, Jeroen J A; Savelkoul, Paul H M; Wever, Peter C

2011-03-24

Q fever is a zoonotic disease caused by Coxiella burnetii, a species of bacteria that is distributed globally. A large Q fever epidemic is currently spreading throughout the Netherlands with more than 3500 human cases notified from 2007 to 2009. Governmental measures to prevent further spread of the disease imposed in December 2009 included vaccination of all dairy goats and sheep and, in parallel, bulk tank milk testing to identify contaminated goat and sheep farms. When bulk tank milk was found to contain C. burnetii DNA, pregnant ruminants were culled. An important, but unsolved issue in this policy was whether vaccine-derived C. burnetii DNA is excreted in milk after vaccination. Using real time PCR and single nucleotide polymorphism (SNP) genotyping techniques, we show here that within hours and up to 9 days after vaccination with Coxevac(®), vaccine-derived C. burnetii DNA can be detected in the milk of dairy goats. This is the first report describing DNAlactia of vaccine-derived DNA after vaccination with a completely inactivated vaccine. This finding had implications for the Dutch policy to combat the Q fever epidemic. A 2-week interval was introduced between vaccination and bulk tank milk testing to identify infected farms. Copyright © 2011 Elsevier Ltd. All rights reserved.

[An analysis of essential health research in Chile].

PubMed

Armas Merino, Rodolfo; Torres Canales, Adrián

2017-07-01

Essential research studies of health problems affecting the majority of the population, aiming at actions that are feasible to be taken, efficiently and effectively implementing there and seeking solutions to unsolved problems. This is a complex process, which requires long lasting participation and coordinated interaction between different relevant sectors, namely the academic world, health policymakers and health-related industries. An analysis of essential health research in Chile is presented, considering factors such as shared efforts between the academic and health care sectors and the role of the Ministry of Health in research promotion. The following suggestions are made: 1) The Ministry of Health, along with universities, should stimulate, guide and monitor research activities that enrich and update the work on priority health issues; 2) To strengthen the capacity building of clinical or public health specialists by training them in applied research within medical centers, mainly teaching centers; 3) To assess the performance of National Fund for Health Research and Development (FONIS) and, if necessary, increase its resources to stimulate applied research in health; 4) To establish priorities for essential research, more specific than those proposed in 2010; 5) To reactivate the National Council for Health Research (CONIS) as an autonomous entity that coordinates applied research within the Ministry of Health.

Measurement of the 1s Hyperfine Transition of Two Tl^80+ Isotopes

NASA Astrophysics Data System (ADS)

Beiersdorfer, P.; Utter, S. B.; Wong, K. L.; Crespo López-Urrutia, J. R.; Britten, J. A.; Chen, H.; Thoe, R. S.; Thorn, D. B.; Träbert, E.; Gustavsson, M. G. H.; Forssén, C.; Mårtenson-Pendrill, A.-M.; Harris, C. L.

2001-05-01

The hyperfine splitting of the 1s ground state has been measured for the two stable isotopes of hydrogen-like Tl using emission spectroscopy in the SuperEBIT electron beam ion trap. The results are 3858.22± 0.30 Åfor ^203Tl^80+ and 3821.84± 0.34 Åfor ^205Tl^80+. These differ by about 60 Å from recent and about 19 Å from very recent calculations, illustrating unsolved issues affecting these transitions in hydrogen-like ions. The wavelength difference Δλ = 36.38± 0.35 Å is consistent with estimates based on hyperfine anomaly data for neutral Tl. By using previously determined nuclear magnetic moments and applying appropriate corrections for the nuclear charge distribution and radiative effects, the experimental splittings can be interpreted in terms of nuclear magnetization radii < r^2_m>^1/2= 5.83(14) fm for ^203Tl and < r^2_m>^1/2= 5.89(14) fm for ^205Tl. These values are 10% larger than derived from single-particle nuclear magnetization models, and are slightly larger than the corresponding charge distributions. *Work performed under the auspices of DOE by UCLLNL under contract W-7405-ENG-48 and supported by the Office of Basic Energy Sciences.

Trojan horses and guided missiles: targeted therapies in the war on arthritis.

PubMed

Ferrari, Mathieu; Onuoha, Shimobi C; Pitzalis, Costantino

2015-06-01

Despite major advances in the treatment of rheumatoid arthritis (RA) led by the success of biologic therapies, the lack of response to therapy in a proportion of patients, as well as therapy discontinuation owing to systemic toxicity, are still unsolved issues. Unchecked RA might develop into progressive structural joint damage, loss of function and long-term disability, disorders which are associated with a considerable health-economic burden. Therefore, new strategies are required to actively target and deliver therapeutic agents to disease sites in order to promote in situ activity and decrease systemic toxicity. Polymer-drug conjugates can improve the pharmacokinetics of therapeutic agents, conferring desirable properties such as increased solubility and tissue penetration at sites of active disease. Additionally, nanotechnology is an exciting modality in which drugs are encapsulated to protect them from degradation or early activation in the circulation, as well as to reduce systemic toxicity. Together with the targeting capacity of antibodies and site-specific peptides, these approaches will facilitate selective accumulation of therapeutic agents in the inflamed synovium, potentially improving drug efficacy at disease sites without affecting healthy tissues. This Review aims to summarize key developments in the past 5 years in polymer conjugation, nanoparticulate drug delivery and antibody or peptide-based targeting--strategies that might constitute the platform for the next generation of RA therapeutics.

Integrating electrochemical oxidation into forward osmosis process for removal of trace antibiotics in wastewater.

PubMed

Liu, Pengxiao; Zhang, Hanmin; Feng, Yujie; Shen, Chao; Yang, Fenglin

2015-10-15

During the rejection of trace pharmaceutical contaminants from wastewater by forward osmosis (FO), disposal of the FO concentrate was still an unsolved issue. In this study, by integrating the advantages of forward osmosis and electrochemical oxidation, a forward osmosis process with the function of electrochemical oxidation (FOwEO) was established for the first time to achieve the aim of rejection of trace antibiotics from wastewater and treatment of the concentrate at the same time. Results demonstrated that FOwEO (current density J=1 mA cm(-2)) exhibited excellent rejections of antibiotics (>98%) regardless of different operation conditions, and above all, antibiotics in the concentrate were well degraded (>99%) at the end of experiment (after 3h). A synergetic effect between forward osmosis and electrochemical oxidation was observed in FOwEO, which lies in that antibiotic rejections by FO were enhanced due to the degradation of antibiotics in the concentrate, while the electrochemical oxidation capacity was improved in the FOwEO channel, of which good mass transfer and the assist of indirect oxidation owing to the reverse NaCl from draw solution were supposed to be the mechanism. This study demonstrated that the FOwEO has the capability to thoroughly remove trace antibiotics from wastewater. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanical power efficiency of modified turbine blades

NASA Astrophysics Data System (ADS)

Mahmud, Syahir; Sampebatu, Limbran; Kwang, Suendy Ciayadi

2017-01-01

Abstract-The problem of energy crisis has become one of the unsolved issues until today. Indonesia has a lot of non-conventional energy sources that does not utilized effectively yet. For that the available resources must utilized efficiently due to the energy crisis and the growing energy needs. Among the abundant resources of energy, one potential source of energy is hydroelectric energy. This research compares the mechanical power efficiency generated by the Darrieus turbine, Savonius turbine and the Darrieus-Savonius turbine. The comparation of the mechanical power amongst the three turbine starts from the measurement of the water flow rate, water temperature, turbine rotation and force on the shaft on each type of turbine. The comparison will show the mechanical power efficiency of each turbine to find the most efficient turbine that can work optimally. The results show that with 0.637m/s flow velocity and 44.827 Watt of water flow power, the Darrieus-Savonius turbine can generate power equal to 29.927 Watt and shaft force around by 17 N. The Darrieus-Savonius turbine provides around 66.76% efficiency betwen the three turbines; Darrieus turbine, Savonius turbine and the Darrieus-Savonius turbine. Overall, the Darrieus Savonius turbine has the ability to work optimally at the research location.

Optimization for ultrasound-assisted extraction of polysaccharides with chemical composition and antioxidant activity from the Artemisia sphaerocephala Krasch seeds.

PubMed

Zheng, Quan; Ren, Daoyuan; Yang, Nana; Yang, Xingbin

2016-10-01

Artemisia sphaerocephala Krasch seeds polysaccharides have been reported to have a variety of important biological activities. However, effective extraction of Artemisia sphaerocephala Krasch seeds polysaccharides is still an unsolved issue. In this study, the orthogonal rotatable central composite design was employed to optimize ultrasound-assisted extraction conditions of Artemisia sphaerocephala Krasch seeds polysaccharides. Based on a single-factor analysis method, ultrasonic power, extraction time, solid-liquid ratio and extraction temperature were shown to significantly affect the yield of polysaccharides extracted from the A. sphaerocephala Krasch seeds. The optimal conditions for extraction of Artemisia sphaerocephala Krasch seeds polysaccharides were determined as following: ultrasonic power 243W, extraction time 125min, solid-liquid ratio 64:1 and extraction temperature 64°C, where the experimental yield was 14.78%, which was well matched with the predicted value of 14.81%. Furthermore, ASKP was identified as a typical heteropolysaccharide with d-galacturonic acid (38.8%) d-galactose (20.2%) and d-xylose (15.5%) being the main constitutive monosaccharides. Moreover, Artemisia sphaerocephala Krasch seeds polysaccharides exhibited high total reducing power and considerable scavenging activities on DPPH, hydroxyl and superoxide radicals, in a concentration-dependent manner in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

Semantic and syntactic interoperability in online processing of big Earth observation data.

PubMed

Sudmanns, Martin; Tiede, Dirk; Lang, Stefan; Baraldi, Andrea

2018-01-01

The challenge of enabling syntactic and semantic interoperability for comprehensive and reproducible online processing of big Earth observation (EO) data is still unsolved. Supporting both types of interoperability is one of the requirements to efficiently extract valuable information from the large amount of available multi-temporal gridded data sets. The proposed system wraps world models, (semantic interoperability) into OGC Web Processing Services (syntactic interoperability) for semantic online analyses. World models describe spatio-temporal entities and their relationships in a formal way. The proposed system serves as enabler for (1) technical interoperability using a standardised interface to be used by all types of clients and (2) allowing experts from different domains to develop complex analyses together as collaborative effort. Users are connecting the world models online to the data, which are maintained in a centralised storage as 3D spatio-temporal data cubes. It allows also non-experts to extract valuable information from EO data because data management, low-level interactions or specific software issues can be ignored. We discuss the concept of the proposed system, provide a technical implementation example and describe three use cases for extracting changes from EO images and demonstrate the usability also for non-EO, gridded, multi-temporal data sets (CORINE land cover).