[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.

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.

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

PubMed Central

Feng, Huizhong

2018-01-01

Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes—glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death. Several key mysteries regarding how cells die during ferroptosis remain unsolved. First, the drivers of lipid peroxidation are not yet clear. Second, the subcellular location of lethal lipid peroxides remains an outstanding question. Finally, how exactly lipid peroxidation leads to cell death is an unsolved mystery. Answers to these questions will provide insights into the mechanisms of ferroptotic cell death and associated human diseases, as well as new therapeutic strategies for such diseases. PMID:29795546

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.

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.

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.

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.

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.

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.

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.

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.

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…

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

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

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.

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.

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.

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)

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.

A survey on hair modeling: styling, simulation, and rendering.

PubMed

Ward, Kelly; Bertails, Florence; Kim, Tae-Yong; Marschner, Stephen R; Cani, Marie-Paule; Lin, Ming C

2007-01-01

Realistic hair modeling is a fundamental part of creating virtual humans in computer graphics. This paper surveys the state of the art in the major topics of hair modeling: hairstyling, hair simulation, and hair rendering. Because of the difficult, often unsolved problems that arise in all these areas, a broad diversity of approaches are used, each with strengths that make it appropriate for particular applications. We discuss each of these major topics in turn, presenting the unique challenges facing each area and describing solutions that have been presented over the years to handle these complex issues. Finally, we outline some of the remaining computational challenges in hair modeling.

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)

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.

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

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

The RNA World as a Model System to Study the Origin of Life.

PubMed

Pressman, Abe; Blanco, Celia; Chen, Irene A

2015-10-05

Understanding how life arose is a fundamental problem of biology. Much progress has been made by adopting a synthetic and mechanistic perspective on originating life. We present a current view of the biochemistry of the origin of life, focusing on issues surrounding the emergence of an RNA World in which RNA dominated informational and functional roles. There is cause for optimism on this difficult problem: the prebiotic chemical inventory may not have been as nightmarishly complex as previously thought; the catalytic repertoire of ribozymes continues to expand, approaching the goal of self-replicating RNA; encapsulation in protocells provides evolutionary and biophysical advantages. Nevertheless, major issues remain unsolved, such as the origin of a genetic code. Attention to this field is particularly timely given the accelerating discovery and characterization of exoplanets. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

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.

'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.

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.

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.

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

USGS Publications Warehouse

Voss, Clifford I.

2003-01-01

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

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.

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…

[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.

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.

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.

Brain Dynamics: Methodological Issues and Applications in Psychiatric and Neurologic Diseases

NASA Astrophysics Data System (ADS)

Pezard, Laurent

The human brain is a complex dynamical system generating the EEG signal. Numerical methods developed to study complex physical dynamics have been used to characterize EEG since the mid-eighties. This endeavor raised several issues related to the specificity of EEG. Firstly, theoretical and methodological studies should address the major differences between the dynamics of the human brain and physical systems. Secondly, this approach of EEG signal should prove to be relevant for dealing with physiological or clinical problems. A set of studies performed in our group is presented here within the context of these two problematic aspects. After the discussion of methodological drawbacks, we review numerical simulations related to the high dimension and spatial extension of brain dynamics. Experimental studies in neurologic and psychiatric disease are then presented. We conclude that if it is now clear that brain dynamics changes in relation with clinical situations, methodological problems remain largely unsolved.

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.

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.

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.

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.

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.

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.

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 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.

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

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.

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,…

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…

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.

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.

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.

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.

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

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…

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…

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.

On the theory of the Frankl problem for equations of mixed type

NASA Astrophysics Data System (ADS)

Sabitov, K. B.

2017-02-01

In 1956 Frankl, while studying subsonic flows past a profile with a supersonic zone terminating with a normal compression shock, arrived at a new mathematical problem for the Chaplygin equation with a non-local boundary condition. In this article we give a survey of classical and recent papers dedicated to this problem. We present theorems on the existence and uniqueness of the solution of the Frankl problem, study the spectral problem for the Lavrent'ev-Bitsadze operator, show applications of these results to the construction of a solution with the aid of a series, and state some unsolved problems.

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

DTIC Science & Technology

1984-01-16

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

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

[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.

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.

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...

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

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

Wharton, Sonia; Newman, Jennifer F.

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

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

DOE PAGES

Wharton, Sonia; Newman, Jennifer F.

2017-09-11

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

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.

User Interface Problems of a Nationwide Inpatient Information System: A Heuristic Evaluation.

PubMed

Atashi, Alireza; Khajouei, Reza; Azizi, Amirabbas; Dadashi, Ali

2016-01-01

While studies have shown that usability evaluation could uncover many design problems of health information systems, the usability of health information systems in developing countries using their native language is poorly studied. The objective of this study was to evaluate the usability of a nationwide inpatient information system used in many academic hospitals in Iran. Three trained usability evaluators independently evaluated the system using Nielsen's 10 usability heuristics. The evaluators combined identified problems in a single list and independently rated the severity of the problems. We statistically compared the number and severity of problems identified by HIS experienced and non-experienced evaluators. A total of 158 usability problems were identified. After removing duplications 99 unique problems were left. The highest mismatch with usability principles was related to "Consistency and standards" heuristic (25%) and the lowest related to "Flexibility and efficiency of use" (4%). The average severity of problems ranged from 2.4 (Major problem) to 3.3 (Catastrophe problem). The experienced evaluator with HIS identified significantly more problems and gave higher severities to problems (p<0.02). Heuristic Evaluation identified a high number of usability problems in a widely used inpatient information system in many academic hospitals. These problems, if remain unsolved, may waste users' and patients' time, increase errors and finally threaten patient's safety. Many of them can be fixed with simple redesign solutions such as using clear labels and better layouts. This study suggests conducting further studies to confirm the findings concerning effect of evaluator experience on the results of Heuristic Evaluation.

User Interface Problems of a Nationwide Inpatient Information System: A Heuristic Evaluation

PubMed Central

Atashi, Alireza; Azizi, Amirabbas; Dadashi, Ali

2016-01-01

Summary Introduction While studies have shown that usability evaluation could uncover many design problems of health information systems, the usability of health information systems in developing countries using their native language is poorly studied. The objective of this study was to evaluate the usability of a nationwide inpatient information system used in many academic hospitals in Iran. Material and Methods Three trained usability evaluators independently evaluated the system using Nielsen’s 10 usability heuristics. The evaluators combined identified problems in a single list and independently rated the severity of the problems. We statistically compared the number and severity of problems identified by HIS experienced and non-experienced evaluators. Results A total of 158 usability problems were identified. After removing duplications 99 unique problems were left. The highest mismatch with usability principles was related to “Consistency and standards” heuristic (25%) and the lowest related to “Flexibility and efficiency of use” (4%). The average severity of problems ranged from 2.4 (Major problem) to 3.3 (Catastrophe problem). The experienced evaluator with HIS identified significantly more problems and gave higher severities to problems (p<0.02). Discussion Heuristic Evaluation identified a high number of usability problems in a widely used inpatient information system in many academic hospitals. These problems, if remain unsolved, may waste users’ and patients’ time, increase errors and finally threaten patient’s safety. Many of them can be fixed with simple redesign solutions such as using clear labels and better layouts. This study suggests conducting further studies to confirm the findings concerning effect of evaluator experience on the results of Heuristic Evaluation. PMID:27081409

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

PubMed

Foster, Z; Hirsch, S; Zaske, K

1991-01-01

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

Influence maximization in complex networks through optimal percolation

NASA Astrophysics Data System (ADS)

Morone, Flaviano; Makse, Hernán A.

2015-08-01

The whole frame of interconnections in complex networks hinges on a specific set of structural nodes, much smaller than the total size, which, if activated, would cause the spread of information to the whole network, or, if immunized, would prevent the diffusion of a large scale epidemic. Localizing this optimal, that is, minimal, set of structural nodes, called influencers, is one of the most important problems in network science. Despite the vast use of heuristic strategies to identify influential spreaders, the problem remains unsolved. Here we map the problem onto optimal percolation in random networks to identify the minimal set of influencers, which arises by minimizing the energy of a many-body system, where the form of the interactions is fixed by the non-backtracking matrix of the network. Big data analyses reveal that the set of optimal influencers is much smaller than the one predicted by previous heuristic centralities. Remarkably, a large number of previously neglected weakly connected nodes emerges among the optimal influencers. These are topologically tagged as low-degree nodes surrounded by hierarchical coronas of hubs, and are uncovered only through the optimal collective interplay of all the influencers in the network. The present theoretical framework may hold a larger degree of universality, being applicable to other hard optimization problems exhibiting a continuous transition from a known phase.

Influence maximization in complex networks through optimal percolation.

PubMed

Morone, Flaviano; Makse, Hernán A

2015-08-06

The whole frame of interconnections in complex networks hinges on a specific set of structural nodes, much smaller than the total size, which, if activated, would cause the spread of information to the whole network, or, if immunized, would prevent the diffusion of a large scale epidemic. Localizing this optimal, that is, minimal, set of structural nodes, called influencers, is one of the most important problems in network science. Despite the vast use of heuristic strategies to identify influential spreaders, the problem remains unsolved. Here we map the problem onto optimal percolation in random networks to identify the minimal set of influencers, which arises by minimizing the energy of a many-body system, where the form of the interactions is fixed by the non-backtracking matrix of the network. Big data analyses reveal that the set of optimal influencers is much smaller than the one predicted by previous heuristic centralities. Remarkably, a large number of previously neglected weakly connected nodes emerges among the optimal influencers. These are topologically tagged as low-degree nodes surrounded by hierarchical coronas of hubs, and are uncovered only through the optimal collective interplay of all the influencers in the network. The present theoretical framework may hold a larger degree of universality, being applicable to other hard optimization problems exhibiting a continuous transition from a known phase.

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.

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.

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.

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.

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.

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.

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.

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.

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,…

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…

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...

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.

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)…

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...

Neural tube defects – recent advances, unsolved questions and controversies

PubMed Central

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

2014-01-01

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

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.

Reasoning by analogy as an aid to heuristic theorem proving.

NASA Technical Reports Server (NTRS)

Kling, R. E.

1972-01-01

When heuristic problem-solving programs are faced with large data bases that contain numbers of facts far in excess of those needed to solve any particular problem, their performance rapidly deteriorates. In this paper, the correspondence between a new unsolved problem and a previously solved analogous problem is computed and invoked to tailor large data bases to manageable sizes. This paper outlines the design of an algorithm for generating and exploiting analogies between theorems posed to a resolution-logic system. These algorithms are believed to be the first computationally feasible development of reasoning by analogy to be applied to heuristic theorem proving.

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

State-of-the-art acute phase management of Kawasaki disease after 2017 scientific statement from the American Heart Association.

PubMed

Liu, Yi-Ching; Lin, Ming-Tai; Wang, Jou-Kou; Wu, Mei-Hwan

2018-03-30

Kawasaki disease (KD) has become the most common form of pediatric systemic vasculitis. Although patients with KD received intravenous immunoglobulin (IVIG) therapy, coronary arterial lesions (CALs) still occurred in 5%-10% of these patients during the acute stage. CALs may persist and even progress to stenosis or obstruction. Therefore, CALs following KD are currently the leading cause of acquired heart diseases in children. The etiology of CALs remains unknown despite more than four decades of research. Two unsolved problems are IVIG unresponsiveness and the diagnosis of incomplete KD. The two subgroups of KD patients with these problems have a high risk of CAL. In April 2017, the American Heart Association (AHA) updated the guidelines for the diagnosis, treatment, and long-term management of KD. Compared with the previous KD guidelines published in 2004, the new guidelines provide solutions to the aforementioned two problems and emphasize risk stratification by using coronary artery Z score systems, as well as coronary severity-based management and long-term follow-up. Therefore, in this study, we merged the AHA Scientific Statement in 2017 with recent findings for Taiwanese KD patients to provide potential future care directions for Taiwanese patients with KD. Copyright © 2018. Published by Elsevier B.V.

Putting the Aero Back into Aeroelasticity

NASA Technical Reports Server (NTRS)

Bousman, William G.

2000-01-01

The lack of progress in understanding the physics of rotorcraft loads and vibration over the last 30 years is addressed in this paper. As befits this extraordinarily difficult problem, the reasons for the lack of progress are complicated and difficult to ascertain. It is proposed here that the difficulty lies within at least three areas: 1) a loss of perspective as to what are the key factors in rotor loads and vibration, 2) the overlooking of serious unsolved problems in the field, and 3) cultural barriers that impede progress. Some criteria are suggested for future research to provide a more concentrated focus on the problem.

Putting the Aero Back Into Aeroelasticity

NASA Technical Reports Server (NTRS)

Bousman, William G.; Aiken, Edwin W. (Technical Monitor)

1999-01-01

The lack of progress in understanding the physics of rotorcraft loads and vibration over the last 30 years is addressed in this paper. As befits this extraordinarily difficult problem, the reasons for the lack of progress are complicated and difficult to ascertain. It is proposed here that the difficulty lies within at least three areas: 1) a loss of perspective as to what are the key factors in rotor loads and vibration, 2) the overlooking of serious unsolved problems in the field, and 3) cultural barriers that impede progress. Some criteria are suggested for future research to provide a more concentrated focus on the problem.

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

PubMed

Dev, Sukhendu B

2015-03-01

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

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…

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.

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.

Patent eligibility of stem cells in Europe: where do we stand after 8 years of case law?

PubMed

Storz, Ulrich; Faltus, Timo

2017-01-01

Since 2006, some of the highest ranking European Courts have issued decisions related to the patent eligibility of human embryonic stem cells. The question of patent eligibility of human embryonic stem cells remains, however, still erratic, at least in some aspects. This article will give a short comprehensive overview of the case history, and discuss questions still unsolved.

Algorithmics - Is There Hope for a Unified Theory?

NASA Astrophysics Data System (ADS)

Hromkovič, Juraj

Computer science was born with the formal definition of the notion of an algorithm. This definition provides clear limits of automatization, separating problems into algorithmically solvable problems and algorithmically unsolvable ones. The second big bang of computer science was the development of the concept of computational complexity. People recognized that problems that do not admit efficient algorithms are not solvable in practice. The search for a reasonable, clear and robust definition of the class of practically solvable algorithmic tasks started with the notion of the class {P} and of {NP}-completeness. In spite of the fact that this robust concept is still fundamental for judging the hardness of computational problems, a variety of approaches was developed for solving instances of {NP}-hard problems in many applications. Our 40-years short attempt to fix the fuzzy border between the practically solvable problems and the practically unsolvable ones partially reminds of the never-ending search for the definition of "life" in biology or for the definitions of matter and energy in physics. Can the search for the formal notion of "practical solvability" also become a never-ending story or is there hope for getting a well-accepted, robust definition of it? Hopefully, it is not surprising that we are not able to answer this question in this invited talk. But to deal with this question is of crucial importance, because only due to enormous effort scientists get a better and better feeling of what the fundamental notions of science like life and energy mean. In the flow of numerous technical results, we must not forget the fact that most of the essential revolutionary contributions to science were done by defining new concepts and notions.

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

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.

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.

Testing Scientific Software: A Systematic Literature Review.

PubMed

Kanewala, Upulee; Bieman, James M

2014-10-01

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

[Substance abuse and toxicity. Fetal drug syndrome].

PubMed

Rodé, Magdolna

2003-08-10

24% of the 16 years old adolescents have already consumed so called substances suitable for abuse. We must make children, teachers, parents, lawyers, priests, physicians and family aware of the effects and outcomes of drug use. This is just one of the many similar unsolved problems of society like AIDS and smoking. It is imperative that education for healthy lifestyle should be thought at every level of social life. Fighting against the hard problems emerging from drug abuse must be continuously kept on the right place in teaching medicine and in our everyday activity.

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

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.

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.

Deterministic theory of Monte Carlo variance

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

Ueki, T.; Larsen, E.W.

1996-12-31

The theoretical estimation of variance in Monte Carlo transport simulations, particularly those using variance reduction techniques, is a substantially unsolved problem. In this paper, the authors describe a theory that predicts the variance in a variance reduction method proposed by Dwivedi. Dwivedi`s method combines the exponential transform with angular biasing. The key element of this theory is a new modified transport problem, containing the Monte Carlo weight w as an extra independent variable, which simulates Dwivedi`s Monte Carlo scheme. The (deterministic) solution of this modified transport problem yields an expression for the variance. The authors give computational results that validatemore » this theory.« less

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.

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

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

Workshop on the Growth of Continental Crust

NASA Technical Reports Server (NTRS)

Ashwal, Lewis D. (Editor)

1988-01-01

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

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

PubMed

Tommasi, M

1976-01-01

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

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

PubMed

Smith, Bradley Philip; Litchfield, Carla Anita

2013-11-01

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

Testing Scientific Software: A Systematic Literature Review

PubMed Central

Kanewala, Upulee; Bieman, James M.

2014-01-01

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

Diffraction of a plane wave on two-dimensional conductive structures and a surface wave

NASA Astrophysics Data System (ADS)

Davidovich, Mikhael V.

2018-04-01

We consider the structures type of two-dimensional electron gas in the form of a thin conductive, in particular, graphene films described by tensor conductivity, which are isolated or located on the dielectric layers. The dispersion equation for hybrid modes, as well as scattering parameters. We show that free wave (eigenwaves) problem follow from the problem of diffraction when linking the amplitude of the current of the linear equations are unsolvable, i.e., the determinant of this system is zero. As a particular case the dispersion equation follow from the conditions of matching (with zero reflection coefficient).

Using Stochastic Spiking Neural Networks on SpiNNaker to Solve Constraint Satisfaction Problems

PubMed Central

Fonseca Guerra, Gabriel A.; Furber, Steve B.

2017-01-01

Constraint satisfaction problems (CSP) are at the core of numerous scientific and technological applications. However, CSPs belong to the NP-complete complexity class, for which the existence (or not) of efficient algorithms remains a major unsolved question in computational complexity theory. In the face of this fundamental difficulty heuristics and approximation methods are used to approach instances of NP (e.g., decision and hard optimization problems). The human brain efficiently handles CSPs both in perception and behavior using spiking neural networks (SNNs), and recent studies have demonstrated that the noise embedded within an SNN can be used as a computational resource to solve CSPs. Here, we provide a software framework for the implementation of such noisy neural solvers on the SpiNNaker massively parallel neuromorphic hardware, further demonstrating their potential to implement a stochastic search that solves instances of P and NP problems expressed as CSPs. This facilitates the exploration of new optimization strategies and the understanding of the computational abilities of SNNs. We demonstrate the basic principles of the framework by solving difficult instances of the Sudoku puzzle and of the map color problem, and explore its application to spin glasses. The solver works as a stochastic dynamical system, which is attracted by the configuration that solves the CSP. The noise allows an optimal exploration of the space of configurations, looking for the satisfiability of all the constraints; if applied discontinuously, it can also force the system to leap to a new random configuration effectively causing a restart. PMID:29311791

Heterogeneous quantum computing for satellite constellation optimization: solving the weighted k-clique problem

NASA Astrophysics Data System (ADS)

Bass, Gideon; Tomlin, Casey; Kumar, Vaibhaw; Rihaczek, Pete; Dulny, Joseph, III

2018-04-01

NP-hard optimization problems scale very rapidly with problem size, becoming unsolvable with brute force methods, even with supercomputing resources. Typically, such problems have been approximated with heuristics. However, these methods still take a long time and are not guaranteed to find an optimal solution. Quantum computing offers the possibility of producing significant speed-up and improved solution quality. Current quantum annealing (QA) devices are designed to solve difficult optimization problems, but they are limited by hardware size and qubit connectivity restrictions. We present a novel heterogeneous computing stack that combines QA and classical machine learning, allowing the use of QA on problems larger than the hardware limits of the quantum device. These results represent experiments on a real-world problem represented by the weighted k-clique problem. Through this experiment, we provide insight into the state of quantum machine learning.

Metabolic and nutritional aspects of cancer.

PubMed

Krawczyk, Joanna; Kraj, Leszek; Ziarkiewicz, Mateusz; Wiktor-Jędrzejczak, Wiesław

2014-08-22

Cancer, being in fact a generalized disease involving the whole organism, is most frequently associated with metabolic deregulation, a latent inflammatory state and anorexia of various degrees. The pathogenesis of this disorder is complex, with multiple dilemmas remaining unsolved. The clinical consequences of the above-mentioned disturbances include cancer-related cachexia and anorexia-cachexia syndrome. These complex clinical entities worsen the prognosis, and lead to deterioration of the quality of life and performance status, and thus require multimodal treatment. Optimal therapy should include nutritional support coupled with pharmacotherapy targeted at underlying pathomechanisms of cachexia. Nevertheless, many issues still need explanation, and efficacious and comprehensive therapy of cancer-related cachexia remains a future objective.

The influence of open goals on the acquisition of problem-relevant information.

PubMed

Moss, Jarrod; Kotovsky, Kenneth; Cagan, Jonathan

2007-09-01

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 conducted to establish the effect of open goals on the acquisition of problem-relevant information. It was found that problem-relevant information, or hints, presented implicitly in a 2nd task in between attempts at solving problems aided problem solving. This effect cannot be attributed to strategic behavior after participants caught on to the manipulation, as most participants were not aware of the relationship. The implications of this research are discussed, including potential contributions to our understanding of insight, incubation, transfer, and creativity. 2007 APA

Human development I: twenty fundamental problems of biology, medicine, and neuro-psychology related to biological information.

PubMed

Hermansen, Tyge Dahl; Ventegodt, Søren; Rald, Erik; Clausen, Birgitte; Nielsen, Maj Lyck; Merrick, Joav

2006-07-06

In a new series of papers, we address a number of unsolved problems in biology today. First of all, the unsolved enigma concerning how the differentiation from a single zygote to an adult individual happens has been object for severe research for decades. By uncovering a new holistic biological paradigm that introduces an energetic-informational interpretation of reality as a new way to experience biology, these papers will try to solve the problems connected with the events of biological ontogenesis involving a fractal hierarchy, from a single cell to the function of the human brain. The problems discussed are interpreted within the frames of a universe of roomy fractal structures containing energetic patterns that are able to deliver biological information. We think biological organization is guided by energetic changes on the level of quantum mechanics, interacting with the intention that again guides the energetic conformation of the fractal structures to gain disorders or healthiness. Furthermore, we introduce two new concepts: "metamorphous top down" evolution and "adult human metamorphosis". The first is a new evolutionary theory involving metamorphosis as a main concept of evolution. The last is tightly linked to the evolutionary principle and explains how human self-recovery is governed. Other subjects of special interest that we shall look deeper into are the immunological self-nonself discrimination, the structure and function of the human brain, the etiology and salutogenesis of mental and somatic diseases, and the structure of the consciousness of a human being. We shall criticize Szentagothai's model for the modulated structure of the human cerebral cortex and Jerne's theory of the immunological regulatory anti-idiotypic network.

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.

Unsolved problems. [the physics of B stars

NASA Technical Reports Server (NTRS)

1982-01-01

The level of understanding of the physics of single, isolated B stars is assessed and unresolved problems are defined. The significant observational results concerning the effective temperatures, radii, masses and mantles are summarized. The results of the theory of the evolution of massive stars are confronted with the observed luminosities and effective temperatures of B stars. In addition the implications of stellar spectra theory are compared with observed spectra and a heuristic model for a mantle is developed. The chief unresolved problems for B stars concern developing detailed models for (1) the internal structure of massive stars which are beginning to evolve rapidly as they complete burning hydrogen in their cores; (2) mantles; and (3) the transfer of radiation in high temperature inhomogeneous moving bodies of gas.

Unsolved Problems in Evolutionary Theory

DTIC Science & Technology

1967-01-01

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

Digital communications: Microwave applications

NASA Astrophysics Data System (ADS)

Feher, K.

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

Condensed Matter Physics: Does Quantum Mechanics Matter?

NASA Astrophysics Data System (ADS)

Fisher, Michael E.

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

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.

Toward a superconducting quantum computer

PubMed Central

Tsai, Jaw-Shen

2010-01-01

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

Toward a superconducting quantum computer. Harnessing macroscopic quantum coherence.

PubMed

Tsai, Jaw-Shen

2010-01-01

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

VOP memory management in MPEG-4

NASA Astrophysics Data System (ADS)

Vaithianathan, Karthikeyan; Panchanathan, Sethuraman

2001-03-01

MPEG-4 is a multimedia standard that requires Video Object Planes (VOPs). Generation of VOPs for any kind of video sequence is still a challenging problem that largely remains unsolved. Nevertheless, if this problem is treated by imposing certain constraints, solutions for specific application domains can be found. MPEG-4 applications in mobile devices is one such domain where the opposite goals namely low power and high throughput are required to be met. Efficient memory management plays a major role in reducing the power consumption. Specifically, efficient memory management for VOPs is difficult because the lifetimes of these objects vary and these life times may be overlapping. Varying life times of the objects requires dynamic memory management where memory fragmentation is a key problem that needs to be addressed. In general, memory management systems address this problem by following a combination of strategy, policy and mechanism. For MPEG4 based mobile devices that lack instruction processors, a hardware based memory management solution is necessary. In MPEG4 based mobile devices that have a RISC processor, using a Real time operating system (RTOS) for this memory management task is not expected to be efficient because the strategies and policies used by the ROTS is often tuned for handling memory segments of smaller sizes compared to object sizes. Hence, a memory management scheme specifically tuned for VOPs is important. In this paper, different strategies, policies and mechanisms for memory management are considered and an efficient combination is proposed for the case of VOP memory management along with a hardware architecture, which can handle the proposed combination.

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.

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

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.

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.

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

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

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.

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.

The Impact of The Fractal Paradigm on Geography

NASA Astrophysics Data System (ADS)

De Cola, L.

2001-12-01

Being itself somewhat fractal, Benoit Mandelbrot's magnum opus THE FRACTAL GEOMETRY OF NATURE may be deconstructed in many ways, including geometrically, systematically, and epistemologically. Viewed as a work of geography it may be used to organize the major topics of interest to scientists preoccupied with the understanding of real-world space in astronomy, geology, meteorology, hydrology, and biology. We shall use it to highlight such recent geographic accomplishments as automated feature detection, understanding urban growth, and modeling the spread of disease in space and time. However, several key challenges remain unsolved, among them: 1. It is still not possible to move continuously from one map scale to another so that objects change their dimension smoothly. I.e. as a viewer zooms in on a map the zero-dimensional location of a city should gradually become a 2-dimensional polygon, then a network of 1-dimensional streets, then 3-dimensional buildings, etc. 2. Spatial autocorrelation continues to be regarded more as an econometric challenge than as a problem of scaling. Similarities of values among closely-spaced observation is not so much a problem to be overcome as a source of information about spatial structure. 3. Although the fractal paradigm is a powerful model for data analysis, its ideas and techniques need to be brought to bear on the problems of understanding such hierarchies as ecosystems (the flow networks of energy and matter), taxonomies (biological classification), and knowledge (hierarchies of bureaucratic information, networks of linked data, etc).

Expressing clinical data sets with openEHR archetypes: a solid basis for ubiquitous computing.

PubMed

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

2007-12-01

The purpose of this paper is to analyse the feasibility and usefulness of expressing clinical data sets (CDSs) as openEHR archetypes. For this, we present an approach to transform CDS into archetypes, and outline typical problems with CDS and analyse whether some of these problems can be overcome by the use of archetypes. Literature review and analysis of a selection of existing Australian, German, other European and international CDSs; transfer of a CDS for Paediatric Oncology into openEHR archetypes; implementation of CDSs in application systems. To explore the feasibility of expressing CDS as archetypes an approach to transform existing CDSs into archetypes is presented in this paper. In case of the Paediatric Oncology CDS (which consists of 260 data items) this lead to the definition of 48 openEHR archetypes. To analyse the usefulness of expressing CDS as archetypes, we identified nine problems with CDS that currently remain unsolved without a common model underpinning the CDS. Typical problems include incompatible basic data types and overlapping and incompatible definitions of clinical content. A solution to most of these problems based on openEHR archetypes is motivated. With regard to integrity constraints, further research is required. While openEHR cannot overcome all barriers to Ubiquitous Computing, it can provide the common basis for ubiquitous presence of meaningful and computer-processable knowledge and information, which we believe is a basic requirement for Ubiquitous Computing. Expressing CDSs as openEHR archetypes is feasible and advantageous as it fosters semantic interoperability, supports ubiquitous computing, and helps to develop archetypes that are arguably of better quality than the original CDS.

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

The geophysical importance of bubbles in the sea

NASA Technical Reports Server (NTRS)

Cirpriano, R. J.

1982-01-01

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

Ultrafast and nanoscale diodes

NASA Astrophysics Data System (ADS)

Zhang, Peng; Lau, Y. Y.

2016-10-01

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

Analytical Solution of a Generalized Hirota-Satsuma Equation

NASA Astrophysics Data System (ADS)

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

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

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.

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

DTIC Science & Technology

1988-07-15

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

Steady state analysis of Boolean molecular network models via model reduction and computational algebra.

PubMed

Veliz-Cuba, Alan; Aguilar, Boris; Hinkelmann, Franziska; Laubenbacher, Reinhard

2014-06-26

A key problem in the analysis of mathematical models of molecular networks is the determination of their steady states. The present paper addresses this problem for Boolean network models, an increasingly popular modeling paradigm for networks lacking detailed kinetic information. For small models, the problem can be solved by exhaustive enumeration of all state transitions. But for larger models this is not feasible, since the size of the phase space grows exponentially with the dimension of the network. The dimension of published models is growing to over 100, so that efficient methods for steady state determination are essential. Several methods have been proposed for large networks, some of them heuristic. While these methods represent a substantial improvement in scalability over exhaustive enumeration, the problem for large networks is still unsolved in general. This paper presents an algorithm that consists of two main parts. The first is a graph theoretic reduction of the wiring diagram of the network, while preserving all information about steady states. The second part formulates the determination of all steady states of a Boolean network as a problem of finding all solutions to a system of polynomial equations over the finite number system with two elements. This problem can be solved with existing computer algebra software. This algorithm compares favorably with several existing algorithms for steady state determination. One advantage is that it is not heuristic or reliant on sampling, but rather determines algorithmically and exactly all steady states of a Boolean network. The code for the algorithm, as well as the test suite of benchmark networks, is available upon request from the corresponding author. The algorithm presented in this paper reliably determines all steady states of sparse Boolean networks with up to 1000 nodes. The algorithm is effective at analyzing virtually all published models even those of moderate connectivity. The problem for large Boolean networks with high average connectivity remains an open problem.

Steady state analysis of Boolean molecular network models via model reduction and computational algebra

PubMed Central

2014-01-01

Background A key problem in the analysis of mathematical models of molecular networks is the determination of their steady states. The present paper addresses this problem for Boolean network models, an increasingly popular modeling paradigm for networks lacking detailed kinetic information. For small models, the problem can be solved by exhaustive enumeration of all state transitions. But for larger models this is not feasible, since the size of the phase space grows exponentially with the dimension of the network. The dimension of published models is growing to over 100, so that efficient methods for steady state determination are essential. Several methods have been proposed for large networks, some of them heuristic. While these methods represent a substantial improvement in scalability over exhaustive enumeration, the problem for large networks is still unsolved in general. Results This paper presents an algorithm that consists of two main parts. The first is a graph theoretic reduction of the wiring diagram of the network, while preserving all information about steady states. The second part formulates the determination of all steady states of a Boolean network as a problem of finding all solutions to a system of polynomial equations over the finite number system with two elements. This problem can be solved with existing computer algebra software. This algorithm compares favorably with several existing algorithms for steady state determination. One advantage is that it is not heuristic or reliant on sampling, but rather determines algorithmically and exactly all steady states of a Boolean network. The code for the algorithm, as well as the test suite of benchmark networks, is available upon request from the corresponding author. Conclusions The algorithm presented in this paper reliably determines all steady states of sparse Boolean networks with up to 1000 nodes. The algorithm is effective at analyzing virtually all published models even those of moderate connectivity. The problem for large Boolean networks with high average connectivity remains an open problem. PMID:24965213

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

Engineering Geodesy - Definition and Core Competencies

NASA Astrophysics Data System (ADS)

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

2014-11-01

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

Modeling Core Collapse Supernovae

NASA Astrophysics Data System (ADS)

Mezzacappa, Anthony

2017-01-01

Core collapse supernovae, or the death throes of massive stars, are general relativistic, neutrino-magneto-hydrodynamic events. The core collapse supernova mechanism is still not in hand, though key components have been illuminated, and the potential for multiple mechanisms for different progenitors exists. Core collapse supernovae are the single most important source of elements in the Universe, and serve other critical roles in galactic chemical and thermal evolution, the birth of neutron stars, pulsars, and stellar mass black holes, the production of a subclass of gamma-ray bursts, and as potential cosmic laboratories for fundamental nuclear and particle physics. Given this, the so called ``supernova problem'' is one of the most important unsolved problems in astrophysics. It has been fifty years since the first numerical simulations of core collapse supernovae were performed. Progress in the past decade, and especially within the past five years, has been exponential, yet much work remains. Spherically symmetric simulations over nearly four decades laid the foundation for this progress. Two-dimensional modeling that assumes axial symmetry is maturing. And three-dimensional modeling, while in its infancy, has begun in earnest. I will present some of the recent work from the ``Oak Ridge'' group, and will discuss this work in the context of the broader work by other researchers in the field. I will then point to future requirements and challenges. Connections with other experimental, observational, and theoretical efforts will be discussed, as well.

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.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary ‘VoxTox’ research programme

PubMed Central

Burnet, Neil G; Scaife, Jessica E; Romanchikova, Marina; Thomas, Simon J; Bates, Amy M; Wong, Emma; Noble, David J; Shelley, Leila EA; Bond, Simon J; Forman, Julia R; Hoole, Andrew CF; Barnett, Gillian C; Brochu, Frederic M; Simmons, Michael PD; Jena, Raj; Harrison, Karl; Yeap, Ping Lin; Drew, Amelia; Silvester, Emma; Elwood, Patrick; Pullen, Hannah; Sultana, Andrew; Seah, Shannon YK; Wilson, Megan Z; Russell, Simon G; Benson, Richard J; Rimmer, Yvonne L; Jefferies, Sarah J; Taku, Nicolette; Gurnell, Mark; Powlson, Andrew S; Schönlieb, Carola-Bibiane; Cai, Xiaohao; Sutcliffe, Michael PF; Parker, Michael A

2017-01-01

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose. PMID:29177202

Classical dense matter physics: some basic methods and results

NASA Astrophysics Data System (ADS)

Čelebonović, Vladan

2002-07-01

This is an introduction to the basic notions, some methods and open problems of dense matter physics and their applications in astrophysics. Experimental topics cover the range from the work of P. W. Bridgman to the discovery and basic results of use of the diamond anvil cell. On the theoretical side, the semiclassical method of P. Savić and R. Kašanin is described. The choice of these topics is conditioned by their applicability in astrophysics and the author's research experience. At the end of the paper is presented a list of some unsolved problems in dense matter physics and astrophysics, some (or all) of which could form a basis of future collaborations.

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

PubMed

Burnet, Neil G; Scaife, Jessica E; Romanchikova, Marina; Thomas, Simon J; Bates, Amy M; Wong, Emma; Noble, David J; Shelley, Leila Ea; Bond, Simon J; Forman, Julia R; Hoole, Andrew Cf; Barnett, Gillian C; Brochu, Frederic M; Simmons, Michael Pd; Jena, Raj; Harrison, Karl; Yeap, Ping Lin; Drew, Amelia; Silvester, Emma; Elwood, Patrick; Pullen, Hannah; Sultana, Andrew; Seah, Shannon Yk; Wilson, Megan Z; Russell, Simon G; Benson, Richard J; Rimmer, Yvonne L; Jefferies, Sarah J; Taku, Nicolette; Gurnell, Mark; Powlson, Andrew S; Schönlieb, Carola-Bibiane; Cai, Xiaohao; Sutcliffe, Michael Pf; Parker, Michael A

2017-06-01

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

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.

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.

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.

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.

Spectrum-to-Spectrum Searching Using a Proteome-wide Spectral Library*

PubMed Central

Yen, Chia-Yu; Houel, Stephane; Ahn, Natalie G.; Old, William M.

2011-01-01

The unambiguous assignment of tandem mass spectra (MS/MS) to peptide sequences remains a key unsolved problem in proteomics. Spectral library search strategies have emerged as a promising alternative for peptide identification, in which MS/MS spectra are directly compared against a reference library of confidently assigned spectra. Two problems relate to library size. First, reference spectral libraries are limited to rediscovery of previously identified peptides and are not applicable to new peptides, because of their incomplete coverage of the human proteome. Second, problems arise when searching a spectral library the size of the entire human proteome. We observed that traditional dot product scoring methods do not scale well with spectral library size, showing reduction in sensitivity when library size is increased. We show that this problem can be addressed by optimizing scoring metrics for spectrum-to-spectrum searches with large spectral libraries. MS/MS spectra for the 1.3 million predicted tryptic peptides in the human proteome are simulated using a kinetic fragmentation model (MassAnalyzer version2.1) to create a proteome-wide simulated spectral library. Searches of the simulated library increase MS/MS assignments by 24% compared with Mascot, when using probabilistic and rank based scoring methods. The proteome-wide coverage of the simulated library leads to 11% increase in unique peptide assignments, compared with parallel searches of a reference spectral library. Further improvement is attained when reference spectra and simulated spectra are combined into a hybrid spectral library, yielding 52% increased MS/MS assignments compared with Mascot searches. Our study demonstrates the advantages of using probabilistic and rank based scores to improve performance of spectrum-to-spectrum search strategies. PMID:21532008

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.

Collisional breakup in a quantum system of three charged particles

PubMed

Rescigno; Baertschy; Isaacs; McCurdy

1999-12-24

Since the invention of quantum mechanics, even the simplest example of the collisional breakup of a system of charged particles, e(-) + H --> H(+) + e(-) + e(-) (where e(-) is an electron and H is hydrogen), has resisted solution and is now one of the last unsolved fundamental problems in atomic physics. A complete solution requires calculation of the energies and directions for a final state in which all three particles are moving away from each other. Even with supercomputers, the correct mathematical description of this state has proved difficult to apply. A framework for solving ionization problems in many areas of chemistry and physics is finally provided by a mathematical transformation of the Schrodinger equation that makes the final state tractable, providing the key to a numerical solution of this problem that reveals its full dynamics.

Military Implications of a Possible World Order Crisis in the 1980s

DTIC Science & Technology

1977-11-01

for "the tardy growth of stable inde- pendent combinations among hired journeymen" in England. They found it "in the prospects of economic...P^^W^WW^: I™T"™ ...»jjiiijiiinwiiiiimnpni —mmumimK 11 ,�ŕ ’ "ll’liH-^B^W^piWI -31- Presldent Ferdinand E. Marcos of the Philippines , who... Philippines (mimeo). 2 Dial Torgerson, "U.N. Economic Talks Close With Most Conference Problems Still Unsolved," The Los Angeles Times, June 1, 1976

Autonomy in the Industrial R&D Lab

DTIC Science & Technology

1984-10-01

engineers. Organizational Behavior and Human Performance, 18, 1977, 329-345. Kubie , L. S. Some unsolved problems of the scientific career. American...MtNS DTK 0U4-2 SE;.EC!I3V k raELIMIVARf . :«I»LDCJIMC SiCTlOV CSMfROM SI«TI3M Mrxa^DPIA. V« 2Z3H JlFt^Jr.1 TtCHMtCSL...iCriill IICH. INFORMATION CTR. » TIN: 3TIC DU«-2 JELECTICIi k . PF(rLlr’ItJAr<Y ; MALUGJl JGSSELT ICN :,\\MEPn^ SIATICN ALEXA’>3RIA

Classical integrable many-body systems disconnected with semi-simple Lie algebras

NASA Astrophysics Data System (ADS)

Inozemtsev, V. I.

2017-05-01

The review of the results in the theory of integrable many-body systems disconnected with semisimple Lie algebras is done. The one-dimensional systems of light Calogero-Sutherland-Moser particles interacting with one particle of infinite mass located at the origin are described in detail. In some cases the exact solutions of the equations of motion are obtained. The general theory of integration of the equations of motion needs the methods of algebraic geometry. The Lax pairs with spectral parameter are constructed for this purpose. The theory still contains many unsolved problems.

On the relativistic micro-canonical ensemble and relativistic kinetic theory for N relativistic particles in inertial and non-inertial rest frames

NASA Astrophysics Data System (ADS)

Alba, David; Crater, Horace W.; Lusanna, Luca

2015-03-01

A new formulation of relativistic classical mechanics allows a reconsideration of old unsolved problems in relativistic kinetic theory and in relativistic statistical mechanics. In particular a definition of the relativistic micro-canonical partition function is given strictly in terms of the Poincaré generators of an interacting N-particle system both in the inertial and non-inertial rest frames. The non-relativistic limit allows a definition of both the inertial and non-inertial micro-canonical ensemble in terms of the Galilei generators.

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.

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.

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

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.

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.

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.

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.

[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.

Cooling and clusters: when is heating needed?

PubMed

Bryan, Greg; Voit, Mark

2005-03-15

There are (at least) two unsolved problems concerning the current state of the ther- mal gas in clusters of galaxies. The first is to identify the source of the heating which onsets cooling in the centres of clusters with short cooling times (the 'cooling-flow' problem). The second to understand the mechanism which boosts the entropy in cluster and group gas. Since both of these problems involve an unknown source of heating it is tempting to identify them with the same process, particularly since active galactic nuclei heating is observed to be operating at some level in a sample of well-observed 'cooling-flow' clusters. Here we show, using numerical simulations of cluster formation, that much of the gas ending up in clusters cools at high redshift and so the heating is also needed at high redshift, well before the cluster forms. This indicates that the same process operating to solve the cooling-flow problem may not also resolve the cluster-entropy problem.

Initial experiments on the end-point control of a flexible one-link robot

NASA Technical Reports Server (NTRS)

Cannon, R. H., Jr.; Schmitz, E.

1984-01-01

The present investigation is concerned with initial experiments regarding a specific unsolved control problem which appeared to be central to advances in the art of robotics. This problem involves the control of a flexible member (one link of a robot system). The position of the end-effector, called the end point or tip, is controlled by measuring that position and using the measurement as a basis for applying control torque to the other end of the flexible member, as for instance, the robot's elbow joint. A description is presented of the features of the first experimental arm which has been made, and an outline is provided of the general strategy for controlling it using its tip sensor and shoulder torquer.

Computational complexity in entanglement transformations

NASA Astrophysics Data System (ADS)

Chitambar, Eric A.

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

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.

Ab initio protein structure assembly using continuous structure fragments and optimized knowledge-based force field.

PubMed

Xu, Dong; Zhang, Yang

2012-07-01

Ab initio protein folding is one of the major unsolved problems in computational biology owing to the difficulties in force field design and conformational search. We developed a novel program, QUARK, for template-free protein structure prediction. Query sequences are first broken into fragments of 1-20 residues where multiple fragment structures are retrieved at each position from unrelated experimental structures. Full-length structure models are then assembled from fragments using replica-exchange Monte Carlo simulations, which are guided by a composite knowledge-based force field. A number of novel energy terms and Monte Carlo movements are introduced and the particular contributions to enhancing the efficiency of both force field and search engine are analyzed in detail. QUARK prediction procedure is depicted and tested on the structure modeling of 145 nonhomologous proteins. Although no global templates are used and all fragments from experimental structures with template modeling score >0.5 are excluded, QUARK can successfully construct 3D models of correct folds in one-third cases of short proteins up to 100 residues. In the ninth community-wide Critical Assessment of protein Structure Prediction experiment, QUARK server outperformed the second and third best servers by 18 and 47% based on the cumulative Z-score of global distance test-total scores in the FM category. Although ab initio protein folding remains a significant challenge, these data demonstrate new progress toward the solution of the most important problem in the field. Copyright © 2012 Wiley Periodicals, Inc.

Small-tip fast recovery imaging using non-slice-selective tailored tip-up pulses and RF-spoiling

PubMed Central

Nielsen, Jon-Fredrik; Yoon, Daehyun; Noll, Douglas C.

2012-01-01

Small-tip fast recovery (STFR) imaging is a new steady-state imaging sequence that is a potential alternative to balanced steady-state free precession (bSSFP). Under ideal imaging conditions, STFR may provide comparable signal-to-noise ratio (SNR) and image contrast as bSSFP, but without signal variations due to resonance offset. STFR relies on a tailored “tip-up”, or “fast recovery”, RF pulse to align the spins with the longitudinal axis after each data readout segment. The design of the tip-up pulse is based on the acquisition of a separate off-resonance (B0) map. Unfortunately, the design of fast (a few ms) slice- or slab-selective RF pulses that accurately tailor the excitation pattern to the local B0 inhomogeneity over the entire imaging volume remains a challenging and unsolved problem. We introduce a novel implementation of STFR imaging based on non-slice-selective tip-up pulses, which simplifies the RF design problem significantly. Out-of-slice magnetization pathways are suppressed using RF-spoiling. Brain images obtained with this technique show excellent gray/white matter contrast, and point to the possibility of rapid steady-state T2/T1-weighted imaging with intrinsic suppression of cerebrospinal fluid, through-plane vessel signal, and off-resonance artifacts. In the future we expect STFR imaging to benefit significantly from parallel excitation hardware and high-order gradient shim systems. PMID:22511367

Experientally guided robots. [for planet exploration

NASA Technical Reports Server (NTRS)

Merriam, E. W.; Becker, J. D.

1974-01-01

This paper argues that an experientally guided robot is necessary to successfully explore far-away planets. Such a robot is characterized as having sense organs which receive sensory information from its environment and motor systems which allow it to interact with that environment. The sensori-motor information which it receives is organized into an experiential knowledge structure and this knowledge in turn is used to guide the robot's future actions. A summary is presented of a problem solving system which is being used as a test bed for developing such a robot. The robot currently engages in the behaviors of visual tracking, focusing down, and looking around in a simulated Martian landscape. Finally, some unsolved problems are outlined whose solutions are necessary before an experientally guided robot can be produced. These problems center around organizing the motivational and memory structure of the robot and understanding its high-level control mechanisms.

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

NASA Technical Reports Server (NTRS)

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

1979-01-01

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

Crossflow effects on the growth rate of inviscid Goertler vortices in a hypersonic boundary layer

NASA Technical Reports Server (NTRS)

Fu, Yibin; Hall, Philip

1992-01-01

The effects of crossflow on the growth rate of inviscid Goertler vortices in a hypersonic boundary layer with pressure gradient are studied. Attention is focused on the inviscid mode trapped in the temperature adjustment layer; this mode has greater growth rate than any other mode. The eigenvalue problem which governs the relationship between the growth rate, the crossflow amplitude, and the wavenumber is solved numerically, and the results are then used to clarify the effects of crossflow on the growth rate of inviscid Goertler vortices. It is shown that crossflow effects on Goertler vortices are fundamentally different for incompressible and hypersonic flows. The neutral mode eigenvalue problem is found to have an exact solution, and as a by-product, we have also found the exact solution to a neutral mode eigenvalue problem which was formulated, but unsolved before, by Bassom and Hall (1991).

Structural qualia: a solution to the hard problem of consciousness.

PubMed

Loorits, Kristjan

2014-01-01

The hard problem of consciousness has been often claimed to be unsolvable by the methods of traditional empirical sciences. It has been argued that all the objects of empirical sciences can be fully analyzed in structural terms but that consciousness is (or has) something over and above its structure. However, modern neuroscience has introduced a theoretical framework in which also the apparently non-structural aspects of consciousness, namely the so called qualia or qualitative properties, can be analyzed in structural terms. That framework allows us to see qualia as something compositional with internal structures that fully determine their qualitative nature. Moreover, those internal structures can be identified which certain neural patterns. Thus consciousness as a whole can be seen as a complex neural pattern that misperceives some of its own highly complex structural properties as monadic and qualitative. Such neural pattern is analyzable in fully structural terms and thereby the hard problem is solved.

Structural qualia: a solution to the hard problem of consciousness

PubMed Central

Loorits, Kristjan

2014-01-01

The hard problem of consciousness has been often claimed to be unsolvable by the methods of traditional empirical sciences. It has been argued that all the objects of empirical sciences can be fully analyzed in structural terms but that consciousness is (or has) something over and above its structure. However, modern neuroscience has introduced a theoretical framework in which also the apparently non-structural aspects of consciousness, namely the so called qualia or qualitative properties, can be analyzed in structural terms. That framework allows us to see qualia as something compositional with internal structures that fully determine their qualitative nature. Moreover, those internal structures can be identified which certain neural patterns. Thus consciousness as a whole can be seen as a complex neural pattern that misperceives some of its own highly complex structural properties as monadic and qualitative. Such neural pattern is analyzable in fully structural terms and thereby the hard problem is solved. PMID:24672510

On the origin of synthetic life: attribution of output to a particular algorithm

NASA Astrophysics Data System (ADS)

Yampolskiy, Roman V.

2017-01-01

With unprecedented advances in genetic engineering we are starting to see progressively more original examples of synthetic life. As such organisms become more common it is desirable to gain an ability to distinguish between natural and artificial life forms. In this paper, we address this challenge as a generalized version of Darwin’s original problem, which he so brilliantly described in On the Origin of Species. After formalizing the problem of determining the samples’ origin, we demonstrate that the problem is in fact unsolvable. In the general case, if computational resources of considered originator algorithms have not been limited and priors for such algorithms are known to be equal, both explanations are equality likely. Our results should attract attention of astrobiologists and scientists interested in developing a more complete theory of life, as well as of AI-Safety researchers.

Structural biology of intrinsically disordered proteins: Revisiting unsolved mysteries.

PubMed

Sigalov, Alexander B

2016-06-01

The emergence of intrinsically disordered proteins (IDPs) has challenged the classical protein structure-function paradigm by introducing a new paradigm of "coupled binding and folding". This paradigm suggests that IDPs fold upon binding to their partners. Further studies, however, revealed a novel and previously unrecognized phenomenon of "uncoupled binding and folding" suggesting that IDPs do not necessarily fold upon interaction with their lipid and protein partners. The complex and often unusual biophysics of IDPs makes structural characterization of these proteins and their complexes not only challenging but often resulting in opposite conclusions. For this reason, some crucial questions in this field remain unsolved for well over a decade. Considering an important role of IDPs in cellular regulation, signaling and control in health and disease, more efforts are needed to solve these mysteries. Here, I focus on two long-standing contradictions in the literature concerning dimerization and membrane-binding activities of IDPs. Molecular explanation of these discrepancies is provided. I also demonstrate how resolution of these critical issues in the field of IDPs results in our expanded understanding of cell function and has multiple applications in biology and medicine. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

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.

Technological hurdles to the application of intercalated graphite fibers

NASA Technical Reports Server (NTRS)

Gaier, James R.

1988-01-01

Before intercalated graphite fibers can be developed as an effective power material, there are several technological hurdles which must be overcome. These include the environmental stability, homogeneity and bulk properties, connection procedures, and costs. Strides were made within the last several years in stability and homogeneity of intercalated graphite fibers. Bulk properties and connection procedures are areas of active research now. Costs are still prohibitive for all but the most demanding applications. None of these problems, however, appear to be unsolvable, and their solution may result in wide spread GOC application. The development of a relatively simple technology application, such as EMI shielding, would stimulate the solution of scale-up problems. Once this technology is developed, then more demanding applications, such as power bus bars, may be possible.

Exact solutions for the source-excited cylindrical electromagnetic waves in a nonlinear nondispersive medium.

PubMed

Es'kin, V A; Kudrin, A V; Petrov, E Yu

2011-06-01

The behavior of electromagnetic fields in nonlinear media has been a topical problem since the discovery of materials with a nonlinearity of electromagnetic properties. The problem of finding exact solutions for the source-excited nonlinear waves in curvilinear coordinates has been regarded as unsolvable for a long time. In this work, we present the first solution of this type for a cylindrically symmetric field excited by a pulsed current filament in a nondispersive medium that is simultaneously inhomogeneous and nonlinear. Assuming that the medium has a power-law permittivity profile in the linear regime and lacks a center of inversion, we derive an exact solution for the electromagnetic field excited by a current filament in such a medium and discuss the properties of this solution.

On the continuity of the stationary state distribution of DPCM

NASA Astrophysics Data System (ADS)

Naraghi-Pour, Morteza; Neuhoff, David L.

1990-03-01

Continuity and singularity properties of the stationary state distribution of differential pulse code modulation (DPCM) are explored. Two-level DPCM (i.e., delta modulation) operating on a first-order autoregressive source is considered, and it is shown that, when the magnitude of the DPCM prediciton coefficient is between zero and one-half, the stationary state distribution is singularly continuous; i.e., it is not discrete but concentrates on an uncountable set with a Lebesgue measure of zero. Consequently, it cannot be represented with a probability density function. For prediction coefficients with magnitude greater than or equal to one-half, the distribution is pure, i.e., either absolutely continuous and representable with a density function, or singular. This problem is compared to the well-known and still substantially unsolved problem of symmetric Bernoulli convolutions.

Minimal perceptrons for memorizing complex patterns

NASA Astrophysics Data System (ADS)

Pastor, Marissa; Song, Juyong; Hoang, Danh-Tai; Jo, Junghyo

2016-11-01

Feedforward neural networks have been investigated to understand learning and memory, as well as applied to numerous practical problems in pattern classification. It is a rule of thumb that more complex tasks require larger networks. However, the design of optimal network architectures for specific tasks is still an unsolved fundamental problem. In this study, we consider three-layered neural networks for memorizing binary patterns. We developed a new complexity measure of binary patterns, and estimated the minimal network size for memorizing them as a function of their complexity. We formulated the minimal network size for regular, random, and complex patterns. In particular, the minimal size for complex patterns, which are neither ordered nor disordered, was predicted by measuring their Hamming distances from known ordered patterns. Our predictions agree with simulations based on the back-propagation algorithm.

Possible relation of water structural relaxation to water anomalies

PubMed Central

Mallamace, Francesco; Corsaro, Carmelo; Stanley, H. Eugene

2013-01-01

The anomalous behavior of thermodynamic response functions is an unsolved problem in the physics of water. The mechanism that gives rise to the dramatic indefinite increase at low temperature in the heat capacity, the compressibility, and the coefficient of thermal expansion, is unknown. We explore this problem by analyzing both new and existing experimental data on the power spectrum S(Q, ω) of bulk and confined water at ambient pressure. When decreasing the temperature, we find that the liquid undergoes a structural transformation coinciding with the onset of an extended hydrogen bond network. This network onset seems to give rise to the marked viscoelastic behavior, consistent with the interesting possibility that the sound velocity and response functions of water depend upon both the frequency and wave vector. PMID:23483053

Proceedings of the NASA Conference on Space Telerobotics, volume 3

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Recent Progress on PEDOT-Based Thermoelectric Materials

PubMed Central

Wei, Qingshuo; Mukaida, Masakazu; Kirihara, Kazuhiro; Naitoh, Yasuhisa; Ishida, Takao

2015-01-01

The thermoelectric properties of poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials have attracted attention recently because of their remarkable electrical conductivity, power factor, and figure of merit. In this review, we summarize recent efforts toward improving the thermoelectric properties of PEDOT-based materials. We also discuss thermoelectric measurement techniques and several unsolved problems with the PEDOT system such as the effect of water absorption from the air and the anisotropic thermoelectric properties. In the last part, we describe our work on improving the power output of thermoelectric modules by using PEDOT, and we outline the potential applications of polymer thermoelectric generators. PMID:28787968

On Frequency Combs in Monolithic Resonators

NASA Astrophysics Data System (ADS)

Savchenkov, A. A.; Matsko, A. B.; Maleki, L.

2016-06-01

Optical frequency combs have become indispensable in astronomical measurements, biological fingerprinting, optical metrology, and radio frequency photonic signal generation. Recently demonstrated microring resonator-based Kerr frequency combs point the way towards chip scale optical frequency comb generator retaining major properties of the lab scale devices. This technique is promising for integrated miniature radiofrequency and microwave sources, atomic clocks, optical references and femtosecond pulse generators. Here we present Kerr frequency comb development in a historical perspective emphasizing its similarities and differences with other physical phenomena. We elucidate fundamental principles and describe practical implementations of Kerr comb oscillators, highlighting associated solved and unsolved problems.

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

NASA Astrophysics Data System (ADS)

Morozov, Oleg I.

2018-06-01

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

Recent Progress on PEDOT-Based Thermoelectric Materials.

PubMed

Wei, Qingshuo; Mukaida, Masakazu; Kirihara, Kazuhiro; Naitoh, Yasuhisa; Ishida, Takao

2015-02-16

The thermoelectric properties of poly(3,4-ethylenedioxythiophene) (PEDOT)-based materials have attracted attention recently because of their remarkable electrical conductivity, power factor, and figure of merit. In this review, we summarize recent efforts toward improving the thermoelectric properties of PEDOT-based materials. We also discuss thermoelectric measurement techniques and several unsolved problems with the PEDOT system such as the effect of water absorption from the air and the anisotropic thermoelectric properties. In the last part, we describe our work on improving the power output of thermoelectric modules by using PEDOT, and we outline the potential applications of polymer thermoelectric generators.

Review of heat transfer problems associated with magnetically-confined fusion reactor concepts

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

Hoffman, M.A.; Werner, R.W.; Carlson, G.A.

1976-04-01

Conceptual design studies of possible fusion reactor configurations have revealed a host of interesting and sometimes extremely difficult heat transfer problems. The general requirements imposed on the coolant system for heat removal of the thermonuclear power from the reactor are discussed. In particular, the constraints imposed by the fusion plasma, neutronics, structure and magnetic field environment are described with emphasis on those aspects which are unusual or unique to fusion reactors. Then the particular heat transfer characteristics of various possible coolants including lithium, flibe, boiling alkali metals, and helium are discussed in the context of these general fusion reactor requirements.more » Some specific areas where further experimental and/or theoretical work is necessary are listed for each coolant along with references to the pertinent research already accomplished. Specialized heat transfer problems of the plasma injection and removal systems are also described. Finally, the challenging heat transfer problems associated with the superconducting magnets are reviewed, and once again some of the key unsolved heat transfer problems are enumerated.« less

Correspondence and challenges as neurologists to Kumamoto Earthquakes in 2016.

PubMed

Nakajima, Makoto; Nakane, Nozomi; Takamatsu, Kotaro; Yamashita, Satoshi; Nakane, Shunya; Yamashita, Taro; Ando, Yukio

2016-12-28

Kumamoto Earthquakes in 2016 severely affected medical circumstances and condition of each patient with neuro-muscular diseases, in addition to having destroyed life circumstances of local residence. Number of neuro-muscular disease patients admitted to the Department of Neurology, Kumamoto University, the only university hospital in the prefecture, increased approximately twice compared to usual years. Most of the related facilities were able to admit emergency patients with neuro-muscular diseases although the hospital buildings were damaged in various degrees. A number of issues remained unsolved as to emergency contact system, securement of emergency beds for severe neuro-muscular diseases, and information system for these patients.

Areas of Unsolved Problems in Caribbean Active Tectonics

NASA Astrophysics Data System (ADS)

Mann, P.

2015-12-01

I review some unsolved problems in Caribbean active tectonics. At the regional and plate scale: 1) confirm the existence of intraplate deformation zones of the central Caribbean plate that are within the margin of error of ongoing GPS measurements; 2) carry out field studies to evaluate block models versus models for distributed fault shear on the densely populated islands of Jamaica, Hispaniola, Puerto Rico, and the Virgin Islands; 3) carry out paleoseismological research of key plate boundary faults that may have accumulated large strains but have not been previously studied in detail; 4) determine the age of onset and far-field effects of the Cocos ridge and the Central America forearc sliver; 4) investigate the origin and earthquake-potential of obliquely-sheared rift basins along the northern coast of Venezuela; 5) determine the age of onset and regional active, tectonic effects of the Panama-South America collision including the continued activation of the Maracaibo block; and 6) validate longterm rates on active subduction zones with improving, tomographic maps of subducted slabs. At the individual fault scale: 1) determine the mode of termination of large and active strike -slip faults and application of the STEP model (Septentrional, Polochic, El Pilar, Bocono, Santa Marta-Bucaramanaga); 2) improve the understanding of the earthquake potential on the Enriquillo-Plantain Garden fault zone given "off-fault" events such as the 2010 Haiti earthquake; how widespread is this behavior?; and 3) estimate size of future tsunamis from studies of historic or prehistoric slump scars and mass transport deposits; what potential runups can be predicted from this information?; and 4) devise ways to keep rapidly growing, circum-Caribbean urban populations better informed and safer in the face of inevitable and future, large earthquakes.

Biomedical engineering strategies in system design space.

PubMed

Savageau, Michael A

2011-04-01

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

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

PubMed

Wasser, Solomon P

2011-03-01

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

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

PubMed

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

2017-09-01

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

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

NASA Astrophysics Data System (ADS)

Jofre-Lora, Pedro

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

The management of newborns with esophageal atresia and right aortic arch: A systematic review or still unsolved problem.

PubMed

Parolini, Filippo; Armellini, Andrea; Boroni, Giovanni; Bagolan, Pietro; Alberti, Daniele

2016-02-01

The management of newborns with esophageal atresia (EA) and right aortic arch (RAA) is still an unsolved problem. This study provides a systematic review of epidemiology, diagnosis, management and short-term results of children with EA and RAA. The PubMed database was searched for original studies on children with EA and RAA. In each study, data were extracted for the following outcomes: number of patients, associated anomalies, type of surgical repair, morbidity and mortality rate. Eight studies were selected, including 54 patients with EA and RAA. RAA was encountered in 3.6% of infants. Preoperative detection of RAA was reported in 7 of them. In these patients, primary anastomosis was achieved through the right approach in 3 (thoracotomy in 2 and thoracoscopy in 1) while the left approach was the primary choice in 4 (thoracotomy in 2 and thoracoscopy in 2). No significant differences were found between the right and left approaches with regard to leaks (P=0.89), strictures (P=1) or mortality (P=1). In 47/54 patients (87%) RAA was noted during right thoracotomy, and primary anastomosis was achieved through the same approach in 29 (61.7%); conversion to other approaches (left thoracotomy or esophageal substitution) was performed in 15 children (38.3%). No significant differences were found between primary left thoracotomy (LT) and LT after RT with regard to leaks (P=0.89), strictures (P=1) or mortality (P=1). Skills and preferences of the surgeon still guide the choice of surgical approach even when preoperatively faced with RAA. A multicenter, prospective randomized study is strongly required. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Considering Planetary Constraints and Dynamic Screening in Solar Evolution Modeling

NASA Astrophysics Data System (ADS)

Wood, Suzannah R.; Mussack, Katie; Guzik, Joyce A.

2018-01-01

The ‘faint early sun problem’ remains unsolved. This problem consists of the apparent contradiction between the standard solar model prediction of lower luminosity (70% of current luminosity) and the observations of liquid water on early Earth and Mars. The presence of liquid water on early Earth and Mars should not be neglected and should be used as a constraint for solar evolution modeling. In addition, modifications to standard solar models are needed to address the discrepancy with solar structure inferred from helioseismology given the latest solar abundance determinations. Here, we will utilize the three different solar abundances: GN93 (Grevesse & Noels, 1993), AGS05 (Asplund et al., 2005), AGSS09 (Asplund et al., 2009). Here, we propose an early mass loss model with an initial solar mass between 1.07 and 1.15 solar masses and an exponentially decreasing mass-loss rate to meet conditions in the early solar system (Wood et al, submitted). Additionally, we investigate the effects of dynamic screening and the new OPLIB opacities from Los Alamos (Colgan et al., 2016). We show the effects of these modifications to the standard solar evolution models on the interior structure, neutrino fluxes, sound speed, p-mode frequencies, convection zone depth, and envelope helium and element abundance of the model sun at the present day.

Morphological Variation of the Scorpionfly Panorpa obtusa Cheng (Mecoptera: Panorpidae) with a New Synonym

PubMed Central

Ma, Na; Hu, Guilin; Zhang, Junxia; Hua, Baozhen

2014-01-01

Background The overabundance of synonyms is an unavoidable by-product of taxonomic practice in insects. How to reduce or even eliminate synonymy has long been a great challenge for insect taxonomists. The scorpionflies Panorpa obtusa Cheng, 1949 and Panorpa leei Cheng, 1949 (Insecta: Mecoptera: Panorpidae) were originally described from Taibaishan in the Qinling Mountains with identical collection data and both are based on a single gender, the former on a male and the latter on two females. However, whether P. leei is conspecific with P. obtusa or a good species remains an unsolved problem. Results On the basis of intensive morphological comparison of 93 males and 53 females of scorpionflies collected from the type locality using light and scanning electron microscopy, we found P. obtusa has considerable morphological variation (especially the wing markings and genitalia in both male and female), and Panorpa leei is totally comprised of one of the morphs of P. obtusa. Conclusions In combination with identical type localities and overlapping morphological variation, P. leei Cheng is proposed as a junior subjective synonym of P. obtusa Cheng. To avoid synonyms, taxonomists should pay more attention to individual variation and base decisions on a series of specimens to describe new species. PMID:25250880

Protein-protein structure prediction by scoring molecular dynamics trajectories of putative poses.

PubMed

Sarti, Edoardo; Gladich, Ivan; Zamuner, Stefano; Correia, Bruno E; Laio, Alessandro

2016-09-01

The prediction of protein-protein interactions and their structural configuration remains a largely unsolved problem. Most of the algorithms aimed at finding the native conformation of a protein complex starting from the structure of its monomers are based on searching the structure corresponding to the global minimum of a suitable scoring function. However, protein complexes are often highly flexible, with mobile side chains and transient contacts due to thermal fluctuations. Flexibility can be neglected if one aims at finding quickly the approximate structure of the native complex, but may play a role in structure refinement, and in discriminating solutions characterized by similar scores. We here benchmark the capability of some state-of-the-art scoring functions (BACH-SixthSense, PIE/PISA and Rosetta) in discriminating finite-temperature ensembles of structures corresponding to the native state and to non-native configurations. We produce the ensembles by running thousands of molecular dynamics simulations in explicit solvent starting from poses generated by rigid docking and optimized in vacuum. We find that while Rosetta outperformed the other two scoring functions in scoring the structures in vacuum, BACH-SixthSense and PIE/PISA perform better in distinguishing near-native ensembles of structures generated by molecular dynamics in explicit solvent. Proteins 2016; 84:1312-1320. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Natalizumab in the treatment of Crohn’s disease

PubMed Central

Guagnozzi, Danila; Caprilli, Renzo

2008-01-01

The pathogenesis of Crohn’s disease (CD) is multifactorial and the activation of specific pathways of immunological system is important. In particular, the adhesion molecules (integrins) mediate the selective binding between the leukocytes and the endothelial cells regulating the migration of leukocytes into the normal and inflamed intestine. Selective adhesion molecule inhibitors interfere with the migration of leukocytes to the sites of inflammation by targeting adhesion molecules (α4-integrin or α4β7-integrin). Natalizumab is a humanized IgG4 anti-α4-integrin monoclonal antibody that inhibits both α4β7-integrin/mucosal addressin-cell adhesion molecule-1 (MadCAM-1) interaction and α4β1/vascular-cell adhesion molecule-1 (VCAM-1) binding. Pooled data from the four studies, analyzed in a Cochrane review, suggest that natalizumab is effective for induction of clinical response and remission in patients with moderately to severely active CD. In particular, natalizumab may be beneficial for patients with active inflammation or chronically active disease despite the use of conventional therapies with high level of C-reactive protein values at baseline time. Nevertheless, many problems about the utilization of natalizumab in CD remain unsolved (such as the high placebo response, the final definition of dosage and timing schedule, the definition of outcomes and the development of adverse events). PMID:19707360

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

Manual Removal of the Placenta after Vaginal Delivery: An Unsolved Problem in Obstetrics

PubMed Central

Zimmermann, Roland

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. PMID:24812585

Min-cut segmentation of cursive handwriting in tabular documents

NASA Astrophysics Data System (ADS)

Davis, Brian L.; Barrett, William A.; Swingle, Scott D.

2015-01-01

Handwritten tabular documents, such as census, birth, death and marriage records, contain a wealth of information vital to genealogical and related research. Much work has been done in segmenting freeform handwriting, however, segmentation of cursive handwriting in tabular documents is still an unsolved problem. Tabular documents present unique segmentation challenges caused by handwriting overlapping cell-boundaries and other words, both horizontally and vertically, as "ascenders" and "descenders" overlap into adjacent cells. This paper presents a method for segmenting handwriting in tabular documents using a min-cut/max-flow algorithm on a graph formed from a distance map and connected components of handwriting. Specifically, we focus on line, word and first letter segmentation. Additionally, we include the angles of strokes of the handwriting as a third dimension to our graph to enable the resulting segments to share pixels of overlapping letters. Word segmentation accuracy is 89.5% evaluating lines of the data set used in the ICDAR2013 Handwriting Segmentation Contest. Accuracy is 92.6% for a specific application of segmenting first and last names from noisy census records. Accuracy for segmenting lines of names from noisy census records is 80.7%. The 3D graph cutting shows promise in segmenting overlapping letters, although highly convoluted or overlapping handwriting remains an ongoing challenge.

The Role of Heart-Rate Variability Parameters in Activity Recognition and Energy-Expenditure Estimation Using Wearable Sensors.

PubMed

Park, Heesu; Dong, Suh-Yeon; Lee, Miran; Youn, Inchan

2017-07-24

Human-activity recognition (HAR) and energy-expenditure (EE) estimation are major functions in the mobile healthcare system. Both functions have been investigated for a long time; however, several challenges remain unsolved, such as the confusion between activities and the recognition of energy-consuming activities involving little or no movement. To solve these problems, we propose a novel approach using an accelerometer and electrocardiogram (ECG). First, we collected a database of six activities (sitting, standing, walking, ascending, resting and running) of 13 voluntary participants. We compared the HAR performances of three models with respect to the input data type (with none, all, or some of the heart-rate variability (HRV) parameters). The best recognition performance was 96.35%, which was obtained with some selected HRV parameters. EE was also estimated for different choices of the input data type (with or without HRV parameters) and the model type (single and activity-specific). The best estimation performance was found in the case of the activity-specific model with HRV parameters. Our findings indicate that the use of human physiological data, obtained by wearable sensors, has a significant impact on both HAR and EE estimation, which are crucial functions in the mobile healthcare system.

The Use of Laser Microdissection in Forensic Sexual Assault Casework: Pros and Cons Compared to Standard Methods.

PubMed

Costa, Sergio; Correia-de-Sá, Paulo; Porto, Maria J; Cainé, Laura

2017-07-01

Sexual assault samples are among the most frequently analyzed in a forensic laboratory. These account for almost half of all samples processed routinely, and a large portion of these cases remain unsolved. These samples often pose problems to traditional analytic methods of identification because they consist most frequently of cell mixtures from at least two contributors: the victim (usually female) and the perpetrator (usually male). In this study, we propose the use of current preliminary testing for sperm detection in order to determine the chances of success when faced with samples which can be good candidates to undergo analysis with the laser microdissection technology. Also, we used laser microdissection technology to capture fluorescently stained cells of interest differentiated by gender. Collected materials were then used for DNA genotyping with commercially available amplification kits such as Minifiler, Identifiler Plus, NGM, and Y-Filer. Both the methodology and the quality of the results were evaluated to assess the pros and cons of laser microdissection compared with standard methods. Overall, the combination of fluorescent staining combined with the Minifiler amplification kit provided the best results for autosomal markers, whereas the Y-Filer kit returned the expected results regardless of the used method. © 2017 American Academy of Forensic Sciences.

Proceedings of the Inaugural Pediatric Dermatology Research Alliance (PeDRA) Conference

PubMed Central

Siegel, Dawn H.; Choate, Keith; Drolet, Beth A.; Frieden, Ilona J.; Teng, Joyce M.; Tom, Wynnis; Williams, Mary; Eichenfield, Lawrence F.; Paller, Amy S.

2014-01-01

Abstract/Statement of the problem Skin disease research involving children currently faces several major hurdles and as a result, many therapies are only available for off-label use in children and many of the most pressing clinical needs of our pediatric population remain unsolved. A strategic planning committee of the Society for Pediatric Dermatology (SPD) identified the need for an organized, inclusive research alliance to augment the resources of individual practitioners and pre-existing smaller collaborative groups and facilitate robust, multicenter basic, translational, and clinical research and therapeutic trials. A December 2011 National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Roundtable on Pediatric Dermatology further detailed the therapeutic gaps and barriers to translation of scientific advances to clinical practice. Building on these forums, in July 2012, a group of interested investigators met in Monterey, CA to develop the infrastructure for collaborative pediatric skin research, now called the Pediatric Dermatology Research Alliance (PeDRA). The vision of PeDRA is to create sustainable collaborative research networks to better understand, prevent, treat and cure dermatologic diseases in children. From that starting point, subcommittees and expert members were added, stakeholders identified, and seed funding garnered, with the first PeDRA stand-alone research meeting* realized in Chicago, IL in October 2013. PMID:25318428

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

Toward seamless hydrologic predictions across spatial scales

NASA Astrophysics Data System (ADS)

Samaniego, Luis; Kumar, Rohini; Thober, Stephan; Rakovec, Oldrich; Zink, Matthias; Wanders, Niko; Eisner, Stephanie; Müller Schmied, Hannes; Sutanudjaja, Edwin H.; Warrach-Sagi, Kirsten; Attinger, Sabine

2017-09-01

Land surface and hydrologic models (LSMs/HMs) are used at diverse spatial resolutions ranging from catchment-scale (1-10 km) to global-scale (over 50 km) applications. Applying the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the chosen resolution, i.e., fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent hydrologic parameter fields. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB, and WaterGAP models demonstrate the pitfalls of deficient parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge's 1982 statement on the unsolved problem of parameterization in these models remains true. Based on a review of existing parameter regionalization techniques, we postulate that the multiscale parameter regionalization (MPR) technique offers a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. Herein, we develop a general model protocol to describe how MPR can be applied to a particular model and present an example application using the PCR-GLOBWB model. Finally, we discuss potential advantages and limitations of MPR in obtaining the seamless prediction of hydrological fluxes and states across spatial scales.

Hybrid digital-analog video transmission in wireless multicast and multiple-input multiple-output system

NASA Astrophysics Data System (ADS)

Liu, Yu; Lin, Xiaocheng; Fan, Nianfei; Zhang, Lin

2016-01-01

Wireless video multicast has become one of the key technologies in wireless applications. But the main challenge of conventional wireless video multicast, i.e., the cliff effect, remains unsolved. To overcome the cliff effect, a hybrid digital-analog (HDA) video transmission framework based on SoftCast, which transmits the digital bitstream with the quantization residuals, is proposed. With an effective power allocation algorithm and appropriate parameter settings, the residual gains can be maximized; meanwhile, the digital bitstream can assure transmission of a basic video to the multicast receiver group. In the multiple-input multiple-output (MIMO) system, since nonuniform noise interference on different antennas can be regarded as the cliff effect problem, ParCast, which is a variation of SoftCast, is also applied to video transmission to solve it. The HDA scheme with corresponding power allocation algorithms is also applied to improve video performance. Simulations show that the proposed HDA scheme can overcome the cliff effect completely with the transmission of residuals. What is more, it outperforms the compared WSVC scheme by more than 2 dB when transmitting under the same bandwidth, and it can further improve performance by nearly 8 dB in MIMO when compared with the ParCast scheme.

Cancer stem cells: a metastasizing menace!

PubMed

Bandhavkar, Saurabh

2016-04-01

Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Code Modernization of VPIC

NASA Astrophysics Data System (ADS)

Bird, Robert; Nystrom, David; Albright, Brian

2017-10-01

The ability of scientific simulations to effectively deliver performant computation is increasingly being challenged by successive generations of high-performance computing architectures. Code development to support efficient computation on these modern architectures is both expensive, and highly complex; if it is approached without due care, it may also not be directly transferable between subsequent hardware generations. Previous works have discussed techniques to support the process of adapting a legacy code for modern hardware generations, but despite the breakthroughs in the areas of mini-app development, portable-performance, and cache oblivious algorithms the problem still remains largely unsolved. In this work we demonstrate how a focus on platform agnostic modern code-development can be applied to Particle-in-Cell (PIC) simulations to facilitate effective scientific delivery. This work builds directly on our previous work optimizing VPIC, in which we replaced intrinsic based vectorisation with compile generated auto-vectorization to improve the performance and portability of VPIC. In this work we present the use of a specialized SIMD queue for processing some particle operations, and also preview a GPU capable OpenMP variant of VPIC. Finally we include a lessons learnt. Work performed under the auspices of the U.S. Dept. of Energy by the Los Alamos National Security, LLC Los Alamos National Laboratory under contract DE-AC52-06NA25396 and supported by the LANL LDRD program.

Leveraging percolation theory to single out influential spreaders in networks

NASA Astrophysics Data System (ADS)

Radicchi, Filippo; Castellano, Claudio

2016-06-01

Among the consequences of the disordered interaction topology underlying many social, technological, and biological systems, a particularly important one is that some nodes, just because of their position in the network, may have a disproportionate effect on dynamical processes mediated by the complex interaction pattern. For example, the early adoption of a commercial product by an opinion leader in a social network may change its fate or just a few superspreaders may determine the virality of a meme in social media. Despite many recent efforts, the formulation of an accurate method to optimally identify influential nodes in complex network topologies remains an unsolved challenge. Here, we present the exact solution of the problem for the specific, but highly relevant, case of the susceptible-infected-removed (SIR) model for epidemic spreading at criticality. By exploiting the mapping between bond percolation and the static properties of the SIR model, we prove that the recently introduced nonbacktracking centrality is the optimal criterion for the identification of influential spreaders in locally tree-like networks at criticality. By means of simulations on synthetic networks and on a very extensive set of real-world networks, we show that the nonbacktracking centrality is a highly reliable metric to identify top influential spreaders also in generic graphs not embedded in space and for noncritical spreading.

CYTOKINES AS THE PREDICTORS OF SEVERE MYCOPLASMA PNEUMONIAE PNEUMONIA IN CHILDREN (REVIEW).

PubMed

Chkhaidze, I; Kapanadze, N

2017-06-01

In spite of many attempts to differentiate bacterial from viral disease and predict severity and outcome, the etiologic diagnosis of paediatric community acquired pneumonia and the estimation of potential outcomes remain unsolved problems in most cases. Mycoplasma pneumoniae is one of the major pathogens causing CAP in children. Although MP infection was traditionally thought to be a self-limited process, more and more severe cases even fatal cases of MP infections were reported in recent years. So it is essential for pediatricians to recognize severe or refractory or severe MP early, treat it promptly and prevent the progress of the disease. In recent years, several new biomarkers have been tested in children with CAP. Some of the biomarkers used for etiologic diagnosis in children with CAP and they also have been used the MP infection severity. Among traditional biomarkers, several cytokines appears to be effective both in selection of bacterial cases and in evaluation of severity. However, a precise cut-off level able to separate bacterial from viral cases and mild from severe cases has not been defined. Further studies enrolled with a large number of children with Mycoplasma pneumoniae is needed to be carried out to identify the potential utility of different cytokines as the good predictors.

There must be a prokaryote somewhere: microbiology's search for itself

NASA Technical Reports Server (NTRS)

Woese, C. R.

1994-01-01

While early microbiologists showed considerable interest in the problem of the natural (evolutionary) relationships among prokaryotes, by the middle of this century that problem had largely been discarded as being unsolvable. In other words, the science of microbiology developed without an evolutionary framework, the lack of which kept it a weak discipline, defined largely by external forces. Modern technology has allowed microbiology finally to develop the needed evolutionary framework, and with this comes a sense of coherence, a sense of identity. Not only is this development radically changing microbiology itself, but also it will change microbiology's relationship to the other biological disciplines. Microbiology of the future will become the primary biological science, the base upon which our future understanding of the living world rests, and the font from which new understanding of it flows.

Addressing the minimum fleet problem in on-demand urban mobility.

PubMed

Vazifeh, M M; Santi, P; Resta, G; Strogatz, S H; Ratti, C

2018-05-01

Information and communication technologies have opened the way to new solutions for urban mobility that provide better ways to match individuals with on-demand vehicles. However, a fundamental unsolved problem is how best to size and operate a fleet of vehicles, given a certain demand for personal mobility. Previous studies 1-5 either do not provide a scalable solution or require changes in human attitudes towards mobility. Here we provide a network-based solution to the following 'minimum fleet problem', given a collection of trips (specified by origin, destination and start time), of how to determine the minimum number of vehicles needed to serve all the trips without incurring any delay to the passengers. By introducing the notion of a 'vehicle-sharing network', we present an optimal computationally efficient solution to the problem, as well as a nearly optimal solution amenable to real-time implementation. We test both solutions on a dataset of 150 million taxi trips taken in the city of New York over one year 6 . The real-time implementation of the method with near-optimal service levels allows a 30 per cent reduction in fleet size compared to current taxi operation. Although constraints on driver availability and the existence of abnormal trip demands may lead to a relatively larger optimal value for the fleet size than that predicted here, the fleet size remains robust for a wide range of variations in historical trip demand. These predicted reductions in fleet size follow directly from a reorganization of taxi dispatching that could be implemented with a simple urban app; they do not assume ride sharing 7-9 , nor require changes to regulations, business models, or human attitudes towards mobility to become effective. Our results could become even more relevant in the years ahead as fleets of networked, self-driving cars become commonplace 10-14 .

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

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.

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.

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.

Ab Initio Protein Structure Assembly Using Continuous Structure Fragments and Optimized Knowledge-based Force Field

PubMed Central

Xu, Dong; Zhang, Yang

2012-01-01

Ab initio protein folding is one of the major unsolved problems in computational biology due to the difficulties in force field design and conformational search. We developed a novel program, QUARK, for template-free protein structure prediction. Query sequences are first broken into fragments of 1–20 residues where multiple fragment structures are retrieved at each position from unrelated experimental structures. Full-length structure models are then assembled from fragments using replica-exchange Monte Carlo simulations, which are guided by a composite knowledge-based force field. A number of novel energy terms and Monte Carlo movements are introduced and the particular contributions to enhancing the efficiency of both force field and search engine are analyzed in detail. QUARK prediction procedure is depicted and tested on the structure modeling of 145 non-homologous proteins. Although no global templates are used and all fragments from experimental structures with template modeling score (TM-score) >0.5 are excluded, QUARK can successfully construct 3D models of correct folds in 1/3 cases of short proteins up to 100 residues. In the ninth community-wide Critical Assessment of protein Structure Prediction (CASP9) experiment, QUARK server outperformed the second and third best servers by 18% and 47% based on the cumulative Z-score of global distance test-total (GDT-TS) scores in the free modeling (FM) category. Although ab initio protein folding remains a significant challenge, these data demonstrate new progress towards the solution of the most important problem in the field. PMID:22411565

Optional real-time display of intraoperative neurophysiological monitoring in the microscopic field of view: avoiding communication failures in the operating room.

PubMed

Stoecklein, Veit M; Faber, Florian; Koch, Mandy; Mattmüller, Rudi; Schaper, Anika; Rudolph, Frank; Tonn, Joerg C; Schichor, Christian

2015-11-01

The use of intraoperative neurophysiological monitoring (IONM) in neurosurgery has improved patient safety and outcomes. However, a pitfall in the use of IONM remains unsolved. Currently, there is no feasible way for surgeons to interpret IONM waves themselves during operations. Instead, they have to rely on verbal feedback from a neurophysiologist. This method is prone to communication failures, which can lead to delayed or false interpretation of the data. Direct visualization of IONM waves is a way to alleviate this problem and make IONM more effective. Microscope-integrated IONM (MI-IONM) was used in 163 cranial and spinal cases. We evaluated the feasibility, system stability and how well the system integrated into the surgical workflow. We used an IONM system that was connected to a surgical microscope. All IONM modalities used at our institution could be visualized as required, superimposed on the surgical field in the eyepiece of the microscope without obstructing the surgeon's field of vision. Use of MI-IONM was safe and reliable. It furthermore provided valuable intraoperative information. The system merely required a short learning curve. Only minor system problems without impact on surgical workflow occurred. MI-IONM proved to be especially useful in surgical cases where careful monitoring of nerve function is required, e.g., cerebellopontine angle surgery. Here, direct assessment of surgical action and IONM wave change was provided to the surgeon, if necessary (on-off control). MI-IONM is a useful extension of conventional IONM that provides optional real-time functional information to the surgeon on demand.

POSSIBLE EVIDENCE FOR A FISK-TYPE HELIOSPHERIC MAGNETIC FIELD. I. ANALYZING ULYSSES/KET ELECTRON OBSERVATIONS

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

Sternal, O.; Heber, B.; Kopp, A.

The propagation of energetic charged particles in the heliospheric magnetic field is one of the fundamental problems in heliophysics. In particular, the structure of the heliospheric magnetic field remains an unsolved problem and is discussed as a controversial topic. The first successful analytic approach to the structure of the heliospheric magnetic field was the Parker field. However, the measurements of the Ulysses spacecraft at high latitudes revealed the possible need for refinements of the existing magnetic field model during solar minimum. Among other reasons, this led to the development of the Fisk field. This approach is highly debated and couldmore » not be ruled out with magnetic field measurements so far. A promising method to trace this magnetic field structure is to model the propagation of electrons in the energy range of a few MeV. Employing three-dimensional and time-dependent simulations of the propagation of energetic electrons, this work shows that the influence of a Fisk-type field on the particle transport in the heliosphere leads to characteristic variations of the electron intensities on the timescale of a solar rotation. For the first time it is shown that the Ulysses count rates of 2.5-7 MeV electrons contain the imprint of a Fisk-type heliospheric magnetic field structure. From a comparison of simulation results and the Ulysses count rates, realistic parameters for the Fisk theory are derived. Furthermore, these parameters are used to investigate the modeled relative amplitudes of protons and electrons, including the effects of drifts.« less

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

[Dichoptic training for amblyopia].

PubMed

Bach, M

2016-04-01

Dichoptic training is a promising new therapeutic approach to amblyopia, which employs simultaneous and separate stimulation of both eyes (thus dichoptic). The contrast for the good eye is reduced thus aiming at a balance with the amblyopic eye. In contrast to monocular patching, binocular vision is trained by video game tasks that can only be solved binocularly. To date the average gain in visual acuity achieved in currently available studies is only 0.20 ± 0.07 logMAR and is not significantly better than competing treatment options. This article explains the basic approach of dichoptic training, summarizes pertinent studies, names unsolved problems and closes with a personal critical assessment.

Tinea capitis: still an unsolved problem?

PubMed

Patel, Gopal A; Schwartz, Robert A

2011-05-01

Tinea capitis is a fungal infection specifically involving the scalp and hair. It is the most common dermatophyte infection in children under 12 years of age, with a predominance in those of sub-Saharan African descent. Common signs include hair loss, scaling, erythema and impetigo-like plaques. Adults may also be affected, but to a lesser degree. The causative species are from the Microsporum and Trichophyton genera. Limited treatment options and diverse modes of transmission complicate the clinician's ability to address this disease adequately. Although dermatophytes are ubiquitous in our environment and tinea capitis is common, therapeutic options can be utilised to reduce morbidity. © 2009 Blackwell Verlag GmbH.

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

PubMed

Gobet, F R

1992-01-01

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

Future scientific exploration of Taurus-Littrow

NASA Technical Reports Server (NTRS)

Taylor, G. Jeffrey

1992-01-01

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

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.

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.

In defense of derivations

NASA Astrophysics Data System (ADS)

Mungan, Carl E.

2016-05-01

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

Crystal growth of device quality GaAs in space

NASA Technical Reports Server (NTRS)

Gatos, H. C.; Lagowski, J.

1985-01-01

The present program has been aimed at solving the fundamental and technological problems associated with Crystal Growth of Device Quality in Space. The initial stage of the program was devoted strictly to ground-based research. The unsolved problems associated with the growth of bulk GaAs in the presence of gravitational forces were explored. Reliable chemical, structural and electronic characterization methods were developed which would permit the direct relation of the salient materials parameters (particularly those affected by zero gravity conditions) to the electronic characteristics of single crystal GaAs, in turn to device performance. These relationships are essential for the development of optimum approaches and techniques. It was concluded that the findings on elemental semiconductors Ge and Si regarding crystal growth, segregation, chemical composition, defect interactions, and materials properties-electronic properties relationships are not necessarily applicable to GaAs (and to other semiconductor compounds). In many instances totally unexpected relationships were found to prevail.

A selection of biomechanical research problems: From modeling to experimentation

NASA Astrophysics Data System (ADS)

Abbasi, Cyrus Omid

The research undertakings within this manuscript illustrate the importance of biomechanics in today's science. Without doubt, biomechanics can be utilized to obtain a better understanding of many unsolved mysteries involved in the field of medicine. Moreover, biomechanics can be used to develop better prosthetic or surgical devices as well. Chapter 2 represents a medical problem, which has not been solved for more than a century. With the use of fundamental principles of biomechanics', a better insight of this problem and its possible causes were obtained. Chapter 3 investigates the mechanical interaction between the human teeth and some processed food products during mastication, which is a routine but crucial daily activity of a human being. Chapter 4 looks at a problem within the field of surgery. In this chapter the stability and reliability of two different Suturing-Techniques are explored. Chapters 5 and 6 represent new patent designs as a result of the investigations made in Chapter 4. Chapter 7 studies the impact and load transfer patterns during the collision between a child's head and the ground. All of the above mentioned chapters show the significance of biomechanics in solving a range of different medical problems that involve physical and or mechanical characters.

Stability-to-instability transition in the structure of large-scale networks

NASA Astrophysics Data System (ADS)

Hu, Dandan; Ronhovde, Peter; Nussinov, Zohar

2012-12-01

We examine phase transitions between the “easy,” “hard,” and “unsolvable” phases when attempting to identify structure in large complex networks (“community detection”) in the presence of disorder induced by network “noise” (spurious links that obscure structure), heat bath temperature T, and system size N. The partition of a graph into q optimally disjoint subgraphs or “communities” inherently requires Potts-type variables. In earlier work [Philos. Mag.1478-643510.1080/14786435.2011.616547 92, 406 (2012)], when examining power law and other networks (and general associated Potts models), we illustrated that transitions in the computational complexity of the community detection problem typically correspond to spin-glass-type transitions (and transitions to chaotic dynamics in mechanical analogs) at both high and low temperatures and/or noise. The computationally “hard” phase exhibits spin-glass type behavior including memory effects. The region over which the hard phase extends in the noise and temperature phase diagram decreases as N increases while holding the average number of nodes per community fixed. This suggests that in the thermodynamic limit a direct sharp transition may occur between the easy and unsolvable phases. When present, transitions at low temperature or low noise correspond to entropy driven (or “order by disorder”) annealing effects, wherein stability may initially increase as temperature or noise is increased before becoming unsolvable at sufficiently high temperature or noise. Additional transitions between contending viable solutions (such as those at different natural scales) are also possible. Identifying community structure via a dynamical approach where “chaotic-type” transitions were found earlier. The correspondence between the spin-glass-type complexity transitions and transitions into chaos in dynamical analogs might extend to other hard computational problems. In this work, we examine large networks (with a power law distribution in cluster size) that have a large number of communities (q≫1). We infer that large systems at a constant ratio of q to the number of nodes N asymptotically tend towards insolvability in the limit of large N for any positive T. The asymptotic behavior of temperatures below which structure identification might be possible, T×=O[1/lnq], decreases slowly, so for practical system sizes, there remains an accessible, and generally easy, global solvable phase at low temperature. We further employ multivariate Tutte polynomials to show that increasing q emulates increasing T for a general Potts model, leading to a similar stability region at low T. Given the relation between Tutte and Jones polynomials, our results further suggest a link between the above complexity transitions and transitions associated with random knots.

Proceedings of the NASA Conference on Space Telerobotics, volume 2

NASA Technical Reports Server (NTRS)

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

1989-01-01

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

Ecological stress and sex evolution in soil microfungi.

PubMed Central

Grishkan, Isabella; Korol, Abraham B; Nevo, Eviatar; Wasser, Solomon P

2003-01-01

The elucidation of the origin and maintenance of sex is a major unsolved problem in evolutionary biology. A number of hypotheses have been elaborated, but the scarcity of empirical data limits further progress. During recent years, the general inclination has changed towards pluralistic models of sex evolution, due partly to an increased diversity of studied organisms. Fungi are among the most promising organisms for testing sexual causation, as demonstrated in recent laboratory experiments. However, reconciling theory and evidence necessitates critical field observations. Here, we report new estimates of the distribution of morphologically sexual and asexual soil microfungi in nature, which indicate a remarkable trend towards increased sexuality with increasing climatic stress. PMID:12590766

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.

Radiocaesium in mushrooms from northeast Italy, 1986-2002.

PubMed

Giovani, C; Garavaglia, M; Scruzzi, E

2004-01-01

Late in the summer of 1986, the Health Physics Departments of Pordenone, Udine and Trieste, entrusted with monitoring radioactivity in the environment and food as a consequence of the Chernobyl accident, started noticing high concentrations of radionuclides--especially radiocaesium--in mushroom samples coming from different areas of the Friuli Venezia Giulia region (northeast Italy). To date, the authors have conducted 14 annual rounds of sampling and gamma spectrometry measurements on mushrooms, generating a total of over 2250 samples belonging to more than 300 species, which were picked in about 30 stations in the region. This surveys the main results from 15 years of macromycetes radiocontamination analysis in the region, the still unsolved problems, and hypotheses for future work.

Institutional Computing: Final Report Quantum Effects on Cosmology: Probing Physics Beyond the Standard Model with Big Bang Nucleosynthesis

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

Paris, Mark W.

The current one-year project allocation (w17 burst) supports the continuation of research performed in the two-year Institutional Computing allocation (w14 bigbangnucleosynthesis). The project has supported development and production runs resulting in several publications[1, 2, 3, 4] in peer-review journals and talks. Most signi cantly, we have recently achieved a signi cant improvement in code performance. This improvement was essential to the prospect of making further progress on this heretofore unsolved multiphysics problem that lies at the intersection of nuclear and particle theory and the kinetic theory of energy transport in a system with internal (quantum) degrees of freedom.

Standardization for oxygen isotope ratio measurement - still an unsolved problem.

PubMed

Kornexl; Werner; Gehre

1999-07-01

Numerous organic and inorganic laboratory standards were gathered from nine European and North American laboratories and were analyzed for their delta(18)O values with a new on-line high temperature pyrolysis system that was calibrated using Vienna standard mean ocean water (VSMOW) and standard light Antartic precipitation (SLAP) internationally distributed reference water samples. Especially for organic materials, discrepancies between reported and measured values were high, ranging up to 2 per thousand. The reasons for these discrepancies are discussed and the need for an exact and reliable calibration of existing reference materials, as well as for the establishment of additional organic and inorganic reference materials is stressed. Copyright 1999 John Wiley & Sons, Ltd.

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.

Navigational potential of e-vector sensing by marine animals

NASA Astrophysics Data System (ADS)

Waterman, Talbot H.

1993-02-01

This essay documents an informal talk about the central theme in the author's research career. That has mainly related to the visual physiology and orientation of aquatic animals, particularly with regard to underwater polarized light. This required pioneer measurements of underwater polarized light patterns, proof that oriented behavior could be determined by e- vector direction independently of intensity patterns or other secondary clues and a demonstration of the retinal dichroic mechanism involved, at least in crustacean compound eyes. The relevant visual data processing by two orthogonal channels was also analyzed with regard to oriented swimming behavior. Some current research by others and major unsolved problems are mentioned and the relevant part of the author's bibliography is appended.

Adaptive Importance Sampling for Control and Inference

NASA Astrophysics Data System (ADS)

Kappen, H. J.; Ruiz, H. C.

2016-03-01

Path integral (PI) control problems are a restricted class of non-linear control problems that can be solved formally as a Feynman-Kac PI and can be estimated using Monte Carlo sampling. In this contribution we review PI control theory in the finite horizon case. We subsequently focus on the problem how to compute and represent control solutions. We review the most commonly used methods in robotics and control. Within the PI theory, the question of how to compute becomes the question of importance sampling. Efficient importance samplers are state feedback controllers and the use of these requires an efficient representation. Learning and representing effective state-feedback controllers for non-linear stochastic control problems is a very challenging, and largely unsolved, problem. We show how to learn and represent such controllers using ideas from the cross entropy method. We derive a gradient descent method that allows to learn feed-back controllers using an arbitrary parametrisation. We refer to this method as the path integral cross entropy method or PICE. We illustrate this method for some simple examples. The PI control methods can be used to estimate the posterior distribution in latent state models. In neuroscience these problems arise when estimating connectivity from neural recording data using EM. We demonstrate the PI control method as an accurate alternative to particle filtering.

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

Heart Lesion After the First Attack of the Rheumatic Fever 22 Years Experience in Single Centre

PubMed Central

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

2015-01-01

Background: 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. Aims: 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. Methods: 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. Conclusion: 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. PMID:25870479

The three-class ideal observer for univariate normal data: Decision variable and ROC surface properties

PubMed Central

Edwards, Darrin C.; Metz, Charles E.

2012-01-01

Although a fully general extension of ROC analysis to classification tasks with more than two classes has yet to be developed, the potential benefits to be gained from a practical performance evaluation methodology for classification tasks with three classes have motivated a number of research groups to propose methods based on constrained or simplified observer or data models. Here we consider an ideal observer in a task with underlying data drawn from three univariate normal distributions. We investigate the behavior of the resulting ideal observer’s decision variables and ROC surface. In particular, we show that the pair of ideal observer decision variables is constrained to a parametric curve in two-dimensional likelihood ratio space, and that the decision boundary line segments used by the ideal observer can intersect this curve in at most six places. From this, we further show that the resulting ROC surface has at most four degrees of freedom at any point, and not the five that would be required, in general, for a surface in a six-dimensional space to be non-degenerate. In light of the difficulties we have previously pointed out in generalizing the well-known area under the ROC curve performance metric to tasks with three or more classes, the problem of developing a suitable and fully general performance metric for classification tasks with three or more classes remains unsolved. PMID:23162165

Instrument-free exothermic heating with phase change temperature control for paper microfluidic devices

NASA Astrophysics Data System (ADS)

Singleton, Jered; Zentner, Chris; Buser, Josh; Yager, Paul; LaBarre, Paul; Weigl, Bernhard H.

2013-03-01

Many infectious diseases, as well as some cancers, that affect global health are most accurately diagnosed through nucleic acid amplification and detection. There is a great need to simplify nucleic acid-based assay systems for use in global health in low-resource settings as well as in settings that do not have convenient access to laboratory staff and equipment such as doctors' offices and home care settings. In developing countries, unreliable electric power, inadequate supply chains, and lack of maintenance for complex diagnostic instruments are all common infrastructure shortfalls. Many elements of instrument-free, disposable, nucleic acid amplification assays have been demonstrated in recent years. However, the problem of instrument-free,1 low-cost, temperature-controlled chemical heating remains unsolved. In this paper we present the current status and results of work towards developing disposable, low-cost, temperature-controlled heaters designed to support isothermal nucleic acid amplification assays that are integrated with a two-dimensional paper network. Our approach utilizes the heat generated through exothermic chemical reactions and controls the heat through use of engineered phase change materials to enable sustained temperatures required for nucleic acid amplification. By selecting appropriate exothermic and phase change materials, temperatures can be controlled over a wide range, suitable for various isothermal amplification methods, and maintained for over an hour at an accuracy of +/- 1°C.

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.

[The origin of homoiothermy--unsolved problem].

PubMed

Dol'nik, V P

2003-01-01

The analysis of allometric dependence of energy expenditure on body mass among reptiles, birds and mammals has shown that standard metabolic rate of reptiles when they are warmed up to the temperature of homoiothermic animals is an order of magnitude lower than that of birds and mammals. Basal metabolism is originated as special feature historically related to the metabolism during active behavior, rather than thermal regulation. Facultative endothermy was not advantageous for large animals because of long time needed to warm up the body. The ancestors of birds and animals escaped negative consequences of van't-Hoff equation by choosing constant body temperature. Heat conductivity of reptile's covers is so great, that it cannot keep endogenous warm of resting animal at any temperature of the body. Reptile "dressed" in covers of bird or mammal would be able to keep warm under conditions of maximal aerobic muscular activity and body temperature similar to that of homoiothermic animals. The base of chemical thermoregulation in birds and mammals is a thermoregulatory muscle tonus which remains unknown. One can suppose that during evolution of birds and mammals the saltation-liked origin of endothermy "fixed" the level of metabolism typical for running reptile and transformed in into the basal metabolism. This event took place at the cell and tissue level. The absence of palaeontological evidences and intermediate forms among recent species does not allow easy understanding of homoiothermy origin.

Biomarkers in Pediatric Community-Acquired Pneumonia.

PubMed

Principi, Nicola; Esposito, Susanna

2017-02-19

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

Instrument-free exothermic heating with phase change temperature control for paper microfluidic devices.

PubMed

Singleton, Jered; Zentner, Chris; Buser, Josh; Yager, Paul; LaBarre, Paul; Weigl, Bernhard H

2013-03-09

Many infectious diseases, as well as some cancers, that affect global health are most accurately diagnosed through nucleic acid amplification and detection. There is a great need to simplify nucleic acid-based assay systems for use in global health in low-resource settings as well as in settings that do not have convenient access to laboratory staff and equipment such as doctors' offices and home care settings. In developing countries, unreliable electric power, inadequate supply chains, and lack of maintenance for complex diagnostic instruments are all common infrastructure shortfalls. Many elements of instrument-free, disposable, nucleic acid amplification assays have been demonstrated in recent years. However, the problem of instrument-free, low-cost, temperature-controlled chemical heating remains unsolved. In this paper we present the current status and results of work towards developing disposable, low-cost, temperature-controlled heaters designed to support isothermal nucleic acid amplification assays that are integrated with a two-dimensional paper network. Our approach utilizes the heat generated through exothermic chemical reactions and controls the heat through use of engineered phase change materials to enable sustained temperatures required for nucleic acid amplification. By selecting appropriate exothermic and phase change materials, temperatures can be controlled over a wide range, suitable for various isothermal amplification methods, and maintained for over an hour at an accuracy of +/- 1°C.

How we hear what is not there: A neural mechanism for the missing fundamental illusion

NASA Astrophysics Data System (ADS)

Chialvo, Dante R.

2003-12-01

How the brain estimates the pitch of a complex sound remains unsolved. Complex sounds are composed of more than one tone. When two tones occur together, a third lower pitched tone is often heard. This is referred to as the "missing fundamental illusion" because the perceived pitch is a frequency (fundamental) for which there is no actual source vibration. This phenomenon exemplifies a larger variety of problems related to how pitch is extracted from complex tones, music and speech, and thus has been extensively used to test theories of pitch perception. A noisy nonlinear process is presented here as a candidate neural mechanism to explain the majority of reported phenomenology and provide specific quantitative predictions. The two basic premises of this model are as follows: (I) The individual tones composing the complex tones add linearly producing peaks of constructive interference whose amplitude is always insufficient to fire the neuron (II): The spike threshold is reached only with noise, which naturally selects the maximum constructive interferences. The spacing of these maxima, and consequently the spikes, occurs at a rate identical to the perceived pitch for the complex tone. Comparison with psychophysical and physiological data reveals a remarkable quantitative agreement not dependent on adjustable parameters. In addition, results from numerical simulations across different models are consistent, suggesting relevance to other sensory modalities.

Is the S-Web the Secret to Observed Heliospheric Particle Distributions?

NASA Astrophysics Data System (ADS)

Higginson, A. K.; Antiochos, S. K.; DeVore, C. R.; Daldorff, L. K. S.; Wyper, P. F.; Ukhorskiy, A. Y.; Sorathia, K.

2017-12-01

Particle transport in the heliosphere remains an unsolved problem across energy regimes. Observations of slow solar wind show that plasma escapes from the closed-field corona, but ends up far away from the heliospheric current sheet, even though the release mechanisms are expected to occur at the HCS. Similarly, some impulsive SEP events have extreme longitudinal extents of 100 degrees or more. Recent theoretical and numerical work has shown that interchange reconnection near a coronal-hole corridor can release plasma from originally closed magnetic field lines into a large swath spread across the heliosphere, forming what is known as an S-Web arc. This is a promising mechanism for explaining both the slow solar wind, with its large latitudinal extent, and impulsive SEP particles, with their large longitudinal extent. Here we compute, for the first time, the dynamics of the S-Web when the photospheric driver is applied over a large portion of the solar surface compared to the scale of the driving. We examine the time scales for the interchange reconnection and compute the angular extent of the plasma released, in the context of understanding both the slow solar wind and flare-accelerated SEPs. We will make predictions for Solar Orbiter and Parker Solar Probe and discuss how these new measurements will help to both pinpoint the source of the slow solar wind and illuminate the transport mechanisms of wide-spread impulsive SEP events.

Current challenges in autonomous vehicle development

NASA Astrophysics Data System (ADS)

Connelly, J.; Hong, W. S.; Mahoney, R. B., Jr.; Sparrow, D. A.

2006-05-01

The field of autonomous vehicles is a rapidly growing one, with significant interest from both government and industry sectors. Autonomous vehicles represent the intersection of artificial intelligence (AI) and robotics, combining decision-making with real-time control. Autonomous vehicles are desired for use in search and rescue, urban reconnaissance, mine detonation, supply convoys, and more. The general adage is to use robots for anything dull, dirty, dangerous or dumb. While a great deal of research has been done on autonomous systems, there are only a handful of fielded examples incorporating machine autonomy beyond the level of teleoperation, especially in outdoor/complex environments. In an attempt to assess and understand the current state of the art in autonomous vehicle development, a few areas where unsolved problems remain became clear. This paper outlines those areas and provides suggestions for the focus of science and technology research. The first step in evaluating the current state of autonomous vehicle development was to develop a definition of autonomy. A number of autonomy level classification systems were reviewed. The resulting working definitions and classification schemes used by the authors are summarized in the opening sections of the paper. The remainder of the report discusses current approaches and challenges in decision-making and real-time control for autonomous vehicles. Suggested research focus areas for near-, mid-, and long-term development are also presented.

Fitness of RNA virus decreased by Muller's ratchet

NASA Astrophysics Data System (ADS)

Chao, Lin

1990-11-01

WHY sex exists remains an unsolved problem in biology1-3. If mutations are on the average deleterious, a high mutation rate can account for the evolution of sex4. One form of this mutational hypothesis is Muller's ratchet5,6. If the mutation rate is high, mutation-free individuals become rare and they can be lost by genetic drift in small populations. In asexual populations, as Muller5 noted, the loss is irreversible and the load of deleterious mutations increases in a ratchet-like manner with the successive loss of the least-mutated individuals. Sex can be advantageous because it increases the fitness of sexual populations by re-creating mutation-free individuals from mutated individuals and stops (or slows) Muller's ratchet. Although Muller's ratchet is an appealing hypothesis, it has been investigated and documented experimentally in only one group of organisms-ciliated protozoa2. I initiated a study to examine the role of Muller's ratchet on the evolution of sex in RNA viruses and report here a significant decrease in fitness due to Muller's ratchet in 20 lineages of the RNA bacteriophage Φ6. These results show that deleterious mutations are generated at a sufficiently high rate to advance Muller's ratchet in an RNA virus and that beneficial, backward and compensatory mutations cannot stop the ratchet in the observed range of fitness decrease.

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

RFID reader with gas sensing capability for monitoring fruit along the logistic chain: array development and signal processing

NASA Astrophysics Data System (ADS)

Llobet, Eduard; Vergara, Alexander; Ramírez, José Luis; Zampolli, Stefano; Becker, Thomas; Fonseca, Luis

2007-05-01

The reliable and low-cost quantitative detection of ethylene for food/fruit applications remains an unsolved problem. Existing commercial systems are able to quantify ethylene (at sub ppm levels) but either they are off-line: require periodic sample collection and use of reagents or high-cost. We will report on the development of an RFID reader with onboard micro-machined metal oxide gas sensors aimed at monitoring climacteric fruit during transport and vending. The developed platform integrates a commercial off the shelf inductive coupling RF transceiver in the 13.56MHz band, fully compliant with the ISO15693 standard, micro-hotplate gas sensors, driving and readout electronics. If the sensors are operated at a fixed temperature, the reader could work as an alarm level monitor able to assess the conservation stage of apples. On the other hand, when the sensors are operated under an optimised temperature-modulation mode, accurate calibration models for the species that are relevant to assess the conservation stage of apples (i.e., ethylene, acetaldehyde and ethanol) can be built. Finally, different feature extraction techniques such as the FFT and the Energy Vector will be used in combination with pattern recognition tools like PLS and PLS-DA to show that our system is able to identify and quantify the species that are relevant for the application considered.

Use of 8-methoxypsoralen and long-wavelength ultraviolet radiation for decontamination of platelet concentrates

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

Lin, L.; Wiesehahn, G.P.; Morel, P.A.

1989-07-01

Transmission of viral diseases through blood products remains an unsolved problem in transfusion medicine. We have developed a psoralen photochemical system for decontamination of platelet concentrates in which platelets are treated with long wavelength ultraviolet radiation (UVA, 320-400 nm) in the presence of 8-methoxypsoralen (8-MOP). Bacteria, RNA viruses, and DNA viruses ranging in genome size from 1.2 x 10(6) daltons, encompassing the size range of human pathogens, were inoculated into platelet concentrates and subjected to treatment. This system inactivated 25 to 30 logs/h of bacteria Escherichia coli or Staphylococcus aureus, 6 logs/h of bacteriophage fd, 0.9 log/h of bacteriophage R17more » and 1.1 logs/h of feline leukemia virus (FeLV) in platelet concentrates maintained in standard storage bags. Platelet integrity and in vitro function before, immediately following photochemical treatment, and during prolonged storage after treatment, were evaluated by measuring: (1) extracellular pH; (2) platelet yields; (3) extracellular lactate dehydrogenase (LDH) levels; (4) platelet morphology; (5) platelet aggregation responsiveness; (6) thromboxane beta-2 (TXB-2) production; (7) dense body secretion; and (8) alpha granule secretion. These assays demonstrated that this photochemical inactivation system inactivated bacteria and viruses in platelet concentrates with minimal adverse effects on the in vitro function of platelets in comparison to untreated control concentrates maintained under current, standard blood bank conditions.« less

Employment of Near Full-Length Ribosome Gene TA-Cloning and Primer-Blast to Detect Multiple Species in a Natural Complex Microbial Community Using Species-Specific Primers Designed with Their Genome Sequences.

PubMed

Zhang, Huimin; He, Hongkui; Yu, Xiujuan; Xu, Zhaohui; Zhang, Zhizhou

2016-11-01

It remains an unsolved problem to quantify a natural microbial community by rapidly and conveniently measuring multiple species with functional significance. Most widely used high throughput next-generation sequencing methods can only generate information mainly for genus-level taxonomic identification and quantification, and detection of multiple species in a complex microbial community is still heavily dependent on approaches based on near full-length ribosome RNA gene or genome sequence information. In this study, we used near full-length rRNA gene library sequencing plus Primer-Blast to design species-specific primers based on whole microbial genome sequences. The primers were intended to be specific at the species level within relevant microbial communities, i.e., a defined genomics background. The primers were tested with samples collected from the Daqu (also called fermentation starters) and pit mud of a traditional Chinese liquor production plant. Sixteen pairs of primers were found to be suitable for identification of individual species. Among them, seven pairs were chosen to measure the abundance of microbial species through quantitative PCR. The combination of near full-length ribosome RNA gene library sequencing and Primer-Blast may represent a broadly useful protocol to quantify multiple species in complex microbial population samples with species-specific primers.

Instrument-free exothermic heating with phase change temperature control for paper microfluidic devices

PubMed Central

Singleton, Jered; Zentner, Chris; Buser, Josh; Yager, Paul; LaBarre, Paul; Weigl, Bernhard H.

2014-01-01

Many infectious diseases, as well as some cancers, that affect global health are most accurately diagnosed through nucleic acid amplification and detection. There is a great need to simplify nucleic acid-based assay systems for use in global health in low-resource settings as well as in settings that do not have convenient access to laboratory staff and equipment such as doctors' offices and home care settings. In developing countries, unreliable electric power, inadequate supply chains, and lack of maintenance for complex diagnostic instruments are all common infrastructure shortfalls. Many elements of instrument-free, disposable, nucleic acid amplification assays have been demonstrated in recent years. However, the problem of instrument-free,1 low-cost, temperature-controlled chemical heating remains unsolved. In this paper we present the current status and results of work towards developing disposable, low-cost, temperature-controlled heaters designed to support isothermal nucleic acid amplification assays that are integrated with a two-dimensional paper network. Our approach utilizes the heat generated through exothermic chemical reactions and controls the heat through use of engineered phase change materials to enable sustained temperatures required for nucleic acid amplification. By selecting appropriate exothermic and phase change materials, temperatures can be controlled over a wide range, suitable for various isothermal amplification methods, and maintained for over an hour at an accuracy of +/- 1°C. PMID:25426269

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.

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.

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

PubMed

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

2012-03-01

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

A NEWLY FORMING COLD FLOW PROTOGALACTIC DISK, A SIGNATURE OF COLD ACCRETION FROM THE COSMIC WEB

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

Martin, D. Christopher; Matuszewski, Mateusz; Morrissey, Patrick

How galaxies form from, and are fueled by, gas from the intergalactic medium (IGM) remains one of the major unsolved problems in galaxy formation. While the classical Cold Dark Matter paradigm posits galaxies forming from cooling virialized gas, recent theory and numerical simulations have highlighted the importance of cold accretion flows—relatively cool ( T ∼ few × 104 K) unshocked gas streaming along filaments into dark matter halos, including hot, massive, high-redshift halos. These flows are thought to deposit gas and angular momentum into the circumgalactic medium resulting in disk- or ring-like structures, eventually coalescing into galaxies forming at filamentarymore » intersections. We earlier reported a bright, Ly α emitting filament near the QSO HS1549+19 at redshift z = 2.843 discovered with the Palomar Cosmic Web Imager. We now report that the bright part of this filament is an enormous ( R > 100 kpc) rotating structure of hydrogen gas with a disk-like velocity profile consistent with a 4 × 10{sup 12} M {sub ⊙} halo. The orbital time of the outer part of the what we term a “protodisk” is comparable to the virialization time and the age of the universe at this redshift. We propose that this protodisk can only have recently formed from cold gas flowing directly from the cosmic web.« less

Mapping the distribution of packing topologies within protein interiors shows predominant preference for specific packing motifs

PubMed Central

2011-01-01

Background Mapping protein primary sequences to their three dimensional folds referred to as the 'second genetic code' remains an unsolved scientific problem. A crucial part of the problem concerns the geometrical specificity in side chain association leading to densely packed protein cores, a hallmark of correctly folded native structures. Thus, any model of packing within proteins should constitute an indispensable component of protein folding and design. Results In this study an attempt has been made to find, characterize and classify recurring patterns in the packing of side chain atoms within a protein which sustains its native fold. The interaction of side chain atoms within the protein core has been represented as a contact network based on the surface complementarity and overlap between associating side chain surfaces. Some network topologies definitely appear to be preferred and they have been termed 'packing motifs', analogous to super secondary structures in proteins. Study of the distribution of these motifs reveals the ubiquitous presence of typical smaller graphs, which appear to get linked or coalesce to give larger graphs, reminiscent of the nucleation-condensation model in protein folding. One such frequently occurring motif, also envisaged as the unit of clustering, the three residue clique was invariably found in regions of dense packing. Finally, topological measures based on surface contact networks appeared to be effective in discriminating sequences native to a specific fold amongst a set of decoys. Conclusions Out of innumerable topological possibilities, only a finite number of specific packing motifs are actually realized in proteins. This small number of motifs could serve as a basis set in the construction of larger networks. Of these, the triplet clique exhibits distinct preference both in terms of composition and geometry. PMID:21605466

Perturbation of a planetary orbit by the Lambda-term (dark energy) in Einstein equations

NASA Astrophysics Data System (ADS)

Dumin, Yurii

The problem of cosmological influences at small (e.g. interplanetary) scales is discussed for a few decades, starting from the early 1930's, but still remains unsolved definitively by now [1]. This subject became especially topical in the context of the dark-energy-dominated cosmology, because the commonly-used arguments against the local Hubble expansion (such as Einstein-Straus theorem [2]) are inapplicable when the most contribution to the energy density of the Universe comes from the perfectly-uniform dark energy (Lambda-term). Moreover, there are some empirical evidences in favor of the local cosmological influences. For example, inclusion of the local Hubble expansion into dynamics of the Earth-Moon system enables us to resolve a long-standing discrepancy in the rates of secular increase of the lunar semi-major axis (a) mea-sured by the lunar laser ranging and (b) derived from the astrometric observations of the Earth's rotation deceleration [3, 4]. The aim of the present report is to provide a detailed mathematical treatment of the respective two-body problem in the framework of General Relativity, which is based on the Kottler metric reduced to the Robertson-Walker cosmological asymptotics, as outlined in our earlier work [5]. References: 1. W.B. Bonnor. Gen. Rel. Grav., v.32, p.1005 (2000). 2. A. Einstein and E.G. Straus. Rev. Mod. Phys., v.17, p.120 (1945). 3. Yu.V. Dumin. Adv. Space Res., v.31, p.2461 (2003). 4. Yu.V. Dumin. In Proc. 11th Marcel Grossmann Meeting on General Relativity, World Sci., Singapore, p.1752 (2008). 5. Yu.V. Dumin. Phys. Rev. Lett., v.98, p.059001 (2007).

The information geometry of chaos

NASA Astrophysics Data System (ADS)

Cafaro, Carlo

2008-10-01

In this Thesis, we propose a new theoretical information-geometric framework (IGAC, Information Geometrodynamical Approach to Chaos) suitable to characterize chaotic dynamical behavior of arbitrary complex systems. First, the problem being investigated is defined; its motivation and relevance are discussed. The basic tools of information physics and the relevant mathematical tools employed in this work are introduced. The basic aspects of Entropic Dynamics (ED) are reviewed. ED is an information-constrained dynamics developed by Ariel Caticha to investigate the possibility that laws of physics---either classical or quantum---may emerge as macroscopic manifestations of underlying microscopic statistical structures. ED is of primary importance in our IGAC. The notion of chaos in classical and quantum physics is introduced. Special focus is devoted to the conventional Riemannian geometrodynamical approach to chaos (Jacobi geometrodynamics) and to the Zurek-Paz quantum chaos criterion of linear entropy growth. After presenting this background material, we show that the ED formalism is not purely an abstract mathematical framework, but is indeed a general theoretical scheme from which conventional Newtonian dynamics is obtained as a special limiting case. The major elements of our IGAC and the novel notion of information geometrodynamical entropy (IGE) are introduced by studying two "toy models". To illustrate the potential power of our IGAC, one application is presented. An information-geometric analogue of the Zurek-Paz quantum chaos criterion of linear entropy growth is suggested. Finally, concluding remarks emphasizing strengths and weak points of our approach are presented and possible further research directions are addressed. At this stage of its development, IGAC remains an ambitious unifying information-geometric theoretical construct for the study of chaotic dynamics with several unsolved problems. However, based on our recent findings, we believe it already provides an interesting, innovative and potentially powerful way to study and understand the very important and challenging problems of classical and quantum chaos.

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.

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

Rotavirus Vaccines: a story of success with challenges ahead

PubMed Central

O’Ryan, Miguel

2017-01-01

Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954

Mechanistic insights for the development of Li-O2 battery materials: addressing Li2O2 conductivity limitations and electrolyte and cathode instabilities.

PubMed

McCloskey, Bryan D; Burke, Colin M; Nichols, Jessica E; Renfrew, Sara E

2015-08-18

The Li-air battery has received significant attention over the past decade given its high theoretical specific energy compared to competing energy storage technologies. Yet, numerous scientific challenges remain unsolved in the pursuit of attaining a battery with modest Coulombic efficiency and high capacity. In this Feature Article, we provide our current perspective on challenges facing the development of nonaqueous Li-O2 battery cathodes. We initially present a review on our understanding of electrochemical processes occurring at the nonaqueous Li-O2 cathode. Electrolyte and cathode instabilities and Li2O2 conductivity limitations are then discussed, and suggestions for future materials research development to alleviate these issues are provided.

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

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

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 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.

Adverse health events associated with domestic violence during pregnancy among Brazilian women.

PubMed

Audi, Celene Aparecida Ferrari; Segall-Corrêa, Ana M; Santiago, Silvia M; Pérez-Escamilla, Rafael

2012-08-01

domestic violence during pregnancy remains an unsolved and neglected social problem despite the recognised adverse physical and mental health consequences. to examine the association between domestic violence (psychological violence and physical or sexual violence) and health problems self-reported by pregnant women. a cross-sectional analysis from a cohort study of 1,379 pregnant women attending prenatal care in public primary care units in Campinas, São Paulo, Brazil. Data were collected by interviewing women when they enroled for prenatal care. Domestic violence and alcohol abuse were ascertained by validated questionnaires. Referred morbidities, undesirable behaviours and sociodemographic characteristics were also recorded. Univariate analyses were used to estimate prevalence and unadjusted odd ratios. Multivariate logistic regression was used to identify the independent association between psychological violence and physical or sexual violence during pregnancy and women's health outcomes. psychological violence and physical or sexual violence were reported by 19.1% (n=263) and 6.5% (n=89) of the pregnant women, respectively. Psychological violence was significantly associated with obstetric problems [odds ratio (OR) 1.95; 95% confidence interval (CI) 1.39-2.73], premature rupture of membranes (OR 1.64, 95% CI 1.01-2.68), urinary tract infection (OR 1.71, 95% CI 1.19-2.42), headache (OR 1.75, 95% CI 1.25-2.40) and sexual risk behaviours (OR 2.28, 95% CI 1.18-4.41). Physical or sexual violence was significantly associated with: obstetric problems (OR 1.72, 95% CI 1.08-2.75), premature rupture of membranes (OR 2.11, 95% CI 1.14-3.88), urinary tract infection (OR 2.05, 95% CI 1.26-3.34), vaginal bleeding (OR 1.95, 95% CI 1.10-3.43) and lack of sexual desire (OR 3.67, 95% CI 2.23-6.09). domestic violence during pregnancy was associated with adverse clinical and psychological outcomes for women. These results suggest that a well-organised health-care system and trained health professionals, as well as multisectorial social support, are necessary to prevent or address the negative influence of domestic violence on women's health in Brazil. Copyright © 2011 Elsevier Ltd. All rights reserved.

Closed-Loop Control of Complex Networks: A Trade-Off between Time and Energy

NASA Astrophysics Data System (ADS)

Sun, Yong-Zheng; Leng, Si-Yang; Lai, Ying-Cheng; Grebogi, Celso; Lin, Wei

2017-11-01

Controlling complex nonlinear networks is largely an unsolved problem at the present. Existing works focus either on open-loop control strategies and their energy consumptions or on closed-loop control schemes with an infinite-time duration. We articulate a finite-time, closed-loop controller with an eye toward the physical and mathematical underpinnings of the trade-off between the control time and energy as well as their dependence on the network parameters and structure. The closed-loop controller is tested on a large number of real systems including stem cell differentiation, food webs, random ecosystems, and spiking neuronal networks. Our results represent a step forward in developing a rigorous and general framework to control nonlinear dynamical networks with a complex topology.

The evolution of tumour phylogenetics: principles and practice

PubMed Central

Schwartz, Russell; Schäffer, Alejandro A.

2018-01-01

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

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

NASA Astrophysics Data System (ADS)

Smarandache, Florentin

2010-10-01

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

Controlling the vocabulary for anatomy.

PubMed Central

Baud, R. H.; Lovis, C.; Rassinoux, A. M.; Ruch, P.; Geissbuhler, A.

2002-01-01

When confronted with the representation of human anatomy, natural language processing (NLP) system designers are facing an unsolved and frequent problem: the lack of a suitable global reference. The available sources in electronic format are numerous, but none fits adequately all the constraints and needs of language analysis. These sources are usually incomplete, difficult to use or tailored to specific needs. The anatomist's or ontologist's view does not necessarily match that of the linguist. The purpose of this paper is to review most recognized sources of knowledge in anatomy usable for linguistic analysis. Their potential and limits are emphasized according to this point of view. Focus is given on the role of the consensus work of the International Federation of Associations of Anatomists (IFAA) giving the Terminologia Anatomica. PMID:12463780

Using Gamification Combined with Indoor Location to Improve Nurses' Hand Hygiene Compliance in an ICU Ward.

PubMed

Lapão, Luís Velez; Marques, Rita; Gregório, João; Pinheiro, Fernando; Póvoa, Pedro; Mira da Silva, Miguel

2016-01-01

Healthcare acquired infections are among the biggest unsolved problems in healthcare, implying an increasing number of deaths, extra-days of hospital stay and hospital costs. Performing hand hygiene is a simple and inexpensive prevention measure, but healthcare workers compliance with it is still far from optimal. Recognized hurdles are lack of time, forgetfulness, wrong technique and lack of motivation. This study aims at exploring gamification to promote nurses' HH compliance self-awareness and action. Real-time data collected from an indoor location system will provide feedback information to a group of nurses working in an ICU ward. In this paper both the research's motivation and methods is presented, along with the first round of results and its discussion.

Remote ultrasound palpation for robotic interventions using absolute elastography.

PubMed

Schneider, Caitlin; Baghani, Ali; Rohling, Robert; Salcudean, Septimiu

2012-01-01

Although robotic surgery has addressed many of the challenges presented by minimally invasive surgery, haptic feedback and the lack of knowledge of tissue stiffness is an unsolved problem. This paper presents a system for finding the absolute elastic properties of tissue using a freehand ultrasound scanning technique, which utilizes the da Vinci Surgical robot and a custom 2D ultrasound transducer for intraoperative use. An external exciter creates shear waves in the tissue, and a local frequency estimation method computes the shear modulus. Results are reported for both phantom and in vivo models. This system can be extended to any 6 degree-of-freedom tracking method and any 2D transducer to provide real-time absolute elastic properties of tissue.

The evolution of tumour phylogenetics: principles and practice.

PubMed

Schwartz, Russell; Schäffer, Alejandro A

2017-04-01

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

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

NASA Technical Reports Server (NTRS)

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

1990-01-01

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

[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.

Cataclysmic variables and related objects

NASA Technical Reports Server (NTRS)

Hack, Margherita; Ladous, Constanze; Jordan, Stuart D. (Editor); Thomas, Richard N. (Editor); Goldberg, Leo; Pecker, Jean-Claude

1993-01-01

This volume begins with an introductory chapter on general properties of cataclysmic variables. Chapters 2 through 5 of Part 1 are devoted to observations and interpretation of dwarf novae and nova-like stars. Chapters 6 through 10, Part 2, discuss the general observational properties of classical and recurrent novae, the theoretical models, and the characteristics and models for some well observed classical novae and recurrent novae. Chapters 11 through 14 of Part 3 are devoted to an overview of the observations of symbiotic stars, to a description of the various models proposed for explaining the symbiotic phenomenon, and to a discussion of a few selected objects, respectively. Chapter 15 briefly examines the many unsolved problems posed by the observations of the different classes of cataclysmic variables and symbiotic stars.

Interventional radiology: a half century of innovation.

PubMed

Baum, Richard A; Baum, Stanley

2014-11-01

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

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.

Selected Schizosaccharomyces pombe Strains Have Characteristics That Are Beneficial for Winemaking

PubMed Central

Benito, Ángel; Jeffares, Daniel; Palomero, Felipe; Calderón, Fernando; Bai, Feng-Yan; Bähler, Jürg; Benito, Santiago

2016-01-01

At present, wine is generally produced using Saccharomyces yeast followed by Oenococus bacteria to complete malolactic fermentation. This method has some unsolved problems, such as the management of highly acidic musts and the production of potentially toxic products including biogenic amines and ethyl carbamate. Here we explore the potential of the fission yeast Schizosaccharomyces pombe to solve these problems. We characterise an extensive worldwide collection of S. pombe strains according to classic biochemical parameters of oenological interest. We identify three genetically different S. pombe strains that appear suitable for winemaking. These strains compare favourably to standard Saccharomyces cerevisiae winemaking strains, in that they perform effective malic acid deacidification and significantly reduce levels of biogenic amines and ethyl carbamate precursors without the need for any secondary bacterial malolactic fermentation. These findings indicate that the use of certain S. pombe strains could be advantageous for winemaking in regions where malic acid is problematic, and these strains also show superior performance with respect to food safety. PMID:27007548

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

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.

[Alternatives to chronic hospitalization in mental health].

PubMed

Gabay, Pablo M; Fernández Bruno, Mónica D

2009-01-01

It is not possible to work on alternatives to chronic institutionalization without taking into account a reform of the mental health care system. A great deal of experience has been accumulated and a lot of unsolved problems have arisen since the beginning of the deinstitutionalization in USA and Europe in the 60s. The aim was the closing of psychiatric hospitals, and so the accent was put on the physical place of treatment instead on the quality of the treatment or on the actual needs of the people involved. A review of the experiences is made and some clues are given to avoid the major problems and errors that have presented. Political decisions, experienced professionals, a stable and sufficient budget, modification of some laws, the creation of community institutions that fulfill the patient's needs before moving them, postgraduate training in rehabilitation, flexibility and creativity with empirical and scientific grounds are needed for a successful reform of the mental health care system.

Black-Hole Binaries, Gravitational Waves, and Numerical Relativity

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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.

Sn/MWCNT Nanocomposites Fabricated by Ultrasonic Dispersion of Ni-Coated MWCNTs in Molten Tin

NASA Astrophysics Data System (ADS)

Billah, Md Muktadir; Chen, Quanfang

2018-04-01

Carbon nanotubes (CNTs) are regarded as a desirable filler to develop advanced composites including advanced solders due to their exceptional mechanical properties. However, some issues remain unsolved for metallic composites owing to "wetting" and nonuniform dispersion of CNTs. In this study, electroless nickel coating onto CNTs was used to overcome these issues. Multiwalled carbon nanotubes (MWCNTs) were used for this study, and Ni-coated MWCNTs were dispersed in molten Sn assisted by sonication and compared with MWCNTs without Ni coating. Adding 3 wt.% Ni-coated MWCNTs, which corresponds to 0.6 wt.% pure CNTs, resulted in an increase in tensile strength by 95% and hardness by 123%. Nickel coating also prevented separation of the CNTs from the molten metal due to buoyancy effects, leading to more uniform dispersion.

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.

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.

A new method to improve network topological similarity search: applied to fold recognition

PubMed Central

Lhota, John; Hauptman, Ruth; Hart, Thomas; Ng, Clara; Xie, Lei

2015-01-01

Motivation: Similarity search is the foundation of bioinformatics. It plays a key role in establishing structural, functional and evolutionary relationships between biological sequences. Although the power of the similarity search has increased steadily in recent years, a high percentage of sequences remain uncharacterized in the protein universe. Thus, new similarity search strategies are needed to efficiently and reliably infer the structure and function of new sequences. The existing paradigm for studying protein sequence, structure, function and evolution has been established based on the assumption that the protein universe is discrete and hierarchical. Cumulative evidence suggests that the protein universe is continuous. As a result, conventional sequence homology search methods may be not able to detect novel structural, functional and evolutionary relationships between proteins from weak and noisy sequence signals. To overcome the limitations in existing similarity search methods, we propose a new algorithmic framework—Enrichment of Network Topological Similarity (ENTS)—to improve the performance of large scale similarity searches in bioinformatics. Results: We apply ENTS to a challenging unsolved problem: protein fold recognition. Our rigorous benchmark studies demonstrate that ENTS considerably outperforms state-of-the-art methods. As the concept of ENTS can be applied to any similarity metric, it may provide a general framework for similarity search on any set of biological entities, given their representation as a network. Availability and implementation: Source code freely available upon request Contact: lxie@iscb.org PMID:25717198

Assessment of the efficacy and safety of a combination of 2 topical retinoids (RetinSphere) in maintaining post-treatment response of acne to oral isotretinoin.

PubMed

Truchuelo, M T; Jiménez, N; Mavura, D; Jaén, P

2015-03-01

The high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. To determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Prospective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. Although the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. This new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

Korean delegation focuses on women.

PubMed

1997-01-01

Among the opportunities and challenges facing the ESCAP region in the 21st century is the full and equal participation of women in all sectors of society, stated one of the representatives of the Republic of Korea at the Senior Officials segment of the 53rd session of the Commission. As a follow-up to the Fourth World Conference on Women, held at Beijing in 1995, her country passed the Women's Development Act, which entered into force in July 1996, she explained. It "provides a strong legal basis for adequate institutional and financial support towards the achievement of gender equality," which is also one of the goals of the Program of Action of the International Conference on Population and Development held at Cairo in 1994. In tandem with domestic efforts, enhancing cooperation at the regional and international levels is essential, she added. In a separate intervention, another member of the Korean delegation elaborated on the comments of his colleague. He pointed out that, "for the past 30 years, the Republic of Korea as a nation has done its best to alleviate the pressure of absolute poverty and has improved the quality of life through continued economic growth." He admitted, though, that rapid economic growth has brought about its own side effects -- "unsolved problems still remain such as residual absolute poverty and increasing relative poverty." Poverty alleviation policies aimed at creating equal opportunities must address four aspects, he noted: 1) maintenance and enhancement of health, 2) promotion of educational opportunities, 3) vocational training, and 4) employment promotion. full text

Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans.

PubMed

Nie, Yu; Littleton, Brad; Kavanagh, Thomas; Abbate, Vincenzo; Bansal, Sukhvinder S; Richards, David; Hylands, Peter; Stürzenbaum, Stephen R

2017-11-01

The incidence of obesity is rising at an alarming rate. Despite its recognition as an urgent healthcare concern, obesity remains largely an unsolved medical problem. A comprehensive screen for functional dietary phytochemicals identified proanthocyanidins as putative targets to ameliorate obesity. A full-scale purification of oligomeric proanthocyanidins (OPCs) derived from grape seed extract yielded pure OPC dimer, trimer, tetramer, and their gallates (pOPCs). Forward chemical screening conducted in Caenorhabditis elegans suggested that pOPCs reduced the activity of lipase in vitro and triglyceride storage capacity in vivo Proanthocyanidin trimer gallate in particular modified lipid desaturation in C. elegans , revealed by hyperspectral coherent anti-Stokes Raman scattering microscopy. Exposure to trimer gallate resulted in the transcriptional down-regulation of nhr-49 (an ortholog of the human peroxisome proliferator-activated receptor-α), and a key regulator of fat metabolism, and 2 downstream genes: fat-5 and acs-2 A combination exposure of 2 or 3 pOPCs (dimer gallate, trimer and/or trimer gallate) suggested the absence of synergistic potential. By using the whole-organism C. elegans coupled with versatile biochemical, biophysical, and genetic tools, we provide an account of the composition and bioactivity of individual OPCs and more generally highlight the potential of traditional Chinese medicine-derived drug leads.-Nie, Y., Littleton, B., Kavanagh, T., Abbate, V., Bansal, S. S., Richards, D., Hylands, P., Sturzenbaum, S. R. Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation in Caenorhabditis elegans . © FASEB.

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

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Progress and promises of human cardiac magnetic resonance at ultrahigh fields: a physics perspective.

PubMed

Niendorf, Thoralf; Graessl, Andreas; Thalhammer, Christof; Dieringer, Matthias A; Kraus, Oliver; Santoro, Davide; Fuchs, Katharina; Hezel, Fabian; Waiczies, Sonia; Ittermann, Bernd; Winter, Lukas

2013-04-01

A growing number of reports eloquently speak about explorations into cardiac magnetic resonance (CMR) at ultrahigh magnetic fields (B0≥7.0 T). Realizing the progress, promises and challenges of ultrahigh field (UHF) CMR this perspective outlines current trends in enabling MR technology tailored for cardiac MR in the short wavelength regime. For this purpose many channel radiofrequency (RF) technology concepts are outlined. Basic principles of mapping and shimming of transmission fields including RF power deposition considerations are presented. Explorations motivated by the safe operation of UHF-CMR even in the presence of conductive implants are described together with the physics, numerical simulations and experiments, all of which detailing antenna effects and RF heating induced by intracoronary stents at 7.0 T. Early applications of CMR at 7.0 T and their clinical implications for explorations into cardiovascular diseases are explored including assessment of cardiac function, myocardial tissue characterization, MR angiography of large and small vessels as well as heteronuclear MR of the heart and the skin. A concluding section ventures a glance beyond the horizon and explores future directions. The goal here is not to be comprehensive but to inspire the biomedical and diagnostic imaging communities to throw further weight behind the solution of the many remaining unsolved problems and technical obstacles of UHF-CMR with the goal to transfer MR physics driven methodological advancements into extra clinical value. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

Maadooliat, Mehdi; Huang, Jianhua Z.

2013-01-01

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

Impact of Heterogeneity and Lattice Bond Strength on DNA Triangle Crystal Growth.

PubMed

Stahl, Evi; Praetorius, Florian; de Oliveira Mann, Carina C; Hopfner, Karl-Peter; Dietz, Hendrik

2016-09-07

One key goal of DNA nanotechnology is the bottom-up construction of macroscopic crystalline materials. Beyond applications in fields such as photonics or plasmonics, DNA-based crystal matrices could possibly facilitate the diffraction-based structural analysis of guest molecules. Seeman and co-workers reported in 2009 the first designed crystal matrices based on a 38 kDa DNA triangle that was composed of seven chains. The crystal lattice was stabilized, unprecedentedly, by Watson-Crick base pairing. However, 3D crystallization of larger designed DNA objects that include more chains such as DNA origami remains an unsolved problem. Larger objects would offer more degrees of freedom and design options with respect to tailoring lattice geometry and for positioning other objects within a crystal lattice. The greater rigidity of multilayer DNA origami could also positively influence the diffractive properties of crystals composed of such particles. Here, we rationally explore the role of heterogeneity and Watson-Crick interaction strengths in crystal growth using 40 variants of the original DNA triangle as model multichain objects. Crystal growth of the triangle was remarkably robust despite massive chemical, geometrical, and thermodynamical sample heterogeneity that we introduced, but the crystal growth sensitively depended on the sequences of base pairs next to the Watson-Crick sticky ends of the triangle. Our results point to weak lattice interactions and high concentrations as decisive factors for achieving productive crystallization, while sample heterogeneity and impurities played a minor role.

Immunomodulatory properties of Concholepas concholepas hemocyanin against francisellosis in a zebrafish model.

PubMed

Lagos, Leidy; Tandberg, Julia I; Becker, María Inés; Winther-Larsen, Hanne C

2017-08-01

The development of vaccines for aquaculture has been an important milestone in providing a continuous and sustainable production. Most of the vaccines currently on the market for aquaculture include oil as adjuvant. Nevertheless, several studies reported an occurrence of side effects after their use in farmed fish. As a result, there is a need for new and improved adjuvants that can stimulate the immune system while causing as few side-effects as possible. Hemocyanins are versatile macromolecules with strong immunogenic and immunomodulatory properties. Due to these characteristics, hemocyanin from Concholepas concholepas (CCH) has been biochemically characterized and evaluated as vaccine adjuvant in mice and humans. Francisellosis is a chronic granulomatous disease, which can result in high mortality depending on the host. The disease is caused by the facultative intracellular Gram-negative bacteria Francisella noatunensis, which remains an unsolved problem for the aquaculture, as no efficient vaccines are available. The aim of the present work was to investigate the immunoregulatory properties of CCH against francisellosis in an experimental zebrafish model. When immunized with CCH, zebrafish were protected from subsequent challenge with a lethal dose of Francisella noatunensis subsp. orientalis. Subsequently the mRNA expression levels of several immune-related genes were studied, including mhcii, il12a, tnfα and ifng1-1. Taken together, the data report the immunoregulatory properties of CCH and its potential use as a vaccine adjuvant for aquaculture. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

A machine learning method for fast and accurate characterization of depth-of-interaction gamma cameras

NASA Astrophysics Data System (ADS)

Pedemonte, Stefano; Pierce, Larry; Van Leemput, Koen

2017-11-01

Measuring the depth-of-interaction (DOI) of gamma photons enables increasing the resolution of emission imaging systems. Several design variants of DOI-sensitive detectors have been recently introduced to improve the performance of scanners for positron emission tomography (PET). However, the accurate characterization of the response of DOI detectors, necessary to accurately measure the DOI, remains an unsolved problem. Numerical simulations are, at the state of the art, imprecise, while measuring directly the characteristics of DOI detectors experimentally is hindered by the impossibility to impose the depth-of-interaction in an experimental set-up. In this article we introduce a machine learning approach for extracting accurate forward models of gamma imaging devices from simple pencil-beam measurements, using a nonlinear dimensionality reduction technique in combination with a finite mixture model. The method is purely data-driven, not requiring simulations, and is applicable to a wide range of detector types. The proposed method was evaluated both in a simulation study and with data acquired using a monolithic gamma camera designed for PET (the cMiCE detector), demonstrating the accurate recovery of the DOI characteristics. The combination of the proposed calibration technique with maximum- a posteriori estimation of the coordinates of interaction provided a depth resolution of  ≈1.14 mm for the simulated PET detector and  ≈1.74 mm for the cMiCE detector. The software and experimental data are made available at http://occiput.mgh.harvard.edu/depthembedding/.

Global QBO in circulation and ozone. Part 2: A simple mechanistic model

NASA Technical Reports Server (NTRS)

Tung, K. K.; Yang, H.

1994-01-01

Although the phenomenon of equatorial quasi-biennial oscillation is relatively well understood, the problem of how the equatorially confined quasi-biennial oscillation (QBO) wave forcing can induce a signal in the extratropics of comparable or larger magnitude remains unsolved. A simple mechanistic model is constructed to provide a quantitative test of the hypothesis that the phenomenon of extratropical QBO is mainly caused by an anomalous seasonal circulation induced by an anomalous Eliassen-Palm (E-P) flux divergence. The anomaly in E-P flux divergence may be caused in turn by the relative poleward and downward shift of the region of irreversible mixing (breaking) of the extratropical planetary waves during the easterly phase of the equatorial QBO as compared to its westerly phase. The hemispheric nature of the anomaly wave forcing in solstice seasons (viz., no wave breaking in the summer hemisphere) induces a global circulation anomaly that projects predominantly into the first few zonal Hough modes of Plumb. Such a global QBO circulation pattern, although difficult to measure directly, is reflected in the distribution of stratospheric tracers transported by it. Our model produces a global pattern of QBO anomaly in column ozone that appears to account for much of the unfiltered interannual variability in the column ozone observed by the total ozone mapping spectrometer (TOMS) instrument aboard the Nimbus satellite. Furthermore, the model produces the characteristic spectrum of the observation with peaks at periods of 20 and 30 months.

Global QBO in circulation and ozone. Part 2: A simple mechanistic model

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

Tung, K.K.; Yang, H.

1994-10-01

Although the phenomenon of equatorial quasi-biennial oscillation is relatively well understood, the problem of how the equatorially confined quasi-biennial oscillation (QBO) wave forcing can induce a signal in the extratropics of comparable or larger magnitude remains unsolved. A simple mechanistic model is constructed to provide a quantitative test of the hypothesis that the phenomenon of extratropical QBO is mainly caused by an anomalous seasonal circulation induced by an anomalous Eliassen-Palm (E-P) flux divergence. The anomaly in E-P flux divergence may be caused in turn by the relative poleward and downward shift of the region of irreversible mixing (breaking) of themore » extratropical planetary waves during the easterly phase of the equatorial QBO as compared to its westerly phase. The hemispheric nature of the anomaly wave forcing in solstice seasons (viz., no wave breaking in the summer hemisphere) induces a global circulation anomaly that projects predominantly into the first few zonal Hough modes of Plumb. Such a global QBO circulation pattern, although difficult to measure directly, is reflected in the distribution of stratospheric tracers transported by it. Our model produces a global pattern of QBO anomaly in column ozone that appears to account for much of the unfiltered interannual variability in the column ozone observed by the total ozone mapping spectrometer (TOMS) instrument aboard the Nimbus satellite. Furthermore, the model produces the characteristic spectrum of the observation with peaks at periods of 20 and 30 months.« less

SUNCT and SUNA: Recognition and Treatment.

PubMed

Pareja, Juan A; Alvarez, Mónica; Montojo, Teresa

2013-02-01

The problem of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) management remains unsolved. Despite a myriad of therapeutic trials, no convincingly effective remedy for SUNCT and SUNA is available at present. Based on open-label communications, some patients seemed to benefit from some pharmacologic, interventional, or invasive procedures. Possible effective preventive drugs are carbamazepine, lamotrigine, gabapentin, and topiramate. At present, the drug of choice for SUNCT seems to be lamotrigine whereas SUNA may better respond to gabapentin. There is no available abortive treatment for the individual attacks. During the worst periods, intravenous lidocaine may decrease the flow of SUNCT/SUNA attacks. In SUNCT, bilateral blockade of the greater occipital nerve, and superior cervical ganglion opioid blockade have been reported as temporary/partially effective in one patient each. Botulinum toxin injected around the symptomatic orbit provided sustained relief to one patient. Owing to the scarcity of reports the results of these interventions should be taken as preliminary. Invasive therapy with interventions directed to the first division of the trigeminal nerve or Gasserian ganglion, with local anesthetics or alcohol, radiofrequency thermocoagulation, microvascular decompression, and gamma-knife neurosurgery, have been tried in the treatment of refractory SUNCT. Some patients seemed to benefit from such interventions, but one should still have a critical attitude to these claims since no convincing results have been obtained as yet. The few SUNCT patients who underwent deep brain hypothalamic stimulation obtained a substantial and persistent relief.

Remotely Telling Humans and Computers Apart: An Unsolved Problem

NASA Astrophysics Data System (ADS)

Hernandez-Castro, Carlos Javier; Ribagorda, Arturo

The ability to tell humans and computers apart is imperative to protect many services from misuse and abuse. For this purpose, tests called CAPTCHAs or HIPs have been designed and put into production. Recent history shows that most (if not all) can be broken given enough time and commercial interest: CAPTCHA design seems to be a much more difficult problem than previously thought. The assumption that difficult-AI problems can be easily converted into valid CAPTCHAs is misleading. There are also some extrinsic problems that do not help, especially the big number of in-house designs that are put into production without any prior public critique. In this paper we present a state-of-the-art survey of current HIPs, including proposals that are now into production. We classify them regarding their basic design ideas. We discuss current attacks as well as future attack paths, and we also present common errors in design, and how many implementation flaws can transform a not necessarily bad idea into a weak CAPTCHA. We present examples of these flaws, using specific well-known CAPTCHAs. In a more theoretical way, we discuss the threat model: confronted risks and countermeasures. Finally, we introduce and discuss some desirable properties that new HIPs should have, concluding with some proposals for future work, including methodologies for design, implementation and security assessment.

Example-based learning: comparing the effects of additionally providing three different integrative learning activities on physiotherapy intervention knowledge.

PubMed

Dyer, Joseph-Omer; Hudon, Anne; Montpetit-Tourangeau, Katherine; Charlin, Bernard; Mamede, Sílvia; van Gog, Tamara

2015-03-07

Example-based learning using worked examples can foster clinical reasoning. Worked examples are instructional tools that learners can use to study the steps needed to solve a problem. Studying worked examples paired with completion examples promotes acquisition of problem-solving skills more than studying worked examples alone. Completion examples are worked examples in which some of the solution steps remain unsolved for learners to complete. Providing learners engaged in example-based learning with self-explanation prompts has been shown to foster increased meaningful learning compared to providing no self-explanation prompts. Concept mapping and concept map study are other instructional activities known to promote meaningful learning. This study compares the effects of self-explaining, completing a concept map and studying a concept map on conceptual knowledge and problem-solving skills among novice learners engaged in example-based learning. Ninety-one physiotherapy students were randomized into three conditions. They performed a pre-test and a post-test to evaluate their gains in conceptual knowledge and problem-solving skills (transfer performance) in intervention selection. They studied three pairs of worked/completion examples in a digital learning environment. Worked examples consisted of a written reasoning process for selecting an optimal physiotherapy intervention for a patient. The completion examples were partially worked out, with the last few problem-solving steps left blank for students to complete. The students then had to engage in additional self-explanation, concept map completion or model concept map study in order to synthesize and deepen their knowledge of the key concepts and problem-solving steps. Pre-test performance did not differ among conditions. Post-test conceptual knowledge was higher (P < .001) in the concept map study condition (68.8 ± 21.8%) compared to the concept map completion (52.8 ± 17.0%) and self-explanation (52.2 ± 21.7%) conditions. Post-test problem-solving performance was higher (P < .05) in the self-explanation (63.2 ± 16.0%) condition compared to the concept map study (53.3 ± 16.4%) and concept map completion (51.0 ± 13.6%) conditions. Students in the self-explanation condition also invested less mental effort in the post-test. Studying model concept maps led to greater conceptual knowledge, whereas self-explanation led to higher transfer performance. Self-explanation and concept map study can be combined with worked example and completion example strategies to foster intervention selection.

Oxidative Stress in Myopia

PubMed Central

Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

2015-01-01

Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem. PMID:25922643

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

NASA Astrophysics Data System (ADS)

Kochanski, K.; Klishin, A.

2015-12-01

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

Periodic activation function and a modified learning algorithm for the multivalued neuron.

PubMed

Aizenberg, Igor

2010-12-01

In this paper, we consider a new periodic activation function for the multivalued neuron (MVN). The MVN is a neuron with complex-valued weights and inputs/output, which are located on the unit circle. Although the MVN outperforms many other neurons and MVN-based neural networks have shown their high potential, the MVN still has a limited capability of learning highly nonlinear functions. A periodic activation function, which is introduced in this paper, makes it possible to learn nonlinearly separable problems and non-threshold multiple-valued functions using a single multivalued neuron. We call this neuron a multivalued neuron with a periodic activation function (MVN-P). The MVN-Ps functionality is much higher than that of the regular MVN. The MVN-P is more efficient in solving various classification problems. A learning algorithm based on the error-correction rule for the MVN-P is also presented. It is shown that a single MVN-P can easily learn and solve those benchmark classification problems that were considered unsolvable using a single neuron. It is also shown that a universal binary neuron, which can learn nonlinearly separable Boolean functions, and a regular MVN are particular cases of the MVN-P.

A Review on Dimension Reduction

PubMed Central

Ma, Yanyuan; Zhu, Liping

2013-01-01

Summary Summarizing the effect of many covariates through a few linear combinations is an effective way of reducing covariate dimension and is the backbone of (sufficient) dimension reduction. Because the replacement of high-dimensional covariates by low-dimensional linear combinations is performed with a minimum assumption on the specific regression form, it enjoys attractive advantages as well as encounters unique challenges in comparison with the variable selection approach. We review the current literature of dimension reduction with an emphasis on the two most popular models, where the dimension reduction affects the conditional distribution and the conditional mean, respectively. We discuss various estimation and inference procedures in different levels of detail, with the intention of focusing on their underneath idea instead of technicalities. We also discuss some unsolved problems in this area for potential future research. PMID:23794782

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.

Receiving instrumental support at work: when help is not welcome.

PubMed

Deelstra, Janna T; Peeters, Maria C W; Schaufeli, Wilmar B; Stroebe, Wolfgang; Zijlstra, Fred R H; van Doornen, Lorenz P

2003-04-01

Although the role of social support in promoting employees' health and well-being has been studied extensively, the evidence is inconsistent, sometimes even suggesting that social support might have negative effects. The authors examined some psychological processes that might explain such effects. On the basis of the threat-to-self-esteem model, the authors tested the hypothesis that receiving imposed support elicits negative reactions, which are moderated by someone's need for support. The authors distinguished 3 different reactions: (a) self-related, (b) interaction-related, and (c) physiological. The results of an experiment with 48 temporary administrative workers generally confirmed the hypothesis. Imposed support elicited negative reactions, except when there was an unsolvable problem, but even then the effect of imposed support was not positive but neutral.

Molecular pathogenesis of American Foulbrood: how Paenibacillus larvae kills honey bee larvae.

PubMed

Poppinga, Lena; Genersch, Elke

2015-08-01

American Foulbrood caused by Paenibacillus larvae is one of the unsolved health problems honey bee colonies are suffering from. In the recent past, considerable progress has been achieved in understanding molecular details of P. larvae infections of honey bee larvae. This was facilitated by the development of molecular tools for manipulating P. larvae and by the availability of complete genome sequences of different P. larvae genotypes. We here report on several peptides and proteins that have recently been identified, biochemically analyzed, and proposed to act as virulence factors of P. larvae. For some of them, experimental proof for their role as virulence factor has been provided allowing presenting a preliminary model for the molecular pathogenesis of American Foulbrood. Copyright © 2015 Elsevier Inc. All rights reserved.

Proceedings of the Workshop on Space Telerobotics, volume 1

NASA Technical Reports Server (NTRS)

Rodriguez, G. (Editor)

1987-01-01

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

New Developments in Magnetostatic Cleanliness Modeling

NASA Astrophysics Data System (ADS)

Mehlem, K.; Wiegand, A.; Weickert, S.

2012-05-01

The paper describes improvements and extensions of the multiple magnetic dipole modeling method (MDM) for cleanliness verification which had been introduced by the author1 in 1977 and then applied during 3 decades to numerous international projects. The solutions of specific modeling problems which had been left unsolved so far, are described in the present paper. Special attention is given to the ambiguities of MDM solutions caused by the limited data coverage available. Constraint handling by the constraint-free NLP solver, optimal MDM sizing and multiple-point far-field compensation techniques are presented. The recent extension of the MDM method to field gradient data is formulated and demonstrated by an example. Finally, a complex MDM application (Ulysses) is presented. Finally, a short description of the MDM software GAMAG, recently introduced by the author1, is given.

Prevention of decompression sickness during extravehicular activity in space: a review.

PubMed

Tokumaru, O

1997-12-01

Extended and more frequent extravehicular activity (EVA) is planned in NASA's future space programs. The more EVAs are conducted, the higher the incidence of decompression sickness (DCS) that is anticipated. Since Japan is also promoting the Space Station Freedom project with NASA, DCS during EVA will be an inevitable complication. The author reviewed the pathophysiology of DCS and detailed four possible ways of preventing decompression sickness during EVA in space: (1) higher pressure suit technology; (2) preoxygenation/prebreathing; (3) staged decompression; and (4) habitat or vehicle pressurization. Among these measures, development of zero-prebreathe higher pressure suit technology seems most ideal, but because of economic and technical reasons and in cases of emergency, other methods must also be improved. Unsolved problems like repeated decompression or oxygen toxicity were also listed.

Light Chemical Elements in Stars: Mysteries and Unsolved Problems

NASA Astrophysics Data System (ADS)

Lyubimkov, L. S.

2018-06-01

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

Quantum Heterogeneous Computing for Satellite Positioning Optimization

NASA Astrophysics Data System (ADS)

Bass, G.; Kumar, V.; Dulny, J., III

2016-12-01

Hard optimization problems occur in many fields of academic study and practical situations. We present results in which quantum heterogeneous computing is used to solve a real-world optimization problem: satellite positioning. Optimization problems like this can scale very rapidly with problem size, and become unsolvable with traditional brute-force methods. Typically, such problems have been approximately solved with heuristic approaches; however, these methods can take a long time to calculate and are not guaranteed to find optimal solutions. Quantum computing offers the possibility of producing significant speed-up and improved solution quality. There are now commercially available quantum annealing (QA) devices that are designed to solve difficult optimization problems. These devices have 1000+ quantum bits, but they have significant hardware size and connectivity limitations. We present a novel heterogeneous computing stack that combines QA and classical machine learning and allows the use of QA on problems larger than the quantum hardware could solve in isolation. We begin by analyzing the satellite positioning problem with a heuristic solver, the genetic algorithm. The classical computer's comparatively large available memory can explore the full problem space and converge to a solution relatively close to the true optimum. The QA device can then evolve directly to the optimal solution within this more limited space. Preliminary experiments, using the Quantum Monte Carlo (QMC) algorithm to simulate QA hardware, have produced promising results. Working with problem instances with known global minima, we find a solution within 8% in a matter of seconds, and within 5% in a few minutes. Future studies include replacing QMC with commercially available quantum hardware and exploring more problem sets and model parameters. Our results have important implications for how heterogeneous quantum computing can be used to solve difficult optimization problems in any field.

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.

Phase Transitions in Planning Problems: Design and Analysis of Parameterized Families of Hard Planning Problems

NASA Technical Reports Server (NTRS)

Hen, Itay; Rieffel, Eleanor G.; Do, Minh; Venturelli, Davide

2014-01-01

There are two common ways to evaluate algorithms: performance on benchmark problems derived from real applications and analysis of performance on parametrized families of problems. The two approaches complement each other, each having its advantages and disadvantages. The planning community has concentrated on the first approach, with few ways of generating parametrized families of hard problems known prior to this work. Our group's main interest is in comparing approaches to solving planning problems using a novel type of computational device - a quantum annealer - to existing state-of-the-art planning algorithms. Because only small-scale quantum annealers are available, we must compare on small problem sizes. Small problems are primarily useful for comparison only if they are instances of parametrized families of problems for which scaling analysis can be done. In this technical report, we discuss our approach to the generation of hard planning problems from classes of well-studied NP-complete problems that map naturally to planning problems or to aspects of planning problems that many practical planning problems share. These problem classes exhibit a phase transition between easy-to-solve and easy-to-show-unsolvable planning problems. The parametrized families of hard planning problems lie at the phase transition. The exponential scaling of hardness with problem size is apparent in these families even at very small problem sizes, thus enabling us to characterize even very small problems as hard. The families we developed will prove generally useful to the planning community in analyzing the performance of planning algorithms, providing a complementary approach to existing evaluation methods. We illustrate the hardness of these problems and their scaling with results on four state-of-the-art planners, observing significant differences between these planners on these problem families. Finally, we describe two general, and quite different, mappings of planning problems to QUBOs, the form of input required for a quantum annealing machine such as the D-Wave II.

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

Bulk solitary waves in elastic solids

NASA Astrophysics Data System (ADS)

Samsonov, A. M.; Dreiden, G. V.; Semenova, I. V.; Shvartz, A. G.

2015-10-01

A short and object oriented conspectus of bulk solitary wave theory, numerical simulations and real experiments in condensed matter is given. Upon a brief description of the soliton history and development we focus on bulk solitary waves of strain, also known as waves of density and, sometimes, as elastic and/or acoustic solitons. We consider the problem of nonlinear bulk wave generation and detection in basic structural elements, rods, plates and shells, that are exhaustively studied and widely used in physics and engineering. However, it is mostly valid for linear elasticity, whereas dynamic nonlinear theory of these elements is still far from being completed. In order to show how the nonlinear waves can be used in various applications, we studied the solitary elastic wave propagation along lengthy wave guides, and remarkably small attenuation of elastic solitons was proven in physical experiments. Both theory and generation for strain soliton in a shell, however, remained unsolved problems until recently, and we consider in more details the nonlinear bulk wave propagation in a shell. We studied an axially symmetric deformation of an infinite nonlinearly elastic cylindrical shell without torsion. The problem for bulk longitudinal waves is shown to be reducible to the one equation, if a relation between transversal displacement and the longitudinal strain is found. It is found that both the 1+1D and even the 1+2D problems for long travelling waves in nonlinear solids can be reduced to the Weierstrass equation for elliptic functions, which provide the solitary wave solutions as appropriate limits. We show that the accuracy in the boundary conditions on free lateral surfaces is of crucial importance for solution, derive the only equation for longitudinal nonlinear strain wave and show, that the equation has, amongst others, a bidirectional solitary wave solution, which lead us to successful physical experiments. We observed first the compression solitary wave in the duct-like polymer shell and proved, that there is no tensile area behind the wave, the bulk soliton propagates on a distance many times longer than its wave length, while both its shape and amplitude remain unchanged. We demonstrated recently how the strain solitons can be used for non-destructive testing (NDT) of laminated composites, used nowadays for various applications, e.g., in microelectronics, aerospace and automotive industries, and bulk strain solitons are among prospective instruments for NDT. Being aimed to propose the bulk strain solitons as an instrument for NDT in solids, we studied numerically the evolution of them in various wave guides with local defects, and shown that the strain soliton undergoes changes in amplitude, phase shift and the shape, that are distinctive and can be estimated. To sum up, now we are able to propose a new NDT technique, based on bulk strain soliton propagation in structural elements.

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.

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.

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.

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.

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.

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

Large Scale Groundwater Flow Model for Ho Chi Minh City and its Catchment Area, Southern Vietnam

NASA Astrophysics Data System (ADS)

Sigrist, M.; Tokunaga, T.; Takizawa, S.

2005-12-01

Ho Chi Minh City (HCMC) has become a fast growing city in recent decades and is still growing at a high pace. The water demand for more than 7 million people has increased tremendously, too. Beside surface water, groundwater is used in big amounts to satisfy the need of water. By now, more than 200,000 wells have been developed with very little control. To investigate the sustainability of the water abstraction, a model had been built for the HCMC area and its surrounding. On the catchment scale (around 24,000km2); however, many questions have remained unsolved. In this study, we first gathered and complied geological and hydrogeological information as well as data on groundwater quality to get an idea on regional groundwater flow pattern and problems related to the temporal change of the groundwater situation. Two problems have been depicted by this study. One is the construction of a water reservoir upstream of the Saigon River. This construction has probably changed the water table of the unconfined aquifer, and hence, has significantly changed the properties of soils in some areas. The other problem is the distribution of salty groundwater. Despite the distance of more than 40km from the seashore, groundwater from some wells in and around HCMC shows high concentrations of chloride. Several wells started to produce non-potable water. The chloride concentrations show a complicated and patchy distribution below HCMC, suggesting the possibility of the remnant saltwater at the time of sediment deposition. On the other hand, seawater invades along the streams far beyond HCMC during the dry season and this might be one of the possible sources of salty groundwater by vertical infiltration. A large-scale geological model was constructed and transformed into a hydrogeological model to better understand and quantify the groundwater flow system and the origin of saltwater. Based on the constructed model and numerical calculation, we discuss the influence of reservoir construction on the groundwater situation at the upstream Saigon River, and possible factors for the existence of salty groundwater underneath HCMC.

Observations on the junction between the Eastern sandstone and the Keweenaw series on Keweenaw Point, Lake Superior

USGS Publications Warehouse

Irving, Roland Duer; Chamberlin, Thomas C.

1885-01-01

Although the copper-bearing rocks of Lake Superior and the adjoining formations have attracted the attention of geologists for fifty years past, there are yet remaining unsolved very many problems with regard to them. We have ourselves, indeed, written at some length with regard to these rocks, and one of us has even attempted a general account of the series as a whole. In the course of our investigations each of us has been obliged to turn away from very many tempting problems in structure and genesis, where there was every promise of successful solutions if only the element of time had not been lacking. Not the least important among the problems which we have hitherto been thus obliged to pass by is that of the exact nature of the structural details at the contact line between the Keweenaw Series and the so-called Eastern Sandstone. This contact line one of us had already examined sufficiently to satisfy himself of the general relations of the two formations concerned, but he had not been able to go further than this. Recently, however, the opportunity has offered for us to make together some additional observations on this line of contact, with results that have proved to be of so conclusive a nature that we think it well to publish them in the form of a bulletin.In what follows the several places at which this junction has been studied by us are taken up in order from east to west. Preceding our own descriptions of each one of these points, we give the descriptions of others, so far as we are acquainted with them. Following these detailed descriptions, we then give an account and a discussion of the various views which have been held with regard to the relations of the two formations concerned, and then close with our own conclusions on this subject, as also in general upon the origin of the phenomena observed along the contact line.

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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-06-01

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

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).

Exact zeros of entanglement for arbitrary rank-two mixtures derived from a geometric view of the zero polytope

NASA Astrophysics Data System (ADS)

Osterloh, Andreas

2016-12-01

Here I present a method for how intersections of a certain density matrix of rank 2 with the zero polytope can be calculated exactly. This is a purely geometrical procedure which thereby is applicable to obtaining the zeros of SL- and SU-invariant entanglement measures of arbitrary polynomial degree. I explain this method in detail for a recently unsolved problem. In particular, I show how a three-dimensional view, namely, in terms of the Bloch-sphere analogy, solves this problem immediately. To this end, I determine the zero polytope of the three-tangle, which is an exact result up to computer accuracy, and calculate upper bounds to its convex roof which are below the linearized upper bound. The zeros of the three-tangle (in this case) induced by the zero polytope (zero simplex) are exact values. I apply this procedure to a superposition of the four-qubit Greenberger-Horne-Zeilinger and W state. It can, however, be applied to every case one has under consideration, including an arbitrary polynomial convex-roof measure of entanglement and for arbitrary local dimension.

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

PubMed

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

2004-01-29

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

Towards a solution of the puzzle posed by superconducting SrTiO3

NASA Astrophysics Data System (ADS)

Malik, G. P.

2015-09-01

Suitably doped SrTiO3 was found in 1964 to undergo a superconducting transition below 1 K with a dome-like Tc versus n (electron concentration) plot. The apex of the dome — a point of inflection — corresponds to the point (n≈9 ×1019cm-3, Tc≈0.30 K). On either side of it, Tc goes down to ≈0.1 K for the extreme values between which n was varied. A single value of Tc is thus observed for two different values of n. The puzzle for the theory has been to explain this result. Treating the problem in all its generality, we present here three equations: the μ1-incorporated BCS equation for Tc, the μ0-incorporated equation for the T = 0 gap Δ0, where μ1 and μ0 are the chemical potentials at T = Tc and T = 0 respectively, and an equation that relates the interaction parameters λ1 and λ0 at these temperatures. Because there are five unknowns in the problem, we tackle these equations via an approximation scheme that includes setting μ1 = μ0 and λ1 = λ0. The latter of these is factually a basic tenet of the BCS theory. Salient features of our findings are: (i) the solutions for Tc and Δ0 on the RHS (LHS) of the dome correspond to μ> kBθD(μ < kBθD); kB = Boltzmann constant, θD = Debye temperature, (ii) for solutions on the LHS the limits of the integrals in the equations need to be curtailed to obtain real solutions and (iii) the point μ = kBθD is a point of inflection in the Tc versus μ plot. Since the puzzle has remained unsolved for a long time, we also offer here a purely mathematical model for λ(μ) — sans physical justification — which leads to a Tc versus μ plot qualitatively in agreement with experiment.

Silicon and Germanium (111) Surface Reconstruction

NASA Astrophysics Data System (ADS)

Hao, You Gong

Silicon (111) surface (7 x 7) reconstruction has been a long standing puzzle. For the last twenty years, various models were put forward to explain this reconstruction, but so far the problem still remains unsolved. Recent ion scattering and channeling (ISC), scanning tunneling microscopy (STM) and transmission electron diffraction (TED) experiments reveal some new results about the surface which greatly help investigators to establish better models. This work proposes a silicon (111) surface reconstruction mechanism, the raising and lowering mechanism which leads to benzene -like ring and flower (raised atom) building units. Based on these building units a (7 x 7) model is proposed, which is capable of explaining the STM and ISC experiment and several others. Furthermore the building units of the model can be used naturally to account for the germanium (111) surface c(2 x 8) reconstruction and other observed structures including (2 x 2), (5 x 5) and (7 x 7) for germanium as well as the (/3 x /3)R30 and (/19 x /19)R23.5 impurity induced structures for silicon, and the higher temperature disordered (1 x 1) structure for silicon. The model is closely related to the silicon (111) surface (2 x 1) reconstruction pi-bonded chain model, which is the most successful model for the reconstruction now. This provides an explanation for the rather low conversion temperature (560K) of the (2 x 1) to the (7 x 7). The model seems to meet some problems in the explanation of the TED result, which is explained very well by the dimer, adatom and stacking fault (DAS) model proposed by Takayanagi. In order to explain the TED result, a variation of the atomic scattering factor is proposed. Comparing the benzene-like ring model with the DAS model, the former needs more work to explain the TED result and the later has to find a way to explain the silicon (111) surface (1 x 1) disorder experiment.

Rationally designed, heterologous S. cerevisiae transcripts expose novel expression determinants

PubMed Central

Ben-Yehezkel, Tuval; Atar, Shimshi; Zur, Hadas; Diament, Alon; Goz, Eli; Marx, Tzipy; Cohen, Rafael; Dana, Alexandra; Feldman, Anna; Shapiro, Ehud; Tuller, Tamir

2015-01-01

Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5′ transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5′UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5′end can modulate protein levels up to 160%–300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r = 0.62 (p=0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple rules for engineering synthetic gene expression in eukaryotes. PMID:26176266

Rationally designed, heterologous S. cerevisiae transcripts expose novel expression determinants.

PubMed

Ben-Yehezkel, Tuval; Atar, Shimshi; Zur, Hadas; Diament, Alon; Goz, Eli; Marx, Tzipy; Cohen, Rafael; Dana, Alexandra; Feldman, Anna; Shapiro, Ehud; Tuller, Tamir

2015-01-01

Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5' transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5'UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5'end can modulate protein levels up to 160%-300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r = 0.62 (p=0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple rules for engineering synthetic gene expression in eukaryotes.

Current status and problems of lung transplantation in Japan

PubMed Central

2016-01-01

Lung transplantation has been performed worldwide and recognized as an effective treatment for patients with various end-stage lung diseases. Shortage of lung donors is one of the main obstacles in most of the countries, especially in Japan. Every effort has been made to promote organ donation during the past 20 years. In 2010, Japanese transplant low was revised so that the family of the brain dead donors can make a decision for organ donation. Since then, the number of cadaveric lung donor has increased by 5-fold. However, the average waiting time is still more than 800 days resulting in considerable number of deaths on the waiting list. Lung transplantation in the use of donation after cardiac death (DCD) has now been increasingly performed in Europe, Australia and North America with promising results. However, controlled death is not permitted in Japan making it difficult to accept this strategy. Use of marginal donors is one of the strategies for organ shortage. In Japan, the rate of lung usage is now well over 60% because of careful donor management by medical consultants and aggressive use of marginal donors. Living-donor lobar lung transplantation (LDLLT) has been developed to offset the mismatch between supply and demand for those patients awaiting cadaveric lung transplantation (CLT) and it is often the most realistic option for very ill patients. Between 1998 and 2015, lung transplantation has been performed in 464 patients (55 children, 419 adults) at 9 lung transplant centers in Japan. CLT was performed in 283 patients (61%) and LDLLT was performed in 181 patients (39%). The 5-year survival was 72.3% and 71.6%, respectively. Of note, only seven children received CLT. In conclusion, lung transplantation in Japan has grown significantly with excellent results but the shortage of cadaveric lung donor remains to be an important unsolved problem. LDLLT is often the only realistic option for very ill patients especially for children. PMID:27651939

Density functional theory for open-shell singlet biradicals

NASA Astrophysics Data System (ADS)

Gräfenstein, Jürgen; Kraka, Elfi; Cremer, Dieter

1998-05-01

The description of open-shell singlet (OSS) σ- π biradicals by density functional theory (DFT) requires at least a two-configurational (TC) or, in general, a MC-DFT approach, which bears many unsolved problems. These can be avoided by reformulating the TC description in the spirit of restricted open shell theory for singlets (ROSS) and developing an exchange-correlation functional for ROSS-DFT. ROSS-DFT turns out to lead to reliable descriptions of geometry and vibrational frequencies for OSS biradicals. The relative energies of the OSS states obtained at the ROSS-B3LYP/6-311G(d,p) level are often better than the corresponding ROSS-MP2 results. However, in those cases where spin polarization in a conjugated π systems plays a role, DFT predicts the triplet state related to the OSS state 2-4 kcal/mol too stable.

U-shaped development: an old but unsolved problem.

PubMed

Pauls, Franz; Macha, Thorsten; Petermann, Franz

2013-01-01

Even today the investigation of U-shaped functions in human development is of considerable importance for different domains of Developmental Psychology. More and more scientific researchers focus their efforts on the challenge to describe and explain the phenomenon by identifying those skills and abilities being affected. The impact of U-shaped functions on diagnostic decision-making and on therapeutic treatment programs highlights the importance of understanding the nature of non-monotonic development. The present article therefore addresses the relevant questions of how U-shaped functions are defined in theory, in which developmental domains such non-monotonic growth curves are suggested to occur, and which implications there are for future methodology and diagnostic practice. Finally, it is recommended to clearly identify those interactions between proximal and distal subcomponents which are expected to contribute to a U-shaped development.

U-Shaped Development: An Old but Unsolved Problem

PubMed Central

Pauls, Franz; Macha, Thorsten; Petermann, Franz

2013-01-01

Even today the investigation of U-shaped functions in human development is of considerable importance for different domains of Developmental Psychology. More and more scientific researchers focus their efforts on the challenge to describe and explain the phenomenon by identifying those skills and abilities being affected. The impact of U-shaped functions on diagnostic decision-making and on therapeutic treatment programs highlights the importance of understanding the nature of non-monotonic development. The present article therefore addresses the relevant questions of how U-shaped functions are defined in theory, in which developmental domains such non-monotonic growth curves are suggested to occur, and which implications there are for future methodology and diagnostic practice. Finally, it is recommended to clearly identify those interactions between proximal and distal subcomponents which are expected to contribute to a U-shaped development. PMID:23750146

The dawn of the RNA World: Toward functional complexity through ligation of random RNA oligomers

PubMed Central

Briones, Carlos; Stich, Michael; Manrubia, Susanna C.

2009-01-01

A main unsolved problem in the RNA World scenario for the origin of life is how a template-dependent RNA polymerase ribozyme emerged from short RNA oligomers obtained by random polymerization on mineral surfaces. A number of computational studies have shown that the structural repertoire yielded by that process is dominated by topologically simple structures, notably hairpin-like ones. A fraction of these could display RNA ligase activity and catalyze the assembly of larger, eventually functional RNA molecules retaining their previous modular structure: molecular complexity increases but template replication is absent. This allows us to build up a stepwise model of ligation-based, modular evolution that could pave the way to the emergence of a ribozyme with RNA replicase activity, step at which information-driven Darwinian evolution would be triggered. PMID:19318464

Finite-time blow-up for quasilinear degenerate Keller-Segel systems of parabolic-parabolic type

NASA Astrophysics Data System (ADS)

Hashira, Takahiro; Ishida, Sachiko; Yokota, Tomomi

2018-05-01

This paper deals with the quasilinear degenerate Keller-Segel systems of parabolic-parabolic type in a ball of RN (N ≥ 2). In the case of non-degenerate diffusion, Cieślak-Stinner [3,4] proved that if q > m + 2/N, where m denotes the intensity of diffusion and q denotes the nonlinearity, then there exist initial data such that the corresponding solution blows up in finite time. As to the case of degenerate diffusion, it is known that a solution blows up if q > m + 2/N (see Ishida-Yokota [13]); however, whether the blow-up time is finite or infinite has been unknown. This paper gives an answer to the unsolved problem. Indeed, the finite-time blow-up of energy solutions is established when q > m + 2/N.

Macroscopic irreversibility and microscopic paradox: A Constructal law analysis of atoms as open systems

PubMed Central

Lucia, Umberto

2016-01-01

The relation between macroscopic irreversibility and microscopic reversibility is a present unsolved problem. Constructal law is introduced to develop analytically the Einstein’s, Schrödinger’s, and Gibbs’ considerations on the interaction between particles and thermal radiation (photons). The result leads to consider the atoms and molecules as open systems in continuous interaction with flows of photons from their surroundings. The consequent result is that, in any atomic transition, the energy related to the microscopic irreversibility is negligible, while when a great number of atoms (of the order of Avogadro’s number) is considered, this energy related to irreversibility becomes so large that its order of magnitude must be taken into account. Consequently, macroscopic irreversibility results related to microscopic irreversibility by flows of photons and amount of atoms involved in the processes. PMID:27762333

Understanding the Accretion Engine in Pre-main Sequence Stars

NASA Astrophysics Data System (ADS)

Gómez de Castro, Ana I.

2009-05-01

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

Vortex cutting in superconductors

DOE PAGES

Glatz, A.; Vlasko-Vlasov, V. K.; Kwok, W. K.; ...

2016-08-09

Vortex cutting and reconnection is an intriguing and still-unsolved problem central to many areas of classical and quantum physics, including hydrodynamics, astrophysics, and superconductivity. Here, in this paper, we describe a comprehensive investigation of the crossing of magnetic vortices in superconductors using time dependent Ginsburg-Landau modeling. Within a macroscopic volume, we simulate initial magnetization of an anisotropic high temperature superconductor followed by subsequent remagnetization with perpendicular magnetic fields, creating the crossing of the initial and newly generated vortices. The time resolved evolution of vortex lines as they approach each other, contort, locally conjoin, and detach, elucidates the fine details ofmore » the vortex-crossing scenario under practical situations with many interacting vortices in the presence of weak pinning. Finally, our simulations also reveal left-handed helical vortex instabilities that accompany the remagnetization process and participate in the vortex crossing events.« less

Theory of the Origin, Evolution, and Nature of Life

PubMed Central

Andrulis, Erik D.

2011-01-01

Life is an inordinately complex unsolved puzzle. Despite significant theoretical progress, experimental anomalies, paradoxes, and enigmas have revealed paradigmatic limitations. Thus, the advancement of scientific understanding requires new models that resolve fundamental problems. Here, I present a theoretical framework that economically fits evidence accumulated from examinations of life. This theory is based upon a straightforward and non-mathematical core model and proposes unique yet empirically consistent explanations for major phenomena including, but not limited to, quantum gravity, phase transitions of water, why living systems are predominantly CHNOPS (carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur), homochirality of sugars and amino acids, homeoviscous adaptation, triplet code, and DNA mutations. The theoretical framework unifies the macrocosmic and microcosmic realms, validates predicted laws of nature, and solves the puzzle of the origin and evolution of cellular life in the universe. PMID:25382118

Vortex cutting in superconductors

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

Glatz, A.; Vlasko-Vlasov, V. K.; Kwok, W. K.

Vortex cutting and reconnection is an intriguing and still-unsolved problem central to many areas of classical and quantum physics, including hydrodynamics, astrophysics, and superconductivity. Here, in this paper, we describe a comprehensive investigation of the crossing of magnetic vortices in superconductors using time dependent Ginsburg-Landau modeling. Within a macroscopic volume, we simulate initial magnetization of an anisotropic high temperature superconductor followed by subsequent remagnetization with perpendicular magnetic fields, creating the crossing of the initial and newly generated vortices. The time resolved evolution of vortex lines as they approach each other, contort, locally conjoin, and detach, elucidates the fine details ofmore » the vortex-crossing scenario under practical situations with many interacting vortices in the presence of weak pinning. Finally, our simulations also reveal left-handed helical vortex instabilities that accompany the remagnetization process and participate in the vortex crossing events.« less

Constraining the evolution of the Hubble Parameter using cosmic chronometers

NASA Astrophysics Data System (ADS)

Dickinson, Hugh

2017-08-01

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

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

PubMed Central

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

2010-01-01

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

The Evolution of the Intergalactic Medium

NASA Astrophysics Data System (ADS)

McQuinn, Matthew

2016-09-01

The bulk of cosmic matter resides in a dilute reservoir that fills the space between galaxies, the intergalactic medium (IGM). The history of this reservoir is intimately tied to the cosmic histories of structure formation, star formation, and supermassive black hole accretion. Our models for the IGM at intermediate redshifts (2≲z≲5) are a tremendous success, quantitatively explaining the statistics of Lyα absorption of intergalactic hydrogen. However, at both lower and higher redshifts (and around galaxies) much is still unknown about the IGM. We review the theoretical models and measurements that form the basis for the modern understanding of the IGM, and we discuss unsolved puzzles (ranging from the largely unconstrained process of reionization at high z to the missing baryon problem at low z), highlighting the efforts that have the potential to solve them.

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.

[Artificial sight: recent developments].

PubMed

Zeitz, O; Keserü, M; Hornig, R; Richard, G

2009-03-01

The implantation of electronic retina stimulators appears to be a future possibility to restore vision, at least partially in patients with retinal degeneration. The idea of such visual prostheses is not new but due to the general technical progress it has become more likely that a functioning implant will be on the market soon. Visual prosthesis may be integrated in the visual system in various places. Thus there are subretinal and epiretinal implants, as well as implants that are connected directly to the optic nerve or the visual cortex. The epiretinal approach is the most promising at the moment, but the problem of appropriate modulation of the image information is unsolved so far. This will be necessary to provide a interpretable visual information to the brain. The present article summarises the concepts and includes some latest information from recent conferences.

Parameterization of the Extinction Coefficient in Ice and Mixed-Phase Arctic Clouds during the ISDAC Field Campaign

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

Korolev, A; Shashkov, A; Barker, H

This report documents the history of attempts to directly measure cloud extinction, the current measurement device known as the Cloud Extinction Probe (CEP), specific problems with direct measurement of extinction coefficient, and the attempts made here to address these problems. Extinction coefficient is one of the fundamental microphysical parameters characterizing bulk properties of clouds. Knowledge of extinction coefficient is of crucial importance for radiative transfer calculations in weather prediction and climate models given that Earth's radiation budget (ERB) is modulated much by clouds. In order for a large-scale model to properly account for ERB and perturbations to it, it mustmore » ultimately be able to simulate cloud extinction coefficient well. In turn this requires adequate and simultaneous simulation of profiles of cloud water content and particle habit and size. Similarly, remote inference of cloud properties requires assumptions to be made about cloud phase and associated single-scattering properties, of which extinction coefficient is crucial. Hence, extinction coefficient plays an important role in both application and validation of methods for remote inference of cloud properties from data obtained from both satellite and surface sensors (e.g., Barker et al. 2008). While estimation of extinction coefficient within large-scale models is relatively straightforward for pure water droplets, thanks to Mie theory, mixed-phase and ice clouds still present problems. This is because of the myriad forms and sizes that crystals can achieve, each having their own unique extinction properties. For the foreseeable future, large-scale models will have to be content with diagnostic parametrization of crystal size and type. However, before they are able to provide satisfactory values needed for calculation of radiative transfer, they require the intermediate step of assigning single-scattering properties to particles. The most basic of these is extinction coefficient, yet it is rarely measured directly, and therefore verification of parametrizations is difficult. The obvious solution is to be able to measure microphysical properties and extinction at the same time and for the same volume. This is best done by in situ sampling by instruments mounted on either balloon or aircraft. The latter is the usual route and the one employed here. Yet the problem of actually measuring extinction coefficient directly for arbitrarily complicated particles still remains unsolved.« less

Challenge of biomechanics.

PubMed

Volokh, K Y

2013-06-01

The application of mechanics to biology--biomechanics--bears great challenges due to the intricacy of living things. Their dynamism, along with the complexity of their mechanical response (which in itself involves complex chemical, electrical, and thermal phenomena) makes it very difficult to correlate empirical data with theoretical models. This difficulty elevates the importance of useful biomechanical theories compared to other fields of engineering. Despite inherent imperfections of all theories, a well formulated theory is crucial in any field of science because it is the basis for interpreting observations. This is all-the-more vital, for instance, when diagnosing symptoms, or planning treatment to a disease. The notion of interpreting empirical data without theory is unscientific and unsound. This paper attempts to fortify the importance of biomechanics and invigorate research efforts for those engineers and mechanicians who are not yet involved in the field. It is not aimed here, however, to give an overview of biomechanics. Instead, three unsolved problems are formulated to challenge the readers. At the micro-scale, the problem of the structural organization and integrity of the living cell is presented. At the meso-scale, the enigma of fingerprint formation is discussed. At the macro-scale, the problem of predicting aneurysm ruptures is reviewed. It is aimed here to attract the attention of engineers and mechanicians to problems in biomechanics which, in the author's opinion, will dominate the development of engineering and mechanics in forthcoming years.

The GALAH survey: chemical tagging of star clusters and new members in the Pleiades

NASA Astrophysics Data System (ADS)

Kos, Janez; Bland-Hawthorn, Joss; Freeman, Ken; Buder, Sven; Traven, Gregor; De Silva, Gayandhi M.; Sharma, Sanjib; Asplund, Martin; Duong, Ly; Lin, Jane; Lind, Karin; Martell, Sarah; Simpson, Jeffrey D.; Stello, Dennis; Zucker, Daniel B.; Zwitter, Tomaž; Anguiano, Borja; Da Costa, Gary; D'Orazi, Valentina; Horner, Jonathan; Kafle, Prajwal R.; Lewis, Geraint; Munari, Ulisse; Nataf, David M.; Ness, Melissa; Reid, Warren; Schlesinger, Katie; Ting, Yuan-Sen; Wyse, Rosemary

2018-02-01

The technique of chemical tagging uses the elemental abundances of stellar atmospheres to 'reconstruct' chemically homogeneous star clusters that have long since dispersed. The GALAH spectroscopic survey - which aims to observe one million stars using the Anglo-Australian Telescope - allows us to measure up to 30 elements or dimensions in the stellar chemical abundance space, many of which are not independent. How to find clustering reliably in a noisy high-dimensional space is a difficult problem that remains largely unsolved. Here, we explore t-distributed stochastic neighbour embedding (t-SNE) - which identifies an optimal mapping of a high-dimensional space into fewer dimensions - whilst conserving the original clustering information. Typically, the projection is made to a 2D space to aid recognition of clusters by eye. We show that this method is a reliable tool for chemical tagging because it can: (i) resolve clustering in chemical space alone, (ii) recover known open and globular clusters with high efficiency and low contamination, and (iii) relate field stars to known clusters. t-SNE also provides a useful visualization of a high-dimensional space. We demonstrate the method on a data set of 13 abundances measured in the spectra of 187 000 stars by the GALAH survey. We recover seven of the nine observed clusters (six globular and three open clusters) in chemical space with minimal contamination from field stars and low numbers of outliers. With chemical tagging, we also identify two Pleiades supercluster members (which we confirm kinematically), one as far as 6° - one tidal radius away from the cluster centre.

Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation.

PubMed

Ferencz, Andrea; Racz, Boglarka; Tamas, Andrea; Reglodi, Dora; Lubics, Andrea; Nemeth, Jozsef; Nedvig, Klara; Kalmar-Nagy, Karoly; Horvath, Ors Peter; Weber, Gyorgy; Roth, Erzsebet

2009-02-01

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.

Development of Modal Analysis for the Study of Global Modes in High Speed Boundary Layer Flows

NASA Astrophysics Data System (ADS)

Brock, Joseph Michael

Boundary layer transition for compressible flows remains a challenging and unsolved problem. In the context of high-speed compressible flow, transitional and turbulent boundary-layers produce significantly higher surface heating caused by an increase in skin-friction. The higher heating associated with transitional and turbulent boundary layers drives thermal protection systems (TPS) and mission trajectory bounds. Proper understanding of the mechanisms that drive transition is crucial to the successful design and operation of the next generation spacecraft. Currently, prediction of boundary-layer transition is based on experimental efforts and computational stability analysis. Computational analysis, anchored by experimental correlations, offers an avenue to assess/predict stability at a reduced cost. Classical methods of Linearized Stability Theory (LST) and Parabolized Stability Equations (PSE) have proven to be very useful for simple geometries/base flows. Under certain conditions the assumptions that are inherent to classical methods become invalid and the use of LST/PSE is inaccurate. In these situations, a global approach must be considered. A TriGlobal stability analysis code, Global Mode Analysis in US3D (GMAUS3D), has been developed and implemented into the unstructured solver US3D. A discussion of the methodology and implementation will be presented. Two flow configurations are presented in an effort to validate/verify the approach. First, stability analysis for a subsonic cylinder wake is performed and results compared to literature. Second, a supersonic blunt cone is considered to directly compare LST/PSE analysis and results generated by GMAUS3D.

Flare Observations

NASA Astrophysics Data System (ADS)

Benz, Arnold O.

2017-12-01

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

Neutron lifetime measurements with a large gravitational trap for ultracold neutrons

NASA Astrophysics Data System (ADS)

Serebrov, A. P.; Kolomensky, E. A.; Fomin, A. K.; Krasnoshchekova, I. A.; Vassiljev, A. V.; Prudnikov, D. M.; Shoka, I. V.; Chechkin, A. V.; Chaikovskiy, M. E.; Varlamov, V. E.; Ivanov, S. N.; Pirozhkov, A. N.; Geltenbort, P.; Zimmer, O.; Jenke, T.; Van der Grinten, M.; Tucker, M.

2018-05-01

Neutron lifetime is one of the most important physical constants: it determines parameters of the weak interaction and predictions of primordial nucleosynthesis theory. There remains the unsolved problem of a 3.9σ discrepancy between measurements of this lifetime using neutrons in beams and those with stored ultracold neutrons (UCN). In our experiment we measure the lifetime of neutrons trapped by Earth's gravity in an open-topped vessel. Two configurations of the trap geometry are used to change the mean frequency of UCN collisions with the surfaces; this is achieved by plunging an additional surface into the trap without breaking the vacuum. The trap walls are coated with a hydrogen-less fluorine-containing polymer to reduce losses of UCN. The stability of this coating over multiple thermal cycles between 80 and 300 K was tested. At 80 K, the probability of UCN loss due to collisions with the trap walls is just 1.5% of the probability of β decay. The free neutron lifetime is determined by extrapolation to an infinitely large trap with zero collision frequency. The result of these measurements is τn=881.5 ±0 .7stat ±0 .6syst s which is consistent with the conventional value of 880.2 ± 1.0 s presented by the Particle Data Group. Future prospects for this experiment are in further cooling to 10 K, which will lead to an improved accuracy of measurement. In conclusion we present an analysis of currently available data on various measurements of the neutron lifetime.

Turning gadflies into allies.

PubMed

Yaziji, Michael

2004-02-01

Multinational companies are the driving force behind globalization, but they are also the source of many of its most painful consequences, including currency crises, cross-border pollution, and overfishing. These problems remain unsolved because they are beyond the scope of individual governments; transnational organizations have also proved unequal to the task. Nonprofit, nongovernmental organizations have leaped into the breach. To force policy changes, they have seized on all forms of modern persuasion to influence public sentiment toward global traders, manufacturers, and investors. By partnering with NGOs instead of opposing them, companies can avoid costly conflict and can use NGOs' assets to gain competitive advantage. So far, however, most companies have proved ill equipped to deal with NGOs. Large companies know how to compete on the basis of product attributes and price. But NGO attacks focus on production methods and their spillover effects, which are often noneconomic. Similarly, NGOs are able to convert companies' standard competitive strengths--such as size and wide market awareness of their brands--into liabilities. That's because the wealthier and better known a company is, the juicier the target it makes. Emboldened by their successes, NGOs continue to take on new causes. By partnering with NGOs instead of reflexively opposing them, companies could draw on NGOs' key strengths--legitimacy, awareness of social forces, distinct networks, and specialized technical expertise--which most companies could use more of. And with NGOs as allies and guides, companies should also be able to accelerate innovation, foresee shifts in demand, shape legislation affecting them, and, in effect, set technical and regulatory standards for their industries.

Distinct regions of the Pseudomonas syringae coiled-coil effector AvrRps4 are required for activation of immunity

PubMed Central

Sohn, Kee Hoon; Hughes, Richard K.; Piquerez, Sophie J.; Jones, Jonathan D. G.; Banfield, Mark J.

2012-01-01

Gram-negative phytopathogenic bacteria translocate effector proteins into plant cells to subvert host defenses. These effectors can be recognized by plant nucleotide-binding–leucine-rich repeat immune receptors, triggering defense responses that restrict pathogen growth. AvrRps4, an effector protein from Pseudomonas syringae pv. pisi, triggers RPS4-dependent immunity in resistant accessions of Arabidopsis. To better understand the molecular basis of AvrRps4-triggered immunity, we determined the crystal structure of processed AvrRps4 (AvrRps4C, residues 134–221), revealing that it forms an antiparallel α-helical coiled coil. Structure-informed mutagenesis reveals an electronegative surface patch in AvrRps4C required for recognition by RPS4; mutations in this region can also uncouple triggering of the hypersensitive response from disease resistance. This uncoupling may result from a lower level of defense activation, sufficient for avirulence but not for triggering a hypersensitive response. Natural variation in AvrRps4 reveals distinct recognition specificities that involve a surface-exposed residue. Recently, a direct interaction between AvrRps4 and Enhanced Disease Susceptibility 1 has been implicated in activation of immunity. However, we were unable to detect direct interaction between AvrRps4 and Enhanced Disease Susceptibility 1 after coexpression in Nicotiana benthamiana or in yeast cells. How intracellular plant immune receptors activate defense upon effector perception remains an unsolved problem. The structure of AvrRps4C, and identification of functionally important residues for its activation of plant immunity, advances our understanding of these processes in a well-defined model pathosystem. PMID:22988101

Transformation products in the water cycle and the unsolved problem of their proactive assessment: A combined in vitro/in silico approach.

PubMed

Menz, Jakob; Toolaram, Anju Priya; Rastogi, Tushar; Leder, Christoph; Olsson, Oliver; Kümmerer, Klaus; Schneider, Mandy

2017-01-01

Transformation products (TPs) emerging from incomplete degradation of micropollutants in aquatic systems can retain the biological activity of the parent compound, or may even possess new unexpected toxic properties. The chemical identities of these substances remain largely unknown, and consequently, the risks caused by their presence in the water cycle cannot be assessed thoroughly. In this study, a combined approach for the proactive identification of hazardous elements in the chemical structures of TPs, comprising analytical, bioanalytical and computational methods, was assessed by the example of the pharmaceutically active micropollutant propranolol (PPL). PPL was photo-transformed using ultraviolet (UV) irradiation and 115 newly formed TPs were monitored in the reaction mixtures by LC-MS analysis. The reaction mixtures were screened for emerging effects using a battery of in vitro bioassays and the occurrence of cytotoxic and mutagenic activities in bacteria was found to be significantly correlated with the occurrence of specific TPs during the treatment process. The follow-up analysis of structure-activity-relationships further illustrated that only small chemical transformations, such as the hydroxylation or the oxidative opening of an aromatic ring system, could substantially alter the biological effects of micropollutants in aquatic systems. In conclusion, more efforts should be made to prevent the occurrence and transformation of micropollutants in the water cycle and to identify the principal degradation pathways leading to their toxicological activation. With regard to the latter, the judicious combination of bioanalytical and computational tools represents an appealing approach that should be developed further. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

Chen, Chang-Zheng

2013-01-01

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

Rational Design and Evaluation of an Artificial Escherichia coli K1 Protein Vaccine Candidate Based on the Structure of OmpA

PubMed Central

Gu, Hao; Liao, Yaling; Zhang, Jin; Wang, Ying; Liu, Zhiyong; Cheng, Ping; Wang, Xingyong; Zou, Quanming; Gu, Jiang

2018-01-01

Escherichia coli (E. coli) K1 causes meningitis and remains an unsolved problem in neonates, despite the application of antibiotics and supportive care. The cross-reactivity of bacterial capsular polysaccharides with human antigens hinders their application as vaccine candidates. Thus, protein antigens could be an alternative strategy for the development of an E. coli K1 vaccine. Outer membrane protein A (OmpA) of E. coli K1 is a potential vaccine candidate because of its predominant contribution to bacterial pathogenesis and sub-cellular localization. However, little progress has been made regarding the use of OmpA for this purpose due to difficulties in OmpA production. In the present study, we first investigated the immunogenicity of the four extracellular loops of OmpA. Using the structure of OmpA, we rationally designed and successfully generated the artificial protein OmpAVac, composed of connected loops from OmpA. Recombinant OmpAVac was successfully produced in E. coli BL21 and behaved as a soluble homogenous monomer in the aqueous phase. Vaccination with OmpAVac induced Th1, Th2, and Th17 immune responses and conferred effective protection in mice. In addition, OmpAVac-specific antibodies were able to mediate opsonophagocytosis and inhibit bacterial invasion, thereby conferring prophylactic protection in E. coli K1-challenged adult mice and neonatal mice. These results suggest that OmpAVac could be a good vaccine candidate for the control of E. coli K1 infection and provide an additional example of structure-based vaccine design. PMID:29876324

Rational Design and Evaluation of an Artificial Escherichia coli K1 Protein Vaccine Candidate Based on the Structure of OmpA.

PubMed

Gu, Hao; Liao, Yaling; Zhang, Jin; Wang, Ying; Liu, Zhiyong; Cheng, Ping; Wang, Xingyong; Zou, Quanming; Gu, Jiang

2018-01-01

Escherichia coli ( E. coli ) K1 causes meningitis and remains an unsolved problem in neonates, despite the application of antibiotics and supportive care. The cross-reactivity of bacterial capsular polysaccharides with human antigens hinders their application as vaccine candidates. Thus, protein antigens could be an alternative strategy for the development of an E. coli K1 vaccine. Outer membrane protein A (OmpA) of E. coli K1 is a potential vaccine candidate because of its predominant contribution to bacterial pathogenesis and sub-cellular localization. However, little progress has been made regarding the use of OmpA for this purpose due to difficulties in OmpA production. In the present study, we first investigated the immunogenicity of the four extracellular loops of OmpA. Using the structure of OmpA, we rationally designed and successfully generated the artificial protein OmpAVac, composed of connected loops from OmpA. Recombinant OmpAVac was successfully produced in E. coli BL21 and behaved as a soluble homogenous monomer in the aqueous phase. Vaccination with OmpAVac induced Th1, Th2, and Th17 immune responses and conferred effective protection in mice. In addition, OmpAVac-specific antibodies were able to mediate opsonophagocytosis and inhibit bacterial invasion, thereby conferring prophylactic protection in E. coli K1-challenged adult mice and neonatal mice. These results suggest that OmpAVac could be a good vaccine candidate for the control of E. coli K1 infection and provide an additional example of structure-based vaccine design.

Challenges for mass production of nematodes in submerged culture.

PubMed

de la Torre, Mayra

2003-08-01

Nematodes of Steinernema and Heterorhabditis genera are used as agents in insect biocontrol programs. They are associated with specific bacteria which are also involved in the mechanism of pathogenicity and which are consumed by nematodes as living food. S. feltiae has various developmental stages in its life cycle, including four juvenile stages, adults and the free living form. During mating, males coil themselves around the female, which is around 1 cm long. Successful commercialization of nematode-bacteria biocontrol products depends on the ability to produce sufficient quantities of these products at competitive prices for a full pest control program. This could be feasible if high cell density submerged cultures are designed and implemented; however, major problems related to nematodes mass production in a bioreactor remain unsolved due to the lack of knowledge about the physiological aspects of the nematode, bacteria and nematode-bacteria association, interaction between the three phases present in the bioreactor (liquid, gas, nematodes-bacteria), possibility of mating under hydrodynamic stress conditions, etc. We have found that the two most important engineering aspects to take into account the mass propagation of nematodes are oxygen transfer rate and hydrodynamics to allow mating and to avoid mechanical damage of juveniles in stage 2. This article focuses on several aspects related to the fermentation system such as kinetics of growth, shear stress, hydrodynamics fields in the bioreactor and oxygen demand. Also, results published by other groups, together with those of our own, will be discussed in relation to the main challenges found during the fermentation process.

When dogs look back: inhibition of independent problem-solving behaviour in domestic dogs (Canis lupus familiaris) compared with wolves (Canis lupus).

PubMed

Udell, Monique A R

2015-09-01

Domestic dogs have been recognized for their social sensitivity and aptitude in human-guided tasks. For example, prior studies have demonstrated that dogs look to humans when confronted with an unsolvable task; an action often interpreted as soliciting necessary help. Conversely, wolves persist on such tasks. While dogs' 'looking back' behaviour has been used as an example of socio-cognitive advancement, an alternative explanation is that pet dogs show less persistence on independent tasks more generally. In this study, pet dogs, shelter dogs and wolves were given up to three opportunities to open a solvable puzzle box: when subjects were with a neutral human caretaker, alone and when encouraged by the human. Wolves were more persistent and more successful on this task than dogs, with 80% average success rate for wolves versus a 5% average success rate for dogs in both the human-in and alone conditions. Dogs showed increased contact with the puzzle box during the encouragement condition, but only a moderate increase in problem-solving success. Social sensitivity appears to play an important role in pet and shelter dogs' willingness to engage in problem-solving behaviour, which could suggest generalized dependence on, or deference to, human action. © 2015 The Author(s).

[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.

The Cosmological Lithium Problem and the Measurement of the 7Be(n, α) Reaction at n_TOF-CERN

NASA Astrophysics Data System (ADS)

Musumarra, Agatino; Barbagallo, Massimo

A possible explanation of the so-called "Cosmological Lithium Problem", an important unsolved problem in Nuclear Astrophysics, involves large systematic uncertainties in the cross-sections of reactions leading to the destruction of 7Be during the Big-Bang Nucleosynthesis (BBN). Among these reactions, the 7Be(n, α) is the most uncertain. So far, only a single measurement with thermal neutrons has been performed. Therefore, BBN calculations had to rely on rather uncertain theoretical extrapolations. The short half-life of 7Be (53.29 d) and the low cross section have prevented, up to now, to obtain experimental data at keV neutron energies typical for BBN studies. We have measured for the first time at n_TOF the 7Be(n, α) reaction in a wide neutron energy range, from thermal up to 10 keV. This measurement has been performed, at the new beam line (EAR2) of the Neutron-Time-Of-Flight facility n_TOF at CERN. The two α-particles, emitted back-to-back in the reaction, have been detected by mean of sandwiches of silicon detectors and, by exploiting the coincidence technique, we were able to suppress the large γ and n-induced background. The 7Be isotope production and purification has been performed by PSI-Zurich Switzerland.

Flow of “stress power-law” fluids between parallel rotating discs with distinct axes

DOE PAGES

Srinivasan, Shriram; Karra, Satish

2015-04-16

The problem of flow between parallel rotating discs with distinct axes corresponds to the case of flow in an orthogonal rheometer and has been studied extensively for different fluids since the instrument's inception. All the prior studies presume a constitutive prescription of the fluid stress in terms of the kinematical variables. In this paper, we approach the problem from a different perspective, i.e., a constitutive specification of the symmetric part of the velocity gradient in terms of the Cauchy stress. Such an approach ensures that the boundary conditions can be incorporated in a manner quite faithful to real world experimentsmore » with the instrument. Interestingly, the choice of the boundary condition is critical to the solvability of the problem for the case of creeping/Stokes flow. Furthermore, when the no-slip condition is enforced at the boundaries, depending on the model parameters and axes offset, the fluid response can show non-uniqueness or unsolvability, features which are absent in a conventional constitutive specification. In case of creeping/Stokes flow with prescribed values of the stress, the fluid response is indeterminate. We also record the response of a particular case of the given “stress power-law” fluid; one that cannot be attained by the conventional power-law fluids.« less

The quest for novel modes of excitation in exotic nuclei

NASA Astrophysics Data System (ADS)

Paar, N.

2010-06-01

This paper provides an insight into several open problems in the quest for novel modes of excitation in nuclei with isospin asymmetry, deformation and finite-temperature characteristics in stellar environments. Major unsolved problems include the nature of pygmy dipole resonances, the quest for various multipole and spin-isospin excitations both in neutron-rich and proton drip-line nuclei mainly driven by loosely bound nucleons, excitations in unstable deformed nuclei and evolution of their properties with the shape phase transition. Exotic modes of excitation in nuclei at finite temperatures characteristic of supernova evolution present open problems with a possible impact in modeling astrophysically relevant weak interaction rates. All these issues challenge self-consistent many-body theory frameworks at the frontiers of on-going research, including nuclear energy density functionals, both phenomenological and constrained by the strong interaction physics of QCD, models based on low-momentum two-nucleon interaction Vlow-k and correlated realistic nucleon-nucleon interaction VUCOM, supplemented by three-body force, as well as two-nucleon and three-nucleon interactions derived from the chiral effective field theory. Joined theoretical and experimental efforts, including research with radioactive isotope beams, are needed to provide insight into dynamical properties of nuclei away from the valley of stability, involving the interplay of isospin asymmetry, deformation and finite temperature.

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

[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.

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.

Cutting to the chase: what physician executives need to know about HIPAA.

PubMed

Fitzmaurice, J M; Rose, J S

2000-01-01

All health care providers, plans, and clearinghouses will be affected by the federally mandated uniform standards for administrative transactions. This article presents distilled core information about the Health Insurance Portability and Accountability Act (HIPAA) legislation--the standards, penalties for violations, and status of final rules. It also raises several key unsolved issues of which clinicians, executives, and health care providers must be aware so they can prepare and plan for the upcoming changes. HIPAA is intended to improve the efficiency and effectiveness of the health care system, as well as to increase the protection and confidentiality of individually identifiable health information. The costs of making the transition to the legislated standards and processes remain a worrisome factor. Although there are two years before these standards must be implemented, and cost and compliance issues resolved, work has already begun in many health institutions to identify and address them.

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.

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.

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.

[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.

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.

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.

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.

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.

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.

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

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

Ahlgren, Björn; Larsson, Josefin; Nymark, Tanja

The origin of the prompt emission in gamma-ray bursts (GRBs) is still an unsolved problem and several different mechanisms have been suggested. We fit Fermi GRB data with a photospheric emission model which includes dissipation of the jet kinetic energy below the photosphere. The resulting spectra are dominated by Comptonization and contain no significant contribution from synchrotron radiation. In order to fit to the data, we span a physically motivated part of the model's parameter space and create DREAM (Dissipation with Radiative Emission as A table Model), a table model for XSPEC. Here, we show that this model can describemore » different kinds of GRB spectra, including GRB 090618, representing a typical Band function spectrum, and GRB 100724B, illustrating a double peaked spectrum, previously fitted with a Band+blackbody model, suggesting they originate from a similar scenario. We also suggest that the main difference between these two types of bursts is the optical depth at the dissipation site.« less

Boolean logic tree of graphene-based chemical system for molecular computation and intelligent molecular search query.

PubMed

Huang, Wei Tao; Luo, Hong Qun; Li, Nian Bing

2014-05-06

The most serious, and yet unsolved, problem of constructing molecular computing devices consists in connecting all of these molecular events into a usable device. This report demonstrates the use of Boolean logic tree for analyzing the chemical event network based on graphene, organic dye, thrombin aptamer, and Fenton reaction, organizing and connecting these basic chemical events. And this chemical event network can be utilized to implement fluorescent combinatorial logic (including basic logic gates and complex integrated logic circuits) and fuzzy logic computing. On the basis of the Boolean logic tree analysis and logic computing, these basic chemical events can be considered as programmable "words" and chemical interactions as "syntax" logic rules to construct molecular search engine for performing intelligent molecular search query. Our approach is helpful in developing the advanced logic program based on molecules for application in biosensing, nanotechnology, and drug delivery.

Transfer Ionization Studies for Proton on He - new Inside into the World of Correlation

NASA Astrophysics Data System (ADS)

Schmidt-Böcking, Horst

2005-04-01

Correlated many-particle dynamics in Coulombic systems, which is one of the unsolved fundamental problems in AMO-physics, can now be experimentally approached with so far unprecedented completeness and precision. The recent development of the COLTRIMS technique (COLd Target Recoil Ion Momentum Spectroscopy) provides a coincident multi-fragment imaging technique for eV and sub-eV fragment detection. In its completeness it is as powerful as the bubble chamber in high energy physics. In recent benchmark experiments quasi snapshots (duration as short an atto-sec) of the correlated dynamics between electrons and nuclei has been made for atomic and molecular objects. This new imaging technique has opened a powerful observation window into the hidden world of many-particle dynamics. Recent transfer ionization studies will be presented and the direct observation of correlated electron pairs will be discussed.

Reputation drives cooperative behaviour and network formation in human groups.

PubMed

Cuesta, Jose A; Gracia-Lázaro, Carlos; Ferrer, Alfredo; Moreno, Yamir; Sánchez, Angel

2015-01-19

Cooperativeness is a defining feature of human nature. Theoreticians have suggested several mechanisms to explain this ubiquitous phenomenon, including reciprocity, reputation, and punishment, but the problem is still unsolved. Here we show, through experiments conducted with groups of people playing an iterated Prisoner's Dilemma on a dynamic network, that it is reputation what really fosters cooperation. While this mechanism has already been observed in unstructured populations, we find that it acts equally when interactions are given by a network that players can reconfigure dynamically. Furthermore, our observations reveal that memory also drives the network formation process, and cooperators assort more, with longer link lifetimes, the longer the past actions record. Our analysis demonstrates, for the first time, that reputation can be very well quantified as a weighted mean of the fractions of past cooperative acts and the last action performed. This finding has potential applications in collaborative systems and e-commerce.

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

PubMed

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

2013-06-21

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

New Results on Contact Binary Stars

NASA Astrophysics Data System (ADS)

He, J.; Qian, S.; Zhu, L.; Liu, L.; Liao, W.

2014-08-01

Contact binary star is a kind of close binary with the strongest interaction binary system. Their formations and evolutions are unsolved problems in astrophysics. Since 2000, our groups have observed and studied more than half a hundred of contact binaries. In this report, I will summarize our new results of some contact binary stars (e.g. UZ CMi, GSC 03526-01995, FU Dra, GSC 0763-0572, V524 Mon, MR Com, etc.). They are as follow: (1) We discovered that V524 Mon and MR Com are shallow-contact binaries with their period decreasing; (2) GSC 03526-01995 is middle-contact binary without a period increasing or decreasing continuously; (3) UZ CMi, GSC 0763-0572 and FU Dra are middle-contact binaries with the period increasing continuously; (4) UZ CMi, GSC 03526-01995, FU Dra and V524 Mon show period oscillation which may imply the presence of additional components in these contact binaries.

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

NASA Astrophysics Data System (ADS)

Bengtson, K. B.

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

Fabrication of nanopore and nanoparticle arrays with high aspect ratio AAO masks.

PubMed

Li, Z P; Xu, Z M; Qu, X P; Wang, S B; Peng, J; Mei, L H

2017-03-03

How to use high aspect ratio anodic aluminum oxide (AAO) membranes as an etching and evaporation mask is one of the unsolved problems in the application of nanostructured arrays. Here we describe the versatile utilizations of the highly ordered AAO membranes with a high aspect ratio of more than 20 used as universal masks for the formation of various nanostructure arrays on various substrates. The result shows that the fabricated nanopore and nanoparticle arrays of substrates inherit the regularity of the AAO membranes completely. The flat AAO substrates and uneven AAO frontages were attached to the Si substrates respectively as an etching mask, which demonstrates that the two kinds of replication, positive and negative, represent the replication of the mirroring of Si substrates relative to the flat AAO substrates and uneven AAO frontages. Our work is a breakthrough for the broad research field of surface nano-masking.

Fabrication of nanopore and nanoparticle arrays with high aspect ratio AAO masks

NASA Astrophysics Data System (ADS)

Li, Z. P.; Xu, Z. M.; Qu, X. P.; Wang, S. B.; Peng, J.; Mei, L. H.

2017-03-01

How to use high aspect ratio anodic aluminum oxide (AAO) membranes as an etching and evaporation mask is one of the unsolved problems in the application of nanostructured arrays. Here we describe the versatile utilizations of the highly ordered AAO membranes with a high aspect ratio of more than 20 used as universal masks for the formation of various nanostructure arrays on various substrates. The result shows that the fabricated nanopore and nanoparticle arrays of substrates inherit the regularity of the AAO membranes completely. The flat AAO substrates and uneven AAO frontages were attached to the Si substrates respectively as an etching mask, which demonstrates that the two kinds of replication, positive and negative, represent the replication of the mirroring of Si substrates relative to the flat AAO substrates and uneven AAO frontages. Our work is a breakthrough for the broad research field of surface nano-masking.

Review of chart recognition in document images

NASA Astrophysics Data System (ADS)

Liu, Yan; Lu, Xiaoqing; Qin, Yeyang; Tang, Zhi; Xu, Jianbo

2013-01-01

As an effective information transmitting way, chart is widely used to represent scientific statistics datum in books, research papers, newspapers etc. Though textual information is still the major source of data, there has been an increasing trend of introducing graphs, pictures, and figures into the information pool. Text recognition techniques for documents have been accomplished using optical character recognition (OCR) software. Chart recognition techniques as a necessary supplement of OCR for document images are still an unsolved problem due to the great subjectiveness and variety of charts styles. This paper reviews the development process of chart recognition techniques in the past decades and presents the focuses of current researches. The whole process of chart recognition is presented systematically, which mainly includes three parts: chart segmentation, chart classification, and chart Interpretation. In each part, the latest research work is introduced. In the last, the paper concludes with a summary and promising future research direction.

Tracked 3D ultrasound in radio-frequency liver ablation

NASA Astrophysics Data System (ADS)

Boctor, Emad M.; Fichtinger, Gabor; Taylor, Russell H.; Choti, Michael A.

2003-05-01

Recent studies have shown that radio frequency (RF) ablation is a simple, safe and potentially effective treatment for selected patients with liver metastases. Despite all recent therapeutic advancements, however, intra-procedural target localization and precise and consistent placement of the tissue ablator device are still unsolved problems. Various imaging modalities, including ultrasound (US) and computed tomography (CT) have been tried as guidance modalities. Transcutaneous US imaging, due to its real-time nature, may be beneficial in many cases, but unfortunately, fails to adequately visualize the tumor in many cases. Intraoperative or laparoscopic US, on the other hand, provides improved visualization and target imaging. This paper describes a system for computer-assisted RF ablation of liver tumors, combining navigational tracking of a conventional imaging ultrasound probe to produce 3D ultrasound imaging with a tracked RF ablation device supported by a passive mechanical arm and spatially registered to the ultrasound volume.

Atomic quantum simulation of the lattice gauge-Higgs model: Higgs couplings and emergence of exact local gauge symmetry.

PubMed

Kasamatsu, Kenichi; Ichinose, Ikuo; Matsui, Tetsuo

2013-09-13

Recently, the possibility of quantum simulation of dynamical gauge fields was pointed out by using a system of cold atoms trapped on each link in an optical lattice. However, to implement exact local gauge invariance, fine-tuning the interaction parameters among atoms is necessary. In the present Letter, we study the effect of violation of the U(1) local gauge invariance by relaxing the fine-tuning of the parameters and showing that a wide variety of cold atoms is still a faithful quantum simulator for a U(1) gauge-Higgs model containing a Higgs field sitting on sites. The clarification of the dynamics of this gauge-Higgs model sheds some light upon various unsolved problems, including the inflation process of the early Universe. We study the phase structure of this model by Monte Carlo simulation and also discuss the atomic characteristics of the Higgs phase in each simulator.

QSAR modeling: where have you been? Where are you going to?

PubMed

Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-06-26

Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.